TY - JOUR T1 - Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer. AN - 78767504; 9816128 AB - Serum anti-p53 antibodies (p53-Abs) may be surrogate markers for both p53 alterations and preclinical cancer. Ancillary to a prospective trial to abate progressive development of clinical stages of chronic obstructive pulmonary disease, we conducted a retrospective, nested case-control study. Twenty-three cases were diagnosed with cancer during the trial. Enzyme immunoassay, immunoblotting, and immunoprecipitation were used to detect p53-Abs in serum, immunohistochemistry (IHC) to detect p53 accumulation, and single-strand conformation polymorphism and DNA sequencing to detect p53 mutations in tumor samples. p53-Abs were detected by three types of assays in five (23%) of the cancer patients, 80% of whom had detectable p53-Abs before diagnosis: 2 lung cancers (7 and 6 months before), 1 prostate cancer (11 months), and 1 breast cancer (5 months). Four Ab-positive patients had IHC-positive tumors. Two of 4 Ab-positive patients and 2 of 14 Ab-negative had p53 missense mutations or base pair deletion and IHC-positive tumors. The 44 noncancer COPD controls, matched with the cancer cases for age, gender, and smoking habits, were negative for p53-Abs. These results indicate that p53-Abs may facilitate the early diagnosis of cancer in a subset of smokers with chronic obstructive pulmonary disease who are at an increased cancer risk. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Trivers, G E AU - De Benedetti, V M AU - Cawley, H L AU - Caron, G AU - Harrington, A M AU - Bennett, W P AU - Jett, J R AU - Colby, T V AU - Tazelaar, H AU - Pairolero, P AU - Miller, R D AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. triversg@intra.nci.nih.gov Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1767 EP - 1775 VL - 2 IS - 10 SN - 1078-0432, 1078-0432 KW - Antibodies KW - 0 KW - Antibodies, Neoplasm KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Antibodies, Neoplasm -- blood KW - Immunoblotting KW - Randomized Controlled Trials as Topic KW - DNA Mutational Analysis KW - Humans KW - Retrospective Studies KW - Prognosis KW - Aged KW - Precipitin Tests KW - Polymorphism, Single-Stranded Conformational KW - Aged, 80 and over KW - Case-Control Studies KW - Middle Aged KW - Mutation KW - Immunohistochemistry KW - Female KW - Immunoenzyme Techniques KW - Male KW - Tumor Suppressor Protein p53 -- analysis KW - Neoplasms -- diagnosis KW - Antibodies -- blood KW - Neoplasms -- blood KW - Tumor Suppressor Protein p53 -- immunology KW - Tumor Suppressor Protein p53 -- genetics KW - Lung Diseases, Obstructive -- immunology KW - Lung Diseases, Obstructive -- blood KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78767504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Anti-p53+antibodies+in+sera+from+patients+with+chronic+obstructive+pulmonary+disease+can+predate+a+diagnosis+of+cancer.&rft.au=Trivers%2C+G+E%3BDe+Benedetti%2C+V+M%3BCawley%2C+H+L%3BCaron%2C+G%3BHarrington%2C+A+M%3BBennett%2C+W+P%3BJett%2C+J+R%3BColby%2C+T+V%3BTazelaar%2C+H%3BPairolero%2C+P%3BMiller%2C+R+D%3BHarris%2C+C+C&rft.aulast=Trivers&rft.aufirst=G&rft.date=1996-10-01&rft.volume=2&rft.issue=10&rft.spage=1767&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug interactions in patients infected with human immunodeficiency virus. AN - 78518494; 8909827 AB - Patients with AIDS who are receiving optimal medical care, including combination therapy with antiretroviral agents and more effective prophylaxis and therapy for opportunistic infections and neoplasms, are surviving longer. However, the potential for drug interactions in these patients is increased because many of the currently used antibiotics and antiviral agents have profound effects on the hepatic cytochrome P-450 enzyme system, on renal tubular function, and on bone marrow function. In this AIDS Commentary, Dr. Piscitelli and colleagues have succinctly reviewed the current state of our knowledge regarding the potential for additive or synergistic drug interactions that can result in enhanced toxicity or, alternatively, augmented therapeutic benefit. Information on these interactions will become more important as more intensive and effective therapy becomes available for persons with far-advanced infection due to human immunodeficiency virus type 1. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Piscitelli, S C AU - Flexner, C AU - Minor, J R AU - Polis, M A AU - Masur, H AD - Department of Pharmacy, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 685 EP - 693 VL - 23 IS - 4 SN - 1058-4838, 1058-4838 KW - Antacids KW - 0 KW - Anti-Allergic Agents KW - Anti-Bacterial Agents KW - Anti-HIV Agents KW - Anti-Infective Agents KW - Antifungal Agents KW - Antitrichomonal Agents KW - Antiviral Agents KW - Contraceptives, Oral KW - Cytokines KW - Enzyme Inhibitors KW - Narcotics KW - Index Medicus KW - AIDS/HIV KW - Contraceptives, Oral -- adverse effects KW - Antifungal Agents -- adverse effects KW - Humans KW - Anti-Bacterial Agents -- adverse effects KW - Kidney -- physiology KW - Anti-HIV Agents -- adverse effects KW - Narcotics -- adverse effects KW - Liver -- metabolism KW - Anti-Allergic Agents -- adverse effects KW - Pharmacokinetics KW - Drug Therapy, Combination KW - Anti-Infective Agents -- adverse effects KW - Enzyme Induction -- drug effects KW - Absorption KW - Enzyme Inhibitors -- pharmacology KW - Cytokines -- physiology KW - Antiviral Agents -- adverse effects KW - Antacids -- adverse effects KW - Antitrichomonal Agents -- adverse effects KW - Drug Interactions KW - HIV Infections -- drug therapy KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78518494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Drug+interactions+in+patients+infected+with+human+immunodeficiency+virus.&rft.au=Piscitelli%2C+S+C%3BFlexner%2C+C%3BMinor%2C+J+R%3BPolis%2C+M+A%3BMasur%2C+H&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1996-10-01&rft.volume=23&rft.issue=4&rft.spage=685&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-27 N1 - Date created - 1997-02-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Infect Dis. 1997 Aug;25(2):344-5 [9332549] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. AN - 78503223; 8902272 AB - Autoantibodies against specific human cytochrome P450s have been found in the sera of patients suffering from a variety of diseases, including those caused by drugs. In the cases of tienilic acid- and dihydralazine-induced hepatitis, patients have serum autoantibodies directed against cytochromes P450 2C9 and P450 1A2, respectively. In the present study, we have found that 25 of 56 (45%) patients diagnosed with halothane hepatitis have autoantibodies that react with human cytochrome P450 2E1 that was purified from a baculovirus expression system. The autoantibodies inhibited the activity of cytochrome P450 2E1 and appeared to be directed against mainly conformational epitopes. In addition, because cytochrome P450 2E1 became trifluoroacetylated when it oxidatively metabolized halothane, it is possible that the covalently altered form of cytochrome P450 2E1 may be able to bypass the immunologic tolerance that normally exists against cytochrome P450 2E1. A similar mechanism may explain the formation of autoantibodies that have been found against other cellular targets of the reactive trifluoroacetyl chloride metabolite of halothane. JF - Chemical research in toxicology AU - Bourdi, M AU - Chen, W AU - Peter, R M AU - Martin, J L AU - Buters, J T AU - Nelson, S D AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 1159 EP - 1166 VL - 9 IS - 7 SN - 0893-228X, 0893-228X KW - Autoantibodies KW - 0 KW - Autoantigens KW - Fluorine KW - 284SYP0193 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Acetylation KW - Fluorine -- metabolism KW - Humans KW - Autoantibodies -- blood KW - Cytochrome P-450 CYP2E1 -- immunology KW - Autoantigens -- immunology KW - Halothane -- toxicity KW - Chemical and Drug Induced Liver Injury -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78503223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Human+cytochrome+P450+2E1+is+a+major+autoantigen+associated+with+halothane+hepatitis.&rft.au=Bourdi%2C+M%3BChen%2C+W%3BPeter%2C+R+M%3BMartin%2C+J+L%3BButers%2C+J+T%3BNelson%2C+S+D%3BPohl%2C+L+R&rft.aulast=Bourdi&rft.aufirst=M&rft.date=1996-10-01&rft.volume=9&rft.issue=7&rft.spage=1159&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Precursor-product relationship between oval cells and hepatocytes: comparison between tritiated thymidine and bromodeoxyuridine as tracers. AN - 78486062; 8895481 AB - The expansion and differentiation of oval cells in the acetylaminofluorene (AAF)/partial hepatectomy (PH) model was studied utilizing pulse-chase labeling with both tritiated thymidine ([3H]TdR) and bromodeoxyuridine (BUdR). Animals in which a significant decrease in serum albumin and increase in alanine aminotransferase and bilirubin were observed demonstrated the most prominent differentiation of oval cells into hepatocytes. Administration of [3H]TdR or BUdR, either individually or together, to the animals on day 6 after partial hepatectomy resulted in labeling of the majority of the oval cells by days 7 and 9 after PH. A striking difference in the distribution of [3H]TdR- and BUdR-labeled cells in the double labeling experiments was observed on day 11, at which time the number of [3H]TdR-labeled cells increased 6-fold and that of double labeled cells decreased 2-fold. Furthermore, on day 11 the basophilic foci were weakly positive for BUdR and negative at later time points in animals receiving BUdR alone or together with [3H]TdR. In contrast, the cells in basophilic foci as well as transitional cells were positive for [3H]TdR. Cells heavily labeled with both [3H]TdR and BUdR were present at all time points, indicating an inhibition of the proliferative activity. Pulse labeling of rat liver epithelial cells with BUdR in vitro demonstrated that immunodetection of BUdR was lost after three or more cell divisions. We conclude that the BUdR tagging method is particularly sensitive to label dilution during cell cycling and may not be suitable for establishment of a precursor-product relationship between cell lineages when the progenitor population proliferates more than three times. JF - Carcinogenesis AU - Evarts, R P AU - Hu, Z AU - Omori, N AU - Omori, M AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 2143 EP - 2151 VL - 17 IS - 10 SN - 0143-3334, 0143-3334 KW - Albumins KW - 0 KW - Tritium KW - 10028-17-8 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Albumins -- metabolism KW - Animals KW - DNA Damage KW - Cell Differentiation KW - Liver Regeneration KW - Rats KW - Rats, Inbred F344 KW - Epithelial Cells KW - Hepatectomy KW - Male KW - Liver -- cytology KW - Liver -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78486062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Precursor-product+relationship+between+oval+cells+and+hepatocytes%3A+comparison+between+tritiated+thymidine+and+bromodeoxyuridine+as+tracers.&rft.au=Evarts%2C+R+P%3BHu%2C+Z%3BOmori%2C+N%3BOmori%2C+M%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Evarts&rft.aufirst=R&rft.date=1996-10-01&rft.volume=17&rft.issue=10&rft.spage=2143&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-05 N1 - Date created - 1996-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol and drug use, abuse, and dependence among welfare recipients. AN - 78448687; 8876518 AB - This paper presents national estimates of heavy drinking, drug use, and alcohol and drug abuse and/or dependence among recipients of selected welfare programs. Data from the 1992 National Longitudinal Alcohol Epidemiologic Survey were analyzed. The percentages of welfare recipients using, abusing, or dependent on alcohol or drugs were relatively small and consistent with the general US population and those not receiving welfare benefits. Although a minority of welfare recipients have alcohol or drug problems, substance abuse prevention and treatment services are needed among high-risk subgroups. JF - American journal of public health AU - Grant, B F AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1450 EP - 1454 VL - 86 IS - 10 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Health Surveys KW - Adult KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Alcoholism -- epidemiology KW - Substance-Related Disorders -- epidemiology KW - Social Welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78448687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+public+health&rft.atitle=Alcohol+and+drug+use%2C+abuse%2C+and+dependence+among+welfare+recipients.&rft.au=Grant%2C+B+F%3BDawson%2C+D+A&rft.aulast=Grant&rft.aufirst=B&rft.date=1996-10-01&rft.volume=86&rft.issue=10&rft.spage=1450&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-26 N1 - Date created - 1996-11-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Drug Alcohol Depend. 1995 Jul;39(1):37-44 [7587973] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - NIDA conference report on cardiopulmonary complications of "crack" cocaine use. Clinical manifestations and pathophysiology. AN - 78447976; 8874270 JF - Chest AU - Thadani, P V Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1072 EP - 1076 VL - 110 IS - 4 KW - Crack Cocaine KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Hemodynamics -- drug effects KW - Animals KW - Endothelium, Vascular -- drug effects KW - Humans KW - Respiration -- drug effects KW - Lung -- drug effects KW - Substance-Related Disorders -- physiopathology KW - Lung Diseases -- etiology KW - Cardiovascular Diseases -- etiology KW - Lung Diseases -- physiopathology KW - Substance-Related Disorders -- complications KW - Crack Cocaine -- pharmacology KW - Cardiovascular Diseases -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78447976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Chest&rft.atitle=NIDA+conference+report+on+cardiopulmonary+complications+of+%22crack%22+cocaine+use.+Clinical+manifestations+and+pathophysiology.&rft.au=Thadani%2C+P+V&rft.aulast=Thadani&rft.aufirst=P&rft.date=1996-10-01&rft.volume=110&rft.issue=4&rft.spage=1072&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-20 N1 - Date created - 1996-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. AN - 78316712; 8815753 AB - Uncertainty exists about the efficacy and toxicity of bolus therapy with methylprednisolone or of the combination of methylprednisolone and cyclophosphamide in the treatment of lupus nephritis. To determine 1) whether intensive bolus therapy with methylprednisolone is an adequate substitute for bolus therapy with cyclophosphamide and 2) whether the combination of methylprednisolone and cyclophosphamide is superior to bolus therapy with methylprednisolone or cyclophosphamide alone. Randomized, controlled trial with at least 5 years of follow-up. Government referral-based research hospital. 82 patients with lupus nephritis who had 10 or more erythrocytes per high-power field, cellular casts, proteinuria (> 1 g of protein per day), and a renal biopsy specimen that showed proliferative nephritis. Bolus therapy with methylprednisolone (1 g/m2 body surface area), given monthly for at least 1 year; bolus therapy with cyclophosphamide (0.5 to 1.0 g/m2 body surface area), given monthly for 6 months and then quarterly; or bolus therapy with both methylprednisolone and cyclophosphamide. 1) Renal remission (defined as < 10 dysmorphic erythrocytes per high-power field, the absence of cellular casts, and excretion of < 1 g of protein per day without doubling of the serum creatinine level), 2) prevention of doubling of the serum creatinine level, and 3) prevention of renal failure requiring dialysis. Renal remission occurred in 17 of 20 patients in the combination therapy group (85%), 13 of 21 patients in the cyclophosphamide group (62%), and 7 of 24 patients in the methylprednisolone group (29%) (P < 0.001). Twenty-eight patients (43%) did not achieve renal remission. By life-table analysis, the likelihood of remission during the study period was greater in the combination therapy group than in the methylprednisolone group (P = 0.028). Combination therapy and cyclophosphamide therapy were not statistically different. Adverse events were amenorrhea (seen in 41% of the cyclophosphamide group, 43% of the combination therapy group, and 7.4% of the methylprednisolone group), cervical dysplasia (seen in 11% of the cyclophosphamide group. 7.1% of the combination therapy group, and 0% of the methylprednisolone group), avascular necrosis (seen in 11% of the cyclophosphamide group, 18% of the combination therapy group, and 22% of the methylprednisolone group), herpes zoster (seen in 15% of the cyclophosphamide group, 21% of the combination therapy group, and 3.7% of the methylprednisolone group) and at least one infection (seen in 26% of the cyclophosphamide group. 32% of the combination therapy group, and 7.4% of the methylprednisolone group). Monthly bolus therapy with methylprednisolone was less effective than monthly bolus therapy with cyclophosphamide. A trend toward greater efficacy with combination therapy was seen. JF - Annals of internal medicine AU - Gourley, M F AU - Austin, H A AU - Scott, D AU - Yarboro, C H AU - Vaughan, E M AU - Muir, J AU - Boumpas, D T AU - Klippel, J H AU - Balow, J E AU - Steinberg, A D AD - National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/10/01/ PY - 1996 DA - 1996 Oct 01 SP - 549 EP - 557 VL - 125 IS - 7 SN - 0003-4819, 0003-4819 KW - Anti-Inflammatory Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Methylprednisolone KW - X4W7ZR7023 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Life Tables KW - Drug Administration Schedule KW - Humans KW - Adult KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Remission Induction KW - Cyclophosphamide -- administration & dosage KW - Methylprednisolone -- therapeutic use KW - Methylprednisolone -- administration & dosage KW - Lupus Nephritis -- drug therapy KW - Cyclophosphamide -- therapeutic use KW - Anti-Inflammatory Agents -- adverse effects KW - Anti-Inflammatory Agents -- therapeutic use KW - Anti-Inflammatory Agents -- administration & dosage KW - Methylprednisolone -- adverse effects KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78316712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Methylprednisolone+and+cyclophosphamide%2C+alone+or+in+combination%2C+in+patients+with+lupus+nephritis.+A+randomized%2C+controlled+trial.&rft.au=Gourley%2C+M+F%3BAustin%2C+H+A%3BScott%2C+D%3BYarboro%2C+C+H%3BVaughan%2C+E+M%3BMuir%2C+J%3BBoumpas%2C+D+T%3BKlippel%2C+J+H%3BBalow%2C+J+E%3BSteinberg%2C+A+D&rft.aulast=Gourley&rft.aufirst=M&rft.date=1996-10-01&rft.volume=125&rft.issue=7&rft.spage=549&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 2002 Sep 17;137(6):545-6; author reply 545-6 [12230360] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Japanese and United States Preschool Children's Responses to Conflict and Distress AN - 61508600; 9709347 AB - Japanese & US preschool children's (N = 60) responses to hypothetical interpersonal dilemmas were examined as a function of culture, gender, & maternal childrearing values, drawing on assessment of experimental tasks composed of distress & conflict dilemmas. US children showed more anger, more aggressive behavior & language, & underregulation of emotion than Japanese children, across different contexts of assessment. Children from the two cultures appeared more similar on prosocial & avoidant patterns, though in some contexts, US children also showed more prosocial themes. Girls from both cultures expressed more prosocial themes & sometimes more anger than boys. Maternal encouragement of children's emotional expressivity was correlated with anger & aggression in children. This behavior was more characteristic of US than Japanese mothers, while emphasis on psychological discipline (reasoning; guilt & anxiety induction) was more characteristic of Japanese than US mothers. The relevance of a conceptual framework that focuses on differences in Eastern & Western cultures in self-construals regarding independence & interdependence is considered. Adapted from the source document. JF - Child Development AU - Zahn-Waxler, Carolyn AU - Friedman, Ruth J AU - Cole, Pamela M AU - Mizuta, Ichiro AU - Hiruma, Noriko AD - National Institute of Mental Health, Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 2462 EP - 2477 VL - 67 IS - 5 SN - 0009-3920, 0009-3920 KW - conflict/distress KW - dilemmas, preschool children's response, Japan vs US KW - maternal influence KW - experimental data KW - Emotions KW - Mothers KW - Interpersonal Conflict KW - Crosscultural Analysis KW - Anger KW - Altruism KW - United States of America KW - Childrearing Practices KW - Self Expression KW - Aggression KW - Preschool Children KW - Japan KW - article KW - 0312: social psychology; personality & social roles (individual traits, social identity, adjustment, conformism, & deviance) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61508600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Japanese+and+United+States+Preschool+Children%27s+Responses+to+Conflict+and+Distress&rft.au=Zahn-Waxler%2C+Carolyn%3BFriedman%2C+Ruth+J%3BCole%2C+Pamela+M%3BMizuta%2C+Ichiro%3BHiruma%2C+Noriko&rft.aulast=Zahn-Waxler&rft.aufirst=Carolyn&rft.date=1996-10-01&rft.volume=67&rft.issue=5&rft.spage=2462&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - CHDEAW N1 - SubjectsTermNotLitGenreText - Interpersonal Conflict; Self Expression; Preschool Children; United States of America; Japan; Childrearing Practices; Mothers; Crosscultural Analysis; Altruism; Aggression; Anger; Emotions ER - TY - JOUR T1 - Effects of overexpressing wild-type and mutant PDGF receptors on translocation of GLUT4 in transfected rat adipose cells. AN - 78383165; 8831662 AB - Activation of phosphatidylinositol 3-kinase (PI3K) by insulin is necessary for the effect of insulin to recruit GLUT4 to the cell surface in insulin target cells. In adipose cells, stimulation of endogenous PDGF receptors (PDGF-R) results in increased PI3K activity without causing recruitment of GLUT4. We overexpressed wild-type or mutant forms of the PDGF-R in rat adipose cells and examined their effects on PDGF- and insulin-stimulated recruitment of co-transfected epitope-tagged GLUT4. Control cells expressing only tagged GLUT4 had a 3-fold increase in cell surface GLUT4 upon insulin stimulation but no response to PDGF. Cells overexpressing wild-type PDGF-R maintained insulin responsiveness and, in addition, acquired the ability to recruit GLUT4 in response to PDGF. Surprisingly, overexpression of F740/ F751 (mutant PDGF-R unable to directly activate PI3K) led to similar results. Nevertheless, wortmannin (an inhibitor of PI3K) blocked effects of both PDGF and insulin to recruit GLUT4. Our data suggest that overexpression of PDGF-R mediates positive effects on GLUT4 translocation by a wortmannin sensitive pathway not dependent on direct interaction of the PDGF-R with PI3K. JF - Biochemical and biophysical research communications AU - Quon, M J AU - Chen, H AU - Lin, C H AU - Zhou, L AU - Ing, B L AU - Zarnowski, M J AU - Klinghoffer, R AU - Kazlauskas, A AU - Cushman, S W AU - Taylor, S I AD - Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/09/24/ PY - 1996 DA - 1996 Sep 24 SP - 587 EP - 594 VL - 226 IS - 3 SN - 0006-291X, 0006-291X KW - Epitopes KW - 0 KW - Glucose Transporter Type 4 KW - Insulin KW - Monosaccharide Transport Proteins KW - Muscle Proteins KW - Platelet-Derived Growth Factor KW - Recombinant Proteins KW - SLC2A4 protein, human KW - Slc2a4 protein, rat KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Phosphotransferases (Alcohol Group Acceptor) KW - Receptor, Platelet-Derived Growth Factor beta KW - EC 2.7.10.1 KW - Receptors, Platelet-Derived Growth Factor KW - Index Medicus KW - Animals KW - Epididymis KW - Humans KW - Protein Processing, Post-Translational KW - Sequence Tagged Sites KW - Insulin -- pharmacology KW - Cloning, Molecular KW - Rats KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Cell Membrane -- metabolism KW - Phosphotransferases (Alcohol Group Acceptor) -- metabolism KW - Male KW - Platelet-Derived Growth Factor -- metabolism KW - Monosaccharide Transport Proteins -- biosynthesis KW - Monosaccharide Transport Proteins -- metabolism KW - Adipose Tissue -- metabolism KW - Platelet-Derived Growth Factor -- pharmacology KW - Receptors, Platelet-Derived Growth Factor -- physiology KW - Receptors, Platelet-Derived Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78383165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Effects+of+overexpressing+wild-type+and+mutant+PDGF+receptors+on+translocation+of+GLUT4+in+transfected+rat+adipose+cells.&rft.au=Quon%2C+M+J%3BChen%2C+H%3BLin%2C+C+H%3BZhou%2C+L%3BIng%2C+B+L%3BZarnowski%2C+M+J%3BKlinghoffer%2C+R%3BKazlauskas%2C+A%3BCushman%2C+S+W%3BTaylor%2C+S+I&rft.aulast=Quon&rft.aufirst=M&rft.date=1996-09-24&rft.volume=226&rft.issue=3&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-07 N1 - Date created - 1996-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo mutagenicity and DNA adduct levels of heterocyclic amines in Muta mice and c-myc/lacZ double transgenic mice. AN - 78389252; 8841498 AB - The cooked meat derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-9H-pyrido[2,3-b]indole (A alpha C) are established mutagens in the Salmonella assay and hepatocarcinogens in mice. The current study uses transgenic mice to examine hepatic HCA-DNA adduct formation and mutagenesis in vivo and the impact of hepatic overexpression of the c-myc oncogene on HCA-induced mutagenesis. C57B1/lacZ and c-myc/lacZ mice strains, produced by crossbreeding Muta Mice (carrying the lacZ mutation target gene) with either C57B1 control or c-myc transgenic mice, respectively, were treated with 10 daily doses of IQ, MelQx or A alpha C (20 micrograms/g, p.o.). Four weeks after dosing, the frequency of mutations in the lacZ gene in liver of either C57B1/lacZ or c-myc/lacZ mice was significantly higher in mice treated with any one of the three HCAs than in mice given vehicle only. In addition, all three HCAs formed hepatic DNA adducts, as measured by the 32P-postlabeling analysis 24 h after dosing. In both strains of mice, hepatic DNA adduct levels were 2-3-fold higher with A alpha C than with either IQ or MeIQx, although the mutant frequencies in the lacZ gene were 30-40% lower in mice dosed with A alpha C. These results suggest that A alpha C-DNA adducts may be less mutagenic in vivo than either IQ- or MeIQx-DNA adducts. The lacZ mutant frequencies observed with all three HCAs appeared to be influenced by c-myc transgene expression: after HCA treatment, transgenic mice carrying the c-myc gene showed a 30-40% higher lacZ mutant frequency than mice not carrying this transgene. Notably, lacZ mutant frequencies were not different among C57B1/lacZ and c-myc/lacZ mice that received vehicle control. DNA adduct studies showed that the levels of IQ- and MeIQx-DNA adducts were 2-3-fold higher in c-myc/lacZ mice than in C57B1/lacZ mice; however, A alpha C DNA adducts were not statistically different between the two strains. In addition, phase 1 metabolic activation of these HCAs, as assessed by hepatic microsomal mutagenic activation, was also similar in both strains of mice. These results support the notion that overexpression of the c-myc oncogene cooperates with the HCAs to enhance in vivo mutagenicity. Further studies are needed to assess the mechanisms of this cooperative effect. JF - Mutation research AU - Davis, C D AU - Dacquel, E J AU - Schut, H A AU - Thorgeirsson, S S AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996/09/23/ PY - 1996 DA - 1996 Sep 23 SP - 287 EP - 296 VL - 356 IS - 2 SN - 0027-5107, 0027-5107 KW - Carbolines KW - 0 KW - DNA Adducts KW - Mutagens KW - Quinolines KW - Quinoxalines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - 2-amino-9H-pyrido(2,3-b)indole KW - P0GZ1ICS6X KW - Index Medicus KW - Animals KW - Liver -- cytology KW - Genes, myc KW - Mice KW - Mice, Transgenic KW - DNA Adducts -- drug effects KW - Liver -- chemistry KW - Gene Expression Regulation, Neoplastic KW - Microsomes -- chemistry KW - Mice, Inbred CBA KW - Liver -- drug effects KW - Mice, Inbred C57BL KW - Lac Operon KW - Female KW - Male KW - Microsomes -- drug effects KW - Quinolines -- toxicity KW - Mutagenesis -- drug effects KW - Quinoxalines -- toxicity KW - Carbolines -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78389252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=In+vivo+mutagenicity+and+DNA+adduct+levels+of+heterocyclic+amines+in+Muta+mice+and+c-myc%2FlacZ+double+transgenic+mice.&rft.au=Davis%2C+C+D%3BDacquel%2C+E+J%3BSchut%2C+H+A%3BThorgeirsson%2C+S+S%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1996-09-23&rft.volume=356&rft.issue=2&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-20 N1 - Date created - 1996-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of SOS mutagenesis by proteolysis. AN - 78352210; 8816793 AB - DNA damage-inducible mutagenesis in Escherichia coli is largely dependent upon the activity of the UmuD (UmuD') and UmuC proteins. The intracellular level of these proteins is tightly regulated at both the transcriptional and the posttranslational levels. Such regulation presumably allows cells to deal with DNA damage via error-free repair pathways before being committed to error-prone pathways. We have recently discovered that as part of this elaborate regulation, both the UmuD and the UmuC proteins are rapidly degraded in vivo. We report here that the enzyme responsible for their degradation is the ATP-dependent serine protease, Lon. In contrast, UmuD' (the posttranslational product and mutagenically active form of UmuD) is degraded at a much reduced rate by Lon, but is instead rapidly degraded by another ATP-dependent protease, ClpXP. Interestingly, UmuD' is rapidly degraded by ClpXP only when it is in a heterodimeric complex with UmuD. Formation of UmuD/UmuD' heterodimers in preference to UmuD' homodimers therefore targets UmuD' protein for proteolysis. Such a mechanism allows cells to reduce the intracellular levels of the mutagenically active Umu proteins and thereby return to a resting state once error-prone DNA repair has occurred. The apparent half-life of the heterodimeric UmuD/D' complex is greatly increased in the clpX::Kan and clpP::Kan strains and these strains are correspondingly rendered virtually UV non-mutable. We believe that these phenotypes are consistent with the suggestion that while the UmuD/D' heterodimer is mutagenically inactive, it still retains the ability to interact with UmuC, and thereby precludes the formation of the mutagenically active UmuD'2C complex. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Frank, E G AU - Ennis, D G AU - Gonzalez, M AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 1996/09/17/ PY - 1996 DA - 1996 Sep 17 SP - 10291 EP - 10296 VL - 93 IS - 19 SN - 0027-8424, 0027-8424 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Molecular Chaperones KW - UmuC protein, E coli KW - 98059-80-4 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Endopeptidase Clp KW - EC 3.4.21.92 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - ClpX protein, E coli KW - Index Medicus KW - Genotype KW - Gene Expression Regulation, Bacterial KW - Genes, Bacterial KW - Bacterial Proteins -- biosynthesis KW - DNA Damage KW - Restriction Mapping KW - Protein Processing, Post-Translational KW - Bacterial Proteins -- metabolism KW - Transcription, Genetic KW - Ultraviolet Rays KW - SOS Response (Genetics) KW - Adenosine Triphosphatases -- metabolism KW - Escherichia coli -- genetics KW - Mutagenesis KW - Escherichia coli -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78352210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Regulation+of+SOS+mutagenesis+by+proteolysis.&rft.au=Frank%2C+E+G%3BEnnis%2C+D+G%3BGonzalez%2C+M%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Frank&rft.aufirst=E&rft.date=1996-09-17&rft.volume=93&rft.issue=19&rft.spage=10291&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-13 N1 - Date created - 1996-11-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Microbiol Rev. 1992 Dec;56(4):592-621 [1480111] Nature. 1996 Apr 25;380(6576):727-30 [8614470] J Biol Chem. 1993 Oct 25;268(30):22618-26 [8226770] Curr Opin Genet Dev. 1993 Oct;3(5):719-25 [8274853] Mol Microbiol. 1994 Mar;11(6):1109-16 [8022280] J Biol Chem. 1994 Jul 8;269(27):18201-8 [8027081] J Bacteriol. 1994 Aug;176(16):5011-21 [8051014] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12218-22 [7991609] J Biol Chem. 1996 May 3;271(18):10767-74 [8631887] J Bacteriol. 1996 Jun;178(12):3550-6 [8655553] Mol Gen Genet. 1972;119(2):93-102 [4565757] Genetics. 1976 Feb;82(2):207-32 [770231] Bacteriol Rev. 1976 Dec;40(4):869-907 [795416] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] J Bacteriol. 1985 Apr;162(1):155-61 [2984171] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4336-40 [2989817] J Bacteriol. 1987 Mar;169(3):981-9 [3029041] Nature. 1987 Sep 10-16;329(6135):131-4 [3306404] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1806-10 [3126496] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1811-5 [3279417] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1816-20 [3279418] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7301-5 [2552436] J Bacteriol. 1989 Nov;171(11):6117-25 [2572581] J Mol Biol. 1990 Mar 5;212(1):79-96 [2108251] J Biol Chem. 1990 May 15;265(14):7886-93 [2186030] Methods Enzymol. 1990;185:119-29 [2199774] Mutat Res. 1990 Sep-Nov;236(2-3):301-11 [2169028] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7190-4 [2205854] J Bacteriol. 1991 Mar;173(5):1738-47 [1999391] Mol Gen Genet. 1991 Sep;229(1):10-6 [1654503] Mol Microbiol. 1991 Jul;5(7):1599-606 [1943696] J Bacteriol. 1992 Feb;174(4):1081-5 [1735703] Experientia. 1992 Feb 15;48(2):178-201 [1740190] J Bacteriol. 1992 May;174(10):3133-9 [1349601] Mol Gen Genet. 1992 Jun;233(3):443-8 [1320188] Mol Microbiol. 1992 Aug;6(16):2213-8 [1406263] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10777-81 [1438275] EMBO J. 1992 Dec;11(13):5121-7 [1464331] Mutat Res. 1995 Jan;336(1):39-48 [7528894] Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3274-7 [7724551] EMBO J. 1995 May 1;14(9):1867-77 [7743994] Trends Biochem Sci. 1995 Oct;20(10):416-20 [8533155] J Bacteriol. 1996 Jan;178(2):470-6 [8550468] EMBO J. 1996 Jan 15;15(2):437-44 [8617219] J Biol Chem. 1993 Oct 25;268(30):22609-17 [8226769] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dependence of agonist activation on a conserved apolar residue in the third intracellular loop of the AT1 angiotensin receptor. AN - 78337856; 8816747 AB - The coupling of agonist-activated seven transmembrane domain receptors to G proteins is known to involve the amino-terminal region of their third cytoplasmic loop. Analysis of the amino acids in this region of the rat type in angiotensin (AT1a) receptor identified Leu-222 as an essential residue in receptor activation by the physiological agonist, angiotensin II (Ang II). Nonpolar replacements for Leu-222 yielded functionally intact AT1 receptors, while polar or charged residues caused progressive impairment of Ang II-induced inositol phosphate generation. The decrease in agonist-induced signal generation was associated with a parallel reduction of receptor internalization, and was most pronounced for the Lys-222 mutant receptor. Although this mutant showed normal binding of the peptide antagonist, [Sar1,Ile6]Ang II, its affinity for Ang II was markedly reduced, consistent with its inability to adopt the high-affinity conformation. A search revealed that many Gq-coupled receptors contain an apolar amino acid (frequently leucine) in the position corresponding to Leu-222 of the AT1 receptor. These findings suggest that such a conserved apolar residue in the third intracellular loop is a crucial element in the agonist-induced activation of the AT1 and possibly many other G protein-coupled receptors. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hunyady, L AU - Zhang, M AU - Jagadeesh, G AU - Bor, M AU - Balla, T AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/09/17/ PY - 1996 DA - 1996 Sep 17 SP - 10040 EP - 10045 VL - 93 IS - 19 SN - 0027-8424, 0027-8424 KW - Inositol Phosphates KW - 0 KW - Receptor, Angiotensin, Type 1 KW - Receptors, Angiotensin KW - Recombinant Proteins KW - Angiotensin II KW - 11128-99-7 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - COS Cells KW - Inositol Phosphates -- metabolism KW - Amino Acid Sequence KW - Rats KW - Mutagenesis, Site-Directed KW - Endocytosis KW - Conserved Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Cytoplasm -- metabolism KW - Kinetics KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Cell Membrane -- metabolism KW - Sequence Homology, Amino Acid KW - Sequence Deletion KW - Muscle, Smooth -- metabolism KW - Protein Structure, Secondary KW - Angiotensin II -- metabolism KW - Receptors, Angiotensin -- chemistry KW - Receptors, Angiotensin -- physiology KW - Receptors, Angiotensin -- biosynthesis KW - Angiotensin II -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78337856?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Dependence+of+agonist+activation+on+a+conserved+apolar+residue+in+the+third+intracellular+loop+of+the+AT1+angiotensin+receptor.&rft.au=Hunyady%2C+L%3BZhang%2C+M%3BJagadeesh%2C+G%3BBor%2C+M%3BBalla%2C+T%3BCatt%2C+K+J&rft.aulast=Hunyady&rft.aufirst=L&rft.date=1996-09-17&rft.volume=93&rft.issue=19&rft.spage=10040&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-13 N1 - Date created - 1996-11-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1994 Mar 25;269(12):8831-41 [8132618] Exp Physiol. 1991 Nov;76(6):859-85 [1662965] Cell Signal. 1993 Sep;5(5):505-18 [8312128] J Biol Chem. 1994 Mar 4;269(9):6651-5 [8120019] J Biol Chem. 1994 Apr 15;269(15):11537-41 [8157684] FEBS Lett. 1994 Aug 8;349(3):365-70 [8050598] J Biol Chem. 1994 Aug 19;269(33):20815-8 [8063694] Receptors Channels. 1994;2(1):1-7 [8081729] J Biol Chem. 1994 Oct 7;269(40):24798-804 [7929158] Annu Rev Biochem. 1994;63:101-32 [7979235] Biochem Biophys Res Commun. 1994 Nov 15;204(3):1292-8 [7980607] J Biol Chem. 1994 Dec 16;269(50):31378-82 [7989302] J Biol Chem. 1995 Jan 6;270(1):207-13 [7814375] Pharmacol Rev. 1994 Dec;46(4):417-47 [7899472] Kidney Int. 1994 Dec;46(6):1492-5 [7699987] Kidney Int. 1994 Dec;46(6):1496-8 [7699988] J Biol Chem. 1995 Mar 31;270(13):7405-10 [7706286] J Biol Chem. 1995 Apr 28;270(17):9702-5 [7730346] J Biol Chem. 1995 Jul 14;270(28):16602-9 [7622467] J Biol Chem. 1995 Jul 14;270(28):16677-82 [7622477] J Biol Chem. 1991 Dec 25;266(36):24719-26 [1662215] J Biol Chem. 1992 Jan 25;267(3):1430-3 [1346134] J Biol Chem. 1982 Apr 25;257(8):4222-9 [6279628] Endocrinology. 1986 Jun;118(6):2312-8 [3698916] Endocrinology. 1986 Jun;118(6):2605-7 [2870918] J Biol Chem. 1987 Oct 25;262(30):14555-62 [2822694] Methods Enzymol. 1987;154:367-82 [3323813] J Clin Invest. 1989 Sep;84(3):840-6 [2760215] Endocr Rev. 1989 Nov;10(4):496-518 [2558878] Mol Pharmacol. 1990 Jun;37(6):775-9 [2163011] J Biol Chem. 1990 Sep 15;265(26):15713-23 [1975591] J Biol Chem. 1991 Feb 15;266(5):2783-8 [1993657] Mol Pharmacol. 1991 Feb;39(2):192-8 [1847493] J Bioenerg Biomembr. 1991 Feb;23(1):7-27 [2010435] Nature. 1991 May 16;351(6323):233-6 [2041570] DNA Cell Biol. 1992 Jan-Feb;11(1):1-20 [1310857] Biochem J. 1992 Apr 1;283 ( Pt 1):1-19 [1314560] Trends Biochem Sci. 1992 Jan;17(1):37-9 [1316650] Mol Pharmacol. 1992 Jun;41(6):1061-5 [1319546] J Biol Chem. 1993 Jan 5;268(1):337-41 [8380158] Biochem Biophys Res Commun. 1992 Dec 15;189(2):677-83 [1472039] Am J Physiol. 1993 Jan;264(1 Pt 1):C179-88 [8430765] J Biol Chem. 1993 Mar 5;268(7):4625-36 [8095262] J Biol Chem. 1993 Apr 15;268(11):8070-7 [8385135] EMBO J. 1993 Apr;12(4):1693-703 [8385611] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5133-7 [8506360] J Biol Chem. 1993 Aug 5;268(22):16483-7 [8393865] Biochem J. 1993 Sep 1;294 ( Pt 2):581-7 [8373373] Am J Kidney Dis. 1993 Nov;22(5):745-54 [8238023] J Biol Chem. 1995 Sep 22;270(38):22153-9 [7673193] Endocr Res. 1995 Feb-May;21(1-2):211-7 [7588383] J Biol Chem. 1994 Jan 7;269(1):402-5 [8276826] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cloning and characterization of a novel human ribonuclease (RNase k6): increasing diversity in the enlarging ribonuclease gene family. AN - 78371772; 8836175 AB - The discovery of Ribonuclease k6 (RNase k6) was an unexpected result of our ongoing efforts to trace the evolutionary history of the ribonuclease gene family. The open reading frame of RNase k6, amplified from human genomic DNA, encodes a 150 amino acid polypeptide with eight cysteines and histidine and lysine residues corresponding to those found in the active site of the prototype, ribonuclease A. The single-copy gene encoding RNase k6 maps to human chromosome 14 and orthologous sequences were detected in both primate and non-primate mammalian species. A single mRNA transcript (1.5 kb) was detected in all human tissues tested, with lung representing the most abundant source. At the cellular level, transcripts encoding RNase k6 were detected in normal human monocytes and neutrophils (but not in eosinophils) suggesting a role for this ribonuclease in host defense. Of the five previously identified human ribonucleases of this group, RNase k6 is most closely related to eosinophil-derived neurotoxin (EDN), with 47% amino acid sequence identity; slight cross-reactivity between RNase k6 and EDN was observed on Western blots probed with polyclonal anti-EDN antiserum. The catalytic constants determined, Km = 5.0 microM and Kcat = 0.13 s-1, indicate that recombinant RNase k6 has approximately 40-fold less ribonuclease activity than recombinant EDN. The identification and characterization of RNase k6 has extended the ribonuclease gene family and suggests the possibility that there are others awaiting discovery. JF - Nucleic acids research AU - Rosenberg, H F AU - Dyer, K D AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/09/15/ PY - 1996 DA - 1996 Sep 15 SP - 3507 EP - 3513 VL - 24 IS - 18 SN - 0305-1048, 0305-1048 KW - Neurotoxins KW - 0 KW - Recombinant Proteins KW - Endoribonucleases KW - EC 3.1.- KW - Eosinophil-Derived Neurotoxin KW - Ribonucleases KW - ribonuclease k6 KW - EC 3.1.27.- KW - Index Medicus KW - Blotting, Northern KW - Open Reading Frames KW - Humans KW - Amino Acid Sequence KW - Chromosomes, Human, Pair 14 KW - Chromosome Mapping KW - Cross Reactions KW - Cloning, Molecular KW - Base Sequence KW - Blotting, Western KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Neurotoxins -- chemistry KW - Genetic Variation KW - Endoribonucleases -- chemistry KW - Endoribonucleases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78371772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Molecular+cloning+and+characterization+of+a+novel+human+ribonuclease+%28RNase+k6%29%3A+increasing+diversity+in+the+enlarging+ribonuclease+gene+family.&rft.au=Rosenberg%2C+H+F%3BDyer%2C+K+D&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1996-09-15&rft.volume=24&rft.issue=18&rft.spage=3507&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-07 N1 - Date created - 1996-11-07 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U64998; GENBANK; U64997 N1 - SuppNotes - Cited By: J Neurosci. 1994 Feb;14(2):538-44 [8301353] J Biol Chem. 1993 May 15;268(14):10686-93 [8486718] Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1677-81 [8127865] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6012-6 [8016107] Biochim Biophys Acta. 1994 Aug 2;1218(3):466-8 [8049276] Biochem Biophys Res Commun. 1994 Sep 30;203(3):1765-72 [7945327] J Biol Chem. 1995 Apr 7;270(14):7876-81 [7713881] Biochem J. 1995 Jun 1;308 ( Pt 2):547-50 [7772040] Eur J Biochem. 1995 May 15;230(1):242-9 [7601106] Nat Genet. 1995 Jun;10(2):219-23 [7663519] J Biol Chem. 1995 Sep 15;270(37):21539-44 [7665566] Nucleic Acids Res. 1995 Nov 11;23(21):4290-5 [7501448] J Reprod Fertil. 1973 May;33(2):263-74 [4707332] Nature. 1969 Jan 25;221(5178):340-4 [4974403] J Mol Evol. 1995 Dec;41(6):850-8 [8587129] Cancer Res. 1980 Oct;40(10):3740-4 [7438057] Anal Biochem. 1984 Jan;136(1):48-64 [6201087] Biochemistry. 1985 Sep 24;24(20):5480-6 [4074709] Biochemistry. 1986 Jun 17;25(12):3527-32 [2424496] J Immunol. 1986 Nov 1;137(9):2913-7 [3760576] Biochemistry. 1986 Nov 18;25(23):7255-64 [3467790] Science. 1987 Jul 17;237(4812):280-2 [2440105] Biochem Biophys Res Commun. 1987 Aug 14;146(3):1240-8 [3619929] Biochemistry. 1987 Apr 21;26(8):2189-94 [3304421] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8330-4 [3479795] Am J Trop Med Hyg. 1988 Mar;38(2):327-34 [2451444] Nucleic Acids Res. 1988 Jun 24;16(12):5491-502 [2838818] Biochemistry. 1988 Jun 14;27(12):4530-8 [3166997] J Biochem. 1988 Aug;104(2):289-96 [3182769] J Biochem. 1988 Dec;104(6):939-45 [3243767] Proc Natl Acad Sci U S A. 1989 Jun;86(12):4460-4 [2734298] J Exp Med. 1989 Jul 1;170(1):163-76 [2473157] Proc Natl Acad Sci U S A. 1989 Aug;86(16):6211-4 [2762324] J Natl Cancer Inst. 1990 Jan 17;82(2):151-3 [2294226] Genomics. 1990 Aug;7(4):535-46 [2387583] Am J Hum Genet. 1990 Dec;47(6):973-81 [1978563] J Biol Chem. 1991 Jan 5;266(1):245-51 [1985896] Trends Biochem Sci. 1991 Mar;16(3):104-6 [2057997] Nucleic Acids Res. 1991 Dec 11;19(23):6469-74 [1754384] Nucleic Acids Res. 1991 Dec 25;19(24):6935-41 [1840677] Nucleic Acids Res. 1992 Feb 11;20(3):612 [1741299] J Biol Chem. 1992 Jul 25;267(21):14859-65 [1634526] Cancer Res. 1992 Sep 1;52(17):4582-6 [1511425] J Biol Chem. 1992 Oct 25;267(30):21982-6 [1400510] Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1217-21 [7679494] J Biol Chem. 1993 Feb 25;268(6):4499-503 [8095049] Cancer Res. 1994 Feb 15;54(4):920-7 [8313382] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular determinants in the plasma clearance and tissue distribution of ribonucleases of the ribonuclease A superfamily. AN - 78318618; 8797589 AB - The similarities and differences among members of the RNase A superfamily provide an ideal opportunity to examine the molecular basis for differences in their pharmacokinetics and biodistribution. Plasma clearances in BALB/c mice are similar among the five RNases studied: human pancreatic RNase, angiogenin, eosinophil-derived neurotoxin, onconase, and bovine seminal RNase. The average clearance is 0.13 ml/min or 60% of the glomerular filtration rate (measured by [14C]inulin clearance during continuous infusion from an i.p. implanted osmotic pump). Angiogenin has a higher volume of distribution and plasma-to-muscle transport rate than the other RNases, suggestive of binding to endothelial cells. Organ distribution differs dramatically among these RNases. The RNase most toxic to tumor cells, onconase, exhibits the longest retention in the kidneys: at 180 min, 50% of the injected dose is found in the kidneys, whereas only 1% or less of the other RNases is retained in the kidneys. Slower elimination of onconase from the kidneys may be due to a higher degree of binding in the kidney or a resistance to proteolytic degradation. To elucidate the molecular determinants involved in tissue uptake, we examined the biodistribution of recombinant onconase and two onconasepancreatic RNase chimeric proteins. The tissue retention property of onconase appears to be located in at least two regions, one of which is in the NH2-terminal 9-amino acid alpha-helix. The NH2-terminal pyroglutamate of onconase, a residue essential for ribonucleolytic activity and cytotoxicity, does not play a role in kidney retention. JF - Cancer research AU - Vasandani, V M AU - Wu, Y N AU - Mikulski, S M AU - Youle, R J AU - Sung, C AD - Biochemistry Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996/09/15/ PY - 1996 DA - 1996 Sep 15 SP - 4180 EP - 4186 VL - 56 IS - 18 SN - 0008-5472, 0008-5472 KW - Proteins KW - 0 KW - Inulin KW - 9005-80-5 KW - Ribonucleases KW - EC 3.1.- KW - angiogenin KW - EC 3.1.27.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Rana pipiens KW - Animals KW - Semen -- enzymology KW - Humans KW - Metabolic Clearance Rate KW - Mice KW - Tissue Distribution KW - Mice, Inbred BALB C KW - Ovum -- enzymology KW - Infusions, Parenteral KW - Seminal Vesicles -- enzymology KW - Proteins -- pharmacokinetics KW - Cattle KW - Glomerular Filtration Rate KW - Inulin -- pharmacokinetics KW - Time Factors KW - Female KW - Male KW - Ribonucleases -- blood KW - Ribonucleases -- isolation & purification KW - Ribonuclease, Pancreatic -- pharmacokinetics KW - Ribonuclease, Pancreatic -- blood KW - Ribonucleases -- pharmacokinetics KW - Ribonuclease, Pancreatic -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78318618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Molecular+determinants+in+the+plasma+clearance+and+tissue+distribution+of+ribonucleases+of+the+ribonuclease+A+superfamily.&rft.au=Vasandani%2C+V+M%3BWu%2C+Y+N%3BMikulski%2C+S+M%3BYoule%2C+R+J%3BSung%2C+C&rft.aulast=Vasandani&rft.aufirst=V&rft.date=1996-09-15&rft.volume=56&rft.issue=18&rft.spage=4180&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HSP binding and mitochondrial localization of p53 protein in human HT1080 and mouse C3H10T1/2 cell lines. AN - 78388801; 8841381 AB - In normal cells, the tumor suppressor actions of p53 protein are mediated by specific DNA binding and protein-protein interactions within the nucleus. Mutant p53 proteins, however, often assume an aberrant conformation devoid of tumor suppressor activity and newly capable of binding to the cognate or inducible HSP70. Recent reports from our laboratory and others show that additional unknown proteins may also complex with mutant p53. In this study, we characterize p53:HSP complexes and their subcellular location in the transformed cell lines, human HT1080 and murine C3H10T1/2, which both contain aberrant p53 conformers. Immunoprecipitation and SDS-PAGE of p53 from whole cell lysates revealed the additional presence of a broad 70 kDa band and a 90 kDa band in both lines, while p53 isolated from nuclear lysates was free from other proteins. 2D-PAGE was used to isolate and identify HSP members from cytoplasmic and nuclear lysates by immunoprecipitation, Western blotting and protein sequencing. Anti-p53 immune complexes from cytoplasmic lysates contained not only HSC70 but also GRP75, GRP78 and a weakly basic 90 kDa protein, which may be related to HSP90. The inducible form of HSP70 was not complexed to p53 protein, even though expressed in these cells. Analysis of anti-HSP70, anti-GRP75 and anti-HSP90 immune complexes suggests that HSP members exist as performed complexes in the cytoplasm, but not the nucleus. The presence of the mitochondrial and endoplasmic reticular chaperones, GRP75 and GRP78, in p53:HSP complexes suggested that p53 might be found in these cytoplasmic organelles which was confirmed in mitochondria by biochemical and immunoelectron microscopic evidence. These studies suggest that newly identified members of p53:HSP complexes represent components of a chaperone program which affects the subcellular distribution of p53 protein in these transformed lines. JF - Biochimica et biophysica acta AU - Merrick, B A AU - He, C AU - Witcher, L L AU - Patterson, R M AU - Reid, J J AU - Pence-Pawlowski, P M AU - Selkirk, J K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. merrick@niehs.nih.gov Y1 - 1996/09/13/ PY - 1996 DA - 1996 Sep 13 SP - 57 EP - 68 VL - 1297 IS - 1 SN - 0006-3002, 0006-3002 KW - Carrier Proteins KW - 0 KW - HSC70 Heat-Shock Proteins KW - HSP70 Heat-Shock Proteins KW - HSP90 Heat-Shock Proteins KW - HSPA8 protein, human KW - Heat-Shock Proteins KW - Hspa8 protein, mouse KW - Membrane Proteins KW - Molecular Chaperones KW - Tumor Suppressor Protein p53 KW - glucose-regulated proteins KW - molecular chaperone GRP78 KW - Index Medicus KW - Fibrosarcoma KW - Animals KW - HSP70 Heat-Shock Proteins -- chemistry KW - Carrier Proteins -- chemistry KW - Molecular Chaperones -- metabolism KW - Humans KW - Cell Nucleus -- chemistry KW - Membrane Proteins -- analysis KW - Molecular Weight KW - Fibroblasts KW - Molecular Chaperones -- analysis KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Protein Conformation KW - HSP70 Heat-Shock Proteins -- metabolism KW - Molecular Chaperones -- chemistry KW - Carrier Proteins -- metabolism KW - Cell Nucleus -- ultrastructure KW - Membrane Proteins -- chemistry KW - Membrane Proteins -- metabolism KW - HSP70 Heat-Shock Proteins -- analysis KW - Amino Acid Sequence KW - Mice KW - Protein Binding KW - Cytoplasm -- chemistry KW - HSP90 Heat-Shock Proteins -- metabolism KW - Carrier Proteins -- analysis KW - Heat-Shock Proteins -- metabolism KW - Heat-Shock Proteins -- analysis KW - Tumor Suppressor Protein p53 -- analysis KW - Mitochondria -- ultrastructure KW - Mitochondria -- chemistry KW - Tumor Suppressor Protein p53 -- metabolism KW - Heat-Shock Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78388801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=HSP+binding+and+mitochondrial+localization+of+p53+protein+in+human+HT1080+and+mouse+C3H10T1%2F2+cell+lines.&rft.au=Merrick%2C+B+A%3BHe%2C+C%3BWitcher%2C+L+L%3BPatterson%2C+R+M%3BReid%2C+J+J%3BPence-Pawlowski%2C+P+M%3BSelkirk%2C+J+K&rft.aulast=Merrick&rft.aufirst=B&rft.date=1996-09-13&rft.volume=1297&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-07 N1 - Date created - 1996-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and characterization of a novel membrane-associated lymphocyte NAD:arginine ADP-ribosyltransferase. AN - 78271258; 8703012 AB - Mono-ADP-ribosylation is a post-translational modification of proteins in which the ADP-ribose moiety of NAD is transferred to proteins and is responsible for the toxicity of some bacterial toxins (e.g. cholera toxin and pertussis toxin). NAD:arginine ADP-ribosyltransferases cloned from human and rabbit skeletal muscle and from mouse lymphoma (Yac-1) cells are glycosylphosphatidylinositol-anchored and have similar enzymatic and physical properties; transferases cloned from chicken heterophils and red cells have signal peptides and may be secreted. We report here the cloning and characterization of an ADP-ribosyltransferase (Yac-2), also from Yac-1 lymphoma cells, that differs in properties from the previously identified eukaryotic transferases. The nucleotide and deduced amino acid sequences of the Yac-1 and Yac-2 transferases are 58 and 33% identical, respectively. The Yac-2 protein is membrane-bound but, unlike the Yac-1 enzyme, appears not to be glycosylphosphatidylinositol-anchored. The Yac-1 and Yac-2 enzymes, expressed as glutathione S-transferase fusion proteins in Escherichia coli, were used to compare their ADP-ribosyltransferase and NAD glycohydrolase activities. Using agmatine as the ADP-ribose acceptor, the Yac-1 enzyme was predominantly an ADP-ribosyltransferase, whereas the transferase and NAD glycohydrolase activities of the recombinant Yac-2 protein were equivalent. The deduced amino acid sequence of the Yac-2 transferase contained consensus regions common to several bacterial toxin and mammalian transferases and NAD glycohydrolases, consistent with the hypothesis that there is a common mechanism of NAD binding and catalysis among ADP-ribosyltransferases. JF - The Journal of biological chemistry AU - Okazaki, I J AU - Kim, H J AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/09/06/ PY - 1996 DA - 1996 Sep 06 SP - 22052 EP - 22057 VL - 271 IS - 36 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - NAD+ Nucleosidase KW - EC 3.2.2.5 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Cell Membrane -- enzymology KW - Humans KW - Rabbits KW - Amino Acid Sequence KW - Mice KW - Chromatography, High Pressure Liquid KW - Cloning, Molecular KW - Base Sequence KW - NAD+ Nucleosidase -- metabolism KW - DNA, Complementary -- chemistry KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - ADP Ribose Transferases -- chemistry KW - Lymphocytes -- enzymology KW - ADP Ribose Transferases -- metabolism KW - ADP Ribose Transferases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78271258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Evidence+for+overlapping+active+sites+for+17+alpha-ethynlestradiol+and+bilirubin+in+the+human+major+bilirubin+UDPglucuronosyltransferase.&rft.au=Ciotti%2C+M%3BOwens%2C+I+S&rft.aulast=Ciotti&rft.aufirst=M&rft.date=1996-08-06&rft.volume=35&rft.issue=31&rft.spage=10119&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U60881; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of neoplastic development in the liver by hepatocyte growth factor in a transgenic mouse model. AN - 78296601; 8790372 AB - Overexpression of the c-myc oncogene is associated with a variety of both human and experimental tumors, and cooperation of other oncogenes and growth factors with the myc family are critical in the evolution of the malignant phenotype. The interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in a transgenic mouse model has been analyzed. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Furthermore, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice, whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Santoni-Rugiu, E AU - Preisegger, K H AU - Kiss, A AU - Audolfsson, T AU - Shiota, G AU - Schmidt, E V AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/09/03/ PY - 1996 DA - 1996 Sep 03 SP - 9577 EP - 9582 VL - 93 IS - 18 SN - 0027-8424, 0027-8424 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Phenobarbital -- pharmacology KW - Apoptosis KW - Genes, myc KW - Humans KW - Mice KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Mice, Transgenic KW - Signal Transduction KW - Cell Division KW - Hepatocyte Growth Factor -- pharmacology KW - Liver Neoplasms, Experimental -- chemically induced KW - Cell Transformation, Neoplastic -- drug effects KW - Liver Neoplasms, Experimental -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78296601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Inhibition+of+neoplastic+development+in+the+liver+by+hepatocyte+growth+factor+in+a+transgenic+mouse+model.&rft.au=Santoni-Rugiu%2C+E%3BPreisegger%2C+K+H%3BKiss%2C+A%3BAudolfsson%2C+T%3BShiota%2C+G%3BSchmidt%2C+E+V%3BThorgeirsson%2C+S+S&rft.aulast=Santoni-Rugiu&rft.aufirst=E&rft.date=1996-09-03&rft.volume=93&rft.issue=18&rft.spage=9577&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1987 May 21-27;327(6119):239-42 [2952888] Oncogene. 1995 Feb 16;10(4):765-8 [7862454] Oncogene. 1989 Jun;4(6):715-24 [2543942] Cell. 1990 Jun 15;61(6):1137-46 [2350785] Biochem Biophys Res Commun. 1990 Jul 16;170(1):397-404 [2142596] Hepatology. 1990 Aug;12(2):295-300 [2167869] Hepatology. 1991 Jan;13(1):1-5 [1824837] Cell Growth Differ. 1990 Feb;1(2):87-95 [2085463] J Clin Invest. 1991 May;87(5):1853-7 [1827130] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7001-5 [1831266] EMBO J. 1991 Oct;10(10):2867-78 [1655405] FEBS Lett. 1991 Oct 21;291(2):229-32 [1657643] Adv Cancer Res. 1991;57:1-46 [1950701] Biochem Biophys Res Commun. 1991 Oct 31;180(2):1151-8 [1835383] Hepatology. 1992 Jan;15(1):1-4 [1530786] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):373-7 [1309612] Carcinogenesis. 1992 Jan;13(1):139-41 [1370768] J Biol Chem. 1992 Oct 5;267(28):20493-6 [1328201] J Cell Biol. 1992 Nov;119(3):629-41 [1383237] Mol Cell Biol. 1993 Jan;13(1):320-30 [8417334] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1937-41 [7680481] J Cell Biol. 1993 Apr;121(1):145-54 [8384622] Cancer Res. 1993 Apr 15;53(8):1719-23 [8467484] Carcinogenesis. 1993 Apr;14(4):731-5 [7682481] Am J Pathol. 1993 Jun;142(6):1823-30 [8506951] Cancer Res. 1993 Sep 15;53(18):4329-36 [8364928] Oncogene. 1994 Apr;9(4):1091-9 [8134112] Hepatology. 1994 Apr;19(4):962-72 [8138271] Hepatology. 1994 May;19(5):1157-63 [8175137] Curr Opin Genet Dev. 1994 Feb;4(1):102-8 [8193530] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4731-5 [8197126] Blood. 1994 Jul 1;84(1):151-7 [7517205] J Med Virol. 1994 Apr;42(4):357-65 [8046425] Cancer Res. 1994 Nov 15;54(22):5775-8 [7954397] J Surg Res. 1994 Dec;57(6):711-7 [7996851] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2572-6 [7708687] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2597-601 [7708691] Cancer Res. 1995 May 1;55(9):1963-70 [7728766] Carcinogenesis. 1995 Apr;16(4):841-3 [7728965] Hepatology. 1995 Jun;21(6):1543-6 [7768498] J Cell Biol. 1995 Jun;129(5):1177-80 [7775566] Jpn J Cancer Res. 1995 Aug;86(8):718-23 [7559093] Prog Clin Biol Res. 1995;391:337-45 [8532726] Hepatology. 1996 Jan;23(1):71-9 [8550051] Mol Biol Cell. 1996 Apr;7(4):495-504 [8730094] Clin Cancer Res. 1995 Feb;1(2):147-54 [9815967] Hepatology. 1995 Jan;21(1):106-12 [7806142] J Cell Biol. 1994 Dec;127(6 Pt 2):1783-7 [7806559] Res Commun Mol Pathol Pharmacol. 1994 Sep;85(3):271-8 [7827802] Nature. 1995 Feb 23;373(6516):699-702 [7854452] Nature. 1995 Feb 23;373(6516):702-5 [7854453] Cancer Res. 1988 Oct 1;48(19):5522-7 [3416306] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factors-beta protect primary rat hippocampal neuronal cultures from degeneration induced by beta-amyloid peptide. AN - 78477015; 8891264 AB - Treatment of primary rat embryo hippocampal neuronal cultures with 10(-5) M beta-amyloid peptide fragment 25-35 (A beta P) for 24 h resulted in a 60% decrease in cell viability as determined by MTT incorporation. When these cells were treated with 0.1-10 ng/ml of either transforming growth factor-beta (TGF-beta) 1, 2 or 3 for 24 h before exposure to A beta P, there was a 2.9-, 1.9-, and 3.2-fold increase in cell survival, respectively, compared to cells treated with A beta P alone. The viability of cells treated with A beta P and 0.1-10 ng/ml TGF-beta was comparable to that of cells not treated with A beta P. The protective effects were less pronounced at lower TGF-beta concentrations. The protective effects of pretreatment with TGF-beta were less striking in mouse CCL-N-2a and human SK-N-SH neuroblastoma cell lines. When all cells were treated with TGF-beta for 24 h following a 24 h exposure to A beta P, there was a trend toward increased cell viability which was less significant than pretreatment with TGFs-beta. An isoform-specific TGF-beta SELISA showed that primary hippocampal neuronal cultures and the neuroblastoma cell lines secrete all 3 TGF-beta isoforms. Based on our results, we propose that the increased expression of TGF-beta observed in brains of patients with Alzheimer's disease may offer some degree of neuroprotection. JF - Brain research AU - Ren, R F AU - Flanders, K C AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892-5055, USA. Y1 - 1996/09/02/ PY - 1996 DA - 1996 Sep 02 SP - 16 EP - 24 VL - 732 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Amyloid beta-Peptides KW - 0 KW - Culture Media, Conditioned KW - Neurotoxins KW - Peptide Fragments KW - Transforming Growth Factor beta KW - amyloid beta-protein (25-35) KW - Index Medicus KW - Rats KW - Fetus KW - Animals KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Humans KW - Mice KW - Neuroblastoma KW - Cell Line KW - Transforming Growth Factor beta -- pharmacology KW - Peptide Fragments -- toxicity KW - Neurons -- drug effects KW - Amyloid beta-Peptides -- toxicity KW - Neurons -- cytology KW - Hippocampus -- cytology KW - Neurotoxins -- toxicity KW - Peptide Fragments -- antagonists & inhibitors KW - Amyloid beta-Peptides -- antagonists & inhibitors KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78477015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Transforming+growth+factors-beta+protect+primary+rat+hippocampal+neuronal+cultures+from+degeneration+induced+by+beta-amyloid+peptide.&rft.au=Ren%2C+R+F%3BFlanders%2C+K+C&rft.aulast=Ren&rft.aufirst=R&rft.date=1996-09-02&rft.volume=732&rft.issue=1-2&rft.spage=16&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-06 N1 - Date created - 1997-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regional MRI measurements of the corpus callosum: a methodological and developmental study. AN - 85222403; pmid-8891233 AB - A technique for quantifying the midsagittal size and shape of the corpus callosum (CC) from magnetic resonance brain scans is presented. The technique utilizes the distances to the ventral and dorsal boundaries of small sectors of the CC from a reference point to compute the size and shape parameters of the CC and its subdivisions. Intrarater and interrater interclass correlation coefficients for the area measurements ranged from 0.88 to 0.99. Correlations between these automated measures and those obtained by pixel counting were equally high. The corpus callosa of 104 (57 male and 47 female) right-handed healthy children and adolescents, ages 4-18, were examined in relation to age and sex. Corpus callosum growth was most striking for the splenium and isthmus with some changes in the midbody regions. The area and perimeter of these regions increased, shapes became more compact, and the boundaries became more regular with age. The length and curvature at the anterior and posterior regions of the CC increased more rapidly in males than in females. These significant and consistent results indicate that the method is reliable and sensitive to developmental changes of the CC. JF - Brain and Development AU - Rajapakse, J C AU - Giedd, J N AU - Rumsey, J M AU - Vaituzis, A C AU - Hamburger, S D AU - Rapoport, J L AD - Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1600, USA. PY - 1996 SP - 379 EP - 388 VL - 18 IS - 5 SN - 0387-7604, 0387-7604 KW - Magnetic Resonance Imaging KW - Regression Analysis KW - Reference Values KW - Reproducibility of Results KW - Sex Characteristics KW - Human KW - Corpus Callosum KW - Child KW - Child, Preschool KW - Observer Variation KW - Adolescent KW - Image Processing, Computer-Assisted KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85222403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+Development&rft.atitle=Regional+MRI+measurements+of+the+corpus+callosum%3A+a+methodological+and+developmental+study.&rft.au=Rajapakse%2C+J+C%3BGiedd%2C+J+N%3BRumsey%2C+J+M%3BVaituzis%2C+A+C%3BHamburger%2C+S+D%3BRapoport%2C+J+L&rft.aulast=Rajapakse&rft.aufirst=J&rft.date=1996-09-01&rft.volume=18&rft.issue=5&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=Brain+and+Development&rft.issn=03877604&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Hodgkin's disease: old and recent clinical concepts. AN - 85172533; pmid-8800065 AB - The diagnosis of Hodgkin's disease (HD) is still primarily based on the histopathologic criteria presented by Lukes et al in 1965. Over the past three decades, however, advances in immunohistochemistry, molecular studies, and virologic findings have provided evidence that HD exhibits significant heterogeneity. Whereas the nodular sclerosis subtype is the major subset of the "classic" disease, it has become evident that the nodular, lymphocytic predominance subtype may represent a minor distinct subset, and possibly a distinct disease entity. Furthermore, there is strong evidence that the mixed cellularity subtype may be an Epstein-Barr virus-related disorder. Finally, based on phenotypic and genotypic features, the existence of a "continuum" between a fraction of HD cases, including the lymphocytic depletion subtype, and CD30-positive anaplastic large cell lymphomas has been suggested. JF - The Annals of Otology, Rhinology, and Laryngology AU - Carbone, A AU - Weiss, L M AU - Gloghini, A AU - Ferlito, A AD - Division of Pathology, National Cancer Institute, IRCCS, Aviano, Italy. PY - 1996 SP - 751 EP - 758 VL - 105 IS - 9 SN - 0003-4894, 0003-4894 KW - HIV Infections KW - Humans KW - Herpesvirus 4, Human KW - Immunophenotyping KW - Reed-Sternberg Cells KW - Hodgkin Disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85172533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+Otology%2C+Rhinology%2C+and+Laryngology&rft.atitle=Hodgkin%27s+disease%3A+old+and+recent+clinical+concepts.&rft.au=Carbone%2C+A%3BWeiss%2C+L+M%3BGloghini%2C+A%3BFerlito%2C+A&rft.aulast=Carbone&rft.aufirst=A&rft.date=1996-09-01&rft.volume=105&rft.issue=9&rft.spage=751&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+Otology%2C+Rhinology%2C+and+Laryngology&rft.issn=00034894&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Protection from radiation-induced alopecia with topical application of nitroxides: fractionated studies. AN - 78778192; 9166544 AB - Hair loss resulting from irradiation of the head and neck or from whole brain irradiation often leads to cosmetic, social, and psychological problems for the radiotherapy patient. Few successful clinical interventions are available. We have shown that nitroxides (stable free radicals) afford radiation protection against single-dose radiation-induced alopecia in a guinea pig model. Here we determine if topical nitroxide application provides protection from fractionated radiation treatment. Two symmetrical and contralateral areas (3 x 5 cm) of skin on the dorsal trunk of guinea pigs were shaved to a hair length of 0.25 cm. A 2 mL solution containing 70 mg/mL nitroxide (Tempo or Tempol) in 70% ethanol was topically applied to the skin surface of one side; 70% ethanol was applied to the contralateral (control) side 10 minutes before irradiation. Animals were placed in a special jig that held skin without decreasing blood flow to the treatment area and fractionated external beam radiation (7 Gy) was delivered daily for eight fractions over 10 days via a 4 MeV linear accelerator. Alopecia (hair density) was scored weekly for 13 to 14 weeks after radiotherapy, using a standardized reference with respect to hair loss and regrowth in the treatment field. After radiation treatment, dry desquamation and gradual hair loss were observed for both control and nitroxide-treated skin; however, over weeks 4 to 11 postirradiation hair loss was much more pronounced in control animals when compared with nitroxide-treated animals. Hair density measurements for Tempol treatment over weeks 9 to 13 were approximately 75% compared with measurements in controls of approximately 25%. Tempo-treated animals exhibited hair density values of approximately 90% compared with 12% in controls over weeks 11 to 14. Tempol and Tempo treatments resulted in significant radioprotection. Histologic evaluation showed that radiation treatment alone in ethanol controls resulted in a marked decrease in the number of hair follicles and poor development of remaining follicles; however, nitroxide pretreatment resulted in no appreciable decrease in hair follicles and hair follicles appeared mature. This was also observed in unirradiated ethanol controls. Electron paramagnetic resonance studies revealed that topical nitroxide application did not result in measurable systemic concentrations of either drug. The results of this study suggest that topical application of nitroxides may be useful in a clinical setting to reduce the undesirable toxicity of radiation-induced alopecia. JF - The cancer journal from Scientific American AU - Cuscela, D AU - Coffin, D AU - Lupton, G P AU - Cook, J A AU - Krishna, M C AU - Bonner, R F AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 273 EP - 278 VL - 2 IS - 5 SN - 1081-4442, 1081-4442 KW - Cyclic N-Oxides KW - 0 KW - Radiation-Protective Agents KW - Spin Labels KW - tempol KW - U78ZX2F65X KW - TEMPO KW - VQN7359ICQ KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Electron Spin Resonance Spectroscopy KW - Head and Neck Neoplasms -- radiotherapy KW - Laser-Doppler Flowmetry KW - Female KW - Administration, Topical KW - Cyclic N-Oxides -- therapeutic use KW - Radiation-Protective Agents -- therapeutic use KW - Radiation-Protective Agents -- administration & dosage KW - Alopecia -- etiology KW - Radiation Injuries, Experimental -- etiology KW - Radiation Injuries, Experimental -- prevention & control KW - Alopecia -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78778192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+cancer+journal+from+Scientific+American&rft.atitle=Protection+from+radiation-induced+alopecia+with+topical+application+of+nitroxides%3A+fractionated+studies.&rft.au=Cuscela%2C+D%3BCoffin%2C+D%3BLupton%2C+G+P%3BCook%2C+J+A%3BKrishna%2C+M+C%3BBonner%2C+R+F%3BMitchell%2C+J+B&rft.aulast=Cuscela&rft.aufirst=D&rft.date=1996-09-01&rft.volume=2&rft.issue=5&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-10-24 N1 - Date created - 2006-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic and antitumor activity of a recombinant tumor necrosis factor-B1(Fv) fusion protein on LeY antigen-expressing human cancer cells. AN - 78773442; 9816329 AB - We have constructed a fusion protein composed of tumor necrosis factor alpha (TNF-alpha) fused at its COOH terminus to the scFv region of monoclonal antibody (mAb) B1, an antibody that recognizes LeY antigen present on many human cancer cells. Our rationale for fusing the scFv to the COOH terminus of TNF was to diminish the binding of the fusion protein to TNF receptors because the COOH terminus of TNF is involved in binding, and thus to partially inactivate (detoxify) the molecule. The Fv region should then target and accumulate the fusion protein on cancer cells, which should compensate for the reduced binding affinity of the TNF moiety and lead to selective killing of TNF-sensitive antigen-expressing cancer cells. The fusion protein was expressed in Escherichia coli and found in insoluble inclusion bodies. After refolding and purification by anion exchange, Ni-NTA affinity, and size-exclusion chromatography, we obtained monomeric TNF-B1(Fv). This molecule binds to LeY antigen on cancer cells with the same affinity as B1(scFv) and B1(scFv) immunotoxins but with significantly lower affinity to the TNF receptor compared to the TNF trimer. TNF-B1(Fv) is very toxic to LeY antigen-expressing cancer cells that are sensitive to TNF (e.g., MCF-7 breast or CRL-1739 gastric cancer cells). This cytotoxicity is antibody targeted and TNF mediated because it can be prevented (as shown on MCF-7 cells) by an antibody competing for LeY antigen binding and by an antibody that neutralizes TNF-alpha. TNF-B1(Fv) kills TNF-alpha-sensitive cells that do not express the target antigen only at much higher doses than TNF trimer, and it does not kill LeY-bearing but TNF-alpha-resistant cells. TNF-B1(Fv) can cause significant tumor regression of MCF-7 tumor xenografts in mice at doses that are not toxic to the mice. Thus, the reduced binding of the TNF moiety to TNF receptors, combined with binding of the B1(Fv) portion to LeY antigen, makes TNF-B1(Fv) an agent for selective killing of LeY-expressing TNF-sensitive cancer cells. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Scherf, U AU - Benhar, I AU - Webber, K O AU - Pastan, I AU - Brinkmann, U AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1523 EP - 1531 VL - 2 IS - 9 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Immunoglobulin Fragments KW - Lewis Blood-Group System KW - Lewis Y antigen KW - Receptors, Tumor Necrosis Factor KW - Recombinant Fusion Proteins KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Plasmids -- genetics KW - Humans KW - Gene Expression KW - Mice KW - Mice, Nude KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Neoplasm Transplantation KW - Antibody Specificity KW - Cytotoxicity, Immunologic KW - Tumor Cells, Cultured -- immunology KW - Breast Neoplasms -- pathology KW - Recombinant Fusion Proteins -- genetics KW - Breast Neoplasms -- prevention & control KW - Transplantation, Heterologous KW - Recombinant Fusion Proteins -- pharmacology KW - Receptors, Tumor Necrosis Factor -- metabolism KW - Mice, SCID KW - Antineoplastic Agents -- therapeutic use KW - Female KW - Lewis Blood-Group System -- metabolism KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Immunoglobulin Fragments -- genetics KW - Lewis Blood-Group System -- biosynthesis KW - Tumor Necrosis Factor-alpha -- metabolism KW - Immunoglobulin Fragments -- immunology KW - Tumor Necrosis Factor-alpha -- genetics KW - Lewis Blood-Group System -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78773442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Cytotoxic+and+antitumor+activity+of+a+recombinant+tumor+necrosis+factor-B1%28Fv%29+fusion+protein+on+LeY+antigen-expressing+human+cancer+cells.&rft.au=Scherf%2C+U%3BBenhar%2C+I%3BWebber%2C+K+O%3BPastan%2C+I%3BBrinkmann%2C+U&rft.aulast=Scherf&rft.aufirst=U&rft.date=1996-09-01&rft.volume=2&rft.issue=9&rft.spage=1523&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ha-ras oncogene transformation abolishes retinoic acid-induced reduction of intracellular fibronectin. AN - 78744286; 9181055 AB - All-trans-retinoic acid (RA) is a master regulator of cell differentiation and in this process it greatly influences cell adhesion and the elaboration of the extracellular matrix. Therefore, we were interested in the effect of RA on the biosynthesis of fibronectin (FN). RA reduced the level of intracellular FN in a time- and concentration-dependent fashion in NIH-3T3 cells, but not in NIH-3T3 cells transformed by an activated Ha-ras oncogene. Since the steady-state level of FN transcripts did not change after treatment of the cells with RA for various times or concentrations, RA probably acts at the translational level. In NIH-3T3 cells, RA had distinct effects on different receptors, from decreasing retinoic acid receptor (RAR)alpha to increasing RAR beta expression to no effect on RAR gamma. Transformation of NIH-3T3 cells with an activated Ha-ras oncogene downmodulated RAR expression and also abolished responsiveness to RA. A variety of approaches permitted the following conclusions: 1) RA-dependent FN downmodulation is mediated by RARs, 2) retinoid X receptors (RXRs) mediate the observed reduction of RAR alpha by RA, and 3) the blockade of RA responsiveness by Ha-ras-transfected cells cannot be overcome by overexpression of RAR alpha. These studies have identified fibronectin and RAR alpha as RA targets in fibroblast cells and have shown that oncogenic transformation renders the cells resistant to RA action. JF - Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas AU - De-Luca, L M AU - Scita, G AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1127 EP - 1131 VL - 29 IS - 9 SN - 0100-879X, 0100-879X KW - Fibronectins KW - 0 KW - Tretinoin KW - 5688UTC01R KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - Index Medicus KW - Humans KW - Intracellular Membranes KW - Gene Expression Regulation KW - Fibronectins -- physiology KW - Tretinoin -- physiology KW - Genes, ras -- physiology KW - Proto-Oncogene Proteins p21(ras) -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78744286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brazilian+journal+of+medical+and+biological+research+%3D+Revista+brasileira+de+pesquisas+medicas+e+biologicas&rft.atitle=Ha-ras+oncogene+transformation+abolishes+retinoic+acid-induced+reduction+of+intracellular+fibronectin.&rft.au=De-Luca%2C+L+M%3BScita%2C+G&rft.aulast=De-Luca&rft.aufirst=L&rft.date=1996-09-01&rft.volume=29&rft.issue=9&rft.spage=1127&rft.isbn=&rft.btitle=&rft.title=Brazilian+journal+of+medical+and+biological+research+%3D+Revista+brasileira+de+pesquisas+medicas+e+biologicas&rft.issn=0100879X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-20 N1 - Date created - 1997-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicological and environmental health information from the National Library of Medicine. AN - 78656696; 8989844 AB - The National Library of Medicine's Toxicology and Environmental Health Information Program is the outgrowth of a 1966 document on "Handling of Toxicological Information," prepared by the Presidents Science Advisory Committee (National Library of Medicine, 1995). The Toxicology and Environmental Health Program is responsible for the creation and deployment of both bibliographic and factual files concerned with toxicology, carcinogenesis, developmental and reproductive effects of chemical substances, toxic chemical releases, and the medical and environmental behavior of chemical substances. The two main computer systems that provide bibliographic and factual data banks are Toxicology Data Network (TOXNET) and ELHILL. A number of the files found in the TOXNET system are built and maintained by other federal agencies such as the National Cancer Institute, the U.S. Environmental Protection Agency, the National Institute for Occupational Safety and Health. JF - Toxicology and industrial health AU - Fonger, G C AD - National Library of Medicine, Division of Specialized Information Services, Toxicology and Environmental Health Information Program, Bethesda, Maryland 20894, USA. tehip@teh.nlm.nih.gov PY - 1996 SP - 639 EP - 649 VL - 12 IS - 5 SN - 0748-2337, 0748-2337 KW - Carcinogens KW - 0 KW - Environmental Pollutants KW - Index Medicus KW - United States KW - Animals KW - United States Environmental Protection Agency KW - Environmental Pollutants -- toxicity KW - Reproduction -- drug effects KW - Humans KW - Carcinogens -- toxicity KW - Terminology as Topic KW - Online Systems -- standards KW - National Library of Medicine (U.S.) KW - Toxicology -- trends KW - Environmental Health -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78656696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Transforming+growth+factor+beta+1+suppresses+genomic+instability+independent+of+a+G1+arrest%2C+p53%2C+and+Rb.&rft.au=Glick%2C+A+B%3BWeinberg%2C+W+C%3BWu%2C+I+H%3BQuan%2C+W%3BYuspa%2C+S+H&rft.aulast=Glick&rft.aufirst=A&rft.date=1996-08-15&rft.volume=56&rft.issue=16&rft.spage=3645&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-24 N1 - Date created - 1997-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2-Methoxyacetic acid (MAA)-induced spermatocyte apoptosis in human and rat testes: an in vitro comparison. AN - 78614431; 8957698 AB - 2-Methoxyethanol (2-ME) produces adverse reproductive effects in humans at an exposure level that is about 60-fold lower (2.6 mg/m3) than the concentration toxic to rat testes (167 mg/m3), suggesting that humans are much more sensitive to the testicular toxicity of 2-ME than rats. Previous studies found that 2-ME-induced germ cell death seen in vivo could be faithfully mimicked in vitro only in cultured seminiferous tubules, using the active metabolite methoxyacetic acid (MAA). To test whether human testis per se is more sensitive than rat testis to MAA, we compared the responses of cultured rat seminiferous tubules (RSTs) and human testicular tissues (HTT) in vitro. Degeneration in spermatocytes was observed in RSTs 19 hours after a 5-hour exposure to MAA at and above 1 mM. The dying germ cells showed necrotic-like morphology, as seen in vivo. Germ cells in HTT were also killed by doses > or = 1 mM, although the dying germ cells appeared apoptotic, rather than necrotic. For both species, doses lower than 1 mM were without visible effect. Interestingly, agarose gel electrophoresis of DNA from tubules of both species showed internucleosomal DNA fragmentation after MAA treatment, indicating that MAA induced apoptosis in both human and rat germ cells, though the dying cells showed different morphology in the two species. Furthermore, MAA-induced germ cell apoptosis in both species could be significantly attenuated by calcium channel blockers such as nifedipine or verapamil, which inhibit calcium movement through plasma membranes. In conclusion, the results suggest that: 1) human testis is equally sensitive to MAA compared to rat testis; and 2) MAA induces germ cell apoptosis both in human and rat, probably through similar, calcium-dependent mechanism(s). The precise steps in this germ cell apoptosis are under investigation. JF - Journal of andrology AU - Li, L H AU - Wine, R N AU - Chapin, R E AD - Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1996 SP - 538 EP - 549 VL - 17 IS - 5 SN - 0196-3635, 0196-3635 KW - Acetates KW - 0 KW - Calcium Channel Blockers KW - Verapamil KW - CJ0O37KU29 KW - methoxyacetic acid KW - F11T1H7Q7W KW - Nifedipine KW - I9ZF7L6G2L KW - Index Medicus KW - Animals KW - Seminiferous Tubules -- drug effects KW - Humans KW - Verapamil -- pharmacology KW - Nifedipine -- pharmacology KW - Rats KW - Culture Techniques KW - Rats, Sprague-Dawley KW - Testis -- drug effects KW - Calcium Channel Blockers -- pharmacology KW - Seminiferous Tubules -- cytology KW - DNA Fragmentation KW - Male KW - Testis -- cytology KW - Apoptosis -- drug effects KW - Spermatocytes -- drug effects KW - Acetates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78614431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+andrology&rft.atitle=2-Methoxyacetic+acid+%28MAA%29-induced+spermatocyte+apoptosis+in+human+and+rat+testes%3A+an+in+vitro+comparison.&rft.au=Li%2C+L+H%3BWine%2C+R+N%3BChapin%2C+R+E&rft.aulast=Li&rft.aufirst=L&rft.date=1996-09-01&rft.volume=17&rft.issue=5&rft.spage=538&rft.isbn=&rft.btitle=&rft.title=Journal+of+andrology&rft.issn=01963635&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-04 N1 - Date created - 1997-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of chronic administration of N-(4-hydroxyphenyl)retinamide (4-HPR) in rats on vitamin A metabolism in the eye. AN - 78593397; 8983293 AB - The retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) effectively inhibits cancer in a variety of tissues. In contrast to many other retinoids, the toxicity problems associated with administration of 4-HPR have been found to be minimal or absent. However, the effects of 4-HPR upon normal metabolism of native physiological forms of vitamin A in vivo have not been adequately investigated. To understand better the interaction between 4-HPR and the native physiological forms of vitamin A, the present study examines the effects of long-term administration of 4-HPR upon normal vitamin A metabolism in the eyes. Male Sprague-Dawley rats were fed either a control diet sufficient in vitamin A (CON group; 0.8 retinol equivalents [RE]/g diet; n = 28) or a CON diet supplemented with 4-HPR (CON + 4-HPR group; 1173 micrograms 4-HPR/g diet; n = 28). Following an i.v. dose of physiologically radiolabelled retinol, associated with its normal plasma transport complex, the vitamin A content and radioactivity of the plasma and eyes were examined at different times over a 41 day period. Mean plasma retinol levels measured during the study period were significantly reduced in the CON + 4-HPR group as compared with the CON group (23.5 +/- 7.0 and 50.3 +/- 5.3 [mean +/- S.D.] micrograms/dl, respectively). From approximately 7 days post-dosing, vitamin A levels in the eyes of the 4-HPR-treated group steadily decreased such that by the end of the study, they were only approximately one-fifth those of the CON group (0.098 +/- 0.075 and 0.50 +/- 0.053 RE, respectively). Kinetic analysis of vitamin A turnover in the eyes indicated that there was no apparent down-regulation of the fraction of vitamin A leaving this tissue on a daily basis; these values were found to be similar in both groups, averaging 0.104 +/- 0.0393 and 0.113 +/- 0.0373 per day (mean +/- fractional standard deviation [F.S.D.]) for the CON and CON + 4-HPR groups, respectively. At the same time, the flow of vitamin A through the eyes was significantly decreased in the CON + 4-HPR group eyes (0.0162 +/- 0.101 microgram/day) as compared with the CON group (0.0604 +/- 0.0672 micrograms/day). Our results suggest that compensatory mechanisms that would normally function to conserve depleting ocular vitamin A stores may be blocked in the 4-HPR-treated animals and further, that the 4-HPR itself appears to be interfering with the normal uptake and/or metabolism of vitamin A in the eye. These findings may help to provide at least a partial explanation for the visual impairment problems that have been reported in human trials that include long-term administration of 4-HPR. JF - European journal of cancer (Oxford, England : 1990) AU - Lewis, K C AU - Zech, L A AU - Phang, J M AD - Laboratory of Nutritional and Molecular Regulation, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1803 EP - 1808 VL - 32A IS - 10 SN - 0959-8049, 0959-8049 KW - Antineoplastic Agents KW - 0 KW - Glycoproteins KW - Seminal Plasma Proteins KW - Zn-alpha-2-glycoprotein KW - Vitamin A KW - 11103-57-4 KW - Fenretinide KW - 187EJ7QEXL KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Administration Schedule KW - Glycoproteins -- analysis KW - Models, Biological KW - Male KW - Vitamin A -- blood KW - Eye -- metabolism KW - Fenretinide -- pharmacology KW - Vitamin A -- metabolism KW - Eye -- drug effects KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78593397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Effects+of+chronic+administration+of+N-%284-hydroxyphenyl%29retinamide+%284-HPR%29+in+rats+on+vitamin+A+metabolism+in+the+eye.&rft.au=Lewis%2C+K+C%3BZech%2C+L+A%3BPhang%2C+J+M&rft.aulast=Lewis&rft.aufirst=K&rft.date=1996-09-01&rft.volume=32A&rft.issue=10&rft.spage=1803&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-07 N1 - Date created - 1997-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Double biochemical modulation of 5-fluorouracil by methotrexate and levo-folinic acid in the treatment of advanced digestive tract malignancies. AN - 78588500; 8983280 AB - The aim of this study was to evaluate the activity and toxicity of a double biochemical modulation of 5-fluorouracil (5-FU) by means of methotrexate (MTX) and levo-folinic acid (LFA) in patients with advanced carcinoma of the digestive tract, and to assess the prognostic significance of MTX serum concentrations achieved in these patients. 94 patients affected by advanced carcinoma of the colon-rectum, stomach or biliary tract (47 of them previously untreated) received a regimen consisting of MTX 500 mg/m2 as a 2-h i.v. infusion on day 1, followed by LFA 250 mg/m2 as a 2-h i.v. infusion and 5-FU 600 mg/m2 as an i.v. bolus on day 2. Cycles were repeated every 2 weeks. Treatment was administered until tumour progression or for a maximum of 24 courses. MTX serum level was assessed soon after and 24 h (24-h MTXs) after its infusion in 61 patients. One complete and 22 partial responses were obtained, giving an overall activity of 24% (95% confidence interval, 16-34%). Response rate was 30% in chemotherapy-naive patients (colorectal, 26%; gastric, 37%; and biliary-tract, 22%) and 19% in those previously treated (all with fluoropyrimidines). A poor performance status adversely affected the response and survival of patients. The toxicity of treatment was very mild, and occurrence of severe diarrhoea (11% of patients) and mucositis (3%) was lower than that reported with other modulations of 5-FU. A cut-off value of 24-h MTXs was identified as a strong prognostic indicator. Patients with 24-h MTXs > or = 2 microM had a significantly better probability of response (37% versus 5%; P = 0.032), longer progression-free survival (5.3 versus 2.3 months; P = 0.023) and overall survival (10.8 versus 8.3 months; P = 0.045) on multivariate analysis. In chemotherapy-naive colorectal cancer patients, those with 24-h MTXs > or = 2 microM had a response rate of 38% (3/8), with a 19.6-month median survival time, as compared to no responses (0/4) and a 9.9-month median survival in the group with a lower serum concentration. The achievement of such MTX serum levels yielded a 31% (4/13) response rate even in colorectal patients who had previously received a 5-FU-FA treatment. JF - European journal of cancer (Oxford, England : 1990) AU - Comella, P AU - Palmieri, G AU - Lorusso, V AU - Catalano, G AU - Nicollela, D AU - Ianniello, G P AU - Casaretti, R AU - Montella, M AU - Frasci, G AU - Perna, M AU - Comella, G AD - National Cancer Institute, Naples, Italy. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1719 EP - 1726 VL - 32A IS - 10 SN - 0959-8049, 0959-8049 KW - Antimetabolites, Antineoplastic KW - 0 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Drug Therapy, Combination KW - Survival Rate KW - Humans KW - Adult KW - Treatment Outcome KW - Leucovorin -- adverse effects KW - Aged KW - Middle Aged KW - Drug Synergism KW - Male KW - Female KW - Leucovorin -- therapeutic use KW - Fluorouracil -- therapeutic use KW - Fluorouracil -- adverse effects KW - Adenocarcinoma -- blood KW - Methotrexate -- blood KW - Methotrexate -- adverse effects KW - Digestive System Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- adverse effects KW - Methotrexate -- therapeutic use KW - Digestive System Neoplasms -- blood KW - Adenocarcinoma -- drug therapy KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78588500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Double+biochemical+modulation+of+5-fluorouracil+by+methotrexate+and+levo-folinic+acid+in+the+treatment+of+advanced+digestive+tract+malignancies.&rft.au=Comella%2C+P%3BPalmieri%2C+G%3BLorusso%2C+V%3BCatalano%2C+G%3BNicollela%2C+D%3BIanniello%2C+G+P%3BCasaretti%2C+R%3BMontella%2C+M%3BFrasci%2C+G%3BPerna%2C+M%3BComella%2C+G&rft.aulast=Comella&rft.aufirst=P&rft.date=1996-09-01&rft.volume=32A&rft.issue=10&rft.spage=1719&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-07 N1 - Date created - 1997-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of two commercial microtiter cytotoxin assays for the detection of Clostridium difficile toxin B in stool specimens. AN - 78587993; 8950530 AB - Two commercial microtiter cytotoxin assays using a fibroblast cell line (Bartels, Baxter Diagnostics, Inc., Deerfield, IL) and an epithelial cell line (Cytotoxi Test, Advanced Clinical Diagnostics, Toledo, OH) were evaluated for their ability to detect Clostridium difficile toxin B in stool specimens. After 48 hours, the assays had comparable sensitivity (90 versus 92%) and specificity (99 versus 98%). Although not statistically significant, the Bartels assay detected more toxin-positive specimens at 24 hours (84 versus 72%, P = 0.089, Fisher's Exact Test) and the Cytotoxi assay had fewer nonspecific reactions requiring repeat testing (2.2 versus 1.1%, P = 0.186, Fisher's Exact Test). Both cytotoxin assays had comparable analytic performance. JF - Diagnostic microbiology and infectious disease AU - Fedorko, D P AU - Williams, E C AD - Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 47 EP - 51 VL - 26 IS - 1 SN - 0732-8893, 0732-8893 KW - Cytotoxins KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Feces -- microbiology KW - False Negative Reactions KW - Cells, Cultured KW - Humans KW - Fibroblasts KW - False Positive Reactions KW - Cytotoxins -- isolation & purification KW - Biological Assay -- methods KW - Enterocolitis, Pseudomembranous -- diagnosis KW - Clostridium difficile -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78587993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diagnostic+microbiology+and+infectious+disease&rft.atitle=Evaluation+of+two+commercial+microtiter+cytotoxin+assays+for+the+detection+of+Clostridium+difficile+toxin+B+in+stool+specimens.&rft.au=Fedorko%2C+D+P%3BWilliams%2C+E+C&rft.aulast=Fedorko&rft.aufirst=D&rft.date=1996-09-01&rft.volume=26&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Diagnostic+microbiology+and+infectious+disease&rft.issn=07328893&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-21 N1 - Date created - 1997-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lupus nephritis. AN - 78569435; 8941444 AB - Both immune and nonimmune mechanisms are operant in lupus nephritis. Recent findings have begun to elucidate fundamental questions in the pathogenesis of the disease. Genetic linkage studies have identified susceptibility loci contributing to nephritis in lupus-prone mice. Polymorphisms of the Fc gamma Rlla gene have been found to correlate with the development of renal disease in black Americans and white Europeans. Genetic factors are important in determining both predisposition to nephritis and outcome (and likely response to therapy). In lupus nephritis, prevention of tissue injury involves effective immunosuppressive therapy and aggressive management of hypertension and hyperlipidemia. Although with intensive immunosuppressive therapy most lupus patients achieve remission, a substantial number of these patients either do not respond, respond partially, or relapse after discontinuation of therapy. Moreover, the toxicity of available immunosuppressive drugs is substantial, suggesting that alternative therapeutic regimens are needed. In the future, other inhibitors of inflammatory, immune, vasoactive, proteolytic, and growth-promoting mediators are likely to play a role in the management of lupus nephritis. JF - Current opinion in rheumatology AU - Davis, J C AU - Tassiulas, I O AU - Boumpas, D T AD - National Institutes of Health, Arthritis and Rheumatism Branch, Bethesda, MD 20892-1828, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 415 EP - 423 VL - 8 IS - 5 SN - 1040-8711, 1040-8711 KW - Index Medicus KW - Animals KW - Humans KW - Kidney Failure, Chronic -- etiology KW - Lupus Nephritis -- therapy KW - Lupus Nephritis -- physiopathology KW - Lupus Nephritis -- diagnosis KW - Lupus Nephritis -- immunology KW - Lupus Nephritis -- complications KW - Lupus Nephritis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78569435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+rheumatology&rft.atitle=Lupus+nephritis.&rft.au=Davis%2C+J+C%3BTassiulas%2C+I+O%3BBoumpas%2C+D+T&rft.aulast=Davis&rft.aufirst=J&rft.date=1996-09-01&rft.volume=8&rft.issue=5&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+rheumatology&rft.issn=10408711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prediction of Salmonella mutagenicity. AN - 78554172; 8921509 AB - The ability of a number of prediction systems was examined to determine how well they could predict Salmonella mutagenicity. The prediction systems included two computer-based systems (CASE and TOPKAT), the measurement of a physiochemical parameter (ke) and the use of structural alerts by an expert chemist. The computer-based systems operators and the chemist were supplied with the structures of 100 chemicals that had been tested for mutagenicity in the Salmonella test; the actual chemicals were needed for the physiochemical measurement. None of the participants was provided with the chemical names or Salmonella test results prior to submitting their predictions. The three systems that predicted the mutagenicity from the structure of the chemicals produced equivalent results (71-76% concordance with the Salmonella results); the physiochemical system produced a lower (60-61%) concordance. JF - Mutagenesis AU - Zeiger, E AU - Ashby, J AU - Bakale, G AU - Enslein, K AU - Klopman, G AU - Rosenkranz, H S AD - Environmental Toxicology Program, NIEHS, Research Triangle Park, NC 27709, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 471 EP - 484 VL - 11 IS - 5 SN - 0267-8357, 0267-8357 KW - Mutagens KW - 0 KW - Index Medicus KW - Mutagenicity Tests -- methods KW - Databases, Factual KW - Predictive Value of Tests KW - Structure-Activity Relationship KW - Software KW - Salmonella -- drug effects KW - Salmonella -- genetics KW - Mutagens -- toxicity KW - Mutagens -- chemistry KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78554172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=Prediction+of+Salmonella+mutagenicity.&rft.au=Zeiger%2C+E%3BAshby%2C+J%3BBakale%2C+G%3BEnslein%2C+K%3BKlopman%2C+G%3BRosenkranz%2C+H+S&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1996-09-01&rft.volume=11&rft.issue=5&rft.spage=471&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-25 N1 - Date created - 1997-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of relapsed Hodgkin's disease. AN - 78553748; 8922246 AB - High-dose chemotherapy with peripheral stem cell or bone marrow transplantation has quickly become accepted as the standard of care for patients with Hodgkin's disease (HD) who are chemotherapy induction failures or who relapsed after a short initial remission. The majority of studies would indicate that high-dose therapy is most effective when used early. As a result of promising pilot studies, high-dose therapy is also being used more frequently in patients at initial relapse after a long remission. Future approaches to improve the efficacy of high-dose therapy in marrow transplantation will require more effective chemotherapeutic agents. Recent studies with the taxanes and camptothecins suggest that these agents may be useful (Devizzi et al, 1994). Biological approaches with CD30 based antibodies and immunotoxins may also be helpful adjuncts to conventional-dose debulking regimens. Radio-immunoconjugates may augment the delivery of myelo-ablative doses of radiation therapy selectively to tumours. When patients relapse after high-dose therapy, there has been no standard approach to management. However, single agent chemotherapy (e.g. weekly low-dose vinblastine) has the potential for significant palliation, occasionally for prolonged periods. JF - Bailliere's clinical haematology AU - Gause, B L AU - Longo, D L AD - Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 559 EP - 572 VL - 9 IS - 3 SN - 0950-3536, 0950-3536 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Treatment Failure KW - Antineoplastic Agents -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Salvage Therapy KW - Antineoplastic Agents -- therapeutic use KW - Recurrence KW - Hodgkin Disease -- radiotherapy KW - Hodgkin Disease -- drug therapy KW - Hodgkin Disease -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78553748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+haematology&rft.atitle=Treatment+of+relapsed+Hodgkin%27s+disease.&rft.au=Gause%2C+B+L%3BLongo%2C+D+L&rft.aulast=Gause&rft.aufirst=B&rft.date=1996-09-01&rft.volume=9&rft.issue=3&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+haematology&rft.issn=09503536&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-18 N1 - Date created - 1997-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prolonged therapy of chronic hepatitis C with ribavirin. AN - 78519081; 8914004 AB - Therapy with ribavirin for 6-12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000-1200 mg of ribavirin daily for 24 months. Serum aminotransferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long-term side-effects. JF - Journal of viral hepatitis AU - Hoofnagle, J H AU - Lau, D AU - Conjeevaram, H AU - Kleiner, D AU - Di Bisceglie, A M AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 247 EP - 252 VL - 3 IS - 5 SN - 1352-0504, 1352-0504 KW - Antiviral Agents KW - 0 KW - RNA, Viral KW - Ribavirin KW - 49717AWG6K KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Index Medicus KW - Liver -- virology KW - Liver -- pathology KW - Cholelithiasis -- complications KW - Hepacivirus -- genetics KW - Fatigue -- complications KW - Humans KW - Alanine Transaminase -- analysis KW - Biopsy KW - Headache -- complications KW - Adult KW - Hematocrit KW - Middle Aged KW - Male KW - Female KW - RNA, Viral -- analysis KW - Bile Duct Diseases -- complications KW - Antiviral Agents -- therapeutic use KW - Antiviral Agents -- administration & dosage KW - Ribavirin -- therapeutic use KW - Hepatitis C -- drug therapy KW - Hepatitis C -- blood KW - Ribavirin -- administration & dosage KW - Antiviral Agents -- adverse effects KW - Ribavirin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78519081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+viral+hepatitis&rft.atitle=Prolonged+therapy+of+chronic+hepatitis+C+with+ribavirin.&rft.au=Hoofnagle%2C+J+H%3BLau%2C+D%3BConjeevaram%2C+H%3BKleiner%2C+D%3BDi+Bisceglie%2C+A+M&rft.aulast=Hoofnagle&rft.aufirst=J&rft.date=1996-09-01&rft.volume=3&rft.issue=5&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Journal+of+viral+hepatitis&rft.issn=13520504&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-03 N1 - Date created - 1997-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination chemotherapy for advanced bilharzial bladder carcinoma. AN - 78513748; 8905036 AB - Carcinoma of the bilharzial bladder, the most common cancer in Egyptian patients has been, until recently, largely treated by surgery. We have studied the activity of a series of single agents in phase II trials and identified a number of active agents. Here we report the results of a trial in which therapeutic combinations of the most active agents were administered in alternating cycles to patients who had never received chemotherapy. The study included 30 patients with histologically proven inoperable (20), recurrent (5, 2 of whom subsequently developed metastases), or metastatic disease (5). There were 27 males and 3 females, with a median age of 48.5 years (range 29-65 years). Fourteen patients had squamous cell carcinoma, 12 had transitional cell carcinoma, 2 had adenocarcinoma, and the remaining 2 had undifferentiated carcinoma. Chemotherapy consisted of epidoxorubicin (120 mg/sqm i.v. d1) and vincristine (1.4 mg/sqm i.v., days 1 and 8) alternating with etoposide (100 mg/sqm i.v. infusion over 1 hour, days 1 to 5) and ifosfamide (1800 mg/sqm i.v. infusion over 2 hours, days 1 to 5). Mesna was given as a uroprotector at 40% of the ifosfamide dose at 0, 4, and 8 hours after the ifosfamide infusion. Courses were repeated every 3-4 weeks. Among the 22 evaluable patients, 8 (36.5%) had a partial and one (4.5%), a complete response, giving a response rate of 46%. Three more patients had responses that were less than a partial remission, and 6 patients showed disease stabilisation on chemotherapy. Toxicities were tolerable and consisted mainly of myelosuppression. Results were further analysed in relation to pathologic subtype, disease status at the start of chemotherapy, and the delivered dose intensity. No relationship was found between any of these parameters and response to therapy. Advanced bilharzial bladder cancer is relatively sensitive to combination chemotherapy, but complete remission and prolonged survival is rare in this subgroup of patients with advanced disease. Further studies will be needed to determine the relative efficacy of single agents and drug combinations. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Khaled, H M AU - Gad el-Mawla, N AU - el-Said, A AU - Hamza, M R AU - Gaafar, R AU - el-Attar, I AU - Abu Rabia, A AU - Magrath, I AD - Department of Medical Oncology, National Cancer Institute, Cairo, Egypt. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 751 EP - 754 VL - 7 IS - 7 SN - 0923-7534, 0923-7534 KW - Antibiotics, Antineoplastic KW - 0 KW - Antineoplastic Agents, Alkylating KW - Antineoplastic Agents, Phytogenic KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Mesna KW - NR7O1405Q9 KW - Ifosfamide KW - UM20QQM95Y KW - Index Medicus KW - Antibiotics, Antineoplastic -- administration & dosage KW - Dose-Response Relationship, Drug KW - Humans KW - Vincristine -- administration & dosage KW - Aged KW - Doxorubicin -- administration & dosage KW - Survival Rate KW - Etoposide -- administration & dosage KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Mesna -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Male KW - Mesna -- therapeutic use KW - Ifosfamide -- administration & dosage KW - Urinary Bladder Neoplasms -- pathology KW - Urinary Bladder Neoplasms -- drug therapy KW - Schistosomiasis -- complications KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Urinary Bladder Neoplasms -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78513748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Combination+chemotherapy+for+advanced+bilharzial+bladder+carcinoma.&rft.au=Khaled%2C+H+M%3BGad+el-Mawla%2C+N%3Bel-Said%2C+A%3BHamza%2C+M+R%3BGaafar%2C+R%3Bel-Attar%2C+I%3BAbu+Rabia%2C+A%3BMagrath%2C+I&rft.aulast=Khaled&rft.aufirst=H&rft.date=1996-09-01&rft.volume=7&rft.issue=7&rft.spage=751&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-14 N1 - Date created - 1997-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2, 4-dichloro phenoxy acetic acid alters monoamine levels, acetylcholinesterase activity & operant learning in rats. AN - 78494717; 8898484 AB - 2, 4-Dichloro phenoxy acetic acid (2, 4-D) was given at 100 mg/kg body weight per day by oral intubation from postnatal days 2 to 25 to assess its effect on the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in olfactory bulb (OB), hippocampus (HI), visual cortex (VC), cerebellum (CB) and brainstem (BS). NE levels were increased in OB, HI, VC and BS at 10 days of age. However, by 25 days, NE levels were decreased in OB, HI and VC. DA levels were also increased in OB, HI, VC and CB at 10 days of age and again decreased by 25 days in OB, HI and VC. 5-HT levels were increased in HI, CB and BS at 10 days and in VC and CB at 25 days of age. Reduced acetylcholinesterase (AChE) activity in OB and HI and monoamines in different brain regions at 25 days of age might be responsible for the observed deficits in both acquisition and rate of pedal press response when animals were exposed chronically to 2, 4-D during postnatal brain development. JF - The Indian journal of medical research AU - Lakshmana, M K AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health & Neurosciences, Bangalore. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 234 EP - 239 VL - 104 SN - 0971-5916, 0971-5916 KW - Biogenic Monoamines KW - 0 KW - Herbicides KW - 2,4-Dichlorophenoxyacetic Acid KW - 2577AQ9262 KW - Acetylcholinesterase KW - EC 3.1.1.7 KW - Index Medicus KW - Rats KW - Animals KW - Conditioning, Operant -- drug effects KW - Herbicides -- pharmacology KW - 2,4-Dichlorophenoxyacetic Acid -- pharmacology KW - Biogenic Monoamines -- metabolism KW - Acetylcholinesterase -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78494717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Indian+journal+of+medical+research&rft.atitle=2%2C+4-dichloro+phenoxy+acetic+acid+alters+monoamine+levels%2C+acetylcholinesterase+activity+%26amp%3B+operant+learning+in+rats.&rft.au=McMillian%2C+M+K%3BPennypacker%2C+K+R%3BThai%2C+L%3BWu%2C+G+C%3BSuh%2C+H+H%3BSimmons%2C+K+L%3BHudson%2C+P+M%3BSawin%2C+S+B%3BHong%2C+J+S&rft.aulast=McMillian&rft.aufirst=M&rft.date=1996-08-19&rft.volume=730&rft.issue=1-2&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-20 N1 - Date created - 1996-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies of oncogene activation and tumor suppressor gene inactivation in normal and neoplastic rodent tissue. AN - 78492221; 8898988 AB - Emerging short-term bioassays for chemically-induced carcinogenesis are dependent for their relevance to human risk assessment on the degree of coincidence of human and rodent tumor pathways. Since these pathways do not always converge, these new tests may have a number of unanticipated pitfalls. Models of liver and renal tumors are described. The results from Rb and p53 tumor suppressor gene transgenic animals are compared to human tumor syndromes. The question of mutagenic and epigenetic fingerprints of chemicals versus the cell-specific selection of spontaneous mutations is debated. Examples of specific pitfalls, such as the recently discovered Helicobacter hepaticus promoted liver tumors in mice are presented. The rat pseudogenes for p53 and the rare role of p53 in most important rodent tumor models other than epithelial tumors present experimental quandaries. The differential effects of carcinogens during various stages of rodent perinatal and adult development are also discussed. It is concluded that the pathways of both animal models and their human counterparts should be better identified so that realistic endpoint markers can be chosen for human carcinogenic risk assessment. JF - Mutation research AU - Buzard, G S AD - Intramural Research Support Program. SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. buzardg@mail.ncifcrf.gov Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 43 EP - 58 VL - 365 IS - 1-3 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Carcinogens -- toxicity KW - Disease Models, Animal KW - Mice KW - Neoplasms -- genetics KW - Gene Expression Regulation, Neoplastic KW - Oncogenes -- genetics KW - Genes, Tumor Suppressor -- genetics KW - Neoplasms, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78492221?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Nursing&rft.atitle=The+Birth-Weight%2FBattering+Connection&rft.au=Bullock%2C+Linda+F%3BMcFarlane%2C+Judith&rft.aulast=Bullock&rft.aufirst=Linda&rft.date=1989-09-01&rft.volume=89&rft.issue=9&rft.spage=1153&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Nursing&rft.issn=0002936X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of transgenic mouse bioassays for identifying carcinogens and noncarcinogens. AN - 78490970; 8898993 AB - Data supporting the use of transgenic lines to identify carcinogens and noncarcinogens are thus far based on a limited number of chemicals for which there are also long-term bioassay results in rats and/or mice. Six chemicals have been tested in the heterozygous p53-deficient mice and 13 in the Tg.AC line. The results show that the p53def responds rapidly to mutagenic carcinogens and the Tg.AC responds rapidly to both mutagenic and nonmutagenic carcinogens. Neither transgenic line responded to the noncarcinogens that were tested. The p53def line failed to respond to two nonmutagenic carcinogens (N-methyloacrylamide and reserpine), the Tg.AC line failed to respond to ethyl acrylate, a nonmutagenic chemical that induced tumors of the forestomach when administered by gavage, and to triethanolamine that caused an increase in hepatocellular tumors in B6C3F1 mice via skin painting. Both of the latter chemicals are examples of highly specific responses related to either route of administration or to strain susceptibility. Further efforts to evaluate the range of chemicals to which these transgenic lines respond are currently in progress. JF - Mutation research AU - Tennant, R W AU - Spalding, J AU - French, J E AD - National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, NC 27709, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 119 EP - 127 VL - 365 IS - 1-3 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Carcinogens -- toxicity KW - Mice KW - Neoplasms, Experimental KW - Mutagenicity Tests -- methods KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78490970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Evaluation+of+transgenic+mouse+bioassays+for+identifying+carcinogens+and+noncarcinogens.&rft.au=Tennant%2C+R+W%3BSpalding%2C+J%3BFrench%2C+J+E&rft.aulast=Tennant&rft.aufirst=R&rft.date=1996-09-01&rft.volume=365&rft.issue=1-3&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of increased DNA replication in the carcinogenic risk of nonmutagenic chemical carcinogens. AN - 78490327; 8898989 AB - DNA replication is not an error-free process; therefore induction of cell proliferation with the requisite increase in DNA replication may be an important mechanism by which carcinogenesis can be induced by chemicals. Data presented in this overview indicate a positive association between increased cell proliferation and carcinogenesis, and illustrate the value of performing mechanistic studies such as cell proliferation assays in conjunction with short-term tests to further investigate the results of cancer bioassays. Whereas chemically-induced cell proliferation per se may not be sufficient to induce carcinogenesis, it creates a favorable environment for tumor development. There are two types of chemically-induced cell proliferation, mitogenic and cytotoxic, and they have different consequences regarding the mechanism of carcinogenesis of a chemical. Mitogenic chemical such as phenobarbital, oxazepam, and the peroxisome proliferating agents exert a short-term cell proliferative response that may exert its primary effect in carcinogenesis at the promotion stages. It is not clear at what stage(s) cytotoxic agents such as methapyrilene, alpha 2u-globulin inducers or saccharin exert their effects in carcinogenesis. A confounding factor in evaluation of cell proliferation in risk assessments is the production of chemical specific pleiotropic effects that may contribute to the carcinogenicity of a chemical. It is clear that mechanistic studies performed to understand the relationship of sex, species and dose in rodent carcinogenicity assays of chemicals is critical for the extrapolation of such data for human health assessments. JF - Mutation research AU - Cunningham, M L AD - Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. cunningl@niehs.nih.gov Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 59 EP - 69 VL - 365 IS - 1-3 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Cytotoxins KW - Mitogens KW - Index Medicus KW - Mitogens -- pharmacology KW - Humans KW - Cytotoxins -- pharmacology KW - Risk Assessment KW - DNA Replication -- physiology KW - Cell Division -- drug effects KW - Carcinogens -- toxicity KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78490327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Role+of+increased+DNA+replication+in+the+carcinogenic+risk+of+nonmutagenic+chemical+carcinogens.&rft.au=Cunningham%2C+M+L&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1996-09-01&rft.volume=365&rft.issue=1-3&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of endotoxin in tumor necrosis factor alpha expression from alveolar macrophages treated with urban air particles. AN - 78484517; 8886760 AB - The effects of urban air and diesel particles on inflammatory cytokine gene expression, tumor necrosis factor alpha (TNF-alpha) in particular, were studied in rat alveolar macrophages. TNF-alpha, interleukin (IL)-1, IL-6, cytokine-induced neutrophil chemoattractant (CINC), and macrophage inflammatory protein (MIP)-2 gene expression and TNF-alpha secretion were increased in cells treated with 50 to 200 micrograms/mL of urban air particles in a concentration-related manner. There was no cytokine induction by diesel particles at any of the concentrations tested. Cytokine expression was not related to reactive oxygen species since antioxidants, such as catalase, TMTU, or DMSO, had no effect on TNF-alpha secretion. However, cytokine induction by urban air particles was completely prevented by polymyxin B, an antibiotic capable of neutralizing bacterial lipopolysaccharide (LPS) activities. Furthermore, LPS was detected on the urban air particles, but not on diesel particle. These results suggest that activation of cytokine gene expression and secretion in rat alveolar macrophages by urban air particles is due to the presence of endotoxin on the particles. JF - Experimental lung research AU - Dong, W AU - Lewtas, J AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. PY - 1996 SP - 577 EP - 592 VL - 22 IS - 5 SN - 0190-2148, 0190-2148 KW - Air Pollutants KW - 0 KW - Culture Media KW - Endotoxins KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Vehicle Emissions KW - RNA KW - 63231-63-0 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Culture Media -- pharmacokinetics KW - L-Lactate Dehydrogenase -- drug effects KW - Reactive Oxygen Species -- physiology KW - Polymerase Chain Reaction -- methods KW - RNA -- isolation & purification KW - Cell Culture Techniques KW - RNA -- chemistry KW - L-Lactate Dehydrogenase -- metabolism KW - Vehicle Emissions -- toxicity KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Endotoxins -- physiology KW - Macrophages, Alveolar -- drug effects KW - Endotoxins -- analysis KW - Air Pollutants -- toxicity KW - Tumor Necrosis Factor-alpha -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78484517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+lung+research&rft.atitle=Role+of+endotoxin+in+tumor+necrosis+factor+alpha+expression+from+alveolar+macrophages+treated+with+urban+air+particles.&rft.au=Dong%2C+W%3BLewtas%2C+J%3BLuster%2C+M+I&rft.aulast=Dong&rft.aufirst=W&rft.date=1996-09-01&rft.volume=22&rft.issue=5&rft.spage=577&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-30 N1 - Date created - 1997-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stereoselective metabolism of a new anticonvulsant drug candidate, losigamone, by human liver microsomes. AN - 78484312; 8886611 AB - Losigamone (LSG) is a new candidate anticonvulsant drug under going preclinical and clinical development. Metabolism of racemic (+/-)-LSG and its two enantiomers, AO-242 [(+)-LSG] and AO-294 [(-)-LSG], was studied using human liver microsomes and recombinant cytochrome P450 isozymes. HPLC with both UV and electrochemical detection was used for analysis of the incubation media. Five metabolites (M1, M2, M3, M4, and M5) were generated from racemic (+/-)-LSG by both human liver microsomes and recombinant enzymes. Stereoselective metabolism was observed when each enantiomer was incubated separately with human liver microsomes. M1 was the major metabolite produced from (+)-LSG, whereas M3, M4, and M5 were primarily produced from (-)-LSG. The production of M1 from (+)-LSG was markedly inhibited by (-)-LSG, indicating a metabolic enantiomer/enantiomer interaction. (+/-)-LSG enantiomers were selectively metabolized by recombinant cytochrome P450 2A6, and the metabolism of (+)-LSG and (-)-LSG by human liver microsomes was preferentially inhibited by coumarin, a cytochrome P450 2A6-selective compound. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Torchin, C D AU - McNeilly, P J AU - Kapetanovic, I M AU - Strong, J M AU - Kupferberg, H J AD - Epilepsy Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1002 EP - 1008 VL - 24 IS - 9 SN - 0090-9556, 0090-9556 KW - Anticonvulsants KW - 0 KW - Coumarins KW - Cytochrome P-450 Enzyme Inhibitors KW - Furans KW - Isoenzymes KW - Recombinant Proteins KW - Triazines KW - Phenytoin KW - 6158TKW0C5 KW - losigame KW - 84R8O3QM2G KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - coumarin KW - A4VZ22K1WT KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP2A6 KW - lamotrigine KW - U3H27498KS KW - Index Medicus KW - Stereoisomerism KW - Drug Interactions KW - Humans KW - Cytochrome P-450 Enzyme System -- metabolism KW - Chromatography, High Pressure Liquid KW - Isoenzymes -- metabolism KW - Phenytoin -- pharmacology KW - Triazines -- pharmacology KW - Mixed Function Oxygenases -- metabolism KW - Coumarins -- pharmacology KW - Mixed Function Oxygenases -- antagonists & inhibitors KW - Recombinant Proteins -- metabolism KW - Gas Chromatography-Mass Spectrometry KW - Furans -- metabolism KW - Microsomes, Liver -- metabolism KW - Microsomes, Liver -- enzymology KW - Anticonvulsants -- metabolism KW - Furans -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78484312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Stereoselective+metabolism+of+a+new+anticonvulsant+drug+candidate%2C+losigamone%2C+by+human+liver+microsomes.&rft.au=Torchin%2C+C+D%3BMcNeilly%2C+P+J%3BKapetanovic%2C+I+M%3BStrong%2C+J+M%3BKupferberg%2C+H+J&rft.aulast=Torchin&rft.aufirst=C&rft.date=2007-03-01&rft.volume=32&rft.issue=2&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=MCN%2C+the+American+Journal+of+Maternal+Child+Nursing&rft.issn=0361929X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-12 N1 - Date created - 1997-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High incidence and histogenesis of seminal vesicle adenocarcinoma and lower incidence of prostate carcinomas in the Lobund-Wistar prostate cancer rat model using N-nitrosomethylurea and testosterone. AN - 78483067; 8885183 AB - The origin of chemically induced male accessory sex gland tumors was studied in Lobund-Wistar rats. Rats were treated at the age of 3 months with a single intravenous injection of 30 mg N-nitrosomethylurea (NMU)/kg body weight and given subcutaneous silastic implants filled with 40 mg testosterone propionate. Previous reports described a high incidence of prostate carcinomas in these rats with this treatment protocol. Additional animal groups included untreated controls, rats that received only an injection of 30 mg NMU/kg, and rats that were subjected to ablation of the seminal vesicle lobes prior to the treatment with NMU and testosterone. Three to 14 rats per group were sacrificed 4 to 10 months after NMU treatment and all remaining rats after 12 months. Twenty-four additional rats died or became moribund during the study. All rats were necropsied and the dorsolateral and ventral prostate and seminal vesicles with coagulating gland (anterior prostate) were examined histologically according to a standardized protocol. Lesions detected included atypical hyperplasia in all glands (resembling prostate intraepithelial neoplasia of human beings), adenomas in seminal vesicles only, and early carcinomas and adenocarcinomas in seminal vesicles and coagulating gland. Early carcinomas of the seminal vesicle, microscopically small and with invasion of the lamina propria and/or tunica muscularis, were detected as rapidly as 4 months after treatment. The vast majority (> 95%) of the grossly visible nodules/masses originated from the seminal vesicles. Testosterone treatment enhanced occurrence and increased the incidence of all lesions, particularly of seminal vesicle adenocarcinomas, from 30% (7/23) to 64% (21/33). Coagulating gland tumors were found in 21% (7/33) of the rats. Ablation of the seminal vesicle lobes reduced the incidence of seminal vesicle adenocarcinomas to 11% (3/29), and these tumors arose from tissues remaining within the parenchyma of the seminal vesicle/prostate complex after ablation. Thus, NMU-induced and testosterone-promoted male sex gland tumors of the Lobund-Wistar rat arise almost exclusively in the seminal vesicles and coagulating gland (anterior prostate), are highly invasive in seminal vesicles before attaining a grossly visible size, and progress rapidly within 4 months, spreading to adjacent tissues and other organs. JF - Veterinary pathology AU - Tamano, S AU - Rehm, S AU - Waalkes, M P AU - Ward, J M AD - Veterinary and Tumor Pathology Section, Office of Laboratory Animal Science, National Cancer Institute, Frederick, MD, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 557 EP - 567 VL - 33 IS - 5 SN - 0300-9858, 0300-9858 KW - Testosterone KW - 3XMK78S47O KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Rats KW - Animals KW - Neoplasm Invasiveness -- pathology KW - Rats, Wistar KW - Incidence KW - Prostatic Hyperplasia -- pathology KW - Drug Synergism KW - Male KW - Prostatic Intraepithelial Neoplasia -- chemically induced KW - Adenocarcinoma -- epidemiology KW - Prostatic Neoplasms -- epidemiology KW - Adenocarcinoma -- chemically induced KW - Prostatic Neoplasms -- chemically induced KW - Testicular Neoplasms -- chemically induced KW - Seminal Vesicles -- pathology KW - Testicular Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78483067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Veterinary+pathology&rft.atitle=High+incidence+and+histogenesis+of+seminal+vesicle+adenocarcinoma+and+lower+incidence+of+prostate+carcinomas+in+the+Lobund-Wistar+prostate+cancer+rat+model+using+N-nitrosomethylurea+and+testosterone.&rft.au=Tamano%2C+S%3BRehm%2C+S%3BWaalkes%2C+M+P%3BWard%2C+J+M&rft.aulast=Tamano&rft.aufirst=S&rft.date=1996-09-01&rft.volume=33&rft.issue=5&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Veterinary+pathology&rft.issn=03009858&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-05 N1 - Date created - 1997-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reducing alcohol-use disorders via decreased consumption: a comparison of population and high-risk strategies. AN - 78480557; 8889402 AB - This study compared three alternative scenarios for effecting a 25% reduction in U.S. alcohol consumption in terms of their respective impacts on the prevalence of alcohol abuse and dependence. The three approaches were (1) an overall 25% reduction in the volume of ethanol intake for all current drinkers, (2) an equivalent absolute reduction taken only among drinkers whose current intake ever exceeds moderate drinking guidelines, and (3) an equivalent reduction taken only among drinkers whose current intake usually exceeds moderate drinking guidelines. The per-occasion cutpoint for moderate consumption was set at the intake level demonstrated to produce psychomotor impairment, and was based on each individual's total body water level. The impact of reducing consumption on the prevalence of alcohol use disorders was estimated by means of a logistic regression model that adjusted for sociodemographic characteristics, family history of alcoholism, and age at first drink, and that took into account interactions between the consumption and other variables. Taking an overall 25% reduction in intake resulted in the same decrease in the prevalence of abuse and dependence (21.7%) as was achieved by taking an equal volume of reduction among only those drinkers whose consumption usually exceeded the moderate drinking cutpoint. Restricting the reduction in consumption to those drinkers whose consumption ever exceeded this cutpoint resulted in a slightly greater reduction in alcohol use disorders, 24.6%. JF - Drug and alcohol dependence AU - Dawson, D A AU - Archer, L D AU - Grant, B F AD - National Institute on Alcohol Abuse and Alcoholism, Division of Biometry and Epidemiology, Bethesda, MD 20892-7003, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 39 EP - 47 VL - 42 IS - 1 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Feasibility Studies KW - Risk Factors KW - Humans KW - Adult KW - Sampling Studies KW - Health Policy -- legislation & jurisprudence KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- prevention & control KW - Alcohol Drinking -- epidemiology KW - Alcoholism -- prevention & control KW - Alcohol Drinking -- legislation & jurisprudence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78480557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Reducing+alcohol-use+disorders+via+decreased+consumption%3A+a+comparison+of+population+and+high-risk+strategies.&rft.au=Dawson%2C+D+A%3BArcher%2C+L+D%3BGrant%2C+B+F&rft.aulast=Dawson&rft.aufirst=D&rft.date=1996-09-01&rft.volume=42&rft.issue=1&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of RFB4-Pseudomonas exotoxin A immunotoxins targeted to CD22 on B-cell malignancies. AN - 78469348; 8889017 AB - To develop an immunotoxin for the treatment of B-cell malignancies, we constructed several candidate conjugates with RFB4, a B-cell specific anti-CD22 IgG1, and truncated forms of Pseudomonas exotoxin (PE). The four versions of PE included PE35 and PE35KDEL, which were linked to RFB4 via a disulfide bond, and PE38 and PE38KDEL, which were linked via a thioether bond. The PE35 truncated forms, which are fully active in ADP ribosylation and lack receptor binding sequences, do not require intracellular proteolytic cleavage in order to be active. PE35KDEL has the consensus endoplasmic reticulum retention signal, KDEL, replacing the wild type PE C-terminal sequence, REDLK. The PE38 forms retain all of domain II and therefore require cleavage to be active within cells. Cytotoxicity experiments on CD22-positive cell lines revealed that the PE35 conjugates were more active than the PE38 versions and the presence of the KDEL sequence generally enhanced toxicity by 5-10-fold compared to that of REDLK. The RFB4-PE35KDEL immunotoxin was most active in cytotoxicity assays against Burkitt's lymphoma cell lines such as Daudi and CA46 (IC50 = 0.2 ng/mL) and displayed little cytotoxicity toward human vascular endothelial cells (IC50 > 20 micrograms/mL). Results of experiments conducted in nude mice showed that both RFB4-PE35KDEL and RFB4-PE35 could inhibit the development of subcutaneous CA46 tumors. JF - Bioconjugate chemistry AU - Mansfield, E AU - Pastan, I AU - FitzGerald, D J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 557 EP - 563 VL - 7 IS - 5 SN - 1043-1802, 1043-1802 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, B-Lymphocyte KW - Bacterial Toxins KW - CD22 protein, human KW - Cd22 protein, mouse KW - Cell Adhesion Molecules KW - Exotoxins KW - Immunotoxins KW - Lectins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Virulence Factors KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Endothelium, Vascular -- drug effects KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Humans KW - Mice KW - Pseudomonas aeruginosa KW - Adenosine Diphosphate Ribose -- metabolism KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Immunotoxins -- chemistry KW - Lymphoma, B-Cell -- immunology KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Exotoxins -- chemistry KW - Exotoxins -- immunology KW - Bacterial Toxins -- immunology KW - Antigens, CD -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78469348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Characterization+of+RFB4-Pseudomonas+exotoxin+A+immunotoxins+targeted+to+CD22+on+B-cell+malignancies.&rft.au=Mansfield%2C+E%3BPastan%2C+I%3BFitzGerald%2C+D+J&rft.aulast=Mansfield&rft.aufirst=E&rft.date=1996-09-01&rft.volume=7&rft.issue=5&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-04 N1 - Date created - 1997-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coupled site-directed mutagenesis/transgenesis identifies important functional domains of the mouse agouti protein. AN - 78459492; 8878691 AB - The agouti locus encodes a novel paracrine signaling molecule containing a signal sequence, an N-linked glycosylation site, a central lysine-rich basic domain, and a C-terminal tail containing 10 cysteine (Cys) residues capable of forming five disulfide bonds. When overexpressed, agouti causes a number of pleiotropic effects including yellow coat and adult-onset obesity. Numerous studies suggest that agouti causes yellow coat color by antagonizing the binding of alpha-melanocyte-stimulating hormone (alpha-MSH) to the alpha-MSH-(Melanocortin-1) receptor. With the goal of identifying functional domains of agouti important for its diverse biological activities, we have generated 14 agouti mutations by in vitro site-directed mutagenesis and analyzed these mutations in transgenic mice for their effects on coat color and obesity. These studies demonstrate that the signal sequence, the N-linked glycosylation site, and the C-terminal Cys residues are important for full biological activity, while at least a portion of the lysine-rich basic domain is dispensable for normal function. They also show that the same functional domains of agouti important to coat color determination are important for inducing obesity, consistent with the hypothesis that agouti induces obesity by antagonizing melanocortin binding to other melanocortin receptors. JF - Genetics AU - Perry, W L AU - Nakamura, T AU - Swing, D A AU - Secrest, L AU - Eagleson, B AU - Hustad, C M AU - Copeland, N G AU - Jenkins, N A AD - Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 255 EP - 264 VL - 144 IS - 1 SN - 0016-6731, 0016-6731 KW - ASIP protein, human KW - 0 KW - Agouti Signaling Protein KW - Intercellular Signaling Peptides and Proteins KW - Proteins KW - RNA, Messenger KW - nonagouti protein, mouse KW - Asparagine KW - 7006-34-0 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Humans KW - Transgenes KW - Amino Acid Sequence KW - Mice KW - Mice, Transgenic KW - Binding Sites KW - Mice, Inbred DBA KW - Mutagenesis, Site-Directed KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Female KW - Male KW - Hair Color -- genetics KW - Obesity -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78459492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Coupled+site-directed+mutagenesis%2Ftransgenesis+identifies+important+functional+domains+of+the+mouse+agouti+protein.&rft.au=Perry%2C+W+L%3BNakamura%2C+T%3BSwing%2C+D+A%3BSecrest%2C+L%3BEagleson%2C+B%3BHustad%2C+C+M%3BCopeland%2C+N+G%3BJenkins%2C+N+A&rft.aulast=Perry&rft.aufirst=W&rft.date=1996-09-01&rft.volume=144&rft.issue=1&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-28 N1 - Date created - 1997-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochimie. 1987 Feb;69(2):87-9 [3105605] Mol Cell Biol. 1986 Jul;6(7):2382-91 [3537718] Nature. 1989 Jun 8;339(6224):483-4 [2657436] Nature. 1989 Oct 5;341(6241):462-4 [2507926] Science. 1990 Mar 16;247(4948):1328-30 [2315700] Biochem Biophys Res Commun. 1991 Jan 31;174(2):586-92 [1993056] Oncogene. 1991 Feb;6(2):323-32 [1705690] J Bacteriol. 1991 Jun;173(11):3539-46 [2045373] J Cell Biol. 1991 Sep;114(6):1125-33 [1894691] Am J Clin Nutr. 1992 Feb;55(2 Suppl):503S-507S [1733119] Science. 1992 Aug 28;257(5074):1248-51 [1325670] Cell. 1992 Dec 24;71(7):1195-204 [1473152] Cell. 1993 Mar 26;72(6):827-34 [8458079] Nature. 1993 Apr 15;362(6421):587-8 [8385273] J Biol Chem. 1993 Jul 15;268(20):15174-9 [8392067] Genes Dev. 1994 Feb 15;8(4):481-90 [8125260] FASEB J. 1994 May;8(8):479-88 [8181666] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5667-71 [8202545] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9760-4 [7937887] Biochem J. 1994 Sep 15;302 ( Pt 3):641-8 [7945187] J Biol Chem. 1994 Dec 2;269(48):30668-75 [7982986] Nature. 1994 Dec 1;372(6505):425-32 [7984236] Nat Genet. 1994 Sep;8(1):59-65 [7987393] Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):97-101 [7816856] J Biol Chem. 1995 Apr 21;270(16):9437-42 [7721869] Hum Mol Genet. 1995 Feb;4(2):223-30 [7757071] Proc Natl Acad Sci U S A. 1995 May 23;92(11):4721-4 [7761389] Proc Natl Acad Sci U S A. 1995 May 23;92(11):4728-32 [7761391] Genetics. 1995 May;140(1):255-65 [7635290] Genetics. 1995 May;140(1):267-74 [7635291] Nat Genet. 1995 Jun;10(2):135-42 [7663508] Biochemistry. 1995 Sep 26;34(38):12341-6 [7547977] Cell. 1995 Dec 29;83(7):1263-71 [8548812] Science. 1996 Feb 16;271(5251):994-6 [8584938] Cell. 1996 Feb 9;84(3):491-5 [8608603] Nature. 1996 Apr 11;380(6574):534-8 [8606774] Cell. 1996 Apr 19;85(2):281-90 [8612280] Nature. 1996 Feb 15;379(6566):632-5 [8628397] J Hered. 1974 May-Jun;65(3):137-40 [4847754] J Hered. 1978 Sep-Oct;69(5):295-8 [744871] Annu Rev Microbiol. 1985;39:615-48 [3904614] Genet Res. 1985 Aug;46(1):95-9 [4065569] Med Clin North Am. 1989 Jan;73(1):67-81 [2643009] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The efficiency of meiotic recombination between dispersed sequences in Saccharomyces cerevisiae depends upon their chromosomal location. AN - 78458923; 8878672 AB - To examine constrains imposed on meiotic recombination by homologue pairing, we measured the frequency of recombination between mutant alleles of the ARG4 gene contained in pBR322-based inserts. Inserts were located at identical loci on homologues (allelic recombination) or at different loci on either homologous or heterologous chromosomes (ectopic recombination). Ectopic recombination between interstitially located inserts on heterologous chromosomes had an efficiency of 6-12% compared to allelic recombination. By contrast, ectopic recombination between interstitial inserts located on homologues had relative efficiencies of 47-99%. These findings suggest that when meiotic ectopic recombination occurs, homologous chromosomes are already colocalized. The efficiency of ectopic recombination between inserts on homologues decreased as the physical distance between insert sites was increased. This result is consistent with the suggestion that during meiotic recombination, homologues are not only close to each other, but also are aligned end to end. Finally, the efficiency of ectopic recombination between inserts near telomeres (within 16 kb) was significantly greater than that observed with inserts > 50 kb from the nearest telomere. Thus, at the time of recombination, there may be a special relationship between the ends of chromosomes not shared with interstitial regions. JF - Genetics AU - Goldman, A S AU - Lichten, M AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. goldman@sunspot.nci.nih.gov Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 43 EP - 55 VL - 144 IS - 1 SN - 0016-6731, 0016-6731 KW - Fungal Proteins KW - 0 KW - Saccharomyces cerevisiae Proteins KW - Arg4 protein, S cerevisiae KW - EC 4.3.2.1 KW - Argininosuccinate Lyase KW - Index Medicus KW - Chromosome Mapping KW - Mutagenesis, Insertional KW - Saccharomyces cerevisiae -- genetics KW - Models, Genetic KW - Recombination, Genetic KW - Mathematical Computing KW - Fungal Proteins -- genetics KW - Chromosomes, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78458923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=The+efficiency+of+meiotic+recombination+between+dispersed+sequences+in+Saccharomyces+cerevisiae+depends+upon+their+chromosomal+location.&rft.au=Goldman%2C+A+S%3BLichten%2C+M&rft.aulast=Goldman&rft.aufirst=A&rft.date=1996-09-01&rft.volume=144&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-28 N1 - Date created - 1997-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1992 Jun;117(5):935-48 [1315786] Nature. 1992 May 7;357(6373):38-46 [1574125] Mol Cell Biol. 1993 Jan;13(1):373-82 [8417336] Cell. 1993 Feb 12;72(3):365-78 [7916652] Mol Cell Biol. 1993 Apr;13(4):2324-31 [8455614] Nucleic Acids Res. 1993 Aug 11;21(16):3902 [8367314] Cell. 1994 Jan 14;76(1):51-63 [8287479] Cell. 1994 Jan 14;76(1):65-75 [8287480] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):619-23 [8290573] Mem Inst Oswaldo Cruz. 1992;87 Suppl 3:95-100 [1343732] Cell. 1994 Jul 1;77(7):977-91 [8020104] EMBO J. 1994 Sep 1;13(17):4174-80 [8076613] Genetics. 1994 Jul;137(3):837-43 [8088528] Science. 1994 Sep 30;265(5181):2077-82 [8091229] J Cell Biol. 1994 Oct;127(2):273-85 [7929575] Cold Spring Harb Symp Quant Biol. 1993;58:553-65 [7956070] Cold Spring Harb Symp Quant Biol. 1993;58:733-46 [7956091] Genetics. 1995 Mar;139(3):1175-88 [7768431] Genetics. 1995 May;140(1):55-66 [7635308] Cell. 1995 Dec 1;83(5):783-91 [8521495] Mol Cell Biol. 1996 Mar;16(3):1085-93 [8622653] Chromosoma. 1975 Sep 15;52(1):27-35 [1175456] Proc Natl Acad Sci U S A. 1975 Dec;72(12):5056-60 [1108011] Hum Genet. 1977 Feb 11;35(2):137-51 [844860] Symp Soc Exp Biol. 1984;38:87-121 [6400221] Genetics. 1986 Nov;114(3):731-52 [3539696] J Cell Biol. 1988 Mar;106(3):567-73 [2450094] Nature. 1989 Mar 2;338(6210):87-90 [2645528] Cell. 1990 Jun 15;61(6):1089-101 [2190690] Mol Cell Biol. 1990 Aug;10(8):4420-3 [2196454] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7653-7 [2217196] Genetics. 1990 Nov;126(3):563-74 [2249756] Genetics. 1991 Jan;127(1):53-60 [2016046] Genome. 1990 Dec;33(6):759-78 [2086352] Cell. 1991 Sep 20;66(6):1239-56 [1913808] Chromosoma. 1992 Oct;101(10):590-5 [1424983] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogenic effect on the expression of estrogen receptor, COUP-TF, and lactoferrin mRNA in developing mouse tissues. AN - 78451973; 8873065 AB - We have previously demonstrated that lactoferrin (LF) is a major estrogen-inducible protein in the mouse uterus. The increase of LF mRNA after estrogen treatment (> 300 fold) is the result of a complex interplay among transcription factors acting on the estrogen response element (ERE) of the LF gene. Two transcription factors-the estrogen receptor (ER) and the chicken ovalbumin upstream promoter transcription factor (COUP-TF)-play opposing roles in the estrogen responsiveness of the LF gene promoter-reporter constructs in transiently transfected human endometrial carcinoma cells. The ratio of ER/COUP-TF in the transfected cells appears to be critical for estrogen-stimulated LF gene promoter activity (Liu et al, 1993). In the current study, ER and COUP-TF mRNA levels are examined and related to LF mRNA expression in various mouse tissues, including the developing uterus with/without estrogen stimulation. Results show that LF mRNA and protein are expressed in various tissues during development, but the potent synthetic estrogen, diethylstilbestrol (DES), does not increase LF mRNA expression in nonreproductive tissues such as liver, spleen, and lung. In contrast, in developing neonatal reproductive tract tissues, DES increases LF mRNA and protein expression as previously reported in immature and mature uterine tissues. DES, however, did not affect ER and COUP-TF expression in developing uterine tissues. Although the uterus has a high ratio of ER/COUP-TF as compared to other tissues examined, COUP-TF may not be the only regulator for LF gene expression in this particular tissue since COUP-TF remains constant during development and following DES treatment. These data point to the complexity of differential expression of LF gene in estrogen responsive and nonresponsive tissues during development. JF - Molecular reproduction and development AU - Shigeta, H AU - Newbold, R R AU - McLachlan, J A AU - Teng, C AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 21 EP - 30 VL - 45 IS - 1 SN - 1040-452X, 1040-452X KW - COUP Transcription Factor I KW - 0 KW - DNA-Binding Proteins KW - Nr2f1 protein, mouse KW - RNA, Messenger KW - Receptors, Estrogen KW - Transcription Factors KW - Diethylstilbestrol KW - 731DCA35BT KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Uterus -- growth & development KW - Animals KW - Blotting, Northern KW - Spleen -- metabolism KW - Liver -- growth & development KW - Liver -- metabolism KW - Lung -- growth & development KW - Mice KW - Lung -- metabolism KW - Uterus -- metabolism KW - RNA, Messenger -- metabolism KW - Spleen -- growth & development KW - Immunohistochemistry KW - Female KW - Receptors, Estrogen -- genetics KW - Lactoferrin -- genetics KW - Gene Expression Regulation, Developmental -- genetics KW - Diethylstilbestrol -- pharmacology KW - DNA-Binding Proteins -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78451973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+reproduction+and+development&rft.atitle=Estrogenic+effect+on+the+expression+of+estrogen+receptor%2C+COUP-TF%2C+and+lactoferrin+mRNA+in+developing+mouse+tissues.&rft.au=Shigeta%2C+H%3BNewbold%2C+R+R%3BMcLachlan%2C+J+A%3BTeng%2C+C&rft.aulast=Shigeta&rft.aufirst=H&rft.date=1996-09-01&rft.volume=45&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Molecular+reproduction+and+development&rft.issn=1040452X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-08 N1 - Date created - 1997-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measurement of organochlorine levels in postprandial serum or in blood collected in serum separator tubes. AN - 78450415; 8877068 AB - Whether organochlorine blood levels in fasting and postprandial specimens provide equivalent measures of exposure and the extent to which collecting blood in tubes containing material to separate serum and blood cells corrupts the specimen are unclear. In this paper, we present data from two studies that address both of these issues. In the first study, 27 women provided fasting blood in plain, silicone-coated Vacutainer tubes (red-topped) and in similar tubes containing serum separator gel (SSTs), as well as a postprandial specimen in a red-topped tube. The specimens collected in SSTs were left to stand overnight, with the gel in contact with the sample. In the second study, the blood of 12 industrial incinerator workers was collected in red-topped tubes and in SSTs. Blood in SSTs was left in contact with the gel for 5 days. Serum organochlorine residue levels ([1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] (DDE)) and polychlorinated biphenyls) in samples collected in red-topped tubes were highly correlated with levels measured in samples collected in SSTs (all Pearson r values were > or = 0.79). Postprandial and fasting organochlorine levels were also highly correlated (Pearson r values > or = 0.89). Our results indicate that timing of the collection of blood in relation to meals and use of SSTs to collect blood specimens did not greatly affect the relative classification of subjects with respect to serum level of DDE or polychlorinated biphenyls. The longer the specimen was in contact with the SST gel, however, the lower the level of organochlorine that was detected and, at least for DDE, the greater the misclassification caused. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Longnecker, M P AU - Bernstein, L AU - Bird, C L AU - Yancey, A K AU - Peterson, J C AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 753 EP - 755 VL - 5 IS - 9 SN - 1055-9965, 1055-9965 KW - Gels KW - 0 KW - Insecticides KW - Silicones KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Occupational Exposure KW - Plasma KW - Chromatography, Gas KW - Humans KW - Aged KW - Blood Cells KW - Fasting -- blood KW - Equipment Design KW - Adult KW - Middle Aged KW - Time Factors KW - Female KW - Male KW - Eating KW - Blood Specimen Collection -- methods KW - Polychlorinated Biphenyls -- blood KW - Blood Specimen Collection -- instrumentation KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78450415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Measurement+of+organochlorine+levels+in+postprandial+serum+or+in+blood+collected+in+serum+separator+tubes.&rft.au=Longnecker%2C+M+P%3BBernstein%2C+L%3BBird%2C+C+L%3BYancey%2C+A+K%3BPeterson%2C+J+C&rft.aulast=Longnecker&rft.aufirst=M&rft.date=1996-09-01&rft.volume=5&rft.issue=9&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-21 N1 - Date created - 1997-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological characterization of the enhancement of apomorphine-induced gnawing in mice by cocaine. AN - 78440975; 8870049 AB - The present study was designed to provide additional information on the behavioral and pharmacological mechanisms associated with the augmentation of apomorphine-induced gnawing in C57BL/6J mice. (-)-Cocaine enhanced apomorphine-induced gnawing at doses devoid of effects on gnawing when given alone. The effect was stereoselective, with (+)-cocaine devoid of activity in this test. Peripheral synapses may also not be critical to the cocaine enhancement, as cocaine methiodide, a charged species, was also without effect. The local anesthetic actions of cocaine were evaluated with lidocaine, a local anesthetic without prominent dopaminergic actions. Like (-)-cocaine, lidocaine augmented the gnawing response to apomorphine without increasing climbing or gnawing when given alone. (+)-Amphetamine enhanced apomorphine-induced gnawing but only at a high dose that increased gnawing by itself. The selective dopamine uptake blocker. GBR 12909, augmented apomorphine-induced gnawing without increasing gnawing when given alone; however, unlike cocaine or lidocaine, GBR 12909 increased climbing at doses that augmented the gnawing response. These data indicate that the cocaine-augmented gnawing response to apomorphine does not appear to be the result of psychomotor stimulation per se. Rather, this effect may be due to blockade of dopamine uptake and/or the local anesthetic actions of cocaine. JF - Pharmacology, biochemistry, and behavior AU - Tirelli, E AU - Witkin, J M AD - Psychobiology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 135 EP - 140 VL - 55 IS - 1 SN - 0091-3057, 0091-3057 KW - Anesthetics, Local KW - 0 KW - Dopamine Agonists KW - Dopamine Uptake Inhibitors KW - Lidocaine KW - 98PI200987 KW - Cocaine KW - I5Y540LHVR KW - Apomorphine KW - N21FAR7B4S KW - Dextroamphetamine KW - TZ47U051FI KW - Index Medicus KW - Animals KW - Anesthetics, Local -- pharmacology KW - Dose-Response Relationship, Drug KW - Mice, Inbred C57BL KW - Mice KW - Lidocaine -- pharmacology KW - Drug Synergism KW - Male KW - Dextroamphetamine -- pharmacology KW - Dopamine Agonists -- pharmacology KW - Apomorphine -- pharmacology KW - Stereotyped Behavior -- drug effects KW - Cocaine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78440975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Family+Violence&rft.atitle=%22He+killed+my+mommy%21%22%3A+Murder+or+attempted+murder+of+a+child%27s+mother&rft.au=Lewandowski%2C+Linda+A%3BMcfarlane%2C+Judith%3BCampbell%2C+Jacquelyn+C%3BFaye%2C+Gary%3BBarenski%2C+Cathleen&rft.aulast=Lewandowski&rft.aufirst=Linda&rft.date=2004-08-01&rft.volume=19&rft.issue=4&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Journal+of+Family+Violence&rft.issn=08857482&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory and noninhibitory monoclonal antibodies to human cytochrome P450 2E1. AN - 78439124; 8870991 AB - A panel of 17 hybridomas producing (MAbs) against human cytochrome P450 2E1 (h2E1) was generated by immunizing mice with baculovirus-expressed h2E1. All 17 hybridoma clones gave positive ELISA or immunoblots with either baculovirus-or vaccinia virus-expressed h2E1. Two of the latter were further developed due to their desirable characteristics. MAb 1-73-18 was found to be a powerful inhibitor of P450 h2E1; however, it did not yield a positive immunoblot. MAb 2-106-12 was found to be noninhibitory but formed a strong positive immunoblot with P450 h2E1. These MAbs to h2E1 were highly specific and did not recognize six other human P450s as tested with ELISA or immunoblot analyses. The MAbs to baculovirus-expressed h2E1 also reacted with h2E1 expressed from a vaccinia virus vector system as well as with microsomal fractions of human and acetone-treated rat liver. MAb 1-73-18 inhibited h2E1 enzyme activity catalyzing the metabolism of phenanthrene by 85%, p-nitroanisole by 90%, 4-methylanisole by 60-80%, toluene by 90%, and chlorzoxazone by 90%. The inhibitory MAb 1-73-18 is uniquely useful for determining the contribution of h2E1 to the metabolism of h2E1 substrates in human liver containing multiple P450s. The quantitatively determined contribution of h2E1 to the metabolism of the above substrates ranged from 25% to 75%. Thus, h2E1 was responsible for the following percentages of the total metabolism in human liver: p-nitroanisole (35%), phenanthrene (23%), methylanisole to cresol (25%), methylanisole to methoxybenzyl alcohol (12%), toluene (40%), and chlorzoxazone (72%). The MAb 2-106-12 forming a strong immunoblot is useful for determining the amount of h2E1 protein in a tissue. Thus the utility of the inhibitory and immunoblot positive MAbs is complementary and can determine both the contribution of h2E1 to the metabolism of specific substrates and the amount of h2E1 protein in human tissue. The analyses of metabolism with the inhibitory MAb 1-73-18 can be generalized and applicable to all h2E1 substrates. JF - Chemical research in toxicology AU - Gelboin, H V AU - Goldfarb, I AU - Krausz, K W AU - Grogan, J AU - Korzekwa, K R AU - Gonzalez, F J AU - Shou, M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1023 EP - 1030 VL - 9 IS - 6 SN - 0893-228X, 0893-228X KW - Anisoles KW - 0 KW - Antibodies, Monoclonal KW - Cytochrome P-450 CYP2E1 Inhibitors KW - Phenanthrenes KW - phenanthrene KW - 448J8E5BST KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - 4-nitroanisole KW - G989Z7WOLH KW - Chlorzoxazone KW - H0DE420U8G KW - Index Medicus KW - Vaccinia virus -- genetics KW - Phenanthrenes -- metabolism KW - Immunoblotting KW - Animals KW - Humans KW - Mice KW - Mice, Inbred BALB C KW - Cross Reactions KW - Immunization KW - Rats KW - Baculoviridae -- enzymology KW - Baculoviridae -- genetics KW - Vaccinia virus -- enzymology KW - Genetic Vectors KW - In Vitro Techniques KW - Enzyme-Linked Immunosorbent Assay KW - Chlorzoxazone -- metabolism KW - Anisoles -- metabolism KW - Female KW - Cytochrome P-450 CYP2E1 -- immunology KW - Microsomes, Liver -- enzymology KW - Hybridomas -- immunology KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78439124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Inhibitory+and+noninhibitory+monoclonal+antibodies+to+human+cytochrome+P450+2E1.&rft.au=Gelboin%2C+H+V%3BGoldfarb%2C+I%3BKrausz%2C+K+W%3BGrogan%2C+J%3BKorzekwa%2C+K+R%3BGonzalez%2C+F+J%3BShou%2C+M&rft.aulast=Gelboin&rft.aufirst=H&rft.date=1996-09-01&rft.volume=9&rft.issue=6&rft.spage=1023&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-16 N1 - Date created - 1997-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Imputation for exposure histories with gaps, under an excess relative risk model. AN - 78437336; 8862979 AB - In reconstructing exposure histories needed to calculate cumulative exposures, gaps often occur. Our investigation was motivated by case-control studies of residential radon exposure and lung cancer, where half or more of the targeted homes may not be measurable. Investigators have adopted various schemes for imputing exposures for such gaps. We first undertook simulations to assess the performance of five such methods under an excess relative risk model, in the presence of random missingness and under assumed independence among the true exposure levels for different epochs of exposure (houses). Assuming no other source of measurement error, one of the methods performed without bias and with coverage of nominally 95% confidence intervals that was close to 95%. This method assigns to the missing residences the arithmetic mean across all measured control residences. We show that its good properties can be explained by the fact that this approach produces approximate "Berkson errors." To take advantage of predictive information that might exist about the missing epochs of exposure, one might prefer to carry out the imputations within strata. In further simulations, we asked whether the method would still perform well if imputations were carried out within many strata. It does, and much of the lost statistical power/precision can be recovered if the stratification system is moderately predictive of the missing exposures. Thus, observed control mean imputation provides a way to impute missing exposures without corrupting the study's validity; and stratifying the imputations can enhance precision. The technique is applicable in other settings where exposure histories contain gaps. JF - Epidemiology (Cambridge, Mass.) AU - Weinberg, C R AU - Moledor, E S AU - Umbach, D M AU - Sandler, D P AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park. NC 27709, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 490 EP - 497 VL - 7 IS - 5 SN - 1044-3983, 1044-3983 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Risk KW - Humans KW - Epidemiologic Methods KW - Environmental Exposure KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78437336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Imputation+for+exposure+histories+with+gaps%2C+under+an+excess+relative+risk+model.&rft.au=Weinberg%2C+C+R%3BMoledor%2C+E+S%3BUmbach%2C+D+M%3BSandler%2C+D+P&rft.aulast=Weinberg&rft.aufirst=C&rft.date=1996-09-01&rft.volume=7&rft.issue=5&rft.spage=490&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-14 N1 - Date created - 1997-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drinking water nitrate and the risk of non-Hodgkin's lymphoma. AN - 78437282; 8862975 AB - The increasing incidence of non-Hodgkin's lymphoma (NHL) in the United States is only partially explained by known risk factors. Nitrate is a contaminant of drinking water in many rural areas. We evaluated its association with NHL after accounting for dietary nitrate intake. For 156 cases and 527 controls who used Nebraska community supplies, average nitrate exposure was estimated from 1947 through 1979. Longterm consumption of community water with average nitrate levels in the highest quartile (> or = 4 mg per liter nitrate-nitrogen) was positively associated with risk [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.1-3.6]. Dietary nitrate, which came mainly from vegetables, was not associated with NHL risk, after adjusting for vitamin C and carotene intakes. Persons with a lower intake of vitamin C were at slightly higher risk of developing NHL than persons whose daily intake was > or = 130 mg, for all levels of intake of drinking water nitrate; our findings were similar for the combined effect of water nitrate and carotene intake. Nitrate levels in private wells were measured at the time of the interview for 51 cases and 150 controls but were not associated with the risk of NHL after adjusting for pesticide use on the farm. These findings indicate that longterm exposure to elevated nitrate levels in drinking water may contribute to the risk of NHL. JF - Epidemiology (Cambridge, Mass.) AU - Ward, M H AU - Mark, S D AU - Cantor, K P AU - Weisenburger, D D AU - Correa-Villaseñor, A AU - Zahm, S H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7364, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 465 EP - 471 VL - 7 IS - 5 SN - 1044-3983, 1044-3983 KW - Nitrates KW - 0 KW - Water Pollutants, Chemical KW - Index Medicus KW - Rural Health KW - Odds Ratio KW - Humans KW - Aged KW - Nebraska -- epidemiology KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Incidence KW - Middle Aged KW - Diet KW - Female KW - Male KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Water Supply -- analysis KW - Water Pollutants, Chemical -- analysis KW - Water Pollutants, Chemical -- adverse effects KW - Nitrates -- adverse effects KW - Nitrates -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78437282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Drinking+water+nitrate+and+the+risk+of+non-Hodgkin%27s+lymphoma.&rft.au=Ward%2C+M+H%3BMark%2C+S+D%3BCantor%2C+K+P%3BWeisenburger%2C+D+D%3BCorrea-Villase%C3%B1or%2C+A%3BZahm%2C+S+H&rft.aulast=Ward&rft.aufirst=M&rft.date=1996-09-01&rft.volume=7&rft.issue=5&rft.spage=465&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-14 N1 - Date created - 1997-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic stem cells in liver regeneration. AN - 78377309; 8836038 AB - The concept that the liver contains epithelial cells that share some of the major properties of stem cells of the well-characterized, stem cell-fed lineages found in bone marrow, intestinal epithelium, and epidermis is now well supported. Nevertheless, the population dynamics of the major types of liver epithelial cells, hepatocytes, and bile epithelia display a striking difference from the population dynamics of the classic stem cell systems. The focus of this review is on recent studies of the activation and expansion of liver stem cells in vivo and the role these cells may play in regeneration of the liver. The requirement for a selective and sustained expression of growth factors during the early stages of stem cell activation is highlighted. In addition, results are presented supporting the hypothesis that after loss of liver mass, both the quiescent stem cells as well as the residual differentiated hepatocytes and bile duct epithelial cells are activated to proliferate. However, significant contribution of the stem cells to the regeneration process only occurs under circumstances in which the residual differentiated cells are functionally compromised and/or cannot proliferate. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1249 EP - 1256 VL - 10 IS - 11 SN - 0892-6638, 0892-6638 KW - Growth Substances KW - 0 KW - Index Medicus KW - Animals KW - Liver -- cytology KW - Stem Cells KW - Liver Regeneration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78377309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Hepatic+stem+cells+in+liver+regeneration.&rft.au=Thorgeirsson%2C+S+S&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1996-09-01&rft.volume=10&rft.issue=11&rft.spage=1249&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-14 N1 - Date created - 1996-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. AN - 78366622; 8824506 AB - Genes coding for the glutathione S-transferase M1 (GSTM1) and Theta 1 (GSTT1) proteins are polymorphic in humans and these genes are absent, or homozygous null, in 10-60% of different ethnic populations. These enzymes catalyze the conjugation of glutathione to numerous carcinogenic chemicals and previous epidemiologic studies have associated the null genotypes of these GST genes with higher risk of cancer. In this study the frequency of GSTM1 and GSTT1 null genotypes was determined in Japanese patients with gastric adenocarcinoma and colorectal adenocarcinoma and compared to frequencies determined in a community-based control group. The frequency of the null GSTM1 genotype in patients with gastric adenocarcinoma (56.8%) showed a statistically significant increase compared to the control group frequency (43.6%) (odds ratio (OR) = 1.70; 95% CI, 1.05-2.76). The frequency of GSTM1 null individuals was also higher among all colorectal adenocarcinoma cases, but this increase did not reach statistical significance. After grouping by tumor site, the GSTM1 null genotype was a risk factor among the subgroup with distal colorectal tumors (61.1%) (OR = 2.03; 95% CI, 1.06-3.90). No consistent difference was observed between smoking patients and corresponding controls for the frequency of the GSTM1 null genotype for either cancer, although a large risk (OR = 5.76; 95% CI 1.18-28.3) was associated with the GSTM1 null genotype in the low smoking group of gastric adenocarcinoma patients. On the other hand, no statistically significant differences were observed in the frequency of null GSTT1 genotypes in gastric (47.5%) or colorectal (48.5%) adenocarcinoma patients when compared with the control population (44.4%). These results suggest that the GSTM1 null genotype may be associated with susceptibility to gastric adenocarcinoma and distal colorectal adenocarcinoma in Japanese; however, the associations observed were relatively weak and additional studies will be needed to confirm these findings. JF - Carcinogenesis AU - Katoh, T AU - Nagata, N AU - Kuroda, Y AU - Itoh, H AU - Kawahara, A AU - Kuroki, N AU - Ookuma, R AU - Bell, D A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1855 EP - 1859 VL - 17 IS - 9 SN - 0143-3334, 0143-3334 KW - Isoenzymes KW - 0 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Genotype KW - Smoking KW - Homozygote KW - Disease Susceptibility KW - Humans KW - Cell Differentiation KW - Middle Aged KW - Male KW - Female KW - Ethnic Groups -- genetics KW - Stomach Neoplasms -- pathology KW - Polymorphism, Genetic KW - Colorectal Neoplasms -- pathology KW - Stomach Neoplasms -- genetics KW - Glutathione Transferase -- genetics KW - Adenocarcinoma -- genetics KW - Colorectal Neoplasms -- genetics KW - Isoenzymes -- genetics KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78366622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Glutathione+S-transferase+M1+%28GSTM1%29+and+T1+%28GSTT1%29+genetic+polymorphism+and+susceptibility+to+gastric+and+colorectal+adenocarcinoma.&rft.au=Katoh%2C+T%3BNagata%2C+N%3BKuroda%2C+Y%3BItoh%2C+H%3BKawahara%2C+A%3BKuroki%2C+N%3BOokuma%2C+R%3BBell%2C+D+A&rft.aulast=Katoh&rft.aufirst=T&rft.date=1996-09-01&rft.volume=9&rft.issue=3&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+haematology&rft.issn=09503536&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-09 N1 - Date created - 1996-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allele-specific restriction analysis of human platelet antigen system 4. AN - 78358404; 8823456 AB - Diagnosis, and occasionally treatment, of disorders involving platelet-specific alloimmunization, including neonatal alloimmune thrombocytopenia and posttransfusion purpura, requires platelet allotyping. Allele-specific restriction analyses for convenient genotyping are available for the major human platelet antigen (HPA) systems except HPA-4. An allele-specific restriction analysis for HPA-4 was developed by designing a polymerase chain reaction primer containing a single-base substitution (A for T) at glycoprotein IIIa cDNA position 529. The resulting mismatch did not interfere with DNA amplification. Digestion of the polymerase chain reaction product with BsmI allowed differentiation of HPA-4a and HPA-4b alleles. A 126-bp polymerase chain reaction product was amplified with the novel primer. BsmI endonuclease cleaved product encoding HPA-4a into 104- and 22-bp fragments and left DNA encoding HPA-4b intact. This rapid allele-specific restriction analysis for genotyping the HPA-4 system complements similar methods for other platelet alloantigenic determinants. JF - Transfusion AU - Matsuo, K AU - Reid, D M AD - Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 809 EP - 812 VL - 36 IS - 9 SN - 0041-1132, 0041-1132 KW - 4a alloantigen, human KW - 0 KW - 4b alloantigen, human KW - Antigens, Human Platelet KW - DNA Primers KW - Platelet Glycoprotein GPIIb-IIIa Complex KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Alleles KW - Polymorphism, Restriction Fragment Length KW - Humans KW - Molecular Sequence Data KW - Japan -- ethnology KW - DNA Primers -- chemistry KW - Antigens, Human Platelet -- genetics KW - Platelet Glycoprotein GPIIb-IIIa Complex -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78358404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transfusion&rft.atitle=Allele-specific+restriction+analysis+of+human+platelet+antigen+system+4.&rft.au=Matsuo%2C+K%3BReid%2C+D+M&rft.aulast=Matsuo&rft.aufirst=K&rft.date=1996-09-01&rft.volume=36&rft.issue=9&rft.spage=809&rft.isbn=&rft.btitle=&rft.title=Transfusion&rft.issn=00411132&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-31 N1 - Date created - 1996-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of tumor development with increased cellular proliferation and transgene overexpression, but not c-Ha-ras mutations, in v-Ha-ras transgenic Tg.AC mice. AN - 78354511; 8824502 AB - The transgenic mouse line Tg.AC carries a v-Ha-ras gene fused to a fetal (zeta) globin promoter and uniquely responds to chemical carcinogens and tumor promoters by the induction of epidermal papillomas. Although the transgene was not constitutively expressed in non-tumor-bearing tissues, expression was induced by exposure to selected chemicals. Tg.AC transgenic mice on the FVB/N background developed occasional spontaneous tumors, including odontomas, squamous cell carcinoma of the salivary gland, leukemias and a rare ovarian yolk sac carcinoma. Both spontaneous and induced tumors are associated with expression of the transgene and, as determined by in situ hybridization, transgene expression is localized to proliferative areas of the tumors. Sequence analysis of the endogenous c-Ha-ras gene in both induced and spontaneous tumors revealed no mutations in codons 12, 59 or 61. These results suggest that expression of the v-Ha-ras transgene induces proliferation of specific cells in diverse tissues which then acquire neoplastic properties. JF - Carcinogenesis AU - Hansen, L A AU - Trempus, C S AU - Mahler, J F AU - Tennant, R W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 1825 EP - 1833 VL - 17 IS - 9 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Codon KW - DNA Primers KW - Proliferating Cell Nuclear Antigen KW - RNA, Messenger KW - Globins KW - 9004-22-2 KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - Index Medicus KW - Animals KW - Fetus KW - Globins -- genetics KW - RNA, Messenger -- analysis KW - Transcription, Genetic KW - Mice KW - Proliferating Cell Nuclear Antigen -- analysis KW - Mice, Transgenic KW - RNA, Messenger -- biosynthesis KW - Mice, Inbred Strains KW - Polymerase Chain Reaction KW - Promoter Regions, Genetic KW - In Situ Hybridization KW - Female KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Proto-Oncogene Proteins p21(ras) -- biosynthesis KW - Papilloma -- pathology KW - Oncogene Protein p21(ras) -- biosynthesis KW - Neoplasms, Experimental -- chemically induced KW - Skin Neoplasms -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Carcinogens -- toxicity KW - Skin Neoplasms -- pathology KW - Papilloma -- genetics KW - Neoplasms, Experimental -- pathology KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78354511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Association+of+tumor+development+with+increased+cellular+proliferation+and+transgene+overexpression%2C+but+not+c-Ha-ras+mutations%2C+in+v-Ha-ras+transgenic+Tg.AC+mice.&rft.au=Hansen%2C+L+A%3BTrempus%2C+C+S%3BMahler%2C+J+F%3BTennant%2C+R+W&rft.aulast=Hansen&rft.aufirst=L&rft.date=1996-09-01&rft.volume=17&rft.issue=9&rft.spage=1825&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-09 N1 - Date created - 1996-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human CSB (ERCC6) gene corrects the transcription-coupled repair defect in the CHO cell mutant UV61. AN - 78353519; 8811084 AB - The human CSB gene, mutated in Cockayne's syndrome group B (partially defective in both repair and transcription) was previously cloned by virtue of its ability to correct the moderate UV sensitivity of the CHO mutant UV61. To determine whether the defect in UV61 is the hamster equivalent of Cockayne's syndrome, the RNA polymerase II transcription and DNA repair characteristics of a repair-proficient CHO cell line (AA8), UV61 and a CSB transfectant of UV61 were compared. In each cell line, formation and removal of UV-induced cyclobutane pyrimidine dimers (CPDs) were measured in the individual strands of the actively transcribed DHFR gene and in a transcriptionally inactive region downstream of DHFR. AA8 cells efficiently remove CPDs from the transcribed strand, but not from either the non-transcribed strand or the inactive region. There was no detectable repair of CPDs in any region of the genome in UV61. Transfection of the human CSB gene into UV61 restores the normal repair pattern (CPD removal in only the transcribed strand), demonstrating that the DNA repair defect in UV61 is homologous to that in Cockayne's syndrome (complementation group B) cells. However, we observe no significant deficiency in RNA polymerase II-mediated transcription in UV61, suggesting that the CSB protein has independent roles in DNA repair and RNA transcription pathways. JF - Nucleic acids research AU - Orren, D K AU - Dianov, G L AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1996/09/01/ PY - 1996 DA - 1996 Sep 01 SP - 3317 EP - 3322 VL - 24 IS - 17 SN - 0305-1048, 0305-1048 KW - Pyrimidine Dimers KW - 0 KW - DNA Polymerase II KW - EC 2.7.7.- KW - DNA Helicases KW - EC 3.6.4.- KW - ERCC6 protein, human KW - EC 3.6.4.12 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Animals KW - Genes, myc KW - Pyrimidine Dimers -- metabolism KW - Humans KW - Dose-Response Relationship, Radiation KW - Cell Survival KW - Transfection KW - DNA Polymerase II -- metabolism KW - Ultraviolet Rays -- adverse effects KW - Genetic Complementation Test KW - CHO Cells KW - Cell-Free System KW - DNA Repair -- genetics KW - Cockayne Syndrome -- genetics KW - DNA Helicases -- genetics KW - Transcription, Genetic KW - Mutation KW - Cricetinae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78353519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=The+human+CSB+%28ERCC6%29+gene+corrects+the+transcription-coupled+repair+defect+in+the+CHO+cell+mutant+UV61.&rft.au=Orren%2C+D+K%3BDianov%2C+G+L%3BBohr%2C+V+A&rft.aulast=Orren&rft.aufirst=D&rft.date=1996-09-01&rft.volume=24&rft.issue=17&rft.spage=3317&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-25 N1 - Date created - 1996-11-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1995 Aug 25;82(4):555-64 [7664335] J Biol Chem. 1996 Apr 5;271(14):8285-94 [8626523] Somatic Cell Genet. 1980 May;6(3):407-18 [7404271] J Biol Chem. 1980 Dec 25;255(24):11992-6 [7440580] Cancer Res. 1982 Apr;42(4):1473-8 [6174225] Somatic Cell Genet. 1982 Nov;8(6):759-73 [7163954] Methods Enzymol. 1983;101:568-82 [6193397] Proc Natl Acad Sci U S A. 1984 Dec;81(23):7397-401 [6390436] Cell. 1985 Feb;40(2):359-69 [3838150] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4394-8 [3925456] Proc Natl Acad Sci U S A. 1986 Dec;83(23):8878-82 [3466163] Cell. 1987 Oct 23;51(2):241-9 [3664636] Mutat Res. 1988 Jan;193(1):53-63 [3275879] Nucleic Acids Res. 1988 Feb 11;16(3):1215 [3344216] Mutagenesis. 1989 Mar;4(2):140-6 [2659925] Mol Cell Biol. 1989 Jul;9(7):2881-9 [2476659] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4707-11 [2352945] Cell. 1995 Mar 24;80(6):859-68 [7697716] Mutat Res. 1995 May;336(3):223-33 [7739610] J Biol Chem. 1990 Aug 15;265(23):13906-13 [2380193] Mol Cell Biol. 1990 Nov;10(11):5806-13 [2172786] Mutat Res. 1991 Sep;255(2):183-91 [1922150] Mutat Res. 1991 Nov;255(3):281-91 [1719400] Cell. 1992 Dec 11;71(6):939-53 [1339317] J Biol Chem. 1993 Jan 25;268(3):1650-7 [8420940] Science. 1993 Apr 2;260(5104):53-8 [8465200] Nature. 1993 May 13;363(6425):114-5 [8483493] Nucleic Acids Res. 1993 Dec 25;21(25):5890-5 [8290349] Mutat Res. 1994 May;314(3):221-31 [7513055] Mutat Res. 1994 May 1;307(1):5-14 [7513823] Nat Genet. 1994 Jun;7(2):189-94 [7920640] EMBO J. 1994 Nov 15;13(22):5361-9 [7957102] EMBO J. 1995 Jan 16;14(2):360-7 [7835346] Cancer Res. 1995 Oct 1;55(19):4325-32 [7671243] Mutat Res. 1995 Oct;338(1-6):25-34 [7565878] Trends Biochem Sci. 1995 Oct;20(10):402-5 [8533152] Carcinogenesis. 1995 Dec;16(12):2885-92 [8603460] Carcinogenesis. 1995 Dec;16(12):3075-81 [8603488] Cell. 1979 Oct;18(2):469-84 [498279] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The genomic structure of the gene encoding the human transforming growth factor beta type II receptor (TGF-beta RII). AN - 78344228; 8812462 AB - The genomic structure of the human transforming growth factor-beta type II receptor gene (TGF-beta RII) was determined by two PCR-based methods, the "long distance sequencer" method and the "promoter finder" method. Genomic fragments containing exons and adjacent introns were amplified by PCR, and the nucleotide sequences were determined by direct sequencing and subcloning sequencing. The TGF-beta RII protein is encoded by 567 codons in 7 exons. This is the first report about the genomic structure of a gene that belongs to the serine/threonine kinase type II receptor subfamily. Knowledge of the genomic structure of the TGF-beta RII gene will facilitate investigation of the TGF-beta signaling pathway in normal human cells and of the aberrations occurring during carcinogenesis. JF - Genomics AU - Takenoshita, S AU - Hagiwara, K AU - Nagashima, M AU - Gemma, A AU - Bennett, W P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Institutes of Health, Bethesda, Maryland, 20892-4255, USA. Y1 - 1996/09/01/ PY - 1996 DA - 1996 Sep 01 SP - 341 EP - 344 VL - 36 IS - 2 SN - 0888-7543, 0888-7543 KW - Receptors, Transforming Growth Factor beta KW - 0 KW - DNA KW - 9007-49-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Receptors, Transforming Growth Factor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78344228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=The+genomic+structure+of+the+gene+encoding+the+human+transforming+growth+factor+beta+type+II+receptor+%28TGF-beta+RII%29.&rft.au=Takenoshita%2C+S%3BHagiwara%2C+K%3BNagashima%2C+M%3BGemma%2C+A%3BBennett%2C+W+P%3BHarris%2C+C+C&rft.aulast=Takenoshita&rft.aufirst=S&rft.date=1996-09-01&rft.volume=36&rft.issue=2&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U52246; GENBANK; U52245; U52244; U52240; U52241; U52242; U52243 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Photosensitization by norfloxacin is a function of pH. AN - 78322414; 8806228 AB - Norfloxacin is a fluoroquinolone (FQ) antibiotic that has been reported to cause cutaneous photosensitivity in animals and occasionally in humans. We have studied the fluorescence and singlet oxygen (1O2)-generating properties of norfloxacin. Upon UV excitation the drug fluoresces in water, and the relative intensities of two major fluorescence bands at ca 420 and 450 nm are affected by pH. The overall quantum yield of fluorescence (phi F) is also strongly pH dependent: phi F is low in 0.2 N HCl solution (0.2), increasing steeply to 0.12 at pH 4, then gradually decreasing to 0.01 at pH 10. The changes in phi F are accompanied by changes in fluorescence lifetime from 0.6 ns at pH 1 to 1.8 ns at pH 4. Norfloxacin exhibits phosphorescence in low temperature glasses. The formation of a triplet state at room temperature is also suggested by 1O2 phosphorescence in aerobic D2O. This phosphorescence is "self-quenched" by norfloxacin itself with an efficiency that is pH dependent: kq is 7.9 x 10(6) M-1 s-1 at pD 4, decreases to 1.9 x 10(6) M-1 s-1 at pD 7.5 but then increases about 20-fold in alkaline D2O solutions. This quenching causes the observed 1O2 production by norfloxacin (0.1 mM) to show a maximum at around pH 8-9. However, after correction for self-quenching, the quantum yield of 1O2 production (phi 50)y measured by using perinaphthenone as a standard, yielded the following values: phi s0 is about 0.07 in 0.2 N DCI solution, 0.08 at pH 7.5 and then increases smoothly to approximately 0.2 in 0.1 M NaOD solution. The relatively high, unquenched 1O2 production at physiological pH 7.4 (phi s0 approximately 0.08) suggests that 1O2 reactions may play an important role in the cutaneous phototoxicity of norfloxacin and other FQ antibiotics. JF - Photochemistry and photobiology AU - Bilski, P AU - Martinez, L J AU - Koker, E B AU - Chignell, C F AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Bilski@NIEHS.NIH.gov Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 496 EP - 500 VL - 64 IS - 3 SN - 0031-8655, 0031-8655 KW - Anti-Infective Agents KW - 0 KW - Singlet Oxygen KW - 17778-80-2 KW - Norfloxacin KW - N0F8P22L1P KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Spectrometry, Fluorescence KW - Hydrogen-Ion Concentration KW - Humans KW - Ultraviolet Rays -- adverse effects KW - Oxygen -- chemistry KW - Anti-Infective Agents -- toxicity KW - Dermatitis, Phototoxic -- metabolism KW - Norfloxacin -- toxicity KW - Dermatitis, Phototoxic -- etiology KW - Norfloxacin -- chemistry KW - Anti-Infective Agents -- radiation effects KW - Anti-Infective Agents -- chemistry KW - Norfloxacin -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78322414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brazilian+journal+of+medical+and+biological+research+%3D+Revista+brasileira+de+pesquisas+medicas+e+biologicas&rft.atitle=Ha-ras+oncogene+transformation+abolishes+retinoic+acid-induced+reduction+of+intracellular+fibronectin.&rft.au=De-Luca%2C+L+M%3BScita%2C+G&rft.aulast=De-Luca&rft.aufirst=L&rft.date=1996-09-01&rft.volume=29&rft.issue=9&rft.spage=1127&rft.isbn=&rft.btitle=&rft.title=Brazilian+journal+of+medical+and+biological+research+%3D+Revista+brasileira+de+pesquisas+medicas+e+biologicas&rft.issn=0100879X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-12 N1 - Date created - 1996-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hydrophilic side chains in the third and seventh transmembrane helical domains of human A2A adenosine receptors are required for ligand recognition. AN - 78313252; 8794889 AB - Hydrophilic residues of the G protein-coupled human A2A adenosine receptor that are potentially involved in the binding of the ribose moiety of adenosine were targeted for mutagenesis. Residues in a T88QSS91 sequence in the third transmembrane helical domain (TM3) were individually replaced with alanine and other amino acids. Two additional serine residues in TM7 that were previously shown to be involved in ligand binding were mutated to other uncharged, hydrophilic amino acids. The binding affinity of agonists at T88 mutant receptors was greatly diminished, although the receptors were well expressed and bound antagonists similar to the wild-type receptor. Thus, mutations that are specific for diminishing the affinity of ribose-containing ligands (i.e., adenosine agonists) have been identified in both TM3 and TM7. The T88A and T88S mutant receptor fully stimulated adenylyl cyclase, with the dose-response curves to CGS 21680 highly shifted to the right. A Q89A mutant gained affinity for all agonist and antagonist ligands examined in binding and functional assays. Q89 likely plays an indirect role in ligand binding. S90A, S91A, and S277C mutant receptors displayed only moderate changes in ligand affinity. A S281N mutant gained affinity for all adenosine derivatives (agonists), but antagonist affinity was generally diminished, with the exception of a novel tetrahydrobenzothiophenone derivative. JF - Molecular pharmacology AU - Jiang, Q AU - Van Rhee, A M AU - Kim, J AU - Yehle, S AU - Wess, J AU - Jacobson, K A AD - Molecular Recognition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 512 EP - 521 VL - 50 IS - 3 SN - 0026-895X, 0026-895X KW - Ligands KW - 0 KW - Oligodeoxyribonucleotides KW - Receptor, Adenosine A2A KW - Receptors, Purinergic P1 KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - Ribose KW - 681HV46001 KW - Cyclic AMP KW - E0399OZS9N KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Adenosine KW - K72T3FS567 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Humans KW - Adenylyl Cyclases -- metabolism KW - Sequence Tagged Sites KW - Amino Acid Sequence KW - Radioligand Assay KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Kinetics KW - Binding, Competitive KW - Point Mutation KW - Cyclic AMP -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Receptors, Purinergic P1 -- chemistry KW - Adenosine -- agonists KW - Protein Structure, Secondary KW - Receptors, Purinergic P1 -- physiology KW - Adenosine -- chemistry KW - Receptors, Purinergic P1 -- metabolism KW - Adenosine -- antagonists & inhibitors KW - Adenosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78313252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Hydrophilic+side+chains+in+the+third+and+seventh+transmembrane+helical+domains+of+human+A2A+adenosine+receptors+are+required+for+ligand+recognition.&rft.au=Jiang%2C+Q%3BVan+Rhee%2C+A+M%3BKim%2C+J%3BYehle%2C+S%3BWess%2C+J%3BJacobson%2C+K+A&rft.aulast=Jiang&rft.aufirst=Q&rft.date=1996-09-01&rft.volume=50&rft.issue=3&rft.spage=512&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-31 N1 - Date created - 1996-10-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuroscience. 1994 Dec;63(3):765-73 [7898676] J Biol Chem. 1994 Nov 11;269(45):27900-6 [7961722] J Comput Aided Mol Des. 1995 Feb;9(1):44-54 [7751869] J Biol Chem. 1995 Jun 9;270(23):13987-97 [7775460] Br J Pharmacol. 1995 Jul;115(6):1096-102 [7582508] J Med Chem. 1996 Jan 19;39(2):398-406 [8558508] N Engl J Med. 1996 Feb 22;334(8):507-12 [8559204] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] Mol Pharmacol. 1983 May;23(3):576-84 [6306429] Mol Pharmacol. 1985 Jun;27(6):595-9 [2987658] Methods Enzymol. 1987;152:684-704 [3657593] J Biol Chem. 1988 Jul 25;263(21):10267-71 [2899076] Science. 1989 May 5;244(4904):569-72 [2541503] J Biol Chem. 1989 Aug 15;264(23):13572-8 [2547766] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6572-6 [2771944] J Pharmacol Exp Ther. 1989 Dec;251(3):888-93 [2600819] Mol Pharmacol. 1989 Dec;36(6):840-7 [2557534] J Mol Recognit. 1989 Dec;2(4):170-8 [2561548] Physiol Rev. 1990 Jul;70(3):761-845 [2194223] J Biol Chem. 1990 Aug 15;265(23):13702-8 [2380182] J Biol Chem. 1991 Jan 5;266(1):5-8 [1670767] J Mol Biol. 1991 Jul 20;220(2):507-30 [1856871] J Biol Chem. 1992 Jan 25;267(3):1430-3 [1346134] J Med Chem. 1992 Feb 7;35(3):407-22 [1738138] J Biol Chem. 1992 May 25;267(15):10764-70 [1587851] J Biol Chem. 1992 Jun 5;267(16):11439-48 [1317867] Mol Pharmacol. 1992 Jul;42(1):123-33 [1635550] Med Res Rev. 1992 Sep;12(5):423-71 [1513184] J Biol Chem. 1992 Oct 15;267(29):20840-3 [1356984] Eur J Pharmacol. 1992 Oct 1;227(2):205-14 [1358663] FEBS Lett. 1992 Nov 9;312(2-3):259-62 [1426261] J Biol Chem. 1992 Dec 25;267(36):25668-71 [1281470] J Biol Chem. 1993 Mar 5;268(7):4661-7 [8444840] Mol Pharmacol. 1993 Jun;43(6):931-40 [8316224] J Biol Chem. 1993 Aug 5;268(22):16483-7 [8393865] Pharmacol Biochem Behav. 1993 Aug;45(4):951-8 [8105493] J Biol Chem. 1994 Jan 28;269(4):2373-6 [8300561] J Med Chem. 1994 Mar 4;37(5):636-46 [8126704] J Biol Chem. 1994 Jul 8;269(27):18016-20 [8027060] Eur J Pharmacol. 1994 May 2;256(3):263-8 [8045270] Prog Neuropsychopharmacol Biol Psychiatry. 1994 May;18(3):545-53 [8078988] Eur J Pharmacol. 1994 Jun 15;268(1):95-104 [7925617] Neuron. 1995 Apr;14(4):825-31 [7718244] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constitutive activation of a phosphoinositidase C-linked G protein in murine fibroblasts decreases agonist-stimulated Ca2+ mobilization. AN - 78311693; 8794886 AB - We compared Ca2+ signaling and inositol polyphosphate metabolism in NIH-3T3 cells stably transfected with cDNA encoding either the wild-type G protein G16 alpha subunit or a GTPase-deficient alpha 16 subunit (Q212L-alpha 16). Constitutive activation of phosphoinositidase C (PIC) in cells expressing Q212L-alpha 16 was demonstrated by 1) an increased basal level of [3H]inositol polyphosphates, 2) an enhanced rate of [3H]inositol polyphosphate accumulation in cells treated with 10 mM LiCl, and 3) an increased rate of incorporation of [3H]inositol into cell lipids. Q212L-alpha 16 cells had a diminished cell growth rate. Basal intracellular Ca2+ concentration was equivalent in Fura-2 acetoxymethyl ester-loaded Q212L-alpha 16 cells compared with controls; however, calcium release in Q212L-alpha 16 cells exposed to ionomycin, ATP (a G protein-linked agonist), or platelet-derived growth factor (a tyrosine kinase-linked agonist) was decreased. Permeabilized, 45Ca-loaded Q212L-alpha 16 cells released less 45Ca at each concentration of inositol-1,4,5-trisphosphate than did control cells. Accordingly, the total amount of inositol trisphosphate (IP3) receptor protein was decreased in Q212L-alpha 16 cells relative to controls. These data demonstrate that Q212L-alpha 16 cells maintain physiological levels of cytoplasmic calcium and partially loaded Ca2+ stores in the face of constitutively active PIC. This is accomplished, at least in part, by down-regulation of IP3 receptor number. Thus, diminution in cell growth rate in Q212L-alpha 16 cells seems to be attributable to a combination of at least two effects: a direct effect of PIC activation leading to partial depletion of Ca2+ stores and an indirect, adaptive response resulting in a decreased IP3 receptor number. JF - Molecular pharmacology AU - Lobaugh, L A AU - Eisfelder, B AU - Gibson, K AU - Johnson, G L AU - Putney, J W AD - Calcium Regulation Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 493 EP - 500 VL - 50 IS - 3 SN - 0026-895X, 0026-895X KW - Chelating Agents KW - 0 KW - Enzyme Inhibitors KW - Inositol Phosphates KW - Platelet-Derived Growth Factor KW - Recombinant Proteins KW - Inositol KW - 4L6452S749 KW - Egtazic Acid KW - 526U7A2651 KW - Ionomycin KW - 56092-81-0 KW - Thapsigargin KW - 67526-95-8 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - glycerophosphoinositol glycerophosphodiesterase KW - EC 3.1.4.44 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Proteins KW - Calcium-Transporting ATPases KW - EC 3.6.3.8 KW - Lithium Chloride KW - G4962QA067 KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid KW - K22DDW77C0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Inositol Phosphates -- metabolism KW - Humans KW - Platelet-Derived Growth Factor -- pharmacology KW - Ionomycin -- pharmacology KW - Inositol -- metabolism KW - Mutagenesis, Site-Directed KW - Chelating Agents -- pharmacology KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Lithium Chloride -- pharmacology KW - Sequence Deletion KW - Cytosol -- metabolism KW - 3T3 Cells KW - Egtazic Acid -- analogs & derivatives KW - HL-60 Cells KW - Calcium-Transporting ATPases -- antagonists & inhibitors KW - Mice KW - Thapsigargin -- pharmacology KW - Protein Kinase C -- metabolism KW - Transfection KW - GTP Phosphohydrolases -- metabolism KW - Kinetics KW - Enzyme Inhibitors -- pharmacology KW - Egtazic Acid -- pharmacology KW - Calcium -- metabolism KW - GTP-Binding Proteins -- biosynthesis KW - GTP-Binding Proteins -- metabolism KW - Phosphoric Diester Hydrolases -- biosynthesis KW - Phosphoric Diester Hydrolases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78311693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Constitutive+activation+of+a+phosphoinositidase+C-linked+G+protein+in+murine+fibroblasts+decreases+agonist-stimulated+Ca2%2B+mobilization.&rft.au=Lobaugh%2C+L+A%3BEisfelder%2C+B%3BGibson%2C+K%3BJohnson%2C+G+L%3BPutney%2C+J+W&rft.aulast=Lobaugh&rft.aufirst=L&rft.date=1996-09-01&rft.volume=50&rft.issue=3&rft.spage=493&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-31 N1 - Date created - 1996-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury. AN - 78303139; 8790049 AB - We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n = 9), VEGF 0.72 mg (n = 9), or saline (n = 10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n = 6) or saline (n = 5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury. Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease. JF - Circulation AU - Lazarous, D F AU - Shou, M AU - Scheinowitz, M AU - Hodge, E AU - Thirumurti, V AU - Kitsiou, A N AU - Stiber, J A AU - Lobo, A D AU - Hunsberger, S AU - Guetta, E AU - Epstein, S E AU - Unger, E F AD - Experimental Physiology and Pharmacology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892-1650, USA. Y1 - 1996/09/01/ PY - 1996 DA - 1996 Sep 01 SP - 1074 EP - 1082 VL - 94 IS - 5 SN - 0009-7322, 0009-7322 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Abridged Index Medicus KW - Index Medicus KW - Hemodynamics -- drug effects KW - Animals KW - Dogs KW - Arteries -- drug effects KW - Male KW - Female KW - Fibroblast Growth Factor 2 -- pharmacology KW - Endothelial Growth Factors -- pharmacology KW - Collateral Circulation -- drug effects KW - Fibroblast Growth Factor 2 -- toxicity KW - Endothelial Growth Factors -- toxicity KW - Lymphokines -- pharmacology KW - Muscle, Smooth, Vascular -- drug effects KW - Lymphokines -- pharmacokinetics KW - Lymphokines -- toxicity KW - Endothelial Growth Factors -- pharmacokinetics KW - Coronary Circulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78303139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Comparative+effects+of+basic+fibroblast+growth+factor+and+vascular+endothelial+growth+factor+on+coronary+collateral+development+and+the+arterial+response+to+injury.&rft.au=Lazarous%2C+D+F%3BShou%2C+M%3BScheinowitz%2C+M%3BHodge%2C+E%3BThirumurti%2C+V%3BKitsiou%2C+A+N%3BStiber%2C+J+A%3BLobo%2C+A+D%3BHunsberger%2C+S%3BGuetta%2C+E%3BEpstein%2C+S+E%3BUnger%2C+E+F&rft.aulast=Lazarous&rft.aufirst=D&rft.date=1996-09-01&rft.volume=94&rft.issue=5&rft.spage=1074&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-17 N1 - Date created - 1996-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pollutants in breast milk. AN - 78297528; 8790132 AB - To review data on the occurrence and toxicity of the commonly reported pesticides and industrial environmental pollutant chemicals in breast milk. Continuous automated literature surveillance plus contact with investigators and governmental agencies. For data on occurrence, the most recent data from the largest data sets on the most representative donors were used. For data on toxicity, the primary report that was publicly available was used. When necessary, data were reexpressed or concentrations were rescaled. The original investigator was contacted if necessary. Although pollutant chemicals are readily detected in most human milk worldwide, there is little evidence for consequent morbidity in nurslings. There have been several mass poisonings in which chemicals that were transmitted through breast milk clearly affected children who were breast-fed, and there is some evidence that prenatal exposure to background levels resulted in mild developmental delay and that lactation per se was disturbed. Breast-feeding is recommended despite the presence of chemical residues. The prenatal period in the child and the initiation of lactation in the mother may be sensitive periods to the toxicity of the chemicals that are considered here, and the potential for poisoning at higher levels is clear. However, in the vast majority of women, the benefits of breast-feeding appear to outweigh the risks, and those who advise women about infant nutrition should continue to support breast-feeding. JF - Archives of pediatrics & adolescent medicine AU - Rogan, W J AD - Office of Clinical Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. rogan@niehs.nih.gov Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 981 EP - 990 VL - 150 IS - 9 SN - 1072-4710, 1072-4710 KW - Environmental Pollutants KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Developmental Disabilities -- chemically induced KW - Primary Prevention KW - Maximum Allowable Concentration KW - Breast Feeding KW - Humans KW - Neoplasms -- chemically induced KW - Infant, Newborn KW - Databases, Factual KW - Maternal Exposure KW - Female KW - Population Surveillance KW - Milk, Human -- chemistry KW - Environmental Pollutants -- analysis KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78297528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+pediatrics+%26+adolescent+medicine&rft.atitle=Pollutants+in+breast+milk.&rft.au=Rogan%2C+W+J&rft.aulast=Rogan&rft.aufirst=W&rft.date=1996-09-01&rft.volume=150&rft.issue=9&rft.spage=981&rft.isbn=&rft.btitle=&rft.title=Archives+of+pediatrics+%26+adolescent+medicine&rft.issn=10724710&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-17 N1 - Date created - 1996-10-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Arch Pediatr Adolesc Med 1996 Dec;150(12):1282 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair. AN - 78296958; 8782829 AB - Many human tumours have length alterations in repetitive sequence elements. Although this microsatellite instability has been attributed to mutations in four DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds, many sporadic tumours exhibit instability but no detectable mutations in these genes. It is therefore of interest to identify other genes that contribute to this instability. In yeast, mutations in several genes, including RTH and MSH3, cause microsatellite instability. Thus, we screened 16 endometrial carcinomas with microsatellite instability for alterations in FEN1 (the human homolog of RTH) and in MSH3 (refs 12-14). Although we found no FEN1 mutations, a frameshift mutation in MSH3 was observed in an endometrial carcinoma and in an endometrial carcinoma cell line. Extracts of the cell line were deficient in repair of DNA substrates containing mismatches or extra nucleotides. Introducing chromosome 5, encoding the MSH3 gene, into the mutant cell line increased the stability of some but not all microsatellites. Extracts of these cells repaired certain substrates containing extra nucleotides, but were deficient in repair of those containing mismatches or other extra nucleotides. A subsequent search revealed a second gene mutation in HHUA cells, a missense mutation in the MSH6 gene. Together the data suggest that the MSH3 gene encodes a product that functions in repair of some but not all pre-mutational intermediates, its mutation in tumours can result in genomic instability and, as in yeast, MSH3 and MSH6 are partially redundant for mismatch repair. JF - Nature genetics AU - Risinger, J I AU - Umar, A AU - Boyd, J AU - Berchuck, A AU - Kunkel, T A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 102 EP - 105 VL - 14 IS - 1 SN - 1061-4036, 1061-4036 KW - DNA, Neoplasm KW - 0 KW - Nucleic Acid Heteroduplexes KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Female KW - DNA Repair KW - Endometrial Neoplasms -- genetics KW - Mutation KW - Endometrial Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78296958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Mutation+of+MSH3+in+endometrial+cancer+and+evidence+for+its+functional+role+in+heteroduplex+repair.&rft.au=Risinger%2C+J+I%3BUmar%2C+A%3BBoyd%2C+J%3BBerchuck%2C+A%3BKunkel%2C+T+A%3BBarrett%2C+J+C&rft.aulast=Risinger&rft.aufirst=J&rft.date=1996-09-01&rft.volume=14&rft.issue=1&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mice homozygous for an insertional mutation in the Zp3 gene lack a zona pellucida and are infertile. AN - 78296166; 8787763 AB - Mammalian oocytes synthesize and secrete a zona pellucida that surrounds the growing oocytes, ovulated eggs and preimplantation embryos. The extracellular zona matrix is composed of three glycoproteins (ZP1, ZP2, ZP3) that are involved in folliculogenesis, species-specific fertilization, and passage of the early embryo down the oviduct. We have established a mouse line in which Zp3 has been inactivated by homologous recombination with an insertional mutation. Neither Zp3 transcripts nor ZP3 protein was detected in female mice homozygous for the mutation (Zp3-/-), whereas both ZP1 and ZP2 were present in mutant oocytes. Homozygous mutant Zp3-/- mice had follicles with germinal-vesicle-intact oocytes but that lacked a zona pellucida matrix and had a disorganized corona radiata. Although mutant oocytes underwent germinal vesicle breakdown (GVBD) prior to ovulation, the cumulus-oocyte complex was markedly disrupted and the oocytes were often separate from the cumulus cells. After hormone-induced ovulation, cumulus masses were present in the oviducts of homozygous mutant mice, but zona-free eggs were observed in only half of the females and, in these, less than 10% of the normal number [correction of mumber] of eggs were detected. No zona-free 2-cell embryos were recovered from homozygous mutant Zp3-/- female mice after mating with males proven to be fertile, and none became visibly pregnant or produced offspring. These results demonstrate that a genetic defect in a zona pellucida gene causes infertility and, given the conserved nature of the zona pellucida, a similar phenotype is expected in other mammals. JF - Development (Cambridge, England) AU - Rankin, T AU - Familari, M AU - Lee, E AU - Ginsberg, A AU - Dwyer, N AU - Blanchette-Mackie, J AU - Drago, J AU - Westphal, H AU - Dean, J AD - Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 2903 EP - 2910 VL - 122 IS - 9 SN - 0950-1991, 0950-1991 KW - Egg Proteins KW - 0 KW - Membrane Glycoproteins KW - RNA, Antisense KW - Receptors, Cell Surface KW - Zona Pellucida Glycoproteins KW - Zp1 protein, mouse KW - Zp2 protein, mouse KW - Zp3 protein, mouse KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - Homozygote KW - Mice KW - RNA, Antisense -- genetics KW - Mice, Transgenic KW - Genotype KW - In Situ Hybridization KW - Ovulation KW - Ovary -- pathology KW - Blotting, Southern KW - RNA, Antisense -- metabolism KW - Gene Targeting KW - Immunohistochemistry KW - Mutagenesis, Insertional KW - Female KW - Male KW - Infertility, Female -- pathology KW - Oocytes -- metabolism KW - Infertility, Female -- etiology KW - Egg Proteins -- genetics KW - Egg Proteins -- metabolism KW - Zona Pellucida -- metabolism KW - Oocytes -- chemistry KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78296166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Inhibitory+and+noninhibitory+monoclonal+antibodies+to+human+cytochrome+P450+2E1.&rft.au=Gelboin%2C+H+V%3BGoldfarb%2C+I%3BKrausz%2C+K+W%3BGrogan%2C+J%3BKorzekwa%2C+K+R%3BGonzalez%2C+F+J%3BShou%2C+M&rft.aulast=Gelboin&rft.aufirst=H&rft.date=1996-09-01&rft.volume=9&rft.issue=6&rft.spage=1023&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-07 N1 - Date created - 1996-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats. AN - 78291851; 8782824 AB - Identification of specific genetic loci that contribute to susceptibility to rheumatoid arthritis (RA) in humans has been hampered by several factors, including: i) multiple interacting genetic loci contributing to susceptibility; ii) complex interactions of environmental and genetic factors; iii) genetic heterogeneity; and iv) low penetrance. We have, therefore, mapped quantitative trait loci (QTLs) that control inflammatory arthritis susceptibility and/or severity in progeny of two inbred rat strains with significantly different susceptibilities to collagen-induced arthritis (CIA), an animal model for RA. Not surprisingly, we identified a major susceptibility factor, Cia1, on chromosome 20 in the vicinity of the rat major histocompatibility complex (MHC). However, by limiting the analysis to animals with arthritis-susceptible MHC genotypes and using genome-wide QTL analytic techniques, we also found four non-MHC QTLs-Cia2, 3, 4 and 5-on chromosomes 1, 4, 7 and 10, that contributed to disease severity. In addition, a QTL on chromosome 8 was suggestive for linkage. Characterization of the genes underlying these QTLs will facilitate the identification of key biochemical pathways regulating experimental autoimmune arthritis in rats and may provide insights into RA and other human autoimmune diseases. These genes may also represent novel targets for therapy. JF - Nature genetics AU - Remmers, E F AU - Longman, R E AU - Du, Y AU - O'Hare, A AU - Cannon, G W AU - Griffiths, M M AU - Wilder, R L AD - Inflammatory Joint Diseases Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 82 EP - 85 VL - 14 IS - 1 SN - 1061-4036, 1061-4036 KW - DNA Primers KW - 0 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Base Sequence KW - Molecular Sequence Data KW - Major Histocompatibility Complex KW - Genome KW - Male KW - Female KW - Arthritis -- genetics KW - Arthritis -- chemically induced KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78291851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=A+genome+scan+localizes+five+non-MHC+loci+controlling+collagen-induced+arthritis+in+rats.&rft.au=Remmers%2C+E+F%3BLongman%2C+R+E%3BDu%2C+Y%3BO%27Hare%2C+A%3BCannon%2C+G+W%3BGriffiths%2C+M+M%3BWilder%2C+R+L&rft.aulast=Remmers&rft.aufirst=E&rft.date=1996-09-01&rft.volume=14&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of Lck in CD45-negative T cells: dominant role of tyrosine 394 phosphorylation in kinase activity. AN - 78251417; 8756658 AB - The CD45 tyrosine phosphatase has been reported to activate the src family tyrosine kinases Lck and Fyn by dephosphorylating regulatory COOH-terminal tyrosine residues 505 and 528, respectively. However, recent studies with CD45- T-cell lines have found that despite the fact that Lck and Fyn were constitutively hyperphosphorylated, the tyrosine kinase activity of both enzymes was actually increased. In the present study, phosphoamino acid analysis revealed that the increased phosphorylation of Lck in CD45- YAC-1 T cells was restricted to tyrosine residues. To understand the relationship between tyrosine phosphorylation and Lck kinase activity, CD45- YAC-1 cells were transfected with forms of Lck in which tyrosines whose phosphorylation is thought to regulate enzyme activity (Tyr-192, Tyr-394, Tyr-505, or both Tyr-394 and Tyr-505) were replaced with phenylalanine. While the Y-to-F mutation at position 192 (192-Y-->F) had little effect, the 505-Y-->F mutation increased enzymatic activity. In contrast, the 394-Y-->F mutation decreased the kinase activity to very low levels, an effect that the double mutation, 394-Y-->F and 505Y-->F, could not reverse. Phosphopeptide analysis of tryptic digests of Lck from CD45- YAC-1 cells revealed that it is hyperphosphorylated on two tyrosine residues, Tyr-505 and, to a lesser extent, Tyr-394. The purified and enzymatically active intracellular portion of CD45 dephosphorylated Lck Tyr-394 in vitro. These results demonstrate that in addition to Tyr-505, CD45 can dephosphorylate Tyr-394, and that in the absence of CD45 the hyperphosphorylation of Tyr-394 can cause an increase in the kinase activity of Lck despite the inhibitory hyperphosphorylation of Tyr-505. Therefore, Lck kinase activity is determined by the balance of activating and inhibitory tyrosine phosphorylations that are, in turn, regulated by CD45. JF - Molecular and cellular biology AU - D'Oro, U AU - Sakaguchi, K AU - Appella, E AU - Ashwell, J D AD - Laboratory of Immune Cell Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 4996 EP - 5003 VL - 16 IS - 9 SN - 0270-7306, 0270-7306 KW - Neoplasm Proteins KW - 0 KW - Proto-Oncogene Proteins KW - Recombinant Fusion Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - FYN protein, human KW - EC 2.7.10.2 KW - Lymphocyte Specific Protein Tyrosine Kinase p56(lck) KW - Proto-Oncogene Proteins c-fyn KW - src-Family Kinases KW - Antigens, CD45 KW - EC 3.1.3.48 KW - Index Medicus KW - Peptide Mapping KW - Enzyme Activation KW - DNA Mutational Analysis KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Phosphotyrosine -- metabolism KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Lymphoma, T-Cell -- pathology KW - Phosphorylation KW - Transfection KW - Neoplasm Proteins -- genetics KW - Molecular Sequence Data KW - Neoplasm Proteins -- metabolism KW - src-Family Kinases -- genetics KW - src-Family Kinases -- metabolism KW - Protein Processing, Post-Translational KW - Antigens, CD45 -- analysis KW - Antigens, CD45 -- physiology KW - T-Lymphocyte Subsets -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78251417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Mutational+analysis+of+Lck+in+CD45-negative+T+cells%3A+dominant+role+of+tyrosine+394+phosphorylation+in+kinase+activity.&rft.au=D%27Oro%2C+U%3BSakaguchi%2C+K%3BAppella%2C+E%3BAshwell%2C+J+D&rft.aulast=D%27Oro&rft.aufirst=U&rft.date=1996-09-01&rft.volume=16&rft.issue=9&rft.spage=4996&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-26 N1 - Date created - 1996-09-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1991 May 2;351(6321):69-72 [1709258] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358-62 [2190221] Methods Enzymol. 1991;201:110-49 [1943760] Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10696-700 [1720546] J Biol Chem. 1991 Dec 25;266(36):24249-52 [1722201] Eur J Immunol. 1992 Mar;22(3):661-8 [1532148] Eur J Immunol. 1992 May;22(5):1173-8 [1533589] J Biol Chem. 1992 May 5;267(13):9248-56 [1577758] Nature. 1992 May 14;357(6374):161-4 [1579166] EMBO J. 1992 Aug;11(8):2919-24 [1639064] Cell. 1992 Aug 21;70(4):585-93 [1505025] J Exp Med. 1992 Sep 1;176(3):835-44 [1380977] Cell. 1992 Sep 4;70(5):741-50 [1387588] Cell. 1992 Sep 4;70(5):751-63 [1516132] J Biol Chem. 1992 Sep 15;267(26):18259-62 [1526965] Mol Cell Biol. 1992 Oct;12(10):4521-30 [1406641] Eur J Immunol. 1992 Nov;22(11):2915-21 [1358625] EMBO J. 1993 Jan;12(1):315-21 [8428589] Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1402-6 [8433999] Science. 1993 Apr 23;260(5107):541-4 [8475386] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5176-80 [8506364] Cell. 1993 Jun 18;73(6):1117-24 [7685657] Mol Cell Biol. 1993 Sep;13(9):5290-300 [7689149] J Biol Chem. 1993 Nov 5;268(31):23275-82 [8226850] J Biol Chem. 1994 Jan 14;269(2):1068-74 [8288563] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2597-601 [7511815] J Biol Chem. 1994 May 6;269(18):13594-600 [8175795] Mol Cell Biol. 1994 Aug;14(8):5249-58 [7518561] Mol Immunol. 1994 Jul;31(10):771-80 [7518569] EMBO J. 1994 Sep 1;13(17):4002-10 [8076596] Mol Cell Biol. 1994 Dec;14(12):8078-84 [7526153] J Inflamm. 1996;46(2):65-77 [8734787] Mol Cell Biol. 1985 Dec;5(12):3610-6 [3915782] Mol Cell Biol. 1988 Feb;8(2):540-50 [3352600] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4247-51 [3380789] Cell. 1988 Oct 21;55(2):301-8 [3262426] Nature. 1989 Mar 16;338(6212):257-9 [2784195] Proc Natl Acad Sci U S A. 1989 Aug;86(16):6302-6 [2548204] Nature. 1989 Nov 16;342(6247):278-81 [2509945] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8959-63 [2530588] Mol Cell Biol. 1989 Oct;9(10):4441-6 [2479826] J Exp Med. 1990 Jul 1;172(1):347-50 [2141630] Oncogene. 1990 Jun;5(6):809-13 [2141684] Nature. 1990 Jul 5;346(6279):66-8 [2164155] J Immunol. 1990 Mar 1;144(5):1591-9 [1689750] Cell. 1990 Mar 9;60(5):755-65 [2107025] FEBS Lett. 1990 Jul 16;267(2):289-94 [2379587] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7722-6 [2217205] Oncogene. 1990 Oct;5(10):1455-62 [2250907] Cell. 1991 Feb 8;64(3):511-20 [1671341] Nature. 1991 Mar 7;350(6313):62-6 [1706070] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2037-41 [1672451] Cell. 1991 Apr 19;65(2):281-91 [2015626] Mol Cell Biol. 1991 Sep;11(9):4415-22 [1652055] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The posttranscriptional control element of the simian retrovirus type 1 forms an extensive RNA secondary structure necessary for its function. AN - 78211819; 8709222 AB - It was previously shown that a 240-nucleotide (nt) RNA element (cis-acting transactivation element [CTE]) located between the env gene and the 3' long terminal repeat of simian retrovirus type 1 (SRV-1) can functionally replace posttranscriptional activation directed by Rev and the Rev-responsive element (RRE) when inserted into a Rev- and RRE-deficient molecular clone of human immunodeficiency virus type 1, resulting in efficient virus replication. Here, we analyze the molecular and structural requirements for function of this RNA element. Deletion mutagenesis demonstrated that the core element spans 173 nt. SRV-2 and Mason-Pfizer monkey virus have highly homologous elements, which function similarly when inserted into the Rev/RRE-deficient human immunodeficiency virus type 1. Computer prediction indicated that the core CTEs of all three viruses have similar extensive secondary structures. Mutagenesis of the SRV-1 CTE revealed that both sequence and secondary structure are essential for function. Nuclease probing of the SRV-1 CTE further supported the genetic analysis and confirmed the predicted structural features of the RNA element. Sequence analysis of the 240-nt SRV-1 CTE, after continuous long-term propagation of the Rev-independent viruses, revealed that the genetically defined core element remained unchanged, while regions outside the core CTE underwent deletions or duplications. These data further support our in vitro mutagenesis data and demonstrate the importance of the sequence and structure of the SRV-1 CTE for appropriate function. JF - Journal of virology AU - Tabernero, C AU - Zolotukhin, A S AU - Valentin, A AU - Pavlakis, G N AU - Felber, B K AD - Human Retrovirus Pathogenesis Group, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 5998 EP - 6011 VL - 70 IS - 9 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - Gene Products, rev KW - HIV Core Protein p24 KW - RNA, Viral KW - Trans-Activators KW - rev Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Sequence Homology, Nucleic Acid KW - HeLa Cells KW - HIV Core Protein p24 -- biosynthesis KW - Humans KW - Nucleic Acid Conformation KW - Mutagenesis KW - HIV Long Terminal Repeat KW - Base Sequence KW - Promoter Regions, Genetic KW - Transfection KW - Kinetics KW - Restriction Mapping KW - RNA, Viral -- chemistry KW - Genes, env KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Species Specificity KW - RNA, Viral -- metabolism KW - Sequence Deletion KW - Virus Replication KW - Retroviruses, Simian -- physiology KW - Trans-Activators -- metabolism KW - HIV-1 -- genetics KW - Retroviruses, Simian -- metabolism KW - Gene Products, rev -- metabolism KW - Trans-Activators -- biosynthesis KW - Retroviruses, Simian -- genetics KW - Trans-Activators -- chemistry KW - RNA Processing, Post-Transcriptional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78211819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=The+posttranscriptional+control+element+of+the+simian+retrovirus+type+1+forms+an+extensive+RNA+secondary+structure+necessary+for+its+function.&rft.au=Tabernero%2C+C%3BZolotukhin%2C+A+S%3BValentin%2C+A%3BPavlakis%2C+G+N%3BFelber%2C+B+K&rft.aulast=Tabernero&rft.aufirst=C&rft.date=1996-09-01&rft.volume=70&rft.issue=9&rft.spage=5998&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-10 N1 - Date created - 1996-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1973 Apr;52(2):456-67 [4705382] Trends Biochem Sci. 1991 Sep;16(9):346-50 [1949157] Cell. 1986 May 9;45(3):375-85 [2421920] J Virol. 1986 Aug;59(2):284-91 [3016298] Mol Cell Biol. 1987 Feb;7(2):725-37 [3821727] Virology. 1987 Apr;157(2):317-29 [2435057] J Virol. 1987 Oct;61(10):3066-71 [3041028] J Virol. 1992 Jan;66(1):150-9 [1727477] Mol Cell Biol. 1992 Mar;12(3):1375-86 [1545819] New Biol. 1991 Dec;3(12):1220-32 [1725960] J Virol. 1992 Jun;66(6):3699-706 [1583728] AIDS. 1993;7 Suppl 1:S51-62 [8363803] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256-60 [8108397] J Virol. 1994 May;68(5):2986-93 [8151769] J Virol. 1994 Dec;68(12):7944-52 [7966585] Nucleic Acids Res. 1994 Nov 11;22(22):4725-32 [7984424] J Virol. 1995 Apr;69(4):2175-86 [7884866] AIDS Res Hum Retroviruses. 1995 Sep;11(9):1063-71 [8554903] Proc Natl Acad Sci U S A. 1988 Apr;85(7):2071-5 [2832844] Nature. 1989 Mar 16;338(6212):254-7 [2784194] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 [2784208] J Virol. 1989 May;63(5):1959-66 [2704072] Cell. 1989 Jun 30;57(7):1155-65 [2736624] Cell. 1990 Feb 23;60(4):685-93 [1689218] J Virol. 1990 Jun;64(6):2519-29 [2335812] Nucleic Acids Res. 1990 Apr 25;18(8):2037-44 [2186373] J Virol. 1990 Dec;64(12):6010-7 [2243384] Genes Dev. 1991 May;5(5):808-19 [1827422] Nucleic Acids Res. 1991 Apr 11;19(7):1577-83 [2027765] J Virol. 1991 Oct;65(10):5305-13 [1895385] J Virol. 1991 Nov;65(11):5732-43 [1656066] Cell. 1991 Nov 1;67(3):529-36 [1934059] Science. 1986 Mar 28;231(4745):1567-72 [3006247] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The structurally diverse intergenic regions of respiratory syncytial virus do not modulate sequential transcription by a dicistronic minigenome. AN - 78209578; 8709239 AB - The first nine genes of respiratory syncytial virus (RSV), a nonsegmented negative-strand RNA virus, are separated by intergenic regions which range in size from 1 to 52 nucleotides for strain A2 and lack obvious consensus elements except that each ends in an A (genome sense). Their significance for gene expression was investigated by using RSV-CAT-LUC RNA, a helper-dependent cDNA-encoded dicistronic analog of RSV genomic RNA in which the viral genes were replaced by a negative-sense copy of the translational open reading frame (ORF) encoding chloramphenicol acetyltransferase (CAT) as the upstream, leader-proximal gene and that encoding luciferase (LUC) as the downstream gene. These foreign ORFs were flanked by the RSV gene-start (GS) and gene-end (GE) transcription signals and separated by the naturally occurring G/F intergenic region. The RSV-CAT-LUC minigenome was synthesized in vitro and transfected into RSV-infected cells, and synthesis of the CAT and LUC mRNAs was monitored by enzyme assay and Northern (RNA) blot hybridization. Surprisingly, substitution of each of the other naturally occurring RSV intergenic regions in turn did not significantly alter the absolute or relative amounts of the two mRNAs. Substitution of a nonnatural 10-nucleotide intergenic region, or elimination of the intergenic region altogether, also had little effect on the level of expression of the two genes. Four of the minigenome variants containing naturally occurring intergenic regions were modified further by replacing part of the LUC ORF with a second copy of the CAT ORF, so that each of the two mRNAs would hybridize equally with a CAT-specific probe and their relative molar amounts could be determined. The level of expression of the downstream gene was 0.30 to 0.36 that of the upstream one. This determined the magnitude of RSV transcriptional polarity across a gene pair and confirmed that this value was very similar among the various intergenic regions. Minigenome transcription also yielded a CAT-LUC readthrough mRNA at a level 0.10 to 0.13 that of the LUC mRNA. In summary, the structurally diverse RSV intergenic regions do not appear to play a role in modulating RSV gene expression. JF - Journal of virology AU - Kuo, L AU - Fearns, R AU - Collins, P L AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0720, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 6143 EP - 6150 VL - 70 IS - 9 SN - 0022-538X, 0022-538X KW - RNA, Messenger KW - 0 KW - RNA, Viral KW - Recombinant Fusion Proteins KW - Viral Structural Proteins KW - Luciferases KW - EC 1.13.12.- KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Humans KW - RNA, Messenger -- chemistry KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Luciferases -- biosynthesis KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Restriction Mapping KW - Molecular Sequence Data KW - Viral Structural Proteins -- genetics KW - Cell Line KW - Respiratory Syncytial Viruses -- genetics KW - RNA, Viral -- chemistry KW - Introns KW - Genes, Viral KW - RNA, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78209578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=The+structurally+diverse+intergenic+regions+of+respiratory+syncytial+virus+do+not+modulate+sequential+transcription+by+a+dicistronic+minigenome.&rft.au=Kuo%2C+L%3BFearns%2C+R%3BCollins%2C+P+L&rft.aulast=Kuo&rft.aufirst=L&rft.date=1996-09-01&rft.volume=70&rft.issue=9&rft.spage=6143&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-10 N1 - Date created - 1996-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1981 Feb;23(2):477-84 [6258804] J Virol. 1996 Aug;70(8):5075-82 [8764015] Proc Natl Acad Sci U S A. 1983 Jun;80(11):3208-12 [6190173] J Virol. 1984 Feb;49(2):572-8 [6546401] J Virol. 1984 Nov;52(2):364-9 [6492254] Virology. 1985 Feb;141(1):102-9 [2983492] Virology. 1984 Apr 30;134(2):277-86 [6152726] Proc Natl Acad Sci U S A. 1986 Jul;83(13):4594-8 [3460060] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5134-8 [2440043] J Gen Virol. 1988 Oct;69 ( Pt 10):2623-8 [3171553] J Gen Virol. 1988 Nov;69 ( Pt 11):2901-6 [3183631] J Virol. 1989 May;63(5):1951-8 [2539496] J Gen Virol. 1990 Feb;71 ( Pt 2):481-5 [2307966] J Gen Virol. 1990 Jul;71 ( Pt 7):1571-6 [2374008] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9663-7 [1946383] Virology. 1993 Apr;193(2):1018-23 [8384742] Virology. 1994 Aug 15;203(1):63-72 [8030285] J Virol. 1995 Apr;69(4):2412-9 [7884888] J Virol. 1995 Sep;69(9):5677-86 [7637014] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11563-7 [8524804] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):81-5 [8552680] Biotechniques. 1996 May;20(5):754-6 [8723910] Cell. 1982 Dec;31(3 Pt 2):635-42 [6297777] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Two-Year and Lifetime Toxicity and Carcinogenicity Studies of Ozone in B6C3F1 Mice AN - 755139333; 13645747 AB - To evaluate the toxicity and carcinogenic potential of long-term exposure to ozone, B6C3F1 mice were exposed by whole-body inhalation to 0, 0.12, 0.5, or 1.0 ppm and 0, 0.5, or 1.0 ppm ozone for 24 or 30 mo (lifetime), respectively. The incidence of alveolar/ bronchiolar adenomas and carcinomas (combined) increased (p 0.05) in male mice exposed to concentrations of 0.5 or 1.0 ppm. An increased incidence of nonneoplastic lesions were observed in the nasal cavities and in the centriacinar region of the lung of mice exposed to 0.5 or 1.0 ppm for 24 and 30 mo. Nasal cavity lesions were mild and included hyaline degeneration, hyperplasia, squamous metaplasia, fibrosis and suppurative inflammation of the transitional and respiratory epithelium of the lateral wall, and atrophy of the olfactory epithelium. Lung lesions included replacement of the epithelium of the alveolar ducts and adjacent alveolar septa with epithelium similar to that normally found in terminal bronchioles (metaplasia) and associated alveolar histiocytosis. Based on the results of these studies, we conclude that inhalation exposure of B6C3F1 mice to ozone for 24 or 30 mo (a) is carcinogenic in female B6C3F1 mice exposed to 1.0 ppm of ozone based on an increased incidence of alveolar/bronchiolar adenoma or carcinoma and (b) results in mild, site-specific, nonneoplastic lesions in the nasal cavity and centriacinar lung of male and female mice exposed to 0.5 or 1.0 ppm of ozone for 2 yrs, which persist with continued exposure to 30 mo. It is uncertain whether or not the marginal increase (p > 0.05) of alveolar/bronchiolar neoplasms in male B6C3F1 mice resulted from exposure to ozone. JF - Toxicologic Pathology AU - Herbert, Ron A AU - Hailey, James R AU - Grumbein, Sondra AU - Chou, Billy J AU - Sills, Robert C AU - Haseman, Joseph K AU - Goehl, Thomas AU - Miller, Rodney A AU - Roycroft, Joseph H AU - Boorman, Gary A AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709 Y1 - 1996/09// PY - 1996 DA - Sep 1996 SP - 539 EP - 548 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 5 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755139333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+rheumatology&rft.atitle=Lupus+nephritis.&rft.au=Davis%2C+J+C%3BTassiulas%2C+I+O%3BBoumpas%2C+D+T&rft.aulast=Davis&rft.aufirst=J&rft.date=1996-09-01&rft.volume=8&rft.issue=5&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+rheumatology&rft.issn=10408711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1177/019262339602400502 ER - TY - JOUR T1 - Thyroid-specific enhancer-binding protein Role in thyroid function and organogenesis. AN - 734283042; 18406755 AB - Thyroid-specific enhancer-binding protein (T/EBP), also known as thyroid-specific transcription factor-1 (TTF-1), is a trans-activating transcription factor known to be involved in the tissue-specific expression of genes encoding thyroglobulin (TG), thyroid peroxidase (TPO), and thyrotropin receptor (TSHR) in the thyroid, and surfactant proteins A, B, and C, and Clara cell secretory protein in the lung. T/EBP is a homeodomain-containing DNA-binding protein found in the thyroid, lung epithelium, and specific areas of the forebrain during early embryogenesis. A mutant mouse lacking T/EBP expression was recently generated that is missing the thyroid, lung, ventral forebrain, and pituitary. These results clearly establish that T/EBP functions not only as a trans-activating factor to regulate expression of genes in the thyroid and lung, but also is required for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. JF - Trends in endocrinology and metabolism: TEM AU - Kimura, S AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 247 EP - 252 VL - 7 IS - 7 SN - 1043-2760, 1043-2760 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/734283042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.atitle=Thyroid-specific+enhancer-binding+protein+Role+in+thyroid+function+and+organogenesis.&rft.au=Kimura%2C+S&rft.aulast=Kimura&rft.aufirst=S&rft.date=1996-09-01&rft.volume=7&rft.issue=7&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.issn=10432760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2012-10-02 N1 - Date created - 2008-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Magnitudo delle colate detritiche nelle Alpi Orientali Italiane TT - Magnitude of debris flows in the eastern Italian Alps AN - 52622242; 1998-019823 JF - GEAM. Geoingegneria Ambientale e Mineraria AU - Marchi, L AU - Tecca, P R Y1 - 1996/09// PY - 1996 DA - September 1996 SP - 79 EP - 86 PB - Associazione Mineraria Subalpina, Torino VL - 33 IS - 2-3 SN - 1121-9041, 1121-9041 KW - geologic hazards KW - Alps KW - morphometry KW - Europe KW - debris flows KW - Italy KW - Southern Europe KW - alluvial fans KW - mass movements KW - volume KW - drainage basins KW - Eastern Alps KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52622242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=GEAM.+Geoingegneria+Ambientale+e+Mineraria&rft.atitle=Magnitudo+delle+colate+detritiche+nelle+Alpi+Orientali+Italiane&rft.au=Marchi%2C+L%3BTecca%2C+P+R&rft.aulast=Marchi&rft.aufirst=L&rft.date=1996-09-01&rft.volume=33&rft.issue=2-3&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=GEAM.+Geoingegneria+Ambientale+e+Mineraria&rft.issn=11219041&rft_id=info:doi/ LA - Italian DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. Reference includes data supplied by CNR, Comitato Scienze Geologiche e Minerarie, Rome, Italy N1 - Date revised - 1998-01-01 N1 - Number of references - 36 N1 - Document feature - illus. incl. 2 tables N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - alluvial fans; Alps; debris flows; drainage basins; Eastern Alps; Europe; geologic hazards; Italy; mass movements; morphometry; Southern Europe; volume ER - TY - JOUR T1 - Non-orthologous gene displacement AN - 17120543; 4427443 AB - Unrelated proteins with the same biochemical activity can evolve independently. Without complete genome information, however, it is not possible to ascertain whether a particular function is encoded by homologous or non-homologous genes in two different species. The chance always remains that the counterpart to a given gene in one species has not been sequenced in the other. In an attempt to prove and to assess quantitatively the postulate that distinct proteins in different species can be responsible for the same function, we compared the first two genomes to be sequenced completely, those of the parasitic bacteria Haemophilus influenzae and Mycoplasma genitalium. For this problem to be addressed, the function of the gene in question has to be essential in both organisms. Despite this limitation, we found a considerable number of cases where apparently indispensable cell functions are encoded by non-orthologous genes. By definition, orthologs are genes that are related by vertical descent from a common ancestor and encode proteins with the same function in different species. By contrast, paralogs are homologous genes that have evolved by duplication and code for proteins with similar, but not identical, functions. Comparison of the 1703 putative proteins encoded by the H. influenzae genome with the 469 M. genitalium protein sequences, revealed that 233 showed sufficiently high similarity for them to be considered orthologs (the criteria for distinguishing orthologs from paralogs are discussed in Ref. 5, in which the genome of H. influenzae was compared with the available 75% of the Escherichia coli genome). In addition, by comparing the remaining M. genitalium and H. influenzae proteins with those in the non-redundant sequence database, we identified 12 clear-cut cases where essential cellular functions in the two bacteria were encoded by non-orthologous (i.e. unrelated or paralogous) genes (Table 1). We call this phenomenon non-orthologous gene displacement, although its origins can be quite diverse (DBO). JF - Trends in Genetics AU - Koonin, Eugene V AU - Mushegian, Arcady R AU - Bork, Peer AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA Y1 - 1996/09// PY - 1996 DA - Sep 1996 SP - 334 EP - 336 VL - 12 IS - 9 SN - 0168-9525, 0168-9525 KW - Haemophilus influenzae KW - Mycoplasma genitalium KW - gene displacement KW - Microbiology Abstracts B: Bacteriology KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17120543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Genetics&rft.atitle=Non-orthologous+gene+displacement&rft.au=Koonin%2C+Eugene+V%3BMushegian%2C+Arcady+R%3BBork%2C+Peer&rft.aulast=Koonin&rft.aufirst=Eugene&rft.date=1996-09-01&rft.volume=12&rft.issue=9&rft.spage=334&rft.isbn=&rft.btitle=&rft.title=Trends+in+Genetics&rft.issn=01689525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Suppression of experimental autoimmune uveitis in Lewis rats by oral administration of recombinant Escherichia coli expressing retinal S-antigen AN - 15830583; 4009093 AB - Experimental autoimmune uveitis (EAU) is an organ-specific T-lymphocyte-mediated autoimmune disease which serves as a model for several human ocular inflammations of an apparently autoimmune nature. S-antigen, a photoreceptor cell protein, is highly efficient in inducing EAU showing severe inflammation of the uveal tract and retina of the eye. We have demonstrated previously that recombinant Escherichia coli expressing retinal S-antigen induces EAU in Lewis rats. The oral administration of S-antigen prior to the uveitopathogenic challenge results in significant suppression of the disease and of the cellular responses. We examined the effect of oral administration of E. coli expressing retinal S-antigen on the development of EAU induced with native S-antigen in Lewis rats. Feeding rats with 1 mg of bacteria on Days 7, 5, 3, 2, and 1 prior to immunization with 50 mu g of retinal S-antigen caused a significant suppression of the disease. Moderate suppression was found in animals fed 0.5 and 0.25 mg of recombinant bacteria. Oral feeding of 1 mg of JM105 transfected with plasmid alone had no significant effect on the subsequent induction of EAU by S-antigen. Feeding recombinant E. coli expressing retinal S-antigen before immunization significantly decreased the proliferative response of lymphocytes to native S-antigen in vitro. Our results indicate that recombinant microorganism-expressing autoantigen administered orally induces suppression of specific autoimmune disease as well as cellular response to particular autoantigen. JF - Cellular Immunology AU - Singh, V K AU - Anand, R AU - Sharma, K AU - Agarwal, S S AD - Bldg. 6, Rm. 310, MSC 2740, LRCMB, NEI, NIH, Bethesda, MD 20892, USA Y1 - 1996/09// PY - 1996 DA - Sep 1996 SP - 158 EP - 162 VL - 172 IS - 2 SN - 0008-8749, 0008-8749 KW - Lewis rats KW - experimental allergic uveitis KW - S antigen KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Escherichia coli KW - retina KW - J 02833:Immune response and immune mechanisms KW - F 06873:Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15830583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+Immunology&rft.atitle=Suppression+of+experimental+autoimmune+uveitis+in+Lewis+rats+by+oral+administration+of+recombinant+Escherichia+coli+expressing+retinal+S-antigen&rft.au=Singh%2C+V+K%3BAnand%2C+R%3BSharma%2C+K%3BAgarwal%2C+S+S&rft.aulast=Singh&rft.aufirst=V&rft.date=1996-09-01&rft.volume=172&rft.issue=2&rft.spage=158&rft.isbn=&rft.btitle=&rft.title=Cellular+Immunology&rft.issn=00088749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; retina ER - TY - JOUR T1 - Effect of dye nature on its adsorption from aqueous solutions onto activated carbon AN - 15825493; 4003803 AB - Liquid-phase adsorption of two dyes on activated carbon was measured in the 283-323 K temperature-range. Higher capacity and faster kinetics of adsorption were obtained for a basic dye than for an acidic dye under comparable conditions, probably due to the different ionic natures of the dyes. The equilibrium data for acidic dye could be well described by the Freundlich equation, but the best-fit model for basic dye changed from the Langmuir to the Freundlich equations when the temperature was raised. In addition, the thermodynamic functions were determined. A plot of the fraction of adsorption against (time) super(1/2) was adopted to describe the adsorption process. It was shown that for an acidic dye the amount of adsorbent used played an important role in the adsorption mechanism. JF - Separation Science and Technology AU - Juang, Ruey-Shin AU - Swei, Show-Ling AD - Dep. Chem. Eng., Yuan-Ze Inst. Technol., Nei-Li, Taoyuan 320, Taiwan Y1 - 1996/09// PY - 1996 DA - Sep 1996 SP - 2143 EP - 2158 VL - 31 IS - 15 SN - 0149-6395, 0149-6395 KW - Water Resources Abstracts KW - activated carbon KW - mathematical models KW - temperature effects KW - adsorption KW - kinetics KW - thermodynamics KW - dyes KW - SW 3040:Wastewater treatment processes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15825493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Awaterresources&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Separation+Science+and+Technology&rft.atitle=Effect+of+dye+nature+on+its+adsorption+from+aqueous+solutions+onto+activated+carbon&rft.au=Juang%2C+Ruey-Shin%3BSwei%2C+Show-Ling&rft.aulast=Juang&rft.aufirst=Ruey-Shin&rft.date=1996-09-01&rft.volume=31&rft.issue=15&rft.spage=2143&rft.isbn=&rft.btitle=&rft.title=Separation+Science+and+Technology&rft.issn=01496395&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - dyes; adsorption; activated carbon; kinetics; temperature effects; thermodynamics; mathematical models ER - TY - JOUR T1 - Differential effects of protein kinase C activation on calcium storage and capacitative calcium entry in NIH 3T3 cells. AN - 78268950; 8702937 AB - In NIH 3T3 cells, treatment with phorbol 12-myristate 13-acetate (PMA) reduced the release of Ca2+ by thapsigargin, but did not activate Ca2+ entry; Ca2+ influx was triggered after the residual pool was emptied by thapsigargin, and this Ca2+ influx was similar to that induced by thapsigargin in control cells. The effect of PMA was due to decreased Ca2+ storage because 1) Ca2+ release by ionomycin was similarly affected by PMA, and in both control and PMA-treated cells, ionomycin did not release Ca2+ following thapsigargin treatment; 2) PMA reduced 45Ca2+ accumulation; and 3) studies with Ca2+ indicator compartmentalized into the endoplasmic reticulum indicated that stored Ca2+ was reduced by PMA. Although PMA did not itself activate Ca2+ entry, PMA potentiated Ca2+ entry with low concentrations of cyclopiazonic acid. With a somewhat higher concentration of cyclopiazonic acid, PMA had no effect on calcium entry. Thus, protein kinase C has two apparent actions on calcium signaling in NIH 3T3 cells: 1) reduced intracellular Ca2+ storage capacity and 2) augmented calcium entry with submaximal intracellular Ca2+ pool depletion. These actions indicate a complex and potentially important role for the protein kinase C system in calcium homeostasis in this cell type. JF - The Journal of biological chemistry AU - Ribeiro, C M AU - Putney, J W AD - NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/08/30/ PY - 1996 DA - 1996 Aug 30 SP - 21522 EP - 21528 VL - 271 IS - 35 SN - 0021-9258, 0021-9258 KW - Enzyme Inhibitors KW - 0 KW - Indoles KW - Terpenes KW - Thapsigargin KW - 67526-95-8 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - cyclopiazonic acid KW - X9TLY4580Z KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Enzyme Activation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Mice KW - Indoles -- pharmacology KW - Terpenes -- pharmacology KW - Homeostasis KW - Ion Transport KW - Protein Kinase C -- metabolism KW - Calcium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78268950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Differential+effects+of+protein+kinase+C+activation+on+calcium+storage+and+capacitative+calcium+entry+in+NIH+3T3+cells.&rft.au=Ribeiro%2C+C+M%3BPutney%2C+J+W&rft.aulast=Ribeiro&rft.aufirst=C&rft.date=1996-08-30&rft.volume=271&rft.issue=35&rft.spage=21522&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of carboxyl-terminal basic amino acids in Gqalpha-dependent activation, particulate association, and nuclear localization of phospholipase C-beta1. AN - 78268672; 8702889 AB - The phospholipase C (PLC)-beta isozymes differ from the PLC-gamma and PLC-delta isozymes in that they possess a long COOH-terminal sequence downstream of their catalytic domain, are activated by alpha subunits of the Gq class of G proteins, associate with the particulate subcellular fraction, and are present in the nucleus. Most of the COOH-terminal domain of PLC-beta isozymes is predicted to be helical, and three regions in this domain, PLC-beta1 residues 911-928 (region 1), 1055-1072 (region 2), and 1109-1126 (region 3), contain a high proportion of basic residues that are highly conserved. Projection of the sequences of these three regions in helical wheels reveals clustering of the basic residues. The role of the COOH terminus and the clustered basic residues in PLC-beta1 was investigated by either truncating the entire COOH-terminal domain (mutant DeltaC) or replacing two or three clustered basic residues with isoleucine (or methionine), and expressing the mutant enzymes in CV-1, Rat-2, or Swiss 3T3 cells. The DeltaC mutant no longer showed the ability to be activated by Gqalpha, to translocate to the nucleus, or to associate with the particulate fraction. Substitution of clusters of basic residues in regions 1 and 2 generally reduced the extent of activation by Gqalpha, whereas substitution of a basic cluster in region 3 had no effect. Substitution of the cluster of lysine residues 914, 921, and 925 in region 1 had the most marked effect, reducing Gqalpha-dependent activity to 10% of that of wild type. All substitution mutants, with the exception of that in which lysine residues 1056, 1063, and 1070 in region 2 were substituted with isoleucine, behaved like the wild-type enzyme in showing an approximately equal distribution between cytoplasm and nucleus; only 12% of the region 2 mutant was present in the nucleus. None of the basic clusters appeared critical for particulate association; however, replacement of each cluster reduced the amount of PLC-beta1 in the particulate fraction by some extent, suggesting that all the basic residues contribute to the association, presumably by interacting with acidic residues in the particulate fraction. Membrane localization of PLC-beta isozymes is therefore likely mediated by both the COOH-terminal domain and the pleckstrin homology domain, the latter of which is known to bind phosphatidylinositol 4,5-biphosphate. JF - The Journal of biological chemistry AU - Kim, C G AU - Park, D AU - Rhee, S G AD - Laboratory of Cell Signaling, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08/30/ PY - 1996 DA - 1996 Aug 30 SP - 21187 EP - 21192 VL - 271 IS - 35 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - DNA Primers KW - Isoenzymes KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C beta KW - EC 3.1.4.11 KW - Plcb1 protein, mouse KW - Plcb1 protein, rat KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Enzyme Activation KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Protein Binding KW - Cell Line KW - Mutagenesis KW - Cell Nucleus -- enzymology KW - Isoenzymes -- isolation & purification KW - GTP-Binding Proteins -- metabolism KW - Amino Acids -- metabolism KW - Type C Phospholipases -- genetics KW - Isoenzymes -- genetics KW - Type C Phospholipases -- isolation & purification KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78268672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+role+of+carboxyl-terminal+basic+amino+acids+in+Gqalpha-dependent+activation%2C+particulate+association%2C+and+nuclear+localization+of+phospholipase+C-beta1.&rft.au=Kim%2C+C+G%3BPark%2C+D%3BRhee%2C+S+G&rft.aulast=Kim&rft.aufirst=C&rft.date=1996-08-30&rft.volume=271&rft.issue=35&rft.spage=21187&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The glycine/NMDA receptor antagonist HA-966 impairs visual recognition memory in rhesus monkeys. AN - 78465929; 8883856 AB - Recent studies have shown that strychnine-insensitive glycine binding sites positively modulate the N-methyl-D-asparate (NMDA) subclass of glutamate receptors, which are important in neural pathways involved in cognitive function. We examined the effect of (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), a highly specific antagonist of this glycine modulatory site on the NMDA receptor, on visual recognition memory in four rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample (DNMS) with a list length of 20 trial-unique graphic symbols. In addition, the effect of HA-966 was compared with that of (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (dizocilpine; MK-801), a noncompetitive NMDA channel blocker. Administration of HA-966 (0.1-10 mg/kg, i.m.) 30 min before testing impaired DNMS performance dose-dependently, starting at doses of 3.2 mg/kg; the memory deficity following the highest dose (10 mg/kg) was associated with prolonged response latencies. Similar impairments in recognition memory were observed following treatment with MK-801, though at much lower doses (3.2-32 micrograms/kg) than those at which HA-966 was effective. Administration of low doses of HA-966 (1 mg/kg) and MK-801 (10 micrograms/kg), each of which had no significant effect on performance when given alone, also failed to impair performance when given concurrently. Combined administration of both drugs, each at amnesia-producing doses (3.2 mg/kg of HA-966 plus 32 micrograms/kg of MK-801), markedly impaired performance in an additive, not a synergistic, manner. From these results, we propose that the recognition memory impairment observed in our monkeys following HA-966 administration is via an action on the glycine modulatory site of the NMDA receptor complex. JF - Brain research AU - Matsuoka, N AU - Aigner, T G AD - Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1996/08/26/ PY - 1996 DA - 1996 Aug 26 SP - 72 EP - 78 VL - 731 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Agonists KW - 0 KW - Excitatory Amino Acid Antagonists KW - Pyrrolidinones KW - Receptors, Glycine KW - Receptors, N-Methyl-D-Aspartate KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 1-hydroxy-3-amino-2-pyrrolidone KW - F2JLV9220T KW - Strychnine KW - H9Y79VD43J KW - Index Medicus KW - Animals KW - Drug Interactions KW - Cognition -- drug effects KW - Macaca mulatta KW - Male KW - Female KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Pattern Recognition, Visual -- drug effects KW - Memory -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Excitatory Amino Acid Agonists -- pharmacology KW - Receptors, Glycine -- antagonists & inhibitors KW - Pyrrolidinones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78465929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=The+glycine%2FNMDA+receptor+antagonist+HA-966+impairs+visual+recognition+memory+in+rhesus+monkeys.&rft.au=Matsuoka%2C+N%3BAigner%2C+T+G&rft.aulast=Matsuoka&rft.aufirst=N&rft.date=1996-08-26&rft.volume=731&rft.issue=1-2&rft.spage=72&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-25 N1 - Date created - 1997-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of the HIV-1 envelope protein gp120 on the production of nitric oxide and proinflammatory cytokines in mixed glial cell cultures. AN - 78334734; 8806809 AB - Although the neurotoxicity induced by the HIV envelope protein, gp120, has been demonstrated to require the presence of glial cells (microglia/astrocytes), the mechanisms for the gp120-induced neurotoxicity are not well understood. Moreover, the neurotoxic potencies of gp120s obtained from various HIV isolates are different. Since nitric oxide (NO) and proinflammatory cytokines (TNF-alpha, IL-1, IL-6) produced by glial cells have been involved in the neuropathogenesis of various diseases, this study examined the effects of gp120 obtained from two strains, HIV-1IIIB and HIV-1SF2, of the HIV-1 virus on the production of NO, TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 in murine primary mixed glial cell cultures. The glial cells exposed to HIV-1IIIB gp120 released NO, TNF-alpha, and IL-6 in a dose-dependent manner, whereas IL-1 alpha and IL-1 beta were undetectable. The cells exposed to HIV-1SF2 gp120 increased the release of IL-6 only. The gp120-induced effects were significantly enhanced by priming glial cells with IFN-gamma. To investigate the cellular sources and mechanisms of the gp120-induced IL-6 production, in situ hybridization with mRNA for IL-6 was performed in HIV-1IIIB gp120- or HIV-1SF2 gp120-stimulated microgliaenriched or astrocyte-enriched cultures. HIV-1IIIB gp120 or HIV-1SF2 gp120 induced the expression of IL-6 mRNA in both microglia-enriched and astrocyte-enriched cultures, indicating that both microglia and astrocytes produce IL-6, and that the transcriptional regulation is involved in the gp120-induced IL-6 production. Taken together, these results demonstrate that the production of NO, TNF-alpha, IL-1, or IL-6 from glial cells is differentially regulated by HIV-1IIIB gp120 and HIV-1SF2 gp120. These results may provide insights into the roles of NO and proinflammatory cytokines in the neurotoxicity of gp120s and the neuropathology of different strains of HIV-1 viruses. JF - Cellular immunology AU - Kong, L Y AU - Wilson, B C AU - McMillian, M K AU - Bing, G AU - Hudson, P M AU - Hong, J S AD - Section of Neuropharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/08/25/ PY - 1996 DA - 1996 Aug 25 SP - 77 EP - 83 VL - 172 IS - 1 SN - 0008-8749, 0008-8749 KW - Cytokines KW - 0 KW - HIV Envelope Protein gp120 KW - Interleukin-1 KW - Interleukin-6 KW - Nitrites KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Interleukin-1 -- biosynthesis KW - Nitrites -- metabolism KW - Cells, Cultured KW - Humans KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Mice KW - Interleukin-6 -- biosynthesis KW - Inflammation KW - Neuroglia -- cytology KW - HIV Envelope Protein gp120 -- pharmacology KW - HIV-1 -- immunology KW - HIV Envelope Protein gp120 -- immunology KW - Cytokines -- biosynthesis KW - Neuroglia -- immunology KW - Nitric Oxide -- biosynthesis KW - Neuroglia -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78334734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+immunology&rft.atitle=The+effects+of+the+HIV-1+envelope+protein+gp120+on+the+production+of+nitric+oxide+and+proinflammatory+cytokines+in+mixed+glial+cell+cultures.&rft.au=Kong%2C+L+Y%3BWilson%2C+B+C%3BMcMillian%2C+M+K%3BBing%2C+G%3BHudson%2C+P+M%3BHong%2C+J+S&rft.aulast=Kong&rft.aufirst=L&rft.date=1996-08-25&rft.volume=172&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Cellular+immunology&rft.issn=00088749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-01 N1 - Date created - 1996-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular analyses of liver tumors in c-myc transgenic mice and c-myc and TGF-alpha double transgenic mice. AN - 78377067; 8827045 AB - It has been demonstrated that co-expression of c-myc and transforming growth factor alpha (TGF-alpha) as transgenes in the mouse liver results in a tremendous acceleration of neoplastic development in this organ as compared to expression of either transgene alone [Murakami, H., et al. (1993) Cancer Res., 53, 1719-1723]. In order to clarify the roles of transgenes and additional other genetic alterations during hepatocarcinogenesis, we analyzed liver tumors developed in albumin/c-myc transgenic mice and albumin/c-myc and MT-1/TGF-alpha double transgenic mice. High expression of TGF-alpha transgene was found in nine of 14 (64%) liver tumors in double transgenic mice, suggesting that TGF-alpha overexpression confers growth advantage during hepatocarcinogenesis. Only one of 14 (7%) liver tumors in double transgenic mice and none of 13 liver tumors in c-myc transgenic mice showed overexpression of insulin-like growth factor II (IGF-II). This result was in contrast to the report by Takagi et al. [Takagi, H., et al. (1992) Cancer Res., 52, 5171-5177] which showed overexpression of IGF-II in 75% of liver tumors in TGF-alpha transgenic mice and suggested that the presence of c-myc transgenes together with TGF-alpha from an early stage of hepatocarcinogenesis may lead to different carcinogenic pathways which are independent of IGF-II overexpression. Expression of c-myc transgene was found in most of the liver tumors, but at lower levels than non-tumorous parts of the liver in c-myc and double transgenic mice. These results suggest that c-myc transgene expression cooperates with TGF-alpha in the early stages of hepatocarcinogenesis but has growth disadvantage in later stages of hepatocarcinogenesis. There was no evidence of mutational activation of the H-ras gene or mutational inactivation of the p53 gene in any liver tumors developed in c-myc or double transgenic mice. JF - Cancer letters AU - Ohgaki, H AU - Sanderson, N D AU - Ton, P AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1996/08/23/ PY - 1996 DA - 1996 Aug 23 SP - 43 EP - 49 VL - 106 IS - 1 SN - 0304-3835, 0304-3835 KW - DNA Primers KW - 0 KW - Proto-Oncogene Proteins c-myc KW - Serum Albumin KW - Transforming Growth Factor alpha KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Index Medicus KW - Animals KW - Exons KW - Serum Albumin -- biosynthesis KW - Insulin-Like Growth Factor II -- biosynthesis KW - Mice KW - Mice, Transgenic KW - Polymorphism, Single-Stranded Conformational KW - Proto-Oncogene Proteins c-myc -- biosynthesis KW - Genes, ras KW - Mice, Inbred CBA KW - Base Sequence KW - Serum Albumin -- genetics KW - Genes, p53 KW - Recombination, Genetic KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Mutation KW - Female KW - Male KW - Liver Neoplasms -- pathology KW - Transforming Growth Factor alpha -- genetics KW - Genes, myc KW - Transforming Growth Factor alpha -- biosynthesis KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78377067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Molecular+analyses+of+liver+tumors+in+c-myc+transgenic+mice+and+c-myc+and+TGF-alpha+double+transgenic+mice.&rft.au=Ohgaki%2C+H%3BSanderson%2C+N+D%3BTon%2C+P%3BThorgeirsson%2C+S+S&rft.aulast=Ohgaki&rft.aufirst=H&rft.date=1996-08-23&rft.volume=106&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-13 N1 - Date created - 1996-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The development and use of a DNA polymerase arrest assay for the evaluation of parameters affecting intrastrand tetraplex formation. AN - 78268762; 8702855 AB - We show here that a K+-dependent block to DNA synthesis is a sensitive and specific indicator of intrastrand tetraplex formation that can be used, both to identify sequences with tetraplex-forming potential and to examine parameters that affect tetraplex formation. We show that tetraplex formation is determined by a complex combination of factors including the size and base composition of its constituent loops and stems. In the process of carrying out this study we have found that the number of sequences with the ability to form tetraplexes is larger than previously thought, and that such sequences are ubiquitous in eukaryote genomes. JF - The Journal of biological chemistry AU - Weitzmann, M N AU - Woodford, K J AU - Usdin, K AD - Section on Genomic Structure and Function, Laboratory of Biochemical Pharmacology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. Y1 - 1996/08/23/ PY - 1996 DA - 1996 Aug 23 SP - 20958 EP - 20964 VL - 271 IS - 34 SN - 0021-9258, 0021-9258 KW - DNA, Single-Stranded KW - 0 KW - Oligodeoxyribonucleotides KW - Sulfuric Acid Esters KW - DNA KW - 9007-49-2 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - dimethyl sulfate KW - JW5CW40Z50 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Potassium -- chemistry KW - Base Composition KW - Oligodeoxyribonucleotides -- chemistry KW - Sulfuric Acid Esters -- chemistry KW - Molecular Sequence Data KW - DNA, Single-Stranded -- chemistry KW - Templates, Genetic KW - Nucleic Acid Conformation -- drug effects KW - Cell-Free System KW - DNA -- metabolism KW - DNA -- chemistry KW - DNA -- biosynthesis KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78268762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+development+and+use+of+a+DNA+polymerase+arrest+assay+for+the+evaluation+of+parameters+affecting+intrastrand+tetraplex+formation.&rft.au=Weitzmann%2C+M+N%3BWoodford%2C+K+J%3BUsdin%2C+K&rft.aulast=Weitzmann&rft.aufirst=M&rft.date=1996-08-23&rft.volume=271&rft.issue=34&rft.spage=20958&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-11 N1 - Date created - 1996-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deficiency in beta1,3-galactosyltransferase of a Leishmania major lipophosphoglycan mutant adversely influences the Leishmania-sand fly interaction. AN - 78266046; 8702802 AB - To study the function of side chain oligosaccharides of the cell-surface lipophosphoglycan (LPG), mutagenized Leishmania major defective in side chain biosynthesis were negatively selected by agglutination with the monoclonal antibody WIC79.3, which recognizes the galactose-containing side chains of L. major LPG. One such mutant, called Spock, lacked the ability to bind significantly to midguts of the natural L. major vector, Phlebotomus papatasi, and to maintain infection in the sand fly after excretion of the digested bloodmeal. Biochemical characterization of Spock LPG revealed its structural similarity to the LPG of Leishmania donovani, a species whose inability to bind to and maintain infections in P. papatasi midguts has been strongly correlated with the expression of a surface LPG lacking galactose-terminated oligosaccharide side chains. An in vitro galactosyltransferase assay using wild-type or Spock membranes was used to determine that the defect in Spock LPG biosynthesis is a result of defective beta1,3-galactosyltransferase activity as opposed to a modification of LPG, which would prevent it from serving as a competent substrate for galactose addition. The results of these experiments show that Spock lacks the beta1, 3-galactosyltransferase for side chain addition and that the LPG side chains are required for L. major to bind to and to produce transmissible infection in P. papatasi. JF - The Journal of biological chemistry AU - Butcher, B A AU - Turco, S J AU - Hilty, B A AU - Pimenta, P F AU - Panunzio, M AU - Sacks, D L AD - Laboratory of Parasitic Diseases, Intracellular Parasite Biology Section, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08/23/ PY - 1996 DA - 1996 Aug 23 SP - 20573 EP - 20579 VL - 271 IS - 34 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Glycosphingolipids KW - Oligosaccharides KW - lipophosphonoglycan KW - Galactosyltransferases KW - EC 2.4.1.- KW - Index Medicus KW - Intestines -- parasitology KW - Animals KW - Repetitive Sequences, Nucleic Acid KW - Oligosaccharides -- chemistry KW - Mutation KW - Structure-Activity Relationship KW - Cell-Free System KW - Antibodies, Monoclonal -- immunology KW - Insect Vectors -- parasitology KW - Phlebotomus -- parasitology KW - Glycosphingolipids -- physiology KW - Galactosyltransferases -- physiology KW - Leishmania major -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78266046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Deficiency+in+beta1%2C3-galactosyltransferase+of+a+Leishmania+major+lipophosphoglycan+mutant+adversely+influences+the+Leishmania-sand+fly+interaction.&rft.au=Butcher%2C+B+A%3BTurco%2C+S+J%3BHilty%2C+B+A%3BPimenta%2C+P+F%3BPanunzio%2C+M%3BSacks%2C+D+L&rft.aulast=Butcher&rft.aufirst=B&rft.date=1996-08-23&rft.volume=271&rft.issue=34&rft.spage=20573&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-11 N1 - Date created - 1996-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of a human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogs. AN - 78212887; 8759039 AB - The aromatic fatty acid phenylacetate and its analogs induce tumor cytostasis and differentiation in experimental models. Although the underlying mechanisms of action are not clear, effects on lipid metabolism are evident. We have now examined whether these compounds, structurally similar to the peroxisome proliferator clofibrate, affect the human peroxisome proliferator-activated receptor (hPPAR), a homolog of the rodent PPAR alpha, a transcriptional factor regulating lipid metabolism and cell growth. Gene transfer experiments showed activation of hPPAR, evident by the increased expression of the reporter gene chloramphenicol acetyltransferase linked to PPAR-response element from either the rat acyl-CoA oxidase or rabbit CYP4A6 genes. The relative potency of tested drugs in the co-transfection assay was: 4-iodophenylbutyrate > 4-chlorophenylbutyrate > clofibrate > phenylbutyrate > naphthylacetate > 2,4-D > 4-chlorophenylacetate > phenylacetate >> indoleacetate. Phenylacetylglutamine, in which the carboxylic acid is blocked, was inactive. The ability of the aromatic fatty acids to activate PPAR was confirmed in vivo, as CYP4A mRNA levels increased in hepatocytes of treated rats. Further studies using human prostate carcinoma, melanoma, and glioblastoma cell lines showed a tight correlation between drug-induced cytostasis, increased expression of the endogenous hPPAR, and receptor activation documented in the gene-transfer model. These results identify phenylacetate and its analogs as a new class of aromatic fatty acids capable of activating hPPAR, and suggest that this nuclear receptor may mediate tumor cytostasis induced by these drugs. JF - Biochemical pharmacology AU - Pineau, T AU - Hudgins, W R AU - Liu, L AU - Chen, L C AU - Sher, T AU - Gonzalez, F J AU - Samid, D AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/08/23/ PY - 1996 DA - 1996 Aug 23 SP - 659 EP - 667 VL - 52 IS - 4 SN - 0006-2952, 0006-2952 KW - Fatty Acids KW - 0 KW - Phenylacetates KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Transfection KW - Dose-Response Relationship, Drug KW - Humans KW - Fatty Acids -- chemistry KW - Rabbits KW - Transcription Factors -- drug effects KW - Phenylacetates -- pharmacology KW - Brain Neoplasms -- drug therapy KW - Liver -- drug effects KW - Receptors, Cytoplasmic and Nuclear -- drug effects KW - Glioblastoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78212887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Activation+of+a+human+peroxisome+proliferator-activated+receptor+by+the+antitumor+agent+phenylacetate+and+its+analogs.&rft.au=Pineau%2C+T%3BHudgins%2C+W+R%3BLiu%2C+L%3BChen%2C+L+C%3BSher%2C+T%3BGonzalez%2C+F+J%3BSamid%2C+D&rft.aulast=Pineau&rft.aufirst=T&rft.date=1996-08-23&rft.volume=52&rft.issue=4&rft.spage=659&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-18 N1 - Date created - 1996-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of genetic instability during mammary tumor progression using a novel selection-based assay for in vivo mutations in a bacteriophage lambda transgene target. AN - 78325538; 8799156 AB - Genetic instability is thought to be responsible for the numerous genotypic changes that occur during neoplastic transformation and metastatic progression. To explore the role of genetic instability at the level of point mutations during mammary tumor development and malignant progression, we combined transgenic mouse models of mutagenesis detection and oncogenesis. Bitransgenic mice were generated that carried both a bacteriophage lambda transgene to assay mutagenesis and a polyomavirus middle T oncogene, mammary gland-targeted expression of which led to metastatic mammary adenocarcinomas. We developed a novel assay for the detection of mutations in the lambda transgene that selects for phage containing forward mutations only in the lambda cII gene, using an hfl- bacterial host. In addition to the relative ease of direct selection, the sensitivity of this assay for both spontaneous and chemically induced mutations was comparable to the widely used mutational target gene, lambda lacI, making the cII assay an attractive alternative for mutant phage recovery for any lambda-based mouse mutagenesis assay system. The frequencies of lambda cII- mutants were not significantly different in normal mammary epithelium, primary mammary adenocarcinomas, and pulmonary metastases. The cII mutational spectra in these tissues consisted mostly of G/C-->A/T transitions, a large fraction of which occurred at CpG dinucleotides. These data suggest that, in this middle T oncogene model of mammary tumor progression, a significant increase in mutagenesis is not required for tumor development or for metastatic progression. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Jakubczak, J L AU - Merlino, G AU - French, J E AU - Muller, W J AU - Paul, B AU - Adhya, S AU - Garges, S AD - Molecular Genetics Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/08/20/ PY - 1996 DA - 1996 Aug 20 SP - 9073 EP - 9078 VL - 93 IS - 17 SN - 0027-8424, 0027-8424 KW - Index Medicus KW - Animals KW - Bacteriophage lambda -- genetics KW - Lung Neoplasms -- secondary KW - Transgenes KW - Disease Progression KW - Mice KW - Sequence Analysis, DNA KW - Mice, Transgenic KW - Selection, Genetic KW - Base Sequence KW - Mutagenicity Tests KW - Molecular Sequence Data KW - Neoplasm Metastasis KW - Female KW - Male KW - Mammary Neoplasms, Animal -- genetics KW - Point Mutation KW - Cell Transformation, Neoplastic -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78325538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Analysis+of+genetic+instability+during+mammary+tumor+progression+using+a+novel+selection-based+assay+for+in+vivo+mutations+in+a+bacteriophage+lambda+transgene+target.&rft.au=Jakubczak%2C+J+L%3BMerlino%2C+G%3BFrench%2C+J+E%3BMuller%2C+W+J%3BPaul%2C+B%3BAdhya%2C+S%3BGarges%2C+S&rft.aulast=Jakubczak&rft.aufirst=J&rft.date=1996-08-20&rft.volume=93&rft.issue=17&rft.spage=9073&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-31 N1 - Date created - 1996-10-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: FASEB J. 1994 May;8(8):545-50 [8181674] Mutat Res. 1994 Apr 15;306(2):119-28 [7512210] Mutagenesis. 1994 Jul;9(4):367-75 [7968580] Environ Mol Mutagen. 1995;25(3):231-45 [7737141] Annu Rev Pharmacol Toxicol. 1995;35:145-64 [7598490] Cancer Res. 1995 Dec 1;55(23):5489-92 [7585619] Science. 1976 Oct 1;194(4260):23-8 [959840] Annu Rev Genet. 1980;14:399-445 [6452089] Proc Natl Acad Sci U S A. 1985 May;82(10):3134-8 [3159014] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7971-5 [2530578] Cell. 1990 Jun 1;61(5):759-67 [2188735] Genet Anal Tech Appl. 1990 Dec;7(8):212-8 [2151115] Cancer Res. 1991 Jun 15;51(12):3075-9 [2039987] Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7958-62 [1832771] Nucleic Acids Res. 1991 Sep 25;19(18):4967-73 [1923765] Environ Mol Mutagen. 1991;18(4):316-21 [1836179] Mol Cell Biol. 1992 Mar;12(3):954-61 [1312220] Bioessays. 1992 Jan;14(1):33-6 [1546979] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10578-82 [1359541] Adv Cancer Res. 1993;60:121-56 [8417498] Carcinogenesis. 1993 Jan;14(1):29-35 [8093862] Toxicol Lett. 1993 Apr;67(1-3):259-81 [8451764] Mutat Res. 1993 Jul;288(1):133-49 [7686257] Cancer Res. 1994 Oct 1;54(19):5059-63 [7923117] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dexamethasone and forskolin synergistically increase [Met5]enkephalin accumulation in mixed brain cell cultures. AN - 78473865; 8883890 AB - Possible synergistic effects of the glucocorticoid dexamethasone (DEX, 10(-7) M) and the adenylate cyclase agonist forskolin (FSK, 10(-5) M) on [Met5]enkephalin (ME) accumulation were examined in enriched rat glial cultures and in mixed neuronal/glial cultures. In enriched glial cultures, DEX and FSK each stimulated the accumulation of ME 2-3-fold over basal media levels, but there was little additional stimulation when these agonists were combined. In contrast, mixed neuronal/glial cultures showed only weak responses to DEX or FSK alone, but the combination of these agonists produced a pronounced synergistic effect on media ME accumulation (6-10-fold over basal levels). The DEX effect was mediated via a classical glucocorticoid receptor, since DEX was potent (acting over a concentration range of 10(-11)-10(-7) M), mimicked by corticosterone (10(-6) M), and blocked by the glucocorticoid receptor antagonist RU486. There was a pronounced time lag (2 days) for the synergistic effects of DEX + FSK to develop. In situ hybridization and immunocytochemical studies suggested that astrocytes were the major source for the increased ME production in all mixed neuronal/glial cultures examined. Creating a mixed culture by plating fetal neurons onto confluent, enriched P7 glial cultures inhibited accumulation of ME in the media. DEX + FSK, but neither agonist alone, overcame this neuronal inhibition and increased accumulation of media ME to levels identical to levels in stimulated enriched glial cultures. The net effect was a 6-fold increase in ME accumulation in the mixed neuronal/glial cultures relative to a 2.5-fold increase in the enriched glial cultures. Neuronal inhibition of basal glial ME production could explain the similar synergistic effects of DEX + FSK observed in all mixed neuronal/glial cultures examined, and may be important in suppressing ME production by astrocytes in the brain. JF - Brain research AU - McMillian, M K AU - Pennypacker, K R AU - Thai, L AU - Wu, G C AU - Suh, H H AU - Simmons, K L AU - Hudson, P M AU - Sawin, S B AU - Hong, J S AD - Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1996/08/19/ PY - 1996 DA - 1996 Aug 19 SP - 67 EP - 74 VL - 730 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Drug Combinations KW - 0 KW - Enkephalins KW - Glucocorticoids KW - Protein Precursors KW - RNA, Messenger KW - Receptors, Glucocorticoid KW - proenkephalin KW - Colforsin KW - 1F7A44V6OU KW - Enkephalin, Methionine KW - 58569-55-4 KW - enkephalin-Met, Arg(6)-Phe(7)- KW - 73024-95-0 KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Neuroglia -- metabolism KW - Animals KW - Rats, Inbred F344 KW - Enkephalins -- genetics KW - Rats -- embryology KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Protein Precursors -- genetics KW - Drug Synergism KW - Receptors, Glucocorticoid -- physiology KW - Astrocytes -- metabolism KW - Colforsin -- pharmacology KW - Neurons -- metabolism KW - Enkephalin, Methionine -- antagonists & inhibitors KW - Brain -- cytology KW - Dexamethasone -- pharmacology KW - Neurons -- physiology KW - Enkephalin, Methionine -- analogs & derivatives KW - Enkephalin, Methionine -- metabolism KW - Brain -- metabolism KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78473865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Hepatic+stem+cells+in+liver+regeneration.&rft.au=Thorgeirsson%2C+S+S&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1996-09-01&rft.volume=10&rft.issue=11&rft.spage=1249&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-28 N1 - Date created - 1997-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytogenetic damage measured in human sperm following cancer chemotherapy. AN - 78286226; 8781585 AB - Germ-line cytogenetic damage is well documented in laboratory animals exposed to anti-cancer agents, but has been harder to verify in the human. This paper reviews published studies demonstrating cytogenetic damage in human sperm following exposure to anti-cancer chemicals, as measured by the human-sperm/ hamster-egg cytogenetic technique and fluorescence in situ hybridization. These two assays have provided important information on one step in the pathway leading to induced, transmissible germ line damage in the human. By way of introduction, a short review of the traditional human endpoints used to address the question of induced, transmissible genetic damage in human germ cells (mutation epidemiology) related to anti-cancer chemicals is presented. JF - Mutation research AU - Robbins, W A AD - School of Public Health, University of North Carolina at Chapel Hill, USA. robbins2@niehs.nih.gov Y1 - 1996/08/17/ PY - 1996 DA - 1996 Aug 17 SP - 235 EP - 252 VL - 355 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Neoplasms -- drug therapy KW - Animals KW - Humans KW - In Situ Hybridization, Fluorescence -- methods KW - Chromosomes -- drug effects KW - Germ-Line Mutation KW - Ovum -- drug effects KW - Male KW - Cricetinae KW - Mutagenicity Tests -- methods KW - Spermatozoa -- drug effects KW - Antineoplastic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78286226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Cytogenetic+damage+measured+in+human+sperm+following+cancer+chemotherapy.&rft.au=Robbins%2C+W+A&rft.aulast=Robbins&rft.aufirst=W&rft.date=1996-08-17&rft.volume=355&rft.issue=1-2&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A C-terminal mutant of the G protein beta subunit deficient in the activation of phospholipase C-beta. AN - 78265811; 8702747 AB - The molecular mechanism by which the G protein betagamma complex modulates multiple mammalian effector pathways is unknown. Homolog-scanning mutagenesis of the G protein beta subunit was employed to identify residues critical for the activation of phospholipase C-beta2 (PLC-beta2). A series of chimeras was made by introducing small segments of the Dictyostelium beta subunit into a background of mammalian beta1 and tested in COS cell cotransfection assays for their ability to activate PLC-beta2 and assemble with mammalian gamma2. A chimera that contained four Dictyostelium beta substitutions within the C-terminal 14 residues was unable to activate PLC-beta2 when cotransfected with gamma, despite its demonstrable expression in a gamma-dependent manner. Cotransfection of the mutant blocked m2 muscarinic receptor activation of PLC by a pertussis toxin-sensitive pathway. This C-terminal mutant retained the ability, however, to stimulate the mitogen-activated protein kinase pathway. These results imply that activation of different betagamma-responsive effectors is mediated by distinct domains. JF - The Journal of biological chemistry AU - Zhang, S AU - Coso, O A AU - Collins, R AU - Gutkind, J S AU - Simonds, W F AD - Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08/16/ PY - 1996 DA - 1996 Aug 16 SP - 20208 EP - 20212 VL - 271 IS - 33 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Recombinant Fusion Proteins KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Type C Phospholipases KW - EC 3.1.4.- KW - PLCB1 protein, human KW - EC 3.1.4.11 KW - PLCB2 protein, human KW - Phospholipase C beta KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Enzyme Activation KW - Humans KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Cattle KW - Sequence Alignment KW - Transfection KW - Cells, Cultured KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Signal Transduction KW - Dictyostelium -- chemistry KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry KW - GTP-Binding Proteins -- genetics KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78265811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=The+efficiency+of+meiotic+recombination+between+dispersed+sequences+in+Saccharomyces+cerevisiae+depends+upon+their+chromosomal+location.&rft.au=Goldman%2C+A+S%3BLichten%2C+M&rft.aulast=Goldman&rft.aufirst=A&rft.date=1996-09-01&rft.volume=144&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-03 N1 - Date created - 1996-10-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M37183; GENBANK; M95678; X73641; M13236; M16404 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of an ATP binding mutant of PKC-delta inhibits Sis-induced transformation of NIH3T3 cells. AN - 78274095; 8761294 AB - In an effort to determine the role of protein kinase C-delta (PKC-delta) in cellular transformation mediated by the sis proto-oncogene, we cotransfected expression vectors containing cDNAs that encode for c-sis with an ATP binding mutant of PKC-delta (PKC-delta K376R) or wild type PKC-delta (PKC-delta WT) into NIH3T3 cells. Our results showed that expression of PKC-delta K376R severely impaired Sis-induced focus formation, whereas cotransfection of PKC-delta WT cDNA had no effect on Sis-mediated transformation. Consistent with this result, PKC-delta K376R expression also inhibited PDGF-BB-mediated anchorage-independent colony formation. While cotransfection of a vector containing a dominant negative mutant of ras (N17 ras) cDNA potently inhibited Sis-induced transformation, the expression of PKC-delta K376R did not block transformation mediated by v-H-Ras or v-Raf. In addition, PDGF-BB-induced Raf and mitogen-activated protein kinase activation, which are known to be downstream molecules in the Ras cascade, were not affected by the expression of PKC-delta K376R, indicating that PKC-delta and Ras are segregated in mediating Sis-induced transformation. Interestingly, expression of PKC-delta K376R strongly reduced TPA responsive element (TRE) transactivation induced by PDGF stimulation, suggesting that activation of TRE-containing genes, which may be involved in Sis-mediated transformation, are negatively regulated by expression of PKC-delta K376R. JF - Oncogene AU - Li, W AU - Michieli, P AU - Alimandi, M AU - Lorenzi, M V AU - Wu, Y AU - Wang, L H AU - Heidaran, M A AU - Pierce, J H AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/08/15/ PY - 1996 DA - 1996 Aug 15 SP - 731 EP - 737 VL - 13 IS - 4 SN - 0950-9232, 0950-9232 KW - DNA Primers KW - 0 KW - Isoenzymes KW - Platelet-Derived Growth Factor KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-sis KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Luciferases KW - EC 1.13.12.- KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Receptor, Platelet-Derived Growth Factor beta KW - EC 2.7.10.1 KW - Receptors, Platelet-Derived Growth Factor KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Receptors, Platelet-Derived Growth Factor -- metabolism KW - 3T3 Cells KW - Animals KW - Mice KW - Protein Binding KW - Luciferases -- biosynthesis KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Phosphorylation KW - Molecular Sequence Data KW - Enzyme Induction KW - ras Proteins -- metabolism KW - Cell Transformation, Neoplastic -- genetics KW - Protein Kinase C -- metabolism KW - Isoenzymes -- antagonists & inhibitors KW - Platelet-Derived Growth Factor -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Protein Kinase C -- genetics KW - Adenosine Triphosphate -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78274095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Expression+of+an+ATP+binding+mutant+of+PKC-delta+inhibits+Sis-induced+transformation+of+NIH3T3+cells.&rft.au=Li%2C+W%3BMichieli%2C+P%3BAlimandi%2C+M%3BLorenzi%2C+M+V%3BWu%2C+Y%3BWang%2C+L+H%3BHeidaran%2C+M+A%3BPierce%2C+J+H&rft.aulast=Li&rft.aufirst=W&rft.date=1996-08-15&rft.volume=13&rft.issue=4&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain-derived neurotrophic factor protects neuroblastoma cells from vinblastine toxicity. AN - 78223379; 8706017 AB - Brain-derived neurotrophic factor (BDNF) and its receptors are necessary for the survival and development of many neuronal cells. Because BDNF and TrkB are expressed in many poor-prognosis neuroblastoma (NB) tumors, we evaluated the role of BDNF in affecting sensitivity to chemotherapeutic agents. We investigated the effects of activation of the BDNF-TrkB signal transduction pathway in two NB cell lines, 15N and SY5Y. 15N cells lack the high-affinity receptor p145TrkB and express BDNF; 15N cells were used along with 15N-TrkB cells, a subline transfected with a TrkB expression vector. In cytotoxicity assays, 15N-TrkB cells were consistently 1.4-2 fold more resistant to vinblastine than 15N cells. Drug accumulation assays showed a 50% reduction in[3H]vinblastine accumulation in 15N-TrkB cells compared with control 15N cells. Addition of 30 ng/ml BDNF resulted in a reduction to 46% of control in 15N cells and a reduction to 28% of control in 15N-TrkB cells. SY5Y cells were chosen as a second model because they lack both endogenous BDNF and TrkB expression. p145TrkB expression is induced by 1 nM retinoic acid. Vinblastine accumulation was not significantly affected by 1 nM retinoic acid in SY5Y cells. Addition of 30 ng/ml BDNF decreased [3H]vinblastine accumulation to 58% of control in SY5Y cells and decreased [3H]vinblastine accumulation to 62% of control in TrkB-expressing SY5Y cells. Although an increase in BDNF expression in seen in multidrug-resistant sublines of SY5Y and BE(2)-C NB cells, the protective effect of BDNF in vinblastine toxicity may be unrelated to mdr-1, because the activity of other agents transported by P-glycoprotein was not affected. There was no increase in mdr-1 expression in 1 nM RA SY5Y cells and 15N-TrkB cells, as assessed by Northern blot analysis. In addition to the effects of BDNF on vinblastine cytotoxicity and accumulation, there was an inhibition in the ability of vinblastine to depolymerize tubulin in BDNF-treated cells. Thus, BDNF and TrkB may partially rescue NB cells from vinblastine toxicity and thereby may contribute to a more chemoresistant phenotype. JF - Cancer research AU - Scala, S AU - Wosikowski, K AU - Giannakakou, P AU - Valle, P AU - Biedler, J L AU - Spengler, B A AU - Lucarelli, E AU - Bates, S E AU - Thiele, C J AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/08/15/ PY - 1996 DA - 1996 Aug 15 SP - 3737 EP - 3742 VL - 56 IS - 16 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Brain-Derived Neurotrophic Factor KW - Nerve Tissue Proteins KW - P-Glycoprotein KW - RNA, Messenger KW - Tubulin KW - Tretinoin KW - 5688UTC01R KW - Vinblastine KW - 5V9KLZ54CY KW - Index Medicus KW - Tretinoin -- pharmacology KW - Tumor Cells, Cultured KW - P-Glycoprotein -- analysis KW - Humans KW - RNA, Messenger -- analysis KW - Tubulin -- metabolism KW - Drug Resistance KW - Vinblastine -- pharmacology KW - Neuroblastoma -- drug therapy KW - Vinblastine -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78223379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Brain-derived+neurotrophic+factor+protects+neuroblastoma+cells+from+vinblastine+toxicity.&rft.au=Scala%2C+S%3BWosikowski%2C+K%3BGiannakakou%2C+P%3BValle%2C+P%3BBiedler%2C+J+L%3BSpengler%2C+B+A%3BLucarelli%2C+E%3BBates%2C+S+E%3BThiele%2C+C+J&rft.aulast=Scala&rft.aufirst=S&rft.date=1996-08-15&rft.volume=56&rft.issue=16&rft.spage=3737&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-10 N1 - Date created - 1996-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ifosfamide and etoposide plus vincristine, doxorubicin, and cyclophosphamide for newly diagnosed Ewing's sarcoma family of tumors. AN - 78221147; 8756388 AB - This study was conducted to determine the feasibility of, and improve outcome by, incorporating ifosfamide and etoposide (IE) into the therapy of newly diagnosed patients with Ewing's sarcoma family of tumors of bone and soft tissue. Fifty-four newly diagnosed patients received 7 cycles of vincristine, doxorubicin, and cyclophosphamide (VAdriaC) and 11 cycles of IE. Radiation therapy after the fifth chemotherapy cycle was the primary approach to local control. Actuarial 5-year event-free survival (EFS) and overall survival rates were 42% and 45%, respectively, with a median duration of potential follow-up of 6.8 years. EFS was significantly better for patients with localized tumors than for those with metastatic lesions (64% v. 13%, P < 0.0001). Actuarial local progression-free survival at 5 years was 74%, and did not correlate with primary tumor size or site, histologic subtype, or the presence of metastases. Febrile neutropenia developed after 49% of cycles, and clinical or sub-clinical cardiac dysfunction was common (7% and 40% respectively). There were four toxic deaths and one case of secondary myelodysplastic syndrome. Despite substantial toxicity, the integration of IE into the front-line, VAdriaC-based therapy of patients with Ewing's sarcoma family of tumors is feasible and appeared to significantly improve the outcome for patients with high risk localized tumors, but had no impact on the poor prognosis of patients with metastatic tumors. Local control can be achieved in the vast majority of patients using radiotherapy exclusively, even among patients with bulky, central axis tumors. Longer follow-up is needed to evaluate the late effects of this intensive therapy. JF - Cancer AU - Wexler, L H AU - DeLaney, T F AU - Tsokos, M AU - Avila, N AU - Steinberg, S M AU - Weaver-McClure, L AU - Jacobson, J AU - Jarosinski, P AU - Hijazi, Y M AU - Balis, F M AU - Horowitz, M E AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892-1928, USA. Y1 - 1996/08/15/ PY - 1996 DA - 1996 Aug 15 SP - 901 EP - 911 VL - 78 IS - 4 SN - 0008-543X, 0008-543X KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Ifosfamide KW - UM20QQM95Y KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Drug Administration Schedule KW - Humans KW - Vincristine -- administration & dosage KW - Ifosfamide -- adverse effects KW - Heart Failure -- chemically induced KW - Neutropenia -- chemically induced KW - Pilot Projects KW - Child KW - Doxorubicin -- administration & dosage KW - Etoposide -- administration & dosage KW - Adult KW - Thrombocytopenia -- chemically induced KW - Etoposide -- adverse effects KW - Adolescent KW - Male KW - Female KW - Ifosfamide -- administration & dosage KW - Bone Neoplasms -- drug therapy KW - Soft Tissue Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Sarcoma, Ewing -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78221147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Ifosfamide+and+etoposide+plus+vincristine%2C+doxorubicin%2C+and+cyclophosphamide+for+newly+diagnosed+Ewing%27s+sarcoma+family+of+tumors.&rft.au=Wexler%2C+L+H%3BDeLaney%2C+T+F%3BTsokos%2C+M%3BAvila%2C+N%3BSteinberg%2C+S+M%3BWeaver-McClure%2C+L%3BJacobson%2C+J%3BJarosinski%2C+P%3BHijazi%2C+Y+M%3BBalis%2C+F+M%3BHorowitz%2C+M+E&rft.aulast=Wexler&rft.aufirst=L&rft.date=1996-08-15&rft.volume=78&rft.issue=4&rft.spage=901&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer 1997 Feb 15;79(4):867 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor beta 1 suppresses genomic instability independent of a G1 arrest, p53, and Rb. AN - 78219369; 8706000 AB - Alterations in expression of or responsiveness to transforming growth factor beta (TGF-beta) are frequently found in human and animal epithelial cancers and are though to be important for loss of growth control in the neoplastic cell. We show here that keratinocyte cell lines from mice with a targeted deletion of the TGF-beta 1 gene have significantly increased frequencies of gene amplification in response to the drug N-phosphonoacetyl-L-aspartate (PALA) compared to TGF-beta 1-expressing control keratinocyte cell lines. In contrast to the control lines, the PALA-mediated G1 arrest did not occur in the TGF-beta 1 null keratinocytes despite the presence of wild-type p53 in both genotypes. Exogenous TGF-beta 1 suppresses gene amplification in the null keratinocytes at concentrations that do not cause a G1 growth arrest and in human tumor cell lines that are insensitive to TGF-beta 1-mediated growth inhibition. The pathway of TGF-beta 1 suppression is independent of the p53 and Rb genes, but requires an intact TGF-beta type II receptor. These studies reveal a novel TGF-beta-mediated pathway regulating genomic stability and suggest that defects in TGF-beta signaling may have profound effects on tumor progression independent of cell proliferation. JF - Cancer research AU - Glick, A B AU - Weinberg, W C AU - Wu, I H AU - Quan, W AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/08/15/ PY - 1996 DA - 1996 Aug 15 SP - 3645 EP - 3650 VL - 56 IS - 16 SN - 0008-5472, 0008-5472 KW - Transforming Growth Factor beta KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - sparfosic acid KW - 78QVZ7RG8L KW - Phosphonoacetic Acid KW - N919E46723 KW - Index Medicus KW - Aspartic Acid -- pharmacology KW - Animals KW - Aspartic Acid -- analogs & derivatives KW - Cells, Cultured KW - Phosphonoacetic Acid -- analogs & derivatives KW - Phosphonoacetic Acid -- pharmacology KW - Mice KW - Gene Amplification KW - Genes, Retinoblastoma -- physiology KW - Transforming Growth Factor beta -- physiology KW - Genes, p53 -- physiology KW - G1 Phase -- drug effects KW - Transforming Growth Factor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78219369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Transforming+growth+factor+beta+1+suppresses+genomic+instability+independent+of+a+G1+arrest%2C+p53%2C+and+Rb.&rft.au=Glick%2C+A+B%3BWeinberg%2C+W+C%3BWu%2C+I+H%3BQuan%2C+W%3BYuspa%2C+S+H&rft.aulast=Glick&rft.aufirst=A&rft.date=1996-08-15&rft.volume=56&rft.issue=16&rft.spage=3645&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-10 N1 - Date created - 1996-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Res 1997 May 15;57(10):2079 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activated B cells express CD28/B7-independent costimulatory activity. AN - 78218890; 8759718 AB - Resting and activated B cells display distinct phenotypes and functional properties. Resting B cells are incompetent accessory cells whereas activated B cells are capable of triggering T cell activation. The up-regulation of expression of the B7 family of molecules has been considered to be the primary reason for this functional conversion of activated B cells. We report here that activation of B cells induces a novel costimulatory activity for induction of T cell proliferation, which is independent of the CD28/B7 costimulatory pathway. B cells activated by different stimuli expressed comparable levels of many of the known counter-receptors for costimulation and intercellular adhesion (B7-1, B7-2, HSA, ICAM-1), but differed markedly in their capacity to activate CD4+ T cells from CD28-deficient (-/-) mice. Activation of B cells via CD40, and to a lesser extent with LPS, induced potent B7/CD28-independent costimulatory activity that resulted in marked augmentation of IL-2-mediated proliferative responses of CD4+ T cells from CD28 -/- mice. The B7/CD28-independent costimulatory pathway was capable of triggering the activation of naive CD4+ T cells, as both sorted CD45RBhigh and isolated high density naive CD4+ T cells from CD28 -/- mice responded vigorously to the costimulation provided by CD40L-activated B cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ding, L AU - Shevach, E M AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/08/15/ PY - 1996 DA - 1996 Aug 15 SP - 1389 EP - 1396 VL - 157 IS - 4 SN - 0022-1767, 0022-1767 KW - Antigens, CD28 KW - 0 KW - Antigens, CD80 KW - Cell Adhesion Molecules KW - Interleukin-2 KW - Ionophores KW - Membrane Glycoproteins KW - CD40 Ligand KW - 147205-72-9 KW - Ionomycin KW - 56092-81-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - L Cells (Cell Line) KW - Membrane Glycoproteins -- physiology KW - Mice KW - Ionomycin -- pharmacology KW - Mice, Knockout KW - Interleukin-2 -- physiology KW - Lymphocyte Activation KW - Ionophores -- pharmacology KW - Transfection KW - Mice, Inbred C57BL KW - Immunologic Memory KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Adhesion Molecules -- physiology KW - Female KW - Cell Adhesion KW - Antigens, CD80 -- physiology KW - Antigens, CD28 -- physiology KW - CD4-Positive T-Lymphocytes -- immunology KW - B-Lymphocytes -- immunology KW - Antigen-Presenting Cells -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78218890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Activated+B+cells+express+CD28%2FB7-independent+costimulatory+activity.&rft.au=Ding%2C+L%3BShevach%2C+E+M&rft.aulast=Ding&rft.aufirst=L&rft.date=1996-08-15&rft.volume=157&rft.issue=4&rft.spage=1389&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-17 N1 - Date created - 1996-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Facile oxidative decarboxylation of 3,4-dihydroxyphenylacetic acid catalyzed by copper and manganese ions. AN - 78266878; 8765124 AB - Under physiological conditions, we observed the rapid, pH- and temperature-dependent, oxidative decarboxylation and hydration of 3,4-dihydroxyphenylacetic acid (DOPAC) to form 3,4-dihydroxybenzyl alcohol (DBAlc). This product was oxidized and underwent tautomerization to form 3,4-dihydroxybenzaldehyde (DBAld). This reaction did not occur in the presence of EDTA, was catalyzed by copper (CuI, CuII) and manganese (MnII) and was oxygen dependent. A variety of mono- and dihydroxyphenyl carboxylic acids were tested and the reaction producing DBAlc as an intermediate was observed to be unique to DOPAC. 3.4-Dihydroxymandelic acid (DOMA) was rapidly oxidatively decarboxylated to form DBAld directly. The substrate and catalyst selectivity of this reaction suggest that this may have physiological relevance in the neurotoxic consequences of manganese and copper to the dopaminergic system in man. JF - Biochimica et biophysica acta AU - Mefford, I N AU - Kincl, L AU - Dykstra, K H AU - Simpson, J T AU - Markey, S P AU - Dietz, S AU - Wightman, R M AD - Section on Clinical Pharmacology, NCRR, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/08/13/ PY - 1996 DA - 1996 Aug 13 SP - 224 EP - 230 VL - 1290 IS - 3 SN - 0006-3002, 0006-3002 KW - Benzaldehydes KW - 0 KW - Benzyl Alcohols KW - Catechols KW - Ions KW - Mandelic Acids KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - 3,4-dihydroxybenzyl alcohol KW - 3897-89-0 KW - Manganese KW - 42Z2K6ZL8P KW - protocatechualdehyde KW - 4PVP2HCH4T KW - 3,4-dihydroxymandelic acid KW - 775-01-9 KW - Copper KW - 789U1901C5 KW - Index Medicus KW - Oxidation-Reduction KW - Gas Chromatography-Mass Spectrometry KW - Catechols -- chemistry KW - Models, Chemical KW - Benzyl Alcohols -- chemistry KW - Benzaldehydes -- chemistry KW - Decarboxylation KW - Mandelic Acids -- chemistry KW - Catalysis KW - 3,4-Dihydroxyphenylacetic Acid -- chemistry KW - Manganese -- chemistry KW - Copper -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78266878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Facile+oxidative+decarboxylation+of+3%2C4-dihydroxyphenylacetic+acid+catalyzed+by+copper+and+manganese+ions.&rft.au=Mefford%2C+I+N%3BKincl%2C+L%3BDykstra%2C+K+H%3BSimpson%2C+J+T%3BMarkey%2C+S+P%3BDietz%2C+S%3BWightman%2C+R+M&rft.aulast=Mefford&rft.aufirst=I&rft.date=1996-08-13&rft.volume=1290&rft.issue=3&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-24 N1 - Date created - 1996-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell protein cross-linking by erbstatin and related compounds. AN - 78121987; 8687502 AB - The protein-tyrosine kinase inhibitor and stable erbstatin analogue methyl 2,5-dihydroxycinnamate (4) cross-links cell proteins by a non-physiological chemical mechanism (Stanwell et al., Cancer Res 55: 4950-4956, 1995). To determine the structural requirements for this effect, erbstatin (1) and fifteen related compounds, including caffeic acid phenylethyl ester (9) were synthesized and examined for their ability to induce cross-linking of cellular protein at concentrations ranging from low micromolar up to 1000 microM. Tests were conducted in NIH3T3 fibroblasts as well as mouse keratinocytes. Potent cross-linking of cellular protein was observed for a number of analogues, including erbstatin, at concentrations as low as 10-50 microM. The inactivity of methoxy and fluoro as compared with their corresponding dihydroxylated counterparts indicated that free aromatic hydroxyls were essential for cross-linking. Additionally, compounds containing phenyl rings with 1,4-dihydroxy substituents were more potent than those having 1,2-dihydroxylated patterns. As with the prototype compound 4, cross-linking was induced at both 37 degrees and 4 degrees, suggesting a chemical rather than physiological mechanism. Consistent with the data, a mechanism of action is proposed which involves initial oxidation to reactive quinone intermediates that subsequently cross-link protein nucleophiles via multiple 1,4-Michael-type additions. Similar alkylation of protein by protein-tyrosine kinase inhibitors, such as herbimycin A, has been invoked. While the latter benzoquinoid ansamycin antibiotics contain performed quinone moieties, results of the present study suggest that other hydroxylated kinase inhibitors can potentially participate in similar phenomena. A large number of potential therapeutics, including HIV integrase inhibitors, possess polyhydroxylated nuclei. The non-specific nature of the protein cross-linking reaction demonstrated for these erbstatin analogues, and the fact that cross-linking can occur at micromolar concentrations, may limit the therapeutic usefulness of such compounds to specific applications. JF - Biochemical pharmacology AU - Stanwell, C AU - Ye, B AU - Yuspa, S H AU - Burke, T R AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/08/09/ PY - 1996 DA - 1996 Aug 09 SP - 475 EP - 480 VL - 52 IS - 3 SN - 0006-2952, 0006-2952 KW - Enzyme Inhibitors KW - 0 KW - Hydroquinones KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - erbstatin KW - WDH83K6T5P KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Mice KW - Hydroquinones -- pharmacology KW - Protein-Tyrosine Kinases -- drug effects KW - Keratinocytes -- drug effects KW - Enzyme Inhibitors -- chemistry KW - Enzyme Inhibitors -- pharmacology KW - Hydroquinones -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78121987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Cell+protein+cross-linking+by+erbstatin+and+related+compounds.&rft.au=Stanwell%2C+C%3BYe%2C+B%3BYuspa%2C+S+H%3BBurke%2C+T+R&rft.aulast=Stanwell&rft.aufirst=C&rft.date=1996-08-09&rft.volume=52&rft.issue=3&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-19 N1 - Date created - 1996-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have different ionization states in the complex formed with the asymmetric drug KNI-272. AN - 78222825; 8756455 AB - In order to improve the design of HIV-1 protease inhibitors, it is essential to understand how they interact with active site residues, particularly the catalytic Asp25 and Asp125 residues. KNI-272 is a promising, potent HIV-1 protease inhibitor (K(i) approximately 5 pM), currently undergoing phase 1 clinical trials. Because KNI-272 is asymmetric, the complex it forms with the homodimeric HIV-1 protease also lacks symmetry, and the two protease monomers can have distinct NMR spectra. Monomer specific signal assignments were obtained for amino acid residues in the drug binding site as well as for six of the eight Asp residues in the protease/KNI-272 complex. Using these assignments, the ionization states of the Asp carboxyl groups were determined from measurements of (a) the pD dependence of the chemical shifts of the Asp carboxyl carbons and (b) the H/D isotope effect upon the Asp carboxyl carbon chemical shifts. The results of these measurements indicate that the carboxyl of Asp25 is protonated while that of Asp125 is not protonated. These findings provide not only the first experimental evidence regarding the distinct protonation states of Asp25/125 in HIV-1 protease/drug complexes, but also shed light on interactions responsible for inhibitor binding that should form the basis for improved drug designs. JF - Biochemistry AU - Wang, Y X AU - Freedberg, D I AU - Yamazaki, T AU - Wingfield, P T AU - Stahl, S J AU - Kaufman, J D AU - Kiso, Y AU - Torchia, D A AD - Molecular Structural Biology Unit, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08/06/ PY - 1996 DA - 1996 Aug 06 SP - 9945 EP - 9950 VL - 35 IS - 31 SN - 0006-2960, 0006-2960 KW - HIV Protease Inhibitors KW - 0 KW - Oligopeptides KW - Recombinant Proteins KW - kynostatin 272 KW - 147318-81-8 KW - DMP 323 KW - 151867-81-1 KW - Aspartic Acid KW - 30KYC7MIAI KW - Urea KW - 8W8T17847W KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Molecular Structure KW - Humans KW - Amino Acid Sequence KW - Urea -- chemistry KW - Urea -- analogs & derivatives KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Magnetic Resonance Spectroscopy -- methods KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Point Mutation KW - Recombinant Proteins -- chemistry KW - Protein Conformation KW - Oligopeptides -- chemistry KW - Oligopeptides -- metabolism KW - HIV-1 -- enzymology KW - HIV Protease -- metabolism KW - HIV Protease -- chemistry KW - HIV Protease Inhibitors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78222825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Solution+NMR+evidence+that+the+HIV-1+protease+catalytic+aspartyl+groups+have+different+ionization+states+in+the+complex+formed+with+the+asymmetric+drug+KNI-272.&rft.au=Wang%2C+Y+X%3BFreedberg%2C+D+I%3BYamazaki%2C+T%3BWingfield%2C+P+T%3BStahl%2C+S+J%3BKaufman%2C+J+D%3BKiso%2C+Y%3BTorchia%2C+D+A&rft.aulast=Wang&rft.aufirst=Y&rft.date=1996-08-06&rft.volume=35&rft.issue=31&rft.spage=9945&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-18 N1 - Date created - 1996-09-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Biochemistry 1997 Jan 7;36(1):280 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for overlapping active sites for 17 alpha-ethynlestradiol and bilirubin in the human major bilirubin UDPglucuronosyltransferase. AN - 78213606; 8756475 AB - The human major bilirubin UDP glucuronosyltransferase (transferase), HUG-Brl, and its mutants were expressed in the COS-1 cells using cDNA-based pSVL expression units to generate isoforms for the comparison of relative activities with 17 alpha-ethynlestradiol (17 alpha-EE) and bilirubin, its natural substrate. In comparison to bilirubin, 17 alpha-EE was a good substrate for HUG-Br1 under typical assay conditions of pH 7.2, confirming published studies [Ebner, T., et al. (1993) Mol. Pharmacol. 43, 649-654]. It was further shown that the estrogen derivative is 1.2-2-fold more effective as a substrate at pH 6.4 than at pH 7.2. The km for 17 alpha-EE was 40 microM under both pH conditions, while the Vmax values were 400 and 200 pmol per hour per 300 micrograms of protein at pH 6.4 and 7.2, respectively. The pattern of glucuronidation was similar for both bilirubin and 17 alpha-EE. Previously, a ratio of 2-3-fold more activity for bilirubin glucuronidation at pH 6.4 versus 7.6 was established, and km values of 2.5 microM at both pH conditions were determined [Ritter, J.K., et al. (1993) J. Biol. Chem. 268, 23573-23579]. In this study, the generation of 17 alpha-EE and bilirubin beta-glucuronides under both pH conditions was confirmed by the sensitivity of the products to beta-glucuronidase treatment. Concurrent glucuronidation reaction mixtures containing equal amounts of wild-type and mutant proteins demonstrated the following. P270G, V273D, and five different G276 mutants nearly or completely inactivated all glucuronidation at both pH levels. V273Q generated 81-94% of the normal activity for 17 alpha-EE and 42% of the normal activity for bilirubin turnover; H173R gave 37-60% of the normal turnover with both substrates, and V275I produced 15-24% of the normal level of glucuronide with both compounds. The most distinguishing amino acid tested was P176G which was approximately 50% normal for 17 alpha-EE at both pH conditions but was totally inactive for bilirubin. A second substitution, P285G, did not affect 17 alpha-EE turnover but was 50% normal for bilirubin. The parallel effects on the metabolism of both substrates by some mutants and the opposite results from two mutants are evidence for a common set of amino acids for their catalysis with the recruitment of additional amino acids to depend upon the substrate to be metabolized. Hence, amino acid substitutions in the protein are not necessarily universally inactivating. JF - Biochemistry AU - Ciotti, M AU - Owens, I S AD - Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1830, USA. Y1 - 1996/08/06/ PY - 1996 DA - 1996 Aug 06 SP - 10119 EP - 10124 VL - 35 IS - 31 SN - 0006-2960, 0006-2960 KW - DNA Primers KW - 0 KW - Isoenzymes KW - Recombinant Proteins KW - Ethinyl Estradiol KW - 423D2T571U KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - bilirubin glucuronoside glucuronosyltransferase KW - EC 2.4.1.95 KW - Bilirubin KW - RFM9X3LJ49 KW - Index Medicus KW - Isoenzymes -- chemistry KW - Animals KW - Humans KW - Hydrogen-Ion Concentration KW - Amino Acid Sequence KW - Isoenzymes -- metabolism KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Cercopithecus aethiops KW - Point Mutation KW - Molecular Sequence Data KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Bilirubin -- metabolism KW - Glucuronosyltransferase -- metabolism KW - Ethinyl Estradiol -- metabolism KW - Glucuronosyltransferase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78213606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Evidence+for+overlapping+active+sites+for+17+alpha-ethynlestradiol+and+bilirubin+in+the+human+major+bilirubin+UDPglucuronosyltransferase.&rft.au=Ciotti%2C+M%3BOwens%2C+I+S&rft.aulast=Ciotti&rft.aufirst=M&rft.date=1996-08-06&rft.volume=35&rft.issue=31&rft.spage=10119&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-18 N1 - Date created - 1996-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Shaking out the cause of addiction. AN - 78246375; 8701316 JF - Science (New York, N.Y.) AU - Hyman, S E AD - National Institute of Mental Health, Rockville, MD 20857, USA. Y1 - 1996/08/02/ PY - 1996 DA - 1996 Aug 02 SP - 611 EP - 612 VL - 273 IS - 5275 SN - 0036-8075, 0036-8075 KW - Cyclic AMP Response Element-Binding Protein KW - 0 KW - Narcotics KW - Receptors, Opioid, mu KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Animals KW - Substance Withdrawal Syndrome -- metabolism KW - Locus Coeruleus -- metabolism KW - Mice KW - Receptors, Opioid, mu -- metabolism KW - Mice, Knockout KW - Drug Tolerance KW - Substance Withdrawal Syndrome -- etiology KW - Cyclic AMP -- metabolism KW - Neurons -- physiology KW - Up-Regulation KW - Locus Coeruleus -- physiology KW - Neuronal Plasticity KW - Signal Transduction KW - Opioid-Related Disorders -- metabolism KW - Cyclic AMP Response Element-Binding Protein -- physiology KW - Cyclic AMP Response Element-Binding Protein -- genetics KW - Narcotics -- adverse effects KW - Narcotics -- administration & dosage KW - Opioid-Related Disorders -- etiology KW - Narcotics -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78246375?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Shaking+out+the+cause+of+addiction.&rft.au=Hyman%2C+S+E&rft.aulast=Hyman&rft.aufirst=S&rft.date=1996-08-02&rft.volume=273&rft.issue=5275&rft.spage=611&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-03 N1 - Date created - 1996-09-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Science. 1996 Aug 2;273(5275):657-9 [8662559] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Non-equivalent roles for the first and second zinc fingers of protein kinase Cdelta. Effect of their mutation on phorbol ester-induced translocation in NIH 3T3 cells. AN - 78220591; 8702464 AB - Classical and novel protein kinase C (PKC) isozymes contain two, so-called cysteine-rich zinc finger domains that represent the binding sites for phorbol esters and the diacylglycerols. X-ray crystallographic, mutational, and modeling studies are providing detailed understanding of the interactions between the phorbol esters and individual PKC zinc fingers. In the present study, we explore the roles of the individual zinc fingers in the context of the intact enzyme. Our approach was to mutate either the first, the second, or both zinc fingers of PKCdelta, to express the mutated enzyme in NIH 3T3 cells, and to monitor the effect of the mutations on the dose-response curve for translocation induced by phorbol 12-myristate 13-acetate. The introduced mutations change into glycine the consensus proline in the phorbol ester binding loop of the zinc finger; in the isolated zinc finger, this mutation causes a 125-fold decrease in phorbol ester binding affinity. We observed that mutation in the first zinc finger caused almost no shift in the dose-response curve for translocation; mutation in the second zinc finger caused a 21-fold shift, whereas mutation in both zinc fingers caused a 138-fold shift. We conclude that the zinc fingers in the intact PKC are not equivalent and that the second zinc finger plays the predominant role in translocation of protein kinase Cdelta in response to phorbol 12-myristate 13-acetate. Our findings have important implications for the understanding and design of PKC inhibitors targeted to the zinc finger domains. JF - The Journal of biological chemistry AU - Szallasi, Z AU - Bogi, K AU - Gohari, S AU - Biro, T AU - Acs, P AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08/02/ PY - 1996 DA - 1996 Aug 02 SP - 18299 EP - 18301 VL - 271 IS - 31 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Isoenzymes KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Molecular Structure KW - Biological Transport, Active -- drug effects KW - Animals KW - 3T3 Cells KW - Base Sequence KW - DNA Primers -- genetics KW - Kinetics KW - Point Mutation KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Zinc Fingers -- physiology KW - Zinc Fingers -- genetics KW - Protein Kinase C -- genetics KW - Protein Kinase C -- chemistry KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78220591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Non-equivalent+roles+for+the+first+and+second+zinc+fingers+of+protein+kinase+Cdelta.+Effect+of+their+mutation+on+phorbol+ester-induced+translocation+in+NIH+3T3+cells.&rft.au=Szallasi%2C+Z%3BBogi%2C+K%3BGohari%2C+S%3BBiro%2C+T%3BAcs%2C+P%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1996-08-02&rft.volume=70&rft.issue=9&rft.spage=6143&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-24 N1 - Date created - 1996-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of nonparental child care on child development: an update. AN - 85272862; pmid-8862852 AB - OBJECTIVE: To review the published literature on the effects of nonparental and out-of-home care on infants, toddlers, and preschoolers. METHOD: Narrative literature review. RESULTS: Although substantial controversy persists, the accumulated evidence suggests that nonparental care does not necessarily have either beneficial or detrimental effects on infants and children, although it can have such effects. In some circumstances, careproviders establish relationships with children that have significant effects on development, and this increases the importance of ensuring that careproviders are well trained, behave sensitively, and are stable rather than ephemeral figures in children's lives. Nonparental care is associated with behaviour problems (including aggression and noncompliance) when the care is of poor quality and opportunities for meaningful relationships with stable careproviders are not available, however. CONCLUSION: The effects of out-of-home care vary depending on the quality of care as well as the characteristics of individual children, including their age, temperaments, and individual backgrounds. JF - Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie AU - Lamb, M E AD - Section on Social and Emotional Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20814, USA. PY - 1996 SP - 330 EP - 342 VL - 41 IS - 6 SN - 0706-7437, 0706-7437 KW - Infant KW - Intelligence KW - Caregivers KW - Child Behavior KW - Mother-Child Relations KW - Human KW - Personality KW - Child KW - Male KW - Female KW - Child, Preschool KW - Child Development KW - Child Care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85272862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Canadian+Journal+of+Psychiatry.+Revue+Canadienne+de+Psychiatrie&rft.atitle=Effects+of+nonparental+child+care+on+child+development%3A+an+update.&rft.au=Lamb%2C+M+E&rft.aulast=Lamb&rft.aufirst=M&rft.date=1996-08-01&rft.volume=41&rft.issue=6&rft.spage=330&rft.isbn=&rft.btitle=&rft.title=Canadian+Journal+of+Psychiatry.+Revue+Canadienne+de+Psychiatrie&rft.issn=07067437&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Viscoelastic relaxation in the membrane of the auditory outer hair cell. AN - 85249160; pmid-8842245 AB - The outer hair cell (OHC) in the mammalian ear has a unique membrane potential-dependent motility, which is considered to be important for frequency discrimination (tuning). The OHC motile mechanism is located at the cell membrane and is strongly influenced by its passive mechanical properties. To study the viscoelastic properties of OHCs, we exposed cells to a hypoosmotic solution for varying durations and then punctured them, to immediately release the osmotic stress. Using video records of the cells, we determined both the imposed strain and the strain after puncturing, when stress was reset to zero. The strain data were described by a simple rheological model consisting of two springs and a dashpot, and the fit to this model gave a time constant of 40 +/- 19 s for the relaxation (reduction) of tension during prolonged strain. For time scales much shorter or longer than this, we would expect essentially elastic behavior. This relaxation process affects the membrane tension of the cell, and because it has been shown that membrane tension has a modulatory role in the OHC's motility, this relaxation process could be part of an adaptation mechanism, with which the motility system of the OHC can adjust to changing conditions and maintain optimum membrane tension. JF - Biophysical Journal AU - Ehrenstein, D AU - Iwasa, K H AD - Biophysics Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-0922, USA. PY - 1996 SP - 1087 EP - 1094 VL - 71 IS - 2 SN - 0006-3495, 0006-3495 KW - Viscosity KW - Hypotonic Solutions KW - Perfusion KW - In Vitro KW - Guinea Pigs KW - Stress, Mechanical KW - Kinetics KW - Hair Cells, Outer KW - Animal KW - Pressure KW - Time Factors KW - Elasticity KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85249160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Viscoelastic+relaxation+in+the+membrane+of+the+auditory+outer+hair+cell.&rft.au=Ehrenstein%2C+D%3BIwasa%2C+K+H&rft.aulast=Ehrenstein&rft.aufirst=D&rft.date=1996-08-01&rft.volume=16&rft.issue=9&rft.spage=4996&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Ionotropic and metabotropic glutamate receptors show unique postsynaptic, presynaptic, and glial localizations in the dorsal cochlear nucleus. AN - 85233282; pmid-8873866 AB - The dorsal cochlear nucleus (DCN) is a major brain center for integration of auditory information, and excitatory amino acid neurotransmission plays a central role in the processing of this information. In this study, the distribution of glutamate receptors was examined with preembedding immunocytochemistry, using 14 antibodies to ionotropic (GluR1, GluR2/3, GluR4, GluR5-7, GluR6/7, KA2, NR1, NR2A/B, delta 1/2) and metabotropic (mGluR1 alpha, mGluR2/3, mGluR5) glutamate receptor subtypes. Each of these antibodies produced a specific immunolabeling pattern, including a variety of postsynaptic, presynaptic, and glial localizations. Some antibodies showed widespread distribution patterns, notably the antibodies to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits, GluR2 and GluR3, and the N-methyl-D-aspartate (NMDA) receptor subunit, NR1. In contrast, antibodies to other glutamate receptor subunits produced more restricted distribution patterns, especially that to GluR1, which stained the outer neuropil of the DCN, cartwheel cells, and a small population of presumptive interneurons associated with the dorsal acoustic stria, but produced little or no staining in fusiform cells or deep DCN neurons. Staining of the postsynaptic density and membrane of the granule cell-parallel fiber/cartwheel cell spins synapse was most prevalent with delta 1/2 and mGluR1 alpha antibodies. A unique pattern of staining was found with mGluR2/3 antibody--with staining concentrated in Golgi cells and unipolar brush cells of the middle to deep DCN. Distribution of some glutamate receptors in the DCN shows similarities to that of the cerebellum, where delta 2 and mGluR1 alpha may modulate neurotransmission at parallel fiber synapses, while mGluR2 and/or mGluR3 may modulate mossy terminal function. JF - The Journal of Comparative Neurology AU - Petralia, R S AU - Wang, Y X AU - Zhao, H M AU - Wenthold, R J AD - Laboratory of Neurochemistry, NIDCD, NIH, Bethesda, Maryland 20892, USA. PY - 1996 SP - 356 EP - 383 VL - 372 IS - 3 SN - 0021-9967, 0021-9967 KW - Rats KW - Rats, Sprague-Dawley KW - Receptors, Metabotropic Glutamate KW - Neuroglia KW - Neural Pathways KW - Presynaptic Terminals KW - Animal KW - Microscopy, Electron KW - Immunohistochemistry KW - Cochlear Nucleus KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85233282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Comparative+Neurology&rft.atitle=Ionotropic+and+metabotropic+glutamate+receptors+show+unique+postsynaptic%2C+presynaptic%2C+and+glial+localizations+in+the+dorsal+cochlear+nucleus.&rft.au=Petralia%2C+R+S%3BWang%2C+Y+X%3BZhao%2C+H+M%3BWenthold%2C+R+J&rft.aulast=Petralia&rft.aufirst=R&rft.date=1996-08-01&rft.volume=372&rft.issue=3&rft.spage=356&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Comparative+Neurology&rft.issn=00219967&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study. AN - 85221574; pmid-8764668 AB - Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O15 water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1-2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks--the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems--and two corresponding sensorimotor control tasks. There were no significant drug or task effects on pCO2 or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task - control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks. In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVA F (1,7) = 16.72, p < 0.0046). In right hippocampus, blood flow decreased during WCST but increased during RPM (ANOVA F(1,7) = 18.7, p < 0.0035). These findings illustrate that dextroamphetamine tends to "focus" neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine. JF - The Journal of Neuroscience AU - Mattay, V S AU - Berman, K F AU - Ostrem, J L AU - Esposito, G AU - Van Horn J D AU - Bigelow, L B AU - Weinberger, D R AD - Clinical Brain Disorders Branch, Intramural Research Porgram, National Institute of Mental Health, National Institutes of Health Neuroscience Center at Saint Elizabeth's, Washington, DC 20032, USA. PY - 1996 SP - 4816 EP - 4822 VL - 16 IS - 15 SN - 0270-6474, 0270-6474 KW - Analysis of Variance KW - Memory KW - Dextroamphetamine KW - Human KW - Adult KW - Brain KW - Tomography, Emission-Computed KW - Cerebrovascular Circulation KW - Cognition KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85221574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Neuroscience&rft.atitle=Dextroamphetamine+enhances+%22neural+network-specific%22+physiological+signals%3A+a+positron-emission+tomography+rCBF+study.&rft.au=Mattay%2C+V+S%3BBerman%2C+K+F%3BOstrem%2C+J+L%3BEsposito%2C+G%3BVan+Horn+J+D%3BBigelow%2C+L+B%3BWeinberger%2C+D+R&rft.aulast=Mattay&rft.aufirst=V&rft.date=1996-08-01&rft.volume=16&rft.issue=15&rft.spage=4816&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A novel approach to data collection in a case-control study of cancer and occupational exposures. AN - 78540081; 8921451 AB - In community and hospital-based case-control studies, the occupational data collected in interviews are usually limited to responses to general questions asked of all study subjects. A procedure is described in which more detailed information can be collected in an efficient, standardized and systematic way. A generic work history is initially collected from all subjects using a computer-assisted interview. The work history includes job title, type of business, job activities, materials and chemicals, and tools and equipment used. After responses are entered into the computer by the interviewer, the computer searches a synonym file to identify possible job-specific modules relevant to the reported job. The modules are detailed questionnaires that address specific jobs administered after obtaining the generic work history. The modules are used to ask questions about the work environment; sources of exposure; factors affecting the movement of the agent from the source to the subject, such as local exhaust ventilation; and individual and job characteristics. After the interview is completed, the work history and responses to the modules are sent electronically to an industrial hygienist who reviews the information using a custom-designed software package. Where ambiguities or contradictions occur in information reported by the respondent, or for jobs for which no module had been developed, the industrial hygienist generates up to 10 additional questions per job. These questions are sent back to the interviewer for administration of a short, second interview. These procedures, which are being successfully implemented in an on-going case-control study of brain tumours, should improve disease risk estimates over those derived from more traditional approaches to exposure assessment. JF - International journal of epidemiology AU - Stewart, P A AU - Stewart, W F AU - Heineman, E F AU - Dosemeci, M AU - Linet, M AU - Inskip, P D AD - National Cancer Institute, Epidemiology and Biostatistics Program, Rockville, MD 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 744 EP - 752 VL - 25 IS - 4 SN - 0300-5771, 0300-5771 KW - Index Medicus KW - Neuroma, Acoustic -- epidemiology KW - Meningeal Neoplasms -- epidemiology KW - Brain Neoplasms -- epidemiology KW - Meningioma -- epidemiology KW - Humans KW - Glioma -- epidemiology KW - User-Computer Interface KW - Information Storage and Retrieval KW - Software Design KW - Occupational Health KW - Occupational Exposure -- statistics & numerical data KW - Surveys and Questionnaires KW - Neoplasms -- epidemiology KW - Case-Control Studies KW - Occupational Exposure -- adverse effects KW - Medical Informatics Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78540081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+epidemiology&rft.atitle=A+novel+approach+to+data+collection+in+a+case-control+study+of+cancer+and+occupational+exposures.&rft.au=Stewart%2C+P+A%3BStewart%2C+W+F%3BHeineman%2C+E+F%3BDosemeci%2C+M%3BLinet%2C+M%3BInskip%2C+P+D&rft.aulast=Stewart&rft.aufirst=P&rft.date=1996-08-01&rft.volume=25&rft.issue=4&rft.spage=744&rft.isbn=&rft.btitle=&rft.title=International+journal+of+epidemiology&rft.issn=03005771&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-16 N1 - Date created - 1997-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparison of antioxidant enzyme activities in organ-cultured rhesus monkey lenses following peroxide challenge. AN - 78538176; 8921227 AB - To analyze the activities of catalase, glutathione peroxidase and superoxide dismutase, three enzymes involved in the detoxification of reactive oxygen species in organ-cultured Rhesus monkey lenses. Lenses freshly obtained from Rhesus monkeys were incubated at 37 degrees C for 2 h and assessed for lens integrity. Lenses were then oxidatively stressed by exposure to a bolus of hydrogen peroxide. The three enzyme activities were assayed 2, 4 and 24 h after exposure to the peroxide challenge. Freshly dissected lenses placed in organ culture exhibited a 20% decrease in catalase activity within 2 h. During the course of a 24 h incubation, catalase activity continued to decrease to a level 58% below that of freshly dissected monkey lenses. In contrast, the activity levels of both glutathione peroxidase and superoxide dismutase increased dramatically within the first 2 h of organ culture, with superoxide dismutase being most affected. Although glutathione peroxidase activity declined with incubation time, its level at the end of 24 h was still 36% greater than that of the fresh lenses. Superoxide dismutase activity remained elevated throughout the 24 h incubation period. The addition of a bolus of 0.25mM H2O2 to monkey lenses in culture had no effect on catalase activity. Two h after the peroxide insult, glutathione peroxidase activity decreased in comparison to control levels while the activity of superoxide dismutase increased by 43%. After 24 h, superoxide dismutase activity returned to values equivalent to the controls. In lenses challenged with 0.50mM H2O2, catalase and glutathione peroxidase activities decreased at 2 h, while superoxide dismutase activity increased 67% above control levels. At subsequent timepoints, catalase activity increased and reached control levels. In contrast, glutathione peroxidase activity continued to decrease with time eventually reaching fresh lens levels. Superoxide dismutase activity levels remained elevated and were equivalent to control values at 24 h. The data indicate that placement of monkey lenses into an organ culture system represents an environmental change sufficient to cause a response in antioxidant enzyme levels. The addition of H2O2 to this environment caused only superoxide dismutase to be stimulated above control lens levels. JF - Current eye research AU - Tumminia, S J AU - Chambers, C AU - Qin, C AU - Zigler, J M AU - Russell, P AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 845 EP - 851 VL - 15 IS - 8 SN - 0271-3683, 0271-3683 KW - Antioxidants KW - 0 KW - Oxidants KW - Reactive Oxygen Species KW - Hydrogen Peroxide KW - BBX060AN9V KW - Catalase KW - EC 1.11.1.6 KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Animals KW - Oxidative Stress KW - Macaca mulatta KW - Organ Culture Techniques KW - Catalase -- metabolism KW - Antioxidants -- metabolism KW - Glutathione Peroxidase -- metabolism KW - Oxidants -- pharmacology KW - Lens, Crystalline -- drug effects KW - Hydrogen Peroxide -- pharmacology KW - Superoxide Dismutase -- metabolism KW - Lens, Crystalline -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78538176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+eye+research&rft.atitle=A+comparison+of+antioxidant+enzyme+activities+in+organ-cultured+rhesus+monkey+lenses+following+peroxide+challenge.&rft.au=Tumminia%2C+S+J%3BChambers%2C+C%3BQin%2C+C%3BZigler%2C+J+M%3BRussell%2C+P&rft.aulast=Tumminia&rft.aufirst=S&rft.date=1996-08-01&rft.volume=15&rft.issue=8&rft.spage=845&rft.isbn=&rft.btitle=&rft.title=Current+eye+research&rft.issn=02713683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-06 N1 - Date created - 1996-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suramin-induced neutropenia. AN - 78517268; 8911114 AB - This paper presents a retrospective review of 6 cases of severe neutropenia attributed to suramin, the response to granulocyte-colony stimulating factor (G-CSF) and the possible mechanism. Plasma suramin concentrations, G-CSF, platelet-derived growth factor-AB (PDGF-AB) and fibroblast growth factor basic (FGF basic) levels were measured and correlated with neutropenic course. The time course of neutropenia was unpredictable and occurred both during and following discontinuation of suramin. Neutropenia rapidly resolved with G-CSF. Neither the measured growth factor levels nor plasma suramin concentrations correlated with neutropenia. We conclude that neutropenia secondary to suramin is unpredictable and responds to G-CSF administration permitting further suramin therapy. The mechanism remains unknown. JF - European journal of cancer (Oxford, England : 1990) AU - Dawson, N A AU - Lush, R M AU - Steinberg, S M AU - Tompkins, A C AU - Headlee, D J AU - Figg, W D AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 1534 EP - 1539 VL - 32A IS - 9 SN - 0959-8049, 0959-8049 KW - Antineoplastic Agents KW - 0 KW - Platelet-Derived Growth Factor KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Suramin KW - 6032D45BEM KW - Index Medicus KW - Granulocyte Colony-Stimulating Factor -- blood KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Humans KW - Retrospective Studies KW - Bayes Theorem KW - Aged KW - Platelet-Derived Growth Factor -- analysis KW - Prostatic Neoplasms -- drug therapy KW - Prostatic Neoplasms -- pathology KW - Adult KW - Prostatic Neoplasms -- blood KW - Fibroblast Growth Factor 2 -- blood KW - Middle Aged KW - Male KW - Suramin -- adverse effects KW - Neutropenia -- blood KW - Neutropenia -- chemically induced KW - Antineoplastic Agents -- therapeutic use KW - Suramin -- blood KW - Neutropenia -- therapy KW - Suramin -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78517268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Suramin-induced+neutropenia.&rft.au=Dawson%2C+N+A%3BLush%2C+R+M%3BSteinberg%2C+S+M%3BTompkins%2C+A+C%3BHeadlee%2C+D+J%3BFigg%2C+W+D&rft.aulast=Dawson&rft.aufirst=N&rft.date=1996-08-01&rft.volume=32A&rft.issue=9&rft.spage=1534&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-02 N1 - Date created - 1996-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alprazolam-induced hypomania. AN - 78475346; 8887708 AB - There are reports of alprazolam-induced hypomania/mania. Here is a case report of a patient who developed hypomania during treatment with alprazolam, but not with diazepam, another benzodiazepine derivative. The illness was of 2 months' duration and the patient received a diagnosis of anxious depression. Following treatment with alprazolam, the patient developed hypomania characterised by euphoria, overactivity, overtalkactivity, racing thoughts, oversocialisation, enhanced self-confidence and disturbed sleep. Hypomania subsided when alprazolam was withdrawn. There was no recurrence with fluoxetine or diazepam that ameliorated the primary condition. The patient was symptom-free on follow-up. Alprazolam can induce hypomania/mania and, perhaps, it differs from other benzodiazepines in its mode of action. Clinicians have to be alert to the possibility of their patients developing hypomania/mania while on alprazolam. JF - The Australian and New Zealand journal of psychiatry AU - Reddy, J AU - Khanna, S AU - Anand, U AU - Banerjee, A AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 550 EP - 552 VL - 30 IS - 4 SN - 0004-8674, 0004-8674 KW - Alprazolam KW - YU55MQ3IZY KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Humans KW - Adult KW - Female KW - Bipolar Disorder -- diagnosis KW - Anxiety Disorders -- drug therapy KW - Alprazolam -- therapeutic use KW - Depressive Disorder -- psychology KW - Anxiety Disorders -- psychology KW - Depressive Disorder -- drug therapy KW - Bipolar Disorder -- psychology KW - Somatoform Disorders -- psychology KW - Somatoform Disorders -- drug therapy KW - Alprazolam -- adverse effects KW - Bipolar Disorder -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78475346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Australian+and+New+Zealand+journal+of+psychiatry&rft.atitle=Alprazolam-induced+hypomania.&rft.au=Reddy%2C+J%3BKhanna%2C+S%3BAnand%2C+U%3BBanerjee%2C+A&rft.aulast=Reddy&rft.aufirst=J&rft.date=1996-08-01&rft.volume=30&rft.issue=4&rft.spage=550&rft.isbn=&rft.btitle=&rft.title=The+Australian+and+New+Zealand+journal+of+psychiatry&rft.issn=00048674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-13 N1 - Date created - 1997-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adverse reactions with 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy'). AN - 78473631; 8884162 AB - 3,4-Methylenedioxymethamphetamine (MDMA; 'ecstasy') is an increasingly popular recreational drug in the US, Western Europe and Australia. In animals, including nonhuman primates, MDMA is known to damage brain serotonin (5-hydroxytryptamine; 5-HT) neurons. It is not known whether MDMA damages serotonin neurons in the human brain but there is some indication that it may. Although the large majority of individuals who have used MDMA recreationally do not develop acute complications, as the popularity of MDMA has increased, so have reports of adverse nonpsychiatric and psychiatric consequences associated with use of the drug. Further, since manifestations of MDMA-induced serotonin injury might only become apparent with age, or under periods of stress, it is possible that some individuals with no apparent abnormalities might develop complications over time. JF - Drug safety AU - McCann, U D AU - Slate, S O AU - Ricaurte, G A AD - Unit on Anxiety Disorders, National Institute of Mental Health, Bethesda, Maryland, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 107 EP - 115 VL - 15 IS - 2 SN - 0114-5916, 0114-5916 KW - Hallucinogens KW - 0 KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Index Medicus KW - Animals KW - Mental Disorders -- chemically induced KW - Humans KW - Brain -- drug effects KW - Substance-Related Disorders KW - Heart -- drug effects KW - N-Methyl-3,4-methylenedioxyamphetamine -- adverse effects KW - Hallucinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78473631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+safety&rft.atitle=Adverse+reactions+with+3%2C4-methylenedioxymethamphetamine+%28MDMA%3B+%27ecstasy%27%29.&rft.au=McCann%2C+U+D%3BSlate%2C+S+O%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1996-08-01&rft.volume=15&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Drug+safety&rft.issn=01145916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-08 N1 - Date created - 1997-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dermatotoxic chemical stimulate of c-jun and c-fos transcription and AP-1 DNA binding in human keratinocytes. AN - 78469893; 8884985 AB - In many organ/tissues rapid and transient increases in early-immediate gene responses, such as those that encode for the AP-1 family of transcription factors, occur in response to exogenous stimuli. Activation of AP-1, in turn, helps regulate the expression of genes involved in cell growth, inflammatory responses, and repair processes. In the present studies, we demonstrate that increases in AP-1 DNA binding activity, as well as c-jun and c-fos mRNA levels, occur in human keratinocytes in response to diverse dermatotoxic chemicals, including phenol and arsenic as well as phorbol ester, the latter employed as a positive control. The AP-1 DNA binding complex has affinity for the consensus AP-1 sequence but not the CRE2 binding sequence of the proenkephalin promoter or the NF kappa B consensus sequence indicating that the response is relatively specific. The binding complex is composed of Jun:Fos heterodimers, including Jun B and Jun D. Evidence is provided suggesting that AP-1 binding is associated with an increase in IL-1 alpha expression, an early mediator of toxic response in the skin. JF - Research communications in molecular pathology and pharmacology AU - Burleson, F G AU - Simeonova, P P AU - Germolec, D R AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 131 EP - 148 VL - 93 IS - 2 SN - 1078-0297, 1078-0297 KW - Interleukin-1 KW - 0 KW - RNA, Messenger KW - Transcription Factor AP-1 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Cells, Cultured KW - Humans KW - RNA, Messenger -- analysis KW - Interleukin-1 -- genetics KW - Transcription, Genetic -- drug effects KW - Skin -- drug effects KW - Transcription Factor AP-1 -- metabolism KW - Keratinocytes -- drug effects KW - DNA -- metabolism KW - Genes, jun -- drug effects KW - Keratinocytes -- metabolism KW - Genes, fos -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78469893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Research+communications+in+molecular+pathology+and+pharmacology&rft.atitle=Dermatotoxic+chemical+stimulate+of+c-jun+and+c-fos+transcription+and+AP-1+DNA+binding+in+human+keratinocytes.&rft.au=Burleson%2C+F+G%3BSimeonova%2C+P+P%3BGermolec%2C+D+R%3BLuster%2C+M+I&rft.aulast=Burleson&rft.aufirst=F&rft.date=1996-08-01&rft.volume=93&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Research+communications+in+molecular+pathology+and+pharmacology&rft.issn=10780297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Workshop on phase I study design. Ninth NCI/EORTC New Drug Development Symposium, Amsterdam, March 12, 1996. AN - 78460065; 8879369 AB - Many of the methods currently used in phase I trial design date back to the 1970's. Recently, some investigators have considered whether it might be possible to perform more efficient phase I trials that minimize the number of patients treated at biologically ineffective doses, maximize the precision of recommended phase II doses, and maintain patient safety. The objective of this Workshop was to examine aspects of phase I trial design, with consideration of both standard and novel approaches. Topics included choice of starting dose level, definition of dose-limiting toxicity, development and incorporation of non-toxicity endpoints, use of alternate dose escalation schemes, and definitions of tumor response and clinical benefit, including consideration of whether these determinations from phase I studies should alter the decision to proceed to phase II drug evaluation. For each topic, this summary includes a description of the standard approach, a summary of the speaker's presentation, and commentary. The Workshop initiated discussion and reassessment that are expected to lead to testing of some of the suggested alternate approaches. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Arbuck, S G AD - Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 567 EP - 573 VL - 7 IS - 6 SN - 0923-7534, 0923-7534 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Clinical Trials, Phase I as Topic -- methods KW - Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78460065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Workshop+on+phase+I+study+design.+Ninth+NCI%2FEORTC+New+Drug+Development+Symposium%2C+Amsterdam%2C+March+12%2C+1996.&rft.au=Arbuck%2C+S+G&rft.aulast=Arbuck&rft.aufirst=S&rft.date=1996-08-01&rft.volume=7&rft.issue=6&rft.spage=567&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-17 N1 - Date created - 1997-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis of bis-gamma-butyrolactones containing conformationally constrained (S)- and (R)-diacylglycerol structures. AN - 78455306; 8879551 AB - The synthesis of two sets of rigid diacylglycerol (DAG) analogues with either the (S)-DAG or (R)-DAG enantiomer embedded into a bis-gamma-butyrolactone template was accomplished stereoselectively from di-O-isopropylidene-alpha-D-apiose. The key step in both syntheses was the assemblage of the bicyclic perhydrofuro[3,4-b]furan ring system via a radical exo-dig intramolecular cyclization. A lipophilic undecanyl alkyl chain attached at C-3 of the fully assembled perhydrofuro[3,4-b]furan-2,4-dione (bis-gamma-butyrolactone) template can adopt two orientations with the one directed away from the concave face of the bicyclic system favored by a 4 to 1 ratio in each case. Evaluation of the final target pairs of enantiomers as PK-C alpha ligands revealed that the template containing an embedded (R)-DAG structure was more effective. The difference in binding affinity was also modulated by the direction of the alkyl chain. JF - Bioorganic & medicinal chemistry AU - Lee, J AU - Lewin, N E AU - Blumberg, P M AU - Marquez, V E AD - Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 1299 EP - 1305 VL - 4 IS - 8 SN - 0968-0896, 0968-0896 KW - Diglycerides KW - 0 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - 4-Butyrolactone KW - OL659KIY4X KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Stereoisomerism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Kinetics KW - Molecular Conformation KW - Magnetic Resonance Spectroscopy KW - Diglycerides -- chemistry KW - 4-Butyrolactone -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78455306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry&rft.atitle=Synthesis+of+bis-gamma-butyrolactones+containing+conformationally+constrained+%28S%29-+and+%28R%29-diacylglycerol+structures.&rft.au=Lee%2C+J%3BLewin%2C+N+E%3BBlumberg%2C+P+M%3BMarquez%2C+V+E&rft.aulast=Lee&rft.aufirst=J&rft.date=1996-08-01&rft.volume=4&rft.issue=8&rft.spage=1299&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry&rft.issn=09680896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-06 N1 - Date created - 1997-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of interferon-gamma gene expression. AN - 78454047; 8877725 AB - Interferon-gamma (IFN-gamma), also known as type II interferon, is an important immunoregulatory gene that has multiple effects on the development, maturation, and function of the immune system. IFN-gamma mRNA and protein are expressed predominantly by T cells and large granular lymphocytes. The IFN-gamma mRNA is induced/inhibited in these cell types by a wide variety of extracellular signals, thus implicating a number of diverse, yet convergent signal transduction pathways in its transcriptional control. In this review, I describe how DNA methylation and specific DNA binding proteins may regulate transcription of the IFN-gamma gene in response to extracellular signals. JF - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research AU - Young, H A AD - Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 563 EP - 568 VL - 16 IS - 8 SN - 1079-9907, 1079-9907 KW - DNA-Binding Proteins KW - 0 KW - Erythroid-Specific DNA-Binding Factors KW - Glucocorticoids KW - NF-kappa B KW - Phytohemagglutinins KW - RNA, Messenger KW - Transcription Factors KW - Ionomycin KW - 56092-81-0 KW - Interferon-gamma KW - 82115-62-6 KW - Cyclosporine KW - 83HN0GTJ6D KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Humans KW - Transcription, Genetic KW - Ionomycin -- pharmacology KW - RNA, Messenger -- genetics KW - Phytohemagglutinins -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Lymphocyte Activation KW - Leukemia-Lymphoma, Adult T-Cell -- pathology KW - Tumor Cells, Cultured KW - Promoter Regions, Genetic -- drug effects KW - Cyclosporine -- pharmacology KW - DNA -- chemistry KW - Transcription Factors -- physiology KW - Mice KW - NF-kappa B -- physiology KW - Glucocorticoids -- pharmacology KW - Signal Transduction -- physiology KW - T-Lymphocytes -- metabolism KW - Enhancer Elements, Genetic KW - DNA -- genetics KW - Signal Transduction -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - DNA-Binding Proteins -- physiology KW - Methylation KW - Interferon-gamma -- genetics KW - Lymphocyte Subsets -- drug effects KW - Interferon-gamma -- biosynthesis KW - Gene Expression Regulation -- drug effects KW - Lymphocyte Subsets -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78454047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+interferon+%26+cytokine+research+%3A+the+official+journal+of+the+International+Society+for+Interferon+and+Cytokine+Research&rft.atitle=Regulation+of+interferon-gamma+gene+expression.&rft.au=Young%2C+H+A&rft.aulast=Young&rft.aufirst=H&rft.date=1996-08-01&rft.volume=16&rft.issue=8&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=Journal+of+interferon+%26+cytokine+research+%3A+the+official+journal+of+the+International+Society+for+Interferon+and+Cytokine+Research&rft.issn=10799907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-06 N1 - Date created - 1997-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of hypoxia on drug resistance phenotype and genotype in human glioma cell lines. AN - 78427179; 8858520 AB - Recurrent gliomas are most often treated by chemotherapy. However, these tumors typically acquire resistance to most drugs administered, and patients will usually die of recurrent tumor. Factors which may play a role include overexpression of putative multidrug resistance genes, such as the multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), 06-alkylguanine, DNA alkyltransferase gene (06MT) and excision repair cross complementing gene 1 (ERCC1). Tumor hypoxia has also been shown to be associated with drug resistance in other soft tissue tumors. Since gliomas have regions of diminished oxygenation, and have clinical resistance to chemotherapy, the relationship between phenotypic resistance to chemotherapy after hypoxic exposure and expression of drug resistance genes was investigated in glioma cell lines (U373 MG, PFAT-MT). After a 24 hour exposure to hypoxia, drugs 1, 3-bis, 2-chloroethyl-1-nitrosurea (BCNU) and cis-diammine, dichloroplatinum II (CDDP) were administered, and cell survival was determined. Hypoxic exposure was associated with increased survival of the cell lines after administration of BCNU and CDDP, with resistance to BCNU 15 to 30-fold when compared to cells which did not undergo hypoxic exposure. Both tumor cell lines also showed some degree of resistance to CDDP, although not to the extent of BCNU (2 to 3-fold increased resistance). The expression of the drug resistance genes was found to be unchanged when comparing cells which had undergone hypoxic exposure and those which had not. Thus, hypoxic exposure is associated with substantial drug resistance in brain tumor cell lines. The lack of correlation between the induced phenotype and known drug resistance genes suggests other mechanisms may be acting in these tumors in hypoxic conditions. JF - Journal of neuro-oncology AU - Liang, B C AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 149 EP - 155 VL - 29 IS - 2 SN - 0167-594X, 0167-594X KW - Antineoplastic Agents KW - 0 KW - DNA-Binding Proteins KW - P-Glycoprotein KW - Methyltransferases KW - EC 2.1.1.- KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Cisplatin KW - Q20Q21Q62J KW - Carmustine KW - U68WG3173Y KW - Index Medicus KW - Protein Biosynthesis KW - Glioblastoma KW - DNA Repair KW - Humans KW - Methyltransferases -- biosynthesis KW - P-Glycoprotein -- biosynthesis KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Phenotype KW - Genotype KW - Brain Neoplasms KW - Tumor Cells, Cultured KW - Kinetics KW - Glioma KW - Cell Line KW - Cell Survival -- drug effects KW - Cisplatin -- toxicity KW - Antineoplastic Agents -- toxicity KW - Drug Resistance, Neoplasm KW - Cell Hypoxia KW - Carmustine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78427179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuro-oncology&rft.atitle=Effects+of+hypoxia+on+drug+resistance+phenotype+and+genotype+in+human+glioma+cell+lines.&rft.au=Liang%2C+B+C&rft.aulast=Liang&rft.aufirst=B&rft.date=1996-08-01&rft.volume=29&rft.issue=2&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuro-oncology&rft.issn=0167594X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-17 N1 - Date created - 1997-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dominant-negative mutants of cJun inhibit AP-1 activity through multiple mechanisms and with different potencies. AN - 78404077; 8853897 AB - We have previously described a dominant-negative mutant of cJun that lacks the transactivation domain (TAD) of cJun and prevents AP-1-mediated transcriptional activation by quenching endogenous Jun or Fos proteins. We now report the development of a panel of cJun mutants that have inactivating mutations in the TAD, DNA-binding domain (DBD), or leucine zipper domain. These mutants are all unable to activate transcription, but only TAD and DBD mutants function in a dominant-negative fashion by inhibiting both cJun-induced transcriptional activation and transformation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in ras-transfected rat embryo cells. Although the TAD and DBD mutants both function as transdominant inhibitors, they work through different mechanisms and with different inhibitory potencies. The DBD mutants, which function by inhibiting DNA binding, are relatively weak inhibitors, whereas the TAD mutants inhibit by quenching and are much more potent. Dimerization assays demonstrate that mutations in the DBD decrease the dimerization affinity of these mutants with cJun. These results demonstrate that the most potent dominant-negative mutants of cJun are proteins that have intact DBDs and quench the activity of the endogenous transcription factors. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Brown, P H AU - Kim, S H AU - Wise, S C AU - Sabichi, A L AU - Birrer, M J AD - Biomarkers and Prevention Research Branch, Division of Clinical Sciences, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 1013 EP - 1021 VL - 7 IS - 8 SN - 1044-9523, 1044-9523 KW - DNA-Binding Proteins KW - 0 KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Animals KW - Tetradecanoylphorbol Acetate -- metabolism KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Genes, ras -- genetics KW - Cells, Cultured KW - Dimerization KW - DNA-Binding Proteins -- genetics KW - Transcription, Genetic KW - Transformation, Genetic -- physiology KW - Structure-Activity Relationship KW - Proto-Oncogene Proteins c-jun -- genetics KW - Mutation -- genetics KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Transcription Factor AP-1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78404077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Dominant-negative+mutants+of+cJun+inhibit+AP-1+activity+through+multiple+mechanisms+and+with+different+potencies.&rft.au=Brown%2C+P+H%3BKim%2C+S+H%3BWise%2C+S+C%3BSabichi%2C+A+L%3BBirrer%2C+M+J&rft.aulast=Brown&rft.aufirst=P&rft.date=1996-08-01&rft.volume=7&rft.issue=8&rft.spage=1013&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-26 N1 - Date created - 1997-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dependence of agonist activation on an aromatic moiety in the DPLIY motif of the gonadotropin-releasing hormone receptor. AN - 78396659; 8843414 AB - In the GnRH receptor, the NPX2-3Y motif that is present in the seventh transmembrane helix of most G protein-coupled receptors is unusual in containing Asp instead of Asn but retains the highly conserved Tyr residue. The importance of this aromatic residue in the DPLIY sequence of the GnRH receptor function was analyzed by replacing Tyr322 with Ala or Phe residues. The Y322A mutant receptor expressed in COS-7 cells had high agonist binding affinity, but its ability to interact with G protein(s) and to activate inositol phosphate production in response to GnRH was abolished. Although functionally inactive, the Y322A mutant receptor was internalized at about 50% of the rate of the wild type receptor in agonist-treated cells. When Tyr322 was replaced with Phe to preserve its aromatic nature, the Y322F mutant receptor displayed normal G protein activation and inositol phosphate responses to GnRH and was internalized in the same manner as the wild type receptor. These findings demonstrate that the aromatic moiety of the Tyr322 component of the DPLIY motif in the GnRH receptor is a critical determinant of agonist-induced receptor activation and signal transduction. JF - Molecular endocrinology (Baltimore, Md.) AU - Arora, K K AU - Cheng, Z AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 979 EP - 986 VL - 10 IS - 8 SN - 0888-8809, 0888-8809 KW - Inositol Phosphates KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tyrosine KW - 42HK56048U KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Inositol Phosphates -- metabolism KW - Humans KW - Gene Expression KW - Amino Acid Sequence KW - GTP-Binding Proteins -- physiology KW - Sequence Homology KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Transfection KW - Cell Line KW - Signal Transduction KW - Gonadotropin-Releasing Hormone -- chemistry KW - Gonadotropin-Releasing Hormone -- genetics KW - Gonadotropin-Releasing Hormone -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78396659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Dependence+of+agonist+activation+on+an+aromatic+moiety+in+the+DPLIY+motif+of+the+gonadotropin-releasing+hormone+receptor.&rft.au=Arora%2C+K+K%3BCheng%2C+Z%3BCatt%2C+K+J&rft.aulast=Arora&rft.aufirst=K&rft.date=1996-08-01&rft.volume=10&rft.issue=8&rft.spage=979&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-08 N1 - Date created - 1997-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebral metabolism of imipramine and a purified flavin-containing monooxygenase from human brain. AN - 78396635; 8840349 AB - Flavin-containing monooxygenase (FMO), previously reported both from hepatic and extrahepatic tissues, including brain, catalyze the oxidation of certain xenobiotics and drugs that contain a nucleophilic heteroatom. Psychoactive drugs, including the antidepressant imipramine, are substrates for the brain FMO. Since FMO-mediated metabolism of these drugs might contribute to local pharmacodynamic modulation within the human brain, the metabolism of imipramine by human brain FMO was studied in further detail. In the present study, the FMO activity was determined in human brain microsomes by estimating the actual amount of imipramine N-oxide formed. It was then compared with the corresponding activity measured using substrate (imipramine)-stimulated rates of nicotinamide adenine dinucleotide phosphate (NADPH) oxidation, which was significantly higher than the activity estimated as the amount of N-oxide assayed using high-pressure liquid chromatography (HPLC). The brain FMO activity was measurable only in the presence of detergents (sodium cholate or Lubrol PX) or in microsomes that were freeze-thawed several times. The activity was inhibited by an antibody to rabbit pulmonary FMO, but an antiserum to the rat liver NADPH cytochrome P-450 reductase had no effect indicating that cytochrome P-450 was not involved in the above metabolic pathway. The optimum pH for N-oxidation of imipramine was found to be 8.5; thermolability experiments indicated that the FMO activity was completely lost only after the incubation of brain microsomes at 45 degrees C for 20 minutes. An FMO purified to apparent homogeneity from a human brain had a molecular weight of 71,000 Da. The purified enzyme cross-reacted with the antibody to rabbit pulmonary FMO and efficiently catalyzed the metabolism of imipramine to its N-oxide. The human brain clearly contains an active FMO system, and it is conceivable that such enzymes are significantly involved in the local metabolism and modulation of pharmacological and/or toxic effects of certain xenobiotics, including psychoactive drugs. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Bhagwat, S V AU - Bhamre, S AU - Boyd, M R AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 133 EP - 142 VL - 15 IS - 2 SN - 0893-133X, 0893-133X KW - Antidepressive Agents, Tricyclic KW - 0 KW - Detergents KW - Oxygenases KW - EC 1.13.- KW - dimethylaniline monooxygenase (N-oxide forming) KW - EC 1.14.13.8 KW - Imipramine KW - OGG85SX4E4 KW - Index Medicus KW - Oxidation-Reduction KW - Microsomes -- metabolism KW - Kinetics KW - Hydrogen-Ion Concentration KW - Humans KW - In Vitro Techniques KW - Temperature KW - Binding, Competitive -- drug effects KW - Middle Aged KW - Microsomes -- enzymology KW - Detergents -- pharmacology KW - Chromatography, High Pressure Liquid KW - Brain -- enzymology KW - Oxygenases -- immunology KW - Oxygenases -- metabolism KW - Oxygenases -- isolation & purification KW - Antidepressive Agents, Tricyclic -- metabolism KW - Antidepressive Agents, Tricyclic -- isolation & purification KW - Imipramine -- metabolism KW - Brain -- metabolism KW - Antidepressive Agents, Tricyclic -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78396635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Cerebral+metabolism+of+imipramine+and+a+purified+flavin-containing+monooxygenase+from+human+brain.&rft.au=Bhagwat%2C+S+V%3BBhamre%2C+S%3BBoyd%2C+M+R%3BRavindranath%2C+V&rft.aulast=Bhagwat&rft.aufirst=S&rft.date=1996-08-01&rft.volume=15&rft.issue=2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-26 N1 - Date created - 1996-12-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - On the origins of the hydrophobic effect: observations from simulations of n-dodecane in model solvents. AN - 78388501; 8842199 AB - The importance of the small size of a water molecule as contributing to the hydrophobic effect is examined from simulations of n-dodecane in different solvents. The earlier observations of the origin of hydrophobicity, derived from cavity formations by Pratt and Pohorille (1992, Proc. Natl. Acad. Sci. USA. 89:2995-2999) and Madan and Lee (1994, Biophys. Chem, 51:279-289), are shown to be largely consistent for a hydrocarbon-induced water pocket. In effect, the small size of a water molecule limits the probability (and hence free energy) of finding an appropriate void in the fluid that will accommodate a solute. In this work a simulated collapse of an n-dodecane molecule in H2O, CCl4, and a water-like Lennard-Jones solvent indicates that the induced entropy and enthalpy changes are qualitatively similar for hydrogen-bonded and Lennard-Jones water solvents. These results suggest that a large part of the hydrophobic response of solutes in aqueous solutions is due to the small size of the solvent. Important quantitative differences between the studied water solvents indicate that the hydrogen-bonded properties for water are still needed to determine the overall hydrophobic response. JF - Biophysical journal AU - Wallqvist, A AU - Covell, D G AD - Frederick Cancer Research and Development Center, National Cancer Institute, Science Applications International Corporation, Frederick, Maryland 21702, USA. wallqvis@ncifcrf.gov Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 600 EP - 608 VL - 71 IS - 2 SN - 0006-3495, 0006-3495 KW - Alkanes KW - 0 KW - Solvents KW - Water KW - 059QF0KO0R KW - n-dodecane KW - 11A386X1QH KW - Index Medicus KW - Computer Simulation KW - Thermodynamics KW - Models, Molecular KW - Molecular Conformation KW - Entropy KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78388501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+journal&rft.atitle=On+the+origins+of+the+hydrophobic+effect%3A+observations+from+simulations+of+n-dodecane+in+model+solvents.&rft.au=Wallqvist%2C+A%3BCovell%2C+D+G&rft.aulast=Wallqvist&rft.aufirst=A&rft.date=1996-08-01&rft.volume=71&rft.issue=2&rft.spage=600&rft.isbn=&rft.btitle=&rft.title=Biophysical+journal&rft.issn=00063495&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-09 N1 - Date created - 1997-01-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biopolymers. 1985 May;24(5):813-23 [4016216] Annu Rev Biophys Biophys Chem. 1989;18:431-92 [2660832] Biochemistry. 1990 Aug 7;29(31):7133-55 [2207096] Science. 1993 Oct 22;262(5133):547-50 [8211182] Annu Rev Phys Chem. 1993;44:369-95 [8257560] Biophys Chem. 1994 Aug;51(2-3):279-86; discussion 286-9 [7919039] J Am Chem Soc. 1990;112(13):5066-74 [11540917] Proc Natl Acad Sci U S A. 1992 Apr;89:2995-9 [11537863] Adv Protein Chem. 1959;14:1-63 [14404936] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PCR mutagenesis and overexpression of tryptophan synthase from Salmonella typhimurium: on the roles of beta2 subunit Lys-382. AN - 78344328; 8812843 AB - We have devised convenient methods for mutagenesis and very high level expression of wild type and mutant tryptophan synthase alpha and beta2 subunits and alpha2beta2 complex from Salmonella typhimurium. The trpBA genes were modified by introduction of five new restriction sites by polymerase chain reaction (PCR) and were then cloned into the plasmid pTrc99A under trc promoter control. The recombinant plasmid pEBA-10 and three plasmids constructed from pEBA-10 were transformed into Escherichia coli CB149, which lacks tryptophan operon genes. Optimization of growth conditions of the transformed cells resulted in 10- to 40-fold higher yields of cells ( approximately 22 g/liter) than attained previously. The improved expression system gave higher yields of tryptophan synthase proteins (23-70% of the soluble protein) and led to correspondingly high yields of purified alpha and beta2 subunits or alpha2beta2 complex (200-800 mg/liter). A plasmid containing 8 copies of the trpA gene gave the highest yield of alpha subunit. The PCR-based mutagenesis method permits mutation of any base pair in the trpBA genes, between suitable pairs of restriction sites, and requires only one new primer per mutation. The method is illustrated by construction of mutant beta2 subunits with any of five amino acid substitutions at Lys-382, the site of a previously described missense mutation. Characterization of the purified mutant alpha2beta2 complexes shows that Lys-382 in the wild type alpha2beta2 complex does not serve an essential catalytic role but may stabilize an active "closed" conformation of the enzyme by forming a salt bridge with Glu-350. JF - Protein expression and purification AU - Yang, L h AU - Ahmed, S A AU - Miles, E W AD - Enzyme Structure and Function Section, National Institutes of Health, Bethesda, Maryland, 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 126 EP - 136 VL - 8 IS - 1 SN - 1046-5928, 1046-5928 KW - Bacterial Proteins KW - 0 KW - DNA Primers KW - Recombinant Proteins KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Models, Molecular KW - Plasmids -- genetics KW - Escherichia coli -- genetics KW - Genes, Bacterial -- genetics KW - Recombinant Proteins -- genetics KW - Cloning, Molecular KW - Transformation, Genetic -- genetics KW - Recombinant Proteins -- isolation & purification KW - Polymerase Chain Reaction KW - Gene Expression -- genetics KW - Mutation -- genetics KW - Recombinant Proteins -- chemistry KW - Protein Conformation KW - Tryptophan Synthase -- metabolism KW - Tryptophan Synthase -- chemistry KW - Mutagenesis -- genetics KW - Tryptophan Synthase -- genetics KW - Salmonella typhimurium -- genetics KW - Salmonella typhimurium -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78344328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+expression+and+purification&rft.atitle=PCR+mutagenesis+and+overexpression+of+tryptophan+synthase+from+Salmonella+typhimurium%3A+on+the+roles+of+beta2+subunit+Lys-382.&rft.au=Yang%2C+L+h%3BAhmed%2C+S+A%3BMiles%2C+E+W&rft.aulast=Yang&rft.aufirst=L&rft.date=1996-08-01&rft.volume=8&rft.issue=1&rft.spage=126&rft.isbn=&rft.btitle=&rft.title=Protein+expression+and+purification&rft.issn=10465928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen induces retinoid receptor expression in mouse cervical epithelia. AN - 78329789; 8806431 AB - Steroid hormones and retinoids are powerful regulators of normal epithelial differentiation and function in the mouse female reproductive tract, where their actions are mediated by nuclear receptors. The expression pattern, heterodimeric interactions, and availability of ligand of these transcription factors are thought to contribute to the biological response. Estrogen (E2) induces proliferation and squamous differentiation of the cervical and vaginal epithelium during the mouse estrous cycle, while progesterone and retinoids maintain the simple columnar epithelium of the endocervix and uterine horns. We wanted to investigate whether retinoid receptors are responsive to estrogen status during cervical epithelial differentiation induced by a single dose of estrogen in ovariectomized adult mice. Northern blot analysis demonstrated a prolonged induction of RXR alpha and RAR gamma gene expression by E2 in the mouse cervix and vagina. When the induction of RXR alpha and RAR gamma was compared to genes known to be responsive to E2, including estrogen receptor (ER) and c-fos, RXR alpha was induced within 0.5 h of hormone treatment, while RAR gamma induction was evident by 4 h. The induction of these retinoid receptors suggests that they may be implicated in epithelial growth and differentiation in response to E2. Moreover, potential heterodimeric interactions among these receptors indicate that normal, cyclical epithelial differentiation results from the interplay of these molecules. Using in situ hybridization analysis, RXR alpha transcripts were localized preferentially in the basal cells, while ER mRNA was expressed throughout the epithelium of the ectocervix and vagina. Furthermore, ER transcripts were highly expressed in the stratified squamous foci induced by mild vitamin A depletion in the columnar epithelium of the endocervix and uterine horns. Therefore, the induction of RXR alpha and RAR gamma by E2 and their expression pattern in relation to ER suggest that they are needed to coordinate specific genetic programs that result in cervical epithelial growth and differentiation. JF - Experimental cell research AU - Celli, G AU - Darwiche, N AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08/01/ PY - 1996 DA - 1996 Aug 01 SP - 273 EP - 282 VL - 226 IS - 2 SN - 0014-4827, 0014-4827 KW - Proto-Oncogene Proteins c-fos KW - 0 KW - RNA, Messenger KW - Receptors, Estrogen KW - Receptors, Retinoic Acid KW - Retinoid X Receptors KW - Transcription Factors KW - retinoic acid receptor gamma KW - Estradiol KW - 4TI98Z838E KW - Keratins KW - 68238-35-7 KW - estradiol-17 beta-benzoate KW - 983-30-2 KW - Index Medicus KW - Vitamin A Deficiency KW - Keratins -- genetics KW - Animals KW - Vagina -- chemistry KW - RNA, Messenger -- analysis KW - Cell Differentiation KW - Receptors, Estrogen -- analysis KW - Mice KW - Keratins -- analysis KW - Mice, Inbred BALB C KW - Epithelium -- drug effects KW - Phenotype KW - Receptors, Estrogen -- genetics KW - Epithelial Cells KW - Proto-Oncogene Proteins c-fos -- genetics KW - Epithelium -- physiology KW - Ovariectomy KW - Epithelium -- chemistry KW - Female KW - Receptors, Retinoic Acid -- genetics KW - Estradiol -- analogs & derivatives KW - Cervix Uteri -- drug effects KW - Cervix Uteri -- physiology KW - Estradiol -- pharmacology KW - Cervix Uteri -- cytology KW - Transcription Factors -- genetics KW - Gene Expression Regulation, Developmental -- drug effects KW - Cervix Uteri -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78329789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=report&rft.jtitle=&rft.atitle=&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2012-04-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=38.93+Venous+catheterization+not+elsewhere+classified%3B+central+venous+catheter+%28CVC%29%3B+peripheral+venous+catheter&rft.title=38.93+Venous+catheterization+not+elsewhere+classified%3B+central+venous+catheter+%28CVC%29%3B+peripheral+venous+catheter&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Knockout mice and dirty drugs. Drug addiction. AN - 78316696; 8805320 AB - Recent studies with knockout mice implicate the dopamine transporter as the target of the locomotor effects of the addictive psychomotor drugs cocaine and amphetamine; studies of reward in these animals are eagerly awaited. JF - Current biology : CB AU - Uhl, G R AU - Vandenbergh, D J AU - Miner, L L AD - Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Addiction Research Center, PO Box 5180, Baltimore, Maryland 21224, USA. Y1 - 1996/08/01/ PY - 1996 DA - 1996 Aug 01 SP - 935 EP - 936 VL - 6 IS - 8 SN - 0960-9822, 0960-9822 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Amphetamine KW - CK833KGX7E KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Dopamine -- metabolism KW - Mice KW - Locomotion -- drug effects KW - Mice, Knockout KW - Opioid-Related Disorders -- metabolism KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- drug effects KW - Carrier Proteins -- genetics KW - Opioid-Related Disorders -- genetics KW - Cocaine -- pharmacology KW - Amphetamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78316696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+biology+%3A+CB&rft.atitle=Knockout+mice+and+dirty+drugs.+Drug+addiction.&rft.au=Uhl%2C+G+R%3BVandenbergh%2C+D+J%3BMiner%2C+L+L&rft.aulast=Uhl&rft.aufirst=G&rft.date=1996-08-01&rft.volume=6&rft.issue=8&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Current+biology+%3A+CB&rft.issn=09609822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-07 N1 - Date created - 1996-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines. AN - 78300379; 8784465 AB - p21/WAF1/CIP1/SDI1 is an important cell-cycle mediator with tumor suppressor gene capabilities, and its inactivation could potentially lead to tumor progression. Because tumor suppressor genes are commonly inactivated by somatic and germline mutations, we analyzed a variety of human tumor cell lines for p21 mutations. We used single-strand conformational analysis and direct sequencing to identify possible mutations in the p21 coding region. Two base-alterations were observed in 41 immortalized human tumor cell lines. A previously reported polymorphism that results in a serine-to-arginine amino-acid substitution at codon 31 was found in 24% (10 of 41) of the tumor cell lines but was also found in 10% (six of 62) of normal parental DNAs tested and 7% (three of 43) of normal DNAs from patients with primary endometrial tumors. Another nucleotide substitution found at codon 80 resulted in the replacement of threonine with methionine. Codon 80 changes were found in 7% (three of 41) of the tumor cell lines (all endometrial) and in 2% (one of 62) of the normal parental DNAs. This change was not found in any of the primary endometrial tumors examined. The biological activity of these base changes was analyzed by using in vitro cyclin-dependent kinase 2-cyclin A kinase assays and calcium phosphate transfections. We observed that wild-type p21 and the p21 variants had similar growth-inhibitory abilities. Thus, our results suggest that mutation of the p21 gene is not prevalent in human tumor cell lines and is not a probable mechanism of inactivation of this gene. JF - Molecular carcinogenesis AU - Terry, L A AU - Boyd, J AU - Alcorta, D AU - Lyon, T AU - Solomon, G AU - Hannon, G AU - Berchuck, A AU - Beach, D AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 221 EP - 228 VL - 16 IS - 4 SN - 0899-1987, 0899-1987 KW - CDKN1A protein, human KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA, Neoplasm KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - Polymorphism, Genetic KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Cell Division -- physiology KW - Neoplasms -- pathology KW - DNA, Neoplasm -- genetics KW - DNA, Neoplasm -- analysis KW - Mutation KW - Neoplasms -- genetics KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78300379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Mutational+analysis+of+the+p21%2FWAF1%2FCIP1%2FSDI1+coding+region+in+human+tumor+cell+lines.&rft.au=Terry%2C+L+A%3BBoyd%2C+J%3BAlcorta%2C+D%3BLyon%2C+T%3BSolomon%2C+G%3BHannon%2C+G%3BBerchuck%2C+A%3BBeach%2C+D%3BBarrett%2C+J+C&rft.aulast=Terry&rft.aufirst=L&rft.date=1996-08-01&rft.volume=16&rft.issue=4&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-15 N1 - Date created - 1996-10-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U03106; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide adducts in native and denatured DNA. AN - 78272855; 8761442 AB - High performance liquid chromatography/UV-absorption and 32P-postlabeling were used to quantitate adducts generated by reaction of the four configurationally isomeric benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxides with native or denatured DNA in vitro. For both the 4R, 3S-dihydrodiol 2S,1R-epoxide and the 4S,3R-dihydrodiol 2S,1R-epoxide, the amount of product resulting from trans-opening of the epoxide ring by the exocyclic amino group of deoxyadenosine in denatured DNA was much less than the level found in native DNA, indicating that the native DNA structure probably intercalates the hydrocarbon residue in a fashion that promotes adenine reaction for 2S,1R-epoxides. JF - Carcinogenesis AU - Agarwal, R AU - Yagi, H AU - Jerina, D M AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 1773 EP - 1776 VL - 17 IS - 8 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Phenanthrenes KW - 1,2-epoxy-3,4-dihydroxy-1,2,3,4-tetrahydrobenzo(c)phenanthrene KW - 111001-48-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Nucleic Acid Denaturation KW - Cattle KW - Molecular Conformation KW - Nucleic Acid Conformation KW - Phenanthrenes -- toxicity KW - Carcinogens -- chemistry KW - Carcinogens -- toxicity KW - DNA -- chemistry KW - Phenanthrenes -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78272855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Benzo%5Bc%5Dphenanthrene+3%2C4-dihydrodiol+1%2C2-epoxide+adducts+in+native+and+denatured+DNA.&rft.au=Agarwal%2C+R%3BYagi%2C+H%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Agarwal&rft.aufirst=R&rft.date=1996-08-01&rft.volume=17&rft.issue=8&rft.spage=1773&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-01 N1 - Date created - 1996-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant human immunodeficiency virus type 1 genomes with tat unconstrained by overlapping reading frames reveal residues in Tat important for replication in tissue culture. AN - 78270965; 8764071 AB - Human immunodeficiency virus type 1 (HIV-1) Tat is essential for virus replication and is a potent trans activator of viral gene expression. Evidence suggests that Tat also influences virus infectivity and cytopathicity. Extensive structure-function studies of Tat in subgenomic settings with point mutagenesis and transient transfection readouts have been performed. These reporter assays have defined certain amino acid residues as being important for trans activation of reporter plasmids. However, they have not directly addressed functions related to virus replication. Here, we have studied Tat structure-function in the setting of replicating viruses. We characterized mutations that emerged in Tat during HIV-1 infections of T lymphocytes. To ensure that the selection pressure for change was directed toward protein function, we constructed HIV-Is in which the Tat reading frame was freed from constraints exerted by overlapping with the reading frames of vpr, rev, and env. When these recombinant viruses were passaged in T cells, 26 novel nucleotide changes in tat were observed from sequencing of 220 independently isolated clones. Recloning of these changes into a pNL4-3 molecular background allowed for the characterization of residues in Tat important for virus replication. Interestingly, many of the changes that affected replication when they were assayed in transient trans activation of plasmid reporters were found to be relatively neutral. We conclude that the structure-function of Tat in virus replication is incompletely reflected by activity measurements based only on subgenomic transient transfections. JF - Journal of virology AU - Neuveut, C AU - Jeang, K T AD - Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 5572 EP - 5581 VL - 70 IS - 8 SN - 0022-538X, 0022-538X KW - DNA, Recombinant KW - 0 KW - DNA, Viral KW - Index Medicus KW - AIDS/HIV KW - Culture Techniques KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Open Reading Frames -- genetics KW - DNA, Viral -- genetics KW - Transcriptional Activation KW - HIV-1 -- genetics KW - Virus Replication -- genetics KW - Gene Expression Regulation, Viral KW - Genome, Viral KW - Genes, tat UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78270965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition&rft.atitle=Usefulness+of+exchanging+a+tunneled+central+venous+catheter+using+a+subcutaneous+fibrous+sheath&rft.au=Masumoto%2C+Kouji%3BEsumi%2C+Genshiro%3BTeshiba%2C+Risa%3BNagata%2C+Kouji%3BTaguchi%2C+Tomoaki&rft.aulast=Masumoto&rft.aufirst=Kouji&rft.date=2011-05-01&rft.volume=27&rft.issue=5&rft.spage=526&rft.isbn=&rft.btitle=&rft.title=Nutrition&rft.issn=08999007&rft_id=info:doi/10.1016%2Fj.nut.2010.05.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-07 N1 - Date created - 1996-11-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1995 Aug;69(8):4906-13 [7609059] AIDS Res Hum Retroviruses. 1995 Apr;11(4):481-9 [7632463] N Engl J Med. 1989 Dec 14;321(24):1621-5 [2586564] J Virol. 1995 Sep;69(9):5743-53 [7637019] Science. 1995 Nov 10;270(5238):988-91 [7481804] J Virol. 1995 Dec;69(12):7699-711 [7494279] EMBO J. 1994 Jun 1;13(11):2650-9 [8013464] EMBO J. 1994 Jun 15;13(12):2886-96 [8026473] J Acquir Immune Defic Syndr. 1994 Sep;7(9):908-15 [7519673] Nature. 1994 Oct 20;371(6499):674-80 [7935812] Annu Rev Biochem. 1994;63:717-43 [7979253] N Engl J Med. 1995 Jan 26;332(4):228-32 [7808489] Nature. 1995 Jan 12;373(6510):117-22 [7529365] Nature. 1995 Jan 12;373(6510):123-6 [7816094] Science. 1995 Jan 27;267(5197):483-9 [7824947] Virology. 1995 Feb 1;206(2):935-44 [7531918] J Virol. 1995 Apr;69(4):2058-67 [7884851] J Virol. 1995 Apr;69(4):2605-10 [7884911] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Virology. 1986 Jan 15;148(1):226-31 [3002031] J Virol. 1986 Aug;59(2):284-91 [3016298] Lancet. 1986 Sep 20;2(8508):660-2 [2429124] J Virol. 1988 Jan;62(1):139-47 [3257102] Nucleic Acids Res. 1988 Jan 11;16(1):369 [3340539] Science. 1988 Apr 1;240(4848):80-2 [2832945] J Virol. 1988 Nov;62(11):4414-9 [2459416] J Virol. 1989 May;63(5):2118-25 [2564898] Nucleic Acids Res. 1989 May 11;17(9):3551-61 [2542902] N Engl J Med. 1989 Dec 14;321(24):1626-31 [2511447] Science. 1989 Dec 22;246(4937):1606-8 [2556795] Nature. 1990 May 3;345(6270):84-6 [2184372] J Biol Chem. 1990 Nov 25;265(33):20091-3 [2243081] Cell. 1991 May 17;65(4):651-62 [2032289] AIDS Res Hum Retroviruses. 1991 Apr;7(4):361-7 [1676896] Virology. 1991 Oct;184(2):723-8 [1716027] J Virol. 1991 Dec;65(12):6931-41 [1658383] Science. 1991 Nov 15;254(5034):963-9 [1683006] J Virol. 1992 Apr;66(4):2232-9 [1548759] Virology. 1992 May;188(1):391-5 [1566581] J Virol. 1992 Jun;66(6):3925-31 [1533883] Virology. 1992 Jul;189(1):161-6 [1604807] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9617-21 [1409674] J Virol. 1992 Dec;66(12):7159-67 [1279199] Science. 1992 Dec 18;258(5090):1938-41 [1470917] Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1571-5 [8434019] J Virol. 1993 Apr;67(4):2182-90 [8445728] J Immunol. 1993 Mar 15;150(6):2544-53 [8095514] Nature. 1993 Mar 25;362(6418):355-8 [8455722] Nature. 1993 Mar 25;362(6418):359-62 [8096068] Science. 1993 Mar 19;259(5102):1749-54 [8096089] Science. 1993 May 28;260(5112):1273-9 [8493571] Science. 1993 May 28;260(5112):1320-2 [8493575] Biotechniques. 1993 Jun;14(6):880, 884-6 [8333948] Virology. 1993 Aug;195(2):441-7 [8337822] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7632-6 [8395050] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7941-5 [7690138] J Biol Chem. 1993 Nov 25;268(33):24940-9 [8227056] J Exp Med. 1994 Jan 1;179(1):101-13 [8270859] J Cell Biol. 1994 Feb;124(3):365-71 [8294518] J Exp Med. 1994 Mar 1;179(3):961-71 [8113688] J Virol. 1994 Apr;68(4):2677-82 [8139045] J Virol. 1994 May;68(5):2906-14 [8151761] Virology. 1994 May 1;200(2):623-31 [8178448] J Virol. 1994 Jul;68(7):4177-85 [8207793] J Virol. 1994 Jul;68(7):4400-8 [7515972] Science. 1995 Apr 21;268(5209):429-31 [7716549] J Virol. 1995 Jul;69(7):4228-36 [7769682] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitogen-activated protein kinase (MAPK) activation by butylated hydroxytoluene hydroperoxide: implications for cellular survival and tumor promotion. AN - 78268685; 8758915 AB - The mitogen-activated protein kinase (MAPK) cascade plays an important role in carcinogenic development. Herein, we show that the skin tumor promoter butylated hydroxytoluene hydroperoxide (BHTOOH) stimulates a rapid and potent (14- to 20-fold) activation of extracellular signal-regulated kinase (ERK) in vivo and in cultured mouse keratinocytes. BHTOOH also moderately (5-fold) activated c-jun-N-terminal kinase, and 38-kDa MAPK-related protein in these same cells. N-acetylcysteine and o-phenanthroline abolished ERK activation by BHTOOH, consistent with a requirement for metal-dependent formation of reactive intermediates. Indeed, 4-CD3-BHTOOH, an analogue that generates less of the metabolite BHT-quinone methide (2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone) and fewer tumors in vivo, accordingly exhibited diminished potency for activating ERK. ERK activation by BHTOOH was inhibited by suramin, and by expression of dominant-negative Ras-N-17 in PC12 cells, suggesting overlap between the pathways for BHTOOH and growth factor signaling. Induction of MAPK-dependent genes c-fos and MAPK phosphatase-1 by BHTOOH was also blocked by Ras-N-17 expression. Moreover, expression of Ras-N-17 or kinase-defective MAPK kinase (MEK) diminished cell survival following BHTOOH exposure. Similarly, pretreatment with suramin or the MEK inhibitor PD098059 also potentiated the toxicity of BHTOOH. On the other hand, expression of constitutively active MEK enhanced cell survival. Thus, we demonstrate that the MAPK cascade is critical to the cellular response to BHTOOH. This study suggests a functional role for MAPK activation in tumor promotion stimulated by oxidants and other agents. JF - Cancer research AU - Guyton, K Z AU - Gorospe, M AU - Kensler, T W AU - Holbrook, N J AD - Section on Gene Expression and Aging, Gerontological Research Center, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA. Y1 - 1996/08/01/ PY - 1996 DA - 1996 Aug 01 SP - 3480 EP - 3485 VL - 56 IS - 15 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Oxidants KW - Quinones KW - Receptors, Growth Factor KW - 2,6-di-tert-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone KW - 6485-57-0 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Skin -- enzymology KW - Receptors, Growth Factor -- physiology KW - Keratinocytes -- drug effects KW - Mice KW - ras Proteins -- physiology KW - Stimulation, Chemical KW - Signal Transduction -- physiology KW - Mice, Inbred Strains KW - Base Sequence KW - Skin -- drug effects KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Signal Transduction -- drug effects KW - Oxidants -- toxicity KW - Enzyme Activation -- drug effects KW - Molecular Sequence Data KW - Cell Survival -- physiology KW - Female KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Skin Neoplasms -- enzymology KW - Quinones -- toxicity KW - Skin Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78268685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Mitogen-activated+protein+kinase+%28MAPK%29+activation+by+butylated+hydroxytoluene+hydroperoxide%3A+implications+for+cellular+survival+and+tumor+promotion.&rft.au=Guyton%2C+K+Z%3BGorospe%2C+M%3BKensler%2C+T+W%3BHolbrook%2C+N+J&rft.aulast=Guyton&rft.aufirst=K&rft.date=1996-08-01&rft.volume=56&rft.issue=15&rft.spage=3480&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-30 N1 - Date created - 1996-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy of poor-prognosis advanced-stage epithelial ovarian cancer. AN - 78265784; 8751547 AB - Epithelial ovarian cancer patients with bulky residual tumor have a poor response to therapy and limited survival. We investigated the addition of dose-intense paclitaxel to cisplatin and cyclophosphamide for patients with FIGO III/IV epithelial ovarian cancer. Paclitaxel dose was intensified from 135 to 250 mg/m2 and administered in combination with cisplatin at > or = 75 mg/m2 and cyclophosphamide at 750 mg/m2. Thirty-one of 36 patients (86%) and 25 (70%) had > or = 2 and > or = 3 cm residual disease after surgery, respectively. One-third had stage IV disease, and 80% had grade 3 tumors. The maximally tolerated doses (MTD) were paclitaxel at 250 mg/m2, cisplatin at 75 mg/m2, and cyclophosphamide at 750 mg/m2 on a 21-day cycle with G-CSF, 10 micrograms/kg/day. Administered dose intensity at the MTD was > or = 86%. Reversible grade 3 peripheral neuropathy occurred in 28% of patients and fever during neutropenia in 2/352 cycles (0.5%). The pathologic response rate is 36% with an additional 25% having minimal microscopic disease. Median progression-free and overall survivals for patients receiving paclitaxel at 250 mg/m2 at a median potential follow-up of 22 months have not been reached for the cohort nor for the > or = 3-cm subgroup. This regimen should be evaluated in a prospective, randomized clinical trial. JF - Gynecologic oncology AU - Kohn, E C AU - Sarosy, G A AU - Davis, P AU - Christian, M AU - Link, C E AU - Ognibene, F P AU - Sindelar, W F AU - Jacob, J AU - Steinberg, S M AU - Premkumar, A AU - Reed, E AD - Medical Ovarian Cancer Section, Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 181 EP - 191 VL - 62 IS - 2 SN - 0090-8258, 0090-8258 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Cyclophosphamide KW - 8N3DW7272P KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Paclitaxel -- administration & dosage KW - Neoplasm Staging KW - Humans KW - Prognosis KW - Aged KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Cisplatin -- administration & dosage KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Survival Analysis KW - Carcinoma -- pathology KW - Ovarian Neoplasms -- pathology KW - Carcinoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78265784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=A+phase+I%2FII+study+of+dose-intense+paclitaxel+with+cisplatin+and+cyclophosphamide+as+initial+therapy+of+poor-prognosis+advanced-stage+epithelial+ovarian+cancer.&rft.au=Kohn%2C+E+C%3BSarosy%2C+G+A%3BDavis%2C+P%3BChristian%2C+M%3BLink%2C+C+E%3BOgnibene%2C+F+P%3BSindelar%2C+W+F%3BJacob%2C+J%3BSteinberg%2C+S+M%3BPremkumar%2C+A%3BReed%2C+E&rft.aulast=Kohn&rft.aufirst=E&rft.date=1996-08-01&rft.volume=62&rft.issue=2&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-18 N1 - Date created - 1996-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of seizures on cerebral blood flow measured with 15O-H2O and positron emission tomography. AN - 78263417; 8764821 AB - To study quantitative alterations in regional cerebral blood flow (rCBF) accompanying seizures, and to assess the utility of ictal activation PET scanning as a noninvasive clinical tool for localization of epileptogenic foci, we used pentylenetetrazole (PTZ) to induce seizures during 15O-water positron emission tomography (PET) CBF measurement in 15 patients with uncontrolled complex partial seizures (CPS) who had been referred for surgical evaluation. Continuous EEG monitoring was performed during the PET scans. After baseline scans were obtained, each patient was injected with 150-300 mg PTZ. Two patients had generalized tonic-clonic seizures (GTCs). CBF increases were asymmetrical. Two patients (in 1 the seizure occurred spontaneously, without PTZ injection) who had CPS had bitemporal 70-80% increases in CBF. Thalamic CBF increased during both CPS and GTCS. Five patients had an increase in focal EEG interictal abnormality, accompanied by focal flow decreases in 3. PTZ injection not accompanied by clinical seizures did not increase CBF. Partial seizures may be associated with bilateral increases in CBF, and subcortical gray regions are involved in ictal activation. JF - Epilepsia AU - Theodore, W H AU - Balish, M AU - Leiderman, D AU - Bromfield, E AU - Sato, S AU - Herscovitch, P AD - Epilepsy Research Branch, National Institute of Neurologic Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 796 EP - 802 VL - 37 IS - 8 SN - 0013-9580, 0013-9580 KW - Oxygen Radioisotopes KW - 0 KW - Water KW - 059QF0KO0R KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Epilepsy, Complex Partial -- diagnostic imaging KW - Epilepsy -- chemically induced KW - Humans KW - Electroencephalography KW - Adult KW - Epilepsy -- diagnostic imaging KW - Monitoring, Physiologic KW - Functional Laterality KW - Epilepsies, Partial -- diagnostic imaging KW - Tomography, Emission-Computed KW - Cerebrovascular Circulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78263417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=Effect+of+seizures+on+cerebral+blood+flow+measured+with+15O-H2O+and+positron+emission+tomography.&rft.au=Theodore%2C+W+H%3BBalish%2C+M%3BLeiderman%2C+D%3BBromfield%2C+E%3BSato%2C+S%3BHerscovitch%2C+P&rft.aulast=Theodore&rft.aufirst=W&rft.date=1996-08-01&rft.volume=37&rft.issue=8&rft.spage=796&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=00139580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-24 N1 - Date created - 1996-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constitutive expression of hepatic cytochrome P450 genes. AN - 78261329; 8751713 AB - Cytochromes P450 are a superfamily of heme proteins involved in oxidative metabolism of endogenous chemicals such as steroid hormones and human-made xenobiotics including drugs and environmental pollutants. Hundreds of P450s have been demonstrated by cDNA and gene cloning in animals, plants, fungi, and bacteria. Most of the mammalian xenobiotic-metabolizing P450s, found within the eight subfamilies comprising the CYP2 family, are constitutively expressed in the liver. Transcriptional activation of individual P450 genes in the liver commences at distinct stages of development. Some P450 genes are preferentially expressed in one sex. The mechanisms of liver-specific expression of the P450 genes are quite diverse. Recent studies have found that several different liver-enriched transcription factors including HNF-1 alpha, HNF-3, HNF-4, and C/EBP beta, and the more ubiquitously expressed factors Sp1, GABP alpha/beta, and NF2d9 are responsible for governing the transcription of P450 genes. In some cases, more than one factor can influence expression depending on the developmental stage of the animal, and ubiquitously expressed factors such as Sp1 have been found to cooperate with liver-enriched factors to maximally activate transcription of P450 genes. STAT protein- and phospholipase A2-mediated signal transduction have also been implicated in sex-dependent expression of certain P450 genes. These studies indicate that P450 genes, even within the same subfamily in the same mammalian species, can have unique regulatory circuits.-Gonzalez, F. J., Lee, Y.-H. Constitutive expression of hepatic cytochrome P450 genes. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Gonzalez, F J AU - Lee, Y H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 1112 EP - 1117 VL - 10 IS - 10 SN - 0892-6638, 0892-6638 KW - Growth Hormone KW - 9002-72-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Phospholipases A KW - EC 3.1.1.32 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Index Medicus KW - Animals KW - Sex Characteristics KW - Humans KW - Growth Hormone -- pharmacology KW - Male KW - Female KW - Phospholipases A -- metabolism KW - Liver -- enzymology KW - Cytochrome P-450 Enzyme System -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78261329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Constitutive+expression+of+hepatic+cytochrome+P450+genes.&rft.au=Gonzalez%2C+F+J%3BLee%2C+Y+H&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1996-08-01&rft.volume=10&rft.issue=10&rft.spage=1112&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-24 N1 - Date created - 1996-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early commitment to the eosinophil lineage by cultured human peripheral blood CD34+ cells: messenger RNA analysis. AN - 78249336; 8757212 AB - Early hematopoietic progenitors expressing the CD34+ phenotype can be harvested from the peripheral blood of normal individuals. We have optimized the liquid culture of human CD34+ peripheral blood progenitors (PBPs) to achieve differentiation into a population of cells consisting almost entirely of eosinophil progenitors and maturing eosinophils. Growth of CD34+ PBPs for 28 days in the presence of the combination of IL-3, granulocyte-macrophage colony-stimulating factor, and IL-5 resulted in an almost 250-fold increase in cell number, yielding a population that contained 83% maturing eosinophils. The residual population consisted of basophils and mast cells (3% by acidic toluidine blue staining, 15.2% by flow cytometric assay for binding to high-affinity IgE receptor) and immature cells. This provides an opportunity to examine the kinetics of the acquisition of specialized mature eosinophil characteristics during eosinophil differentiation. Several host-defense and bioactive proteins are found almost exclusively in eosinophil granules. In addition, stimulated eosinophils, like neutrophils, produce copious amounts of toxic oxygen radicals. We used our culture system and the sensitive technique of reverse-transcriptase polymerase chain reaction to analyze the kinetics of production of messenger RNA transcripts encoding several eosinophil proteins, including five eosinophil granule proteins and four subunit peptides of the superoxide-generating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in small numbers of differentiating eosinophils from peripheral blood CD34+ cells. Freshly isolated CD34+ PBPs contained transcripts for the ubiquitously present housekeeping protein phosphoglucokinase but contained no eosinophil granule protein transcripts and barely detectable amounts of some oxidase protein transcripts. On day 3 of culture, no cells recognizable by histochemical staining as eosinophils could be detected, but transcripts for all five eosinophil granule proteins were present. These transcripts increased several fold during the entire culture period. Similar kinetics were seen for all but one of the NADPH oxidase protein transcripts. However, transcripts for the p67phox NADPH oxidase protein were not detected until day 7, and functional oxidase activity did not appear until day 12. From that point, oxidase activity increased dramatically over the culture period. These studies demonstrate that commitment of CD34+ PBPs to the eosinophil lineage occurs very early, by day 3, but that further events in differentiation must take place before the appearance of histologically staining eosinophil granules and acquisition of functional oxidase capacity. JF - The Journal of allergy and clinical immunology AU - Shalit, M AU - Sekhsaria, S AU - Mauhorter, S AU - Mahanti, S AU - Malech, H L AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 344 EP - 354 VL - 98 IS - 2 SN - 0091-6749, 0091-6749 KW - Antigens, CD34 KW - 0 KW - RNA, Messenger KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - NADPH Oxidase KW - EC 1.6.3.1 KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - NADH, NADPH Oxidoreductases -- genetics KW - Luminescent Measurements KW - Cells, Cultured KW - Humans KW - Adult KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation -- genetics KW - Hematopoietic Stem Cells -- immunology KW - Hematopoietic Stem Cells -- classification KW - Eosinophils -- enzymology KW - Hematopoietic Stem Cells -- enzymology KW - RNA, Messenger -- analysis KW - Eosinophils -- classification KW - Antigens, CD34 -- genetics KW - Antigens, CD34 -- physiology KW - Eosinophils -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78249336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+allergy+and+clinical+immunology&rft.atitle=Early+commitment+to+the+eosinophil+lineage+by+cultured+human+peripheral+blood+CD34%2B+cells%3A+messenger+RNA+analysis.&rft.au=Shalit%2C+M%3BSekhsaria%2C+S%3BMauhorter%2C+S%3BMahanti%2C+S%3BMalech%2C+H+L&rft.aulast=Shalit&rft.aufirst=M&rft.date=1996-08-01&rft.volume=98&rft.issue=2&rft.spage=344&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+allergy+and+clinical+immunology&rft.issn=00916749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-22 N1 - Date created - 1996-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - bcl-2 alters the antigen-driven selection of B cells in mukappa but not in mu-only Xid transgenic mice. AN - 78235294; 8757609 AB - A point mutation in the pleckstrin homology domain of the mouse Bruton's tyrosine kinase (btk) gene results in an X-linked immune defect, Xid, characterized by immunologic unresponsiveness to polymeric carbohydrate Ags. In Xid mice, B cells specific for phosphocholine (PC) do not develop in peripheral lymphoid tissues because they either fail to be positively selected from the marrow or they are clonally deleted via an Ag-driven, receptor-mediated process. Overexpression of the bcl-2 gene allows PC-specific B cells to survive and mature in Xid mukappa anti-PC transgenic mice, but PC-specific B cells are not rescued by bcl-2 in Xid mu-only transgenic mice. The failure of bcl-2 to rescue PC-specific B cells, in mu-only transgenic mice suggests that either it does not correct the btk defect in the Ag-driven selection process that occurs in pre-B cells and/or in very immature B cells or that a btk-dependent proliferative phase is required for the selection and amplification of the PC-specific B cells in mu-only transgenic mice. The rescue of PC-specific B cells in mukappa transgenic mice indicates that bcl-2 can alter receptor-mediated B cell selection at late stages in B cell development. The rescued PC-specific B cells in Xid male mice do not exhibit an altered proliferation profile in response to B cell-stimulating agents compared with B cells from unmanipulated Xid mice; thus, they fail to respond to soluble anti-mu, or PC-dextran, but they proliferate in response to PC, anti-mu, or anti-id conjugated to Sepharose. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kenny, J J AU - Fischer, R T AU - Lustig, A AU - Dintzis, H AU - Katsumata, M AU - Reed, J C AU - Longo, D L AD - Biologic Carcinogenesis Development Program/Science Applications International Corporation-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 1996/08/01/ PY - 1996 DA - 1996 Aug 01 SP - 1054 EP - 1061 VL - 157 IS - 3 SN - 0022-1767, 0022-1767 KW - Antigens, T-Independent KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Receptors, IgE KW - Phosphorylcholine KW - 107-73-3 KW - Abridged Index Medicus KW - Index Medicus KW - Phosphorylcholine -- analysis KW - Animals KW - Spleen -- cytology KW - Receptors, IgE -- analysis KW - Cell Division -- drug effects KW - Cell Differentiation KW - Mice KW - Mice, Transgenic KW - Phenotype KW - Bone Marrow Cells KW - Base Sequence KW - Molecular Sequence Data KW - Antigens, T-Independent -- pharmacology KW - Flow Cytometry KW - Clonal Deletion KW - Female KW - Male KW - B-Lymphocytes -- cytology KW - B-Lymphocytes -- immunology KW - Proto-Oncogene Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78235294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=bcl-2+alters+the+antigen-driven+selection+of+B+cells+in+mukappa+but+not+in+mu-only+Xid+transgenic+mice.&rft.au=Kenny%2C+J+J%3BFischer%2C+R+T%3BLustig%2C+A%3BDintzis%2C+H%3BKatsumata%2C+M%3BReed%2C+J+C%3BLongo%2C+D+L&rft.aulast=Kenny&rft.aufirst=J&rft.date=1996-08-01&rft.volume=157&rft.issue=3&rft.spage=1054&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-26 N1 - Date created - 1996-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple cerebral lesions complicating therapy with interleukin-2. AN - 78232897; 8757014 AB - We reviewed the records and radiologic studies of eight patients who developed new focal neurologic abnormalities while receiving interleukin-2 (IL2)-based immunotherapy for malignancy or HIV infection. Initial confusion and delirium in the patients evolved into coma, ataxia, hemiparesis, seizures, and cortical syndromes including aphasia, apraxia, and cortical blindness. Imaging studies showed multiple white and gray matter lesions with a predilection for the occipital poles, centrum semiovale, and cerebellum. After cessation of IL2 treatment, seven patients improved to normal or near-normal neurologic function paralleled by resolution of the lesions on scans. One patient improved only minimally. Possible etiologies for the lesions include an IL2-induced cerebral vasculopathy, a direct toxic effect of IL2, or immunologically mediated damage. JF - Neurology AU - Karp, B I AU - Yang, J C AU - Khorsand, M AU - Wood, R AU - Merigan, T C AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 417 EP - 424 VL - 47 IS - 2 SN - 0028-3878, 0028-3878 KW - Interleukin-2 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Kidney Neoplasms -- therapy KW - Humans KW - HIV Infections -- therapy KW - Adult KW - Middle Aged KW - Melanoma -- therapy KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- therapeutic use KW - Brain Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78232897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Multiple+cerebral+lesions+complicating+therapy+with+interleukin-2.&rft.au=Karp%2C+B+I%3BYang%2C+J+C%3BKhorsand%2C+M%3BWood%2C+R%3BMerigan%2C+T+C&rft.aulast=Karp&rft.aufirst=B&rft.date=1996-08-01&rft.volume=47&rft.issue=2&rft.spage=417&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-26 N1 - Date created - 1996-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer. AN - 78220053; 8708712 AB - Although high-dose interleukin-2 (IL-2) can produce durable remissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity. The purpose of this study is to define the maximum-tolerated dosage (MTD) of IL-2 and interferon alfa-2a (IFN alpha-2a) that can be administered chronically on an outpatient basis. Fifty-three patients with advanced cancer of variable histology with good prognostic features were treated in six cohorts. Patients in cohorts one through five received IL-2 (1.5 or 3.0 x 10(6) million units (mU)/m2) Monday through Friday and IFN alpha-2a (1.5 or 3 x 10(6) mU/m2) daily for a 4-week cycle. In cohort six, IFN alpha-2a was given three times a week. Immunologic monitoring, including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (NK) activity, were measured. Patients were evaluated for toxicity, response, and survival. Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were most severe with the first treatment of each week. Dose-limiting toxicities included grade III fatigue, hypotension, and creatinine elevations. The MTD was 1.5 mU/m2 daily x 5 given subcutaneously repeated weekly for IL-2 and 1.5 mU/m2 daily subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with RCC (24%) achieved a partial response (PR), including four of eight patients who were previously untreated. There were no objective responses in patients with other tumors, including 12 melanoma patients. IL-2 and IFN alpha-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Gause, B L AU - Sznol, M AU - Kopp, W C AU - Janik, J E AU - Smith, J W AU - Steis, R G AU - Urba, W J AU - Sharfman, W AU - Fenton, R G AU - Creekmore, S P AU - Holmlund, J AU - Conlon, K C AU - VanderMolen, L A AU - Longo, D L AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD, USA. bgause@mail.ncifcrf.gov Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 2234 EP - 2241 VL - 14 IS - 8 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Interferon-alpha KW - Interleukin-2 KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Biopterin KW - 22150-76-1 KW - interferon alfa-2a KW - 47RRR83SK7 KW - Neopterin KW - 670-65-5 KW - Index Medicus KW - Kidney Neoplasms -- therapy KW - Carcinoma, Renal Cell -- therapy KW - Humans KW - Aged KW - Biopterin -- analogs & derivatives KW - Receptors, Interleukin-2 -- metabolism KW - Biopterin -- blood KW - Adult KW - Cohort Studies KW - Injections, Subcutaneous KW - Middle Aged KW - Carcinoma, Renal Cell -- immunology KW - Male KW - Killer Cells, Natural -- immunology KW - Female KW - Remission Induction KW - Kidney Neoplasms -- immunology KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Interferon-alpha -- therapeutic use KW - Interferon-alpha -- adverse effects KW - Interleukin-2 -- therapeutic use KW - Neoplasms -- therapy KW - Antineoplastic Agents -- therapeutic use KW - Neoplasms -- immunology KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78220053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+study+of+subcutaneously+administered+interleukin-2+in+combination+with+interferon+alfa-2a+in+patients+with+advanced+cancer.&rft.au=Gause%2C+B+L%3BSznol%2C+M%3BKopp%2C+W+C%3BJanik%2C+J+E%3BSmith%2C+J+W%3BSteis%2C+R+G%3BUrba%2C+W+J%3BSharfman%2C+W%3BFenton%2C+R+G%3BCreekmore%2C+S+P%3BHolmlund%2C+J%3BConlon%2C+K+C%3BVanderMolen%2C+L+A%3BLongo%2C+D+L&rft.aulast=Gause&rft.aufirst=B&rft.date=1996-08-01&rft.volume=14&rft.issue=8&rft.spage=2234&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-06 N1 - Date created - 1996-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II evaluation of topotecan for pediatric central nervous system tumors. AN - 78203005; 8697400 AB - Topotecan is a topoisomerase I inhibitor that has good penetration across the blood-brain barrier and significant antitumor activity against human brain tumor xenografts. In a Phase I trial in children with refractory cancer, topotecan was well tolerated when administered as a 24-hour infusion. The maximum tolerated dose was 5.5 mg/m2 and the dose-limiting toxicity was myelosuppression. This Phase II study of topotecan was performed to assess the activity of topotecan against childhood brain tumors. Forty-five children with either a previously treated primary brain tumor that was refractory to standard therapy, or an untreated brain stem glioma or glioblastoma multiforme, received topotecan administered as a 24-hour intravenous infusion every 21 days. The initial dose was 5.5 mg/m2 with escalation to 7.5 mg/m2 on the second and subsequent doses in patients who did not experience dose-limiting toxicity. There were no complete or partial responses in the patients with high grade glioma (n=9), medulloblastoma (n=9), or brain stem glioma (n=14). One of 2 patients with a low grade glioma had a partial response lasting more than 17 months; 3 patients with a brain stem glioma had stable disease for 12 to 28 weeks; and 1 patient with a malignant neuroepithelial tumor and 1 patient with an optic glioma had stable disease for 41 weeks and 22 weeks, respectively. Dose escalation from 5.5 mg/m2 to 7.5 mg/m2 was well tolerated in the first 11 patients enrolled on this study who had not received prior craniospinal radiation therapy. The starting dose was subsequently increased to 7.5 mg/m2 for patients without prior craniospinal radiation. Topotecan administered as a 24-hour infusion every 21 days is inactive in high grade gliomas, medulloblastomas, and brain stem tumors. JF - Cancer AU - Blaney, S M AU - Phillips, P C AU - Packer, R J AU - Heideman, R L AU - Berg, S L AU - Adamson, P C AU - Allen, J C AU - Sallan, S E AU - Jakacki, R I AU - Lange, B J AU - Reaman, G H AU - Horowitz, M E AU - Poplack, D G AU - Balis, F M AD - The Pediatric Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1996/08/01/ PY - 1996 DA - 1996 Aug 01 SP - 527 EP - 531 VL - 78 IS - 3 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Topotecan KW - 7M7YKX2N15 KW - Camptothecin KW - XT3Z54Z28A KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Child KW - Glioblastoma -- drug therapy KW - Child, Preschool KW - Infant KW - Glioma -- drug therapy KW - Adult KW - Brain Stem KW - Adolescent KW - Male KW - Female KW - Brain Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- therapeutic use KW - Camptothecin -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Camptothecin -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78203005?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Cloning+and+characterization+of+a+novel+membrane-associated+lymphocyte+NAD%3Aarginine+ADP-ribosyltransferase.&rft.au=Okazaki%2C+I+J%3BKim%2C+H+J%3BMoss%2C+J&rft.aulast=Okazaki&rft.aufirst=I&rft.date=1996-09-06&rft.volume=271&rft.issue=36&rft.spage=22052&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-05 N1 - Date created - 1996-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of peptidyl-glycine alpha-amidating mono-oxygenase (PAM) enzymes in morphological abnormalities adjacent to pulmonary tumors. AN - 78197640; 8702008 AB - Carboxyl-terminal amidated peptide hormones are known to be autocrine growth factors for lung tumors and tumor cell lines. Expression of the enzymes necessary for the biosynthesis of active amidated peptide hormones is therefore necessary for autocrine growth stimulation in lung tumors and possibly in the early proliferative stages of lung carcinogenesis. The peptidyl amidating enzymes have previously been identified in cell lines of all histological types of lung cancer and in lung tumors by immunohistochemistry and in situ hybridization. In this study we analyzed the expression of the peptidyl amidating enzymes in histological abnormalities found in the proximity of pulmonary tumors from a series of 59 patients. Most of the lesions in both the proximal airways (basal cell hyperplasia, carcinoma in situ, and some squamous metaplasia) and the alveoli (type II cell hyperplasia, bronchiolization of the alveoli, atypical alveolar hyperplasia, and isolated atypias) had a high proportion of cells strongly positive for the peptidyl amidating enzymes. The intense expression of peptidyl amidating enzymes in type II cell hyperplasia and atypical alveolar cells, together with the high frequency of these abnormalities in the alveoli, which is an area that does not express these enzymes in normal lung, points to the involvement of peptide hormones in the growth biology of pulmonary tumors. These findings suggest that peptide hormone stimulation of mitogenesis is an early event in tumor progression and merits additional investigation as a target for early detection and chemo-intervention of lung carcinogenesis. JF - The American journal of pathology AU - Martínez, A AU - Treston, A M AU - Saldise, L AU - Montuenga, L M AU - Linnoila, R I AD - Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, MD 20850-3300, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 707 EP - 716 VL - 149 IS - 2 SN - 0002-9440, 0002-9440 KW - Biomarkers, Tumor KW - 0 KW - Multienzyme Complexes KW - Peptides KW - Mixed Function Oxygenases KW - EC 1.- KW - peptidylglycine monooxygenase KW - EC 1.14.17.3 KW - Abridged Index Medicus KW - Index Medicus KW - Carcinoma, Small Cell -- pathology KW - Pulmonary Alveoli -- pathology KW - Carcinoma in Situ -- pathology KW - Carcinoma, Small Cell -- metabolism KW - Carcinoma in Situ -- chemistry KW - Chi-Square Distribution KW - Humans KW - Peptides -- metabolism KW - Aged KW - Bronchi -- pathology KW - In Situ Hybridization KW - Adult KW - Pulmonary Alveoli -- chemistry KW - Middle Aged KW - Immunohistochemistry KW - Male KW - Female KW - Mixed Function Oxygenases -- biosynthesis KW - Carcinoma -- pathology KW - Precancerous Conditions -- metabolism KW - Carcinoma -- metabolism KW - Precancerous Conditions -- pathology KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78197640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Expression+of+peptidyl-glycine+alpha-amidating+mono-oxygenase+%28PAM%29+enzymes+in+morphological+abnormalities+adjacent+to+pulmonary+tumors.&rft.au=Mart%C3%ADnez%2C+A%3BTreston%2C+A+M%3BSaldise%2C+L%3BMontuenga%2C+L+M%3BLinnoila%2C+R+I&rft.aulast=Mart%C3%ADnez&rft.aufirst=A&rft.date=1996-08-01&rft.volume=149&rft.issue=2&rft.spage=707&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-04 N1 - Date created - 1996-09-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Lab Invest. 1972 Feb;26(2):210-9 [5059985] Acta Cytol. 1963 Mar-Apr;7:97-106 [13937612] J Histochem Cytochem. 1981 Apr;29(4):577-80 [6166661] Neurosci Lett. 1988 Feb 29;85(2):169-71 [3374833] J Clin Oncol. 1988 Nov;6(11):1685-93 [2846790] Biochem Biophys Res Commun. 1990 Jun 15;169(2):551-8 [2357221] Mod Pathol. 1990 Nov;3(6):684-7 [2263593] Cancer Res. 1991 Jan 1;51(1):400-4 [1670993] Lab Invest. 1992 Mar;66(3):337-46 [1311398] Annu Rev Neurosci. 1992;15:57-85 [1575450] Cancer Res. 1992 Jun 1;52(11):3164-73 [1591728] J Natl Cancer Inst Monogr. 1992;(13):169-75 [1389690] J Natl Cancer Inst Monogr. 1992;(13):61-6 [1327036] Chest. 1993 Jan;103(1 Suppl):4S-11S [8380133] J Histochem Cytochem. 1993 Mar;41(3):375-80 [8094086] Thorax. 1992 Dec;47(12):1041-3 [1494768] Am J Pathol. 1993 Jun;142(6):1831-40 [8389528] Oncology (Williston Park). 1993 Jun;7(6):19-26; discussion 31-2, 37 [8318356] Cancer. 1993 Oct 15;72(8):2331-40 [8402446] J Cell Biochem Suppl. 1993;17F:175-83 [8412189] Cell Growth Differ. 1993 Nov;4(11):911-20 [8297797] J Clin Invest. 1994 Mar;93(3):1298-306 [8132770] Enzyme Microb Technol. 1994 Jun;16(6):450-6 [7764886] Int J Cancer. 1994 Sep 1;58(5):629-37 [7521325] Chest. 1994 Dec;106(6 Suppl):385S-390S [7988270] Biochem Biophys Res Commun. 1994 Nov 30;205(1):282-90 [7999037] Cancer Res. 1995 Jan 1;55(1):135-40 [7805023] J Pathol. 1994 Dec;174(4):249-56 [7884586] Mod Pathol. 1995 Feb;8(2):165-9 [7777478] J Histochem Cytochem. 1996 Jan;44(1):3-12 [8543779] CA Cancer J Clin. 1996 Jan-Feb;46(1):5-27 [8548526] Cancer. 1953 Sep;6(5):963-8 [13094644] N Engl J Med. 1961 Aug 10;265:253-67 [13685078] Cancer. 1974 Jan;33(1):256-70 [4810100] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha. AN - 78191642; 8701981 AB - We have previously shown that co-expression of c-myc and transforming growth factor (TGF)-alpha as transgenes in mouse liver results in major enhancement of neoplastic development in this organ as compared with expression of either of these transgenes alone. In this report we describe in detail the progression from liver cell dysplasia to hepatocellular carcinomas (HCCs) occurring in the liver of c-myc/TGF-alpha and c-myc transgenic mice. Despite morphological similarities in the sequence of events between the two transgenic lines, the dramatic acceleration, extent, and severity of hepatic lesions in c-myc/TGF-alpha mice clearly demonstrated the synergistic effects of this transgenic combination. Although c-myc/TGF-alpha and c-myc females displayed longer latency and lower tumor incidence, the pathological changes were the same as those seen in the male mice, including the formation of HCCs, which are absent in TGF-alpha single-transgenic females. Tumors in single- and double-transgenic mice showed induction of the endogenous c-myc and TGF-alpha and, most frequently, unchanged or decreased epidermal growth factor receptor, further indicating the collaborative role of c-myc and TGF-alpha in providing a selective growth advantage to tumor cells independently of the epidermal growth factor receptor levels. To identify possible tumor precursors, we focused particularly on the dysplastic changes preceding and accompanying the appearance of preneoplastic and neoplastic lesions in the double-transgenic mice. Early on, these changes were characterized by the appearance of large dysplastic hepatocytes, mostly pericentrally, expressing high levels of TGF-alpha and uPA, as well as TGF-beta 1, particularly in apoptotic cells. After a short period of replication and expansion into the liver parenchyma, as well as penetration into the central veins, these cells underwent apoptotic cell death while preneoplastic and neoplastic lesions were forming. The peritumorous tissues also contained small dysplastic hepatocytes and oval-like cells, similar to those found in the tumors. Transplantation of the transgenic liver tissues harboring only dysplasia with or without vascular lesions onto nude mice was able to yield HCCs composed of small diploid cells, suggesting that initiated cells are generated during the early dysplastic phase and can progress to HCC. It is therefore likely that large dysplastic hepatocytes undergo apoptosis, which may be closely associated with the up-regulation of TGF-beta 1 and uPA, whereas other cells evolve into the precursor population for HCC. Due to the simultaneous presence of c-myc, TGF-alpha, and dysplasia in premalignant human liver diseases, our transgenic mouse system appears to be an appropriate model for studying human hepatocarcinogenesis. JF - The American journal of pathology AU - Santoni-Rugiu, E AU - Nagy, P AU - Jensen, M R AU - Factor, V M AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 407 EP - 428 VL - 149 IS - 2 SN - 0002-9440, 0002-9440 KW - Proto-Oncogene Proteins c-myc KW - 0 KW - Transforming Growth Factor alpha KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Apoptosis KW - Blotting, Northern KW - Disease Progression KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Organ Size KW - Liver Transplantation KW - Phenotype KW - Gene Expression Regulation, Neoplastic KW - Incidence KW - Immunohistochemistry KW - Female KW - Male KW - Proto-Oncogene Proteins c-myc -- biosynthesis KW - Liver Neoplasms -- pathology KW - Transforming Growth Factor alpha -- genetics KW - Precancerous Conditions -- physiopathology KW - Transforming Growth Factor alpha -- biosynthesis KW - Proto-Oncogene Proteins c-myc -- genetics KW - Liver Neoplasms -- physiopathology KW - Precancerous Conditions -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78191642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Evolution+of+neoplastic+development+in+the+liver+of+transgenic+mice+co-expressing+c-myc+and+transforming+growth+factor-alpha.&rft.au=Santoni-Rugiu%2C+E%3BNagy%2C+P%3BJensen%2C+M+R%3BFactor%2C+V+M%3BThorgeirsson%2C+S+S&rft.aulast=Santoni-Rugiu&rft.aufirst=E&rft.date=1996-08-01&rft.volume=149&rft.issue=2&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-04 N1 - Date created - 1996-09-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1988 Oct 1;48(19):5522-7 [3416306] Hepatology. 1988 Nov-Dec;8(6):1684-8 [2847969] J Cell Biol. 1989 Feb;108(2):653-60 [2465297] Am J Pathol. 1994 Aug;145(2):409-22 [8053498] Hepatology. 1994 Nov;20(5):1162-72 [7927248] Cancer Res. 1994 Nov 15;54(22):5964-73 [7525051] Cell. 1994 Nov 18;79(4):573-82 [7954824] Oncogene. 1995 Feb 16;10(4):765-8 [7862454] J Histochem Cytochem. 1991 Mar;39(3):341-9 [1899685] Differentiation. 1990 Oct;45(1):29-37 [2292360] Dig Dis Sci. 1991 May;36(5):642-52 [2022166] Cancer Metastasis Rev. 1990 Dec;9(4):353-67 [2129023] Hepatology. 1991 Jun;13(6):1112-6 [1646759] Am J Pathol. 1991 Jul;139(1):231-41 [1649555] Cancer Res. 1991 Aug 1;51(15):4080-3 [1649698] Cancer Res. 1991 Oct 1;51(19):5238-44 [1717143] Adv Cancer Res. 1991;57:1-46 [1950701] Lab Invest. 1991 Nov;65(5):497-9 [1753699] Lab Invest. 1991 Nov;65(5):511-7 [1753701] Cancer Res. 1992 Apr 1;52(7):1717-20 [1372529] Cell Regul. 1990 Dec;1(13):1003-14 [2134746] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5408-12 [1608949] Cancer. 1992 Sep 1;70(5):1049-56 [1325266] Cancer Res. 1992 Oct 1;52(19):5162-70 [1327502] Cancer Res. 1992 Oct 1;52(19):5171-7 [1394122] J Med Virol. 1992 Aug;37(4):271-3 [1328501] Mol Cell Biol. 1993 Jan;13(1):320-30 [8417334] Br J Cancer. 1993 Mar;67(3):531-6 [8439503] Cancer Res. 1993 Apr 15;53(8):1719-23 [8467484] Liver. 1993 Jun;13(3):151-5 [8393123] Am J Pathol. 1993 Aug;143(2):381-9 [8393616] Am J Pathol. 1993 Sep;143(3):949-58 [8362987] Cancer Res. 1993 Sep 15;53(18):4329-36 [8364928] Hepatology. 1993 Nov;18(5):1238-46 [8225231] Am J Pathol. 1993 Nov;143(5):1326-36 [7694468] Nat Genet. 1993 Nov;5(3):217-24 [8275084] J Cell Physiol. 1994 Mar;158(3):398-407 [8126064] Hepatology. 1994 Apr;19(4):810-9 [8138251] Curr Opin Genet Dev. 1994 Feb;4(1):102-8 [8193530] Nature. 1994 Jul 7;370(6484):14-5 [8015594] J Med Virol. 1994 Apr;42(4):357-65 [8046425] Am J Pathol. 1994 Aug;145(2):398-408 [8053497] J Clin Pathol. 1973 Mar;26(3):217-23 [4700503] Histopathology. 1977 Jul;1(4):225-46 [615837] Cancer. 1979 Nov;44(5):1671-6 [227574] Cancer Res. 1983 Feb;43(2):702-8 [6184154] Cancer. 1983 Jun 15;51(12):2197-205 [6303546] Am J Pathol. 1983 Jul;112(1):89-100 [6190407] Cancer. 1986 Apr 15;57(8):1515-21 [2418942] Cancer. 1986 Apr 15;57(8):1535-8 [3004693] Nature. 1986 Nov 20-26;324(6094):276-9 [3024010] Hepatology. 1995 Mar;21(3):760-6 [7875675] Toxicol Appl Pharmacol. 1995 Jun;132(2):227-36 [7785051] Lab Invest. 1995 Jul;73(1):118-27 [7603034] Mol Carcinog. 1995 Aug;13(4):233-44 [7646762] Cell Growth Differ. 1995 Jun;6(6):737-48 [7669729] Am J Pathol. 1995 Nov;147(5):1228-37 [7485387] Oncogene. 1995 Nov 2;11(9):1899-905 [7478620] Cancer Res. 1996 May 1;56(9):2137-42 [8616862] Oncogene. 1989 Jun;4(6):715-24 [2543942] Cancer Res. 1989 Nov 1;49(21):6108-17 [2551499] Mol Carcinog. 1989;2(6):345-54 [2619882] J Cell Biol. 1990 Apr;110(4):1361-7 [2139036] J Clin Invest. 1990 Jun;85(6):1833-43 [1693377] Cell. 1990 Jun 15;61(6):1121-35 [1693546] Cell. 1990 Jun 15;61(6):1137-46 [2350785] Cell. 1990 Oct 19;63(2):245-7 [2208284] Cell. 1991 Jan 25;64(2):249-70 [1988147] Arch Pathol Lab Med. 1987 Feb;111(2):170-3 [3028314] Biochem Biophys Res Commun. 1987 Feb 13;142(3):932-8 [3030308] Mol Cell Biol. 1987 May;7(5):1585-91 [3299049] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1539-43 [3422749] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased cyclic adenosine 3',5'-monophosphate inhibits G protein-coupled activation of phospholipase C in rat FRTL-5 thyroid cells. AN - 78168262; 8754735 AB - Thyroid cell growth and function are regulated by several hormones and growth factors that bind to cell surface receptors coupled via G proteins, Gs and Gq, to stimulation of adenylyl cyclase and phospholipase C (PLC), respectively. We created a permanently transfected FRTL-5 cell line (TG8) in which the thyroglobulin gene promoter directs expression of the cholera toxin (CT) A1 subunit (CTA1). CTA1 catalyzes ADP ribosylation of Gs alpha, which results in persistent activation of Gs alpha. Activated Gs alpha causes constitutive stimulation of adenylyl cyclase and increases levels of intracellular cAMP. Because G protein-coupled signaling pathways exhibit cross-talk, we compared TG8 cells to FRTL-5 cells transfected with the neomycin resistance gene (TG4) to determine whether constitutive stimulation of adenylyl cyclase influences the PLC pathway. PLC activity was assessed by measuring levels of total inositol phosphates (IPs) in TG4 and TG8 cells that had been preincubated with myo-[3H]inositol for 2 days. Baseline values of [3H]IP production were similar for the two cell lines. Incubation of TG4 control cells with 10(-8) M TSH, 300 microM ATP, and 100 microM norepinephrine for 60 min stimulated 2.5-, 8.1-, and 3.4-fold increases, respectively, in [3H]IP production over the control value. By contrast, there was no [3H]IP response to any of these ligands in TG8 cells. TG8 cells exhibit a decrease in [35S]adenosine 5'-(gamma-thio)triphosphate binding to their cell surface compared to TG4 control cells counterparts, but no decrease in [125I]TSH binding. Treatment of TG4 cells with 100 ng/ml CT, 50 microM forskolin, or 1 mM 8-bromo-cAMP for 2 days reproduced the loss of ligand-stimulated [3H]IP synthesis present in TG8 cells. Although levels of immunoreactive Gq alpha and Gq alpha 11 were normal in TG8 cells, sodium fluoride-induced [3H]IP production was also inhibited. Levels of immunoreactive PLC beta 3, the dominant subtype of PLC beta in FRTL-5 cells, were not altered in TG8 cells or by CT treatment of TG4 cells. These data indicate that elevated levels of cAMP can inhibit the activity of G protein-coupled PLC. Further study of this model will elucidate our understanding of the exact mechanism responsible for this interaction. JF - Endocrinology AU - Laglia, G AU - Zeiger, M A AU - Leipricht, A AU - Caturegli, P AU - Levine, M A AU - Kohn, L D AU - Saji, M AD - Section on Cell Regulation, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/08// PY - 1996 DA - August 1996 SP - 3170 EP - 3176 VL - 137 IS - 8 SN - 0013-7227, 0013-7227 KW - Inositol Phosphates KW - 0 KW - Isoenzymes KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Thyrotropin KW - 9002-71-5 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Type C Phospholipases KW - EC 3.1.4.- KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Transfection KW - Inositol Phosphates -- metabolism KW - Cholera Toxin -- genetics KW - Adenosine Triphosphate -- metabolism KW - Enzyme Activation -- physiology KW - Cell Line, Transformed KW - Thyrotropin -- metabolism KW - Isoenzymes -- metabolism KW - Cholera Toxin -- metabolism KW - Cyclic AMP -- metabolism KW - GTP-Binding Proteins -- physiology KW - Thyroid Gland -- cytology KW - Type C Phospholipases -- metabolism KW - Thyroid Gland -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78168262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Increased+cyclic+adenosine+3%27%2C5%27-monophosphate+inhibits+G+protein-coupled+activation+of+phospholipase+C+in+rat+FRTL-5+thyroid+cells.&rft.au=Laglia%2C+G%3BZeiger%2C+M+A%3BLeipricht%2C+A%3BCaturegli%2C+P%3BLevine%2C+M+A%3BKohn%2C+L+D%3BSaji%2C+M&rft.aulast=Laglia&rft.aufirst=G&rft.date=1996-08-01&rft.volume=137&rft.issue=8&rft.spage=3170&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-18 N1 - Date created - 1996-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug addiction: Knockout mice and dirty drugs AN - 16441772; 4346104 AB - Recent studies with knockout mice implicate the dopamine transporter as the target of the locomotor effects of the addictive psychomotor drugs cocaine and amphetamine; studies of reward in these animals are eagerly awaited. JF - Current Biology AU - Uhl, G R AU - Vandenbergh, D J AU - Miner, L L AD - Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, Addiction Research Center, PO Box 5180, Baltimore, Maryland 21224, USA Y1 - 1996/08// PY - 1996 DA - Aug 1996 SP - 935 EP - 936 VL - 6 IS - 8 SN - 0960-9822, 0960-9822 KW - amphetamine KW - amphetamines KW - cocaine KW - dopamine transporter KW - drug addiction KW - locomotion KW - mice KW - reviews KW - CSA Neurosciences Abstracts; Toxicology Abstracts; Genetics Abstracts KW - G 07397:Rodentia (mice) KW - X 24180:Social poisons & drug abuse KW - N3 11139:Toxicological and psychoactive drug correlates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16441772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Biology&rft.atitle=Drug+addiction%3A+Knockout+mice+and+dirty+drugs&rft.au=Uhl%2C+G+R%3BVandenbergh%2C+D+J%3BMiner%2C+L+L&rft.aulast=Uhl&rft.aufirst=G&rft.date=1996-08-01&rft.volume=6&rft.issue=8&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Current+Biology&rft.issn=09609822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Overproduction of three genes leads to camphor resistance and chromosome condensation in Escherichia coli AN - 15924283; 4045345 AB - We isolated and characterized three genes, crcA, cspE and crcB, which when present in high copy confer camphor resistance on a cell and suppress mutations in the chromosomal partition gene mukB. Both phenotypes require the same genes. Unlike chromosomal camphor resistant mutants, high copy number crcA, cspE and crcB do not result in an increase in the ploidy of the cells. The cspE gene has been previously identified as a cold shock-like protein with homologues in all organisms tested. We also demonstrate that camphor causes the nucleoids to decondense in vivo and when the three genes are present in high copy, the chromosomes do not decondense. Our results implicate camphor and mukB mutations as interfering with chromosome condensation and high copy crcA, cspE and crcB as promoting or protecting chromosome folding. JF - Genetics AU - Hu, KH AU - Liu, E AU - Dean, K AU - Gingras, M AU - DeGraff, W AU - Trun, N J AD - NCI-NIH, Bldg. 37, Rm. 2D21, 37 Convent Dr. MSC4255, Bethesda, MD 20892-4255, USA Y1 - 1996/08// PY - 1996 DA - Aug 1996 SP - 1521 EP - 1532 VL - 143 IS - 4 SN - 0016-6731, 0016-6731 KW - camphor KW - crcA gene KW - cspE gene KW - crcB gene KW - mukB gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - chromosomes KW - Escherichia coli KW - J 02814:Drug resistance KW - G 07321:GENERAL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15924283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Overproduction+of+three+genes+leads+to+camphor+resistance+and+chromosome+condensation+in+Escherichia+coli&rft.au=Hu%2C+KH%3BLiu%2C+E%3BDean%2C+K%3BGingras%2C+M%3BDeGraff%2C+W%3BTrun%2C+N+J&rft.aulast=Hu&rft.aufirst=KH&rft.date=1996-08-01&rft.volume=143&rft.issue=4&rft.spage=1521&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; chromosomes ER - TY - JOUR T1 - Mutagenicity of anticancer drugs in mammalian germ cells AN - 15905626; 4043338 AB - The evidence for mammalian germ cell mutagenicity induced by anticancer drugs is summarized. Primary attention is paid to the three major mouse germ cell mutagenicity tests - the dominant lethal, heritable translocation, and morphological specific locus tests - from which most germ cell mutagenicity data historically have been obtained. Of the 21 anticancer drugs reviewed, 16 have been tested in one or more of these three tests; with all 16 tested in the most common germ cell test, the male dominant lethal test, and 9 of the 16 also tested in the female dominant lethal test. The patterns of germ cell stage specificity for most of the anticancer drugs are similar, and generally resemble the patterns seen with other types of chemicals; however, some of the patterns are unique. For example, 2 of the 8 chemicals shown to induce dominant lethal mutations in female oocytes, do not induce dominant lethal mutations in male germ cells (adriamycin and platinol). Ten of the 16 chemicals tested in the dominant lethal test were positive in post-meiotic stages (spermatids through mature sperm), and seven also induced reciprocal translocations and/or specific locus mutations in post-meiotic stages. This propensity to induce mutations in post-meiotc stages has been observed with most mutagens. However, 5 of the anticancer drugs also induced dominant lethal mutations in spermatocytes (meiotic prophase cells) and one of them, 6-mercaptopurine, uniquely induced dominant lethal mutations exclusively in preleptotene spermatocytes. Finally, three of the anticancer drugs (melphalan, mitomycin C, procarbazine) are members of a very select group of chemicals shown to induce specific locus mutations in spermatogonial stem cells of mice. The implications for human risk are discussed. JF - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis AU - Witt, K L AU - Bishop, J B AD - NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996/08// PY - 1996 DA - Aug 1996 SP - 209 EP - 234 VL - 355 IS - 1-2 SN - 0027-5107, 0027-5107 KW - man KW - carcinoma KW - doxorubicin KW - cisplatin KW - 6-mercaptopurine KW - melphalan KW - mitomycin C KW - procarbazine KW - Toxicology Abstracts; Genetics Abstracts KW - meiosis KW - spermatocytes KW - germ cells KW - antitumor agents KW - cancer KW - X 24117:Biochemistry KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15905626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.atitle=Mutagenicity+of+anticancer+drugs+in+mammalian+germ+cells&rft.au=Witt%2C+K+L%3BBishop%2C+J+B&rft.aulast=Witt&rft.aufirst=K&rft.date=1996-08-01&rft.volume=355&rft.issue=1-2&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Mutagenicity of Anticancer Drugs. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - germ cells; carcinoma; meiosis; spermatocytes; cancer; antitumor agents ER - TY - JOUR T1 - New pyranocoumarins isolated from Calophyllum lanigerum and Calophyllum teysmannii AN - 15831166; 4006739 AB - During a chemotaxonomic survey of Calophyllum extracts present in the National Cancer Institute s natural product repository, our new pyranocoumarins were isolated from extracts of C. lanigerum var. austrocoriaceum and C. teysmannii var. inophylloide (King.) P. F. Stevens (Clusiaceae). The structure elucidation and anti-HIV activity of calanolide E2 (4), cordatolide E (5), pseudocordatolide C (6), and calanolide F (9), along with a simple prenylated coumarin precursor (11), are described here. JF - Journal of Natural Products AU - McKee, T C AU - Fuller, R W AU - Covington, C D AU - Cardellina, JH II AU - Gulakowski, R J AU - Krepps, B L AU - McMahon, J B AU - Boyd, M R AD - Lab. Drug Discovery Res. and Dev., Dev. Therap. Prog., Div. Cancer Treatment, Diagnosis and Centers, Natl. Cancer Inst., NCI-FCRDC Bldg., Bldg. 1052, Rm. 121, Frederick, MD 21702-1201, USA Y1 - 1996/08// PY - 1996 DA - Aug 1996 SP - 754 EP - 758 VL - 59 IS - 8 SN - 0163-3864, 0163-3864 KW - Calophyllum lanigerum KW - Calophyllum teysmannii KW - pyranocoumarins KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15831166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Natural+Products&rft.atitle=New+pyranocoumarins+isolated+from+Calophyllum+lanigerum+and+Calophyllum+teysmannii&rft.au=McKee%2C+T+C%3BFuller%2C+R+W%3BCovington%2C+C+D%3BCardellina%2C+JH+II%3BGulakowski%2C+R+J%3BKrepps%2C+B+L%3BMcMahon%2C+J+B%3BBoyd%2C+M+R&rft.aulast=McKee&rft.aufirst=T&rft.date=1996-08-01&rft.volume=59&rft.issue=8&rft.spage=754&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 ER - TY - JOUR T1 - Genetic regulation of protective immune response in congenic strains of mice vaccinated with a subunit malaria vaccine AN - 15821268; 4004379 AB - The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background. Multiple H-2-linked loci were found to contribute, each with a different mechanism. One locus mapped to the I-A region based on the strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice. Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent. Two loci mapped to the right of I-A (I-E, H-2S, or H-2D) based on a correlation with the number of H-2 super(k) loci to the right of I-A in mice that were I-A super(k). One effect was Ab independent and may correspond to a possible negative effect of the I-E super(k) locus. T cells from protected and nonprotected strains differed in their production of IFN- gamma and TNF- alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection. Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms. These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population. JF - Journal of Immunology AU - Tian, Jing-Hui AU - Miller, L H AU - Kaslow, D C AU - Ahlers, J AU - Good, M F AU - Alling, D W AU - Berzofsky, JA AU - Kumar, S AD - Bldg. 4, Rm. 126, NIAID, Natl. Institutes Health, Bethesda, MD 20892, USA Y1 - 1996/08// PY - 1996 DA - Aug 1996 SP - 1176 EP - 1183 VL - 157 IS - 3 SN - 0022-1767, 0022-1767 KW - merozoite surface protein 1 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts KW - vaccines KW - malaria KW - Plasmodium yoelii KW - immune response KW - Plasmodium falciparum KW - W3 33365:Vaccines (other) KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15821268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Genetic+regulation+of+protective+immune+response+in+congenic+strains+of+mice+vaccinated+with+a+subunit+malaria+vaccine&rft.au=Tian%2C+Jing-Hui%3BMiller%2C+L+H%3BKaslow%2C+D+C%3BAhlers%2C+J%3BGood%2C+M+F%3BAlling%2C+D+W%3BBerzofsky%2C+JA%3BKumar%2C+S&rft.aulast=Tian&rft.aufirst=Jing-Hui&rft.date=1996-08-01&rft.volume=157&rft.issue=3&rft.spage=1176&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vaccines; malaria; immune response; Plasmodium yoelii; Plasmodium falciparum ER - TY - JOUR T1 - Cisplatin-DNA adduct formation in maternal and fetal rat tissues after transplacental cisplatin exposure AN - 15780134; 3989083 AB - Cis-diamminedichloroplatinum (II) (cisplatin), given to pregnant rats at 5 mg/kg body weight (bw) is a trans placental carcinogen for fetal liver, kidney, nervous system and lung, resulting in tumor incidences of 22.5, 10.5, 6.1 and 7.5% respectively, in offspring grown to adulthood. In this study, the capacity of cisplatin to pass through the placental barrier and bind covalently to DNA in maternal and fetal tissues was evaluated. Pregnant F344/NCr rats were injected i.p. with single doses of 5, 10 or 15 mg cisplatin/kg bw at 18 days of gestation and sacrificed 24 h later. Cisplatin-DNA adducts were determined by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) using both High (90 pmol/ mu g DNA) and Low (0.50 pmol/ mu g DNA) Modified cisplatin-DNA standards and atomic absorbance spectrometry (AAS). The adduct quantities determined by the two DELFIAs varied in concert, but the DELFIA with Low Modified standard gave actual values similar to those observed with AAS. In maternal and fetal tissues, with the exception of placenta in one experiment and maternal kidney in another experiment, the extent of cisplatin-DNA adduct formation increased with dose. In maternal kidney, the low adduct levels observed at the 15 mg/kg dose may reflect kidney toxicity. Fetal kidney, liver and lung contained fewer cisplatin-DNA adducts than the corresponding maternal tissues. In contrast, at 5 and 15 mg/kg, fetal brain DNA contained higher adduct levels than maternal brain DNA. This study demonstrates the presence of DNA damage induced by cisplatin in multiple maternal and fetal rat tissues at tumorigenic doses of drug; the results are therefore consistent with the hypothesis that genotoxic mechanisms play an important role in the drug-induced tumor incidence. JF - Carcinogenesis AU - Giurgiovich, A J AU - Diwan, BA AU - Lee, K B AU - Anderson, L M AU - Rice, J M AU - Poirier, M C AD - National Cancer Institute, NIH, Bldg 37, Rm 3B25, MSC-4255, 37 Convent Drive, Bethesda, MD, 20892-4255, USA Y1 - 1996/08// PY - 1996 DA - Aug 1996 SP - 1665 EP - 1669 VL - 17 IS - 8 SN - 0143-3334, 0143-3334 KW - rats KW - cisplatin KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA adducts KW - tumorigenesis KW - genotoxicity KW - placenta KW - intrauterine exposure KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15780134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Cisplatin-DNA+adduct+formation+in+maternal+and+fetal+rat+tissues+after+transplacental+cisplatin+exposure&rft.au=Giurgiovich%2C+A+J%3BDiwan%2C+BA%3BLee%2C+K+B%3BAnderson%2C+L+M%3BRice%2C+J+M%3BPoirier%2C+M+C&rft.aulast=Giurgiovich&rft.aufirst=A&rft.date=1996-08-01&rft.volume=17&rft.issue=8&rft.spage=1665&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA adducts; intrauterine exposure; placenta; genotoxicity; tumorigenesis ER - TY - JOUR T1 - Mechanism of apoptosis suppression by phorbol ester in IL-6-starved murine plasmacytomas: role of PKC modulation and cell cycle. AN - 78191102; 8703964 AB - We show here that the mode of cell death in IL-6-starved T1165 and T1198 plasmacytoma cell lines is apoptosis, and that it can be suppressed by phorbol ester (PMA) treatment in a protein kinase C (PKC)-mediated process that involves alpha and/or delta isozymes. PMA-induced PKC activation, but not the depletion that follows it, participates in the suppression of apoptosis. Extended PKC activation is necessary but not sufficient for the apoptosis suppression. In addition, the cells must be in a "competent" state, which appears not to be determined by PKC. We observed two points of "competence" during the time between withdrawal of IL-6 and the start of massive cell death: one, immediately after withdrawal, and another, just before onset of apoptosis, at the time corresponding to maximal accumulation of cells in a G0/G1 block imposed by IL-6 withdrawal. Treatment with PMA and other PKC activators resulted in a shift of the cell population to S phase, lifting the G0/G1 block. We propose a model in which cells are rescued in a certain stage of the G1 phase of cell cycle. Death suppression occurs when a transient PMA-induced PKC activation occurs when a significant number of cells are in this part of G1, allowing them to pass the restriction point safely without initiating the cell death program. JF - Biochemistry AU - Romanova, L Y AU - Alexandrov, I A AU - Schwab, G AU - Hilbert, D M AU - Mushinski, J F AU - Nordan, R P AD - Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA. Y1 - 1996/07/30/ PY - 1996 DA - 1996 Jul 30 SP - 9900 EP - 9906 VL - 35 IS - 30 SN - 0006-2960, 0006-2960 KW - Alkaloids KW - 0 KW - Benzophenanthridines KW - Enzyme Inhibitors KW - Indoles KW - Interleukin-6 KW - Isoenzymes KW - Lactams KW - Maleimides KW - Phenanthridines KW - Phorbol Esters KW - 7-octylindolactam V KW - 109346-66-9 KW - thymeleatoxin KW - 94482-56-1 KW - chelerythrine KW - E3B045W6X0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Cytosol -- enzymology KW - Mice KW - Isoenzymes -- metabolism KW - Lactams -- pharmacology KW - Isoenzymes -- antagonists & inhibitors KW - Phorbol Esters -- pharmacology KW - Tumor Cells, Cultured KW - Plasmacytoma KW - Phenanthridines -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Indoles -- pharmacology KW - Cell Line KW - Maleimides -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Tetradecanoylphorbol Acetate -- analogs & derivatives KW - Apoptosis -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Interleukin-6 -- pharmacology KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78191102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Mechanism+of+apoptosis+suppression+by+phorbol+ester+in+IL-6-starved+murine+plasmacytomas%3A+role+of+PKC+modulation+and+cell+cycle.&rft.au=Romanova%2C+L+Y%3BAlexandrov%2C+I+A%3BSchwab%2C+G%3BHilbert%2C+D+M%3BMushinski%2C+J+F%3BNordan%2C+R+P&rft.aulast=Romanova&rft.aufirst=L&rft.date=1996-07-30&rft.volume=35&rft.issue=30&rft.spage=9900&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-10 N1 - Date created - 1996-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serine phosphorylation, chromosomal localization, and transforming growth factor-beta signal transduction by human bsp-1. AN - 78134902; 8663601 AB - The transforming growth factor-beta (TGF-beta) superfamily regulates a multitude of cellular and developmental events. TGF-beta family ligands signal through transmembrane serine/threonine kinase receptors whose downstream effectors are largely unknown. Using genetic data from the fruit fly, we have identified a downstream effector of TGF-beta-induced signaling. TGF-beta signaling protein-1 (BSP-1) is rapidly phosphorylated in response to TGF-beta. Localization of bsp-1 to chromosome 4q28 suggests a role in carcinogenesis. These data suggest that BSP-1 is the prototype of a new class of signaling molecules. JF - The Journal of biological chemistry AU - Lechleider, R J AU - de Caestecker, M P AU - Dehejia, A AU - Polymeropoulos, M H AU - Roberts, A B AD - Laboratory of Chemoprevention, NCI, National Institutes of Health, Bethesda, Maryland 20892-5055. USA. Y1 - 1996/07/26/ PY - 1996 DA - 1996 Jul 26 SP - 17617 EP - 17620 VL - 271 IS - 30 SN - 0021-9258, 0021-9258 KW - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors KW - 0 KW - DNA-Binding Proteins KW - MXD1 protein, human KW - Proteins KW - Repressor Proteins KW - Smad Proteins KW - Trans-Activators KW - Transforming Growth Factor beta KW - Serine KW - 452VLY9402 KW - Index Medicus KW - Humans KW - DNA-Binding Proteins -- genetics KW - Amino Acid Sequence KW - Chromosome Mapping KW - Chromosomes, Human, Pair 4 KW - Serine -- metabolism KW - Cloning, Molecular KW - Base Sequence KW - Phosphorylation KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Transforming Growth Factor beta -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78134902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Serine+phosphorylation%2C+chromosomal+localization%2C+and+transforming+growth+factor-beta+signal+transduction+by+human+bsp-1.&rft.au=Lechleider%2C+R+J%3Bde+Caestecker%2C+M+P%3BDehejia%2C+A%3BPolymeropoulos%2C+M+H%3BRoberts%2C+A+B&rft.aulast=Lechleider&rft.aufirst=R&rft.date=1996-07-26&rft.volume=271&rft.issue=30&rft.spage=17617&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-03 N1 - Date created - 1996-09-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U57456; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of the 82-kDa subunit of the vaccinia virus early transcription factor heterodimer with the promoter core sequence directs downstream DNA binding of the 70-kDa subunit. AN - 78271453; 8755510 AB - The vaccinia virus early transcription factor (VETF), a heterodimeric protein composed of 82- and 70-kDa subunits, interacts with viral early promoters at both a sequence-specific core region upstream and a sequence-independent region downstream of the RNA start site. To determine the VETF subunit-promoter interactions, 32P-labeled DNA targets were chemically synthesized with uniquely positioned phosphorothioates to which azidophenacyl bromide moieties were coupled. After incubating the derivatized promoter with VETF and exposing the complex to 302-nm light, the protein was denatured and the individual subunits with or without covalently bound DNA were isolated with specific antiserum and analyzed by SDS/polyacrylamide gel electrophoresis. Using a set of 26 duplex probes, with uniquely positioned aryl azide moieties on the coding or template strands, we found that the 82-kDa subunit interacted primarily with the core region of the promoter, whereas the 70-kDa subunit interacted with the downstream region. Nucleotide substitutions in the core region that downregulate transcription affected the binding of both subunits: the 82-kDa subunit no longer exhibited specificity for upstream regions of the promoter but also bound to downstream regions, whereas the binding of the 70-kDa subunit was abolished even though the mutations were far upstream of its binding site. These results suggested mechanisms by which the interaction of the 82-kDa subunit with the core sequence directs binding of the 70-kDa subunit to DNA downstream. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Cassetti, M A AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0455, USA. Y1 - 1996/07/23/ PY - 1996 DA - 1996 Jul 23 SP - 7540 EP - 7545 VL - 93 IS - 15 SN - 0027-8424, 0027-8424 KW - Azides KW - 0 KW - DNA, Viral KW - Macromolecular Substances KW - Oligodeoxyribonucleotides KW - Thionucleotides KW - Transcription Factors KW - Viral Proteins KW - early transcription factor protein, Vaccinia virus KW - 4-azidophenacyl bromide KW - 57018-46-9 KW - Index Medicus KW - Base Sequence KW - Models, Structural KW - DNA Footprinting KW - Molecular Sequence Data KW - Protein Binding KW - Molecular Weight KW - Mutagenesis KW - Vaccinia virus -- genetics KW - Viral Proteins -- isolation & purification KW - Promoter Regions, Genetic KW - DNA, Viral -- chemistry KW - Transcription Factors -- metabolism KW - Transcription Factors -- isolation & purification KW - Viral Proteins -- metabolism KW - Vaccinia virus -- metabolism KW - DNA, Viral -- isolation & purification KW - DNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78271453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Interaction+of+the+82-kDa+subunit+of+the+vaccinia+virus+early+transcription+factor+heterodimer+with+the+promoter+core+sequence+directs+downstream+DNA+binding+of+the+70-kDa+subunit.&rft.au=Cassetti%2C+M+A%3BMoss%2C+B&rft.aulast=Cassetti&rft.aufirst=M&rft.date=1996-07-23&rft.volume=93&rft.issue=15&rft.spage=7540&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-29 N1 - Date created - 1996-10-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1967 Jul;58(1):134-41 [5231593] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12183-7 [7991603] Gene. 1995 Feb 3;153(1):1-8 [7883172] Science. 1996 Feb 9;271(5250):778-84 [8628992] Proc Natl Acad Sci U S A. 1975 Jan;72(1):318-22 [164018] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6069-73 [3476927] J Biol Chem. 1988 Aug 5;263(22):10754-60 [3392040] J Biol Chem. 1988 Aug 5;263(22):10761-5 [2839505] J Mol Biol. 1989 Dec 20;210(4):749-69 [2515286] J Virol. 1990 Apr;64(4):1523-9 [2138681] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4401-5 [2190222] J Biol Chem. 1991 Aug 15;266(23):15539-44 [1869571] J Biol Chem. 1991 Aug 15;266(23):15545-8 [1869572] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3536-40 [1565650] J Biol Chem. 1993 Feb 5;268(4):2773-80 [8428951] J Virol. 1993 Sep;67(9):5677-80 [8350421] J Biol Chem. 1993 Sep 25;268(27):20016-21 [8376362] J Biol Chem. 1994 Mar 11;269(10):7552-7 [8125977] J Biol Chem. 1994 May 13;269(19):14323-8 [8188718] J Virol. 1994 Sep;68(9):6052-6 [8057480] Proc Natl Acad Sci U S A. 1967 Dec;58(6):2280-7 [5242206] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A knock-out model of paroxysmal nocturnal hemoglobinuria: Pig-a(-) hematopoiesis is reconstituted following intercellular transfer of GPI-anchored proteins. AN - 78270334; 8755581 AB - We created a "knockout" embryonic stem cell via targeted disruption of the phosphatidylinositol glycan class A (Pig-a) gene, resulting in loss of expression of cell surface glycosyl phosphatidylinositol-anchored proteins and reproducing the mutant phenotype of the human disease paroxysmal nocturnal hemoglobinuria. Morphogenesis of Pig-a- embryoid bodies (EB) in vitro was grossly aberrant and, unlike EB derived from normal embryonic stem cells, Pig-A EB produced no secondary hematopoietic colonies. Chimeric EB composed of control plus Pig-A- cells, however, appeared normal, and hematopoiesis from knock-out cells was reconstituted. Transfer in situ of glycosyl phosphatidylinositol-anchored proteins from normal to knock-out cells was demonstrated by two-color fluorescent analysis, suggesting a possible mechanism for these functional effects. Hematopoietic cells with mutated PIG-A genes in humans with paroxysmal nocturnal hemoglobinuria may be subject to comparable pathophysiologic processes and amenable to similar therapeutic protein transfer. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Dunn, D E AU - Yu, J AU - Nagarajan, S AU - Devetten, M AU - Weichold, F F AU - Medof, M E AU - Young, N S AU - Liu, J M AD - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA. Y1 - 1996/07/23/ PY - 1996 DA - 1996 Jul 23 SP - 7938 EP - 7943 VL - 93 IS - 15 SN - 0027-8424, 0027-8424 KW - Glycosylphosphatidylinositols KW - 0 KW - Membrane Proteins KW - Index Medicus KW - Coculture Techniques KW - Animals KW - Cells, Cultured KW - Humans KW - Membrane Proteins -- biosynthesis KW - Cell Differentiation KW - Mice KW - Models, Biological KW - Embryo, Mammalian KW - Mutagenesis, Insertional KW - Mice, Knockout KW - Hemoglobinuria, Paroxysmal -- pathology KW - Stem Cells -- cytology KW - Glycosylphosphatidylinositols -- genetics KW - Hemoglobinuria, Paroxysmal -- genetics KW - Glycosylphosphatidylinositols -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78270334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=A+knock-out+model+of+paroxysmal+nocturnal+hemoglobinuria%3A+Pig-a%28-%29+hematopoiesis+is+reconstituted+following+intercellular+transfer+of+GPI-anchored+proteins.&rft.au=Dunn%2C+D+E%3BYu%2C+J%3BNagarajan%2C+S%3BDevetten%2C+M%3BWeichold%2C+F+F%3BMedof%2C+M+E%3BYoung%2C+N+S%3BLiu%2C+J+M&rft.aulast=Dunn&rft.aufirst=D&rft.date=1996-07-23&rft.volume=93&rft.issue=15&rft.spage=7938&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-29 N1 - Date created - 1996-10-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1995 Sep 8;269(5229):1435-9 [7660128] Science. 1995 Jul 7;269(5220):89-92 [7541557] N Engl J Med. 1995 Nov 9;333(19):1253-8 [7566002] Blood. 1995 Nov 1;86(9):3381-6 [7579441] Development. 1988 Mar;102(3):471-8 [2460305] J Exp Med. 1989 Sep 1;170(3):637-54 [2475570] Proc Natl Acad Sci U S A. 1990 Jan;87(2):801-5 [2300563] J Immunol. 1990 May 1;144(9):3478-83 [1691760] N Engl J Med. 1990 Oct 25;323(17):1184-9 [1699124] Annu Rev Cell Biol. 1990;6:1-39 [2148872] Genes Dev. 1991 May;5(5):728-40 [1709130] Development. 1991 Feb;111(2):259-67 [1893864] New Biol. 1991 Jul;3(7):698-708 [1721533] Blood. 1992 Mar 15;79(6):1385-92 [1547338] Development. 1992 Feb;114(2):303-16 [1591994] Science. 1992 Jun 26;256(5065):1805-7 [1377404] Br J Haematol. 1967 Mar;13(2):236-51 [6019033] Scand J Haematol. 1979 Feb;22(2):121-8 [285455] Biochemistry. 1980 Sep 30;19(20):4601-7 [7426618] Blood. 1982 Jul;60(1):157-9 [7082835] N Engl J Med. 1983 Sep 22;309(12):690-3 [6888440] J Exp Med. 1984 Nov 1;160(5):1558-78 [6238120] Proc Natl Acad Sci U S A. 1985 May;82(9):2980-4 [2581259] J Embryol Exp Morphol. 1985 Jun;87:27-45 [3897439] Exp Hematol. 1986 Mar;14(3):222-9 [3512279] J Exp Med. 1987 Mar 1;165(3):848-64 [2434600] Science. 1988 Jan 15;239(4837):268-75 [3276003] Blood. 1995 Aug 15;86(4):1487-92 [7632956] Biol Reprod. 1992 Aug;47(2):271-6 [1327207] Mol Cell Biol. 1993 Jan;13(1):473-86 [8417345] Science. 1993 Feb 26;259(5099):1318-20 [7680492] Blood. 1993 Jun 1;81(11):2903-15 [8499630] Cell. 1993 May 21;73(4):703-11 [8500164] Biochemistry. 1993 Nov 16;32(45):12218-28 [8218299] Methods Enzymol. 1993;225:900-18 [7694046] Neuron. 1993 Dec;11(6):1163-74 [8274281] Blood. 1994 Feb 1;83(3):853-9 [7507738] EMBO J. 1994 Jan 1;13(1):110-7 [8306954] Lancet. 1994 Apr 16;343(8903):951-3 [7909012] J Pathol. 1994 Feb;172(2):189-97 [7513354] Blood. 1994 Jun 1;83(11):3126-31 [8193350] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6245-8 [7517044] Immunology. 1994 May;82(1):28-33 [7519171] Semin Immunol. 1994 Apr;6(2):89-95 [8054540] Mol Endocrinol. 1994 Jun;8(6):746-56 [7935490] EMBO J. 1994 Nov 1;13(21):5070-4 [7525274] Science. 1995 Apr 14;268(5208):221-5 [7716512] J Virol. 1995 Jun;69(6):3873-7 [7538177] Blood. 1995 Jun 1;85(11):3058-65 [7756640] Blood. 1995 Jun 15;85(12):3367-77 [7780125] Trends Biochem Sci. 1995 Sep;20(9):367-71 [7482705] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-1 nucleocapsid protein induces "maturation" of dimeric retroviral RNA in vitro. AN - 78269298; 8755517 AB - After a retrovirus particle is released from the cell, the dimeric genomic RNA undergoes a change in conformation. We have previously proposed that this change, termed maturation of the dimer, is due to the action of nucleocapsid (NC) protein on the RNA within the virus particle. We now report that treatment of a 345-base synthetic fragment of Harvey sarcoma virus RNA with recombinant or synthetic HIV-1 NC protein converts a less stable form of dimeric RNA to a more stable form. This phenomenon thus appears to reproduce the maturation of dimeric retroviral RNA in a completely defined system in vitro. To our knowledge, maturation of dimeric RNA within a retrovirus particle is the first example of action of an "RNA chaperone" protein in vivo. Studies with mutant NC proteins suggest that the activity depends upon basic amino acid residues flanking the N-terminal zinc finger and upon residues within the N-terminal finger, including an aromatic amino acid, but do not require the zinc finger structures themselves. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Feng, Y X AU - Copeland, T D AU - Henderson, L E AU - Gorelick, R J AU - Bosche, W J AU - Levin, J G AU - Rein, A AD - Retroviral Genetics Section, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996/07/23/ PY - 1996 DA - 1996 Jul 23 SP - 7577 EP - 7581 VL - 93 IS - 15 SN - 0027-8424, 0027-8424 KW - RNA, Double-Stranded KW - 0 KW - RNA, Viral KW - Recombinant Proteins KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Thermodynamics KW - Recombinant Proteins -- biosynthesis KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Zinc Fingers KW - Transcription, Genetic KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Harvey murine sarcoma virus -- metabolism KW - HIV-1 -- metabolism KW - Nucleocapsid -- metabolism KW - RNA, Viral -- biosynthesis KW - RNA, Double-Stranded -- biosynthesis KW - Harvey murine sarcoma virus -- genetics KW - Nucleocapsid -- chemistry KW - Nucleocapsid -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78269298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=HIV-1+nucleocapsid+protein+induces+%22maturation%22+of+dimeric+retroviral+RNA+in+vitro.&rft.au=Feng%2C+Y+X%3BCopeland%2C+T+D%3BHenderson%2C+L+E%3BGorelick%2C+R+J%3BBosche%2C+W+J%3BLevin%2C+J+G%3BRein%2C+A&rft.aulast=Feng&rft.aufirst=Y&rft.date=1996-07-23&rft.volume=93&rft.issue=15&rft.spage=7577&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-29 N1 - Date created - 1996-10-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1975 Nov;16(5):1161-70 [171447] Biochemistry. 1994 Sep 6;33(35):10693-700 [8075069] J Biol Chem. 1987 Apr 15;262(11):4961-7 [2435721] Virology. 1988 Jun;164(2):531-6 [3369091] EMBO J. 1988 Jun;7(6):1777-83 [2458920] J Virol. 1990 Feb;64(2):774-83 [2153242] Nucleic Acids Res. 1990 Jan 11;18(1):119-27 [2155394] J Mol Biol. 1994 Sep 30;242(4):422-9 [7932701] J Virol. 1995 Apr;69(4):2486-90 [7884897] J Biol Chem. 1995 Sep 8;270(36):20871-4 [7545662] Biochemistry. 1996 Feb 6;35(5):1589-98 [8634290] J Virol. 1990 Oct;64(10):5076-92 [1697912] Adv Inorg Biochem. 1990;8:199-248 [2119553] J Mol Biol. 1990 Dec 5;216(3):689-99 [2124274] J Virol. 1992 Apr;66(4):1856-65 [1548743] J Biol Chem. 1992 Apr 5;267(10):6689-95 [1551877] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6472-6 [1631144] Protein Sci. 1993 Jan;2(1):3-19 [8443588] Protein Sci. 1993 Feb;2(2):231-43 [8443601] J Virol. 1993 Jul;67(7):4027-36 [8510214] J Biol Chem. 1993 Aug 5;268(22):16519-27 [8344933] J Virol. 1993 Sep;67(9):5443-9 [8350405] Science. 1993 Oct 1;262(5130):99-102 [7692597] EMBO J. 1994 Jun 15;13(12):2904-12 [8026475] EMBO J. 1994 Jun 15;13(12):2913-24 [8026476] J Virol. 1994 Aug;68(8):5013-8 [8035501] J Virol. 1994 Sep;68(9):5863-70 [8057466] J Virol. 1985 Mar;53(3):899-907 [3882995] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro effects of anti-HIV immunotoxins directed against multiple epitopes on HIV type 1 envelope glycoprotein 160. AN - 78357926; 8827220 AB - We have used a panel of anti-gp160 MAbs to construct anti-HIV immunotoxins by coupling antibodies to ricin A chain (RAC). The ability of the immunotoxins to kill HIV-1-infected cells and halt the spread of infection was tested in tissue culture on persistently and acutely infected cell lines and primary lymphocyte cultures stimulated with phytohemagglutinin (PHA blasts). Laboratory strains and clinical isolates of HIV both were tested. The constitution and antigen-binding capacity of the immunotoxins were confirmed by ELISA and indirect immunofluorescence. Immunotoxins that bind epitopes exposed on the cell surface effectively killed persistently infected cells, although killing was not directly proportional to binding of immunotoxin to cell. The activity of anti-gp41, but not anti-gp120, immunotoxins was markedly enhanced in the presence of soluble CD4 or peptides corresponding to the CDR3 region of CD4. CD4-mediated enhancement of anti-gp41 immunotoxin activity was observed for laboratory strains neutralized by sCD4 and for clinical isolates that were resistant to neutralization by sCD4. Immunotoxin action was potentiated by brefeldin A, bafilomycin A1, cortisone, and an amphipathic fusion peptide, but not by cytochalasin D, nocodazol, monodansyl cadaverine, or trans-retinoic acid. Anti-HIV immunotoxins are useful tool with which to study the functional expression of gp120/gp41 antigens on the surface of HIV-infected cells, as well as potential AIDS therapeutics. Because these studies relate to the accessibility of viral antigens to antibody-mediated attack, these studies also have relevance for vaccine development. JF - AIDS research and human retroviruses AU - Pincus, S H AU - Wehrly, K AU - Cole, R AU - Fang, H AU - Lewis, G K AU - McClure, J AU - Conley, A J AU - Wahren, B AU - Posner, M R AU - Notkins, A L AU - Tilley, S A AU - Pinter, A AU - Eiden, L AU - Teintze, M AU - Dorward, D AU - Tolstikov, V V AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. Y1 - 1996/07/20/ PY - 1996 DA - 1996 Jul 20 SP - 1041 EP - 1051 VL - 12 IS - 11 SN - 0889-2229, 0889-2229 KW - Anti-Bacterial Agents KW - 0 KW - Antifungal Agents KW - Cyclopentanes KW - Epitopes KW - HIV Envelope Protein gp160 KW - HIV Envelope Protein gp41 KW - Immunotoxins KW - Macrolides KW - Phytohemagglutinins KW - Brefeldin A KW - 20350-15-6 KW - Cytochalasin D KW - 22144-77-0 KW - bafilomycin A1 KW - 88899-55-2 KW - Nocodazole KW - SH1WY3R615 KW - Cortisone KW - V27W9254FZ KW - Index Medicus KW - AIDS/HIV KW - Cyclopentanes -- pharmacology KW - Cortisone -- pharmacology KW - Antifungal Agents -- pharmacology KW - Phytohemagglutinins -- immunology KW - Humans KW - Anti-Bacterial Agents -- pharmacology KW - HIV Envelope Protein gp41 -- immunology KW - Enzyme-Linked Immunosorbent Assay KW - Nocodazole -- pharmacology KW - Cell Line KW - Microscopy, Electron, Scanning KW - Cytochalasin D -- metabolism KW - HIV Envelope Protein gp160 -- immunology KW - HIV-1 -- immunology KW - Immunotoxins -- pharmacology KW - Epitopes -- immunology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78357926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=In+vitro+effects+of+anti-HIV+immunotoxins+directed+against+multiple+epitopes+on+HIV+type+1+envelope+glycoprotein+160.&rft.au=Pincus%2C+S+H%3BWehrly%2C+K%3BCole%2C+R%3BFang%2C+H%3BLewis%2C+G+K%3BMcClure%2C+J%3BConley%2C+A+J%3BWahren%2C+B%3BPosner%2C+M+R%3BNotkins%2C+A+L%3BTilley%2C+S+A%3BPinter%2C+A%3BEiden%2C+L%3BTeintze%2C+M%3BDorward%2C+D%3BTolstikov%2C+V+V&rft.aulast=Pincus&rft.aufirst=S&rft.date=1996-07-20&rft.volume=12&rft.issue=11&rft.spage=1041&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-02 N1 - Date created - 1997-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of domains in human beta-hexosaminidase that determine substrate specificity. AN - 78179428; 8663217 AB - The lysosomal beta-hexosaminidases are dimers composed of alpha and beta subunits. beta-Hexosaminidase A (alphabeta) is a heterodimer, whereas hexosaminidase B (betabeta) and S (alphaalpha) are homodimers. Although containing a high degree of amino acid identity, each subunit expresses a unique active site that can be distinguished by a differential ability to hydrolyze charged substrates. The site on the beta-subunit primarily degrades neutral substrates, whereas the alpha-subunit site is, in addition, active against sulfated substrates. Isozyme specificity is also exhibited with glycolipid substrates. Among human isozymes, only beta-hexosaminidase A together with the GM2 activator protein can degrade the natural substrate, GM2 ganglioside, at physiologically significant rates. To identify the domains of the human beta-hexosaminidase subunits that determine substrate specificity, we have generated chimeric subunits containing both alpha- and beta-subunit sequences. The chimeric constructs were expressed in HeLa cells to screen for activity and then selected constructs were produced in the baculovirus expression system to assess their ability to degrade GM2 ganglioside in the presence of GM2 activator protein. Generation of activity against the sulfated substrate required the substitution of two noncontinuous alpha-subunit sequences (amino acids 1-191 and 403-529) into analogous positions of the beta-subunit. Chimeric constructs containing only one of these regions linked to the beta-subunit sequence showed either neutral substrate activity only (amino acids 1-191) or lacked enzyme activity entirely (amino acids 403-529). Neither the chimeras nor the wild-type subunits displayed activator-dependent GM2-hydrolyzing activity when expressed alone. However, one chimeric subunit containing alpha amino acids 1-191 fused with beta amino acids 225 to 556, when co-expressed with the wild-type alpha-subunit, showed activity comparable with that of recombinant beta-hexosaminidase A formed by the co-expression of the alpha- and beta-subunits. This result indicates that the beta-subunit amino acids 225-556 contribute an essential function in the GM2-hydrolyzing activity of beta-hexosaminidase A. JF - The Journal of biological chemistry AU - Pennybacker, M AU - Liessem, B AU - Moczall, H AU - Tifft, C J AU - Sandhoff, K AU - Proia, R L AD - Section on Biochemical Genetics, Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/07/19/ PY - 1996 DA - 1996 Jul 19 SP - 17377 EP - 17382 VL - 271 IS - 29 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Isoenzymes KW - Macromolecular Substances KW - Recombinant Fusion Proteins KW - G(M2) Ganglioside KW - 19600-01-2 KW - Hexosaminidase B KW - EC 3.2.1.52 KW - beta-N-Acetylhexosaminidases KW - Index Medicus KW - Isoenzymes -- chemistry KW - Genetic Variation KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - G(M2) Ganglioside -- chemistry KW - Isoenzymes -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Carbohydrate Sequence KW - Substrate Specificity KW - G(M2) Ganglioside -- metabolism KW - beta-N-Acetylhexosaminidases -- metabolism KW - beta-N-Acetylhexosaminidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78179428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+domains+in+human+beta-hexosaminidase+that+determine+substrate+specificity.&rft.au=Pennybacker%2C+M%3BLiessem%2C+B%3BMoczall%2C+H%3BTifft%2C+C+J%3BSandhoff%2C+K%3BProia%2C+R+L&rft.aulast=Pennybacker&rft.aufirst=M&rft.date=1996-07-19&rft.volume=271&rft.issue=29&rft.spage=17377&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-12 N1 - Date created - 1996-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparative study on expression of mucin related antigens in preneoplastic and neoplastic rat colorectal mucosa. AN - 78160027; 8689626 AB - A polyclonal antibody (PAb35) defined antigen (Ag) was characterized in association with two monoclonal antibody (MAbM1 and MAb660) defined mucin M1 and 660 Ags in colorectal mucosa during 20-methylcholanthrene-induced rat carcinogenesis in the same organ. Immunohistochemistry and ELISA revealed that these three antibodies were reactive with most of the colorectal carcinomas. MAbM1 and MAb660 were reactive with preneoplastic colorectal mucosa in rats with no detectable carcinoma, in contrast to non-reactivity with PAb35. PAb35 reacted with preneoplastic mucosa, present adjacent to the cancerous tissues only. Staining was mainly localized in the cytoplasm of cancer cells, goblet cells and luminal mucous deposits. In control rats, M1 and 660 Ags were present in gastric mucosa, but not in colorectum. PAb35 defined Ag was absent in gastrointestinal mucosa of controls. ELISA revealed 82% reduction in reactivity, when PAb35 was reacted with 2-mercaptoethanol (2ME) treated colorectal mucosal extracts. Ninety percent reduction was seen in the case of MAbM1. However, 50% reduction was demonstrated when MAb660 was reacted with 2ME treated extracts. JF - Cancer letters AU - Baral, R AU - Sautya, D K AU - Maity, P AD - Department of Cell Biology, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1996/07/19/ PY - 1996 DA - 1996 Jul 19 SP - 15 EP - 22 VL - 105 IS - 1 SN - 0304-3835, 0304-3835 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Neoplasm KW - Mucins KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Time Factors KW - Male KW - Immunoenzyme Techniques KW - Mucins -- immunology KW - Mucins -- metabolism KW - Colorectal Neoplasms -- immunology KW - Precancerous Conditions -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78160027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=A+comparative+study+on+expression+of+mucin+related+antigens+in+preneoplastic+and+neoplastic+rat+colorectal+mucosa.&rft.au=Baral%2C+R%3BSautya%2C+D+K%3BMaity%2C+P&rft.aulast=Baral&rft.aufirst=R&rft.date=1996-07-19&rft.volume=105&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-26 N1 - Date created - 1996-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Obtaining information about susceptibility from the epidemiological literature. AN - 78208414; 8711741 AB - Whether people become ill after encountering environmental pollutants depends on the magnitude of their exposure and their capacity to respond. Exposure and intrinsic response capabilities vary within the population. Those that become ill when the general population remains largely unaffected are considered to be highly susceptible. The U.S. Environmental Protection Agency (USEPA), responsible for protecting the public from environmental pollutants, has developed risk assessment procedures to assist in evaluating the likelihood of health effects. However, the Agency's ability to evaluate the risk faced by highly susceptible populations is often hindered by the paucity of adequate health effects data. Response variability can be assessed with animal models and human epidemiological studies. Although animal models are useful when evaluating the effect of gender and developmental stage on susceptibility, inbred rodent strains underestimate the genetic and lifestyle-induced variability in susceptibility found in human populations. Epidemiological approaches are the preferred source of information on variability. This paper reviews the epidemiological literature from the perspective of a risk assessor seeking data suitable for estimating the risk to highly susceptible populations. Epidemiological approaches do not measure the full range of population response variability. Rather, "susceptibility factors" are evaluated either as risk factors or by focusing on the susceptible population, e.g. children. Susceptibility factors due to genetics, developmental stage, gender, ethnicity, disease state and lifestyle are most frequently encountered. Often, the information describing the health impact of the susceptibility factor is incomplete due to, (1) a failure to consider factors modifying susceptibility; (2) inadequate exposure data; (3) a failure to evaluate the health impact of the susceptibility factor. In addition, for a given exposure agent, several susceptibility factors may be relevant. While incomplete data describing susceptibility factors limits the opportunity for quantitative estimations of risk, available information can supplement qualitative evaluations and risk management. JF - Toxicology AU - Grassman, J A AD - School of Public Health, Columbia University, New York USA. grassman@niehs.nich.gov Y1 - 1996/07/17/ PY - 1996 DA - 1996 Jul 17 SP - 253 EP - 270 VL - 111 IS - 1-3 SN - 0300-483X, 0300-483X KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - United States KW - Animals KW - United States Environmental Protection Agency KW - Humans KW - Risk Assessment KW - Environmental Illness -- epidemiology KW - Disease Susceptibility -- epidemiology KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78208414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Precursor-product+relationship+between+oval+cells+and+hepatocytes%3A+comparison+between+tritiated+thymidine+and+bromodeoxyuridine+as+tracers.&rft.au=Evarts%2C+R+P%3BHu%2C+Z%3BOmori%2C+N%3BOmori%2C+M%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Evarts&rft.aufirst=R&rft.date=1996-10-01&rft.volume=17&rft.issue=10&rft.spage=2143&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-11 N1 - Date created - 1996-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. AN - 78150876; 8667426 AB - Arrest of the cell cycle in G2 phase following DNA damage helps protect cell viability by allowing time for DNA repair before entry into mitosis (M phase). Abrogation of G2 arrest sensitizes cells to the effects of DNA-damaging agents. UCN-01 (7-hydroxystaurosporine), a protein kinase C inhibitor that may block G2 checkpoint regulation, has been reported to enhance the cytotoxicity of mitomycin C, a known DNA-damaging agent. We studied the effect of UCN-01 on G2 checkpoint control in human lymphoma CA46 cells, whose sensitivity to various DNA-damaging agents and G2 response to DNA damage have been characterized. We also assessed the ability of UCN-01 to enhance the cytotoxicity of gamma irradiation in CA46 cells and human colon carcinoma HT-29 cells, both of which are mutant for p53 function. The influence of p53 function on UCN-01-mediated abrogation of the G2 checkpoint and enhancement of DNA-damaging agent cytotoxicity was studied in transfected human breast carcinoma MCF-7 cells that either expressed or did not express the human papillomavirus type-16 E6 protein. MCF-7 cells have normal p53 function, and the E6 protein binds p53 protein and promotes its destruction. The effect of UCN-01 on cell cycle arrest induced by gamma irradiation was studied in CA46 cells and in transfected MCF-7 cells by use of flow cytometry. A histone H1 phosphorylation assay was employed to measure cyclin B1/Cdc2 kinase activity in extracts derived from irradiated and nonirradiated CA46 cells that had been either treated or not treated with UCN-01; the phosphorylation status of Cdc2 kinase protein in the same extracts was determined by use of western blotting. The effect of UCN-01 on the cytotoxicity of gamma irradiation in CA46 and HT-29 cells was determined by use of MTT (thiazolyl blue) and clonogenic (colony-forming) assays, respectively; a clonogenic assay was also used to measure the effect of UCN-01 on the cytotoxicity of cisplatin in transfected and nontransfected MCF-7 cells. G2 arrest induced in CA46 cells by gamma irradiation was minibited by treatment with UCN-01 in a dose-dependent manner; arrest in G2 was completely abrogated by exposure to 300 nM UCN-01. Biochemical markers indicative of the G2/M transition, including the activation of cyclin B1/Cdc2 kinase and the suppression of Cdc2 threonine-14 and tyrosine-15 phosphorylation, were detected in irradiated cells treated with UCN-01. UCN-01 enhanced the cytotoxicity of gamma irradiation in CA46 and HT-29 cells. MCF-7 cells with functional p53 protein were more resistant to G2 checkpoint abrogation by UCN-01 than MCF-7 cells with disrupted p53 function. UCN-01 markedly enhanced the cell-killing activity of cisplatin in MCF-7 cells defective for p53 function. UCN-01 is a potent abrogator of G2 checkpoint control in cancer cells with disrupted p53 function. UCN-01 might be capable of enhancing the effectiveness of DNA-damaging agents in the treatment of tumors with cells lacking normal p53 function. JF - Journal of the National Cancer Institute AU - Wang, Q AU - Fan, S AU - Eastman, A AU - Worland, P J AU - Sausville, E A AU - O'Connor, P M AD - Laboratory of Biological Chemistry, Division of Basic Science, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/07/17/ PY - 1996 DA - 1996 Jul 17 SP - 956 EP - 965 VL - 88 IS - 14 SN - 0027-8874, 0027-8874 KW - Alkaloids KW - 0 KW - Antineoplastic Agents KW - CCNB1 protein, human KW - Cyclin B KW - Cyclin B1 KW - Cyclins KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Staurosporine KW - H88EPA0A3N KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - CDC2 Protein Kinase -- radiation effects KW - Radiation Dosage KW - Immunoblotting KW - Gamma Rays KW - Cyclins -- drug effects KW - Humans KW - Precipitin Tests KW - Staurosporine -- analogs & derivatives KW - Cyclins -- radiation effects KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Colonic Neoplasms -- drug therapy KW - Cisplatin -- pharmacology KW - CDC2 Protein Kinase -- drug effects KW - Mitotic Index KW - Flow Cytometry KW - Cell Survival -- radiation effects KW - Drug Synergism KW - Mutation KW - Burkitt Lymphoma -- drug therapy KW - G2 Phase -- radiation effects KW - G2 Phase -- drug effects KW - Genes, p53 -- genetics KW - Cell Division -- drug effects KW - Alkaloids -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Cell Division -- genetics KW - Cell Division -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78150876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=UCN-01%3A+a+potent+abrogator+of+G2+checkpoint+function+in+cancer+cells+with+disrupted+p53.&rft.au=Wang%2C+Q%3BFan%2C+S%3BEastman%2C+A%3BWorland%2C+P+J%3BSausville%2C+E+A%3BO%27Connor%2C+P+M&rft.aulast=Wang&rft.aufirst=Q&rft.date=1996-07-17&rft.volume=88&rft.issue=14&rft.spage=956&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-07 N1 - Date created - 1996-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Telomere reduction and telomerase inactivation during neuronal cell differentiation. AN - 78161261; 8702416 AB - Telomerase adds (TTAGGG)n hexanucleotide repeats to the ends of mammalian telomeres. This compensates for telomeric loss with successive rounds of cellular replication. Telomerase activity is detected in many neoplastic cells, but not in most normal somatic cells. To determine whether telomeric length and telomerase activity are associated with cellular differentiation, we measured telomeric lengths and telomerase activity in embryonic NT2 precursor cells prior to and following differentiation into post mitotic hNT neurons. This system allows for studies in a direct neuronal cell lineage and, thus, provides a unique model for studying the role of neuronal telomerase activity. Our results show that telomerase activity was present in precursor cells, but not in neuronal cells. Telomeres were consistently longer in NT2 cells than in hNT cells. These results suggest that changes in telomeric length and loss of telomerase activity play a role in neuronal cellular differentiation. JF - Biochemical and biophysical research communications AU - Kruk, P A AU - Balajee, A S AU - Rao, K S AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1996/07/16/ PY - 1996 DA - 1996 Jul 16 SP - 487 EP - 492 VL - 224 IS - 2 SN - 0006-291X, 0006-291X KW - DNA Primers KW - 0 KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Teratocarcinoma KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Cell Line KW - Telomerase -- antagonists & inhibitors KW - Telomere -- physiology KW - Neurons -- cytology KW - Neurons -- enzymology KW - Cell Differentiation KW - Telomerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78161261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Telomere+reduction+and+telomerase+inactivation+during+neuronal+cell+differentiation.&rft.au=Kruk%2C+P+A%3BBalajee%2C+A+S%3BRao%2C+K+S%3BBohr%2C+V+A&rft.aulast=Kruk&rft.aufirst=P&rft.date=1996-07-16&rft.volume=224&rft.issue=2&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-30 N1 - Date created - 1996-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calculating tumor incidence rates in stochastic models of carcinogenesis. AN - 78180165; 8768218 AB - Multistage models of carcinogenesis are increasingly used in the estimation of risks from exposure to environmental agents. The two-stage model of carcinogenesis is routinely used because it agrees with much of the existing tumor incidence data, parallels the biological two-stage model, and has much of its mathematical details derived. However, recent findings on the mechanisms of carcinogenesis has led researchers to believe that there are a greater number of stages and a more complex structure to these models than a single pathway. In this paper, a method for readily computing tumor incidence rates for arbitrarily complex multistage models is derived. The formulas for the two-stage model with time-varying rates are given explicitly. Simple rules for more complicated models are given, and computer code able to implement these formulas are provided. JF - Mathematical biosciences AU - Portier, C J AU - Kopp-Schneider, A AU - Sherman, C D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1996/07/15/ PY - 1996 DA - 1996 Jul 15 SP - 129 EP - 146 VL - 135 IS - 2 SN - 0025-5564, 0025-5564 KW - Index Medicus KW - Animals KW - Humans KW - Stochastic Processes KW - Models, Biological KW - Mathematics KW - Cocarcinogenesis KW - Neoplasms -- epidemiology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78180165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mathematical+biosciences&rft.atitle=Calculating+tumor+incidence+rates+in+stochastic+models+of+carcinogenesis.&rft.au=Portier%2C+C+J%3BKopp-Schneider%2C+A%3BSherman%2C+C+D&rft.aulast=Portier&rft.aufirst=C&rft.date=1996-07-15&rft.volume=135&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Mathematical+biosciences&rft.issn=00255564&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-19 N1 - Date created - 1996-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of various nitric oxide-donor agents on hydrogen peroxide-mediated toxicity: a direct correlation between nitric oxide formation and protection. AN - 78168044; 8660704 AB - The role that nitric oxide (NO) plays in various degenerative and disease states has remained a mystery since its discovery as a biological messenger, prompting the question, "NO, friend or foe?" Some reports have suggested that NO is cytotoxic, and yet others have shown that it possesses protective properties against reactive oxygen species (ROS). Many studies have used various NO donor complexes arriving at seemingly different conclusions. This report will address the effects of various NO donor compounds on ROS-mediated toxicity. Consistent with our previous study, the NO donor compound, DEA/NO ((C2H5)2N[N(O)NO]-Na+), afforded protection against hydrogen peroxide-mediated cytotoxicity in V79 Chinese hamster lung fibroblasts at concentrations as low as 10 microM DEA/NO. Furthermore, a survey of other NO donor complexes revealed that some either protected or potentiated hydrogen peroxide-mediated cytotoxicity. 3-Morpholinosynodiomine.HCl (SIN-1) and sodium nitroprusside (SNP) enhanced hydrogen peroxide-mediated cytotoxicity, while S-nitrosoglutathione (GSNO), and S-nitroso-N-acetylpenicillamine (SNAP) afforded protection. Electrochemical detection of NO in cell culture medium revealed that neither 1000 microM SIN-1 nor SNP yielded appreciable NO concentrations (1.0 microM. Thus, a direct correlation between inhibition of hydrogen peroxide cytotoxicity and NO production was observed: agents that release NO during hydrogen peroxide treatment afford significant protection, whereas agents that do not release NO do not protect. Similar results were observed for NO donors studied when hypoxanthinesolidusxanthine oxidase was used as the source for ROS, although the S-nitrosothiol agents were much less protective. These results demonstrate that NO possesses properties which protect against ROS toxicity and demonstrate how the use of different NO donor compounds can lead to different conclusions about the role that NO can play in the cytotoxicity of ROS. JF - Archives of biochemistry and biophysics AU - Wink, D A AU - Cook, J A AU - Pacelli, R AU - DeGraff, W AU - Gamson, J AU - Liebmann, J AU - Krishna, M C AU - Mitchell, J B AD - Tumor Biology Section, National Cancer Institute, Bethesda, Maryland, 20892, USA. Y1 - 1996/07/15/ PY - 1996 DA - 1996 Jul 15 SP - 241 EP - 248 VL - 331 IS - 2 SN - 0003-9861, 0003-9861 KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Animals KW - Cricetulus KW - Dose-Response Relationship, Drug KW - Cell Line KW - Cricetinae KW - Hydrogen Peroxide -- toxicity KW - Cell Survival -- drug effects KW - Nitric Oxide -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78168044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=The+effect+of+various+nitric+oxide-donor+agents+on+hydrogen+peroxide-mediated+toxicity%3A+a+direct+correlation+between+nitric+oxide+formation+and+protection.&rft.au=Wink%2C+D+A%3BCook%2C+J+A%3BPacelli%2C+R%3BDeGraff%2C+W%3BGamson%2C+J%3BLiebmann%2C+J%3BKrishna%2C+M+C%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1996-07-15&rft.volume=331&rft.issue=2&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-28 N1 - Date created - 1996-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Advances in the management of AIDS-related cytomegalovirus retinitis. AN - 78143769; 8678367 AB - Cytomegalovirus (CMV) retinitis, a common complication of the acquired immunodeficiency syndrome (AIDS), is increasing in frequency as patients infected with the human immunodeficiency virus (HIV) live longer. In recent years, the lifetime risk for CMV disease in HIV-infected persons has increased from 24.9% to 44.9%. Cytomegalovirus retinitis is usually diagnosed clinically: Almost all patients are CMV seropositive and have CD4+ counts less than 50 cells/mm3. Specific diagnostic tests that use antigen detection or quantitation of circulating nucleic acid to detect CMV are being developed, but they have not been validated for routine clinical use. Such tests would help predict disease, diagnose acute retinitis, and monitor therapy. Therapy with systemic agents, including intravenous ganciclovir, intravenous foscarnet, and intravenous cidofovir, is effective. However, it is cumbersome, costly, and associated with considerable toxicity, therapy encouraging investigation of other therapeutic approaches. Intravitreous injections with antiviral agents are effective, but the short half-life of available agents makes these injections inconvenient. Intraocular implants that slowly release ganciclovir have been effective for both acute therapy and long-term maintenance, but they need to be directly compared with intravenous and oral regimens to determine which regimen will optimally maximize convenience, preserve vision, and improve survival. Cytomegalovirus retinitis could be prevented by improved antiretroviral therapies or by immune-based therapies that would prolong the time during which patients remain immunocompetent. Once patients become immunologically susceptible to CMV end-organ disease (when their CD4+ counts decrease to < 50 cells/ mm3), specific chemotherapy with oral ganciclovir is promising, but the cost, inconvenience, toxicity, and conflicting reports of efficacy associated with this strategy mean that it needs careful assessment before it can be considered standard treatment. Management of CMV retinitis is on the verge of major changes. In the next few years, improvements in diagnostic, therapeutic, and preventive tools should reduce morbidity and mortality from this disease. JF - Annals of internal medicine AU - Masur, H AU - Whitcup, S M AU - Cartwright, C AU - Polis, M AU - Nussenblatt, R AD - Critical Care Medicine Department, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/07/15/ PY - 1996 DA - 1996 Jul 15 SP - 126 EP - 136 VL - 125 IS - 2 SN - 0003-4819, 0003-4819 KW - Antiviral Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Antiviral Agents -- therapeutic use KW - Diagnosis, Differential KW - Humans KW - Vision Screening KW - Prognosis KW - Cytomegalovirus Infections -- drug therapy KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Retinitis -- drug therapy KW - Retinitis -- virology KW - Retinitis -- diagnosis KW - AIDS-Related Opportunistic Infections -- diagnosis KW - Cytomegalovirus Infections -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78143769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Anti-p53+antibodies+in+sera+from+patients+with+chronic+obstructive+pulmonary+disease+can+predate+a+diagnosis+of+cancer.&rft.au=Trivers%2C+G+E%3BDe+Benedetti%2C+V+M%3BCawley%2C+H+L%3BCaron%2C+G%3BHarrington%2C+A+M%3BBennett%2C+W+P%3BJett%2C+J+R%3BColby%2C+T+V%3BTazelaar%2C+H%3BPairolero%2C+P%3BMiller%2C+R+D%3BHarris%2C+C+C&rft.aulast=Trivers&rft.aufirst=G&rft.date=1996-10-01&rft.volume=2&rft.issue=10&rft.spage=1767&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-13 N1 - Date created - 1996-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 1996 Jul 15;125(2):144-5 [8678370] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Atm-deficient mice: a paradigm of ataxia telangiectasia. AN - 78166905; 8689683 AB - A murine model of ataxia telangiectasia was created by disrupting the Atm locus via gene targeting. Mice homozygous for the disrupted Atm allele displayed growth retardation, neurologic dysfunction, male and female infertility secondary to the absence of mature gametes, defects in T lymphocyte maturation, and extreme sensitivity to gamma-irradiation. The majority of animals developed malignant thymic lymphomas between 2 and 4 months of age. Several chromosomal anomalies were detected in one of these tumors. Fibroblasts from these mice grew slowly and exhibited abnormal radiation-induced G1 checkpoint function. Atm-disrupted mice recapitulate the ataxia telangiectasia phenotype in humans, providing a mammalian model in which to study the pathophysiology of this pleiotropic disorder. JF - Cell AU - Barlow, C AU - Hirotsune, S AU - Paylor, R AU - Liyanage, M AU - Eckhaus, M AU - Collins, F AU - Shiloh, Y AU - Crawley, J N AU - Ried, T AU - Tagle, D AU - Wynshaw-Boris, A AD - Laboratory of Genetic Disease Research, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/07/12/ PY - 1996 DA - 1996 Jul 12 SP - 159 EP - 171 VL - 86 IS - 1 SN - 0092-8674, 0092-8674 KW - Cell Cycle Proteins KW - 0 KW - DNA-Binding Proteins KW - Proteins KW - Tumor Suppressor Proteins KW - ATM protein, human KW - EC 2.7.11.1 KW - Ataxia Telangiectasia Mutated Proteins KW - Atm protein, mouse KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Animals KW - Germ Cells -- physiology KW - Neurologic Examination KW - Mutation -- immunology KW - Disease Models, Animal KW - Mice KW - Fibroblasts -- cytology KW - Dose-Response Relationship, Radiation KW - Mutation -- radiation effects KW - Germ Cells -- cytology KW - Fibroblasts -- physiology KW - Mice, Mutant Strains KW - Leucine Zippers -- genetics KW - Mutation -- physiology KW - Lymphoma -- genetics KW - Thymus Neoplasms -- genetics KW - Cell Cycle -- genetics KW - Male KW - Cell Division -- genetics KW - Female KW - Ataxia Telangiectasia -- genetics KW - Ataxia Telangiectasia -- physiopathology KW - Ataxia Telangiectasia -- immunology KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78166905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Drug+interactions+in+patients+infected+with+human+immunodeficiency+virus.&rft.au=Piscitelli%2C+S+C%3BFlexner%2C+C%3BMinor%2C+J+R%3BPolis%2C+M+A%3BMasur%2C+H&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1996-10-01&rft.volume=23&rft.issue=4&rft.spage=685&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-26 N1 - Date created - 1996-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanisms of cocaine addiction. AN - 78118637; 8649475 JF - The New England journal of medicine AU - Leshner, A I AD - National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1996/07/11/ PY - 1996 DA - 1996 Jul 11 SP - 128 EP - 129 VL - 335 IS - 2 SN - 0028-4793, 0028-4793 KW - Dopamine Agonists KW - 0 KW - Receptors, Dopamine KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Dopamine Agonists -- pharmacology KW - Humans KW - Dopamine -- metabolism KW - Vaccination KW - Cocaine -- pharmacology KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78118637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Molecular+mechanisms+of+cocaine+addiction.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=1996-07-11&rft.volume=335&rft.issue=2&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-25 N1 - Date created - 1996-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An improved circularly permuted interleukin 4-toxin is highly cytotoxic to human renal cell carcinoma cells. Introduction of gamma c chain in RCC cells does not improve sensitivity. AN - 78170254; 8660841 AB - We have previously demonstrated that a chimeric protein composed of human IL-4 and Pseudomonas exotoxin, termed IL4-PE4E, is cytotoxic to primary cells derived from human renal cell carcinoma (RCC). To improve the cytotoxicity of IL4-toxins such as IL4-PE4E and IL4-PE38KDEL to IL-4 receptor (IL-4R) positive tumor cells, a circularly permuted chimeric toxin was prepared by fusing a truncated PE gene encoding PE38KDEL 3' to a circularly permuted IL-4 mutant gene encoding IL4 amino acids 38-129, the linker GGNGG, and IL4 amino acids 1-37. The resulting chimeric protein, termed IL4(38-37)-PE38KDEL, was tested on five RCC cell lines and its cytotoxicity was compared to that of the native IL4-toxins IL4-PE4E and IL4-PE38KDEL. IL4(38-37)-PE38KDEL was found to be 5 to 10 times more cytotoxic to all cell cultures tested compared to either native IL4-toxin. The cytotoxic activity of IL4(38-37)-PE38KDEL was competible by excess IL-4 and was confirmed by clonogenic assay. IL4(38-37)-PE38KDEL bound to IL-4R on RCC cells with 6- to 12-fold higher affinity than IL4-PE38KDEL or IL4-PE4E. RCC tumor cells were found to lack the common gamma chain (gamma c) of the IL-4R reported to be present on immune cells. The stable transfection of RCC cells with the gamma c chain gene did not significantly change their sensitivity to IL4(38-37)-PE38KDEL. Taken together, our results indicate that the CPIL4-toxin IL4(38-37)-PE38KDEL is highly cytotoxic to human RCC cells due to increased binding affinity to IL-4R while it is not cytotoxic or slightly cytotoxic to T and B cells, monocytic cell lines, and fresh resting or activated bone marrow-derived cells. The gamma c does not seem to increase the internalization rate and/or processing of IL4-toxins in RCC cells. CPIL4-toxin may be a useful agent for the treatment of human RCC. JF - Cellular immunology AU - Puri, R K AU - Leland, P AU - Obiri, N I AU - Husain, S R AU - Mule, J AU - Pastan, I AU - Kreitman, R J AD - Laboratory of Molecular Tumor Biology, Food and Drug Administration, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/07/10/ PY - 1996 DA - 1996 Jul 10 SP - 80 EP - 86 VL - 171 IS - 1 SN - 0008-8749, 0008-8749 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Receptors, Interleukin-2 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - Interleukin-4 KW - 207137-56-2 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Bone Marrow Cells KW - Pseudomonas aeruginosa -- immunology KW - Transfection -- immunology KW - Tumor Cells, Cultured KW - Humans KW - Receptors, Interleukin-2 -- biosynthesis KW - Bone Marrow -- metabolism KW - Flow Cytometry KW - Colony-Forming Units Assay KW - Protein Binding -- immunology KW - Interleukin-4 -- genetics KW - Kidney Neoplasms -- genetics KW - Exotoxins -- genetics KW - Recombinant Fusion Proteins -- immunology KW - Interleukin-4 -- immunology KW - Recombinant Fusion Proteins -- toxicity KW - Bacterial Toxins -- immunology KW - Bacterial Toxins -- genetics KW - Interleukin-4 -- toxicity KW - Exotoxins -- toxicity KW - Bacterial Toxins -- toxicity KW - Carcinoma, Renal Cell -- genetics KW - Carcinoma, Renal Cell -- immunology KW - Kidney Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78170254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+immunology&rft.atitle=An+improved+circularly+permuted+interleukin+4-toxin+is+highly+cytotoxic+to+human+renal+cell+carcinoma+cells.+Introduction+of+gamma+c+chain+in+RCC+cells+does+not+improve+sensitivity.&rft.au=Puri%2C+R+K%3BLeland%2C+P%3BObiri%2C+N+I%3BHusain%2C+S+R%3BMule%2C+J%3BPastan%2C+I%3BKreitman%2C+R+J&rft.aulast=Puri&rft.aufirst=R&rft.date=1996-07-10&rft.volume=171&rft.issue=1&rft.spage=80&rft.isbn=&rft.btitle=&rft.title=Cellular+immunology&rft.issn=00088749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-22 N1 - Date created - 1996-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differentiation of mouse keratinocytes is accompanied by PKC-dependent changes in AP-1 proteins. AN - 78155425; 8700543 AB - The conversion of cultured basal keratinocytes to the spinous and granular cell phenotypes seen in the skin can be stimulated by raising the levels of extracellular calcium. Here we show that AP-1 DNA binding activity is very low in primary cultures of basal keratinocytes, but that this activity is induced 24-48 h after increasing the concentration of extracellular calcium from 0.05 to 0.12 mM. As such, the induction of AP-1 DNA binding activity correlates with events occurring during the terminal stages of keratinocyte differentiation. Calcium-induced AP-1 DNA binding complexes consist of Fra-1, Fra-2, c-Jun, JunB and JunD and are independent of c-Fos, since the induction of DNA binding activity and the composition of the AP-1 binding complexes are identical in differentiating keratinocytes derived from c-fos null and wild type mice. The formation of calcium-induced AP-1 binding complexes is regulated by protein kinase C (PKC) and requires a functional PKCalpha isozyme, as determined through pharmacological down-modulation of specific PKC isozymes in differentiating keratinocytes. Moreover, PKC activation is required for the increased expression of Fra-2, JunB and JunD in the nucleus of differentiating cells in vitro. This observation provides a link between the obligate activation of PKC during keratinocyte differentiation and the nuclear response required to alter gene expression. In vivo expression patterns suggest that the predominant AP-1 heterodimer in the granular layer consists of Fra-2 and JunB while a JunD and Fra-1 complex predominates the spinous layer of mouse epidermis. These findings suggest distinct functions for different AP-1 proteins in the regulation of events related to keratinocyte maturation. JF - Oncogene AU - Rutberg, S E AU - Saez, E AU - Glick, A AU - Dlugosz, A A AU - Spiegelman, B M AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/07/04/ PY - 1996 DA - 1996 Jul 04 SP - 167 EP - 176 VL - 13 IS - 1 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - Enzyme Inhibitors KW - Fos-Related Antigen-2 KW - Fosl2 protein, mouse KW - Indoles KW - Macromolecular Substances KW - Maleimides KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Transcription Factors KW - fos-related antigen 1 KW - DNA KW - 9007-49-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Calcium -- pharmacology KW - Proto-Oncogene Proteins c-jun -- biosynthesis KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Proto-Oncogene Proteins c-fos -- genetics KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Cell Differentiation -- drug effects KW - Maleimides -- pharmacology KW - Proto-Oncogene Proteins c-fos -- biosynthesis KW - DNA -- metabolism KW - Mice KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Base Sequence KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Enzyme Inhibitors -- pharmacology KW - Proto-Oncogene Proteins c-jun -- genetics KW - Genes, fos KW - Indoles -- pharmacology KW - Transcription Factor AP-1 -- metabolism KW - Keratinocytes -- drug effects KW - Keratinocytes -- cytology KW - Protein Kinase C -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78155425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Differentiation+of+mouse+keratinocytes+is+accompanied+by+PKC-dependent+changes+in+AP-1+proteins.&rft.au=Rutberg%2C+S+E%3BSaez%2C+E%3BGlick%2C+A%3BDlugosz%2C+A+A%3BSpiegelman%2C+B+M%3BYuspa%2C+S+H&rft.aulast=Rutberg&rft.aufirst=S&rft.date=1996-07-04&rft.volume=13&rft.issue=1&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-04 N1 - Date created - 1996-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of v-abl uniquely cooperates with c-myc dysregulation in induction of plasma cell tumors, bypassing the need for T-lymphocytic help and overcoming T-lymphocytic interference. AN - 78137921; 8690515 AB - We have investigated the effects of T lymphocytes on induction of mouse plasma cell tumors. We show that ABL-MYC, a plasmacytomagenic retrovirus that constitutively expresses v-abl and c-myc, is able to induce plasmacytomas in 100% of athymic BALB/c mice, with or without intraperitoneal pristane pretreatment. Other induction regimens are ineffective under these conditions, indicating that the combination of v-abl and c-myc oncogenes is uniquely able to transform plasma cells in mice that are deficient in T lymphocytes. Furthermore, in the absence of pristane, ABL-MYC-infected athymic congenics developed plasmacytomas in half the time required for euthymic BALB/c mice, suggesting that T lymphocytes can have a negative effect and can retard, but not totally inhibit, the outgrowth of plasmacytomas. This phenomenon could not be appreciated in other regimens of plasmacytoma induction, because only ABL-MYC is sufficient to induce plasmacytomas in athymic mice or in euthymic mice in the absence of pristane pretreatment. JF - International journal of cancer AU - Weissinger, E M AU - Byrd, L G AU - Henderson, D W AU - Mushinski, J F AD - Laboratory of Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/07/03/ PY - 1996 DA - 1996 Jul 03 SP - 142 EP - 147 VL - 67 IS - 1 SN - 0020-7136, 0020-7136 KW - Interleukin-6 KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Mice, Nude KW - Mice KW - Interleukin-6 -- pharmacology KW - Immunoglobulin Class Switching KW - Terpenes -- pharmacology KW - Mice, Inbred BALB C KW - Plasmacytoma -- etiology KW - Plasmacytoma -- genetics KW - Genes, myc KW - Plasmacytoma -- pathology KW - T-Lymphocytes -- physiology KW - Genes, abl UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78137921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Overexpression+of+v-abl+uniquely+cooperates+with+c-myc+dysregulation+in+induction+of+plasma+cell+tumors%2C+bypassing+the+need+for+T-lymphocytic+help+and+overcoming+T-lymphocytic+interference.&rft.au=Weissinger%2C+E+M%3BByrd%2C+L+G%3BHenderson%2C+D+W%3BMushinski%2C+J+F&rft.aulast=Weissinger&rft.aufirst=E&rft.date=1996-07-03&rft.volume=67&rft.issue=1&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-29 N1 - Date created - 1996-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant single-chain and disulfide-stabilized Fv-immunotoxins that cause complete regression of a human colon cancer xenograft in nude mice. AN - 78137919; 8690511 AB - Monoclonal antibody (MAb) 55.1 specifically recognizes an antigen on the surface of human colon adenocarcinoma cells. We constructed recombinant immunotoxins composed of the heavy- and light-chain variable regions of MAb 55.1 fused to a recombinant form of Pseudomonas exotoxin (PE). The heavy- and light-chain variable regions are stabilized by 2 means. One is by a flexible peptide linker to form a single-chain antigen binding protein (scFv) and the second by an interchain disulfide bond engineered between structurally conserved framework regions. These are termed disulfide stabilized Fvs (dsFv). The 2 Fv forms are fused to truncated forms of PE lacking the cell binding domain. The recombinant scFv- and dsFv-immunotoxins were expressed in E. coli and purified to near homogeneity. The scFv- and dsFv-immunotoxins were shown to be specifically cytotoxic to human colon adenocarcinoma cell lines. The scFv-immunotoxin containing PE38KDEL was more active than the immunotoxin containing PE38 with the native carboxyl terminus (REDLK). However, the PE38KDEL immunotoxin is about 2-fold more toxic in mice, and therefore it does not appreciably increase the therapeutic window in mice. Intravenous administration of the scFv- and dsFv- recombinant immunotoxins caused complete regression of a human colon carcinoma (Colo205) growing subcutaneously in immunodeficient mice. The dsFv-immunotoxin has better antitumor activity compared with its scFv-immunotoxin counterpart. JF - International journal of cancer AU - Reiter, Y AU - Wright, A F AU - Tonge, D W AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Insitutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1996/07/03/ PY - 1996 DA - 1996 Jul 03 SP - 113 EP - 123 VL - 67 IS - 1 SN - 0020-7136, 0020-7136 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunotoxins KW - Recombinant Proteins KW - Virulence Factors KW - immunoglobulin Fv KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Amino Acid Sequence KW - Mice, Inbred BALB C KW - Recombinant Proteins -- therapeutic use KW - Female KW - Antibodies, Monoclonal -- therapeutic use KW - Immunoglobulin Fragments -- therapeutic use KW - Colonic Neoplasms -- therapy KW - Immunotoxins -- therapeutic use KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78137919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Recombinant+single-chain+and+disulfide-stabilized+Fv-immunotoxins+that+cause+complete+regression+of+a+human+colon+cancer+xenograft+in+nude+mice.&rft.au=Reiter%2C+Y%3BWright%2C+A+F%3BTonge%2C+D+W%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1996-07-03&rft.volume=67&rft.issue=1&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-29 N1 - Date created - 1996-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging. AN - 85253024; pmid-8660125 AB - BACKGROUND: There are significant age and sex effects in cognitive ability and brain disease. However, sex differences in aging of human brain areas associated with nonreproductive behavior have not been extensively studied. We hypothesized that there would be significant sex differences in aging of brain areas that subserve speech, visuospatial, and memory function. METHODS: We investigated sex differences in the effect of aging on human brain morphometry by means of volumetric magnetic resonance imaging and on regional cerebral metabolism for glucose by positron emission tomography. In the magnetic resonance imaging study, we examined 69 healthy right-handed subjects (34 women and 35 men), divided into young (age range, 20 to 35 years) and old (60 to 85 years) groups. In the positron emission tomography study, we investigated 120 healthy right-handed subjects (65 women and 55 men) aged 21 to 91 years. RESULTS: In the magnetic resonance imaging study, age-related volume loss was significantly greater in men than women in whole brain and frontal and temporal lobes, whereas it was greater in women than men in hippocampus and parietal lobes. In the positron emission tomography study, significant sex differences existed in the effect of age on regional brain metabolism, and asymmetry of metabolism, in the temporal and parietal lobes, Broca's area, thalamus, and hippocampus. CONCLUSIONS: We found significant sex differences in aging of brain areas that are essential to higher cognitive functioning. Thus, our findings may explain some of the age-sex differences in human cognition and response to brain injury and disease. JF - Archives of General Psychiatry AU - Murphy, D G AU - DeCarli, C AU - McIntosh, A R AU - Daly, E AU - Mentis, M J AU - Pietrini, P AU - Szczepanik, J AU - Schapiro, M B AU - Grady, C L AU - Horwitz, B AU - Rapoport, S I AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Md, USA. PY - 1996 SP - 585 EP - 594 VL - 53 IS - 7 SN - 0003-990X, 0003-990X KW - Sex Factors KW - Hippocampus KW - Human KW - Aging KW - Brain KW - Glucose KW - Aged KW - Parietal Lobe KW - Cognition KW - Frontal Lobe KW - Memory KW - Aged, 80 and over KW - Adult KW - Temporal Lobe KW - Middle Age KW - Space Perception KW - Neuropsychological Tests KW - Speech KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Sex Characteristics KW - Tomography, Emission-Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85253024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+General+Psychiatry&rft.atitle=Sex+differences+in+human+brain+morphometry+and+metabolism%3A+an+in+vivo+quantitative+magnetic+resonance+imaging+and+positron+emission+tomography+study+on+the+effect+of+aging.&rft.au=Murphy%2C+D+G%3BDeCarli%2C+C%3BMcIntosh%2C+A+R%3BDaly%2C+E%3BMentis%2C+M+J%3BPietrini%2C+P%3BSzczepanik%2C+J%3BSchapiro%2C+M+B%3BGrady%2C+C+L%3BHorwitz%2C+B%3BRapoport%2C+S+I&rft.aulast=Murphy&rft.aufirst=D&rft.date=1996-07-01&rft.volume=53&rft.issue=7&rft.spage=585&rft.isbn=&rft.btitle=&rft.title=Archives+of+General+Psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A. AN - 85235930; pmid-8659547 AB - Waardenburg syndrome type 2 (WS2) is a dominantly inherited disorder characterized by a pigmentation anomaly and hearing impairment due to lack of melanocyte. Previous work has linked a subset of families with WS2 (WS2A) to the MITF gene that encodes a transcription factor with a basic-helix-loop-helix-leucine zipper (bHLH-Zip) motif and that is involved in melanocyte differentiation. Several splice-site and missense mutations have been reported in individuals affected with WS2A. In this report, we have identified two novel point mutations in the MITF gene in affected individuals from two different families with WS2A. The two mutations (C760--> T and C895--> T) create stop codons in exons 7 and 8, respectively. Corresponding mutant alleles predict the truncated proteins lacking HLH-Zip or Zip structure. To understand how these mutations cause WS2 in heterozygotes, we generated mutant MITF cDNAs and used them for DNA-binding and luciferase reporter assays. The mutated MITF proteins lose the DNA-binding activity and fail to transactivate the promoter of tyrosinase, a melanocyte-specific enzyme. However, these mutated proteins do not appear to interfere with the activity of wild-type MITF protein in these assays, indicating that they do not show a dominant-negative effect. These findings suggest that the phenotypes of the two families with WS2A in the present study are caused by loss-of-function mutations in one of the two alleles of the MITF gene, resulting in haploinsufficiency of the MITF protein, the protein necessary for normal development of melanocytes. JF - American Journal of Human Genetics AU - Nobukuni, Y AU - Watanabe, A AU - Takeda, K AU - Skarka, H AU - Tachibana, M AD - Clinical Neurogenetics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, USA. PY - 1996 SP - 76 EP - 83 VL - 59 IS - 1 SN - 0002-9297, 0002-9297 KW - Pedigree KW - Codon, Terminator KW - DNA-Binding Proteins KW - Human KW - Amino Acid Sequence KW - Leucine Zippers KW - Codon, Nonsense KW - DNA Probes KW - Base Sequence KW - Helix-Loop-Helix Motifs KW - Haplotypes KW - Transcription Factors KW - Genes, Dominant KW - Waardenburg's Syndrome KW - Molecular Sequence Data KW - Male KW - Female KW - Point Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85235930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Human+Genetics&rft.atitle=Analyses+of+loss-of-function+mutations+of+the+MITF+gene+suggest+that+haploinsufficiency+is+a+cause+of+Waardenburg+syndrome+type+2A.&rft.au=Nobukuni%2C+Y%3BWatanabe%2C+A%3BTakeda%2C+K%3BSkarka%2C+H%3BTachibana%2C+M&rft.aulast=Nobukuni&rft.aufirst=Y&rft.date=1996-07-01&rft.volume=59&rft.issue=1&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Human+Genetics&rft.issn=00029297&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Abnormal processing of visual motion in dyslexia revealed by functional brain imaging. AN - 85233037; pmid-8657305 AB - It is widely accepted that dyslexics have deficits in reading and phonological awareness, but there is increasing evidence that they also exhibit visual processing abnormalities that may be confined to particular portions of the visual system. In primate visual pathways, inputs from parvocellular or magnocellular layers of the lateral geniculate nucleus remain partly segregated in projections to extrastriate cortical areas specialized for processing colour and form versus motion. In studies of dyslexia, psychophysical and anatomical evidence indicate an anomaly in the magnocellular visual subsystem. To investigate the pathophysiology of dyslexia, we used functional magnetic resonance imaging (fMRI) to study visual motion processing in normal and dyslexic men. In all dyslexics, presentation of moving stimuli failed to produce the same task-related functional activation in area V5/MT (part of the magnocellular visual subsystem) observed in controls. In contrast, presentation of stationary patterns resulted in equivalent activations in V1/V2 and extrastriate cortex in both groups. Although previous studies have emphasized language deficits, our data reveal differences in the regional functional organization of the cortical visual system in dyslexia. JF - Nature AU - Eden, G F AU - VanMeter, J W AU - Rumsey, J M AU - Maisog, J M AU - Woods, R P AU - Zeffiro, T A AD - Section on Functional Brain Imaging NIMH, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 66 EP - 69 VL - 382 IS - 6586 SN - 0028-0836, 0028-0836 KW - Magnetic Resonance Imaging KW - Visual Cortex KW - Feasibility Studies KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Adult KW - Case-Control Studies KW - Dyslexia KW - Support, Non-U.S. Gov't KW - Male KW - Motion Perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85233037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Abnormal+processing+of+visual+motion+in+dyslexia+revealed+by+functional+brain+imaging.&rft.au=Eden%2C+G+F%3BVanMeter%2C+J+W%3BRumsey%2C+J+M%3BMaisog%2C+J+M%3BWoods%2C+R+P%3BZeffiro%2C+T+A&rft.aulast=Eden&rft.aufirst=G&rft.date=1996-07-01&rft.volume=382&rft.issue=6586&rft.spage=66&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - An investigation of semantic space in patients with schizophrenia. AN - 85219880; pmid-9375174 AB - There has been increasing interest in the semantic cognitive system in schizophrenia. Recent findings suggest a possible breakdown of semantic information processing in this disorder. The current study attempts to further examine semantic organization in schizophrenia. Twenty-eight chronic, early-onset schizophrenic patients and 32 controls were matched for premorbid intelligence and compared in their ability to spontaneously cluster exemplars from a specific category during a fluency task. Using multidimensional scaling and clustering techniques, 11 exemplars occurring most frequently in both groups were chosen for examination of their relative "proximity" during word generation. Patients with schizophrenia showed a less stable two-dimensional organization of exemplars and were less likely to group exemplars into subordinate clusters than were normals. These results suggest that semantic networks are disorganized in these patients. These findings may have some implications for the debate over the origin of "thought disorder" in schizophrenia. JF - Journal of the International Neuropsychological Society AU - Aloia, M S AU - Gourovitch, M L AU - Weinberger, D R AU - Goldberg, T E AD - Clinical Brain Disorders Branch, National Institute of Mental Health, Neuroscience Center at St. Elizabeths, Washington, DC 20032, USA. PY - 1996 SP - 267 EP - 273 VL - 2 IS - 4 SN - 1355-6177, 1355-6177 KW - Schizophrenia KW - Concept Formation KW - Verbal Behavior KW - Thinking KW - Human KW - Adult KW - Middle Age KW - Chronic Disease KW - Paired-Associate Learning KW - Male KW - Female KW - Schizophrenic Language KW - Semantics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85219880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+International+Neuropsychological+Society&rft.atitle=An+investigation+of+semantic+space+in+patients+with+schizophrenia.&rft.au=Aloia%2C+M+S%3BGourovitch%2C+M+L%3BWeinberger%2C+D+R%3BGoldberg%2C+T+E&rft.aulast=Aloia&rft.aufirst=M&rft.date=1996-07-01&rft.volume=2&rft.issue=4&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+International+Neuropsychological+Society&rft.issn=13556177&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Involuntary attentional shifts due to orientation differences. AN - 85186131; pmid-8710445 AB - We tested the ability of orientation differences to cause involuntary shifts of visual attention and found that these attentional shifts can occur in response to an orientation "pop-out" display. Texture-like cue stimuli consisting of discrete oriented bars, with either uniform orientation or containing a noninformative orthogonally oriented bar, were presented for a variable duration. Subsequent to or partially coincident with the cue stimulus was the target display of a localization or two-interval forced-choice task, followed by a mask display. Naive subjects consistently showed greater accuracy in trials with the target at the location of the orthogonal orientation compared with trials with uniformly oriented bars, with only 100 msec between the cue and mask onsets. Discriminating these orientations required a stimulus onset asynchrony (SOA) of 50-70 msec. The attentional facilitation is transient, in most cases absent with a cue-mask SOA of 250 msec [corrected]. These results suggest that the preattentive character of some texture discrimination tasks with SOAs of only 100 msec is vitiated by the involuntary attentional shifts that are caused by orientation differences. JF - Perception and Psychophysics AU - Joseph, J S AU - Optican, L M AD - Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. PY - 1996 SP - 651 EP - 665 VL - 58 IS - 5 SN - 0031-5117, 0031-5117 KW - Human KW - Adult KW - Field Dependence-Independence KW - Adolescent KW - Psychophysics KW - Perceptual Masking KW - Male KW - Female KW - Reaction Time KW - Discrimination Learning KW - Orientation KW - Pattern Recognition, Visual KW - Attention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85186131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Perception+and+Psychophysics&rft.atitle=Involuntary+attentional+shifts+due+to+orientation+differences.&rft.au=Joseph%2C+J+S%3BOptican%2C+L+M&rft.aulast=Joseph&rft.aufirst=J&rft.date=1996-07-01&rft.volume=58&rft.issue=5&rft.spage=651&rft.isbn=&rft.btitle=&rft.title=Perception+and+Psychophysics&rft.issn=00315117&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Understanding emotional prosody activates right hemisphere regions. AN - 85165062; pmid-8929174 AB - BACKGROUND: Defects in expressing or understanding the affective or emotional tone of speech (aprosodias) have been associated with right hemisphere dysfunction, while defects of propositional language have been linked to left hemisphere disease. The brain regions involved in recognition of emotional prosody in healthy subjects is less clear. OBJECTIVES: To investigate the brain regions involved in understanding emotional prosody and to determine whether these differ from those involved in understanding emotion based on propositional content. METHODS: We studied 13 healthy subjects using water labeled with radioactive oxygen 15 and positron emission tomography while they listened to 3 similar sets of spoken English sentences. In different tasks, their responses were based on the emotional propositional content, on the emotional intonation of the sentence (prosody), or on their ability to repeat the second word in the sentence (control). RESULTS: Understanding propositional content activated the prefrontal cortex bilaterally, on the left more than on the right. In contrast, responding to the emotional prosody activated the right prefrontal cortex. CONCLUSION: Neurologically healthy subjects activate right hemisphere regions during emotional prosody recognition. JF - Archives of Neurology AU - George, M S AU - Parekh, P I AU - Rosinsky, N AU - Ketter, T A AU - Kimbrell, T A AU - Heilman, K M AU - Herscovitch, P AU - Post, R M AD - Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Md, USA. PY - 1996 SP - 665 EP - 670 VL - 53 IS - 7 SN - 0003-9942, 0003-9942 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85165062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+Neurology&rft.atitle=Understanding+emotional+prosody+activates+right+hemisphere+regions.&rft.au=George%2C+M+S%3BParekh%2C+P+I%3BRosinsky%2C+N%3BKetter%2C+T+A%3BKimbrell%2C+T+A%3BHeilman%2C+K+M%3BHerscovitch%2C+P%3BPost%2C+R+M&rft.aulast=George&rft.aufirst=M&rft.date=1996-07-01&rft.volume=53&rft.issue=7&rft.spage=665&rft.isbn=&rft.btitle=&rft.title=Archives+of+Neurology&rft.issn=00039942&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A 2 week pair-fed study of early X-irradiation effects on rat major salivary gland function. AN - 78689752; 9015574 AB - Salivary gland function is affected shortly after irradiation of the head and neck. An intense oral mucositis develops after exposure and may interfere with ingestion. The effects of restricted food and water intake on the secretory output of rat major salivary glands were examined. Parotid and submandibular salivary output and body weight were measured in rats at 4, 8, 11 and 14 days after 15 Gy X-irradiation of the head and neck. Comparisons were made with two groups: a non-irradiated group with food and water intake restricted to that of the irradiated group (pair-fed), and a non-irradiated, ad libitum-fed control group. Parotid saliva output was significantly decreased in the irradiated group at 4, 8, and 11 days compared with the control group. The pair-fed rats also had significantly decreased parotid output at these time points and their parotid function did not differ from that of the irradiated animals. At 14 days, all three groups demonstrated similar parotid function. Submandibular salivary output was not affected to the same extent. Only at a single time point (11 days) was flow significantly decreased in the irradiated group. Total body weight was less than that of control rats for both the irradiated and pair-fed animals at all time points. These results suggest that the early effects of radiation on salivary glands are due, in part, to limited intake of food and water during the immediate post-irradiation period. JF - Archives of oral biology AU - Nagler, R M AU - Baum, B J AU - Fox, P C AD - Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-1190, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 713 EP - 717 VL - 41 IS - 7 SN - 0003-9969, 0003-9969 KW - Dentistry KW - Index Medicus KW - Rats KW - Body Weight KW - Animals KW - Analysis of Variance KW - Submandibular Gland -- radiation effects KW - Parotid Gland -- secretion KW - Saliva -- secretion KW - Rats, Wistar KW - Eating -- radiation effects KW - Secretory Rate KW - Parotid Gland -- radiation effects KW - Statistics, Nonparametric KW - Male KW - Submandibular Gland -- secretion KW - Salivary Glands -- radiation effects KW - Salivary Glands -- secretion KW - Salivation -- radiation effects KW - Nutrition Disorders -- etiology KW - Cranial Irradiation -- adverse effects KW - Nutrition Disorders -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78689752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+oral+biology&rft.atitle=A+2+week+pair-fed+study+of+early+X-irradiation+effects+on+rat+major+salivary+gland+function.&rft.au=Nagler%2C+R+M%3BBaum%2C+B+J%3BFox%2C+P+C&rft.aulast=Nagler&rft.aufirst=R&rft.date=1996-07-01&rft.volume=41&rft.issue=7&rft.spage=713&rft.isbn=&rft.btitle=&rft.title=Archives+of+oral+biology&rft.issn=00039969&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-28 N1 - Date created - 1997-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Colloid cyst xanthogranuloma of the third ventricle--a case report. AN - 78631643; 8972153 AB - A colloid xanthogranuloma of the third ventricle is described. Presenting features were symptoms of raised intracranial tensions and two episodes of seizures. The pathogenesis, clinical and radiological features, differential diagnosis and treatment of this rare benign lesion are briefly discussed. JF - Indian journal of pathology & microbiology AU - Kudesia, S AU - Das, S AU - Shankar, S K AU - Santosh, V AU - Reddy, A K AD - Dept. of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 221 EP - 223 VL - 39 IS - 3 SN - 0377-4929, 0377-4929 KW - Colloids KW - 0 KW - Index Medicus KW - Humans KW - Adolescent KW - Female KW - Xanthogranuloma, Juvenile -- pathology KW - Cysts -- pathology KW - Cerebral Ventricles -- pathology KW - Colloids -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78631643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+journal+of+pathology+%26+microbiology&rft.atitle=Colloid+cyst+xanthogranuloma+of+the+third+ventricle--a+case+report.&rft.au=Kudesia%2C+S%3BDas%2C+S%3BShankar%2C+S+K%3BSantosh%2C+V%3BReddy%2C+A+K&rft.aulast=Kudesia&rft.aufirst=S&rft.date=1996-07-01&rft.volume=39&rft.issue=3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Indian+journal+of+pathology+%26+microbiology&rft.issn=03774929&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-06 N1 - Date created - 1997-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational epidemiologic study design and application. AN - 78475267; 8887376 AB - Occupational epidemiologic investigations have provided, and will continue to provide, important information to understand environmental causes of disease. High-quality investigations designed to test hypotheses have several requirements. They must include valid quantitative assessments of exposure, some information on lifestyle risk factors, and include biologic monitoring and marker components whenever possible. Availability of these data allows a clear evaluation of potential confounders and biases, assessment of interaction among risk factors, and provides the opportunity to identify susceptible subgroups. JF - Occupational medicine (Philadelphia, Pa.) AU - Blair, A AU - Hayes, R B AU - Stewart, P A AU - Zahm, S H AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892-7364, USA. PY - 1996 SP - 403 EP - 419 VL - 11 IS - 3 SN - 0885-114X, 0885-114X KW - Index Medicus KW - Life Style KW - Environmental Monitoring KW - Reproducibility of Results KW - Risk Factors KW - Humans KW - Cohort Studies KW - Occupational Diseases -- etiology KW - Case-Control Studies KW - Occupational Diseases -- epidemiology KW - Epidemiological Monitoring KW - Bias (Epidemiology) KW - Epidemiologic Methods KW - Research Design KW - Occupational Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78475267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+medicine+%28Philadelphia%2C+Pa.%29&rft.atitle=Occupational+epidemiologic+study+design+and+application.&rft.au=Blair%2C+A%3BHayes%2C+R+B%3BStewart%2C+P+A%3BZahm%2C+S+H&rft.aulast=Blair&rft.aufirst=A&rft.date=1996-07-01&rft.volume=11&rft.issue=3&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Occupational+medicine+%28Philadelphia%2C+Pa.%29&rft.issn=0885114X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biliary tract cancers among textile and other workers in Shanghai, China. AN - 78377467; 8837680 AB - Using occupational data for more than 500 patients with cancers of the biliary tract (CBT) diagnosed between 1980 and 1984 in Shanghai, and employment information from the 1982 census for the Shanghai population, the associations between CBT and occupational categories were examined by standardized incidence ratios (SIR). Compared to the general population, risk was elevated by nearly 40% among textile workers (SIR for women = 137, 95% CI = 106-175 and SIR for men = 137, 95% CI = 76-217), consistent with other investigations linking CBT to textile work. Increased risks were observed also among waiters/ waitresses, male sanitation personnel and chemical workers, and female janitor and similar workers. Although causal inferences cannot be firmly drawn, our findings add to the limited evidence linking CBT to occupational exposures, especially in the textile industry. JF - American journal of industrial medicine AU - Chow, W H AU - Ji, B T AU - Dosemeci, M AU - McLaughlin, J K AU - Gao, Y T AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 36 EP - 40 VL - 30 IS - 1 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Registries KW - Occupational Exposure KW - Sanitation KW - Restaurants KW - Risk Factors KW - Humans KW - China -- epidemiology KW - Case-Control Studies KW - Population KW - Incidence KW - Male KW - Female KW - Chemical Industry KW - Biliary Tract Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Textile Industry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78377467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Biliary+tract+cancers+among+textile+and+other+workers+in+Shanghai%2C+China.&rft.au=Chow%2C+W+H%3BJi%2C+B+T%3BDosemeci%2C+M%3BMcLaughlin%2C+J+K%3BGao%2C+Y+T%3BFraumeni%2C+J+F&rft.aulast=Chow&rft.aufirst=W&rft.date=1996-07-01&rft.volume=30&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-30 N1 - Date created - 1997-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New diet (NTP-2000) for rats in the National Toxicology Program toxicity and carcinogenicity studies. AN - 78375162; 8812243 AB - Composition of diet may influence growth, diseases, tumor rates, and responses to chemical treatment. Since 1980 the NIH-07 open formula nonpurified diet has been the selected diet for the National Toxicology Program (NTP) toxicity and carcinogenicity studies in rodents. Studies with nonpurified experimental diets with lower protein and higher fat and fiber than the NIH-07 diet indicated that the diet for Fischer-344 (F344) rats in long-term studies could be modified to decrease the severity of chronic diseases and to decrease/delay the development of spontaneous tumors. Based on the results of these studies a new open formula nonpurified diet designated as NTP-2000 was formulated to contain approximately 14.5% protein, approximately 8.5% fat, and approximately 9.5% fiber. Corn, wheat, and wheat middlings contribute to about 60% of the ingredients; soybean meal, fish meal, and alfalfa meal are the additional sources of protein; purified cellulose, oat hulls, and alfalfa meal are the major sources of fiber; and soy oil and corn oil are the major sources of fat in the NTP-2000 diet. The Ca:P ratio and mineral and vitamin concentrations were reformulated based on AIN-93 and NRC-95 recommendations. The NIH-07 and the NTP-2000 diets were fed to groups of 6-week-old F344 rats for 13 weeks and evaluated for growth patterns, food and water consumptions, hematology and clinical chemistry parameters, and organ weights and pathological changes. Growth patterns and body weights were similar for both diets. Food consumptions were slightly higher and water consumptions were slightly lower for the groups fed NTP-2000 diet. There were no differences in hematological parameters between the groups fed the above diets. Serum levels of cholesterol, alkaline phosphatase, and 5' nucleotidase were slightly higher in groups fed the NTP-2000 diet possibly due to higher fat content of this diet. However, the serum triglyceride levels were slightly lower in groups fed the NTP-2000 diet and it may be related to higher fiber content of the NTP-2000 diet. The liver and kidney weights of the groups fed NTP-2000 diet were significantly lower possibly due to lower protein content of this diet and lower protein consumption associated changes in Phase I and Phase II drug metabolizing enzyme systems. The adrenal weights were also lower in groups fed the new diet. The NTP-2000 diet prevented nephrocalcinosis and decreased the severity of nephropathy and cardiomyopathy, the common lesions of F344 rats in 13-week studies. These results indicate that the NTP-2000 diet is adequate for growth and maintenance of rats and appears to prevent or decrease the severity of diet-associated lesions. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Rao, G N AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 102 EP - 108 VL - 32 IS - 1 SN - 0272-0590, 0272-0590 KW - Index Medicus KW - United States KW - Rats KW - Animals KW - Rats, Inbred F344 KW - National Institutes of Health (U.S.) KW - Male KW - Female KW - Animal Nutritional Physiological Phenomena KW - Animal Feed KW - Carcinogenicity Tests -- methods KW - Toxicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78375162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=New+diet+%28NTP-2000%29+for+rats+in+the+National+Toxicology+Program+toxicity+and+carcinogenicity+studies.&rft.au=Rao%2C+G+N&rft.aulast=Rao&rft.aufirst=G&rft.date=1996-07-01&rft.volume=32&rft.issue=1&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-20 N1 - Date created - 1996-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modified oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis. AN - 78358553; 8826554 AB - To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed. A before-after prospective observational pilot project. A federal research hospital. Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75-1.0 g/m2 had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting at 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4-16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion. The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated. To account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule, in which ondansetron is administered prior to chemotherapy. No emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the true rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/dexamethasone tablets and oral administration of ondansetron using the intravenous formula. This study suggests that a modified oral ondansetron/dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis. JF - The Annals of pharmacotherapy AU - Yarboro, C H AU - Wesley, R AU - Amantea, M A AU - Klippel, J H AU - Pucino, F AD - National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD 20892, USA. PY - 1996 SP - 752 EP - 755 VL - 30 IS - 7-8 SN - 1060-0280, 1060-0280 KW - Antiemetics KW - 0 KW - Antineoplastic Agents KW - Ondansetron KW - 4AF302ESOS KW - Dexamethasone KW - 7S5I7G3JQL KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Drug Therapy, Combination KW - Administration, Oral KW - Prospective Studies KW - Ondansetron -- administration & dosage KW - Dexamethasone -- adverse effects KW - Humans KW - Adult KW - Dexamethasone -- administration & dosage KW - Pilot Projects KW - Ondansetron -- adverse effects KW - Male KW - Female KW - Vomiting -- economics KW - Antiemetics -- administration & dosage KW - Vomiting -- drug therapy KW - Lupus Nephritis -- drug therapy KW - Vomiting -- chemically induced KW - Lupus Nephritis -- economics KW - Antiemetics -- economics KW - Antiemetics -- adverse effects KW - Cyclophosphamide -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78358553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+pharmacotherapy&rft.atitle=Modified+oral+ondansetron+regimen+for+cyclophosphamide-induced+emesis+in+lupus+nephritis.&rft.au=Yarboro%2C+C+H%3BWesley%2C+R%3BAmantea%2C+M+A%3BKlippel%2C+J+H%3BPucino%2C+F&rft.aulast=Yarboro&rft.aufirst=C&rft.date=1996-07-01&rft.volume=30&rft.issue=7-8&rft.spage=752&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+pharmacotherapy&rft.issn=10600280&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-13 N1 - Date created - 1996-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of human metabolites of CAI [5-amino-1-1(4'-chlorobenzoyl-3,5-dichlorobenzyl)-1,2,3-triazole- 4-carboxamide). AN - 78348306; 8818579 AB - The calcium influx inhibitor and cytostatic agent, 5-amino-1-1(4'-chlorobenzoyl-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide (CAI), is in phase I clinical trial for patients with refractory cancer. Additional chromatography peaks were observed during HPLC analysis of patient samples. Identification and characterization of physiological metabolites were undertaken using HPLC techniques developed for their purification from blood, pleural fluid, and urine samples. A hydrophobic metabolite, M1, was purified and functionally characterized. Structural analysis of the purified compound indicated that it is a 3,5-dichloro-4(p-chlorobenzoyl)-benzoic acid. Quantitative analysis of M1 concentration during CAI administration indicated that the rise in M1 concentration lagged behind that of CAI and persisted after CAI was no longer detectable. No clear relationship between CAI or M1 and either toxicity or efficacy was observed. Chromatography of patient blood and urine samples under conditions favoring hydrophilic metabolite detection suggested the presence of a glucuronide compound; this was also indicated by sample treatment with beta-glucuronidase. Attempts at purification did not yield a compound stable for structural analysis. The benzophenone metabolite, M1, was nonfunctional in assays of calcium influx inhibition or proliferation. No pharmacodynamic associations were observed for these metabolites, nor was there pharmacological activity of the M1 as an individual agent. These data suggest that CAI is processed into triazole and benzophenone moieties by phase I metabolism, and these metabolites or the parent compound may be conjugated for excretion by glucuronidation. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Soltis, M J AU - Yeh, H J AU - Cole, K A AU - Whittaker, N AU - Wersto, R P AU - Kohn, E C AD - Signal Transduction and Prevention Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 799 EP - 806 VL - 24 IS - 7 SN - 0090-9556, 0090-9556 KW - Antineoplastic Agents KW - 0 KW - Benzoates KW - Glucuronates KW - Triazoles KW - 3,5-dichloro-4-(4-chlorobenzoyl)benzoic acid KW - 179999-39-4 KW - Arachidonic Acid KW - 27YG812J1I KW - carboxyamido-triazole KW - 99519-84-3 KW - Glucuronidase KW - EC 3.2.1.31 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Benzoates -- metabolism KW - Cell Division -- drug effects KW - Lung -- metabolism KW - Glucuronates -- metabolism KW - Benzoates -- pharmacology KW - Arachidonic Acid -- metabolism KW - Chromatography, High Pressure Liquid KW - Exudates and Transudates -- metabolism KW - Calcium -- metabolism KW - Benzoates -- chemistry KW - Glucuronates -- isolation & purification KW - Glucuronidase -- chemistry KW - Glucuronates -- chemistry KW - Ascitic Fluid -- metabolism KW - Cell Line KW - Antineoplastic Agents -- pharmacokinetics KW - Triazoles -- chemistry KW - Triazoles -- blood KW - Triazoles -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78348306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Identification+and+characterization+of+human+metabolites+of+CAI+%5B5-amino-1-1%284%27-chlorobenzoyl-3%2C5-dichlorobenzyl%29-1%2C2%2C3-triazole-+4-carboxamide%29.&rft.au=Soltis%2C+M+J%3BYeh%2C+H+J%3BCole%2C+K+A%3BWhittaker%2C+N%3BWersto%2C+R+P%3BKohn%2C+E+C&rft.aulast=Soltis&rft.aufirst=M&rft.date=1996-07-01&rft.volume=24&rft.issue=7&rft.spage=799&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-31 N1 - Date created - 1997-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EPR spin trapping study of the decomposition of azo compounds in aqueous solutions by ultrasound: potential for use as sonodynamic sensitizers for cell killing. AN - 78338504; 8814440 AB - Sonodynamic therapy, a promising new approach to cancer treatment, is based on synergistic cell killing by combination of certain drugs (sonosensitizers) and ultrasound. Although the mechanism of sonodynamic action is not understood, the role of free radicals produced from sonosensitizers by ultrasound is implicated. In this work, we studied formation of free radicals during the decomposition of several water-soluble azo compounds by 50 kHz ultrasound in aqueous solutions. Using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) tertiary carbon-centered radicals from 2,2'-azobis (N,N'-dimethyleneisobutyramidine) dihydrochloride (VA-044), 2-(carbamoylazo)-isobutyronitrile (V-30), and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) and .CH3 radicals from 1,1'-azobis (N,N'-dimethylformamide) (ADMF) were detected in argon-saturated solutions and the corresponding oxygen-centered radicals (alkoxyl and peroxyl) from VA-044, V-30, and AAPH were identified using the spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) in aerated sonicated solutions. No free radicals from 4,4'-dihydroxyazobenzene-3,3'-dicarboxylic acid, disodium salt (DHAB) could be found in either system. While VA-044 and AAPH could also be readily decomposed by heat (42.5 degrees C and 80 degrees C), V-30 decomposition only occurred in the ultrasound-exposed solutions. The most likely mechanism of decomposition of azo compounds by ultrasound is their thermolysis in the heated shell of the liquid surrounding cavitating bubbles driven by ultrasound and/or by pyrolysis inside these bubbles. Experiments using scavengers of .OH and .H, which are produced by sonolysis in aqueous solutions, demonstrated that these radicals are not involved in the ultrasound-mediated radical production from the azo compounds. Due to the known cytotoxic potential of free radicals produced from azo compounds, the use of these compounds as ultrasound sensitizers appears to be a promising approach for sonodynamic cell killing. JF - Free radical research AU - Misík, V AU - Miyoshi, N AU - Riesz, P AD - Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 13 EP - 22 VL - 25 IS - 1 SN - 1071-5762, 1071-5762 KW - Azo Compounds KW - 0 KW - Free Radicals KW - Solutions KW - Water KW - 059QF0KO0R KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Electron Spin Resonance Spectroscopy -- methods KW - Oxygen -- chemistry KW - Free Radicals -- chemistry KW - Dose-Response Relationship, Radiation KW - Ultrasonics KW - Azo Compounds -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78338504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+research&rft.atitle=EPR+spin+trapping+study+of+the+decomposition+of+azo+compounds+in+aqueous+solutions+by+ultrasound%3A+potential+for+use+as+sonodynamic+sensitizers+for+cell+killing.&rft.au=Mis%C3%ADk%2C+V%3BMiyoshi%2C+N%3BRiesz%2C+P&rft.aulast=Mis%C3%ADk&rft.aufirst=V&rft.date=1996-07-01&rft.volume=25&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Free+radical+research&rft.issn=10715762&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-10 N1 - Date created - 1996-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized, controlled phase I/II, trial of combination therapy with delavirdine (U-90152S) and conventional nucleosides in human immunodeficiency virus type 1-infected patients. AN - 78323074; 8807058 AB - Delavirdine mesylate (DLV) is a potent nonnucleoside reverse transcriptase inhibitor with activity specific for human immunodeficiency virus type 1. In the present phase I/II study we evaluated the safety, toxicity, pharmacokinetics, and antiretroviral activities of two-drug and three-drug combinations of DLV and conventional doses of nucleoside analogs compared with those of both DLV monotherapy and two-drug nucleoside analog therapy. A total of 85 human immunodeficiency virus type 1 infected patients with CD4 counts of 100 to 300 cells per mm3 were enrolled in two periods: in the first period patients were randomized to receive either zidovudine (ZDV) plus didanosine (group 1) or ZDV plus didanosine plus escalating doses (400 to 1,200 mg/day) of DLV (group 2). In the second period, patients were randomized to receive either 1,200 mg of DLV alone per day (group 3) or ZDV plus 1,200 mg of DLV per day (group 4). DLV demonstrated good oral bioavailability at all five doses tested. The major toxicity was a transient mild rash which appeared in 44% of all DLV recipients. Overall, group 2 patients demonstrated more sustained improvements in CD4 counts, percent CD4 cells, branched DNA levels, p24 antigen levels, and virus titers in plasma than group 1, 3, or 4 patients. The magnitude of the response correlated with the intensity of prior nucleoside analog treatment, the non-syncytium-inducing or syncytium-inducing viral phenotype at baseline, and the presence of a wild-type codon at amino acid position 215 in the baseline reverse transcriptase genotype. Despite a transient rash, DLV therapy was well tolerated. Combination therapy with DLV and nucleoside analogs appears promising, with the three-drug combination appearing to be more potent that either two-drug combinations or monotherapy. JF - Antimicrobial agents and chemotherapy AU - Davey, R T AU - Chaitt, D G AU - Reed, G F AU - Freimuth, W W AU - Herpin, B R AU - Metcalf, J A AU - Eastman, P S AU - Falloon, J AU - Kovacs, J A AU - Polis, M A AU - Walker, R E AU - Masur, H AU - Boyle, J AU - Coleman, S AU - Cox, S R AU - Wathen, L AU - Daenzer, C L AU - Lane, H C AD - National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. rdavey@pop.niaid.nih.gov Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 1657 EP - 1664 VL - 40 IS - 7 SN - 0066-4804, 0066-4804 KW - Anti-HIV Agents KW - 0 KW - Indoles KW - Piperazines KW - Reverse Transcriptase Inhibitors KW - Zidovudine KW - 4B9XT59T7S KW - Delavirdine KW - DOL5F9JD3E KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Biological Availability KW - Zidovudine -- therapeutic use KW - Piperazines -- pharmacokinetics KW - Didanosine -- therapeutic use KW - Indoles -- pharmacokinetics KW - Anti-HIV Agents -- therapeutic use KW - Piperazines -- therapeutic use KW - Indoles -- adverse effects KW - HIV Infections -- drug therapy KW - Indoles -- therapeutic use KW - Piperazines -- adverse effects KW - Reverse Transcriptase Inhibitors -- therapeutic use KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78323074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Randomized%2C+controlled+phase+I%2FII%2C+trial+of+combination+therapy+with+delavirdine+%28U-90152S%29+and+conventional+nucleosides+in+human+immunodeficiency+virus+type+1-infected+patients.&rft.au=Davey%2C+R+T%3BChaitt%2C+D+G%3BReed%2C+G+F%3BFreimuth%2C+W+W%3BHerpin%2C+B+R%3BMetcalf%2C+J+A%3BEastman%2C+P+S%3BFalloon%2C+J%3BKovacs%2C+J+A%3BPolis%2C+M+A%3BWalker%2C+R+E%3BMasur%2C+H%3BBoyle%2C+J%3BColeman%2C+S%3BCox%2C+S+R%3BWathen%2C+L%3BDaenzer%2C+C+L%3BLane%2C+H+C&rft.aulast=Davey&rft.aufirst=R&rft.date=1996-07-01&rft.volume=40&rft.issue=7&rft.spage=1657&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-22 N1 - Date created - 1996-11-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Infect Dis. 1995 Jan;171(1):61-7 [7528253] J Infect Dis. 1994 Nov;170(5):1172-9 [7963710] J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Feb 1;8(2):141-51 [7530585] J Infect Dis. 1995 Feb;171(2):297-304 [7531207] Ann Intern Med. 1995 Mar 15;122(6):401-8 [7856987] J Infect Dis. 1995 Mar;171 Suppl 2:S150-4 [7861020] FEBS Lett. 1995 Feb 13;359(2-3):233-8 [7532595] J Infect Dis. 1995 Mar;171(3):537-45 [7533197] J Virol. 1995 Jun;69(6):3510-6 [7745698] J Clin Microbiol. 1995 Oct;33(10):2777-80 [8567926] Rev Infect Dis. 1990 Sep-Oct;12(5):912-30 [2237133] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8806-10 [1717988] J Biol Chem. 1992 Jan 5;267(1):27-30 [1370445] Ann Intern Med. 1993 May 1;118(9):681-8 [8096374] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4713-7 [7685109] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5608-12 [8516307] Antimicrob Agents Chemother. 1993 May;37(5):1127-31 [7685995] J Virol. 1993 Sep;67(9):5353-9 [7688822] J Virol. 1994 Mar;68(3):1660-6 [7509000] AIDS Res Hum Retroviruses. 1994 Aug;10(8):901-5 [7811540] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic mouse models in carcinogenesis: interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis. AN - 78321940; 8807143 AB - 1. Overexpression of the c-myc oncogene is associated with a variety of both human and experimental tumours, and cooperation of other oncogenes and growth factors with the myc family are critical in the evolution of the malignant phenotype. 2. Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human transforming growth factor (TGF-alpha) cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumourigenesis. 3. Coexpression of c-myc and TGF-alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumours were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. 4. These observations suggest that the interaction of c-myc and TGF-alpha, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. 5. We have now extended these studied and examined the interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in the transgenic mouse model. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Similarly, tumour promotion by phenobarbitone was completely inhibited in the c-myc/HGF double transgenic mice whereas phenobarbitone was an effective tumour promoter in the c-myc single transgenic mice. 6. The results indicate that HGF may function as a tumour suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. Furthermore, we show for the first time that interaction of c-myc with HGF or TGF-alpha results in profoundly different outcomes of the neoplastic process in the liver. JF - British journal of clinical pharmacology AU - Thorgeirsson, S S AU - Santoni-Rugiu, E AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 43 EP - 52 VL - 42 IS - 1 SN - 0306-5251, 0306-5251 KW - Albumins KW - 0 KW - Transforming Growth Factor alpha KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Metallothionein KW - 9038-94-2 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Mice, Inbred CBA KW - Albumins -- genetics KW - Mice, Inbred C57BL KW - Metallothionein -- genetics KW - Disease Models, Animal KW - Mice KW - Phenobarbital -- toxicity KW - Phenobarbital -- antagonists & inhibitors KW - Mice, Transgenic KW - Female KW - Liver Neoplasms, Experimental -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Liver Neoplasms, Experimental -- metabolism KW - Genes, myc KW - Hepatocyte Growth Factor -- genetics KW - Hepatocyte Growth Factor -- metabolism KW - Liver Neoplasms, Experimental -- chemically induced KW - Transforming Growth Factor alpha -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78321940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+clinical+pharmacology&rft.atitle=Transgenic+mouse+models+in+carcinogenesis%3A+interaction+of+c-myc+with+transforming+growth+factor+alpha+and+hepatocyte+growth+factor+in+hepatocarcinogenesis.&rft.au=Thorgeirsson%2C+S+S%3BSantoni-Rugiu%2C+E&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1996-07-01&rft.volume=42&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=British+journal+of+clinical+pharmacology&rft.issn=03065251&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-27 N1 - Date created - 1996-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraocular production of a cytokine (CINC) responsible for neutrophil infiltration in endotoxin induced uveitis. AN - 78319114; 8795380 AB - The subcutaneous injection of bacterial endotoxin in Lewis rats produces an acute intraocular inflammation evolving over a 24 hour period. This endotoxin induced uveitis (EIU) is characterised by a biphasic protein exudation and a cellular infiltrate composed of macrophages and polymorphonuclear neutrophils (PMNs). This model was used to study the mechanism of cellular infiltration in ocular inflammation. EIU was induced by a subcutaneous injection of lipopolysaccharide (LPS) (S typhimurium) at 350 micrograms/kg. The levels of cytokine induced neutrophil chemoattractant (CINC) were measured every 2 hours in the serum and in the aqueous humour by ELISA. The intraocular inflammation was quantified by protein measurement and leucocyte counting. The kinetics of CINC production in the systemic circulation showed a rapid rise, peaking 2 hours after LPS injection, followed by a progressive decline over the next 8 hours. In the eye, the CINC levels increased above the serum levels 10 hours after EIU induction corresponding to the time of cellular infiltration. When leucocyte entry in the eye was inhibited by 56% and 64% with an antiadhesion molecule antibody, there was only a slight reduction in the aqueous humour CINC levels of 9% and 16%, respectively, indicating that CINC was produced by ocular tissue cells. The specific effect of CINC in the eye was confirmed when a direct intraocular injection of 250 ng of purified CINC was followed by significant PMN infiltration, in the absence of protein exudation. The data indicate that the production of the CINC chemotactic factor by ocular tissue participates in the inflammatory reaction in EIU. JF - The British journal of ophthalmology AU - Guex-Crosier, Y AU - Wittwer, A J AU - Roberge, F G AD - National Institutes of Health, National Eye Institute, Bethesda, Maryland, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 649 EP - 653 VL - 80 IS - 7 SN - 0007-1161, 0007-1161 KW - Antibodies KW - 0 KW - Chemokines KW - Chemokines, CXC KW - Chemotactic Factors KW - Growth Substances KW - Intercellular Signaling Peptides and Proteins KW - Lipopolysaccharides KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Antibodies -- administration & dosage KW - Aqueous Humor -- chemistry KW - Cell Movement -- drug effects KW - Enzyme-Linked Immunosorbent Assay KW - Disease Models, Animal KW - Male KW - Chemokines -- biosynthesis KW - Neutrophils -- drug effects KW - Chemokines -- pharmacology KW - Chemotactic Factors -- blood KW - Chemotactic Factors -- biosynthesis KW - Growth Substances -- pharmacology KW - Growth Substances -- biosynthesis KW - Growth Substances -- blood KW - Uveitis -- metabolism KW - Uveitis -- chemically induced KW - Chemotactic Factors -- pharmacology KW - Chemokines -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78319114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+ophthalmology&rft.atitle=Intraocular+production+of+a+cytokine+%28CINC%29+responsible+for+neutrophil+infiltration+in+endotoxin+induced+uveitis.&rft.au=Guex-Crosier%2C+Y%3BWittwer%2C+A+J%3BRoberge%2C+F+G&rft.aulast=Guex-Crosier&rft.aufirst=Y&rft.date=1996-07-01&rft.volume=80&rft.issue=7&rft.spage=649&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+ophthalmology&rft.issn=00071161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-08 N1 - Date created - 1996-10-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Infect Dis. 1995 Jan;171(1):145-52 [7528250] J Neuroimmunol. 1994 Nov;55(1):1-9 [7962479] Curr Eye Res. 1986 Nov;5(11):869-76 [3536320] J Immunol. 1988 Apr 1;140(7):2193-6 [2965182] N Engl J Med. 1988 Jun 9;318(23):1481-6 [2835680] Graefes Arch Clin Exp Ophthalmol. 1988;226(6):553-8 [2463214] J Immunol. 1989 Apr 1;142(7):2321-4 [2784459] Biochem Biophys Res Commun. 1989 Jun 30;161(3):1093-9 [2662972] J Med Microbiol. 1990 Feb;31(2):73-83 [2406448] J Exp Med. 1990 Apr 1;171(4):1155-62 [1969919] Curr Eye Res. 1990 May;9(5):501-5 [2166639] Science. 1990 Sep 21;249(4975):1431-3 [1698311] FASEB J. 1991 Mar 1;5(3):338-43 [1825816] J Exp Med. 1991 Apr 1;173(4):1021-4 [2007851] J Immunol. 1991 May 15;146(10):3478-82 [2026876] Invest Ophthalmol Vis Sci. 1992 Mar;33(3):532-9 [1544781] Inflammation. 1992 Apr;16(2):187-96 [1592490] Clin Infect Dis. 1992 Jun;14(6):1213-28 [1623078] Immunology. 1992 Nov;77(3):385-93 [1478684] Biochem Biophys Res Commun. 1993 Jan 15;190(1):104-10 [8422237] J Pharmacobiodyn. 1992 Sep;15(9):461-6 [1337556] Invest Ophthalmol Vis Sci. 1993 Mar;34(3):673-81 [8095493] JAMA. 1993 Apr 14;269(14):1829-35 [8459516] J Immunol. 1993 Jun 15;150(12):5556-65 [7685797] J Cell Physiol. 1993 Aug;156(2):421-7 [8344996] Adv Exp Med Biol. 1993;329:599-604 [8379432] Adv Immunol. 1994;55:97-179 [8304236] Invest Ophthalmol Vis Sci. 1994 Mar;35(3):1100-6 [8125720] Eur J Pharmacol. 1994 Apr 4;270(2-3):143-9 [8039544] Invest Ophthalmol Vis Sci. 1994 Oct;35(11):3873-83 [7928184] Exp Eye Res. 1995 Feb;60(2):199-207 [7781749] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RAR and RXR selective ligands cooperatively induce apoptosis and neuronal differentiation in P19 embryonal carcinoma cells. AN - 78314736; 8801169 AB - Retinoids cause differentiation in embryonal carcinoma (EC) cells, thus mimicking events in mammalian development. Here, we show that retinoids also cause apoptosis in P19 EC cells. Characteristic DNA fragmentation was observed within 36 h after addition of retinoic acid (RA). Synthetic retinoids that are selective for RA receptors (RAR) were also effective in inducing apoptosis, whereas RXR selective ligands were without effect. The combination of RAR and RXR ligands resulted in a synergistic increase in apoptotic cell death. As with apoptosis, neuronal differentiation of P19 cells was synergistically induced by the combination of RAR and RXR ligands. Data obtained with an RAR antagonist and with P19 cells carrying a dominant negative RXR indicate that the two processes are receptor mediated. Together, our results indicate that retinoid-induced apoptosis and neuronal differentiation are closely coupled, and that both RAR and RXR play a role in these processes as active receptors for their respective ligands. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Horn, V AU - Minucci, S AU - Ogryzko, V V AU - Adamson, E D AU - Howard, B H AU - Levin, A A AU - Ozato, K AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 1071 EP - 1077 VL - 10 IS - 9 SN - 0892-6638, 0892-6638 KW - Ligands KW - 0 KW - Receptors, Retinoic Acid KW - Retinoid X Receptors KW - Retinoids KW - Transcription Factors KW - Index Medicus KW - Carcinoma, Embryonal KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - DNA Damage KW - Cell Differentiation KW - Drug Synergism KW - Cell Cycle -- drug effects KW - Cell Adhesion KW - Receptors, Retinoic Acid -- metabolism KW - Apoptosis KW - Neurons -- cytology KW - Retinoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78314736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=RAR+and+RXR+selective+ligands+cooperatively+induce+apoptosis+and+neuronal+differentiation+in+P19+embryonal+carcinoma+cells.&rft.au=Horn%2C+V%3BMinucci%2C+S%3BOgryzko%2C+V+V%3BAdamson%2C+E+D%3BHoward%2C+B+H%3BLevin%2C+A+A%3BOzato%2C+K&rft.aulast=Horn&rft.aufirst=V&rft.date=1996-07-01&rft.volume=10&rft.issue=9&rft.spage=1071&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethylene oxide exposure may increase the risk of spontaneous abortion, preterm birth, and postterm birth. AN - 78306984; 8793361 AB - Ethylene oxide is a gas used in some dental offices to sterilize equipment. In pregnant laboratory animals, ethylene oxide increases malformations and feral loss. Increased gestation length has also been reported. In humans, two studies have reported increased spontaneous abortions among ethylene oxide-exposed women, but few other data exist. We sent questionnaires to 7,000 dental assistants, age 18-39 years, registered in California in 1987; 4,856 responded (69%). We based our analysis on 1,320 women whose most recent pregnancy was conceived while working full-time. Thirty-two women reported exposure to ethylene oxide; unexposed dental assistants comprised the comparison group. We estimated relative risks of spontaneous abortion and preterm birth using a person-week model. We estimated relative risks of postterm birth (> or = 42 weeks) and a combined adverse outcomes model using logistic regression. Among exposed women, the age-adjusted relative risk of spontaneous abortion was 2.5 [95% confidence interval (CI) = 1.0-6.3], for preterm birth 2.7 (95% CI = 0.8-8.8), and for postterm birth 2.1 (95% CI = 0.7-5.9). The estimated relative risk of any of these adverse outcomes among exposed women was 2.5 (95% CI = 1.0-6.1) after adjusting for age, nitrous oxide, and number of mercury amalgams prepared. These data further implicate ethylene oxide as a possible reproductive toxicant in humans. JF - Epidemiology (Cambridge, Mass.) AU - Rowland, A S AU - Baird, D D AU - Shore, D L AU - Darden, B AU - Wilcox, A J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 363 EP - 368 VL - 7 IS - 4 SN - 1044-3983, 1044-3983 KW - Ethylene Oxide KW - JJH7GNN18P KW - Index Medicus KW - Regression Analysis KW - Humans KW - Gestational Age KW - Infant, Newborn KW - Pregnancy KW - Cross-Sectional Studies KW - Risk Factors KW - Adult KW - Cohort Studies KW - Surveys and Questionnaires KW - Incidence KW - Adolescent KW - California -- epidemiology KW - Female KW - Pregnancy Outcome KW - Obstetric Labor, Premature -- epidemiology KW - Abortion, Spontaneous -- chemically induced KW - Ethylene Oxide -- adverse effects KW - Occupational Exposure -- adverse effects KW - Abortion, Spontaneous -- epidemiology KW - Occupational Diseases -- chemically induced KW - Obstetric Labor, Premature -- chemically induced KW - Infant, Postmature UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78306984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Ethylene+oxide+exposure+may+increase+the+risk+of+spontaneous+abortion%2C+preterm+birth%2C+and+postterm+birth.&rft.au=Rowland%2C+A+S%3BBaird%2C+D+D%3BShore%2C+D+L%3BDarden%2C+B%3BWilcox%2C+A+J&rft.aulast=Rowland&rft.aufirst=A&rft.date=1996-07-01&rft.volume=7&rft.issue=4&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-18 N1 - Date created - 1996-11-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Epidemiology. 1997 Jul;8(4):465-6 [9209871] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monitoring the source of memory in detoxified alcoholics. AN - 78283282; 8780854 AB - The ability to monitor the source of remembered information and related reflective cognitive processes was examined in normal volunteers and detoxified alcoholics. Normal volunteers were very accurate judges of whether remembered events were presented as stimuli or were self-generated, even when memory was tested 2 days later. In contrast, a subgroup of otherwise cognitively unimpaired alcoholics demonstrated impairments in the ability to track the source of remembered knowledge and were also less able to inhibit intrusion errors in recalling information from memory. These findings provide preliminary evidence of an impairment in cognitive control functions in certain alcoholics. This conclusion is supported by associated findings indicating that, among alcoholics, performance on explicit memory tasks that required reflective cognitive operations were positively correlated with glucose utilization rates in left prefrontal, temporal, and posterior orbital frontal cortical regions. JF - Biological psychiatry AU - Weingartner, H J AU - Andreason, P J AU - Hommer, D W AU - Sirocco, K Y AU - Rio, D E AU - Ruttimann, U E AU - Rawlings, R R AU - Eckardt, M J AD - Section of Brain Electrophysiology and Imaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-1250, USA. Y1 - 1996/07/01/ PY - 1996 DA - 1996 Jul 01 SP - 43 EP - 53 VL - 40 IS - 1 SN - 0006-3223, 0006-3223 KW - Blood Glucose KW - 0 KW - Index Medicus KW - Frontal Lobe -- physiopathology KW - Dominance, Cerebral -- physiology KW - Reference Values KW - Blood Glucose -- metabolism KW - Humans KW - Prefrontal Cortex -- physiopathology KW - Verbal Learning -- physiology KW - Reality Testing KW - Adult KW - Tomography, Emission-Computed KW - Attention -- physiology KW - Middle Aged KW - Female KW - Male KW - Temporal Lobe -- physiopathology KW - Retention (Psychology) -- physiology KW - Alcoholism -- rehabilitation KW - Awareness -- physiology KW - Mental Recall -- physiology KW - Alcohol Amnestic Disorder -- physiopathology KW - Alcohol Amnestic Disorder -- psychology KW - Alcohol Amnestic Disorder -- diagnosis KW - Alcoholism -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78283282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Monitoring+the+source+of+memory+in+detoxified+alcoholics.&rft.au=Weingartner%2C+H+J%3BAndreason%2C+P+J%3BHommer%2C+D+W%3BSirocco%2C+K+Y%3BRio%2C+D+E%3BRuttimann%2C+U+E%3BRawlings%2C+R+R%3BEckardt%2C+M+J&rft.aulast=Weingartner&rft.aufirst=H&rft.date=1996-07-01&rft.volume=40&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-18 N1 - Date created - 1996-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role for protein phosphatase in the regulation of Ca2+ influx in parotid gland acinar cells. AN - 78222152; 8760057 AB - Stimulation of Ca2+ (and Mn2+) entry in salivary epithelial cells by carbachol, or thapsigargin, is mediated by an, as yet, unknown mechanism that is dependent on the depletion of Ca2+ from intracellular Ca2+ stores. This study assesses the possible role of protein phosphorylation in the regulation of Ca2+ entry in rat parotid gland acinar cells. Treatment of cells with the protein phosphatase inhibitors okadaic acid, calyculin A, and pervanadate induced a dose-dependent inhibition of carbachol and thapsigargin stimulation of Ca2+ and Mn2+ entry. All three inhibitors decreased carbachol stimulation of internal Ca2+ release, which likely accounts for the inhibition of carbachol-stimulated Ca2+ entry. Thapsigargin-induced internal Ca2+ release was not affected by the treatments. Additionally, all three phosphatase inhibitors decreased Mn2+ entry into cells with depleted internal Ca2+ store(s) (achieved by incubation with either carbachol or thapsigargin in Ca2+-free medium). Treatment of cells with phorbol 12-myristate 13-acetate, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, or staurosporine did not affect divalent cation entry into unstimulated cells or thapsigargin treated cells. Importantly, when cells with depleted internal Ca2+ store(s) were pretreated with staurosporine, or K-252a, the inhibition of Ca2+ entry by calyculin A and okadaic acid, but not by pervanadate, was attenuated. Although the effect of pervanadate remains to be clarified, these results demonstrate a role for protein phosphorylation in the regulation of divalent cation influx in rat parotid acinar cells. JF - The American journal of physiology AU - Sakai, T AU - Ambudkar, I S AD - Secretory Physiology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - C284 EP - C294 VL - 271 IS - 1 Pt 1 SN - 0002-9513, 0002-9513 KW - Enzyme Inhibitors KW - 0 KW - Oxazoles KW - Protein Kinase Inhibitors KW - pervanadate KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Vanadates KW - 3WHH0066W5 KW - Manganese KW - 42Z2K6ZL8P KW - Thapsigargin KW - 67526-95-8 KW - calyculin A KW - 7D07U14TK3 KW - Carbachol KW - 8Y164V895Y KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Manganese -- metabolism KW - Vanadates -- pharmacology KW - Rats KW - Stimulation, Chemical KW - Thapsigargin -- pharmacology KW - Oxazoles -- pharmacology KW - Okadaic Acid -- pharmacology KW - Rats, Wistar KW - Enzyme Inhibitors -- pharmacology KW - Carbachol -- pharmacology KW - Male KW - Calcium -- metabolism KW - Phosphoprotein Phosphatases -- physiology KW - Parotid Gland -- metabolism KW - Parotid Gland -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78222152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Role+for+protein+phosphatase+in+the+regulation+of+Ca2%2B+influx+in+parotid+gland+acinar+cells.&rft.au=Sakai%2C+T%3BAmbudkar%2C+I+S&rft.aulast=Sakai&rft.aufirst=T&rft.date=1996-07-01&rft.volume=271&rft.issue=1+Pt+1&rft.spage=C284&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Action of protein kinase C in endothelin-induced contractions in rat aortic rings. AN - 78220642; 8760071 AB - Endothelin (ET) is a potent vasoconstrictor peptide that induces characteristically long-lasting contractions. We used both intact and endothelium-denuded rat aortic rings to investigate the role of protein kinase C (PKC) in ET-induced contractions. ET (10(-9) M) and phorbol 12,13-dibutyrate (PDBu), a PKC activator, produced a gradual and sustained contraction of greater magnitude in denuded aortic rings than in intact rings. When aortic rings were pretreated with graded concentrations of different PKC inhibitors, inhibition of ET-induced contractions began at 10(-9)M and was nearly complete at 10(-3)M, and the reduction was greater in intact than in denuded rings. Pretreatment of aortic rings with PDBu or NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, potentiated ET-induced contractions. PKC enzyme assay showed activation of PKC in aortic rings that were treated with either ET or PDBu, inhibition after pretreatment with PKC inhibitors, and no change with 4 alpha-phorbol 12,13-didecanoate (PDD), an inactive phorbol ester. ET significantly increased nitrate and nitrite production, which was further increased by pretreatment with PKC inhibitors. PDBu prevented ET-induced nitrate/nitrite production, and PDD had no effect. These results strongly suggest that PKC mediates, in part, ET-induced contractions in rat aortic rings and that an intact endothelium is required for maximum inhibition by PKC inhibitors because PKC stimulated by ET inhibits nitric oxide release. JF - The American journal of physiology AU - Oriji, G K AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - C398 EP - C404 VL - 271 IS - 1 Pt 1 SN - 0002-9513, 0002-9513 KW - Endothelins KW - 0 KW - Enzyme Inhibitors KW - Nitrates KW - Nitrites KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Rats KW - Animals KW - Nitrites -- metabolism KW - Nitrates -- metabolism KW - In Vitro Techniques KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Male KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Endothelium, Vascular -- physiology KW - Vasoconstriction -- physiology KW - Protein Kinase C -- metabolism KW - Endothelins -- pharmacology KW - Protein Kinase C -- antagonists & inhibitors KW - Aorta -- physiology KW - Aorta -- drug effects KW - Aorta -- enzymology KW - Vasoconstriction -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78220642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Action+of+protein+kinase+C+in+endothelin-induced+contractions+in+rat+aortic+rings.&rft.au=Oriji%2C+G+K%3BKeiser%2C+H+R&rft.aulast=Oriji&rft.aufirst=G&rft.date=1996-07-01&rft.volume=271&rft.issue=1+Pt+1&rft.spage=C398&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-resistant breast cancer cells frequently retain expression of a functional wild-type p53 protein. AN - 78208428; 8706243 AB - Abnormalities in the p53 tumor suppressor gene have been shown to affect cellular processes related to cell cycle control and gene amplification. In this study we compare the status and function of wild-type p53 in MCF-7 breast cancer cells with sublines selected for resistance to chemotherapeutic agents having different mechanisms of action. Sublines that were resistant to melphalan, pyrazafurin, mitoxantrone, etoposide and PALA all retained expression of wild-type p53. Methotrexate-resistant MCF-7 cells were unusual heterozygotes that expressed a wild-type and dominant, in-frame p53 deletion mutant and the doxorubicin-resistant cells expressed only mutant p53. Analysis of the G1 checkpoint after treatment with ionizing radiation revealed that the pyrazafurin-, melphalan- and mitoxantrone-resistant cells arrested strongly in G1. The etoposide- and PALA-resistant cells had an intermediate G1 arrest phenotype and the methotrexate- and doxorubicin-resistant cells had a minimal G1 arrest phenotype. mRNA and protein analyses of downstream effector genes, including P21CIP1/Waf1, mdm2, Gadd 45 and the retinoblastoma protein, did not entirely differentiate sublines having a strong versus intermediate G1 arrest phenotype. Neither the p53 status nor the strength of the G1 arrest could be correlated with cell survival after ionizing radiation. When drug-sensitive MCF-7 cells were treated with the same chemotherapeutic agents, p53 and p21CIP1/Waf1 levels increased between 2- and 14-fold. Together these data suggest that other cellular factors likely play a role in overcoming the inhibitory effects of ionizing radiation on p53 in drug-resistant breast cancer cells. JF - Carcinogenesis AU - Gudas, J M AU - Nguyen, H AU - Li, T AU - Sadzewicz, L AU - Robey, R AU - Wosikowski, K AU - Cowan, K H AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 1417 EP - 1427 VL - 17 IS - 7 SN - 0143-3334, 0143-3334 KW - Antineoplastic Agents KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Enzyme Inhibitors KW - Neoplasm Proteins KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Ribonucleosides KW - Tumor Suppressor Protein p53 KW - Aspartic Acid KW - 30KYC7MIAI KW - pyrazofurin KW - 4B15044GQZ KW - Etoposide KW - 6PLQ3CP4P3 KW - sparfosic acid KW - 78QVZ7RG8L KW - Mitoxantrone KW - BZ114NVM5P KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Phosphonoacetic Acid KW - N919E46723 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Clone Cells KW - Aspartic Acid -- toxicity KW - Cyclins -- biosynthesis KW - Phosphonoacetic Acid -- toxicity KW - Humans KW - Phosphonoacetic Acid -- analogs & derivatives KW - Gene Expression KW - Melphalan -- toxicity KW - Ribonucleosides -- toxicity KW - Proto-Oncogene Proteins -- biosynthesis KW - Tumor Cells, Cultured KW - Mitoxantrone -- toxicity KW - Flow Cytometry KW - Neoplasm Proteins -- analysis KW - Cell Cycle KW - Neoplasm Proteins -- biosynthesis KW - Proto-Oncogene Proteins -- analysis KW - Etoposide -- toxicity KW - Cyclins -- analysis KW - Polymerase Chain Reaction KW - Blotting, Western KW - Aspartic Acid -- analogs & derivatives KW - Enzyme Inhibitors -- analysis KW - Immunohistochemistry KW - Female KW - Breast Neoplasms -- genetics KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Tumor Suppressor Protein p53 -- analysis KW - Genes, p53 KW - Antineoplastic Agents -- toxicity KW - Drug Resistance, Neoplasm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78208428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Drug-resistant+breast+cancer+cells+frequently+retain+expression+of+a+functional+wild-type+p53+protein.&rft.au=Gudas%2C+J+M%3BNguyen%2C+H%3BLi%2C+T%3BSadzewicz%2C+L%3BRobey%2C+R%3BWosikowski%2C+K%3BCowan%2C+K+H&rft.aulast=Gudas&rft.aufirst=J&rft.date=1996-07-01&rft.volume=17&rft.issue=7&rft.spage=1417&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-09 N1 - Date created - 1996-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel approaches to tumor detection and therapy using a combination of monoclonal antibody and cytokine. AN - 78198201; 8694532 AB - Cytokine-based tumor antigen augmentation is one of the approaches researchers and clinicians are using to improve the effectiveness of MAb-directed tumor diagnosis and therapy. Other efforts encompass the use of dose-fractionation for multiple administrations of radioimmunoconjugates, exploitation of genetic engineering to construct antibody molecules with specific biological properties (i.e., altered pharmacokinetics, activation of cellular immune responses, etc.) and use of MAb-directed conjugates that can enhance tumor MAb uptake by altering tumor perfusion. The studies summarized here as well as those from other laboratories have served as the framework for clinical investigations designed to determine the effectiveness of the interferons and other differentiation-inducing agents to alter the tumor antigen phenotype in patients. In an earlier study, patients given IFN-alpha had improved tumor uptake of an antimelanoma MAb. Subsequently, we reported that i.p. IFN-gamma administration substantially upregulated TAG-72 and CEA on the surface of human tumor cells isolated from malignant ascites. A seminal investigation showed significant increase of TAG-72 and CEA levels in tumor biopsies from patients diagnosed with colorectal carcinoma and given systemic IFN-alpha. Those studies led to a clinical trial in which late stage breast cancer patients were administered interferon in combination with therapeutic doses of CC49. Some clinical responses were observed, however, the cytokine and MAb combination may have also enhanced marrow toxicity. Future studies will continue to evaluate the ability to enhance tumor antigen expression in the context of genetically engineered MAbs designed to minimize normal organ toxicity. JF - Anticancer research AU - Greiner, J W AU - Guadagni, F AU - Roselli, M AU - Nieroda, C A AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1996 SP - 2129 EP - 2133 VL - 16 IS - 4B SN - 0250-7005, 0250-7005 KW - Antibodies, Monoclonal KW - 0 KW - Biomarkers, Tumor KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Radioimmunotherapy KW - Humans KW - Biomarkers, Tumor -- analysis KW - Neoplasms -- diagnosis KW - Radioimmunodetection KW - Interferon-gamma -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78198201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Novel+approaches+to+tumor+detection+and+therapy+using+a+combination+of+monoclonal+antibody+and+cytokine.&rft.au=Greiner%2C+J+W%3BGuadagni%2C+F%3BRoselli%2C+M%3BNieroda%2C+C+A&rft.aulast=Greiner&rft.aufirst=J&rft.date=1996-07-01&rft.volume=16&rft.issue=4B&rft.spage=2129&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-29 N1 - Date created - 1996-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized, masked, cross-over trial of acetazolamide for cystoid macular edema in patients with uveitis. AN - 78193400; 8684794 AB - To study the effect of acetazolamide on cystoid macular edema in patients with uveitis. Forty patients with chronic intermediate, posterior, or panuveitis associated cystoid macular edema were randomized into a masked, cross-over trial comparing acetazolamide versus placebo. Patients received an initial 4-week course of either acetazolamide or placebo (course A) followed by a 4-week washout period. They then received a 4-week course of the opposite study medication (course B). Primary endpoints included area of cystoid macular edema measured on late-phase views of fluorescein angiography and visual acuity. Thirty-seven patients completed the trial and were available for analysis; 17 (46%) were randomized to receive acetazolamide and 20 (54%) to receive placebo during course A. Acetazolamide resulted in a 0.5-disc area (25%) decrease in cystoid macular edema over that of placebo (P = 0.01; estimated treatment effect = -0.5 disc areas; 95% confidence interval, -0.9 to -0.1). However, there was no statistically significant effect of acetazolamide on visual acuity (P = 0.61; estimated treatment effect = 0.6 letters; 95% confidence interval, -2 to 3). A 4-week course of acetazolamide therapy results in a statistically significant but small decrease in cystoid macular edema in patients with chronic uveitis, and does not improve visual acuity. In contrast to previous studies in the literature, acetazolamide may have a more limited clinical benefit in patients with long-standing cystoid macular edema associated with chronic uveitis. JF - Ophthalmology AU - Whitcup, S M AU - Csaky, K G AU - Podgor, M J AU - Chew, E Y AU - Perry, C H AU - Nussenblatt, R B AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 1054 EP - 62; discussion 1062-3 VL - 103 IS - 7 SN - 0161-6420, 0161-6420 KW - Carbonic Anhydrase Inhibitors KW - 0 KW - Acetazolamide KW - O3FX965V0I KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Fluorescein Angiography KW - Aged KW - Fundus Oculi KW - Adult KW - Cross-Over Studies KW - Chronic Disease KW - Middle Aged KW - Adolescent KW - Visual Acuity KW - Female KW - Male KW - Macular Edema -- etiology KW - Acetazolamide -- adverse effects KW - Macular Edema -- pathology KW - Acetazolamide -- therapeutic use KW - Uveitis -- complications KW - Carbonic Anhydrase Inhibitors -- adverse effects KW - Carbonic Anhydrase Inhibitors -- therapeutic use KW - Macular Edema -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78193400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ophthalmology&rft.atitle=A+randomized%2C+masked%2C+cross-over+trial+of+acetazolamide+for+cystoid+macular+edema+in+patients+with+uveitis.&rft.au=Whitcup%2C+S+M%3BCsaky%2C+K+G%3BPodgor%2C+M+J%3BChew%2C+E+Y%3BPerry%2C+C+H%3BNussenblatt%2C+R+B&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1996-07-01&rft.volume=103&rft.issue=7&rft.spage=1054&rft.isbn=&rft.btitle=&rft.title=Ophthalmology&rft.issn=01616420&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-22 N1 - Date created - 1996-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ophthalmology. 1996 Nov;103(11):1717; author reply 1717-8 [8942860] Ophthalmology. 1996 Nov;103(11):1715-6; author reply 1716-7 [8942859] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retreatment of patients surviving cancer-free 2 or more years after initial treatment of small cell lung cancer. AN - 78169708; 8681622 AB - To assess the outcome after retreatment of patients with small cell lung cancer (SCLC) who redevelop small cell cancer (SCC) 2 or more years after initial therapy. Retrospective analysis. Single government institution: the National Cancer Institute. Twenty patients who redeveloped SCC among 65 patients who survived 2 or more years after starting treatment for their initial cancer. The response rate of patients after retreatment, the survival duration from the time of redevelopment of SCC, and the toxicities of retreatment. Twenty patients redeveloped SCC: 18 with a relapse and 2 with a second primary cancer. Sixteen received treatment after they redeveloped SCLC while four did not. Eleven patients were retreated with chemotherapy alone, two patients received chemotherapy plus chest radiotherapy, one patient received radiotherapy alone, one patient underwent lobectomy, and one patient was treated with a monoclonal antibody followed by chemotherapy. Nine of 16 patients (56%) treated after they redeveloped SCLC had an objective response (3 complete and 6 partial). The median survival of all 20 patients after they redeveloped SCC was 3.9 months (range, 0 to 46 months). The median survival of the patients who were retreated was 6.5 months (range, 1 to 46 months). Patients who suffer relapses with SCLC 2 or more years from diagnosis are candidates for retreatment. JF - Chest AU - Chute, J P AU - Kelley, M J AU - Venzon, D AU - Williams, J AU - Roberts, A AU - Johnson, B E AD - National Cancer Institute, Navy Medical Oncology Branch, National Naval Medical Center, Bethesda MD 20889-5105, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 165 EP - 171 VL - 110 IS - 1 SN - 0012-3692, 0012-3692 KW - Abridged Index Medicus KW - Index Medicus KW - Disease-Free Survival KW - Survival Rate KW - Lung -- diagnostic imaging KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Radiography KW - Time Factors KW - Male KW - Female KW - Carcinoma, Small Cell -- therapy KW - Carcinoma, Small Cell -- mortality KW - Carcinoma, Small Cell -- secondary KW - Lung Neoplasms -- therapy KW - Carcinoma, Small Cell -- diagnostic imaging KW - Neoplasm Recurrence, Local -- therapy KW - Lung Neoplasms -- mortality KW - Lung Neoplasms -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78169708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chest&rft.atitle=Retreatment+of+patients+surviving+cancer-free+2+or+more+years+after+initial+treatment+of+small+cell+lung+cancer.&rft.au=Chute%2C+J+P%3BKelley%2C+M+J%3BVenzon%2C+D%3BWilliams%2C+J%3BRoberts%2C+A%3BJohnson%2C+B+E&rft.aulast=Chute&rft.aufirst=J&rft.date=1996-07-01&rft.volume=110&rft.issue=1&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-21 N1 - Date created - 1996-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Weaver granule neurons are rescued by calcium channel antagonists and antibodies against a neurite outgrowth domain of the B2 chain of laminin. AN - 78168107; 8707831 AB - The weaver mutation impairs migration of the cerebellar granular neurons and induces neuronal death during the first two weeks of postnatal life. To elucidate the molecular mechanisms for the impaired neuronal migration, we investigated the rescue mechanisms of the weaver (wv/wv) granule neurons in vitro. We found that Fab2 fragments of antibodies against a neurite outgrowth domain of the B2 chain of laminin enhanced neurite outgrowth and neuronal migration of the weaver granule neurons on a laminin substratum and in the established cable culture system. The rescue of the weaver granule neurons by antibodies against the B2 chain of laminin may result from the neutralizing effect of these antibodies against the elevated B2 chain levels of the weaver brain. The L-type calcium channel blocker, verapamil (1-5 microM), also rescued the weaver granule neurons. High concentrations of MK-801 (10-20 microM), a glutamate receptor antagonist and voltage-gated calcium channel blocker, rescued the weaver granule neurons similar to verapamil, but low concentrations of MK-801 (1 microM) had no rescue effect. Simultaneous patch-clamp studies indicated that the weaver granule neurons did not express functional N-methyl-D-aspartate receptors further indicating that the rescue of the weaver granule neurons by MK-801 resulted from its known inhibition of voltage-gated calcium channels. The present results indicate that antibodies against the B2 chain of laminin, verapamil, and high concentrations of MK-801 protect the weaver granule neurons from the otherwise destructive action of the weaver gene. Thus, both the laminin system and calcium channel function contribute to the migration deficiency of the weaver granule neurons. JF - The Journal of cell biology AU - Liesi, P AU - Wright, J M AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA. liesi@helix.nih.gov Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 477 EP - 486 VL - 134 IS - 2 SN - 0021-9525, 0021-9525 KW - Antibodies, Monoclonal KW - 0 KW - Calcium Channel Blockers KW - Laminin KW - Leukocyte L1 Antigen Complex KW - Neural Cell Adhesion Molecules KW - Peptides KW - Receptors, N-Methyl-D-Aspartate KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 2-amino-5-phosphopentanoic acid KW - 76326-31-3 KW - omega-Conotoxin GVIA KW - 92078-76-7 KW - Verapamil KW - CJ0O37KU29 KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Cell Movement KW - Animals KW - Rabbits KW - Mice KW - Valine -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Verapamil -- pharmacology KW - Peptides -- pharmacology KW - Neurites -- physiology KW - Neural Cell Adhesion Molecules -- metabolism KW - Antibodies, Monoclonal -- immunology KW - Dizocilpine Maleate -- pharmacology KW - Cerebellum -- cytology KW - Mice, Mutant Strains KW - Calcium Channel Blockers -- pharmacology KW - Cells, Cultured KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Valine -- analogs & derivatives KW - Laminin -- physiology KW - Neurons -- drug effects KW - Laminin -- antagonists & inhibitors KW - Neurons -- cytology KW - Neurons -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78168107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=Weaver+granule+neurons+are+rescued+by+calcium+channel+antagonists+and+antibodies+against+a+neurite+outgrowth+domain+of+the+B2+chain+of+laminin.&rft.au=Liesi%2C+P%3BWright%2C+J+M&rft.aulast=Liesi&rft.aufirst=P&rft.date=1996-07-01&rft.volume=134&rft.issue=2&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-10 N1 - Date created - 1996-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genomics. 1989 Oct;5(3):522-6 [2575584] Trends Neurosci. 1988 Oct;11(10):465-9 [2469166] Brain Res Dev Brain Res. 1990 Mar 1;52(1-2):63-73 [2331801] J Neurophysiol. 1990 Jun;63(6):1373-84 [1972740] Experientia. 1990 Sep 15;46(9):900-7 [2209799] Experientia. 1990 Sep 15;46(9):907-16 [2209800] Cell. 1992 Mar 6;68(5):841-54 [1547486] Science. 1992 Aug 7;257(5071):806-9 [1323145] Exp Neurol. 1992 Aug;117(2):103-13 [1499690] J Neurosci Res. 1992 Jun;32(2):261-73 [1404496] J Neurosci Res. 1992 Sep;33(1):170-6 [1453481] J Physiol. 1992 Oct;456:85-105 [1338108] Science. 1993 Apr 2;260(5104):95-7 [8096653] Science. 1993 Apr 16;260(5106):367-9 [8469990] Neuropharmacology. 1993 Nov;32(11):1239-48 [7509049] Nature. 1994 Mar 24;368(6469):335-9 [7907398] FEBS Lett. 1994 Oct 10;353(1):37-42 [7926018] Dev Biol. 1995 Apr;168(2):635-48 [7729594] J Neurosci Res. 1995 Feb 1;40(2):207-19 [7745614] Nat Genet. 1995 Oct;11(2):126-9 [7550338] Protein Profile. 1995;2(9):963-1108 [8574878] Neuron. 1996 Feb;16(2):321-31 [8789947] Genome Res. 1995 Dec;5(5):453-63 [8808466] Proc Natl Acad Sci U S A. 1973 Jan;70(1):240-4 [4509657] J Comp Neurol. 1973 Nov 15;152(2):103-32 [4128371] J Comp Neurol. 1973 Nov 15;152(2):133-61 [4761656] Brain Res. 1974 Sep 13;77(3):484-91 [4136558] Brain Res. 1975 Aug 22;94(1):19-44 [1148865] J Cell Biol. 1977 Dec;75(3):915-40 [562889] Neuroscience. 1978;3(11):1093-1100 [570653] Pflugers Arch. 1981 Aug;391(2):85-100 [6270629] J Neurosci. 1982 Oct;2(10):1474-85 [7119868] Nature. 1983 Sep 29-Oct 5;305(5933):427-30 [6621692] EMBO J. 1984 Jan;3(1):1-10 [6368220] Nature. 1985 Aug 1-7;316(6027):440-3 [2410796] J Neurosci. 1986 Sep;6(9):2676-83 [3528411] Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104-8 [3529096] FEBS Lett. 1989 Feb 13;244(1):141-8 [2924902] Annu Rev Neurosci. 1989;12:491-516 [2648958] Neuron. 1989 Jun;2(6):1565-75 [2627379] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor alpha required for gene induction by dehydroepiandrosterone-3 beta-sulfate. AN - 78159632; 8700121 AB - Peroxisome proliferator-activated receptor alpha (PPAR alpha) mediates the effects of foreign chemical peroxisome proliferators on liver and kidney, including the induction of peroxisomal, mitochondrial, and microsomal enzymes involved in beta-oxidation of fatty acids. However, the role of this receptor in the peroxisome proliferative effects of the endogenous steroid dehydroepiandrosterone (DHEA) is not known. DHEA-3 beta-sulfate fd(DHEA-S) is shown to induce a liver peroxisome proliferative response in rats in vivo at a dose at which DHEA is much less active, which is consistent with cultured hepatocyte studies indicating a requirement for sulfation for the activation of DHEA. Transient transfection experiments demonstrated that in contrast to the prototypic foreign chemical peroxisome proliferator pirinixic acid, DHEA-S and its 17 beta-reduced metabolite, 5-androstene-3 beta, 17 beta-diol-3 beta-sulfate, are inactive in mediating trans-activation by PPAR alpha in COS-1 cells. Two other mammalian PPAR isoforms, gamma and delta/Nucl, were also inactive with respect to DHEA-S trans-activation. To test whether PPAR alpha mediates peroxisomal gene induction by DHEA-S in intact animals, we administered DHEA-S or clofibrate to mice lacking a functional PPAR alpha gene. Both peroxisome proliferators markedly increased hepatic expression of two microsomal cytochrome P450 4A proteins as well as six mRNAs known to be associated with the peroxisomal proliferative response in wild-type mice. In contrast, neither DHEA-S nor clofibrate induced these hepatic proteins and mRNAs in PPAR alpha-deficient mice. Clofibrate-induced expression of kidney CYP4A mRNAs was also blocked in the PPAR alpha gene knockout mice. Thus, despite its unresponsiveness to steroidal peroxisome proliferators in transfection assays, PPAR alpha is obligatory for DHEA-S-stimulated hepatic peroxisomal gene induction. DHEA-S, or one of its metabolites, may thus serve as an important endogenous regulator of liver peroxisomal enzyme expression via a PPAR alpha-mediated pathway. JF - Molecular pharmacology AU - Peters, J M AU - Zhou, Y C AU - Ram, P A AU - Lee, S S AU - Gonzalez, F J AU - Waxman, D J AD - Laboratory of Molecular Carcinogenesis, National Cancer institute, National Institutes of health, Bethesda, Maryland 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 67 EP - 74 VL - 50 IS - 1 SN - 0026-895X, 0026-895X KW - Acetophenones KW - 0 KW - Anticholesteremic Agents KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Tetrazoles KW - Transcription Factors KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Dehydroepiandrosterone Sulfate KW - 57B09Q7FJR KW - pirinixic acid KW - 86C4MRT55A KW - LY 171883 KW - 88107-10-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Cytochrome P-450 CYP4A KW - EC 1.14.15.3 KW - Clofibrate KW - HPN91K7FU3 KW - Index Medicus KW - Animals KW - Mammals KW - Liver -- metabolism KW - Mice, Knockout KW - Rats KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Male KW - Organ Size -- drug effects KW - Kidney -- metabolism KW - Acetophenones -- pharmacology KW - Kidney -- drug effects KW - Pyrimidines -- pharmacology KW - Anticholesteremic Agents -- pharmacology KW - Mice KW - Microsomes -- enzymology KW - Clofibrate -- pharmacology KW - Mice, Inbred Strains KW - Tetrazoles -- pharmacology KW - Transfection KW - Cercopithecus aethiops KW - Mice, Inbred C57BL KW - Cell Line KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Transcriptional Activation -- drug effects KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptors, Cytoplasmic and Nuclear -- biosynthesis KW - Dehydroepiandrosterone -- analogs & derivatives KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Mixed Function Oxygenases -- biosynthesis KW - Microsomes, Liver -- enzymology KW - Gene Expression Regulation -- drug effects KW - Microbodies -- drug effects KW - Microbodies -- metabolism KW - Dehydroepiandrosterone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78159632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Peroxisome+proliferator-activated+receptor+alpha+required+for+gene+induction+by+dehydroepiandrosterone-3+beta-sulfate.&rft.au=Peters%2C+J+M%3BZhou%2C+Y+C%3BRam%2C+P+A%3BLee%2C+S+S%3BGonzalez%2C+F+J%3BWaxman%2C+D+J&rft.aulast=Peters&rft.aufirst=J&rft.date=1996-07-01&rft.volume=50&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-03 N1 - Date created - 1996-09-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of leukemia inhibitory factor and its receptor during liver regeneration in the adult rat. AN - 78159297; 8683936 AB - Leukemia inhibitory factor (LIF) is a polyfunctional cytokine that was discovered in the conditioned medium from Buffalo rat liver cells. In the liver, LIF is known to induce acute phase proteins in the hepatocytes. No comprehensive study has yet been performed on the physiological role of this cytokine during liver regeneration. Thus, we studied the level of expression and cellular distribution of transcripts for LIF, its receptor (LIFR), and signal transducing subunit gp13O during rat liver regeneration after both simple partial hepatectomy (PH) and the oval cell activation induced by the combination of 2-acetylaminofluorene and PH. In addition, the expression of an acute phase protein alpha1-acidglycoprotein was examined. The level of transcripts for LIF and its receptor subunits increased and remained elevated during oval cell expansion. In contrast, after PH, the transcripts were induced only transiently, showing a peak 24 hours after the operation. LIF and receptor subunits were expressed in both parenchymal and nonparenchymal fractions in the 2-acetylaminofluorene/PH model, but the level of expression was most pronounced in the nonparenchymal fraction. In situ hybridization clearly revealed a strong expression of LIF, LIFR, and gp13O in the oval cells and demonstrated only a weak expression in the parenchyma. Interestingly, transcripts of alpha1-acidglycoprotein were exclusively detected in the parenchyma. These results suggest a phenotypic difference between oval cells and hepatocytes in their signaling through gp130. We hypothesize that the LIF/LIFR gp130 system may be involved in the expansion and differentiation of the liver stem cell compartment. JF - Laboratory investigation; a journal of technical methods and pathology AU - Omori, N AU - Evarts, R P AU - Omori, M AU - Hu, Z AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 15 EP - 24 VL - 75 IS - 1 SN - 0023-6837, 0023-6837 KW - Acute-Phase Proteins KW - 0 KW - Antigens, CD KW - Growth Inhibitors KW - Il6st protein, rat KW - Interleukin-6 KW - Leukemia Inhibitory Factor KW - Lymphokines KW - Membrane Glycoproteins KW - Orosomucoid KW - RNA, Messenger KW - Receptors, Cytokine KW - Cytokine Receptor gp130 KW - 133483-10-0 KW - Index Medicus KW - Animals KW - Antigens, CD -- analysis KW - Bile Ducts -- chemistry KW - Orosomucoid -- genetics KW - Blotting, Northern KW - Acute-Phase Proteins -- genetics KW - RNA, Messenger -- analysis KW - Orosomucoid -- analysis KW - Acute-Phase Proteins -- analysis KW - Membrane Glycoproteins -- analysis KW - Antigens, CD -- genetics KW - Rats KW - Rats, Inbred F344 KW - In Situ Hybridization KW - Bile Ducts -- cytology KW - Cells, Cultured KW - Hepatectomy KW - Signal Transduction KW - Male KW - Epithelium -- chemistry KW - Membrane Glycoproteins -- genetics KW - Receptors, Cytokine -- analysis KW - Growth Inhibitors -- analysis KW - Liver -- cytology KW - Growth Inhibitors -- genetics KW - Lymphokines -- genetics KW - Lymphokines -- analysis KW - Liver Regeneration KW - Liver -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78159297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Expression+of+leukemia+inhibitory+factor+and+its+receptor+during+liver+regeneration+in+the+adult+rat.&rft.au=Omori%2C+N%3BEvarts%2C+R+P%3BOmori%2C+M%3BHu%2C+Z%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Omori&rft.aufirst=N&rft.date=1996-07-01&rft.volume=75&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-20 N1 - Date created - 1996-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of eosinophils generated in vitro from CD34+ peripheral blood progenitor cells. AN - 78156523; 8690047 AB - Methods for isolation and cultivation of CD34+ peripheral blood progenitor cells (PBPCs) have facilitated their use in autologous transplantation and as potential targets for gene therapy. In this work, we present the possibility of using these isolated cells to study lineage-specific hematopoietic differentiation. We have shown that differentiating PBPCs faithfully replicate transcriptional events that occur during maturation of the eosinophil lineage; messenger RNAs encoding the five eosinophil granule proteins were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) after 2-3 days of cytokine-stimulated growth. Only three of the five proteins were detected by immunofluorescence staining after 14 days of cytokine-stimulated growth; the percentage of Charcot-Leyden crystal protein (CLC)-containing cells (16-18%) exceeded that of eosinophil peroxidase (EPO)-containing cells (7-8%), which in turn exceeded that of eosinophil-derived neurotoxin (EDN)-containing cells (2-4%). While the electrophoretic mobilities of both CLC and EPO synthesized by differentiating PBPCs were similar to those of their normal counterparts, immunoreactive EDN was found to be heterogeneous and of higher molecular weight that EDN found in mature eosinophils. It is not clear whether our results, which show progressive, but incomplete, differentiation of PBPCs into eosinophils, reflect a lack of knowledge as to what factors are essential for complete differentiation in vitro or relate to the inherent capacity of PBPCs to differentiate along this lineage. JF - Experimental hematology AU - Rosenberg, H F AU - Dyer, K D AU - Li, F AD - Laboratory of Host Defences, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 888 EP - 893 VL - 24 IS - 8 SN - 0301-472X, 0301-472X KW - Antigens, CD KW - 0 KW - Antigens, CD34 KW - Blood Proteins KW - Cytokines KW - DNA Primers KW - Eosinophil Granule Proteins KW - Glycoproteins KW - Neurotoxins KW - Oligonucleotide Probes KW - Eosinophil Peroxidase KW - EC 1.11.1.- KW - Peroxidases KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Lysophospholipase KW - EC 3.1.1.5 KW - lysolecithin acylhydrolase KW - Index Medicus KW - Glycoproteins -- analysis KW - Glycoproteins -- biosynthesis KW - Fluorescent Antibody Technique, Indirect KW - Humans KW - Cell Differentiation KW - Peroxidases -- biosynthesis KW - Polymerase Chain Reaction KW - Base Sequence KW - Molecular Sequence Data KW - Peroxidases -- analysis KW - Neurotoxins -- biosynthesis KW - Cytokines -- pharmacology KW - Eosinophils -- physiology KW - Hematopoietic Stem Cells -- cytology KW - Neurotoxins -- analysis KW - Hematopoietic Stem Cells -- physiology KW - Blood Proteins -- analysis KW - Hematopoietic Stem Cells -- drug effects KW - Blood Proteins -- biosynthesis KW - Eosinophils -- chemistry KW - Eosinophils -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78156523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+hematology&rft.atitle=Characterization+of+eosinophils+generated+in+vitro+from+CD34%2B+peripheral+blood+progenitor+cells.&rft.au=Rosenberg%2C+H+F%3BDyer%2C+K+D%3BLi%2C+F&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1996-07-01&rft.volume=24&rft.issue=8&rft.spage=888&rft.isbn=&rft.btitle=&rft.title=Experimental+hematology&rft.issn=0301472X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-23 N1 - Date created - 1996-08-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - X16546; GENBANK; M29904; L01664; M29905; X16545; M34462 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxygen distributions partly explain the radiation response of human squamous cell carcinomas. AN - 78143656; 8763877 AB - The oxygen tension of human tumours has often been thought to alter tumour response to radiation therapy. The purpose of this analysis is to determine to what extent the observed results of radiotherapy fit predictions based on in situ human tumour pO2 distributions. The radiation dose-response curve for patients treated with radiation alone for squamous cell cancers of the cervix and oropharynx were calculated based on published data. pO2 histograms were obtained from 30 women with cervical cancer and 11 patients with neck nodes from head and neck cancers. An average of 76 +/- 35 (range 28-174) measurements were made from each patient. Hypoxia was assumed to be a purely dose-modifying factor with a maximum OER of 2.5. Assuming patients are treated with daily radiation doses of 2 Gy, the squamous cell carcinoma alpha/beta ratio is 10 Gy, and that tumours have a mean of 10(8) clonogens, it was possible to estimate tumour control probability. Tumour oxygenation was an extremely important modifier of the slope of the dose-response curve and alone was sufficient to account for the slope of the clinically observed dose-response curve for neck nodes. The response curve for uterine cervical cancers is very shallow, and the oxygen distribution did not completely account for heterogeneity of response of these tumours. The results support the conclusion that oxygen tension distribution is an important modifier of human radiation treatment response. JF - The British journal of cancer. Supplement AU - Okunieff, P AU - de Bie, J AU - Dunphy, E P AU - Terris, D J AU - Höckel, M AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - S185 EP - S190 VL - 27 SN - 0306-9443, 0306-9443 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oropharyngeal Neoplasms -- radiotherapy KW - Humans KW - Head and Neck Neoplasms -- radiotherapy KW - Dose-Response Relationship, Radiation KW - Uterine Cervical Neoplasms -- radiotherapy KW - Female KW - Carcinoma, Squamous Cell -- pathology KW - Oxygen -- metabolism KW - Carcinoma, Squamous Cell -- metabolism KW - Carcinoma, Squamous Cell -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78143656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+cancer.+Supplement&rft.atitle=Oxygen+distributions+partly+explain+the+radiation+response+of+human+squamous+cell+carcinomas.&rft.au=Okunieff%2C+P%3Bde+Bie%2C+J%3BDunphy%2C+E+P%3BTerris%2C+D+J%3BH%C3%B6ckel%2C+M&rft.aulast=Okunieff&rft.aufirst=P&rft.date=1996-07-01&rft.volume=27&rft.issue=&rft.spage=S185&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+cancer.+Supplement&rft.issn=03069443&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-14 N1 - Date created - 1999-07-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Radiat Oncol Biol Phys. 1986 Apr;12(4):459-67 [3516949] Int J Radiat Oncol Biol Phys. 1985 Nov;11(11):1903-9 [4055450] Int J Radiat Oncol Biol Phys. 1988 Jan;14(1):205-7 [3335454] Int J Radiat Oncol Biol Phys. 1988 May;14(5):831-8 [3360652] Radiat Res. 1988 Dec;116(3):482-502 [3205910] Int J Radiat Oncol Biol Phys. 1989 Jan;16(1):37-42 [2912956] Adv Exp Med Biol. 1989;248:835-45 [2782192] Cancer Res. 1989 Dec 1;49(23):6449-65 [2684393] Int J Radiat Biol. 1989 Nov;56(5):761-5 [2573674] Int J Radiat Biol. 1989 Nov;56(5):801-11 [2573679] Br J Radiol. 1990 Jan;63(745):79-80 [2306594] Radiat Res. 1990 Dec;124(3):273-82 [2263727] Int J Radiat Oncol Biol Phys. 1991 Aug;21(3):667-73 [1869461] Radiat Res. 1991 Sep;127(3):297-307 [1886986] Cancer Res. 1991 Nov 15;51(22):6098-102 [1933873] Radiother Oncol. 1992 Dec;25(4):251-60 [1480770] Adv Exp Med Biol. 1992;317:139-51 [1288121] Radiother Oncol. 1993 Jan;26(1):45-50 [8438086] Int J Radiat Oncol Biol Phys. 1993 Jul 15;26(4):631-6 [8330993] Gynecol Oncol. 1993 Nov;51(2):141-9 [8276286] Int J Radiat Oncol Biol Phys. 1995 Jun 15;32(3):567-76 [7790241] Lancet. 1977 Jul 16;2(8029):104-5 [69192] Int J Radiat Oncol Biol Phys. 1977 Nov-Dec;2(11-12):1227-8 [599075] Br J Radiol. 1978 Nov;51(611):879-87 [361144] Int J Radiat Oncol Biol Phys. 1982 Aug;8(8):1277-86 [7141906] Int J Radiat Oncol Biol Phys. 1984 May;10(5):695-712 [6735758] Cancer. 1985 May 1;55(9 Suppl):2118-22 [3919926] Radiology. 1985 Jul;156(1):211-4 [4001408] Clin Neurol Neurosurg. 1985;87(3):167-71 [2996816] Int J Radiat Oncol Biol Phys. 1986 May;12(5):793-9 [3710861] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mecillinam resistance in Escherichia coli is conferred by loss of a second activity of the AroK protein. AN - 78140734; 8682786 AB - Mecillinam, a beta-lactam antibiotic specific to penicillin-binding protein 2 (PBP 2) in Escherichia coli, blocks cell wall elongation and, indirectly, cell division, but its lethality can be overcome by increased levels of ppGpp, the nucleotide effector of the stringent response. We have subjected an E. coli K-12 strain to random insertional mutagenesis with a mini-Tn10 element. One insertion, which was found to confer resistance to mecillinam in relA+ and relA strains, was mapped at 75.5 min on the E. coli map and was located between the promoters and the coding sequence of the aroK gene, which codes for shikimate kinase 1, one of two E. coli shikimate kinases, both of which are involved in aromatic amino acid biosynthesis. The mecillinam resistance conferred by the insertion was abolished in a delta relA delta spoT strain completely lacking ppGpp, and it thus depends on the presence of ppGpp. Furthermore, the insertion increased the ppGpp pool approximately twofold in a relA+ strain. However, this increase was not observed in relA strains, although the insertion still conferred mecillinam resistance in these backgrounds, showing that mecillinam resistance is not due to an increased ppGpp pool. The resistance was also abolished in an ftsZ84(Ts) strain under semipermissive conditions, and the aroK::mini-Tn10 allele partially suppressed ftsZ84(Ts); however, it did not increase the concentration of the FtsZ cell division protein. The insertion greatly decreased or abolished the shikimate kinase activity of AroK in vivo and in vitro. The two shikimate kinases of E. coli are not equivalent; the loss of AroK confers mecillinam resistance, whereas the loss of Arol, does not. Furthermore, the ability of the aroK mutation to confer mecillinam resistance is shown to be independent of polar effects on operon expression and of effects on the availability of aromatic amino acids or shikimic acid. Instead, we conclude that the AroK protein has a second activity, possibly related to cell division regulation, which confers mecillinam sensitivity. We were able to separate the AroK activities mutationally with an aroK mutant allele lacking shikimate kinase activity but still able to confer mecillinam sensitivity. JF - Journal of bacteriology AU - Vinella, D AU - Gagny, B AU - Joseleau-Petit, D AU - D'Ari, R AU - Cashel, M AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2785, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 3818 EP - 3828 VL - 178 IS - 13 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - Carrier Proteins KW - Cytoskeletal Proteins KW - DNA, Bacterial KW - FtsZ protein, Bacteria KW - Penicillin-Binding Proteins KW - Penicillins KW - Guanosine Tetraphosphate KW - 33503-72-9 KW - Peptidyl Transferases KW - EC 2.3.2.12 KW - Hexosyltransferases KW - EC 2.4.1.- KW - Phosphotransferases (Alcohol Group Acceptor) KW - EC 2.7.1.- KW - shikimate kinase KW - EC 2.7.1.71 KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Transposases KW - Muramoylpentapeptide Carboxypeptidase KW - EC 3.4.17.8 KW - Amdinocillin KW - V10579P3QZ KW - Index Medicus KW - Carrier Proteins -- metabolism KW - Penicillin Resistance -- physiology KW - Bacterial Proteins -- metabolism KW - Muramoylpentapeptide Carboxypeptidase -- metabolism KW - Amino Acid Sequence KW - Guanosine Tetraphosphate -- metabolism KW - Base Sequence KW - Molecular Sequence Data KW - Suppression, Genetic KW - Mutagenesis, Insertional KW - Penicillins -- pharmacology KW - Escherichia coli -- metabolism KW - Escherichia coli -- drug effects KW - Phosphotransferases (Alcohol Group Acceptor) -- metabolism KW - Amdinocillin -- pharmacology KW - Phosphotransferases (Alcohol Group Acceptor) -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78140734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Mecillinam+resistance+in+Escherichia+coli+is+conferred+by+loss+of+a+second+activity+of+the+AroK+protein.&rft.au=Vinella%2C+D%3BGagny%2C+B%3BJoseleau-Petit%2C+D%3BD%27Ari%2C+R%3BCashel%2C+M&rft.aulast=Vinella&rft.aufirst=D&rft.date=1996-07-01&rft.volume=178&rft.issue=13&rft.spage=3818&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-20 N1 - Date created - 1996-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trends Genet. 1990 Jan;6(1):22-5 [2183414] J Bacteriol. 1968 Apr;95(4):1283-94 [4869215] Nature. 1969 Mar 1;221(5183):838-41 [4885263] J Biol Chem. 1969 Jun 25;244(12):3133-41 [4893338] Nat New Biol. 1972 Apr 5;236(66):135-7 [4402006] J Bacteriol. 1974 Feb;117(2):578-87 [4590478] J Bacteriol. 1974 Sep;119(3):736-47 [4604283] Nature. 1975 Apr 10;254(5500):516-7 [1091862] J Bacteriol. 1975 Jun;122(3):1283-92 [168179] Proc Natl Acad Sci U S A. 1975 Aug;72(8):2999-3003 [1103132] Biochem Biophys Res Commun. 1976 Apr 5;69(3):751-8 [773380] J Antimicrob Chemother. 1977 Jul;3 Suppl B:13-9 [330482] J Biol Chem. 1991 Mar 25;266(9):5980-90 [2005134] J Biol Chem. 1991 Mar 25;266(9):5991-9 [2005135] Mol Microbiol. 1991 Jan;5(1):49-59 [1849609] J Bacteriol. 1991 Jun;173(11):3500-6 [2045370] Mol Microbiol. 1991 Apr;5(4):791-5 [1649945] EMBO J. 1991 Nov;10(11):3363-72 [1915297] Methods Enzymol. 1991;204:139-80 [1658561] Nature. 1991 Nov 14;354(6349):161-4 [1944597] J Bacteriol. 1992 Jan;174(2):525-9 [1309529] J Bacteriol. 1992 Apr;174(7):2388-90 [1551854] Mol Microbiol. 1992 Mar;6(5):615-20 [1372677] EMBO J. 1992 Apr;11(4):1493-501 [1563353] Mol Microbiol. 1992 Jul;6(13):1841-51 [1630320] Nucleic Acids Res. 1990 Aug 11;18(15):4631 [2201955] Nature. 1992 Sep 17;359(6392):251-4 [1528267] Nature. 1992 Sep 17;359(6392):254-6 [1528268] Mol Gen Genet. 1992 Nov;235(2-3):242-6 [1465098] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1053-7 [8430073] J Bacteriol. 1993 Feb;175(4):1118-25 [8432706] J Bacteriol. 1993 Oct;175(20):6704-10 [8407846] J Bacteriol. 1994 Feb;176(4):966-72 [8106339] J Bacteriol. 1994 May;176(9):2754-8 [8169229] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5813-7 [8016071] EMBO J. 1994 Oct 17;13(20):4919-25 [7957059] Mol Microbiol. 1994 Sep;13(5):911-7 [7815948] Cell. 1995 Feb 10;80(3):367-70 [7859278] J Bacteriol. 1995 Mar;177(6):1627-9 [7883721] Mol Gen Genet. 1995 Jun 10;247(5):546-54 [7603433] Bioessays. 1995 Jun;17(6):527-36 [7575494] J Mol Biol. 1977 Jul;114(1):153-68 [20509] J Bacteriol. 1979 Feb;137(2):839-45 [217866] J Mol Biol. 1978 Dec 15;126(3):367-80 [370402] J Bacteriol. 1979 Mar;137(3):1100-10 [374338] J Bacteriol. 1980 Sep;143(3):1374-83 [6997269] J Biol Chem. 1982 Aug 25;257(16):9759-69 [6286632] Antimicrob Agents Chemother. 1983 Apr;23(4):622-5 [6344786] J Bacteriol. 1985 Aug;163(2):615-22 [3894330] Cell. 1985 Oct;42(3):941-9 [2996784] J Bacteriol. 1986 Jan;165(1):226-32 [3001024] J Bacteriol. 1986 Jan;165(1):331-3 [3001029] J Mol Biol. 1986 Sep 5;191(1):39-58 [3540312] J Bacteriol. 1987 Nov;169(11):4935-40 [2822655] Gene. 1987;61(1):63-74 [3327753] J Bacteriol. 1988 Sep;170(9):4338-42 [2842315] Microbiol Rev. 1989 Mar;53(1):1-24 [2540407] EMBO J. 1989 Jan;8(1):317-23 [2540960] J Bacteriol. 1989 Jun;171(6):3025-30 [2656638] J Bacteriol. 1989 Jun;171(6):3123-7 [2656641] Mol Gen Genet. 1989 May;217(1):85-96 [2549371] J Bacteriol. 1989 Dec;171(12):6493-502 [2687238] J Bacteriol. 1989 Dec;171(12):6511-6 [2687239] J Biol Chem. 1989 Dec 15;264(35):21146-52 [2556396] J Bacteriol. 1990 Mar;172(3):1392-9 [2106510] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group. AN - 78116353; 8655986 AB - The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decrease slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens. JF - The Journal of infectious diseases AU - Lewis, L L AU - Venzon, D AU - Church, J AU - Farley, M AU - Wheeler, S AU - Keller, A AU - Rubin, M AU - Yuen, G AU - Mueller, B AU - Sloas, M AU - Wood, L AU - Balis, F AU - Shearer, G M AU - Brouwers, P AU - Goldsmith, J AU - Pizzo, P A AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 16 EP - 25 VL - 174 IS - 1 SN - 0022-1899, 0022-1899 KW - Antiviral Agents KW - 0 KW - HIV Core Protein p24 KW - RNA, Viral KW - Lamivudine KW - 2T8Q726O95 KW - Zalcitabine KW - 6L3XT8CB3I KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Disease Progression KW - Child KW - HIV Core Protein p24 -- drug effects KW - RNA, Viral -- drug effects KW - Child, Preschool KW - Infant KW - Risk Factors KW - Treatment Outcome KW - Adolescent KW - Female KW - Male KW - Pancreatitis -- chemically induced KW - Antiviral Agents -- therapeutic use KW - HIV Infections -- blood KW - Antiviral Agents -- pharmacokinetics KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - HIV Infections -- genetics KW - Zalcitabine -- pharmacokinetics KW - Zalcitabine -- therapeutic use KW - Antiviral Agents -- adverse effects KW - Zalcitabine -- analogs & derivatives KW - Zalcitabine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78116353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Lamivudine+in+children+with+human+immunodeficiency+virus+infection%3A+a+phase+I%2FII+study.+The+National+Cancer+Institute+Pediatric+Branch-Human+Immunodeficiency+Virus+Working+Group.&rft.au=Lewis%2C+L+L%3BVenzon%2C+D%3BChurch%2C+J%3BFarley%2C+M%3BWheeler%2C+S%3BKeller%2C+A%3BRubin%2C+M%3BYuen%2C+G%3BMueller%2C+B%3BSloas%2C+M%3BWood%2C+L%3BBalis%2C+F%3BShearer%2C+G+M%3BBrouwers%2C+P%3BGoldsmith%2C+J%3BPizzo%2C+P+A&rft.aulast=Lewis&rft.aufirst=L&rft.date=1996-07-01&rft.volume=174&rft.issue=1&rft.spage=16&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-31 N1 - Date created - 1996-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incidence of salivary gland tumors among atomic bomb survivors, 1950-1987. Evaluation of radiation-related risk. AN - 78113493; 8677295 AB - A wide-ranging search for benign and malignant tumors of the major and minor salivary glands among members of the Life Span Study sample of the Radiation Effects Research Foundation identified 41 malignant and 94 benign incident tumors, including 14 malignant and 12 benign tumors of the minor salivary gland, plus 10 major gland tumors of unknown behavior. Dose-response analyses found statistically significant increases in risk with increasing A-bomb dose for both cancer and benign tumors. Estimated relative risks at 1 Sv weighted tissue kerma (RR1Sv, with 90% confidence interval in parentheses) were 4.5 (2.5-8.5) for cancer and 1.7 (1.1-2.7) for benign tumors. When analyzed by histological subtype within these two broad groups, it appeared that most of the dose response for malignant tumors was provided by an exceptionally strong dose response for mucoepidermoid carcinoma [11 exposed cases with dose estimates, RR1Sv = 9.3 (3.5-30.6)], and most or all of that for benign tumors corresponded to Warthin's tumor [12 cases, RR1Sv = 4.1 (1.6-11.3)]. There was a marginal dose response for malignant tumors other than mucoepidermoid carcinoma [RR1Sv = 2.4 (0.99-5.7)] but no significant trend for benign tumors other than Warthin's tumor [RR1Sv = 1.3 (0.9-2.2)]. Re-examination of the original data from published studies of other irradiated populations may shed new light on the remarkable type specificity of the salivary tumor dose response observed in the present study. JF - Radiation research AU - Land, C E AU - Saku, T AU - Hayashi, Y AU - Takahara, O AU - Matsuura, H AU - Tokuoka, S AU - Tokunaga, M AU - Mabuchi, K AD - Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20892, USA. Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 28 EP - 36 VL - 146 IS - 1 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Risk KW - Humans KW - Incidence KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Japan KW - Nuclear Warfare KW - Neoplasms, Radiation-Induced -- epidemiology KW - Salivary Gland Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78113493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Incidence+of+salivary+gland+tumors+among+atomic+bomb+survivors%2C+1950-1987.+Evaluation+of+radiation-related+risk.&rft.au=Land%2C+C+E%3BSaku%2C+T%3BHayashi%2C+Y%3BTakahara%2C+O%3BMatsuura%2C+H%3BTokuoka%2C+S%3BTokunaga%2C+M%3BMabuchi%2C+K&rft.aulast=Land&rft.aufirst=C&rft.date=1996-07-01&rft.volume=146&rft.issue=1&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-09 N1 - Date created - 1996-08-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Radiat Res 1996 Sep;146(3):356 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased sensitivity to cisplatin by nm23-transfected tumor cell lines. AN - 78099837; 8674043 AB - We report a functional link between expression of the metastasis suppressor gene nm23 and cancer cell sensitivity to the alkylating agent cisplatin. Cisplatin was 2-15-fold more inhibitory to the growth in vitro of nm23 transfectants of the K-1735 TK murine melanoma, MDA-MB-435 human breast carcinoma, and OVCAR-3 human ovarian carcinoma cell lines as compared to matched control transfectants. Administration of a single dose of cisplatin i.v. after injection of control- or nm23-1-transfected K-1735 TK melanoma cells resulted in a more pronounced inhibition of pulmonary metastatic colonization by the nm23-1 transfectants. The mechanism of nm23-dependent sensitivity to cisplatin is unknown, but was correlated with increased formation of interstrand DNA cross-links in nm23-H1 transfected breast carcinoma cells. These data suggest that elevation of tumor cell nm23 expression may be considered as a potential therapeutic strategy in combination with cisplatin treatment. JF - Cancer research AU - Ferguson, A W AU - Flatow, U AU - MacDonald, N J AU - Larminat, F AU - Bohr, V A AU - Steeg, P S AD - Women's Cancers Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/07/01/ PY - 1996 DA - 1996 Jul 01 SP - 2931 EP - 2935 VL - 56 IS - 13 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Cross-Linking Reagents KW - DNA, Neoplasm KW - NM23 Nucleoside Diphosphate Kinases KW - Neoplasm Proteins KW - Transcription Factors KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nme1 protein, mouse KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- genetics KW - Animals KW - Drug Screening Assays, Antitumor KW - Tumor Cells, Cultured -- drug effects KW - Ovarian Neoplasms -- genetics KW - DNA Damage KW - Cross-Linking Reagents -- pharmacology KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Ovarian Neoplasms -- drug therapy KW - DNA, Neoplasm -- drug effects KW - Melanoma -- genetics KW - Transfection KW - Melanoma -- drug therapy KW - DNA, Neoplasm -- metabolism KW - Female KW - Transcription Factors -- physiology KW - Neoplasms -- drug therapy KW - Neoplasm Proteins -- physiology KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Neoplasm Proteins -- genetics KW - Cisplatin -- pharmacology KW - Transcription Factors -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78099837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Increased+sensitivity+to+cisplatin+by+nm23-transfected+tumor+cell+lines.&rft.au=Ferguson%2C+A+W%3BFlatow%2C+U%3BMacDonald%2C+N+J%3BLarminat%2C+F%3BBohr%2C+V+A%3BSteeg%2C+P+S&rft.aulast=Ferguson&rft.aufirst=A&rft.date=1996-07-01&rft.volume=56&rft.issue=13&rft.spage=2931&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-12 N1 - Date created - 1996-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Work and Personality: Use of the NEO-PI-R in Industrial/Organisational Psychology AN - 61493134; 9706042 AB - The Revised NEO Personality Inventory (NEO-PI-R), developed by P. T. Costa, Jr., & R. R. McCrae (1992), is a contemporary measure of 30 traits that define the five basic factors -- neuroticism, extraversion, openness to experience, agreeableness, & conscientiousness -- of normal personality. In both research & applied samples, it has shown evidence of reliability & validity, & several studies suggest that it has utility in the prediction of job performance. The domain & facet features of the NEO-PI-R are discussed along with some issues in its use in industrial/organisational psychology. 2 Tables, 52 References. Adapted from the source document. JF - Applied Psychology: An International Review/Psychologie Appliquee: Revue Internationale AU - Costa, Paul T, Jr AD - Laboratory Personality & Cognition National Instit Aging NIH, 4940 Eastern Ave Baltimore MD 21224 paulc@mvx.grc.nia.nih.gov Y1 - 1996/07// PY - 1996 DA - July 1996 SP - 225 EP - 241 VL - 45 IS - 3 SN - 0269-994X, 0269-994X KW - industrial/organizational psychology, Revised NEO Personality Inventory, reliability/validity KW - Organizational Research KW - Psychological Research KW - Reliability KW - Validity KW - Personality Measures KW - article KW - 0104: methodology and research technology; research methods/tools UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61493134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+Psychology%3A+An+International+Review%2FPsychologie+Appliquee%3A+Revue+Internationale&rft.atitle=Work+and+Personality%3A+Use+of+the+NEO-PI-R+in+Industrial%2FOrganisational+Psychology&rft.au=Costa%2C+Paul+T%2C+Jr&rft.aulast=Costa&rft.aufirst=Paul&rft.date=1996-07-01&rft.volume=45&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Applied+Psychology%3A+An+International+Review%2FPsychologie+Appliquee%3A+Revue+Internationale&rft.issn=0269994X&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - ADPYE4 N1 - SubjectsTermNotLitGenreText - Psychological Research; Personality Measures; Organizational Research; Validity; Reliability ER - TY - JOUR T1 - Macromolecular crowding and the mandatory condensation of DNA in bacteria AN - 16446763; 4344554 AB - Cellular DNA in bacteria is localized into nucleoids enclosed by cytoplasm. The forces which cause condensation of the DNA into nucleoids are poorly understood. We suggest that direct and indirect macromolecular crowding forces from the surrounding cytoplasm are critical factors for nucleoid condensation, and that within a bacterial cell these crowding forces are always present at such high levels that the DNA is maintained in a condensed state. The DNA affected includes not only the preexisting genomic DNA but also DNA that is newly introduced by viral infection, replication or other means. JF - FEBS Letters AU - Zimmerman, S B AU - Murphy, L D AD - Laboratory of Molecular Biology, Bldg. 5, Room 328W, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0560, USA Y1 - 1996/07// PY - 1996 DA - Jul 1996 SP - 245 EP - 248 VL - 390 IS - 3 SN - 0014-5793, 0014-5793 KW - DNA KW - condensation KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02725:DNA KW - N 14630:Chemical reactions & interactions, including effects of radiation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16446763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+Letters&rft.atitle=Macromolecular+crowding+and+the+mandatory+condensation+of+DNA+in+bacteria&rft.au=Zimmerman%2C+S+B%3BMurphy%2C+L+D&rft.aulast=Zimmerman&rft.aufirst=S&rft.date=1996-07-01&rft.volume=390&rft.issue=3&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=FEBS+Letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Large scale recovery and purification of periplasmic recombinant protein from E. coli using expanded bed adsorption chromatography followed by new ion exchange media AN - 15917433; 4045145 AB - Expanded bed chromatography was used for the recovery and purification of modified Pseudomonas aeruginosa exotoxin A. The exotoxin accumulates in the periplasmic space of E. coli BL21( lambda DE3), was released from the cells by osmotic shock and captured by applying the open cell suspension directly to an anion exchanger (STREAMLINE super(TM) DEAE) using an expanded bed (STREAMLINE registered ) column. Processing of 4.5 kg of E. coli using the expanded bed process was 3 times faster and did not require clarification of the bacterial extract, in comparison with the conventional purification method. Also, the recovered protein solution was 3 times more concentrated and the yield slightly higher. JF - Journal of Biotechnology AU - Johansson, HJ AU - Jaegersten, C AU - Shiloach, J AD - Biotechnol. Unit NIDDK, Bldg. 6 Rm. B1-33, NIH, Bethesda, MD 20892, USA Y1 - 1996/07// PY - 1996 DA - Jul 1996 SP - 9 EP - 14 VL - 48 IS - 1-2 SN - 0168-1656, 0168-1656 KW - exotoxin A KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - periplasmic space KW - chromatography KW - Escherichia coli KW - Pseudomonas aeruginosa KW - W2 32340:Other peptides, proteins, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15917433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biotechnology&rft.atitle=Large+scale+recovery+and+purification+of+periplasmic+recombinant+protein+from+E.+coli+using+expanded+bed+adsorption+chromatography+followed+by+new+ion+exchange+media&rft.au=Johansson%2C+HJ%3BJaegersten%2C+C%3BShiloach%2C+J&rft.aulast=Johansson&rft.aufirst=HJ&rft.date=1996-07-01&rft.volume=48&rft.issue=1-2&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biotechnology&rft.issn=01681656&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - periplasmic space; chromatography; Escherichia coli; Pseudomonas aeruginosa ER - TY - JOUR T1 - Influence of interleukin-2 regimens on circulating populations of lymphocytes after adoptive transfer of anti-CD3-stimulated T cells: Results from a phase I trial in cancer patients AN - 15826283; 4008514 AB - The adoptive transfer of anti-CD3-stimulated T killer (T-AK) cells was tested with different bolus and infusional interleukin-2 (IL-2) regimens, and anti-CD3 stimulation procedures to determine immunologic and antitumor effects in patients with a variety of advanced cancers. Indium-111 labeling was used to observe traffic patterns of the infused T-AK. Autologous peripheral blood mononuclear cells were obtained by leukapheresis. Cyclophosphamide (300 mg/m super(2)) was given to most patients immediately after leukapheresis. The harvested cells were activated ex vivo with anti-CD3 overnight or for 4 days, at which time cells were reinfused and an IL-2 regimen was begun. Treatment was repeated 28 days later. This treatment regimen induced significant increases in leukocytes, lymphocytes, and eosinophils in patients in most treatment cohorts. Circulating lymphocytes were predominantly CD3 super(+) T cells with preferential expansion of the CD8 super(+) subset. Patients receiving cells stimulated in vitro for 4 days had significant T-cell lymphocytosis with either infusional or bolus plus infusional IL-2 regimens. T-cell viability was decreased in culture after a second 4-day stimulation with anti-CD3 at day 28; this decrease could be prevented by adding IL-2 to the culture media. Cells stimulated overnight required both bolus and infusional IL-2 to show an atypical lymphocytosis in vivo. Overnight-stimulated T-AK did not show decreases in in vitro viability at the day 28 restimulation. Indium-111-labeled cells trafficked to the liver, spleen, and bone marrow. No increase in uptake was observed in tumor deposits. There were 2 patients with partial responses, 5 with minor responses, 19 with stable disease, and 88 with progressive disease. The length of in vitro anti-CD3 stimulation, and the dose and timing of IL-2 administration in vivo results in different circulating leukocyte populations after adoptive T-AK infusion. Generally, the CD8 super(+) T-cell subset was preferentially expanded by this treatment approach. Repeated ex vivo stimulation with anti-CD3 may cause cell death. JF - Journal of Immunotherapy with Emphasis on Tumor Biology AU - Curti, B D AU - Ochoa, A C AU - Urba, W J AU - Alvord, W G AU - Kopp, W C AU - Powers, G AU - Hawk, C AU - Creekmore, S P AU - Gause, B L AU - Janik, JE AU - Holmlund, J T AU - Kremers, P AU - Fenton, R G AU - Miller, L AD - NCI-FCRDC, BRMP, 501 West Seventh St., Suite 3, Frederick, MD 21701, USA Y1 - 1996/07// PY - 1996 DA - Jul 1996 SP - 296 EP - 308 VL - 19 IS - 4 SN - 1067-5582, 1067-5582 KW - CD3 antigen KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - interleukin 2 KW - lymphocytes T KW - adoptive transfer KW - cancer KW - F 06818:Cancer immunotherapy KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15826283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.atitle=Influence+of+interleukin-2+regimens+on+circulating+populations+of+lymphocytes+after+adoptive+transfer+of+anti-CD3-stimulated+T+cells%3A+Results+from+a+phase+I+trial+in+cancer+patients&rft.au=Curti%2C+B+D%3BOchoa%2C+A+C%3BUrba%2C+W+J%3BAlvord%2C+W+G%3BKopp%2C+W+C%3BPowers%2C+G%3BHawk%2C+C%3BCreekmore%2C+S+P%3BGause%2C+B+L%3BJanik%2C+JE%3BHolmlund%2C+J+T%3BKremers%2C+P%3BFenton%2C+R+G%3BMiller%2C+L&rft.aulast=Curti&rft.aufirst=B&rft.date=1996-07-01&rft.volume=19&rft.issue=4&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - interleukin 2; lymphocytes T; cancer; adoptive transfer ER - TY - JOUR T1 - A covalently bound catalytic intermediate in Escherichia coli asparaginase: Crystal structure of a Thr-89-Val mutant AN - 15816779; 3998693 AB - Escherichia coli asparaginase II catalyzes the hydrolysis of L-asparagine to L-aspartate via a threonine-bound acyl-enzyme intermediate. A nearly inactive mutant in which one of the active site threonines, Thr-89, was replaced by valine was constructed, expressed, and crystallized. Its structure, solved at 2.2 angstrom resolution, shows high overall similarity to the wild-type enzyme, but an aspartyl moiety is covalently bound to Thr-12, resembling a reaction intermediate. Kinetic analysis confirms the deacylation deficiency, which is also explained on a structural basis. The previously identified oxyanion hole is described in more detail. JF - FEBS Letters AU - Palm, G J AU - Lubkowski, J AU - Derst, C AU - Schleper, S AU - Roehm, K-H AU - Wlodawer, A AD - Macromolecular Struct. Lab., NCI-Frederick Cancer Res. and Dev. Cent., ABL-Basic Res. Prog., Frederick, MD 21702-1201, USA Y1 - 1996/07// PY - 1996 DA - Jul 1996 SP - 211 EP - 216 VL - 390 IS - 2 SN - 0014-5793, 0014-5793 KW - asparaginase II KW - Microbiology Abstracts B: Bacteriology KW - deacylation KW - Escherichia coli KW - crystal structure KW - mutants KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15816779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+Letters&rft.atitle=A+covalently+bound+catalytic+intermediate+in+Escherichia+coli+asparaginase%3A+Crystal+structure+of+a+Thr-89-Val+mutant&rft.au=Palm%2C+G+J%3BLubkowski%2C+J%3BDerst%2C+C%3BSchleper%2C+S%3BRoehm%2C+K-H%3BWlodawer%2C+A&rft.aulast=Palm&rft.aufirst=G&rft.date=1996-07-01&rft.volume=390&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=FEBS+Letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; mutants; crystal structure; deacylation ER - TY - JOUR T1 - Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. AN - 78066267; 8637513 AB - For many people infected with the hepatitis C virus (HCV), the route of exposure, risk of transmission, and severity of associated liver disease are unknown. We studied these variables in people who donated blood voluntarily. Blood donors who tested positive for HCV antibodies on enzyme immunoassay were classified according to whether the results of a confirmatory second-generation recombinant immunoblot assay (RIBA) for HCV were positive, negative, or indeterminate. The evaluations also included an assessment of risk factors, a physical examination, serial determinations of alanine aminotransferase levels and HCV serologic assays, a polymerase-chain-reaction assay for HCV RNA, testing of sexual contacts and family members, and liver biopsies in some participants who were HCV-positive by RIBA. A total of 481 donors were studied, among whom 248 were positive for HCV by RIBA, 102 had indeterminate results, and 131 were HCV-negative. In a logistic-regression analysis, significant risk factors for HCV infection among the HCV-positive participants were a history of blood transfusion in 66 (27 percent; P < 0.001 for the comparison with RIBA-negative donors), intranasal cocaine use in 169 (68 percent, P < 0.001), intravenous drug use in 103 (42 percent, P = 0.001), sexual promiscuity in 132 (53 percent, P = 0.002), and ear piercing among men (P < 0.05). Nine of 85 sexual partners of HCV-positive donors were anti-HCV-positive; 8 had used intravenous drugs or received transfusions. HCV RNA was found in 213 HCV-positive donors (86 percent), 3 who had indeterminate results by RIBA (2 of these 3 tested positive with a more specific, third-generation RIBA), and none who were HCV-negative. Of the HCV-positive donors, 69 percent had biochemical evidence of chronic liver disease; among 77 donors positive for HCV by RIBA who underwent liver biopsy, 5 had severe chronic hepatitis or cirrhosis, 66 had mild-to-moderate chronic hepatitis, and 6 had no evidence of hepatitis. Among volunteer blood donors, prior blood transfusion, intranasal cocaine use, intravenous drug use, sexual promiscuity, and ear piercing in men are risk factors for HCV infection. The high frequency of intravenous drug use was unexpected, because these donors had denied such use when questioned directly at the time of their blood donations. JF - The New England journal of medicine AU - Conry-Cantilena, C AU - VanRaden, M AU - Gibble, J AU - Melpolder, J AU - Shakil, A O AU - Viladomiu, L AU - Cheung, L AU - DiBisceglie, A AU - Hoofnagle, J AU - Shih, J W AD - Department of Transfusion Medicine, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md 20892, USA. Y1 - 1996/06/27/ PY - 1996 DA - 1996 Jun 27 SP - 1691 EP - 1696 VL - 334 IS - 26 SN - 0028-4793, 0028-4793 KW - Hepatitis C Antibodies KW - 0 KW - RNA, Viral KW - Cocaine KW - I5Y540LHVR KW - Abridged Index Medicus KW - Index Medicus KW - Immunoblotting KW - Hepacivirus -- immunology KW - Hepacivirus -- isolation & purification KW - Hepatitis C Antibodies -- blood KW - Humans KW - Cocaine -- administration & dosage KW - Viremia -- diagnosis KW - Sexual Behavior KW - Liver Diseases -- epidemiology KW - Logistic Models KW - Risk Factors KW - Adult KW - Substance-Related Disorders KW - Middle Aged KW - Female KW - Male KW - Substance Abuse, Intravenous KW - RNA, Viral -- blood KW - Ear, External -- surgery KW - Hepatitis C -- transmission KW - Hepatitis C -- diagnosis KW - Hepatitis C -- etiology KW - Blood Donors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78066267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Routes+of+infection%2C+viremia%2C+and+liver+disease+in+blood+donors+found+to+have+hepatitis+C+virus+infection.&rft.au=Conry-Cantilena%2C+C%3BVanRaden%2C+M%3BGibble%2C+J%3BMelpolder%2C+J%3BShakil%2C+A+O%3BViladomiu%2C+L%3BCheung%2C+L%3BDiBisceglie%2C+A%3BHoofnagle%2C+J%3BShih%2C+J+W&rft.aulast=Conry-Cantilena&rft.aufirst=C&rft.date=1996-06-27&rft.volume=334&rft.issue=26&rft.spage=1691&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-05 N1 - Date created - 1996-07-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1996 Jun 27;334(26):1734-5 [8637520] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a novel inhibitor (NSC 665564) of dihydroorotate dehydrogenase with a potency equivalent to brequinar. AN - 78125893; 8687451 AB - A novel inhibitor of dihydroorotate dehydrogenase (DHO-DH) has been discovered using data from the National Cancer Institute's in vitro drug screen. Upon analysis of cytotoxicity results from the sixty tumor cell lines used in this screen, the COMPARE program predicted that NSC 665564 was likely to have the same mechanism of inhibition as brequinar, a known potent inhibitor of DHO-DH. We validated this prediction experimentally using MOLT-4 lymphoblast and found the IC50 of brequinar (0.5 microM) and NSC 665564 (0.3 microM) were comparable and that this induced cytotoxicity was reversed by either uridine or cytidine. The enzyme target of NSC 665564 was shown to be identical to that of brequinar when incubation with each drug followed by a 1 h pulse with [14C] sodium bicarbonate resulted in cellular accumulation of [14C]N-carbamyl-L-aspartic acid and [14C]L-dihydroorotic acid, with concurrent marked depletion of CTP and UTP. The Ki's for NSC 665564 and brequinar were 0.14 and 0.24 microM, respectively, when partially purified MOLT-4 mitochondria (the site of DHO-DH) were used. These results show that mechanistic predictions obtained using correlations from the COMPARE algorithm are independent of structure since the structure of NSC 665564 is dissimilar to that of other established DHO-DH inhibitors. JF - Biochemical and biophysical research communications AU - Cleaveland, E S AU - Zaharevitz, D W AU - Kelley, J A AU - Paull, K AU - Cooney, D A AU - Ford, H AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892, USA. Y1 - 1996/06/25/ PY - 1996 DA - 1996 Jun 25 SP - 654 EP - 659 VL - 223 IS - 3 SN - 0006-291X, 0006-291X KW - Antineoplastic Agents KW - 0 KW - Biphenyl Compounds KW - Carbolines KW - Enzyme Inhibitors KW - NSC 665564 KW - Ribonucleotides KW - 4,5-dihydroorotic acid KW - 155-54-4 KW - Aspartic Acid KW - 30KYC7MIAI KW - brequinar KW - 5XL19F49H6 KW - Orotic Acid KW - 61H4T033E5 KW - Sodium Bicarbonate KW - 8MDF5V39QO KW - ureidosuccinic acid KW - 923-37-5 KW - Oxidoreductases KW - EC 1.- KW - Oxidoreductases Acting on CH-CH Group Donors KW - EC 1.3.- KW - dihydroorotate dehydrogenase KW - EC 1.3.5.2 KW - Index Medicus KW - Aspartic Acid -- metabolism KW - Software KW - Ovarian Neoplasms KW - Mitochondria -- enzymology KW - Humans KW - Orotic Acid -- metabolism KW - Breast Neoplasms KW - Central Nervous System Neoplasms KW - Orotic Acid -- analogs & derivatives KW - Melanoma KW - Leukemia KW - Aspartic Acid -- analogs & derivatives KW - Tumor Cells, Cultured KW - Kidney Neoplasms KW - Lung Neoplasms KW - Kinetics KW - Ribonucleotides -- metabolism KW - Sodium Bicarbonate -- metabolism KW - Prostatic Neoplasms KW - Carcinoma, Non-Small-Cell Lung KW - Colonic Neoplasms KW - Male KW - Female KW - Enzyme Inhibitors -- toxicity KW - Biphenyl Compounds -- toxicity KW - Carbolines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Oxidoreductases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78125893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Identification+of+a+novel+inhibitor+%28NSC+665564%29+of+dihydroorotate+dehydrogenase+with+a+potency+equivalent+to+brequinar.&rft.au=Cleaveland%2C+E+S%3BZaharevitz%2C+D+W%3BKelley%2C+J+A%3BPaull%2C+K%3BCooney%2C+D+A%3BFord%2C+H&rft.aulast=Cleaveland&rft.aufirst=E&rft.date=1996-06-25&rft.volume=223&rft.issue=3&rft.spage=654&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-16 N1 - Date created - 1996-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation analysis of the transforming growth factor beta type II receptor in sporadic human cancers of the pancreas, liver, and breast. AN - 78124231; 8687435 AB - The transforming growth factor beta (TGF beta) binds the type II TGF beta growth factor receptor (TGF beta RII) to inhibit growth of most epithelial tissues. Most human colon cancers with microsatellite instability have frameshift mutations in two microsatellites within the TGF beta RII coding region; such mutations truncate the receptor to produce resistance to TGF beta. To investigate this pathway in other tissues, we surveyed sporadic human cancers of the pancreas, liver and breast to determine the frequency of microsatellite mutations in the TGF beta RII. We amplified genomic DNA segments containing two microsatellites plus 72% of domain XI of the serine-threonine kinase region. SSCP analysis showed no evidence of mutation in 32 sporadic cancers (12 pancreas, 10 liver, and 10 breast). We conclude that microsatellite mutations in TGF beta RII are uncommon in sporadic tumors of the pancreas, liver and breast. JF - Biochemical and biophysical research communications AU - Vincent, F AU - Hagiwara, K AU - Ke, Y AU - Stoner, G D AU - Demetrick, D J AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/06/25/ PY - 1996 DA - 1996 Jun 25 SP - 561 EP - 564 VL - 223 IS - 3 SN - 0006-291X, 0006-291X KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - DNA, Satellite KW - Receptors, Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - DNA, Satellite -- genetics KW - Polymerase Chain Reaction KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Protein-Serine-Threonine Kinases -- genetics KW - Polymorphism, Single-Stranded Conformational KW - Female KW - Breast Neoplasms -- genetics KW - Receptors, Transforming Growth Factor beta -- genetics KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Pancreatic Neoplasms -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78124231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Mutation+analysis+of+the+transforming+growth+factor+beta+type+II+receptor+in+sporadic+human+cancers+of+the+pancreas%2C+liver%2C+and+breast.&rft.au=Vincent%2C+F%3BHagiwara%2C+K%3BKe%2C+Y%3BStoner%2C+G+D%3BDemetrick%2C+D+J%3BBennett%2C+W+P&rft.aulast=Vincent&rft.aufirst=F&rft.date=1996-06-25&rft.volume=223&rft.issue=3&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-16 N1 - Date created - 1996-08-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M85079; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A segment of five amino acids in the second extracellular loop of the cholecystokinin-B receptor is essential for selectivity of the peptide agonist gastrin. AN - 78134897; 8663021 AB - The two known receptors mediating the actions of cholecystokinin (CCK) and gastrin, CCK type A (CCKAR) and CCK type B (CCKBR) receptors, are G protein-coupled receptors having approximately 50% amino acid homology. Both the CCKAR and CCKBR have high affinity for sulfated CCK peptides, while only the CCKBR has high affinity for gastrin peptides. To determine the structural basis for the selectivity of the CCKBR for gastrin, we first constructed a series of CCKB/AR chimeras in which restriction endonuclease-defined segments of the CCKBR were replaced with the corresponding segments of the CCKAR. Chimeras transiently expressed in COS-1 cells were screened for the selective loss of gastrin affinity according to the displacement of 125I-labeled Bolton-Hunter-CCK-8 binding by gastrin-17-I and CCK-8. The sequence spanning from transmembrane domain III (TM III) to TM V was the only segment that resulted in the selective loss of gastrin affinity. This segment could account for 100 of the expected 300-fold lower affinity of gastrin-17-I observed for the control CCKAR compared to the control CCKBR. Using site-directed mutagenesis in this segment of the CCKBR, we identified a sequence of 5 amino acids in the second extracellular loop responsible for this 100-fold selective loss in gastrin affinity. 125I-labeled Bolton-Hunter-CCK-8 binding displacement by L365,260 (a CCKBR selective antagonist) was unaffected by the changes in these 5 amino acids. These results present for the first time the identification of the amino acid sequence of the CCKBR conferring the majority of the selectivity for gastrin. JF - The Journal of biological chemistry AU - Silvente-Poirot, S AU - Wank, S A AD - Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1804, USA. Y1 - 1996/06/21/ PY - 1996 DA - 1996 Jun 21 SP - 14698 EP - 14706 VL - 271 IS - 25 SN - 0021-9258, 0021-9258 KW - Benzodiazepinones KW - 0 KW - Bolton Hunter-cholecystokinin octapeptide KW - Gastrins KW - Indicators and Reagents KW - Phenylurea Compounds KW - Receptor, Cholecystokinin B KW - Receptors, Cholecystokinin KW - Recombinant Fusion Proteins KW - Succinimides KW - L 365260 KW - 370JHF4586 KW - Sincalide KW - M03GIQ7Z6P KW - Index Medicus KW - Animals KW - Models, Structural KW - Humans KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Succinimides -- metabolism KW - Transfection KW - Kinetics KW - Sincalide -- metabolism KW - Binding, Competitive KW - Cercopithecus aethiops KW - Point Mutation KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- agonists KW - Cell Membrane -- metabolism KW - Sincalide -- analogs & derivatives KW - Sequence Homology, Amino Acid KW - Benzodiazepinones -- pharmacology KW - Cell Line KW - Protein Structure, Secondary KW - Gastrins -- metabolism KW - Receptors, Cholecystokinin -- agonists KW - Receptors, Cholecystokinin -- metabolism KW - Gastrins -- pharmacology KW - Receptors, Cholecystokinin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78134897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=A+segment+of+five+amino+acids+in+the+second+extracellular+loop+of+the+cholecystokinin-B+receptor+is+essential+for+selectivity+of+the+peptide+agonist+gastrin.&rft.au=Silvente-Poirot%2C+S%3BWank%2C+S+A&rft.aulast=Silvente-Poirot&rft.aufirst=S&rft.date=1996-06-21&rft.volume=271&rft.issue=25&rft.spage=14698&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-13 N1 - Date created - 1996-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular modeling and site-directed mutagenesis studies of a phorbol ester-binding site in protein kinase C. AN - 78123689; 8691452 AB - The protein kinase C (PKC) binding site used by PKC activators such as phorbol esters and diacylglycerols (DAGs) has been characterized by means of molecular modeling and site-directed mutagenesis studies. Based upon a NMR-determined solution structure of the second cysteinerich domain of PKC alpha, molecular modeling was used to study the structures of the complexes formed between the PKC receptor and a number of PKC ligands, phorbol esters, and DAGs. Site-directed mutagenesis studies identified a number of residues important to the binding of phorbol esters to PKC. Analysis of the molecular modeling and mutagenesis results allows the development of a binding model for PKC ligands for which the precise binding nature is defined. The calculated hydrogen bond energies between the protein and various ligands in this binding model are consistent with their measured binding affinities. The binding site for phorbol esters and DAGs is located in a highly conserved, hydrophobic loop region formed by residues 6-12 and 20-27. For the binding elements in phorbol esters, the oxygen at C20 contributes most to the overall binding energy, and that at C3 plays a significant role. The oxygen atom at C12 is not directly involved in the interaction between phorbol esters and PKC. Our results also suggest that the oxygens at C9 and C13 are involved in PKC binding, while the oxygen at C4 is of minimal significance. These results are consistent with known structure-activity relationships in the phorbol ester family of compounds. Comparisons with the X-ray structure showed that although the X-ray data support the results for oxygens at C3, C12, and C20 of phorbol esters, they suggest different roles for oxygens at C4, C9, and C13. Several factors which may contribute to these discrepancies are discussed. JF - Journal of medicinal chemistry AU - Wang, S AU - Kazanietz, M G AU - Blumberg, P M AU - Marquez, V E AU - Milne, G W AD - Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996/06/21/ PY - 1996 DA - 1996 Jun 21 SP - 2541 EP - 2553 VL - 39 IS - 13 SN - 0022-2623, 0022-2623 KW - Diglycerides KW - 0 KW - Isoenzymes KW - Ligands KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Molecular Structure KW - Isoenzymes -- chemistry KW - Computer Simulation KW - Models, Molecular KW - Mutagenesis, Site-Directed -- genetics KW - Computer Graphics KW - Amino Acid Sequence KW - Isoenzymes -- metabolism KW - Binding Sites KW - Magnetic Resonance Spectroscopy KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Hydrogen Bonding KW - Protein Kinase C -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Protein Kinase C -- genetics KW - Protein Kinase C -- chemistry KW - Diglycerides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78123689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Molecular+modeling+and+site-directed+mutagenesis+studies+of+a+phorbol+ester-binding+site+in+protein+kinase+C.&rft.au=Wang%2C+S%3BKazanietz%2C+M+G%3BBlumberg%2C+P+M%3BMarquez%2C+V+E%3BMilne%2C+G+W&rft.aulast=Wang&rft.aufirst=S&rft.date=1996-06-21&rft.volume=39&rft.issue=13&rft.spage=2541&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-23 N1 - Date created - 1996-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate. AN - 78054899; 8628358 AB - Hereditary angioedema results from a congenital deficiency of functional C1 inhibitor and is characterized by episodic bouts of edema, which may be life-threatening when they involve the larynx. We evaluated the effectiveness of a C1 inhibitor concentrate in the prevention and treatment of attacks of hereditary angioedema. The concentrate was vapor-heated to inactivate hepatitis and human immunodeficiency viruses. We conducted two double-blind, placebo-controlled studies. The first was a crossover study consisting of two 17-day trials in which prophylactic infusions of either C1 inhibitor (25 plasma units per kilogram of body weight) or placebo were given intravenously every third day to six patients with hereditary angioedema. The second study was conducted in patients with acute attacks of hereditary angioedema and assessed the length of time to a clinical response after infusions of either 25 plasma units of C1 inhibitor per kilogram (55 infusions in 11 patients) or placebo (49 infusions in 11 patients). The infusions of C1 inhibitor concentrate resulted in close to normal functional levels of C1 inhibitor and C4. As compared with placebo, prophylactic infusions of C1 inhibitor resulted in significantly lower daily symptom scores for the severity of edema of the extremities (P<0.01), larynx (P<0.05), abdomen (P<0.05), and genitourinary tract (P<0.05). Likewise, during the treatment study the time from the start of an infusion to the beginning of improvement in symptoms was shorter for the C1 inhibitor infusions than the placebo infusions (55 vs. 563 minutes, P<0.001). There was no evidence of toxicity. Infusions of a vapor-heated C1 inhibitor concentrate are a safe and effective means of both preventing attacks of hereditary angioedema and treating acute attacks. JF - The New England journal of medicine AU - Waytes, A T AU - Rosen, F S AU - Frank, M M AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md, USA. Y1 - 1996/06/20/ PY - 1996 DA - 1996 Jun 20 SP - 1630 EP - 1634 VL - 334 IS - 25 SN - 0028-4793, 0028-4793 KW - Complement C1 Inactivator Proteins KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Hot Temperature KW - Double-Blind Method KW - Humans KW - Treatment Outcome KW - Cross-Over Studies KW - Sterilization KW - Complement C1 Inactivator Proteins -- therapeutic use KW - Angioedema -- therapy KW - Angioedema -- genetics KW - Angioedema -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78054899?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Treatment+of+hereditary+angioedema+with+a+vapor-heated+C1+inhibitor+concentrate.&rft.au=Waytes%2C+A+T%3BRosen%2C+F+S%3BFrank%2C+M+M&rft.aulast=Waytes&rft.aufirst=A&rft.date=1996-06-20&rft.volume=334&rft.issue=25&rft.spage=1630&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-27 N1 - Date created - 1996-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1996 Jun 20;334(25):1666-7 [8628365] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Second cancers after adjuvant tamoxifen therapy for breast cancer. AN - 78062413; 8637050 JF - Journal of the National Cancer Institute AU - Curtis, R E AU - Boice, J D AU - Shriner, D A AU - Hankey, B F AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/06/19/ PY - 1996 DA - 1996 Jun 19 SP - 832 EP - 834 VL - 88 IS - 12 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Estrogen Antagonists KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Risk KW - Odds Ratio KW - Humans KW - SEER Program KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Breast Neoplasms -- drug therapy KW - Neoplasms, Second Primary -- epidemiology KW - Tamoxifen -- therapeutic use KW - Estrogen Antagonists -- adverse effects KW - Tamoxifen -- adverse effects KW - Estrogen Antagonists -- therapeutic use KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Antineoplastic Agents, Hormonal -- adverse effects KW - Neoplasms, Second Primary -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78062413?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Second+cancers+after+adjuvant+tamoxifen+therapy+for+breast+cancer.&rft.au=Curtis%2C+R+E%3BBoice%2C+J+D%3BShriner%2C+D+A%3BHankey%2C+B+F%3BFraumeni%2C+J+F&rft.aulast=Curtis&rft.aufirst=R&rft.date=1996-06-19&rft.volume=88&rft.issue=12&rft.spage=832&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-11 N1 - Date created - 1996-07-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1997 May 7;89(9):657-9 [9150192] J Natl Cancer Inst. 1996 Oct 16;88(20):1497-9; author reply, 1497-9 [8841030] J Natl Cancer Inst. 1996 Oct 16;88(20):1496-7; author reply, 1497-9 [8841029] J Natl Cancer Inst. 2001 Nov 21;93(22):1753-4 [11717338] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of protein kinase C inhibits calcium-activated potassium channels in rat pituitary tumour cells. AN - 78340796; 8799890 AB - 1. The regulation of large-conductance, calcium- and voltage-dependent potassium (BK) channels by protein kinase C (PKC) was investigated in clonal rat anterior pituitary cells (GH4C1), which were voltage clamped at -40 mV in a physiological potassium gradient through amphotericin-perforated patches. 2. Maximal activation of PKC by 100 nM phorbol 12, 13-dibutyrate (PdBu) almost completely inhibited the voltage-activated outward current through BK channels. In contrast PdBu had no significant effect on the residual outward current after block of BK channels with 2 mM TEA or 30 nM charybdotoxin. In single-channel recordings from cell-attached patches, PdBu reduced the open probability of BK channels more than eightfold with no significant effect on mean open lifetime or unitary conductance. 3. The effects of PdBu on BK channels were not mimicked by the 4 alpha-isomer, which does not activate PKC, and were blocked almost completely by 25 microM chelerythrine, a specific, noncompetitive PKC inhibitor. 4. PdBu had no significant effect on the amplitude of the pharmacologically isolated, high voltage-activated calcium current. 5. Inhibition of BK channel activity by PKC provides the first molecular mechanism linking hormonal activation of phospholipase C to sustained excitability in pituitary cells. JF - The Journal of physiology AU - Shipston, M J AU - Armstrong, D L AD - Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. mshipston@srv2.med.ed.ac.uk Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 665 EP - 672 VL - 493 ( Pt 3) SN - 0022-3751, 0022-3751 KW - Anti-Bacterial Agents KW - 0 KW - Potassium Channels KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Amphotericin B KW - 7XU7A7DROE KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Anti-Bacterial Agents -- pharmacology KW - Enzyme Activation -- physiology KW - Cyclic AMP -- physiology KW - Amphotericin B -- pharmacology KW - Biotransformation -- drug effects KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Ion Channel Gating -- drug effects KW - Protein Kinase C -- metabolism KW - Potassium Channels -- metabolism KW - Calcium -- physiology KW - Potassium Channels -- drug effects KW - Pituitary Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78340796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+physiology&rft.atitle=Activation+of+protein+kinase+C+inhibits+calcium-activated+potassium+channels+in+rat+pituitary+tumour+cells.&rft.au=Shipston%2C+M+J%3BArmstrong%2C+D+L&rft.aulast=Shipston&rft.aufirst=M&rft.date=1996-06-15&rft.volume=493+%28+Pt+3%29&rft.issue=&rft.spage=665&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=00223751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-05 N1 - Date created - 1996-12-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1984 May 10;259(9):5827-32 [6425298] Biochem Biophys Res Commun. 1993 Jan 15;190(1):263-9 [8422251] J Biol Chem. 1985 Jul 15;260(14):8366-71 [3159731] J Biol Chem. 1986 Feb 25;261(6):2684-9 [2869031] Physiol Rev. 1986 Oct;66(4):887-952 [3532145] FEBS Lett. 1993 Dec 28;336(3):433-9 [8282106] Pflugers Arch. 1994 Aug;428(1):17-25 [7971157] Endocrinology. 1987 Aug;121(2):793-802 [3036484] J Neurosci. 1988 Nov;8(11):4069-78 [2846795] J Gen Physiol. 1988 Oct;92(4):531-48 [2849631] Eur J Biochem. 1989 Aug 1;183(2):397-406 [2569396] Brain Res. 1989 Sep 4;496(1-2):113-23 [2553198] J Physiol. 1990 Jun;425:117-32 [1698974] Acta Physiol Scand. 1990 Oct;140(2):269-78 [2176434] Endocrinology. 1991 Apr;128(4):2015-26 [1900783] Nature. 1991 Jun 13;351(6327):570-3 [1710783] Mol Endocrinol. 1992 Jan;6(1):120-31 [1738365] Endocrinology. 1992 Dec;131(6):2873-80 [1332850] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4282-6 [2408278] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A simplified method for the repeated replacement of yeast chromosomal sequences with in vitro mutations. AN - 78329537; 8810040 AB - A strategy for gene replacement in Saccharomyces cerevisiae has been modified to facilitate the repeated substitution of a chromosomal locus with in vitro generated variant sequences, so that the resulting locus contains only the desired mutation and is free of extraneous vector DNA. The construction of an internally deleted chromosomal target locus carrying the counterselectable CYH2S marker and a second positively selectable marker has been simplified; the design of the locus has been altered to increase the frequency of authentic gene replacements obtained upon the subsequent integration of in vitro mutated DNA. The modified chromosomal target locus is amenable to replacement using either of two transformation protocols: (i) integration of a second positively selectable plasmid carrying mutant sequences to form a tandem intermediate structure at the locus; upon counterselection on cycloheximide, all vector sequence is excised to give the desired replacement at high frequency (> 70%); (ii) single-step integration of a linear segment of mutated genomic DNA by selection for cycloheximide resistance. A subsequent screen for the loss of the positively selectable target locus marker detects the desired replacement at modest frequency (> 2%). Polymerase chain reaction using multiple primers in a single amplification reaction is useful for monitoring these variously modified chromosomal loci. JF - Yeast (Chichester, England) AU - Szent-Gyorgyi, C AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 667 EP - 672 VL - 12 IS - 7 SN - 0749-503X, 0749-503X KW - DNA, Fungal KW - 0 KW - Genetic Markers KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Polymerase Chain Reaction KW - Genes, Fungal KW - Cycloheximide -- pharmacology KW - Drug Resistance, Microbial -- genetics KW - DNA, Fungal -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Chromosomes, Fungal -- genetics KW - Genetic Techniques KW - Saccharomyces cerevisiae -- drug effects KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78329537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Yeast+%28Chichester%2C+England%29&rft.atitle=A+simplified+method+for+the+repeated+replacement+of+yeast+chromosomal+sequences+with+in+vitro+mutations.&rft.au=Szent-Gyorgyi%2C+C&rft.aulast=Szent-Gyorgyi&rft.aufirst=C&rft.date=1996-06-15&rft.volume=12&rft.issue=7&rft.spage=667&rft.isbn=&rft.btitle=&rft.title=Yeast+%28Chichester%2C+England%29&rft.issn=0749503X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-24 N1 - Date created - 1997-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cognitive enhancement. New strategies for stimulating cholinergic, glutamatergic, and nitric oxide systems. AN - 78142966; 8687034 AB - The development of treatments for AD is being pursued along many diverse lines. While the ACh hypothesis has generated abundant development efforts, little clinical progress has been achieved to date. Recent efforts aimed at developing more potent, more specific, and safer ChE inhibitors appear to offer greater potential for therapeutic success than achieved to date. Treatments aimed at the NMDA Glu system lag much further behind in their development. Progress in this area must be tempered by the potential for glutamate excitotoxicity mediated through this neurotransmitter system. Development of indirect agonists operating at the glycine and polyamine modulatory sites on the NMDA receptor might offer the safest alternative to applying more direct agonists. While a great degree of interest had been generated by the reports of NO involvement in signal transduction through the NMDA system, this area of research has been complicated by conflicting reports regarding NO involvement in learning and LTP. Moreover, the interaction of drugs acting on NOS with the vascular effects mediated by eNOS has also complicated development of drugs that act specifically on the neural actions of NO. This area will continue to receive extensive research attention; but similar to the development of Glu agonists, attention must be given to the potential neurotoxic effects of overstimulating this system. Perhaps targeting other presynaptic mechanisms that effect glutamate release might be a safer strategy to pursue. Considerable progress has been made over the last two decades in identifying the genetic and neural mechanisms involved in AD. Progress in developing treatments will remain highly correlated with this effort, and with basic research geared to comprehending how memories are formed and why neurons degenerate and regenerate. JF - Annals of the New York Academy of Sciences AU - Ingram, D K AU - Shimada, A AU - Spangler, E L AU - Ikari, H AU - Hengemihle, J AU - Kuo, H AU - Greig, N AD - Molecular Physiology and Genetics Section, National Institute of Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 348 EP - 361 VL - 786 SN - 0077-8923, 0077-8923 KW - Nitric Oxide KW - 31C4KY9ESH KW - Glutamic Acid KW - 3KX376GY7L KW - Spermidine KW - U87FK77H25 KW - Index Medicus KW - Maze Learning KW - Animals KW - Spermidine -- pharmacology KW - Glutamic Acid -- metabolism KW - Cognition -- drug effects KW - Nitric Oxide -- metabolism KW - Cholinergic Fibers -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78142966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Cognitive+enhancement.+New+strategies+for+stimulating+cholinergic%2C+glutamatergic%2C+and+nitric+oxide+systems.&rft.au=Ingram%2C+D+K%3BShimada%2C+A%3BSpangler%2C+E+L%3BIkari%2C+H%3BHengemihle%2C+J%3BKuo%2C+H%3BGreig%2C+N&rft.aulast=Ingram&rft.aufirst=D&rft.date=1996-06-15&rft.volume=786&rft.issue=&rft.spage=348&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-19 N1 - Date created - 1996-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of hydroxyl radical formation and protection of nigral neurons by l-deprenyl (selegiline). AN - 78141780; 8687036 AB - The present study clearly demonstrated that l-deprenyl confers a substantial protective effect against MPP+ in the substantia nigra zona compacta in vivo. 32.39. The protection provided by l-deprenyl may not depend on its inhibition of type B monoamine oxidase. A unique antioxidant property of l-deprenyl by suppression of cycotoxic. OH formation and associated oxidative damage induced by MPP+ in the A9 melanized nigral neurons may contribute to the protection against MPP+ toxicity in the nigrostriatal system. The likelihood that l-deprenyl may confer neuroprotection against MPP+ toxicity through antioxidant effect is further strongly supported by our recent data that U-78517F (2-methlaminochromans) a potent inhibitor of ironcatalyzed lipid peroxidation, and DMSO an effective. OH scavenger also protect nigral neurons against MPP(+)-induced severe oxidative injury in the substantia nigra. This putative antioxidant effect of deprenyl may explore another mechanism which may in part contribute to its overt neuroprotection against several toxins, including 6-OHDA, DSP-4, and MPTP, and the possible clinical effects on slowing the neuronal degeneration in early Parkinson's disease, Alzheimer's disorder and even senescent changes. JF - Annals of the New York Academy of Sciences AU - Wu, R M AU - Murphy, D L AU - Chiueh, C C AD - Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 379 EP - 390 VL - 786 SN - 0077-8923, 0077-8923 KW - Selegiline KW - 2K1V7GP655 KW - Hydroxyl Radical KW - 3352-57-6 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dopamine -- metabolism KW - Time Factors KW - Male KW - 1-Methyl-4-phenylpyridinium -- pharmacology KW - Selegiline -- pharmacology KW - Hydroxyl Radical -- metabolism KW - Neurons -- drug effects KW - Corpus Striatum -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78141780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Suppression+of+hydroxyl+radical+formation+and+protection+of+nigral+neurons+by+l-deprenyl+%28selegiline%29.&rft.au=Wu%2C+R+M%3BMurphy%2C+D+L%3BChiueh%2C+C+C&rft.aulast=Wu&rft.aufirst=R&rft.date=1996-06-15&rft.volume=786&rft.issue=&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-19 N1 - Date created - 1996-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 'Long distance sequencer' method; a novel strategy for large DNA sequencing projects. AN - 78140182; 8710525 JF - Nucleic acids research AU - Hagiwara, K AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 2460 EP - 2461 VL - 24 IS - 12 SN - 0305-1048, 0305-1048 KW - Index Medicus KW - Base Sequence KW - Molecular Sequence Data KW - Sequence Analysis, DNA -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78140182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=%27Long+distance+sequencer%27+method%3B+a+novel+strategy+for+large+DNA+sequencing+projects.&rft.au=Hagiwara%2C+K%3BHarris%2C+C+C&rft.aulast=Hagiwara&rft.aufirst=K&rft.date=1996-06-15&rft.volume=24&rft.issue=12&rft.spage=2460&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-09 N1 - Date created - 1996-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1990 May 25;18(10):3095-6 [2349129] Nucleic Acids Res. 1990 May 25;18(10):2887-90 [2161516] Nature. 1994 Jun 23;369(6482):684-5 [8208299] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-acetyltransferase expression and metabolic activation of the food-derived heterocyclic amines in the human mammary gland. AN - 78132274; 8665493 AB - The heterocyclic amines (HCAs) found in cooked meat are procarcinogens that are metabolically activated by N-hydroxylation followed by O-acetylation by the N-acetyltransferases NAT1 and NAT2. Despite the importance of metabolic activation in HCA carcinogenicity and the finding that several HCAs are rodent mammary gland carcinogens, nothing was known about O-acetylation activity in the human mammary gland. The current study examines the expression and catalytic activity of NAT toward the N-hydroxy-HCAs 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP) and 2-hydroxy-amino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ) in the human mammary gland. Mammary gland cytosol from 10 women and lysates from a primary culture of human mammary epithelial cells metabolically activated 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline by NAT-mediated 0-acetyltransferase, as measured by the acetyl CoA-enhanced binding of the N-hydroxylamines to calf thymus DNA in vitro. N-acetylation of p-aminosalicylic, an activity specific to NAT1, but not N-acetylation of sulfamethazine, an activity specific to NAT2, was detected in the mammary gland cytosols and human mammary epithelial cell lysates. Immunohistochemical analysis of human mammary gland sections showed positive staining for NAT1 protein in the epithelial cells lining the mammary gland ducts. Reverse transcription-PCR analysis showed that mRNA transcripts for both NAT1 and NAT2 were present in human mammary gland; however, no NAT2 catalytic activity was detectable. Our data demonstrate for the first time that the human mammary gland is catalytically active toward the metabolic activation of HCA food mutagens, and that this activity is most likely contributed by NAT1 expressed in the ductular epithelial cells of the mammary gland. JF - Cancer research AU - Sadrieh, N AU - Davis, C D AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 2683 EP - 2687 VL - 56 IS - 12 SN - 0008-5472, 0008-5472 KW - DNA Adducts KW - 0 KW - Imidazoles KW - Isoenzymes KW - Mutagens KW - Pyridines KW - Quinolines KW - 2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 124489-20-9 KW - Sulfamethazine KW - 48U51W007F KW - RNA KW - 63231-63-0 KW - 2-hydroxyamino-3-methylimidazolo(4,5-f)quinoline KW - 77314-23-9 KW - Acetyltransferases KW - EC 2.3.1.- KW - acetyl-CoA - lysine N6-acetyltransferase KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - N-acetyltransferase 1 KW - NAT2 protein, human KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Humans KW - Aged KW - DNA Adducts -- metabolism KW - Rats KW - Acetylation KW - Sulfamethazine -- metabolism KW - Rats, Sprague-Dawley KW - RNA -- metabolism KW - Polymorphism, Restriction Fragment Length KW - Biotransformation KW - Mammary Glands, Animal -- metabolism KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Quinolines -- metabolism KW - Acetyltransferases -- metabolism KW - Mutagens -- metabolism KW - Imidazoles -- metabolism KW - Pyridines -- metabolism KW - Arylamine N-Acetyltransferase -- metabolism KW - Isoenzymes -- metabolism KW - Breast -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78132274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=N-acetyltransferase+expression+and+metabolic+activation+of+the+food-derived+heterocyclic+amines+in+the+human+mammary+gland.&rft.au=Sadrieh%2C+N%3BDavis%2C+C+D%3BSnyderwine%2C+E+G&rft.aulast=Sadrieh&rft.aufirst=N&rft.date=1996-06-15&rft.volume=56&rft.issue=12&rft.spage=2683&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-06 N1 - Date created - 1996-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. AN - 78111549; 8675700 AB - Receptor tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. C-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). HGF/c-met plays diverse role in regulation of cell growth, shape and movement. Constitutively activated met, such as tpr-met, is a potent oncogene in vitro, but its carcinogenic role in vivo remains unclear. Our study demonstrates that expression of tpr-met leads to development of mammary tumors and other malignancies in transgenic mice, and suggests that deregulated met expression may be involved in mammary carcinogenesis. JF - The Journal of clinical investigation AU - Liang, T J AU - Reid, A E AU - Xavier, R AU - Cardiff, R D AU - Wang, T C AD - Department of Medicine, Massachusetts General Hospital, Boston 02114, USA. liangt@bdg.niddk.nih.gov Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 2872 EP - 2877 VL - 97 IS - 12 SN - 0021-9738, 0021-9738 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Hyperplasia KW - Base Sequence KW - Molecular Sequence Data KW - Mice KW - Mice, Transgenic KW - Female KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Mammary Glands, Animal -- pathology KW - Mammary Neoplasms, Experimental -- etiology KW - Proto-Oncogenes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78111549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Transgenic+expression+of+tpr-met+oncogene+leads+to+development+of+mammary+hyperplasia+and+tumors.&rft.au=Liang%2C+T+J%3BReid%2C+A+E%3BXavier%2C+R%3BCardiff%2C+R+D%3BWang%2C+T+C&rft.aulast=Liang&rft.aufirst=T&rft.date=1996-06-15&rft.volume=97&rft.issue=12&rft.spage=2872&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-12 N1 - Date created - 1996-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1985 May;41(1):211-9 [2859927] Hepatology. 1995 Jun;21(6):1543-6 [7768498] Cell. 1986 Jun 20;45(6):895-904 [2423252] Proc Natl Acad Sci U S A. 1987 Sep;84(18):6379-83 [2819873] Oncogene. 1987 May;1(2):229-33 [3325883] Science. 1988 Jun 24;240(4860):1759-64 [3289117] Cell. 1988 Dec 23;55(6):965-77 [2849512] Cell. 1988 Dec 23;55(6):979-88 [2974321] Mol Cell Biol. 1990 Apr;10(4):1805-10 [1690852] Oncogene. 1990 May;5(5):645-55 [2140597] J Cell Biol. 1990 Nov;111(5 Pt 1):2097-108 [2146276] Science. 1991 Feb 15;251(4995):802-4 [1846706] Am J Pathol. 1991 Sep;139(3):495-501 [1887859] Cancer Cells. 1991 Jun;3(6):227-32 [1832923] Oncogene. 1991 Nov;6(11):1997-2003 [1719465] Cell. 1991 Nov 29;67(5):901-8 [1835669] Lancet. 1992 Jan 18;339(8786):139-43 [1346009] Prog Growth Factor Res. 1991;3(1):67-85 [1838014] Science. 1992 Aug 28;257(5074):1258-61 [1387731] EXS. 1993;65:107-30 [8380734] EXS. 1993;65:131-65 [8380735] Mol Cell Biol. 1993 Nov;13(11):6711-22 [8413267] Cancer Res. 1993 Nov 15;53(22):5355-60 [7693339] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4731-5 [8197126] Nature. 1994 Jun 23;369(6482):669-71 [8208295] Cell. 1986 Jun 6;45(5):649-57 [2871941] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. AN - 78083935; 8652811 JF - Blood AU - Cheson, B D AU - Bennett, J M AU - Grever, M AU - Kay, N AU - Keating, M J AU - O'Brien, S AU - Rai, K R AD - National Cancer Institute, Bethesda, MD 20892-7436, USA. Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 4990 EP - 4997 VL - 87 IS - 12 SN - 0006-4971, 0006-4971 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Bone Marrow -- pathology KW - Diagnosis, Differential KW - Neoplasm Staging KW - Humans KW - Neutropenia -- complications KW - Neutropenia -- chemically induced KW - Clinical Trials as Topic -- standards KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Patient Selection KW - Clinical Trials as Topic -- methods KW - Infection -- etiology KW - Lymphocyte Count KW - National Institutes of Health (U.S.) KW - Treatment Outcome KW - Chromosome Aberrations KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Immunophenotyping KW - Leukemia, Lymphocytic, Chronic, B-Cell -- diagnosis KW - Leukemia, Lymphocytic, Chronic, B-Cell -- pathology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78083935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=National+Cancer+Institute-sponsored+Working+Group+guidelines+for+chronic+lymphocytic+leukemia%3A+revised+guidelines+for+diagnosis+and+treatment.&rft.au=Cheson%2C+B+D%3BBennett%2C+J+M%3BGrever%2C+M%3BKay%2C+N%3BKeating%2C+M+J%3BO%27Brien%2C+S%3BRai%2C+K+R&rft.aulast=Cheson&rft.aufirst=B&rft.date=1996-06-15&rft.volume=87&rft.issue=12&rft.spage=4990&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-31 N1 - Date created - 1996-07-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Blood. 2010 Sep 9;116(10):1817; author reply 1817-8 [20829381] Blood. 2009 Jun 18;113(25):6496-7; author reply 6497-8 [19541838] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pseudouridine synthases: four families of enzymes containing a putative uridine-binding motif also conserved in dUTPases and dCTP deaminases. AN - 20112537; 8731162 AB - Using a combination of several methods for protein sequence comparison and motif analysis, it is shown that the four recently described pseudouridine syntheses with different specificities belong to four distinct families. Three of these families share two conserved motifs that are likely to be directly involved in catalysis. One of these motifs is detected also in two other families of enzymes that specifically bind uridine, namely deoxycitidine triphosphate deaminases and deoxyuridine triphosphatases. It is proposed that this motif is an essential part of the uridine-binding site. Two of the pseudouridine syntheses, one of which modifies the anticodon arm of tRNAs and the other is predicted to modify a portion of the large ribosomal subunit RNA belonging to the peptidyltransferase center, are encoded in all extensively sequenced genomes, including the 'minimal' genome of Mycoplasma genitalium. These particular RNA modifications and the respective enzymes are likely to be essential for the functioning of any cell. JF - Nucleic Acids Research AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. Y1 - 1996/06/15/ PY - 1996 DA - 1996 Jun 15 SP - 2411 EP - 2415 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 24 IS - 12 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Genomes KW - Anticodons KW - Mycoplasma genitalium KW - tRNA KW - Enzymes KW - Ribosomal subunits KW - dUTP pyrophosphatase KW - dCTP deaminase KW - Triphosphatase KW - pseudouridine synthase KW - rRNA KW - RNA modification KW - Peptidyltransferase KW - Conserved sequence KW - Uridine KW - Catalysis KW - Amino acid sequence KW - J 02310:Genetics & Taxonomy KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20112537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Pseudouridine+synthases%3A+four+families+of+enzymes+containing+a+putative+uridine-binding+motif+also+conserved+in+dUTPases+and+dCTP+deaminases.&rft.au=Koonin%2C+E+V&rft.aulast=Koonin&rft.aufirst=E&rft.date=1996-06-15&rft.volume=24&rft.issue=12&rft.spage=2411&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Genomes; Anticodons; tRNA; Enzymes; Ribosomal subunits; dUTP pyrophosphatase; dCTP deaminase; rRNA; pseudouridine synthase; Triphosphatase; RNA modification; Peptidyltransferase; Conserved sequence; Uridine; Amino acid sequence; Catalysis; Mycoplasma genitalium ER - TY - JOUR T1 - Arrested DNA replication in Xenopus and release by Escherichia coli mutagenesis proteins. AN - 78078277; 8658137 AB - Xenopus oocytes and oocyte nuclear extracts repair ultraviolet photoproducts on double-stranded (ds) DNA and replicate single-stranded (ss) to ds DNA. M13 ss DNA molecules containing cyclobutane pyrimidine dimers were maintained but not replicated in Xenopus oocytes yet were replicated in progesterone-matured oocytes. The replication arrest functioned only in cis. The replication arrest was alleviated by injection into oocytes of messenger RNAs encoding the prokaryotic mutagenesis proteins UmuD'C or MucA'B. These results may help explain how cells stabilize repair or replication events on DNA with unrepairable lesions. JF - Science (New York, N.Y.) AU - Oda, N AU - Levin, J D AU - Spoonde, A Y AU - Frank, E G AU - Levine, A S AU - Woodgate, R AU - Ackerman, E J AD - Office of Scientific Director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/06/14/ PY - 1996 DA - 1996 Jun 14 SP - 1644 EP - 1646 VL - 272 IS - 5268 SN - 0036-8075, 0036-8075 KW - Bacterial Proteins KW - 0 KW - DNA, Single-Stranded KW - Escherichia coli Proteins KW - MucA protein, Bacteria KW - MucB protein, Bacteria KW - DNA KW - 9007-49-2 KW - UmuC protein, E coli KW - 98059-80-4 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - DNA Repair KW - DNA Damage KW - Xenopus KW - Bacteriophage phi X 174 -- genetics KW - Bacteriophage M13 -- genetics KW - DNA -- biosynthesis KW - DNA, Single-Stranded -- biosynthesis KW - Oocytes -- metabolism KW - Escherichia coli -- genetics KW - DNA Replication KW - Bacterial Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78078277?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Arrested+DNA+replication+in+Xenopus+and+release+by+Escherichia+coli+mutagenesis+proteins.&rft.au=Oda%2C+N%3BLevin%2C+J+D%3BSpoonde%2C+A+Y%3BFrank%2C+E+G%3BLevine%2C+A+S%3BWoodgate%2C+R%3BAckerman%2C+E+J&rft.aulast=Oda&rft.aufirst=N&rft.date=1996-06-14&rft.volume=272&rft.issue=5268&rft.spage=1644&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-01 N1 - Date created - 1996-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gastric chief cells possess NK1 receptors which mediate pepsinogen secretion and are regulated by agents that increase cAMP and phospholipase C. AN - 78129663; 8672532 AB - In order to determine whether tachykinins alter the function of chief cells and to characterize the receptors mediating the effect, we investigated the abilities of various substance P (SP)-related peptides to inhibit the binding of 125I-Bolton-Hunter labeled substance P (125I-BH-SP) and their abilities to alter cell function in dispersed chief cells from guinea pig stomach. Binding of 125I-BH-SP was saturable, reversible, time- and temperature-dependent and was inhibited by several SP-related peptides with relative potencies of SP = physalaemin (IC50:0.19 nM) > SP methyl ester (SP-ME) (IC50:3.3 nM) > eledoisin (IC50:6.1 nM) > neurokinin A (NKA) (IC50: 65 nM) > neurokinin B (NKB) (IC50:80 nM). Analyses of these binding data demonstrated that chief cells possess a high and low affinity class of binding sites. Neither 125I-NKA nor [phenylalanyl-3,4,5-3H]senktide demonstrated saturable binding to chief cells. Acid stripping experiments demonstrated rapid ligand internalization with 55% of the bound radioligand internalized by 10 min. Phospholipase C activating agents (carbachol, CCK-8), adenylate cyclase activating agents (secretin, VIP), TPA and the calcium ionophore, A23187, all inhibited the binding of 125I-BH-SP and it was due to inhibition of ligand internalization with no change in surface bound parameters. SP (0.1 microM) stimulated pepsinogen secretion but was 4-times less efficacious than CCK-8 (10 nM) or carbachol (1 mM). 10 nM SP stimulated a rapid increase in cytoplasmic free calcium concentration ([Ca2+]i) followed by a sustained elevation lasting 2 min. Single cell spectroscopy demonstrated SP (10 pM to 1 microM) did not cause calcium oscillations. The NK1 receptor antagonist, CP96,345 specifically inhibited the SP-stimulated changes in [Ca2+]i and pepsinogen secretion. The relative potencies of SP-related peptides to stimulate pepsinogen secretion and [Ca2+]i demonstrated a close agreement with their abilities to inhibit the binding of 125I-BH-SP, and comparison of the dose-response curves suggests occupation of the low affinity sites mediate changes in biologic activity. In conclusion, the present study demonstrates that chief cells possess a NK1 subtype of tachykinin receptor, occupation of the low affinity sites of this receptor cause calcium mobilization and pepsinogen secretion, and that binding to this receptor is regulated by agents that activate phospholipase C, adenylate cyclase, protein kinase C and calcium mobilization. JF - Biochimica et biophysica acta AU - Kitsukawa, Y AU - Turner, R J AU - Pradhan, T K AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1804, USA. Y1 - 1996/06/13/ PY - 1996 DA - 1996 Jun 13 SP - 105 EP - 116 VL - 1312 IS - 2 SN - 0006-3002, 0006-3002 KW - Neurokinin-1 Receptor Antagonists KW - 0 KW - Pepsinogens KW - Peptides KW - Receptors, Neurokinin-1 KW - Tachykinins KW - Secretin KW - 1393-25-5 KW - Substance P KW - 33507-63-0 KW - Cyclic AMP KW - E0399OZS9N KW - Type C Phospholipases KW - EC 3.1.4.- KW - Sincalide KW - M03GIQ7Z6P KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Temperature KW - Peptides -- pharmacology KW - Sincalide -- pharmacology KW - Calcium -- metabolism KW - Kinetics KW - Protein Binding -- drug effects KW - Binding, Competitive KW - Endocytosis -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Secretin -- pharmacology KW - Male KW - Substance P -- pharmacology KW - Pepsinogens -- secretion KW - Substance P -- metabolism KW - Cyclic AMP -- metabolism KW - Receptors, Neurokinin-1 -- metabolism KW - Gastric Mucosa -- drug effects KW - Gastric Mucosa -- cytology KW - Receptors, Neurokinin-1 -- agonists KW - Tachykinins -- pharmacology KW - Substance P -- analogs & derivatives KW - Type C Phospholipases -- metabolism KW - Gastric Mucosa -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78129663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Gastric+chief+cells+possess+NK1+receptors+which+mediate+pepsinogen+secretion+and+are+regulated+by+agents+that+increase+cAMP+and+phospholipase+C.&rft.au=Kitsukawa%2C+Y%3BTurner%2C+R+J%3BPradhan%2C+T+K%3BJensen%2C+R+T&rft.aulast=Kitsukawa&rft.aufirst=Y&rft.date=1996-06-13&rft.volume=1312&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-09 N1 - Date created - 1996-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the GADD45 response to ionizing radiation in WI-L2-NS cells, a p53 mutant cell line. AN - 78171562; 8676920 AB - We have previously reported that WI-L2-NS, a human lymphoblastoid cell line, has very high basal levels of GADD45 mRNA and protein in spite of a p53 mutation at amino acid 237. Regardless of the amount of Gadd45 in this cell line, no growth suppression activity was detected. We report here that in WI-L2-NS, the mutated p53 protein adopts predominantly a wild type (wt) conformation and binds to the p53 binding site in the GADD45 third intron. In this cell line, the already high levels of mutated p53 protein can be induced further by ionizing radiation (IR) but the response of the p53 downstream effector genes is altered. Induction of GADD45 and CIP1/WAF1 is reduced compared to p53 wt cell lines but is still substantially higher than the average fold induction obtained from 39 p53 mutant cell lines. Induction of the MDM2 gene was not detected in WI-L2-NS following IR. The induction pattern of the three p53 effector genes by the alkylating agent methylmethane sulfonate (MMS) was also attenuated in WI-L2-NS cells. In TK6 cells, a WI-L2-NS sister cell line having a p53 wt genotype, the induction of the p53 downstream effectors is normal, i.e. induced, both at the protein and the mRNA levels. These results indicate that the DNA binding activity of the mutated p53 protein in WI-L2-NS might be responsible, at least in part, for the high basal levels of GADD45 but can not mediate the full induction of the p53 downstream effector genes. The reason(s) for the inability of Gadd45 to suppress growth in this cell line remains however unknown. JF - Mutation research AU - Carrier, F AU - Bae, I AU - Smith, M L AU - Ayers, D M AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, DTP, DCT, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. carrier@Box-c.nih.gov Y1 - 1996/06/10/ PY - 1996 DA - 1996 Jun 10 SP - 79 EP - 86 VL - 352 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Alkylating Agents KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Nuclear Proteins KW - Proteins KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - DNA KW - 9007-49-2 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - Alkylating Agents -- pharmacology KW - DNA -- metabolism KW - Humans KW - Lymphocytes KW - RNA, Messenger -- biosynthesis KW - Introns -- genetics KW - Binding Sites KW - Methyl Methanesulfonate -- pharmacology KW - Proto-Oncogene Proteins -- genetics KW - Mutation KW - Cell Line KW - Cyclins -- genetics KW - Protein Conformation KW - Tumor Suppressor Protein p53 -- analysis KW - Gene Expression Regulation -- radiation effects KW - Gene Expression Regulation -- physiology KW - Tumor Suppressor Protein p53 -- chemistry KW - Proteins -- analysis KW - Gene Expression Regulation -- drug effects KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Proteins -- genetics KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78171562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Characterization+of+the+GADD45+response+to+ionizing+radiation+in+WI-L2-NS+cells%2C+a+p53+mutant+cell+line.&rft.au=Carrier%2C+F%3BBae%2C+I%3BSmith%2C+M+L%3BAyers%2C+D+M%3BFornace%2C+A+J&rft.aulast=Carrier&rft.aufirst=F&rft.date=1996-06-10&rft.volume=352&rft.issue=1-2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-15 N1 - Date created - 1996-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-performance liquid chromatography method with light-scattering detection for measurements of lipid class composition: analysis of brains from alcoholics. AN - 78354634; 8811429 AB - A high-performance liquid chromatographic method with evaporative light-scattering detection was developed for the analysis of intact lipid classes in nervous tissue. The method had the ability to resolve plasmalogen-phosphatidyl-ethanolamine and diacyl-phosphatidylethanolamine along with other major phospholipid classes in a single run. This technique was employed for the investigation of the effects of chronic alcohol consumption on the membrane lipid class composition of human brains (alcoholics, n = 13; controls, n = 11). Measurements were performed on cholesterol, cerebrosides, sulfatides, phospholipids and sphingolipids in total lipid extracts of white matter, gray matter and cerebellar regions of human brains. No significant differences in the lipid class composition between the groups were observed. JF - Journal of chromatography. B, Biomedical applications AU - Olsson, N U AU - Harding, A J AU - Harper, C AU - Salem, N AD - Laboratory of Membrane Biochemistry and Biophysics, NIAAA, National Institutes of Health, MD 20852, USA. Y1 - 1996/06/07/ PY - 1996 DA - 1996 Jun 07 SP - 213 EP - 218 VL - 681 IS - 2 SN - 1572-6495, 1572-6495 KW - Cerebrosides KW - 0 KW - Membrane Lipids KW - Phosphatidylethanolamines KW - Phospholipids KW - Plasmalogens KW - Sphingolipids KW - Sulfoglycosphingolipids KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Cerebrosides -- analysis KW - Plasmalogens -- analysis KW - Humans KW - Phospholipids -- analysis KW - Cholesterol -- analysis KW - Sulfoglycosphingolipids -- analysis KW - Sphingolipids -- analysis KW - Phosphatidylethanolamines -- analysis KW - Scattering, Radiation KW - Membrane Lipids -- analysis KW - Brain Chemistry KW - Chromatography, High Pressure Liquid -- methods KW - Alcoholism -- metabolism KW - Light UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78354634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+B%2C+Biomedical+applications&rft.atitle=High-performance+liquid+chromatography+method+with+light-scattering+detection+for+measurements+of+lipid+class+composition%3A+analysis+of+brains+from+alcoholics.&rft.au=Olsson%2C+N+U%3BHarding%2C+A+J%3BHarper%2C+C%3BSalem%2C+N&rft.aulast=Olsson&rft.aufirst=N&rft.date=1996-06-07&rft.volume=681&rft.issue=2&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+B%2C+Biomedical+applications&rft.issn=15726495&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-10 N1 - Date created - 1996-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and biological activities of flavonoid derivatives as A3 adenosine receptor antagonists. AN - 78112908; 8691424 AB - A broad screening of phytochemicals has demonstrated that certain flavone and flavonol derivatives have a relatively high affinity at A3 adenosine receptors, with Ki values of > or = 1 microM (Ji et al. J. Med. Chem. 1996, 39, 781-788). We have further modified the flavone structure to achieve a degree of selectivity for cloned human brain A3 receptors, determined in competitive binding assays versus [125I]AB-MECA[N6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methylur onamide)]. Affinity was determined in radioligand binding assays at rat brain A1 and A2a receptors using [3H]-N6-PIA ([3H]-(R)-N6-phenylisopropyladenosine) and [3H]CGS21680 [[3H]-2-[[4-(2-carboxyethyl)phenyl]ethylamino]-5'-(N-ethylcarbamoyl++ +)adenosine], respectively. The triethyl and tripropyl ether derivatives of the flavonol galangin, 4, had Ki values of 0.3 - 0.4 microM at human A3 receptors. The presence of a 5-hydroxyl group increased selectivity of flavonols for human A3 receptors. The 2',3,4',7-tetraethyl ether derivative of the flavonol morin, 7, displayed a Ki value of 4.8 microM at human A3 receptors and was inactive at rat A1/A2a receptors. 3,6-Dichloro-2'-(isopropyloxy)-4'-methylflavone, 11e, was both potent and highly selective (approximately 200-fold) for human A3 receptors (Ki = 0.56 microM). Among dihydroflavonol analogues, the 2-styryl instead of the 2-aryl substituent, in 15, afforded selectivity for human A3 vs rat A1 or A2A receptors. The 2-styryl-6-propoxy derivative, 20, of the furanochromone visnagin was 30-fold selective for human A3 receptors vs either rat A1 or A2A receptors. Several of the more potent derivatives effectively antagonized the effects of an agonist in a functional A3 receptor assay, i.e. inhibition of adenylyl cyclase in CHO cells expressing cloned rat A3 receptors. In conclusion, these series of flavonoids provide leads for the development of novel potent and subtype selective A3 antagonists. JF - Journal of medicinal chemistry AU - Karton, Y AU - Jiang, J L AU - Ji, X D AU - Melman, N AU - Olah, M E AU - Stiles, G L AU - Jacobson, K A AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA. Y1 - 1996/06/07/ PY - 1996 DA - 1996 Jun 07 SP - 2293 EP - 2301 VL - 39 IS - 12 SN - 0022-2623, 0022-2623 KW - Flavonoids KW - 0 KW - Nerve Tissue Proteins KW - Purinergic P1 Receptor Antagonists KW - Receptor, Adenosine A2A KW - Receptors, Purinergic P1 KW - Recombinant Fusion Proteins KW - galangin KW - 142FWE6ECS KW - Index Medicus KW - Recombinant Fusion Proteins -- antagonists & inhibitors KW - Molecular Structure KW - Animals KW - Brain Chemistry KW - Humans KW - Radioligand Assay KW - Receptors, Purinergic P1 -- metabolism KW - Drug Design KW - Protein Binding KW - Structure-Activity Relationship KW - Rats KW - Kinetics KW - CHO Cells KW - Cricetinae KW - Flavonoids -- chemical synthesis KW - Flavonoids -- chemistry KW - Nerve Tissue Proteins -- antagonists & inhibitors KW - Flavonoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78112908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Synthesis+and+biological+activities+of+flavonoid+derivatives+as+A3+adenosine+receptor+antagonists.&rft.au=Karton%2C+Y%3BJiang%2C+J+L%3BJi%2C+X+D%3BMelman%2C+N%3BOlah%2C+M+E%3BStiles%2C+G+L%3BJacobson%2C+K+A&rft.aulast=Karton&rft.aufirst=Y&rft.date=1996-06-07&rft.volume=39&rft.issue=12&rft.spage=2293&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-23 N1 - Date created - 1996-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental estrogens: can two "alrights" make a wrong? AN - 78071482; 8633235 JF - Science (New York, N.Y.) AU - Simons, S S AD - Steroid Hormones Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. steroids@helix.nih.gov Y1 - 1996/06/07/ PY - 1996 DA - 1996 Jun 07 SP - 1451 VL - 272 IS - 5267 SN - 0036-8075, 0036-8075 KW - Environmental Pollutants KW - 0 KW - Estrogens, Non-Steroidal KW - Insecticides KW - Receptors, Estrogen KW - Estradiol KW - 4TI98Z838E KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae -- metabolism KW - Receptors, Estrogen -- drug effects KW - Humans KW - Binding, Competitive KW - Receptors, Estrogen -- metabolism KW - Drug Synergism KW - Estradiol -- metabolism KW - Insecticides -- metabolism KW - Environmental Pollutants -- pharmacology KW - Environmental Pollutants -- metabolism KW - Polychlorinated Biphenyls -- pharmacology KW - Estrogens, Non-Steroidal -- pharmacology KW - Insecticides -- pharmacology KW - Estrogens, Non-Steroidal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78071482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Environmental+estrogens%3A+can+two+%22alrights%22+make+a+wrong%3F&rft.au=Simons%2C+S+S&rft.aulast=Simons&rft.aufirst=S&rft.date=1996-06-07&rft.volume=272&rft.issue=5267&rft.spage=1451&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-01 N1 - Date created - 1996-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Science. 1996 Jun 7;272(5267):1489-92 [8633243] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship between DSM-IV alcohol use disorders and DSM-IV major depression: examination of the primary-secondary distinction in a general population sample. AN - 78306236; 8791180 AB - This study examined the primary-secondary distinction with respect to DSM-IV alcohol use disorders and major depression in a large representative sample of the USA. Primary, secondary and concurrent depressives (i.e. the comorbid groups), respondents classified with major depression only and respondents classified with alcohol use disorders only were compared on a large number of sociodemographic, alcohol-related, depression-related and drug-related variables. Results were at variance with a majority of findings from the treatment literature with regard to familial aggregation of alcohol use disorders and sociodemographic, alcohol and depression profiles. Implications of the results are discussed in terms of the diagnostic and prognostic significance of the primary-secondary distinction. JF - Journal of affective disorders AU - Grant, B F AU - Hasin, D S AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1996/06/05/ PY - 1996 DA - 1996 Jun 05 SP - 113 EP - 128 VL - 38 IS - 2-3 SN - 0165-0327, 0165-0327 KW - Index Medicus KW - Severity of Illness Index KW - Marital Status KW - Psychiatric Status Rating Scales KW - Social Class KW - Random Allocation KW - Humans KW - Adult KW - Retrospective Studies KW - Adolescent KW - Male KW - Female KW - Comorbidity KW - Depressive Disorder -- psychology KW - Depressive Disorder -- diagnosis KW - Alcoholism -- genetics KW - Alcoholism -- psychology KW - Alcoholism -- complications KW - Depressive Disorder -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78306236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+affective+disorders&rft.atitle=The+relationship+between+DSM-IV+alcohol+use+disorders+and+DSM-IV+major+depression%3A+examination+of+the+primary-secondary+distinction+in+a+general+population+sample.&rft.au=Grant%2C+B+F%3BHasin%2C+D+S%3BDawson%2C+D+A&rft.aulast=Grant&rft.aufirst=B&rft.date=1996-06-05&rft.volume=38&rft.issue=2-3&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Journal+of+affective+disorders&rft.issn=01650327&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-22 N1 - Date created - 1996-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of various domains of protein kinase C epsilon on its PMA-induced translocation from the Golgi to the plasma membrane. AN - 78111436; 8660386 AB - Subcellular redistribution (translocation) was initiated by treatment of NIH 3T3 cells overexpressing different epitope-tagged fragments of PKC epsilon with PMA, and was analyzed by immunocytochemistry. The PMA-induced translocation of holo PKC epsilon, as well as fragments epsilon 2 (zinc finger domain + pseudosubstrate domain) and epsilon 7 (zinc finger domain + hinge region) from the Golgi to the plasma membrane was rapid (<10 min), while translocation of fragment epsilon 3 (zinc finger domain) was much slower (30-60 min). These results, combined with results of studies carried out at 20 degrees C to inhibit exocytotic vesicle traffic, indicated that PMA-induced translocation from the Golgi to the plasma membrane may proceed by two distinct mechanisms: a rapid, vesicle independent process noted with holo PKC epsilon (which requires the presence of the pseudosubstrate and/or hinge regions), and a slow, vesicle-dependent pathway observed with the zinc finger fragment. JF - Biochemical and biophysical research communications AU - Lehel, C AU - Oláh, Z AU - Petrovics, G AU - Jakab, G AU - Anderson, W B AD - Laboratory of Cellular Oncology, NCI, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996/06/05/ PY - 1996 DA - 1996 Jun 05 SP - 98 EP - 103 VL - 223 IS - 1 SN - 0006-291X, 0006-291X KW - Acetates KW - 0 KW - Isoenzymes KW - Recombinant Proteins KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Acetic Acid KW - Q40Q9N063P KW - Index Medicus KW - Gene Expression -- drug effects KW - Isoenzymes -- chemistry KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Cell Membrane -- enzymology KW - Exocytosis KW - Sequence Tagged Sites KW - Mice KW - Isoenzymes -- metabolism KW - Mutagenesis KW - Acetates -- pharmacology KW - Cloning, Molecular KW - Transfection KW - Recombinant Proteins -- metabolism KW - Isoenzymes -- biosynthesis KW - Zinc Fingers KW - Recombinant Proteins -- chemistry KW - Immunohistochemistry KW - Protein Kinase C -- metabolism KW - Golgi Apparatus -- enzymology KW - Protein Kinase C -- chemistry KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Kinase C -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78111436?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Influence+of+various+domains+of+protein+kinase+C+epsilon+on+its+PMA-induced+translocation+from+the+Golgi+to+the+plasma+membrane.&rft.au=Lehel%2C+C%3BOl%C3%A1h%2C+Z%3BPetrovics%2C+G%3BJakab%2C+G%3BAnderson%2C+W+B&rft.aulast=Lehel&rft.aufirst=C&rft.date=1996-06-05&rft.volume=223&rft.issue=1&rft.spage=98&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-01 N1 - Date created - 1996-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversible phosphorylation as a controlling factor for sustaining calcium oscillations in HeLa cells: Involvement of calmodulin-dependent kinase II and a calyculin A-inhibitable phosphatase. AN - 78074865; 8679550 AB - The role of reversible phosphorylation in histamine-induced Ca2+ oscillations in HeLa cells has been investigated by using various activators and inhibitors of protein kinases and phosphatases. Electroporation was employed to introduce impermeable materials into single cells, which proved to be a useful and convenient tool. Of the kinases examined, cAMP-dependent kinase, protein kinase C, and calmodulin-dependent kinase II (CaMK II), only CaMK II was essential. When added during oscillations, both W-7, a calmodulin antagonist, and KN-62, a specific CaMK II inhibitor, caused one large Ca2+ spike before halting the process. Introduction of the Ca2+/calmodulin-independent catalytic domain of CaMK II into the cells forestalled their response to histamine. These results show that intracellular Ca2+ cannot oscillate when CaMK II is locked in either the inactive or the stimulated state. External Ca2+ electroporated into cells preloaded with the catalytic domains was quickly removed (but not when the cells were pretreated with the endoplasmic reticulum Ca(2+)-ATPase inhibitor, tapsigargin), indicating that the ATP-driven Ca2+ pump was somehow activated by CaMK II. Protein phosphatase inhibitors calyculin A and okadaic acid abolished ongoing oscillations and, when added at low concentrations, prolonged the interspike interval. Immunoprecipitation experiments with 32P(i)-labeled cells provided the first evidence that inositol 1,4,5-trisphosphate receptor (IP3R) was phosphorylated by CaMK II in vivo. The extent of phosphorylation was increased in the presence of histamine, significantly enhanced by calyculin A, and greatly reduced by W-7. Our observations are consistent with the concept that repetitive phosphorylation-dephosphorylation cycles regulating IP3R and Ca2+ pumps are a controlling factor for sustained Ca2+ oscillations in HeLa, and possibly other, cells. JF - Biochemistry AU - Zhu, D M AU - Tekle, E AU - Chock, P B AU - Huang, C Y AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0340, USA. Y1 - 1996/06/04/ PY - 1996 DA - 1996 Jun 04 SP - 7214 EP - 7223 VL - 35 IS - 22 SN - 0006-2960, 0006-2960 KW - Alkaloids KW - 0 KW - Calcium Channels KW - Enzyme Inhibitors KW - Ethers, Cyclic KW - ITPR1 protein, human KW - Indoles KW - Inositol 1,4,5-Trisphosphate Receptors KW - Isoquinolines KW - Maleimides KW - Oxazoles KW - Piperazines KW - Receptors, Cytoplasmic and Nuclear KW - Sulfonamides KW - Ro 31-7549 KW - 125313-65-7 KW - Ryanodine KW - 15662-33-6 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - KN 62 KW - 63HM46XPOW KW - W 7 KW - 65595-90-6 KW - calyculin A KW - 7D07U14TK3 KW - Histamine KW - 820484N8I3 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Calcium-Transporting ATPases KW - EC 3.6.3.8 KW - Staurosporine KW - H88EPA0A3N KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Calcium Channels -- metabolism KW - Spectrometry, Fluorescence KW - Humans KW - Piperazines -- pharmacology KW - Phosphorylation KW - Sulfonamides -- pharmacology KW - Molecular Sequence Data KW - Alkaloids -- pharmacology KW - Ryanodine -- pharmacology KW - Protein Kinase C -- pharmacology KW - Maleimides -- pharmacology KW - HeLa Cells KW - Amino Acid Sequence KW - Ethers, Cyclic -- pharmacology KW - Binding Sites KW - Inositol 1,4,5-Trisphosphate -- metabolism KW - Isoquinolines -- pharmacology KW - Histamine -- pharmacology KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Indoles -- pharmacology KW - Calcium-Transporting ATPases -- metabolism KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Calcium -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Oxazoles -- pharmacology KW - Phosphoprotein Phosphatases -- metabolism KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78074865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Reversible+phosphorylation+as+a+controlling+factor+for+sustaining+calcium+oscillations+in+HeLa+cells%3A+Involvement+of+calmodulin-dependent+kinase+II+and+a+calyculin+A-inhibitable+phosphatase.&rft.au=Zhu%2C+D+M%3BTekle%2C+E%3BChock%2C+P+B%3BHuang%2C+C+Y&rft.aulast=Zhu&rft.aufirst=D&rft.date=1996-06-04&rft.volume=35&rft.issue=22&rft.spage=7214&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-16 N1 - Date created - 1996-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Somatostatin as a Trophic Factor Analysis of Transgenic Mice Overexpressing Somatostatin in Astrocytes AN - 864401459; 14376846 AB - Abstract not available. JF - Annals of the New York Academy of Sciences AU - Schwartz, Joan P AU - TANIWAKI, TAKAYUKI AU - Messing, Albee AU - Brenner, Michael AD - Molecular Genetics Section Clinical Neuroscience Branch Stroke Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Building 10, Room 3N256 Bethesda, Maryland 20892-1279 Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 29 EP - 35 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 780 IS - 1 SN - 0077-8923, 0077-8923 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Astrocytes KW - Trophic factors KW - Transgenic mice KW - Somatostatin KW - W 30925:Genetic Engineering KW - N3 11150:General and miscellaneous topics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864401459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Somatostatin+as+a+Trophic+Factor+Analysis+of+Transgenic+Mice+Overexpressing+Somatostatin+in+Astrocytes&rft.au=Schwartz%2C+Joan+P%3BTANIWAKI%2C+TAKAYUKI%3BMessing%2C+Albee%3BBrenner%2C+Michael&rft.aulast=Schwartz&rft.aufirst=Joan&rft.date=1996-06-01&rft.volume=780&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fj.1749-6632.1996.tb15109.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-11-01 N1 - Last updated - 2015-03-19 N1 - SubjectsTermNotLitGenreText - Astrocytes; Trophic factors; Transgenic mice; Somatostatin DO - http://dx.doi.org/10.1111/j.1749-6632.1996.tb15109.x ER - TY - JOUR T1 - Transgenic Mice: Preproenkephalin and the Mu Opiate Receptor AN - 864400940; 14376859 AB - Abstract not available. JF - Annals of the New York Academy of Sciences AU - Donovan, D M AU - Miner, L L AU - Sharpe, L AU - Cho, Hj AU - Takemura, M AU - Unterwald, E AU - Nyberg, F AU - Kreek, MJ AU - Uhl, G R AD - Molecular Neurobiology Branch Division of Intramural Research National Institute on Drug Abuse National Institutes of Health PO Box 5180 Baltimore, Maryland 21224 Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 19 EP - 28 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 780 IS - 1 SN - 0077-8923, 0077-8923 KW - Biotechnology and Bioengineering Abstracts KW - Opioid receptors (type mu) KW - Preproenkephalin KW - Transgenic mice KW - W 30925:Genetic Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864400940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Transgenic+Mice%3A+Preproenkephalin+and+the+Mu+Opiate+Receptor&rft.au=Donovan%2C+D+M%3BMiner%2C+L+L%3BSharpe%2C+L%3BCho%2C+Hj%3BTakemura%2C+M%3BUnterwald%2C+E%3BNyberg%2C+F%3BKreek%2C+MJ%3BUhl%2C+G+R&rft.aulast=Donovan&rft.aufirst=D&rft.date=1996-06-01&rft.volume=780&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fj.1749-6632.1996.tb15108.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-02-01 N1 - Last updated - 2015-04-09 N1 - SubjectsTermNotLitGenreText - Opioid receptors (type mu); Transgenic mice; Preproenkephalin DO - http://dx.doi.org/10.1111/j.1749-6632.1996.tb15108.x ER - TY - JOUR T1 - Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. AN - 85262708; pmid-8648326 AB - OBJECTIVE--To analyse the natural history of progressive supranuclear palsy (PSP or Steele-Richardson-Olszewski syndrome) and clinical predictors of survival in 24 patients with PSP confirmed by necropsy, who fulfilled the NINDS criteria for a neuropathological diagnosis of typical PSP. METHODS--Patients were selected from the research and clinical files of seven medical centres involving tertiary centres of Austria, England, France, and the United States. Clinical features were analysed in detail. The patients' mean age at onset of PSP was 63 (range 45-73) years. RESULTS--The most frequent clinical features (occurring in at least 75% of the patients) were early postural instability and falls, vertical supranuclear palsy, akinetic-rigid predominant parkinsonian disorder characterised by symmetric bradykinesia and axial rigidity unrelieved by levodopa, pseudobulbar palsy, and frontal release signs. Occasionally, segmental dystonia or myoclonus were described, but neither aphasia nor alien limb syndrome was reported. Fractures occurred in 25% of the patients but were unrelated to the severity of the gait or to the presence of falls. Median survival time was 5.6 (range 2-16.6) years. Onset of falls during the first year, early dysphagia, and incontinence predicted a shorter survival time. Age at onset, sex, early onset of dementia, vertical supranuclear palsy, or axial rigidity had no effect on prognosis of survival. Pneumonia was the most common immediate cause of death. PSP was most often clinically misdiagnosed as Parkinson's disease. Errors in diagnosis suggest that PSP is underdiagnosed. CONCLUSION--Progressive onset of early postural instability with falls or supranuclear vertical palsy in the fifth decade, should suggest the diagnosis of PSP. Onset of falls during the first year are emphasised, as they could lead to an early diagnosis and influence the prognosis of patients with PSP. Whether appropriate treatment of the dysphagia could prolong the survival of PSP patients needs to be explored. JF - Journal of Neurology, Neurosurgery, and Psychiatry AU - Litvan, I AU - Mangone, C A AU - McKee, A AU - Verny, M AU - Parsa, A AU - Jellinger, K AU - D'Olhaberriague, L AU - Chaudhuri, K R AU - Pearce, R K AD - Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 615 EP - 620 VL - 60 IS - 6 SN - 0022-3050, 0022-3050 KW - Magnetic Resonance Imaging KW - Diet Therapy KW - Levodopa KW - Medical Records KW - Tomography, Emission-Computed, Single-Photon KW - Diagnosis, Differential KW - Human KW - Tomography, X-Ray Computed KW - Aged KW - Antiparkinson Agents KW - Pneumonia, Aspiration KW - Diagnostic Errors KW - Deglutition Disorders KW - Survival Rate KW - Parkinson Disease KW - Supranuclear Palsy, Progressive KW - Middle Age KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85262708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurology%2C+Neurosurgery%2C+and+Psychiatry&rft.atitle=Natural+history+of+progressive+supranuclear+palsy+%28Steele-Richardson-Olszewski+syndrome%29+and+clinical+predictors+of+survival%3A+a+clinicopathological+study.&rft.au=Litvan%2C+I%3BMangone%2C+C+A%3BMcKee%2C+A%3BVerny%2C+M%3BParsa%2C+A%3BJellinger%2C+K%3BD%27Olhaberriague%2C+L%3BChaudhuri%2C+K+R%3BPearce%2C+R+K&rft.aulast=Litvan&rft.aufirst=I&rft.date=1996-06-01&rft.volume=60&rft.issue=6&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurology%2C+Neurosurgery%2C+and+Psychiatry&rft.issn=00223050&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Risk factors related to age-associated hearing loss in the speech frequencies. AN - 85240266; pmid-8780987 AB - This paper examines the relationship between several risk factors and the development of age-associated hearing loss in the speech frequencies. Hearing loss is defined as an average threshold level of 30 dB HL or greater at the frequencies of 0.5, 1, 2, and 3 kHz. Hearing thresholds from 0.5 to 8 kHz using a pulse-tone tracking procedure were collected on participants of the Baltimore Longitudinal study of Aging since 1965. A proportional hazards regression model was used to study the relationship between several risk factors that have previously been found to be associated with numerous health-related outcomes and the length of follow-up time until the occurrence of unilateral or bilateral hearing loss in a screened group of 531 men. Risk factors considered are age, blood pressure, and alcohol and cigarette consumption. After controlling for age, only systolic blood pressure showed a significant relationship with hearing loss in the speech frequencies (p < .05). Since blood pressure is a modifiable risk factor, these results suggest that preventing hypertension might contribute to an effective program for the prevention of apparent age-associated hearing loss. JF - Journal of the American Academy of Audiology AU - Brant, L J AU - Gordon-Salant, Sandra M AU - Pearson, J D AU - Klein, L L AU - Morrell, C H AU - Metter, E J AU - Fozard, J L AD - Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 21224, USA.; Department of Speech and Hearing Sciences, College of Behavioral and Social Sciences, University of Maryland PY - 1996 SP - 152 EP - 160 VL - 7 IS - 3 SN - 1050-0545, 1050-0545 KW - Audiometry, Pure-Tone KW - Auditory Threshold KW - Human KW - Aging KW - Aged KW - Longitudinal Studies KW - Hearing Disorders KW - Comparative Study KW - Risk Factors KW - Adult KW - Middle Age KW - Follow-Up Studies KW - Male KW - Female KW - Speech Perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85240266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Audiology&rft.atitle=Risk+factors+related+to+age-associated+hearing+loss+in+the+speech+frequencies.&rft.au=Brant%2C+L+J%3BGordon-Salant%2C+Sandra+M%3BPearson%2C+J+D%3BKlein%2C+L+L%3BMorrell%2C+C+H%3BMetter%2C+E+J%3BFozard%2C+J+L&rft.aulast=Brant&rft.aufirst=L&rft.date=1996-06-01&rft.volume=7&rft.issue=3&rft.spage=152&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Audiology&rft.issn=10500545&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Abnormalities in sustained attention and anterior cingulate metabolism in subjects with resistance to thyroid hormone. AN - 85233855; pmid-8813378 AB - Attention deficit disorders are a frequent manifestation of resistance to thyroid hormone (RTH), a disorder caused by mutations in the hormone-binding domain of the human thyroid hormone receptor beta gene. Positron emission tomography was used to measure cerebral glucose metabolism in regions known to be biological determinants of sustained attention in 13 adult RTH and 13 unaffected subjects. Compared to the control group, performance on a continuous auditory discrimination task was severely impaired in the RTH subjects, while metabolism was higher both in the right parietal cortex and the anterior cingulate gyrus. Abnormally high functional activity of the anterior cingulate during sustained attention may be associated with a decreased signal-to-noise ratio for the neural processing of task stimuli in subjects with RTH. JF - Brain Research AU - Matochik J A AU - Zametkin A J AU - Cohen, R M AU - Hauser, P AU - Weintraub, B D AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892, USA. PY - 1996 SP - 23 EP - 28 VL - 723 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Attention Deficit Disorder with Hyperactivity KW - Gyrus Cinguli KW - Human KW - Adult KW - Glucose KW - Middle Age KW - Tomography, Emission-Computed KW - Female KW - Male KW - Thyroid Hormones UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85233855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+Research&rft.atitle=Abnormalities+in+sustained+attention+and+anterior+cingulate+metabolism+in+subjects+with+resistance+to+thyroid+hormone.&rft.au=Matochik+J+A%3BZametkin+A+J%3BCohen%2C+R+M%3BHauser%2C+P%3BWeintraub%2C+B+D&rft.aulast=Matochik+J+A&rft.aufirst=&rft.date=1996-06-01&rft.volume=723&rft.issue=1-2&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Functional mapping of human learning: a positron emission tomography activation study of eyeblink conditioning. AN - 85221301; pmid-8656296 AB - Regional cerebral blood flow (rCBF) was measured using positron emission tomography during eyeblink conditioning in young adults. Subjects were scanned in three experimental conditions: delay conditioning, in which binaural tones preceded air puffs to the right eye by 400 msec; pseudoconditioning, in which presentations of tone and air puff stimuli were not correlated in time; and fixation rest, which served as a baseline control. Compared with fixation, pseudoconditioning produced rCBF increases in frontal and temporal cortex, basal ganglia, left hippocampal formation, and pons. Learning-specific activations were observed in conditioning as compared with pseudoconditioning in bilateral frontal cortex, left thalamus, right medial hippocampal formation, left lingual gyrus, pons, and bilateral cerebellum; decreases in rCBF were observed for bilateral temporal cortex, and in the right hemisphere in putamen, cerebellum, and the lateral aspect of hippocampal formation. Blood flow increased as the level of learning increased in the left hemisphere in caudate, hippocampal formation, fusiform gyrus, and cerebellum, and in right temporal cortex and pons. In contrast, activation in left frontal cortex decreased as learning increased. These functional imaging results implicate many of the same structures identified by previous lesion and recording studies of eyeblink conditioning in animals and humans and suggest that the same brain regions in animals and humans mediate multiple forms of associative learning that give meaning to a previously neutral stimulus. JF - The Journal of Neuroscience AU - Blaxton, T A AU - Zeffiro, T A AU - Gabrieli, J D AU - Bookheimer, S Y AU - Carrillo, M C AU - Theodore, W H AU - Disterhoft, J F AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA. PY - 1996 SP - 4032 EP - 4040 VL - 16 IS - 12 SN - 0270-6474, 0270-6474 KW - Learning KW - Support, U.S. Gov't, P.H.S. KW - Hippocampus KW - Human KW - Cerebellum KW - Cerebrovascular Circulation KW - Basal Ganglia KW - Frontal Lobe KW - Conditioning, Eyelid KW - Adult KW - Blinking KW - Data Interpretation, Statistical KW - Tomography, Emission-Computed KW - Female KW - Male KW - Brain Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85221301?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Neuroscience&rft.atitle=Functional+mapping+of+human+learning%3A+a+positron+emission+tomography+activation+study+of+eyeblink+conditioning.&rft.au=Blaxton%2C+T+A%3BZeffiro%2C+T+A%3BGabrieli%2C+J+D%3BBookheimer%2C+S+Y%3BCarrillo%2C+M+C%3BTheodore%2C+W+H%3BDisterhoft%2C+J+F&rft.aulast=Blaxton&rft.aufirst=T&rft.date=1996-06-01&rft.volume=16&rft.issue=12&rft.spage=4032&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Assessing the clinical utility of the magnetic stimulator for measuring response latencies in the laryngeal muscles. AN - 85202072; pmid-8643300 AB - Our purpose was to assess the use of magnetic stimulation for measuring conduction time of the recurrent and superior laryngeal nerves In 10 normal volunteers (7 male, 3 female). Subjects underwent laryngeal electromyography and magnetic stimulation of the vagus nerve bilaterally at the mastoid tip with a figure 8 coil. Mean muscle response latencies were measured and examined for consistent differences. Thyroarytenoid muscle response latencies were consistently longer than those in the cricothyroid muscle. Left thyroarytenoid muscle latencies were consistently longer than those on the right in agreement with bilateral asymmetry of these nerves. No appreciable differences were observed in cricothyroid muscle latencies when the right side was compared with the left. Results were consistent and reproducible within a broad range, but appreciable intersubject variability was observed. The limited sample size was unable to support a correlation with anthropometric variables, although an association was indicated. Magnetic stimulation with this technique has great potential for use in neurolaryngologic studies. JF - Otolaryngology--Head and Neck Surgery AU - Sims, H S AU - Yamashita, T AU - Rhew, K AU - Ludlow, C L AD - Voice and Speech Section, VSLB, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA. PY - 1996 SP - 761 EP - 767 VL - 114 IS - 6 SN - 0194-5998, 0194-5998 KW - Anthropometry KW - Laryngeal Nerves KW - Evaluation Studies KW - Laryngeal Muscles KW - Reproducibility of Results KW - Human KW - Adult KW - Middle Age KW - Electromagnetics KW - Male KW - Female KW - Neural Conduction KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85202072?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=Assessing+the+clinical+utility+of+the+magnetic+stimulator+for+measuring+response+latencies+in+the+laryngeal+muscles.&rft.au=Sims%2C+H+S%3BYamashita%2C+T%3BRhew%2C+K%3BLudlow%2C+C+L&rft.aulast=Sims&rft.aufirst=H&rft.date=1996-06-01&rft.volume=114&rft.issue=6&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Morphologic patterns and molecular pathways of AIDS-related head and neck and other systemic lymphomas. AN - 85172045; pmid-8638905 AB - Head and neck manifestations of human immunodeficiency virus (HIV) infection include lymph nodal and extranodal localization of non-Hodgkin's lymphoma (NHL). A histopathologic characteristic common to head and neck NHLs and to all the other systemic lymphomas in HIV patients is the frequent occurrence of cases displaying pleomorphic features and some overlap between established histologic subtypes. This article highlights the difficulties in defining HIV-related NHLs correctly, and proposes a specific pathologic categorization of these disorders accounting for their pathogenic aspects as gathered from molecular data. JF - The Annals of Otology, Rhinology, and Laryngology AU - Carbone, A AU - Gaidano, G AU - Gloghini, A AU - Tirelli, U AU - Rinaldo, A AU - Ferlito, A AD - Division of Pathology, National Cancer Institute, IRCCS, Aviano, Italy. PY - 1996 SP - 495 EP - 499 VL - 105 IS - 6 SN - 0003-4894, 0003-4894 KW - Antigens, CD30 KW - Lymphoma, Large-Cell, Ki-1 KW - Comparative Study KW - Burkitt Lymphoma KW - Humans KW - Acquired Immunodeficiency Syndrome KW - Lymphoma, Low-Grade KW - Lymphoma, Non-Hodgkin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85172045?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+Otology%2C+Rhinology%2C+and+Laryngology&rft.atitle=Morphologic+patterns+and+molecular+pathways+of+AIDS-related+head+and+neck+and+other+systemic+lymphomas.&rft.au=Carbone%2C+A%3BGaidano%2C+G%3BGloghini%2C+A%3BTirelli%2C+U%3BRinaldo%2C+A%3BFerlito%2C+A&rft.aulast=Carbone&rft.aufirst=A&rft.date=1996-06-01&rft.volume=105&rft.issue=6&rft.spage=495&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+Otology%2C+Rhinology%2C+and+Laryngology&rft.issn=00034894&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Retroviral transfer of the human MDR1 gene confers resistance to bisantrene-specific hematotoxicity. AN - 78761450; 9816258 AB - In this work, we demonstrate a protective effect conferred by the human multidrug resistance gene (MDR1) to populations of the murine hematopoietic system against the toxic effects of bisantrene, a novel intercalating cytotoxic agent under investigation as an anticancer agent. In vitro, MDR1-expressing cell lines are highly cross-resistant to bisantrene, and low levels of P-glycoprotein (the MDR1 gene product cell surface protein) confer resistance to the drug. MDR1-positive mice were generated after transplantation of bone marrow cells (BMC) transduced in vitro with a MDR1 retrovirus. Control mice were transplanted with BMC transduced with the neomycin resistance gene. Administration of a single i.v. dose of 50 mg/kg of bisantrene resulted in a decrease of the total WBC count of approximately 40%. In contrast, a decrease of the total WBC count of only 17% was observed in mice transplanted with MDR1-transduced BMC. Immunofluorescence studies with cell lineage-specific monoclonal antibodies showed that bisantrene was specifically toxic for B lymphocytes and macrophages. Double-staining with MRK16 (a monoclonal antibody specific for P-glycoprotein) demonstrated that a single dose of bisantrene increased the relative number of MDR1-transduced positive B cells, macrophages, and (to some extent) granulocytes when compared to the number found in MDR1-untreated mice or the bisantrene-treated neomycin-transduced control mice. These results provide in vivo evidence that bisantrene is a hematotoxic drug capable of selecting for MDR1-transduced hematopoietic cells. Bisantrene might be useful for gene therapy as an in vivo selective agent for cells transduced with MDR1 vectors that also coexpress therapeutic genes of interest. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Aksentijevich, I AU - Cardarelli, C O AU - Pastan, I AU - Gottesman, M M AD - Laboratories of Cell Biology and Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 973 EP - 980 VL - 2 IS - 6 SN - 1078-0432, 1078-0432 KW - Anthracenes KW - 0 KW - Antibiotics, Antineoplastic KW - P-Glycoprotein KW - bisantrene KW - 39C34M111K KW - Index Medicus KW - B-Lymphocytes -- drug effects KW - Animals KW - 3T3 Cells KW - Leukopenia -- chemically induced KW - Dose-Response Relationship, Drug KW - Humans KW - Mice, Inbred C57BL KW - Mice KW - Drug Resistance, Neoplasm KW - Macrophages -- drug effects KW - Anthracenes -- toxicity KW - P-Glycoprotein -- genetics KW - Gene Transfer Techniques KW - Retroviridae -- genetics KW - Antibiotics, Antineoplastic -- toxicity KW - Leukocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78761450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Retroviral+transfer+of+the+human+MDR1+gene+confers+resistance+to+bisantrene-specific+hematotoxicity.&rft.au=Aksentijevich%2C+I%3BCardarelli%2C+C+O%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Aksentijevich&rft.aufirst=I&rft.date=1996-06-01&rft.volume=2&rft.issue=6&rft.spage=973&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-03 N1 - Date created - 1999-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acetaminophen-induced hepatotoxicity is associated with early changes in AP-1 DNA binding activity. AN - 78369985; 8827825 AB - The AP-1 transcription factor family, which is involved in early response genes, consists of two groups of proteins, Fos-related antigens (fra) and Jun proteins. AP-1 is usually expressed at low basal cellular levels, but can be up-regulated by a variety of exogenous stimuli which results in synthesis of Fos and Jun proteins and increased AP-1 DNA binding activity. Changes in early immediate gene responses are associated with liver necrosis, inflammation and repair, although investigations into their role in drug-induced hepatotoxicity have not been actively examined. In the present studies, we determined that exposure to necrogenic doses of acetaminophen (APAP) was associated with increased AP-1 DNA binding activity in mouse liver. The APAP-induced hepatic AP-1 DNA binding complex had affinity for both the consensus AP-1 and CRE sequences. Furthermore, c-jun, but not c-fos, mRNA transcripts were transiently increased following exposure to hepatotoxic doses of APAP. When endotoxin was administered to mice in order to elicit a hepatic inflammatory response without necrosis, increases in c-jun expression occurred without accompanying changes in AP-1 activity, indicating a different mechanism of action. When compared to conventional indicators of hepatotoxicity, such as plasma levels of liver-associated enzymes, changes in gene expression occurred much earlier and, at least with AP-1 activity, remained activated following normalization of liver enzyme levels. These studies suggest that the AP-1 transcription factor and associated genes are associated in the hepatotoxic response of liver to APAP and may serve as useful molecular biomarkers for chemical-induced hepatotoxicity. JF - Research communications in molecular pathology and pharmacology AU - Blazka, M E AU - Bruccoleri, A AU - Simeonova, P P AU - Germolec, D R AU - Pennypacker, K R AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 259 EP - 273 VL - 92 IS - 3 SN - 1078-0297, 1078-0297 KW - Transcription Factor AP-1 KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Necrosis KW - Liver -- pathology KW - Liver -- drug effects KW - Dimerization KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Mice KW - Protein Binding KW - Female KW - Chemical and Drug Induced Liver Injury -- etiology KW - Transcription, Genetic -- drug effects KW - Transcription Factor AP-1 -- metabolism KW - DNA -- metabolism KW - Chemical and Drug Induced Liver Injury -- genetics KW - Genes, jun -- drug effects KW - Transcription Factor AP-1 -- chemistry KW - Gene Expression Regulation -- drug effects KW - Genes, fos -- drug effects KW - Transcription Factor AP-1 -- genetics KW - Acetaminophen -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78369985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Research+communications+in+molecular+pathology+and+pharmacology&rft.atitle=Acetaminophen-induced+hepatotoxicity+is+associated+with+early+changes+in+AP-1+DNA+binding+activity.&rft.au=Blazka%2C+M+E%3BBruccoleri%2C+A%3BSimeonova%2C+P+P%3BGermolec%2C+D+R%3BPennypacker%2C+K+R%3BLuster%2C+M+I&rft.aulast=Blazka&rft.aufirst=M&rft.date=1996-06-01&rft.volume=92&rft.issue=3&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Research+communications+in+molecular+pathology+and+pharmacology&rft.issn=10780297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-10 N1 - Date created - 1997-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - (-) deprenyl attenuates aluminium induced neurotoxicity in primary cortical cultures. AN - 78359941; 8819137 AB - The role of (-) deprenyl in offering neuroprotection to cortical neurons exposed to Aluminium chloride (AlCl3) was examined. Primary cortical cultures derived from newborn rats were exposed to AlCl3 on 6th day in vitro, at 100,200,400,600,800 and 1000 microM concentrations of AlCl3. After 48 h of AlCl3 exposure, many nerve cell bodies were swollen; a beading of neurites and a disruption of the neuritic network were also observed suggesting neurodegeneration. Lactate dehydrogenase (LDH) efflux increased in a dose-dependent manner (59-120%). (-) Deprenyl co-exposure at concentrations of 10(-7), 10(-8) and 10(-9) M significantly attenuated both the morphological alterations and the LDH efflux induced by AlCl3. This in vitro study has demonstrated that (-) deprenyl can protect neurons from aluminium induced neurotoxicity. JF - Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration AU - Munirathinam, S AU - Lakshmana, M K AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 161 EP - 167 VL - 5 IS - 2 SN - 1055-8330, 1055-8330 KW - Aluminum Compounds KW - 0 KW - Biomarkers KW - Chlorides KW - Neurotoxins KW - Selegiline KW - 2K1V7GP655 KW - aluminum chloride KW - 3CYT62D3GA KW - Pargyline KW - 9MV14S8G3E KW - Amphetamine KW - CK833KGX7E KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Pargyline -- pharmacology KW - Rats, Wistar KW - Amphetamine -- pharmacology KW - Chlorides -- toxicity KW - Selegiline -- pharmacology KW - Cerebral Cortex -- drug effects KW - Neurons -- drug effects KW - Neurons -- cytology KW - Aluminum Compounds -- toxicity KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78359941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurodegeneration+%3A+a+journal+for+neurodegenerative+disorders%2C+neuroprotection%2C+and+neuroregeneration&rft.atitle=%28-%29+deprenyl+attenuates+aluminium+induced+neurotoxicity+in+primary+cortical+cultures.&rft.au=Munirathinam%2C+S%3BLakshmana%2C+M+K%3BRaju%2C+T+R&rft.aulast=Munirathinam&rft.aufirst=S&rft.date=1996-06-01&rft.volume=5&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Neurodegeneration+%3A+a+journal+for+neurodegenerative+disorders%2C+neuroprotection%2C+and+neuroregeneration&rft.issn=10558330&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beta-carotene increases lung cancer incidence in cigarette smokers. AN - 78342491; 8810825 AB - Clinical trials were designed to validate the protective effect of beta-carotene in populations of cigarette smokers at high risk for lung cancer development. Strikingly, an increase in lung cancer resulted following beta-carotene supplementation in two separate studies in Finland and the United States. These trials were conducted without any evidence that beta-carotene prevents lung cancer in animal models. JF - Nutrition reviews AU - De Luca, L M AU - Ross, S A AD - Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 178 EP - 180 VL - 54 IS - 6 SN - 0029-6643, 0029-6643 KW - beta Carotene KW - 01YAE03M7J KW - Index Medicus KW - United States KW - Animals KW - Finland KW - Humans KW - Clinical Trials as Topic KW - Aged KW - Middle Aged KW - Male KW - Female KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Smoking -- adverse effects KW - beta Carotene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78342491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+reviews&rft.atitle=Beta-carotene+increases+lung+cancer+incidence+in+cigarette+smokers.&rft.au=De+Luca%2C+L+M%3BRoss%2C+S+A&rft.aulast=De+Luca&rft.aufirst=L&rft.date=1996-06-01&rft.volume=54&rft.issue=6&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Nutrition+reviews&rft.issn=00296643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-01 N1 - Date created - 1996-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental regulation of the chicken beta B1-crystallin promoter in transgenic mice. AN - 78341048; 8817455 AB - The cis-elements responsible for the high-level, lens-specific expression of the chicken beta B1-crystallin gene were investigated by generating mice harboring beta B1-crystallin promoter/chloramphenicol acetyl transferase (CAT) transgenes. Deletion of promoter sequences -434/-153 and -152/-127 as well as site-directed mutagenesis of the PL1 (-116/-102) and Pl2 (-90/-76) elements significantly decreased CAT gene expression in the lenses of adult transgenic mice. Transfection studies using multimerized PL1 and PL2 elements fused to the chicken beta-actin basal promoter indicated that PL1 is a general activating element while PL2 is involved in the lens-specificity of the chicken beta B1-crystallin promoter. CAT histochemistry demonstrated that the chicken beta B1-crystallin promoter (-434/+30) was active in both primary and secondary lens fiber cells from 12.5 days post coitum (dpc) until adulthood. Activity of the -152/+30/CAT transgene was relatively low and confined to the primary lens fiber cells of 16.5 dpc mice. Together, these data suggest that the reduced activity of this promoter in the adult lens is due both to this developmentally restricted expression pattern and a reduction in promoter activity. RNA hybridization studies demonstrated that the chicken beta B1-crystallin/CAT (-434/+30) transgene was expressed at similar levels in the same cells as the endogenous mouse beta B1-crystallin gene in 16.5 dpc transgenic mouse embryos. These data show a strict conservation of the lens-specific spatial and temporal regulation of the chicken and mouse beta B1-crystallin genes. JF - Mechanisms of development AU - Duncan, M K AU - Li, X AU - Ogino, H AU - Yasuda, K AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute/National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 79 EP - 89 VL - 57 IS - 1 SN - 0925-4773, 0925-4773 KW - Crystallins KW - 0 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Animals KW - Age Factors KW - Mice KW - Tissue Distribution KW - Mice, Transgenic KW - Animals, Newborn KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Base Sequence KW - In Situ Hybridization KW - Promoter Regions, Genetic KW - Transfection KW - Blotting, Southern KW - Embryo, Mammalian KW - Gene Expression Regulation, Developmental KW - Crystallins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78341048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mechanisms+of+development&rft.atitle=Developmental+regulation+of+the+chicken+beta+B1-crystallin+promoter+in+transgenic+mice.&rft.au=Duncan%2C+M+K%3BLi%2C+X%3BOgino%2C+H%3BYasuda%2C+K%3BPiatigorsky%2C+J&rft.aulast=Duncan&rft.aufirst=M&rft.date=1996-06-01&rft.volume=57&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Mechanisms+of+development&rft.issn=09254773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-11 N1 - Date created - 1997-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mid-trimester prenatal sonographic diagnosis of a pericardial cyst. AN - 78340598; 8809897 AB - Prenatal diagnosis of pericardial masses are infrequent and usually consist of intrapericardial teratomas or haemangiomas. We present the first report of prenatal diagnosis of a suspected pericardial cyst at 14 weeks' gestation which was subsequently confirmed by neonatal computed tomography. JF - Prenatal diagnosis AU - Lewis, K M AU - Sherer, D M AU - Gonçalves, L F AU - Fromberg, R A AU - Eglinton, G S AD - Department of Obstetrics and Gynecology, National Institute of Child Health and Human Development, National Institutes of Health, Georgetown University Medical Center, Washington, DC, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 549 EP - 553 VL - 16 IS - 6 SN - 0197-3851, 0197-3851 KW - Index Medicus KW - Pregnancy Trimester, Second KW - Humans KW - Adult KW - Tomography, X-Ray Computed KW - Infant, Newborn KW - Female KW - Pregnancy KW - Fetal Diseases -- diagnostic imaging KW - Ultrasonography, Prenatal KW - Mediastinal Cyst -- diagnostic imaging KW - Gestational Age UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78340598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prenatal+diagnosis&rft.atitle=Mid-trimester+prenatal+sonographic+diagnosis+of+a+pericardial+cyst.&rft.au=Lewis%2C+K+M%3BSherer%2C+D+M%3BGon%C3%A7alves%2C+L+F%3BFromberg%2C+R+A%3BEglinton%2C+G+S&rft.aulast=Lewis&rft.aufirst=K&rft.date=1996-06-01&rft.volume=16&rft.issue=6&rft.spage=549&rft.isbn=&rft.btitle=&rft.title=Prenatal+diagnosis&rft.issn=01973851&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-21 N1 - Date created - 1996-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats. AN - 78325791; 8806915 AB - We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection. JF - Journal of applied physiology (Bethesda, Md. : 1985) AU - Freeman, B D AU - Correa, R AU - Karzai, W AU - Natanson, C AU - Patterson, M AU - Banks, S AU - Fitz, Y AU - Danner, R L AU - Wilson, L AU - Eichacker, P Q AD - Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892-1662, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 2066 EP - 2076 VL - 80 IS - 6 SN - 8750-7587, 8750-7587 KW - Antibodies, Monoclonal KW - 0 KW - Integrins KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Escherichia coli KW - Antibodies, Monoclonal -- pharmacology KW - Male KW - Oxygen -- toxicity KW - Integrins -- immunology KW - Lung Injury KW - Pneumonia -- drug therapy KW - Granulocyte Colony-Stimulating Factor -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78325791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+physiology+%28Bethesda%2C+Md.+%3A+1985%29&rft.atitle=Controlled+trials+of+rG-CSF+and+CD11b-directed+MAb+during+hyperoxia+and+E.+coli+pneumonia+in+rats.&rft.au=Freeman%2C+B+D%3BCorrea%2C+R%3BKarzai%2C+W%3BNatanson%2C+C%3BPatterson%2C+M%3BBanks%2C+S%3BFitz%2C+Y%3BDanner%2C+R+L%3BWilson%2C+L%3BEichacker%2C+P+Q&rft.aulast=Freeman&rft.aufirst=B&rft.date=1996-06-01&rft.volume=80&rft.issue=6&rft.spage=2066&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+physiology+%28Bethesda%2C+Md.+%3A+1985%29&rft.issn=87507587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A nonhuman primate model of type II excessive alcohol consumption? Part 1. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption. AN - 78324035; 8800378 AB - Developmental, biochemical, and behavioral concomitants of excessive alcohol consumption were investigated using a nonhuman primate model. The variables of interest were: (1) interindividual stability of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) from infancy to adulthood, (2) effect of parental deprivation early in life on adult CSF 5-HIAA concentrations; (3) correlations between CSF 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations and alcohol consumption; and (4) correlation between the frequency of competent social behaviors and alcohol consumption. Twenty-nine rhesus macaques were reared for their first 6 months either with their mothers or without adults in peer-only conditions. At 6 and 50 months of age, each subject underwent a series of four, 4-day social separations. Cisternal CSF was sampled before and during the first and last separations; concomitantly, observational data were collected on social dominance behavior in the home-cage. When they reached 50 months of age, the monkeys were provided free access to a palatable alcohol solution daily for 1-hr periods before, during, and after the social separations. Before and after the 50-month separations, data were collected on all types of social behavior in the home-cage. Results showed that peer-reared subjects consumed more alcohol than mother-reared subjects during baseline conditions. Mother-reared subjects, however, increased their rates of consumption to equal peer-reared subjects' rates of consumption during the conditions of a social separation stressor. Peer-reared subjects also exhibited lower CSF 5-HIAA concentrations in infancy and adulthood than their mother-reared counterparts. With rearing condition held constant, interindividual differences in CSF 5-HIAA, MHPG, and homovanillic acid were stable from infancy to adulthood, and high rates of alcohol were consumed by the young adult monkeys with low CSF 5-HIAA and MHPG concentrations, particularly when the CSF was obtained during the social separations. High rates of alcohol consumption were also observed in subjects with infrequent social interactions and less competent social behaviors. In contrast to the human data, we found no gender differences in rates of alcohol consumption, nor in the correlations between alcohol consumption and the other variables. With some exceptions, findings from the study are generally consistent with predictions from Cloninger's type II model of excessive alcohol consumption in men with low CSF 5-HIAA, who also exhibit impaired impulse control and violent and antisocial behaviors. JF - Alcoholism, clinical and experimental research AU - Higley, J D AU - Suomi, S J AU - Linnoila, M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Animal Center, Poolesville, Maryland 20837, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 629 EP - 642 VL - 20 IS - 4 SN - 0145-6008, 0145-6008 KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Animals KW - Age Factors KW - Affect -- physiology KW - Humans KW - Arousal -- physiology KW - Disease Models, Animal KW - Peer Group KW - Homovanillic Acid -- cerebrospinal fluid KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Adult KW - Alcohol Drinking -- physiopathology KW - Alcohol Drinking -- psychology KW - Macaca mulatta KW - Male KW - Female KW - Social Environment KW - Maternal Deprivation KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78324035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=A+nonhuman+primate+model+of+type+II+excessive+alcohol+consumption%3F+Part+1.+Low+cerebrospinal+fluid+5-hydroxyindoleacetic+acid+concentrations+and+diminished+social+competence+correlate+with+excessive+alcohol+consumption.&rft.au=Higley%2C+J+D%3BSuomi%2C+S+J%3BLinnoila%2C+M&rft.aulast=Higley&rft.aufirst=J&rft.date=1996-06-01&rft.volume=20&rft.issue=4&rft.spage=629&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-27 N1 - Date created - 1996-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlates of past-year status among treated and untreated persons with former alcohol dependence: United States, 1992. AN - 78323186; 8800398 AB - Past-year status was investigated in a sample of 4,585 adults with prior DSM-IV alcohol dependence. Those who had and had not received treatment for alcohol problems were compared in terms of past-year status and its correlates, to see if the experience of treatment samples would be reflective of the course of alcoholism in the general population. In the past year, 27.8% of the total sample met the criteria for alcohol abuse or dependence, 22.3% were abstinent, and 49.9% were drinkers who did not satisfy the criteria for either abuse or dependence. Persons who had been treated for alcohol problems were about twice as likely to be abstainers as those who had not been treated (38.8% vs. 16.4%), but only about half as likely to fall into the past-year category of drinking without abuse or dependence (28.0% vs. 57.8%). These differentials were of constant magnitude, regardless of the interval since the onset of dependence. For the sample as a whole, persons who had received treatment were slightly more likely than their untreated counterparts to have had alcohol abuse or dependence in the past year (33.2% vs. 25.8%), and this differential increased with the interval since the onset of dependence. The odds of both past-year abstinence and drinking without abuse or dependence were decreased by male gender, Black race, rapidity of the onset of dependence and ethanol intake per drinking day, and were increased by ever having been married and by later ages at onset of dependence. The odds of drinking without abuse or dependence relative to abstinence were increased by college attendance and reduced by the number of dependence symptoms, and having been a daily drinker was associated with increased odds of past-year abstinence. Treatment history modified the associations between past-year status and race, marital and educational status, number of past alcohol problems, and rapidity of onset of dependence and age at onset. These results suggest that treatment studies may not be generalizable to alcoholics who do not seek treatment. JF - Alcoholism, clinical and experimental research AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 771 EP - 779 VL - 20 IS - 4 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Adult KW - Treatment Outcome KW - Follow-Up Studies KW - Alcohol Drinking -- epidemiology KW - Adolescent KW - United States -- epidemiology KW - Recurrence KW - Male KW - Female KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Temperance -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78323186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Correlates+of+past-year+status+among+treated+and+untreated+persons+with+former+alcohol+dependence%3A+United+States%2C+1992.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1996-06-01&rft.volume=20&rft.issue=4&rft.spage=771&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-27 N1 - Date created - 1996-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A nonhuman primate model of type II alcoholism? Part 2. Diminished social competence and excessive aggression correlates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. AN - 78321046; 8800379 AB - The purpose of this study was to develop an animal model for behavioral features of type II, early-onset alcohol abuse. To perform this research, cerebrospinal fluid (CSF) monoamine metabolite concentrations and home-cage social behaviors of 29 rhesus macaque subjects were examined in a 4-year longitudinal study. Half of the monkeys were reared for their first 6 months with their mothers, and the other half were reared without adults, instead with access only to monkeys of similar age. When the subjects were 6 months old, and again when they were 50 months old, they underwent a series of four, 4-day social separations. We obtained cisternal CSF before and during the first and last separation of each series to quantify 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylgycol (MHPG), and homovanillic acid concentrations. After the 6-month separations, subjects were placed into social groups, and social dominance rankings were assessed. Before and after the 50-month separations, social dominance rankings were evaluated again, and home-cage aggression and social behavior data were collected. Over the 3 1/2 years between CSF samplings, records were maintained of subjects' removal from their social groups for excessive aggression or treatment for wounding. Our results showed that among infants, reduced CSF 5-HIAA was correlated with low social dominance. As young adults, subjects from both rearing groups with low CSF 5-HIAA and MHPG concentrations exhibited reduced rates of social interaction and low social dominance rankings. In addition, peer-reared subjects with low CSF 5-HIAA concentrations exhibited inept social behaviors, and were frequently removed from their social groups for excessive aggression and deviant social behaviors. From these results, we conclude that the peer-rearing paradigm aggravates the untoward social consequences associated with low CSF 5-HIAA concentrations over and beyond reducing CSF 5-HIAA concentrations, suggesting that early experiences may contribute to CNS serotonin changes that increase the disposition to type II-related behaviors. JF - Alcoholism, clinical and experimental research AU - Higley, J D AU - Suomi, S J AU - Linnoila, M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Animal Center, Poolesville, Maryland 20837, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 643 EP - 650 VL - 20 IS - 4 SN - 0145-6008, 0145-6008 KW - Serotonin KW - 333DO1RDJY KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Norepinephrine KW - X4W3ENH1CV KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Animals KW - Age Factors KW - Serotonin -- physiology KW - Humans KW - Antisocial Personality Disorder -- psychology KW - Social Dominance KW - Norepinephrine -- physiology KW - Homovanillic Acid -- cerebrospinal fluid KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Adult KW - Alcohol Drinking -- physiopathology KW - Alcohol Drinking -- psychology KW - Macaca mulatta KW - Female KW - Male KW - Antisocial Personality Disorder -- physiopathology KW - Aggression -- psychology KW - Social Behavior KW - Maternal Deprivation KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology KW - Aggression -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78321046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=A+nonhuman+primate+model+of+type+II+alcoholism%3F+Part+2.+Diminished+social+competence+and+excessive+aggression+correlates+with+low+cerebrospinal+fluid+5-hydroxyindoleacetic+acid+concentrations.&rft.au=Higley%2C+J+D%3BSuomi%2C+S+J%3BLinnoila%2C+M&rft.aulast=Higley&rft.aufirst=J&rft.date=1996-06-01&rft.volume=20&rft.issue=4&rft.spage=643&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-27 N1 - Date created - 1996-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modification of kainate-induced behavioral and electrographic seizures following inhibition of nitric oxide synthase in mice. AN - 78316681; 8796356 AB - We assessed the effects of N(omega)-nitro-L-arginine-methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on behavioral and electrographic seizures elicited in mice by convulsant doses of kainate. In Expt. 1, L-NAME dose-dependently potentiated the convulsant effects of kainate (44 mg/kg s.c.), transforming long-latency clonic convulsions into short-latency fits of wild-running, and increased the incidence of kainate-induced mortality. The proconvulsant effects of L-NAME (5 mg/kg i.p.) did not reflect shortened latency to kainate-induced epileptiform afterdischarge recorded via electrodes chronically implanted into the hippocampus, amygdala, frontal cortex or mesencephalic reticular formation (Expt. 2). We also observed a dramatic uncoupling of behavioral and electrographic seizures in mice treated with L-NAME 30 min prior to kainate: 4/6 mice treated with L-NAME failed to express afterdischarge from any of the sites assessed during fits of wild-running. The proconvulsant effects of L-NAME were dependent on the route of administration of kainate, as the inhibitor of NOS failed to alter behavioral (clonic) or electrographic seizures elicited by intrahippocampal kainate (1 nmol, Expt. 3) yet shortened latency to fits of wild-running following i.c.v. kainate (1 nmol, Expt. 4) and reduced the dose of systemic kainate required for either clonic convulsions or wild-running (Expt. 5). The observations that L-NAME potentiates kainate-induced wild-running but not necessarily clonus suggest the involvement of tectopontine mechanisms. JF - Epilepsy research AU - Kirkby, R D AU - Forbes, R A AU - Subramaniam, S AD - Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 79 EP - 90 VL - 24 IS - 2 SN - 0920-1211, 0920-1211 KW - Enzyme Inhibitors KW - 0 KW - Excitatory Amino Acid Agonists KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Kainic Acid KW - SIV03811UC KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Index Medicus KW - Animals KW - Hippocampus KW - Dose-Response Relationship, Drug KW - Electroencephalography -- drug effects KW - Mice KW - Microinjections KW - Male KW - Injections, Intraventricular KW - Seizures -- chemically induced KW - Kainic Acid -- administration & dosage KW - Behavior, Animal -- drug effects KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Kainic Acid -- pharmacology KW - Seizures -- psychology KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Excitatory Amino Acid Agonists -- pharmacology KW - Excitatory Amino Acid Agonists -- administration & dosage KW - Enzyme Inhibitors -- pharmacology KW - Seizures -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78316681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=Modification+of+kainate-induced+behavioral+and+electrographic+seizures+following+inhibition+of+nitric+oxide+synthase+in+mice.&rft.au=Kirkby%2C+R+D%3BForbes%2C+R+A%3BSubramaniam%2C+S&rft.aulast=Kirkby&rft.aufirst=R&rft.date=1996-06-01&rft.volume=24&rft.issue=2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-27 N1 - Date created - 1996-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Granulocyte transfusions. Time for a second look. AN - 78316104; 8803623 AB - Among the available therapies to support neutropenic patients with infection, granulocyte transfusions have generated considerable controversy. Plagued by the inconvenience of harvesting cells, infusion-associated toxicity, and marginal efficacy, granulocyte transfusions, once in vogue in the 1980s, had been relegated to a secondary role. Several recent developments, however, have given new impetus to re-evaluating the role of granulocyte transfusions. The two most notable reasons include the ability to increase the number of circulating granulocytes in the donor by treatment with one or two doses of recombinant hematopoietic growth factors, such as granulocyte- and granulocyte-macrophage colony stimulating factor, and improvements in the efficiency of the collection process. Armed with these advances, it is an appropriate time to review the existing data and consider studies designed to determine the appropriate role of granulocyte transfusions in neutropenic hosts. JF - Infectious disease clinics of North America AU - Chanock, S J AU - Gorlin, J B AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 327 EP - 343 VL - 10 IS - 2 SN - 0891-5520, 0891-5520 KW - Cytokines KW - 0 KW - Hematopoietic Cell Growth Factors KW - Index Medicus KW - Cytokines -- pharmacology KW - Infection -- therapy KW - Humans KW - Hematopoietic Cell Growth Factors -- pharmacology KW - Leukapheresis -- standards KW - Infection -- complications KW - Leukocyte Transfusion -- statistics & numerical data KW - Granulocytes -- transplantation KW - Neutropenia -- complications KW - Neutropenia -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78316104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infectious+disease+clinics+of+North+America&rft.atitle=Granulocyte+transfusions.+Time+for+a+second+look.&rft.au=Chanock%2C+S+J%3BGorlin%2C+J+B&rft.aulast=Chanock&rft.aufirst=S&rft.date=1996-06-01&rft.volume=10&rft.issue=2&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Infectious+disease+clinics+of+North+America&rft.issn=08915520&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-13 N1 - Date created - 1997-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors determining proconvulsant and anticonvulsant effects of inhibitors of nitric oxide synthase in rodents. AN - 78311046; 8796357 AB - Although a majority of studies suggest that inhibitors of nitric oxide synthase (NOS) are proconvulsant, a substantial minority indicate the opposite (i.e. that inhibitors of NOS are anticonvulsant). As a consequence, the role of endogenous nitric oxide (NO) in the expression of seizures is unclear. In the present series of experiments, we therefore assessed factors governing pro- and anticonvulsant effects of inhibitors of NOS. In mice receiving systemic injections of kainate or picrotoxin, we confirmed the hypothesis that the effects of inhibitors of NOS vary with the model of seizure: Whereas 7-nitroindazole (7-NI) reduced the latency and increased the severity of kainate-induced convulsions (Expt. 1), both 7-NI and N(omega)-nitro-L-arginine methyl ester (L-NAME) slightly delayed clonus following the systemic administration of picrotoxin at doses > or = 3.5 mg/kg but not at doses < or = 3.0 mg/kg (Expts. 2-5). Paradoxically, L-NAME but not 7-NI significantly reduced the CD50 of picrotoxin, which was approximately 2 mg/kg in control mice (Expt. 4), revealing inhibitor-specific interactions with the dose of the convulsant. Finally, we determined in rats that the effects of L-NAME on kainate-induced seizures vary as a function of genetic factors: L-NAME significantly potentiated kainate-induced convulsions in Sprague-Dawley rats but not in Wistar rats (Expt. 6). JF - Epilepsy research AU - Kirkby, R D AU - Carroll, D M AU - Grossman, A B AU - Subramaniam, S AD - Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA. nacnud@helix.nih.gov Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 91 EP - 100 VL - 24 IS - 2 SN - 0920-1211, 0920-1211 KW - Anticonvulsants KW - 0 KW - Convulsants KW - Enzyme Inhibitors KW - Excitatory Amino Acid Agonists KW - Indazoles KW - Picrotoxin KW - 124-87-8 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Kainic Acid KW - SIV03811UC KW - 7-nitroindazole KW - UX0N37CMVH KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Index Medicus KW - Animals KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Indazoles -- pharmacology KW - Electroencephalography -- drug effects KW - Mice KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - Rats, Wistar KW - Species Specificity KW - Male KW - Seizures -- chemically induced KW - Anticonvulsants -- pharmacology KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Convulsants -- pharmacology KW - Seizures -- genetics KW - Enzyme Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78311046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=Factors+determining+proconvulsant+and+anticonvulsant+effects+of+inhibitors+of+nitric+oxide+synthase+in+rodents.&rft.au=Kirkby%2C+R+D%3BCarroll%2C+D+M%3BGrossman%2C+A+B%3BSubramaniam%2C+S&rft.aulast=Kirkby&rft.aufirst=R&rft.date=1996-06-01&rft.volume=24&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-27 N1 - Date created - 1996-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the estrogen receptor ligand-binding domain: influence of ligand structure and stereochemistry on transactivation. AN - 78289350; 8782086 AB - The mouse estrogen receptor (mER) exhibits ligand stereochemical specificity for indenestrol A (IA), a stilbestrol estrogen. IA has a chiral C3 methyl group, and the mER preferentially binds the S-enantiomer (IA-S), resulting in elevated biological activity when compared with the IA-R enantiomer. To elucidate the mechanisms for this stereochemical recognition, we have constructed a series of mERs with individual amino acid substitutions at Met521, His528, Met532, and Val537. The abilities of yeast-expressed wild-type and mutant mERs to transactivate an estrogen-responsive reporter gene construct were measured in the presence of diethylstilbestrol (DES) and IA enantiomers. The concentration of IA-S required to induce half-maximal transactivation by wild-type mER was 10-fold lower than IA-R, which is attributed to the 15-fold greater binding affinity for IA-S. Wild-type mER displayed similar dose-response curves for IA-R and demethyl IA, which lacks a C3 methyl group, demonstrating that the presence and correct orientation of the C3 methyl group on the IA compound is required for high-affinity ligand binding and transcriptional activity. Each mutant exhibited a reduced preference for IA-S enantiomer with respect to transactivation, suggesting that this region of the mER functions in ligand stereochemical recognition and activation. A mutation at Met532 diminished DES- and IA-S-induced transactivation by 7.5-fold and 40-fold respectively, with minimal change on their binding affinity. These data suggest that Met532 is required for transactivation induced by the potent agonist, IA-S, and the M532G mutation effectively uncouples IA-S ligand binding from transactivation. Use of these stereochemically different ligands in combination with mutagenesis of the mER demonstrates that ligand structure could influence transactivation by specifically altering the conformation of the mER AF-2 region. JF - Journal of molecular endocrinology AU - Kohno, H AU - Bocchinfuso, W P AU - Gandini, O AU - Curtis, S W AU - Korach, K S AD - Receptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 277 EP - 285 VL - 16 IS - 3 SN - 0952-5041, 0952-5041 KW - Estrogens, Non-Steroidal KW - 0 KW - Indenes KW - Ligands KW - Receptors, Estrogen KW - Recombinant Proteins KW - indenestrol KW - 4A464K3BSI KW - Histidine KW - 4QD397987E KW - Estradiol KW - 4TI98Z838E KW - Diethylstilbestrol KW - 731DCA35BT KW - Methionine KW - AE28F7PNPL KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Recombinant Proteins -- biosynthesis KW - DNA Mutational Analysis KW - Mice KW - Amino Acid Sequence KW - Saccharomyces cerevisiae KW - Binding Sites KW - Cloning, Molecular KW - Estradiol -- metabolism KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Diethylstilbestrol -- pharmacology KW - Genes, Reporter KW - Diethylstilbestrol -- analogs & derivatives KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Estrogens, Non-Steroidal -- metabolism KW - Receptors, Estrogen -- biosynthesis KW - Transcriptional Activation -- drug effects KW - Receptors, Estrogen -- chemistry KW - Receptors, Estrogen -- metabolism KW - Indenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78289350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+endocrinology&rft.atitle=Mutational+analysis+of+the+estrogen+receptor+ligand-binding+domain%3A+influence+of+ligand+structure+and+stereochemistry+on+transactivation.&rft.au=Kohno%2C+H%3BBocchinfuso%2C+W+P%3BGandini%2C+O%3BCurtis%2C+S+W%3BKorach%2C+K+S&rft.aulast=Kohno&rft.aufirst=H&rft.date=1996-06-01&rft.volume=16&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+endocrinology&rft.issn=09525041&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-29 N1 - Date created - 1996-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenesis of amino acids 33-44 of the common alpha-subunit reveals different structural requirements for heterodimer expression among the glycoprotein hormones and suggests that cyclic adenosine 3',5'-monophosphate production and growth promotion are potentially dissociable functions of human thyrotropin. AN - 78287212; 8776737 AB - Amino acid residues 33-44 of the common alpha-subunit of the glycoprotein hormones have been implicated in heterodimerization as well as high affinity receptor binding of human (h) CG. In the present study, we compared the role of specific amino acids within this region for glycoprotein hormone heterodimer formation, using a transient transfection system to coexpress different mutant alpha-subunit constructs with the beta-subunit of either hTSH, hCG, or hFSH. Our results identified a crucial role for alpha Pro38 in the heterodimer expression of hTSH as well as hFSH, similiar to what had been described for hCG. In contrast, alpha Ala38, which had been critical for hCG, was not essential for hTSH heterodimer expression and less important for hFSH, whereas alpha Phe33 and alpha Arg35 appeared uniquely important for hFSH. Furthermore, we assessed the role of these residues for bioactivity and receptor binding of hTSH. Mutation of the surface-exposed residues alpha Arg42-Ser43-Lys44, which form part of a unique alpha-helical structure, to Ala42-Ala43-Ala44, decreased TSH receptor binding using porcine thyroid membranes as well as rat FRTL-5 cells. Residues alpha Phe33 and alpha Arg35, in contrast, were not important for high affinity binding of hTSH. In the signal transduction of hTSH, alpha Ala36 was necessary for efficient growth induction in FRTL-5 cells but not for cAMP production in either FRTL-5 cells or Chinese hamster ovary cells expressing the human TSH receptor (JP09). Similarly, residues alpha Arg42-Ser43-Lys44 were more important for hTSH-mediated induction of cell growth than cAMP production. Mutating alpha Arg35 to Ala reduced cAMP induction but not receptor binding of hTSH. In summary, using site-directed mutagenesis, we identified a domain, residues 33-44 of the common alpha-subunit, important in heterodimer expression, receptor binding, and activation of hTSH. The comparison of the relative roles of specific amino acids within this region in hTSH with hCG and hFSH highlights previously unrecognized differences in the structural requirements for heterodimer expression among the members of the glycoprotein hormone family. Moreover, our findings revealed a novel role for residues alpha 33-44 in triggering different postreceptor events, suggesting that cAMP production and growth promotion may, at least in part, be dissociable functions of hTSH. JF - Molecular endocrinology (Baltimore, Md.) AU - Grossmann, M AU - Szkudlinski, M W AU - Dias, J A AU - Xia, H AU - Wong, R AU - Puett, D AU - Weintraub, B D AD - Molecular and Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, Maryland 20892-1758, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 769 EP - 779 VL - 10 IS - 6 SN - 0888-8809, 0888-8809 KW - Chorionic Gonadotropin KW - 0 KW - Receptors, Thyrotropin KW - Recombinant Proteins KW - Thyrotropin KW - 9002-71-5 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Receptors, Thyrotropin -- metabolism KW - Animals KW - Cyclic AMP -- biosynthesis KW - CHO Cells -- metabolism KW - Models, Molecular KW - Chorionic Gonadotropin -- chemistry KW - Humans KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Thyroid Gland -- cytology KW - Rats KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - Chorionic Gonadotropin -- metabolism KW - Recombinant Proteins -- chemistry KW - Cell Division -- genetics KW - Thyroid Gland -- metabolism KW - Cricetinae KW - Protein Conformation KW - Thyrotropin -- chemistry KW - Mutagenesis, Site-Directed KW - Thyrotropin -- genetics KW - Thyrotropin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78287212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Site-directed+mutagenesis+of+amino+acids+33-44+of+the+common+alpha-subunit+reveals+different+structural+requirements+for+heterodimer+expression+among+the+glycoprotein+hormones+and+suggests+that+cyclic+adenosine+3%27%2C5%27-monophosphate+production+and+growth+promotion+are+potentially+dissociable+functions+of+human+thyrotropin.&rft.au=Grossmann%2C+M%3BSzkudlinski%2C+M+W%3BDias%2C+J+A%3BXia%2C+H%3BWong%2C+R%3BPuett%2C+D%3BWeintraub%2C+B+D&rft.aulast=Grossmann&rft.aufirst=M&rft.date=1996-06-01&rft.volume=10&rft.issue=6&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-30 N1 - Date created - 1996-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor beta 1 supports autonomous growth of human papillomavirus-immortalized cervical keratinocytes under conditions promoting squamous differentiation. AN - 78283936; 8780894 AB - Transforming growth factor beta (TGF-beta) inhibits proliferation of keratinocytes cultured from normal anogenital epithelia; however, human papillomavirus (HPV)-immortalized cell lines often exhibit increased resistance. Present results demonstrate that TGF-beta 1 (1-10 pM) stimulates growth of multiple HPV-immortalized cell lines when cultures are maintained under conditions promoting squamous differentiation (MCDB153-LB medium with 1.0 mM calcium and without epidermal growth factor and bovine pituitary extract). Growth stimulation by TGF-beta 1 was not due to altered expression of type I or II receptors, but was increased after extended passage of cells in culture. Differentiation of immortal keratinocytes resulted in induction of RNAs encoding two markers of squamous differentiation, involucrin and keratin 1, and decreased expression of RNAs for the epidermal growth factor (EGF) receptor and two ligands, amphiregulin and TGF-alpha. Growth stimulation by TGF-beta 1 occurred indirectly via establishment of an autocrine loop. TGF-beta 1 increased expression of RNAs encoding the EGF-R and amphiregulin, and also increased numbers of cell-surface EGF-Rs without altering their affinity. In contrast, TGF-beta 1 inhibited autonomous growth and transcription of amphiregulin RNA in normal keratinocytes. Growth stimulation by TGF-beta 1 could be blocked by a monoclonal antibody that competes for binding to the EGF-R or by a mixture of monoclonal antibodies that neutralize amphiregulin activity, confirming the importance of this autocrine pathway. Thus, partial abrogation of the growth inhibitory response to TGF-beta 1 sensitizes HPV-immortalized keratinocytes to a growth stimulatory signal mediated by an EGF-R-dependent pathway involving autocrine stimulation by amphiregulin. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Woodworth, C D AU - Chung, J AU - McMullin, E AU - Plowman, G D AU - Simpson, S AU - Iglesias, M AD - Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. craigd@helix.nih.gov Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 811 EP - 820 VL - 7 IS - 6 SN - 1044-9523, 1044-9523 KW - Growth Inhibitors KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Receptors, Transforming Growth Factor beta -- analysis KW - Animals KW - Humans KW - Cell Division -- drug effects KW - Receptor, Epidermal Growth Factor -- analysis KW - Stimulation, Chemical KW - Cattle KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Kinetics KW - Growth Inhibitors -- pharmacology KW - Cell Differentiation -- drug effects KW - Female KW - Cervix Uteri -- drug effects KW - Transforming Growth Factor beta -- pharmacology KW - Carcinoma, Squamous Cell -- pathology KW - Papillomaviridae -- physiology KW - Keratinocytes -- drug effects KW - Cervix Uteri -- cytology KW - Carcinoma, Squamous Cell -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78283936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Transforming+growth+factor+beta+1+supports+autonomous+growth+of+human+papillomavirus-immortalized+cervical+keratinocytes+under+conditions+promoting+squamous+differentiation.&rft.au=Woodworth%2C+C+D%3BChung%2C+J%3BMcMullin%2C+E%3BPlowman%2C+G+D%3BSimpson%2C+S%3BIglesias%2C+M&rft.aulast=Woodworth&rft.aufirst=C&rft.date=1996-06-01&rft.volume=7&rft.issue=6&rft.spage=811&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-17 N1 - Date created - 1997-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renal secretion of organic anions and cations. AN - 78237081; 8743470 AB - The renal proximal tubule actively transports charged, potentially toxic xenobiotics from blood to lumen. Basolateral uptake of organic anions is indirectly coupled to the sodium gradient through Na-dicarboxylate cotransport and dicarboxylate-organic anion exchange. Upon entry, a significant fraction of intracellular organic anion is sequestered within vesicles. Disruption of the cellular microtubular network can lead to both diminished vesicular movement and reduced transepithelial secretion. Luminal efflux of organic anions is energetically downhill, but carrier mediated. Both anion exchange and potential driven transport are present, but neither completely accounts for transport from cell to lumen. For organic cations, basolateral entry is downhill via potential driven facilitated diffusion. Intracellular sequestration of organic cations in vesicles is substantial, but its role in secretion is uncertain. Multiple carriers are available to drive organic cations uphill into the tubular lumen. The classical system indirectly taps the energy of the luminal Na gradient to drive organic cation efflux via Na(+)-H+ and proton-organic cation exchange. In addition, the multidrug resistance ATPase can pump organic cations into the tubular lumen. Thus, although much detailed information has been added over the last 50 years, it is not yet possible to provide a detailed, quantitative understanding of these important excretory systems. JF - Kidney international AU - Pritchard, J B AU - Miller, D S AD - Laboratory of Cellular and Molecular Pharmacology, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. pritchard@niehs.nih.gov Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 1649 EP - 1654 VL - 49 IS - 6 SN - 0085-2538, 0085-2538 KW - Anions KW - 0 KW - Cations KW - Index Medicus KW - Animals KW - Biological Transport -- physiology KW - Kidney -- metabolism KW - Kidney -- secretion KW - Anions -- metabolism KW - Cations -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78237081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=Renal+secretion+of+organic+anions+and+cations.&rft.au=Pritchard%2C+J+B%3BMiller%2C+D+S&rft.aulast=Pritchard&rft.aufirst=J&rft.date=1996-06-01&rft.volume=49&rft.issue=6&rft.spage=1649&rft.isbn=&rft.btitle=&rft.title=Kidney+international&rft.issn=00852538&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-15 N1 - Date created - 1996-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. AN - 78221123; 8726753 AB - This study investigates the possible interactions of antidepressant agents and hallucinogens in humans through structured interviews using a standardized questionnaire. Volunteer subjects recruited through announcements placed on the Internet or other sources were asked to describe the somatic, hallucinatory, and psychological effects of self-administered LSD prior to and during chronic administration of an antidepressant. Twenty-eight out of 32 subjects (88%) who had taken an antidepressant with inhibitory effects on serotonin (5-HT) reuptake (fluoxetine, paroxetine, sertraline, trazodone) for over 3 weeks had a subjective decrease or virtual elimination of their responses to LSD. An additional subject who had taken fluoxetine for only 1 week had an increased response to LSD. These data are in contrast to our previous study that reported increased responses to LSD during chronic administration of tricyclic antidepressants or lithium. Possible mechanisms of action for the effects from serotonergic antidepressants involve 5-HT2 and 5-HT1A receptors, changes in extracellular brain serotonin concentrations, and changes in brain catecholamine systems. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Bonson, K R AU - Buckholtz, J W AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892, USA. kbonson@codon.nih.gov Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 425 EP - 436 VL - 14 IS - 6 SN - 0893-133X, 0893-133X KW - Antidepressive Agents KW - 0 KW - Hallucinogens KW - Serotonin Uptake Inhibitors KW - Fluoxetine KW - 01K63SUP8D KW - Lysergic Acid Diethylamide KW - 8NA5SWF92O KW - Index Medicus KW - Fluoxetine -- pharmacology KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Male KW - Female KW - Drug Interactions KW - Antidepressive Agents -- pharmacology KW - Hallucinogens -- pharmacology KW - Serotonin Uptake Inhibitors -- pharmacology KW - Lysergic Acid Diethylamide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78221123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Chronic+administration+of+serotonergic+antidepressants+attenuates+the+subjective+effects+of+LSD+in+humans.&rft.au=Bonson%2C+K+R%3BBuckholtz%2C+J+W%3BMurphy%2C+D+L&rft.aulast=Bonson&rft.aufirst=K&rft.date=1996-06-01&rft.volume=14&rft.issue=6&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-27 N1 - Date created - 1996-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spectroscopic determination of cytochrome c oxidase content in tissues containing myoglobin or hemoglobin. AN - 78167753; 8660576 AB - A simple spectroscopic method for determining the cytochrome c oxidase, cytochrome a, a3, content in tissue and mitochondria samples independent of myoglobin or blood contamination is described. Using tissue homogenates solubilized in Triton X-100, this assay relies on the selective reduction of mitochondrial cytochromes by the action of potassium cyanide. Monitoring the optical absorbance of these samples at 605 nm provided a quantitative determination of cytochrome c oxidase content in the presence of myoglobin or blood. The cytochrome c oxidase content of porcine heart mitochondria and whole tissue was determined to be 0.85 nmol/mg protein and 30.5 nmol/g wet wt, respectively. JF - Analytical biochemistry AU - Balaban, R S AU - Mootha, V K AU - Arai, A AD - National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/06/01/ PY - 1996 DA - 1996 Jun 01 SP - 274 EP - 278 VL - 237 IS - 2 SN - 0003-2697, 0003-2697 KW - Detergents KW - 0 KW - Hemoglobins KW - Myoglobin KW - Octoxynol KW - 9002-93-1 KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Potassium Cyanide KW - MQD255M2ZO KW - Index Medicus KW - Swine KW - Evaluation Studies as Topic KW - Animals KW - Myocardium -- chemistry KW - Mitochondria, Heart -- chemistry KW - Hemoglobins -- analysis KW - Electron Transport Complex IV -- analysis KW - Myoglobin -- analysis KW - Spectrophotometry -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78167753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=Spectroscopic+determination+of+cytochrome+c+oxidase+content+in+tissues+containing+myoglobin+or+hemoglobin.&rft.au=Balaban%2C+R+S%3BMootha%2C+V+K%3BArai%2C+A&rft.aulast=Balaban&rft.aufirst=R&rft.date=1996-06-01&rft.volume=237&rft.issue=2&rft.spage=274&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-25 N1 - Date created - 1996-09-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Anal Biochem 1996 Oct 15;241(2):274 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current topics in neuroleptic-induced extrapyramidal symptoms in Japan. AN - 78156232; 8683905 AB - This article reviews current topics in neuroleptic-induced extrapyramidal symptoms in Japan, focusing especially on the clinical features of akathisia and dystonia. Akathisia is a common side effect associated with antipsychotic drugs. It is most commonly characterized by subjective inner restlessness and objective motor signs, especially in the lower extremities. The mechanisms underlying akathisia remain unclear and controversial; however, an increase in the activity of beta-adrenergic systems relative to dopaminergic systems has been hypothesized, based on clinical therapeutic observations that beta-blocking agents are effective in this condition. A Japanese version of the Barnes Akathisia Scale has recently been established and uses a standardized videotape method for its precise evaluation. Various acute and chronic manifestations of neuroleptic-induced dystonia have been reported in Japan, including blepharospasm, difficulty in opening the eye lids, torticollis, retrocollis, oculogyric crisis, and Pisa syndrome. This review also introduces several other topics related to drug-induced extrapyramidal symptoms in Japan. These include; 1) the Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), which has recently been established, 2) studies on the discontinuation of anticholinergic drugs, and 3) a summary of extrapyramidal symptoms induced by drugs other than neuroleptics. JF - The Keio journal of medicine AU - Inada, T AU - Yagi, G AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 95 EP - 99 VL - 45 IS - 2 SN - 0022-9717, 0022-9717 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Severity of Illness Index KW - Japan -- epidemiology KW - Humans KW - Dystonia -- chemically induced KW - Dystonia -- epidemiology KW - Dystonia -- complications KW - Akathisia, Drug-Induced -- complications KW - Akathisia, Drug-Induced -- epidemiology KW - Antipsychotic Agents -- adverse effects KW - Basal Ganglia Diseases -- epidemiology KW - Basal Ganglia Diseases -- complications KW - Basal Ganglia Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78156232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Keio+journal+of+medicine&rft.atitle=Current+topics+in+neuroleptic-induced+extrapyramidal+symptoms+in+Japan.&rft.au=Inada%2C+T%3BYagi%2C+G&rft.aulast=Inada&rft.aufirst=T&rft.date=1996-06-01&rft.volume=45&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=The+Keio+journal+of+medicine&rft.issn=00229717&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-22 N1 - Date created - 1996-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulated expression of telomerase activity in human T lymphocyte development and activation. AN - 78148019; 8676067 AB - Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation required RNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of S pi protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion. JF - The Journal of experimental medicine AU - Weng, N P AU - Levine, B L AU - June, C H AU - Hodes, R J AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/06/01/ PY - 1996 DA - 1996 Jun 01 SP - 2471 EP - 2479 VL - 183 IS - 6 SN - 0022-1007, 0022-1007 KW - Antigens, CD KW - 0 KW - Antigens, CD28 KW - Antigens, CD3 KW - Ionomycin KW - 56092-81-0 KW - Telomerase KW - EC 2.7.7.49 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Humans KW - Child KW - Ionomycin -- pharmacology KW - Child, Preschool KW - Antigens, CD3 -- immunology KW - Infant KW - Thymus Gland -- immunology KW - T-Lymphocyte Subsets -- immunology KW - Palatine Tonsil -- immunology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Flow Cytometry KW - Antigens, CD -- immunology KW - Antigens, CD28 -- immunology KW - Lymphocyte Activation KW - Telomerase -- biosynthesis KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - T-Lymphocytes -- enzymology KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78148019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Regulated+expression+of+telomerase+activity+in+human+T+lymphocyte+development+and+activation.&rft.au=Weng%2C+N+P%3BLevine%2C+B+L%3BJune%2C+C+H%3BHodes%2C+R+J&rft.aulast=Weng&rft.aufirst=N&rft.date=1996-06-01&rft.volume=183&rft.issue=6&rft.spage=2471&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-15 N1 - Date created - 1996-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Theor Biol. 1973 Sep 14;41(1):181-90 [4754905] Mol Med Today. 1995 Nov;1(8):378-84 [9415184] Cell. 1985 Dec;43(2 Pt 1):405-13 [3907856] Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:213-9 [3034483] Mol Cell Biol. 1987 Dec;7(12):4472-81 [2830495] J Immunol. 1988 Dec 1;141(11):3747-52 [3263432] Nature. 1990 May 31;345(6274):458-60 [2342578] Nature. 1990 Aug 30;346(6287):866-8 [2392154] Nature. 1991 Apr 18;350(6319):569-73 [1708110] Curr Opin Immunol. 1991 Apr;3(2):204-9 [1676890] Cell. 1991 Aug 23;66(4):807-15 [1715244] J Immunol. 1991 Oct 15;147(8):2461-6 [1717561] Methods Enzymol. 1991;201:370-9 [1658554] Annu Rev Biochem. 1992;61:113-29 [1497307] Bone Marrow Transplant. 1992;9 Suppl 1:46-8 [1324045] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114-8 [1438199] Int Immunol. 1992 Nov;4(11):1201-10 [1472473] Am J Hum Genet. 1993 Apr;52(4):661-7 [8460632] J Immunol. 1993 Apr 15;150(8 Pt 1):3254-63 [7682237] Eur J Immunol. 1993 Dec;23(12):3072-81 [8258320] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2882-5 [8159672] Annu Rev Immunol. 1994;12:675-705 [8011294] Curr Opin Genet Dev. 1994 Apr;4(2):203-11 [8032197] EMBO J. 1994 Jul 1;13(13):3211-7 [8039513] Immunol Today. 1994 Jul;15(7):321-31 [7522010] J Biol Chem. 1994 Sep 30;269(39):24027-33 [7929054] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9857-60 [7937905] Am J Hum Genet. 1994 Nov;55(5):876-82 [7977349] Science. 1994 Dec 23;266(5193):2011-5 [7605428] Blood. 1995 May 1;85(9):2315-20 [7727765] Immunity. 1995 Jun;2(6):555-9 [7540940] Curr Opin Genet Dev. 1995 Apr;5(2):249-55 [7613096] Exp Cell Res. 1995 Jul;219(1):130-6 [7628529] Science. 1995 Sep 1;269(5228):1236-41 [7544491] Science. 1995 Sep 1;269(5228):1267-70 [7544492] Science. 1995 Sep 15;269(5230):1533-4 [7545310] J Immunol. 1995 Oct 15;155(8):3711-5 [7561072] Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9082-6 [7568077] Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11091-4 [7479943] Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11190-4 [7479963] Immunol Today. 1995 Jul;16(7):306-10 [7576059] J Biol Chem. 1995 Dec 1;270(48):28557-64 [7499370] Int Immunol. 1995 Jun;7(6):891-904 [7577797] Science. 1995 Dec 8;270(5242):1601-7 [7502069] Nature. 1985 Jan 24-30;313(6000):318-20 [3918270] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 tumor suppressor gene: from the basic research laboratory to the clinic--an abridged historical perspective. AN - 78140526; 8681432 JF - Carcinogenesis AU - Harris, C C AD - Chief, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 1187 EP - 1198 VL - 17 IS - 6 SN - 0143-3334, 0143-3334 KW - Index Medicus KW - Animals KW - Humans KW - Research -- trends KW - Genes, p53 KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78140526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=p53+tumor+suppressor+gene%3A+from+the+basic+research+laboratory+to+the+clinic--an+abridged+historical+perspective.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1996-06-01&rft.volume=17&rft.issue=6&rft.spage=1187&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-22 N1 - Date created - 1996-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Staurosporine induces a complete program of terminal differentiation in neoplastic mouse keratinocytes via activation of protein kinase C. AN - 78139956; 8681440 AB - Staurosporine (stsp) is a kinase inhibitor which induces cornified envelope assembly and terminal differentiation in normal and neoplastic mouse keratinocytes. In the tumorigenic cell lines 308 and SP-1 experiments were performed to determine if this effect was due only to activation of transglutaminases (TGases) already residing within the cell, or whether stsp was capable of inducing a full program of differentiation. Assessment of keratinocyte differentiation-specific protein expression in neoplastic cells revealed that expression of the suprabasal marker SPR-1 and the granular markers loricrin and filaggrin were induced by stsp. Protein expression was controlled by changes in mRNA expression, determined by Northern blotting. Transcripts for the TGase isoforms TGK and TGE were also induced by stsp in SP-1 cells, whereas only TGK expression was increased in 308 cells, which appear not to express TGE. Protein kinase C (PKC) activation is required for differentiation in normal mouse keratinocytes. To determine if stsp induces differentiation in neoplastic cells by regulation of this signaling pathway cells were treated with the specific PKC inhibitor GF 109203X or with different concentrations of bryostatin 1 to down-regulate specific isoforms of PKC prior to and during treatment with stsp. Stsp-induced protein cross-linking and marker expression were inhibited by GF 109203X, suggesting paradoxical activation of PKC by stsp. PKC alpha, epsilon and delta, but not PKC eta and zeta, were down-regulated by treating both cell types with bryostatin; pre-treatment of cells with bryostatin inhibited stsp-induced protein cross-linking and marker expression, suggesting a necessity for the alpha, delta and/or epsilon isoforms in stsp-induced differentiation. JF - Carcinogenesis AU - Stanwell, C AU - Dlugosz, A A AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4355, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 1259 EP - 1265 VL - 17 IS - 6 SN - 0143-3334, 0143-3334 KW - Alkaloids KW - 0 KW - Biomarkers, Tumor KW - Enzyme Inhibitors KW - Isoenzymes KW - Neoplasm Proteins KW - RNA, Messenger KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Neoplasm Proteins -- biosynthesis KW - Animals KW - Mice KW - Mice, Inbred BALB C KW - RNA, Messenger -- biosynthesis KW - Isoenzymes -- metabolism KW - Isoenzymes -- antagonists & inhibitors KW - Signal Transduction -- physiology KW - Base Sequence KW - Down-Regulation KW - Cells, Cultured KW - Molecular Sequence Data KW - Enzyme Activation -- drug effects KW - Mice, Inbred SENCAR KW - Cell Differentiation -- drug effects KW - Biomarkers, Tumor -- biosynthesis KW - Papilloma -- pathology KW - Keratinocytes -- drug effects KW - Skin Neoplasms -- pathology KW - Papilloma -- drug therapy KW - Protein Kinase C -- metabolism KW - Skin Neoplasms -- drug therapy KW - Protein Kinase C -- antagonists & inhibitors KW - Skin Neoplasms -- enzymology KW - Papilloma -- enzymology KW - Keratinocytes -- enzymology KW - Alkaloids -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Keratinocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78139956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Staurosporine+induces+a+complete+program+of+terminal+differentiation+in+neoplastic+mouse+keratinocytes+via+activation+of+protein+kinase+C.&rft.au=Stanwell%2C+C%3BDlugosz%2C+A+A%3BYuspa%2C+S+H&rft.aulast=Stanwell&rft.aufirst=C&rft.date=1996-06-01&rft.volume=17&rft.issue=6&rft.spage=1259&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-22 N1 - Date created - 1996-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen receptor levels and occupancy in hepatic sinusoidal endothelial and Kupffer cells are enhanced by initiation with diethylnitrosamine and promotion with 17alpha-ethinylestradiol in rats. AN - 78137097; 8681437 AB - We report the presence of estrogen receptors (ER) in rat liver sinusoidal endothelial (SEC) and Kupffer cells (KC), which exhibited comparable saturation kinetics and receptor affinity (Kd) for 17alpha-estradiol, as characterized for the rat hepatocyte ER. The ER levels in both cell types were significantly decreased by ovariectomy, indicating a regulatory role of estrogens. Initiation of ovariectomized rats with a single dose (200 mg/kg) of diethylnitrosamine (DEN) or saline (S), followed by chronic exposure to 17alalpha-ethinylestradiol (EE2), 90 microg/kg/day for 30 weeks packed in cholesterol (C) resulted in significant changes of ER levels in both the endothelial and Kupffer cells. The isolation of enriched liver SEC and KC populations by centrifugal elutriation allowed for the evaluation of chronic EE2 exposure and DEN-induced alterations on each cell type. The DEN-EE2 regime significantly enhanced gamma-gluta-myltranspeptidase activity in SEC (5-fold) and KC (6.6-fold) compared to the S/C treated animals. Nuclear ER levels were elevated 5.1-fold in the SEC and 6.5-fold in the KC, and both cell types exhibited significant increases in the proportion of occupied nuclear ER compared to the S/C derived cells, suggesting that exogenous estrogens could influence SEC and KC function through changes in ER levels and occupancy. ER occupancy was approximately 50% of the total ER in SEC and KC from DEN-EE2 rats. Increases in ER and occupancy for SEC and KC were similar to those observed for hepatocytes. Cellular growth was clearly modified in DEN-EE2 animals as indicated by a 4- to 10-fold increase in the proportion of SEC, KC or hepatocytes in S-phase as shown by flow cytometry. However, unlike hepatocytes, the epidermal growth factor receptor (EGFR) was not detected in SEC or KC using a monoclonal EGFR antibody. These findings suggest that the EGFR at 30 weeks is not involved in EE2-mediated stimulation of mitogenesis in SEC and KC which may be different from hepatocytes. In summary, our studies demonstrate that SEC and KC contain significant amounts of high-affinity ER and that ER pathways may modulate some activities of the SEC and KC, but that ER-EGFR interactions may be different in these cells from hepatocytes. JF - Carcinogenesis AU - Vickers, A E AU - Lucier, G W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 1235 EP - 1242 VL - 17 IS - 6 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Receptors, Estrogen KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Ethinyl Estradiol KW - 423D2T571U KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Rats KW - Endothelium -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Receptor, Epidermal Growth Factor -- metabolism KW - Endothelium -- ultrastructure KW - Cell Nucleus -- metabolism KW - gamma-Glutamyltransferase -- metabolism KW - Ovariectomy KW - Ploidies KW - Female KW - Liver -- ultrastructure KW - Receptors, Estrogen -- drug effects KW - Cocarcinogenesis KW - Liver -- drug effects KW - Liver Neoplasms, Experimental -- ultrastructure KW - Kupffer Cells -- ultrastructure KW - Liver Neoplasms, Experimental -- chemically induced KW - Kupffer Cells -- drug effects KW - Receptors, Estrogen -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78137097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Estrogen+receptor+levels+and+occupancy+in+hepatic+sinusoidal+endothelial+and+Kupffer+cells+are+enhanced+by+initiation+with+diethylnitrosamine+and+promotion+with+17alpha-ethinylestradiol+in+rats.&rft.au=Vickers%2C+A+E%3BLucier%2C+G+W&rft.aulast=Vickers&rft.aufirst=A&rft.date=1996-06-01&rft.volume=17&rft.issue=6&rft.spage=1235&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-22 N1 - Date created - 1996-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bladder calcifications after photodynamic therapy: analysis of a rare complication. AN - 78132615; 8677572 AB - We analyzed bladder calcifications occurring after photodynamic therapy administered for the treatment of superficial bladder cancer, a finding not previously reported after this treatment. Bladder biopsies from 20 patients undergoing photodynamic therapy were evaluated. Bladder calcifications were identified in 2 patients and analyzed for composition. One patient had diffuse microcrystalline deposition in two biopsies composed of calcium oxalate monohydrate A. A second patient had a focal stone at a healing biopsy site composed of monoclinic calcium hydrogen phosphate dihydrate (brushite) (66%), calcium oxalate (25%), hydroxyapatite (6%), and protein (3%). Rare calcium oxalate and brushite calcifications were identified after photodynamic therapy and presumed to occur because of tissue injury associated with treatment. JF - Urology AU - Walther, M M AU - Eanes, E D AU - Delaney, T F AU - Travis, W D AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20898, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 831 EP - 835 VL - 47 IS - 6 SN - 0090-4295, 0090-4295 KW - Index Medicus KW - Crystallization KW - Humans KW - Carcinoma in Situ -- drug therapy KW - Urinary Bladder Neoplasms -- drug therapy KW - Aged KW - Middle Aged KW - Male KW - Urinary Bladder Diseases -- etiology KW - Photochemotherapy -- adverse effects KW - Calcinosis -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78132615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urology&rft.atitle=Bladder+calcifications+after+photodynamic+therapy%3A+analysis+of+a+rare+complication.&rft.au=Walther%2C+M+M%3BEanes%2C+E+D%3BDelaney%2C+T+F%3BTravis%2C+W+D&rft.aulast=Walther&rft.aufirst=M&rft.date=1996-06-01&rft.volume=47&rft.issue=6&rft.spage=831&rft.isbn=&rft.btitle=&rft.title=Urology&rft.issn=00904295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-12 N1 - Date created - 1996-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA filter elution: a window on DNA damage in mammalian cells. AN - 78123010; 8787538 AB - This personal account traces a series of studies that led from DNA physical chemistry to anticancer drug mechanisms. Chemical crosslinking as a basis for anticancer drug actions had been suspected since the time of the first clinical reports of the effectiveness of nitrogen mustard in 1946. After the elucidation of the DNA helix-coil transition, several nearly concurrent findings in the early 1960s established the paradigm of DNA interstrand crosslinking. The DNA filter elution phenomenon was discovered in the early 1970s, and lent itself to the development of practical assays for DNA crosslinks and other DNA lesions in mammalian cells. The assays allowed studies of the effects of DNA damaging agents at pharmacologically or toxicologically relevant doses, and have been widely applied in studies of mutagenic and chemotherapeutic agents. During the period 1979-1986, DNA filter elution studies led to the paradigm of DNA topoisomerases as targets of anticancer drug action, and this has become one of the most active areas of anticancer drug development. JF - BioEssays : news and reviews in molecular, cellular and developmental biology AU - Kohn, K W AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 505 EP - 513 VL - 18 IS - 6 SN - 0265-9247, 0265-9247 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Cross-Linking Reagents KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - History of medicine KW - Kohn KW - United States KW - DNA Topoisomerases, Type I -- drug effects KW - Animals KW - History, 20th Century KW - DNA Repair KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Research -- history KW - Humans KW - DNA -- isolation & purification KW - DNA Damage KW - DNA -- chemistry KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78123010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioEssays+%3A+news+and+reviews+in+molecular%2C+cellular+and+developmental+biology&rft.atitle=DNA+filter+elution%3A+a+window+on+DNA+damage+in+mammalian+cells.&rft.au=Kohn%2C+K+W&rft.aulast=Kohn&rft.aufirst=K&rft.date=1996-06-01&rft.volume=18&rft.issue=6&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=BioEssays+%3A+news+and+reviews+in+molecular%2C+cellular+and+developmental+biology&rft.issn=02659247&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-20 N1 - Date created - 1996-09-20 N1 - Date revised - 2017-01-13 N1 - People - Kohn N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Kohn ER - TY - JOUR T1 - In vivo stability of the Umu mutagenesis proteins: a major role for RecA. AN - 78102719; 8655553 AB - The Escherichia coli Umu proteins play critical roles in damage-inducible SOS mutagenesis. To avoid any gratuitous mutagenesis, the activity of the Umu proteins is normally kept to a minimum by tight transcriptional and posttranslational regulation. We have, however, previously observed that compared with an isogenic recA+ strain, the steady-state levels of the Umu proteins are elevated in a recA730 background (R. Woodgate and D. G. Ennis, Mol. Gen. Genet. 229:10-16, 1991). We have investigated this phenomenon further and find that another coprotease-constitutive (recA*) mutant, a recA432 strain, exhibits a similar phenotype. Analysis revealed that the increased steady-state levels of the Umu proteins in the recA* strains do indeed reflect an in vivo stabilization of the proteins. We have investigated the basis for the phenomenon and find that the mutant RecA* protein stabilizes the Umu proteins by not only converting the labile UmuD protein to the much more stable (and mutagenically active) UmuD' protein but by directly stabilizing UmuD' itself. In contrast, UmuC does not appear to be directly stabilized by RecA* but is instead dramatically stabilized in the presence of UmuD'. On the basis of these observations, we suggest that formation of a UmuD'C-RecA*-DNA quaternary complex protects the UmuD'C proteins from proteolytic degradation and as a consequence helps to promote the switch from error-free to error-prone mechanisms of DNA repair. JF - Journal of bacteriology AU - Frank, E G AU - Gonzalez, M AU - Ennis, D G AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-2725, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 3550 EP - 3556 VL - 178 IS - 12 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - DNA, Bacterial KW - Escherichia coli Proteins KW - UmuC protein, E coli KW - 98059-80-4 KW - Rec A Recombinases KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Index Medicus KW - DNA Repair KW - SOS Response (Genetics) KW - DNA, Bacterial -- genetics KW - Protein Binding KW - Mutagenesis KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics KW - Rec A Recombinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78102719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=In+vivo+stability+of+the+Umu+mutagenesis+proteins%3A+a+major+role+for+RecA.&rft.au=Frank%2C+E+G%3BGonzalez%2C+M%3BEnnis%2C+D+G%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Frank&rft.aufirst=E&rft.date=1996-06-01&rft.volume=178&rft.issue=12&rft.spage=3550&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-30 N1 - Date created - 1996-07-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1988 Mar;85(6):1816-20 [3279418] Nature. 1996 Apr 25;380(6576):727-30 [8614470] Nature. 1980 Jan 3;283(5742):26-30 [6444245] J Biol Chem. 1981 Aug 10;256(15):8039-44 [6455420] Cell. 1982 Dec;31(3 Pt 2):565-73 [6218885] J Bacteriol. 1984 May;158(2):636-43 [6233260] Mol Gen Genet. 1984;195(1-2):83-9 [6238224] J Bacteriol. 1985 Apr;162(1):155-61 [2984171] Proc Natl Acad Sci U S A. 1985 May;82(10):3325-9 [3159017] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4193-7 [3889923] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4336-40 [2989817] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1806-10 [3126496] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1811-5 [3279417] J Bacteriol. 1989 May;171(5):2533-41 [2651406] Nature. 1989 Jul 20;340(6230):245-6 [2547163] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7301-5 [2552436] Proc Natl Acad Sci U S A. 1989 Nov;86(21):8363-7 [2554312] J Mol Biol. 1990 Mar 5;212(1):79-96 [2108251] J Bacteriol. 1990 Jun;172(6):3030-6 [2188949] Mutat Res. 1990 Sep-Nov;236(2-3):301-11 [2169028] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7190-4 [2205854] J Biol Chem. 1990 Nov 25;265(33):20641-5 [2147025] Genes Dev. 1990 Dec;4(12A):2202-9 [2269429] Mol Gen Genet. 1991 Sep;229(1):10-6 [1654503] Biochimie. 1991 Apr;73(4):479-84 [1911948] Mutat Res. 1992 Mar;281(3):221-5 [1371846] J Bacteriol. 1992 May;174(10):3133-9 [1349601] Mol Microbiol. 1992 Aug;6(16):2213-8 [1406263] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10777-81 [1438275] EMBO J. 1992 Dec;11(13):5121-7 [1464331] J Bacteriol. 1993 Sep;175(17):5411-9 [8366028] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8169-73 [8367479] J Bacteriol. 1993 Nov;175(22):7373-82 [8226685] Curr Opin Genet Dev. 1993 Oct;3(5):719-25 [8274853] Plasmid. 1994 Jan;31(1):60-71 [8171126] J Bacteriol. 1994 Aug;176(16):4825-37 [8050995] J Bacteriol. 1994 Aug;176(16):5011-21 [8051014] J Biol Chem. 1994 Sep 23;269(38):23824-9 [7916347] Mol Microbiol. 1993 Dec;10(5):963-71 [7934872] Mutat Res. 1995 Jan;336(1):39-48 [7528894] J Bacteriol. 1996 May;178(9):2559-63 [8626322] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokine signaling in mesothelial cells: receptor expression closes the autocrine loop. AN - 78099690; 8652178 JF - American journal of respiratory cell and molecular biology AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 505 EP - 507 VL - 14 IS - 6 SN - 1044-1549, 1044-1549 KW - Cytokines KW - 0 KW - Receptors, Cytokine KW - Index Medicus KW - Epithelial Cells KW - Epithelium -- physiology KW - Epithelium -- ultrastructure KW - Gene Expression -- physiology KW - Signal Transduction -- physiology KW - Receptors, Cytokine -- genetics KW - Cytokines -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78099690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Cytokine+signaling+in+mesothelial+cells%3A+receptor+expression+closes+the+autocrine+loop.&rft.au=Gerwin%2C+B+I&rft.aulast=Gerwin&rft.aufirst=B&rft.date=1996-06-01&rft.volume=14&rft.issue=6&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-01 N1 - Date created - 1996-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Use of transgenic animals in carcinogenesis studies. AN - 78078903; 8645427 JF - Molecular carcinogenesis AU - Gonzalez, F J Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 63 EP - 67 VL - 16 IS - 2 KW - Index Medicus KW - Animals KW - Humans KW - Carcinogenicity Tests KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic -- genetics KW - Mice, Knockout -- genetics KW - Neoplasms, Experimental -- genetics KW - Animals, Genetically Modified -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78078903?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Use+of+transgenic+animals+in+carcinogenesis+studies.&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1996-06-01&rft.volume=16&rft.issue=2&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-22 N1 - Date created - 1996-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute glucocorticoid deficiency is associated with plasma elevations of interleukin-6: does the latter participate in the symptomatology of the steroid withdrawal syndrome and adrenal insufficiency? AN - 78072749; 8964868 AB - The cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and IL-6 are secreted at inflammatory sites in tandem and play a crucial role in the inflammatory and wound-healing processes. All three cytokines are potent activators of the hypothalamic-pituitary-adrenal axis, through which they restrain inflammation, whereas IL-6 itself plays a role in the termination of inflammation as well. To test the hypothesis that endogenous glucocorticoids exert a negative tonic effect on the secretion of these cytokines, we studied 17 patients with Cushing's disease and 2 patients with primary adrenal Cushing's syndrome before and after surgery. Plasma TNF alpha, IL-1 beta and IL-6 were measured before surgery, while the patients were hypercortisolemic; on postoperative day 4 or 5, when they were hypocortisolemic; and on postoperative day 9 or 10, when they were receiving glucocorticoid replacement. During severe hypocortisolism, on postoperative day 4 or 5, plasma IL-6 levels rose significantly, compared to the preoperative values (P < 0.001). During the same interval, TNF alpha and IL-1 beta also rose, albeit to a lesser extent. Over the same interval, patients with severe hypocortisolism experienced temperature elevation, fatigue, somnolence, flu-like symptoms, and anorexia, symptoms that have been traditionally attributed to glucocorticoid deficiency; these were also experienced by subjects that received recombinant human IL-6. There was no postoperative increase in any of the cytokines studied in the patients who were not hypocortisolemic after surgery and who also lacked the corresponding symptomatology. Plasma IL-6 concentrations decreased significantly, albeit not to normal levels, in the hypocortisolemic group of patients on postoperative day 9 or 10, when they were receiving glucocorticoid replacement. We conclude that the peripheral levels of IL-6 and to a lesser extent, those of TNF alpha and IL-1 beta are tonically inhibited by basal levels of glucocorticoids. The increased IL-6 production that occurs when cortisol levels fall might explain the symptomatology of acute glucocorticoid deficiency. JF - The Journal of clinical endocrinology and metabolism AU - Papanicolaou, D A AU - Tsigos, C AU - Oldfield, E H AU - Chrousos, G P AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 2303 EP - 2306 VL - 81 IS - 6 SN - 0021-972X, 0021-972X KW - Glucocorticoids KW - 0 KW - Interleukin-1 KW - Interleukin-6 KW - Tumor Necrosis Factor-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Acute Disease KW - Substance Withdrawal Syndrome -- physiopathology KW - Body Temperature KW - Interleukin-1 -- blood KW - Humans KW - Adrenal Glands -- surgery KW - Adult KW - Tumor Necrosis Factor-alpha -- analysis KW - Aged KW - Middle Aged KW - Adrenal Insufficiency -- physiopathology KW - Male KW - Female KW - Interleukin-6 -- blood KW - Glucocorticoids -- administration & dosage KW - Glucocorticoids -- deficiency KW - Glucocorticoids -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78072749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Acute+glucocorticoid+deficiency+is+associated+with+plasma+elevations+of+interleukin-6%3A+does+the+latter+participate+in+the+symptomatology+of+the+steroid+withdrawal+syndrome+and+adrenal+insufficiency%3F&rft.au=Papanicolaou%2C+D+A%3BTsigos%2C+C%3BOldfield%2C+E+H%3BChrousos%2C+G+P&rft.aulast=Papanicolaou&rft.aufirst=D&rft.date=1996-06-01&rft.volume=81&rft.issue=6&rft.spage=2303&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-11 N1 - Date created - 1996-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics. AN - 78071939; 8656248 AB - COL-1 is a high-affinity murine monoclonal antibody (MAb) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (131I) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of COL-1 labeled with 131I, with doses from 10 mCi/m2 to 75 mCi/m2. In this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean +/- SD, 500 +/- 639). Nuclear imaging detected at least one tumor site in all 18 patients; 82% of all tumor involved organs were positive and 58% of all lesions > or = 1.0 cm were detected. Immune complexes were detected in 89% of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm2) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting. The maximal-tolerated dose is 65 mCi/m2. The correlation between dose (millicuries per square meter) and thrombocytopenia was made stronger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. 131I-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Yu, B AU - Carrasquillo, J AU - Milenic, D AU - Chung, Y AU - Perentesis, P AU - Feuerestein, I AU - Eggensperger, D AU - Qi, C F AU - Paik, C AU - Reynolds, J AU - Grem, J AU - Curt, G AU - Siler, K AU - Schlom, J AU - Allegra, C AD - Navy Medical Oncology Branch, National Cancer Institute National Institutes of Health, Bethesda, MD USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 1798 EP - 1809 VL - 14 IS - 6 SN - 0732-183X, 0732-183X KW - Antibodies, Monoclonal KW - 0 KW - Carcinoembryonic Antigen KW - Iodine Radioisotopes KW - Index Medicus KW - Pancreatic Neoplasms -- radiotherapy KW - Colorectal Neoplasms -- radiotherapy KW - Stomach Neoplasms -- radiotherapy KW - Radiotherapy Dosage KW - Humans KW - Dose-Response Relationship, Radiation KW - Radionuclide Imaging KW - Iodine Radioisotopes -- therapeutic use KW - Carcinoembryonic Antigen -- immunology KW - Radioimmunotherapy -- adverse effects KW - Iodine Radioisotopes -- adverse effects KW - Gastrointestinal Neoplasms -- radiotherapy KW - Carcinoembryonic Antigen -- blood KW - Gastrointestinal Neoplasms -- pathology KW - Gastrointestinal Neoplasms -- diagnostic imaging KW - Iodine Radioisotopes -- pharmacokinetics KW - Gastrointestinal Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78071939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+trial+of+iodine+131-labeled+COL-1+in+patients+with+gastrointestinal+malignancies%3A+influence+of+serum+carcinoembryonic+antigen+and+tumor+bulk+on+pharmacokinetics.&rft.au=Yu%2C+B%3BCarrasquillo%2C+J%3BMilenic%2C+D%3BChung%2C+Y%3BPerentesis%2C+P%3BFeuerestein%2C+I%3BEggensperger%2C+D%3BQi%2C+C+F%3BPaik%2C+C%3BReynolds%2C+J%3BGrem%2C+J%3BCurt%2C+G%3BSiler%2C+K%3BSchlom%2C+J%3BAllegra%2C+C&rft.aulast=Yu&rft.aufirst=B&rft.date=1996-06-01&rft.volume=14&rft.issue=6&rft.spage=1798&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-30 N1 - Date created - 1996-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BRCA2 mutations in primary breast and ovarian cancers. AN - 78061889; 8640235 AB - The second hereditary breast cancer gene, BRCA2, was recently isolated. Germline mutations of this gene predispose carriers to breast cancer, and, to a lesser extent, ovarian cancer. Loss of heterozygosity (LOH) at the BRCA2 locus has been observed in 30-40% of sporadic breast and ovarian tumours, implying that BRCA2 may act as a tumour suppressor gene in a proportion of sporadic cases. To define the role of BRCA2 in sporadic breast and ovarian cancer, we screened the entire gene for mutations using a combination of techniques in 70 primary breast carcinomas and in 55 primary epithelial ovarian carcinomas. Our analysis revealed alterations in 2/70 breast tumours and none of the ovarian carcinomas. One alteration found in the breast cancers was a 2-basepair (bp) deletion (4710delAG) which was subsequently shown to be a germline mutation, the other was a somatic missense mutation (Asp3095Glu) of unknown significance. Our results suggest that BRCA2 is a very infrequent target for somatic inactivation in breast and ovarian carcinomas, similar to the results obtained for BRCA1. JF - Nature genetics AU - Lancaster, J M AU - Wooster, R AU - Mangion, J AU - Phelan, C M AU - Cochran, C AU - Gumbs, C AU - Seal, S AU - Barfoot, R AU - Collins, N AU - Bignell, G AU - Patel, S AU - Hamoudi, R AU - Larsson, C AU - Wiseman, R W AU - Berchuck, A AU - Iglehart, J D AU - Marks, J R AU - Ashworth, A AU - Stratton, M R AU - Futreal, P A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 238 EP - 240 VL - 13 IS - 2 SN - 1061-4036, 1061-4036 KW - BRCA2 Protein KW - 0 KW - DNA Primers KW - Genetic Markers KW - Neoplasm Proteins KW - Retinoblastoma Protein KW - Transcription Factors KW - Index Medicus KW - Base Sequence KW - Humans KW - Heterozygote KW - Molecular Sequence Data KW - Aged KW - Middle Aged KW - Lymphocytes -- physiology KW - Retinoblastoma Protein -- genetics KW - Female KW - Sequence Deletion KW - Breast Neoplasms -- genetics KW - Ovarian Neoplasms -- genetics KW - Neoplasm Proteins -- genetics KW - Transcription Factors -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78061889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=BRCA2+mutations+in+primary+breast+and+ovarian+cancers.&rft.au=Lancaster%2C+J+M%3BWooster%2C+R%3BMangion%2C+J%3BPhelan%2C+C+M%3BCochran%2C+C%3BGumbs%2C+C%3BSeal%2C+S%3BBarfoot%2C+R%3BCollins%2C+N%3BBignell%2C+G%3BPatel%2C+S%3BHamoudi%2C+R%3BLarsson%2C+C%3BWiseman%2C+R+W%3BBerchuck%2C+A%3BIglehart%2C+J+D%3BMarks%2C+J+R%3BAshworth%2C+A%3BStratton%2C+M+R%3BFutreal%2C+P+A&rft.aulast=Lancaster&rft.aufirst=J&rft.date=1996-06-01&rft.volume=13&rft.issue=2&rft.spage=238&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental toxicity of inorganic arsenic in whole embryo: culture oxidation state, dose, time, and gestational age dependence. AN - 78061182; 8658531 AB - Arsenic is a known teratogen and developmental toxicant in many animal models. The aim of the present study was to determine the influence of arsenic oxidation state, concentration, duration of exposure, and embryonic gestational age on arsenic-induced developmental toxicity. For these studies whole embryo culture was used since this experimental model allows an assessment of the direct effect of the toxicant on the embryo and precise control of the variables of interest. ICR and CD1 mouse embryos were prepared for whole embryo culture and exposed to concentrations of trivalent (1, 2, 5, 7.5, 10, 20, and 30 microM of sodium arsenite) and pentavalent arsenic (5, 10, 20, 50, and 100 microM of sodium arsenate) at different developmental stages (3, 4-6, 8-10, or 20-23 pairs of somites) and for different exposure periods (1, 4, 6, or 24 hr). Embryonic growth, development, malformation rates, and viability were evaluated. A comparison of the ED50s of the two oxidation states showed that arsenite was about three times more potent than arsenate with respect to both malformations and lethality. The pattern of malformations was similar for both arsenite and arsenate and involved nonclosure of the cranial neural tube, prosencephalic hypoplasia, dysmorphogenesis of the optic and otic anlagen, and pharyngeal arch defects. ICR conceptuses were more sensitive than CD1s with regard to perturbation in embryonic growth by both forms of arsenic. ICRs were also more sensitive to otic, pharyngeal arch, and somite dysmorphogenesis induced by arsenite. With increasing gestational age there was an increasing resistance to arsenic-induced effects. In comparison to the 4-6 somite stage, the ED50 for induction of dysmorphogenesis was increased about twice at the 8-10 somite and over three times in 20-23 somite stage embryos. Exposure to arsenite/arsenate for a 1-hr period was sufficient to induce maldevelopment. A 6-hr exposure induced prosencephalic, otic, and optic abnormal development at a rate similar to that produced by a 24-hr exposure. The malformation pattern produced by exposure to arsenite/arsenate in vitro closely corresponds to that produced by maternal administration at the same gestational stage. This indicates that the arsenic embryopathy may be the result of a direct impact of the agent on the conceptus. JF - Toxicology and applied pharmacology AU - Tabocova, S AU - Hunter, E S AU - Gladen, B C AD - Developmental Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle, North Carolina 27709, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 298 EP - 307 VL - 138 IS - 2 SN - 0041-008X, 0041-008X KW - Arsenates KW - 0 KW - Arsenites KW - Teratogens KW - arsenite KW - N5509X556J KW - arsenic acid KW - N7CIZ75ZPN KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Oxidation-Reduction -- drug effects KW - Dose-Response Relationship, Drug KW - Mice KW - Time Factors KW - Species Specificity KW - Organ Culture Techniques KW - Gestational Age KW - Arsenites -- toxicity KW - Arsenates -- toxicity KW - Teratogens -- toxicity KW - Embryonic and Fetal Development -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78061182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Developmental+toxicity+of+inorganic+arsenic+in+whole+embryo%3A+culture+oxidation+state%2C+dose%2C+time%2C+and+gestational+age+dependence.&rft.au=Tabocova%2C+S%3BHunter%2C+E+S%3BGladen%2C+B+C&rft.aulast=Tabocova&rft.aufirst=S&rft.date=1996-06-01&rft.volume=138&rft.issue=2&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-26 N1 - Date created - 1996-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Localization of the human vascular endothelial growth factor gene, VEGF, at chromosome 6p12. AN - 78058267; 8641698 AB - Using overlapping cosmids representing the vascular endothelial growth factor (VEGF) locus, the VEGF gene was mapped by fluorescence in situ hybridization to chromosome 6p12. This localization permits linkage analysis and the identification of gene interaction in the region, as well as alterations of the VEGF structure or expression in cancer cells with chromosome abnormalities. JF - Human genetics AU - Wei, M H AU - Popescu, N C AU - Lerman, M I AU - Merrill, M J AU - Zimonjic, D B AD - Biological Carcinogenesis and Development Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 794 EP - 797 VL - 97 IS - 6 SN - 0340-6717, 0340-6717 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Index Medicus KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - In Situ Hybridization, Fluorescence KW - Cosmids KW - Chromosomes, Human, Pair 6 -- genetics KW - Lymphokines -- genetics KW - Endothelial Growth Factors -- genetics KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78058267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+genetics&rft.atitle=Localization+of+the+human+vascular+endothelial+growth+factor+gene%2C+VEGF%2C+at+chromosome+6p12.&rft.au=Wei%2C+M+H%3BPopescu%2C+N+C%3BLerman%2C+M+I%3BMerrill%2C+M+J%3BZimonjic%2C+D+B&rft.aulast=Wei&rft.aufirst=M&rft.date=1996-06-01&rft.volume=97&rft.issue=6&rft.spage=794&rft.isbn=&rft.btitle=&rft.title=Human+genetics&rft.issn=03406717&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-12 N1 - Date created - 1996-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary. AN - 78054661; 8641614 AB - We have conducted a disease specific phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary. This was done to take advantage of the cellular and molecular synergism between paclitaxel and DNA-damaging agents, with the hope of avoiding paclitaxel-cisplatin toxicities. Paclitaxel was given as a 24-hr CIVI, after which cyclophosphamide was given as a 60-min infusion. Cycles of therapy were repeated every 3 weeks; and granulocyte colony-simulating factor (G-CSF) was given in a "flexible" dosing fashion. Starting doses were 170 mg/m2 paclitaxel and 750 mg/m2 cyclophosphamide. Dose-limiting toxicity (DLT) was seen at the doses of 250 mg/m2 paclitaxel and 1250 mg/m2 cyclophosphamide. DLT was cumulative thrombocytopenia. There were six nonhematologic grade 3 or 4 toxicities experienced in the study. Eleven of 20 evaluable patients (55%) have achieved an objective response (4 CCR;7 PR). Three of four CCRs were confirmed by negative findings at peritoneoscopy. The median number of prior therapies was 2 (range 1-4) and 17 individuals had platinum-refractory disease. We conclude that paclitaxel followed by cyclophosphamide is an active combination in recurrent ovarian cancer and that further study is needed to determine if this combination is truly better than paclitaxel alone. JF - Gynecologic oncology AU - Reed, E AU - Sarosy, G AU - Kohn, E AU - Christian, M AU - Link, C J AU - Goldspiel, B AU - Davis, P AU - Jacob, J AU - Maher, M AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 349 EP - 353 VL - 61 IS - 3 SN - 0090-8258, 0090-8258 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Cyclophosphamide KW - 8N3DW7272P KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Drug Administration Schedule KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Neoplasm Recurrence, Local -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78054661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=A+phase+I+study+of+paclitaxel+and+cyclophosphamide+in+recurrent+adenocarcinoma+of+the+ovary.&rft.au=Reed%2C+E%3BSarosy%2C+G%3BKohn%2C+E%3BChristian%2C+M%3BLink%2C+C+J%3BGoldspiel%2C+B%3BDavis%2C+P%3BJacob%2C+J%3BMaher%2C+M&rft.aulast=Reed&rft.aufirst=E&rft.date=1996-06-01&rft.volume=61&rft.issue=3&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-12 N1 - Date created - 1996-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b. AN - 78053070; 8639820 AB - Lymphomatoid granulomatosis (LyG) is an angiodestructive lymphoproliferative disorder (LPD) often involving the lungs. Its etiology is uncertain, but a number of previous studies had suggested it is a T-cell LPD associated with Epstein-Barr virus (EBV). Because of the similarity between LYG and nasal angiocentric lymphoma, the term angiocentric immunoproliferative lesion was proposed for both entities. Optimal therapy is unknown, but chemotherapy is often used. We studied four patients with LYG over a 5-year period. Biopsy samples were analyzed by immunohistochemistry, EBV in situ hybridization, and for Ig heavy-chain (IgH) gene rearrangements, Clinically, we assessed EBV serology, lymphocyte subsets, and the efficacy of interferon-alpha2b (IFN-alpha2b), All biopsy samples showed an exuberant T-cell infiltrate with scattered atypical large B cells. Double labeling showed EBV in the B cells but not T cells. Clonal IgH gene rearrangements were detected in 2 of 3 patients studied, 1 of whom had three distinct clones, and light-chain restriction showed two clones in an additional patient. All patients had positive EBV serologies. and markedly abnormal lymphocyte subsets. With IFN, 3 patients are alive and disease free at 36, 43, and 60 months; 1 patient achieved a partial response for 16 months but discontinued therapy and died with lymphoma. These results indicate that LYG is a T-cell-rich EBV-associated B-cell LPD in which the infiltrating T cells are numerous but reactive. IgH gene rearrangements may be polyclonal, monoclonal, or oligoclonal. Its association with immune defects suggests it is related to posttransplant LPD. However, LYG and nasal angiocentric lymphoma are distinct entities and should no longer be included together under the term angiocentric immunoproliferative lesion. IFN is effective therapy and should be studied further. JF - Blood AU - Wilson, W H AU - Kingma, D W AU - Raffeld, M AU - Wittes, R E AU - Jaffe, E S AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/06/01/ PY - 1996 DA - 1996 Jun 01 SP - 4531 EP - 4537 VL - 87 IS - 11 SN - 0006-4971, 0006-4971 KW - Adjuvants, Immunologic KW - 0 KW - Interferon-alpha KW - RNA, Viral KW - Recombinant Proteins KW - interferon alfa-2b KW - 43K1W2T1M6 KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Fatal Outcome KW - Humans KW - Gene Rearrangement, B-Lymphocyte, Heavy Chain KW - Lymphocytes, Tumor-Infiltrating -- pathology KW - Lymphocyte Count KW - In Situ Hybridization KW - Adult KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Adolescent KW - Lymphocyte Subsets KW - Male KW - Prednisone -- administration & dosage KW - Combined Modality Therapy KW - Vincristine -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Clone Cells -- virology KW - Lung -- pathology KW - T-Lymphocytes -- pathology KW - Gene Rearrangement, B-Lymphocyte, Light Chain KW - Middle Aged KW - Female KW - RNA, Viral -- analysis KW - Remission Induction KW - Herpesvirus 4, Human -- pathogenicity KW - Lymphomatoid Granulomatosis -- virology KW - Interferon-alpha -- therapeutic use KW - B-Lymphocytes -- virology KW - Lymphomatoid Granulomatosis -- therapy KW - Tumor Virus Infections -- therapy KW - Adjuvants, Immunologic -- therapeutic use KW - Herpesvirus 4, Human -- isolation & purification KW - Herpesviridae Infections -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78053070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Association+of+lymphomatoid+granulomatosis+with+Epstein-Barr+viral+infection+of+B+lymphocytes+and+response+to+interferon-alpha+2b.&rft.au=Wilson%2C+W+H%3BKingma%2C+D+W%3BRaffeld%2C+M%3BWittes%2C+R+E%3BJaffe%2C+E+S&rft.aulast=Wilson&rft.aufirst=W&rft.date=1996-06-01&rft.volume=87&rft.issue=11&rft.spage=4531&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-18 N1 - Date created - 1996-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of hypoxia on Na(+)-K(+)-Cl- cotransport in cultured brain capillary endothelial cells of the rat. AN - 78038817; 8632184 AB - The effect of hypoxia on Na+, K(+)-ATPase and Na(+)-K(+)-Cl- cotransport activity in cultured rat brain capillary endothelial cells (RBECs) was investigated by measuring 86Rb+ uptake as a tracer for K+. RBECs expressed both Na+, K(+)-ATPase and Na(+)-K(+)-Cl- cotransport activity (4.6 and 5.5 nmol/mg of protein/min, respectively). Hypoxia (24 h) decreased cellular ATP content by 43.5% and reduced Na+, K(+)-ATPase activity by 38.9%, whereas it significantly increased Na(+)-K(+)-Cl- cotransport activity by 49.1% in RBECs. To clarify further the mechanism responsible for these observations, the effect of oligomycin-induced ATP depletion on these ion transport systems was examined. Exposure of RBECs to oligomycin led to a time-dependent decrease of cellular ATP content (by approximately 65%) along with a complete inhibition of Na+, K(+)-ATPase and a coordinated increase of Na(+)-K(+)-Cl- cotransport activity (up to 100% above control values). Oligomycin augmentation of Na(+)-K(+)-Cl- cotransport activity was not observed in the presence of 2-deoxy-D-glucose (a competitive inhibitor of glucose transport and glycolysis) or in the absence of glucose. These results strongly suggest that under hypoxic conditions when Na+, K(+)-ATPase activity is reduced, RBECs have the ability to increase K+ uptake through Na(+)-K(+)-Cl-cotransport. JF - Journal of neurochemistry AU - Kawai, N AU - McCarron, R M AU - Spatz, M AD - Stroke Branch, NINDS, NIH, Bethesda, Maryland 20892-4128, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 2572 EP - 2579 VL - 66 IS - 6 SN - 0022-3042, 0022-3042 KW - Antimetabolites KW - 0 KW - Buffers KW - Carrier Proteins KW - Chloride Channels KW - Oligomycins KW - Rubidium Radioisotopes KW - Sodium-Potassium-Chloride Symporters KW - Uncoupling Agents KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Deoxyglucose KW - 9G2MP84A8W KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Glucose KW - IY9XDZ35W2 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Animals KW - Cell Hypoxia -- physiology KW - Oligomycins -- pharmacology KW - Uncoupling Agents -- pharmacology KW - Glucose -- deficiency KW - Sodium-Potassium-Exchanging ATPase -- physiology KW - Potassium -- metabolism KW - Sodium-Potassium-Exchanging ATPase -- drug effects KW - Biological Transport -- drug effects KW - Rats KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Antimetabolites -- pharmacology KW - Protein Kinase C -- antagonists & inhibitors KW - Cells, Cultured -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Adenosine Triphosphate -- deficiency KW - Biological Transport -- physiology KW - Deoxyglucose -- pharmacology KW - Endothelium, Vascular -- metabolism KW - Carrier Proteins -- drug effects KW - Chloride Channels -- physiology KW - Chloride Channels -- drug effects KW - Carrier Proteins -- physiology KW - Capillaries -- metabolism KW - Capillaries -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78038817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Effect+of+hypoxia+on+Na%28%2B%29-K%28%2B%29-Cl-+cotransport+in+cultured+brain+capillary+endothelial+cells+of+the+rat.&rft.au=Kawai%2C+N%3BMcCarron%2C+R+M%3BSpatz%2C+M&rft.aulast=Kawai&rft.aufirst=N&rft.date=1996-06-01&rft.volume=66&rft.issue=6&rft.spage=2572&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-01 N1 - Date created - 1996-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic in vivo sodium azide infusion induces selective and stable inhibition of cytochrome c oxidase. AN - 78030064; 8632188 AB - The effect of chronic subcutaneous infusion of sodium azide on the activity of mitochondrial respiratory chain enzymes was investigated in Sprague-Dawley rats. Treatment with approximately 1 mg/kg/h sodium azide induced chronic, partial inhibition of cytochrome c oxidase, whereas the activities of respiratory complexes I and III were not significantly affected. The inhibition of cytochrome c oxidase was evident by 7 days after infusion began, and the effect was stable for at least 3 weeks. The selectivity of azide for cytochrome c oxidase is discussed in the context of other findings of azide effects on enzymes. The results of the present study indicate that the sodium azide infusion paradigm described here provides a useful tool for the evaluation of selective and stable cytochrome oxidase inhibition in vivo. JF - Journal of neurochemistry AU - Bennett, M C AU - Mlady, G W AU - Kwon, Y H AU - Rose, G M AD - National Institute on Aging, Laboratory of Neurosciences, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 2606 EP - 2611 VL - 66 IS - 6 SN - 0022-3042, 0022-3042 KW - Azides KW - 0 KW - Mutagens KW - Sodium Azide KW - 968JJ8C9DV KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Index Medicus KW - Rats KW - Brain -- enzymology KW - Animals KW - Rats, Sprague-Dawley KW - Analysis of Variance KW - Mitochondria -- enzymology KW - Brain -- drug effects KW - Brain -- ultrastructure KW - Time Factors KW - Male KW - Electron Transport Complex IV -- antagonists & inhibitors KW - Azides -- pharmacology KW - Mutagens -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78030064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Chronic+in+vivo+sodium+azide+infusion+induces+selective+and+stable+inhibition+of+cytochrome+c+oxidase.&rft.au=Bennett%2C+M+C%3BMlady%2C+G+W%3BKwon%2C+Y+H%3BRose%2C+G+M&rft.aulast=Bennett&rft.aufirst=M&rft.date=1996-06-01&rft.volume=66&rft.issue=6&rft.spage=2606&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-01 N1 - Date created - 1996-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Basic fibroblast growth factor regulates the conversion of pro-luteinizing hormone-releasing hormone (Pro-LHRH) to LHRH in immortalized hypothalamic neurons. AN - 78025570; 8641215 AB - Growth factors are commonly associated with the regulation of cellular proliferation and differentiation. In established cells, growth factors can also serve as trophic agents. Immortalized LHRH neurons contain basic fibroblast growth factor (bFGF) receptors. Although these receptors are coupled to activation of protein kinase C, and phorbol esters are strong activators of protein kinase C-stimulated LHRH release, bFGF did not influence LHRH secretion from these cells. To clarify this discrepancy, the effects of bFGF and phorbol ester on pro-LHRH biosynthesis, protein processing, and secretion were examined in GT1-7 cells. Phorbol ester stimulated LHRH secretion, whereas bFGF either had no effect or stimulated LHRH release depending upon the antiserum used. Pro-LHRH levels in lysate and medium were depressed by phorbol esters; concentrations in bFGF-treated cells were somewhat lower than those in unstimulated controls. HPLC analyses revealed that both agents enhanced the release of LHRH intermediate products into the medium. C-Terminally extended forms of LHRH, especially LHRH-[Gly11], were prominent in medium from bFGF-stimulated neurons. Levels of LHRH were depressed relative to those in the control or phorbol ester groups. These data indicate that phorbol esters control the biosynthesis, secretion, and, to some extent, processing of pro-LHRH. The effects of bFGF are novel because this factor regulates processing of the prohormone so that LHRH-intermediate products are predominantly secreted instead of LHRH. By enhancing the secretion of these intermediates over that of LHRH, bFGF can control the biological activity of the decapeptide and regulate LHRH neuronal function. JF - Endocrinology AU - Wetsel, W C AU - Hill, D F AU - Ojeda, S R AD - Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. wetsel@niehs.nih.gov Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 2606 EP - 2616 VL - 137 IS - 6 SN - 0013-7227, 0013-7227 KW - Protein Precursors KW - 0 KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Amino Acid Sequence KW - Cell Line, Transformed KW - Chromatography, High Pressure Liquid KW - Cell Line KW - Fibroblast Growth Factor 2 -- pharmacology KW - Gonadotropin-Releasing Hormone -- metabolism KW - Protein Precursors -- metabolism KW - Neurons -- metabolism KW - Protein Precursors -- biosynthesis KW - Hypothalamus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78025570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Basic+fibroblast+growth+factor+regulates+the+conversion+of+pro-luteinizing+hormone-releasing+hormone+%28Pro-LHRH%29+to+LHRH+in+immortalized+hypothalamic+neurons.&rft.au=Wetsel%2C+W+C%3BHill%2C+D+F%3BOjeda%2C+S+R&rft.aulast=Wetsel&rft.aufirst=W&rft.date=1996-06-01&rft.volume=137&rft.issue=6&rft.spage=2606&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-18 N1 - Date created - 1996-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parenting Style and Adolescent Depressive Symptoms, Smoking, and Academic Achievement: Ethnic, Gender, and SES Differences AN - 61425022; 9701999 AB - Examines whether the relationship between parenting style & adolescent depressive symptoms, smoking, & academic grades varies according to ethnicity, gender, & socioeconomic status. Four parenting styles are distinguished: autocratic, authoritative, permissive, & unengaged. Data from a questionnaire survey of 3,993 white, Hispanic, African-American, & Asian adolescent ninth-grade students from public schools in Los Angeles & San Diego counties, CA, are generally consistent with previous findings. Adolescents with authoritative parents have the best outcomes & those with unengaged parents are least well adjusted, while the permissive & the autocratic styles produce intermediate results. For the most part, this pattern holds across ethnic & sociodemographic subgroups, except for a finding that the relationship between parenting styles, especially the unengaged style, & depressive symptoms may vary according to gender & ethnicity. More research is needed to replicate & explain this pattern in terms of ecological factors, cultural norms, & socialization goals & practices. 2 Tables, 2 Figures, 1 Appendix, 32 References. Adapted from the source document. JF - Journal of Behavioral Medicine AU - Radziszewska, Barbara AU - Richardson, Jean L AU - Dent, Clyde W AU - Flay, Brian R AD - Prevention Research Branch Division Epidemiology/Statistics/Prevention Research NICHD NIH, 6100 Executive Blvd Room 7B05 Bethesda MD 20892 Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 289 EP - 305 VL - 19 IS - 3 SN - 0160-7715, 0160-7715 KW - parenting style-adolescent depressive symptoms relationship KW - ethnicity/gender/socioeconomic status KW - survey KW - white/Hispanic/African-American/Asian public school students, San Diego/Los Angeles counties, California KW - Black Americans KW - Depression (Psychology) KW - Ethnicity KW - Socioeconomic Status KW - Academic Achievement KW - Racial Differences KW - Whites KW - California KW - Smoking KW - Hispanic Americans KW - Sex Differences KW - Asian Americans KW - Childrearing Practices KW - Class Differences KW - Adolescents KW - Sex KW - article KW - 1939: the family and socialization; adolescence & youth KW - 2046: sociology of health and medicine; social psychiatry (mental health) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61425022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Behavioral+Medicine&rft.atitle=Parenting+Style+and+Adolescent+Depressive+Symptoms%2C+Smoking%2C+and+Academic+Achievement%3A+Ethnic%2C+Gender%2C+and+SES+Differences&rft.au=Radziszewska%2C+Barbara%3BRichardson%2C+Jean+L%3BDent%2C+Clyde+W%3BFlay%2C+Brian+R&rft.aulast=Radziszewska&rft.aufirst=Barbara&rft.date=1996-06-01&rft.volume=19&rft.issue=3&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Journal+of+Behavioral+Medicine&rft.issn=01607715&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JBMEDD N1 - SubjectsTermNotLitGenreText - Adolescents; Smoking; Academic Achievement; Depression (Psychology); Childrearing Practices; Racial Differences; Sex Differences; Class Differences; California; Ethnicity; Sex; Socioeconomic Status; Black Americans; Asian Americans; Hispanic Americans; Whites ER - TY - JOUR T1 - Hypochondroplasia: Molecular Analysis of the Fibroblast Growth Factor Receptor 3 Gene AN - 1780507169; PQ0002829550 JF - Annals of the New York Academy of Sciences AU - Bellus, Gary A AU - Mcintosh, Iain AU - Szabo, Jinny AU - Aylsworth, Arthur AU - Kaitila, Ilkka AU - Francomano, Clair A AD - Medical Genetics Branch National Center for Human Genome Research National Institutes of Health Bethesda, Maryland 20892. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 182 EP - 187 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 785 IS - 1 SN - 0077-8923, 0077-8923 KW - Environment Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780507169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Hypochondroplasia%3A+Molecular+Analysis+of+the+Fibroblast+Growth+Factor+Receptor+3+Gene&rft.au=Bellus%2C+Gary+A%3BMcintosh%2C+Iain%3BSzabo%2C+Jinny%3BAylsworth%2C+Arthur%3BKaitila%2C+Ilkka%3BFrancomano%2C+Clair+A&rft.aulast=Bellus&rft.aufirst=Gary&rft.date=1996-06-01&rft.volume=785&rft.issue=1&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fj.1749-6632.1996.tb56257.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-04-13 DO - http://dx.doi.org/10.1111/j.1749-6632.1996.tb56257.x ER - TY - JOUR T1 - The C-Propeptide of Type II Procollagen Binds to the Enhancer Region of the Type II Procollagen Gene and Regulates its Transcription AN - 1780505856; PQ0002829547 JF - Annals of the New York Academy of Sciences AU - Nakata, Ken AU - Miyamoto, Shingo AU - Bernier, Suzanne AU - Tanaka, Masahiko AU - Utani, Atsushi AU - Krebsbach, Paul AU - Rhodes, Craig AU - Yamada, Yoshihiko AD - National Institute of Dental Research National Institutes of Health. Y1 - 1996/06// PY - 1996 DA - June 1996 SP - 307 EP - 308 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 785 IS - 1 SN - 0077-8923, 0077-8923 KW - Environment Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780505856?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+C-Propeptide+of+Type+II+Procollagen+Binds+to+the+Enhancer+Region+of+the+Type+II+Procollagen+Gene+and+Regulates+its+Transcription&rft.au=Nakata%2C+Ken%3BMiyamoto%2C+Shingo%3BBernier%2C+Suzanne%3BTanaka%2C+Masahiko%3BUtani%2C+Atsushi%3BKrebsbach%2C+Paul%3BRhodes%2C+Craig%3BYamada%2C+Yoshihiko&rft.aulast=Nakata&rft.aufirst=Ken&rft.date=1996-06-01&rft.volume=785&rft.issue=1&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fj.1749-6632.1996.tb56292.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-04-13 DO - http://dx.doi.org/10.1111/j.1749-6632.1996.tb56292.x ER - TY - JOUR T1 - Escherichia coli RNase HI inhibits murine leukaemia virus reverse transcription in vitro and yeast retrotransposon Ty1 transposition in vivo AN - 16031521; 4097919 AB - Reverse transcription, which converts an RNA genome into double-stranded DNA, requires both the polymerase and RNase H activities of reverse transcriptase (RT). In vitro, poorly processive RT dissociates from partially copied RNA-DNA hybrids, that are usually extended by a second RT molecule. Despite similar structures, RNase HI of Escherichia coli can degrade RNA-DNA hybrids that are resistant to RNase H of RT. E. coli RNase HI is used to determine the accessibility to and requirement for RNA-DNA hybrids in reverse transcription in vivo and in vitro. In the presence of E. coli RNase HI, reverse transcription yields incomplete cDNA molecules due to degradation of RNA-DNA hybrids. Delivery of E. coli RNase HI to Ty1 particles via fusion to the capsid protein can reduce retrotransposition by more than 99%, also indicating inhibition of DNA synthesis in vivo. Inhibition of both reverse transcription in vitro and retrotransposition in vivo by E. coli RNase HI indicates that the poor processivity of RT exposes RNA-DNA hybrids critical for reverse transcription to degradation. Targeting a cellular RNase H to HIV may help define the site(s) of RNA-DNA hybrids that are susceptible to non-retroviral RNase H and may be useful for gene therapy to inhibit retroviral replication. JF - Genes to Cells AU - Ma, Wu-Po AU - Crouch, R J AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 581 EP - 593 VL - 1 IS - 6 SN - 1356-9597, 1356-9597 KW - DNA KW - budding yeast KW - ribonuclease HI KW - transposon Ty1 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - murine leukemia virus KW - transposition KW - Saccharomyces cerevisiae KW - RNA KW - Escherichia coli KW - J 02726:RNA and ribosomes KW - N 14711:RNases KW - V 22044:Viral nucleic acid synthesis & synthesis of virus-coded proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16031521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+to+Cells&rft.atitle=Escherichia+coli+RNase+HI+inhibits+murine+leukaemia+virus+reverse+transcription+in+vitro+and+yeast+retrotransposon+Ty1+transposition+in+vivo&rft.au=Ma%2C+Wu-Po%3BCrouch%2C+R+J&rft.aulast=Ma&rft.aufirst=Wu-Po&rft.date=1996-06-01&rft.volume=1&rft.issue=6&rft.spage=581&rft.isbn=&rft.btitle=&rft.title=Genes+to+Cells&rft.issn=13569597&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Saccharomyces cerevisiae; murine leukemia virus; transposition; RNA; DNA ER - TY - JOUR T1 - Selecting chemicals and assays for assessing mammalian germ cell mutagenicity AN - 15929316; 4046478 JF - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis AU - Shelby, MD AD - National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 159 EP - 167 VL - 352 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Toxicology Abstracts KW - toxicity testing KW - germ cells KW - mammalian cells KW - mutagenicity KW - xenobiotics KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15929316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.atitle=Selecting+chemicals+and+assays+for+assessing+mammalian+germ+cell+mutagenicity&rft.au=Shelby%2C+MD&rft.aulast=Shelby&rft.aufirst=MD&rft.date=1996-06-01&rft.volume=352&rft.issue=1-2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - xenobiotics; toxicity testing; mutagenicity; germ cells; mammalian cells ER - TY - JOUR T1 - Comparative metabolism and disposition of ethoxyquin in rat and mouse. I. Disposition AN - 15914321; 4043278 AB - 1. The biological fate of the antioxidant [3- super(14)C]ethoxyquin (EQ) was investigated in the male F344 rat and the B6C3F sub(1) mouse following either p.o. or i.v. administration. 2. The disposition of single doses up to 25 mg/kg was similar in the rat and mouse. About 90% of a total dose was excreted in urine and faeces within 24 h post-dosing. In contrast, no more than 60% of a higher dose of 250 mg/kg was excreted within 24 h following p.o. administration. 3. Metabolism of EQ was rapid in both the rat and mouse following either p.o. or i.v. administration. Little or no parent compound was detected in cumulative 24-h excreta. 5. EQ-derived radioactivity bioaccumulated in some tissues following repeated exposure to rat of either 25 or 250 mg/kg by gavage. However, the fold-increases in concentrations of EQ-derived radioactivity in tissues following repeated administration of the higher dose were generally less than those observed following repeated administration of the lower dose. Repeated high dose administration may overcome delayed gastric emptying (observed following single dose administration of 250 mg/kg) and /or lead to auto-induction of EQ metabolism. JF - Xenobiotica AU - Sanders, J M AU - Burka, L T AU - Matthews, H B AD - Chemistry Branch, Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 583 EP - 595 VL - 26 IS - 6 SN - 0049-8254, 0049-8254 KW - metabolism KW - rats KW - mice KW - ethoxyquin KW - Toxicology Abstracts KW - feeds KW - antioxidants KW - preservatives KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15914321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica&rft.atitle=Comparative+metabolism+and+disposition+of+ethoxyquin+in+rat+and+mouse.+I.+Disposition&rft.au=Sanders%2C+J+M%3BBurka%2C+L+T%3BMatthews%2C+H+B&rft.aulast=Sanders&rft.aufirst=J&rft.date=1996-06-01&rft.volume=26&rft.issue=6&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=Xenobiotica&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - preservatives; feeds; antioxidants ER - TY - JOUR T1 - Comparative metabolism and disposition of ethoxyquin in rat and mouse. II. Metabolism AN - 15913314; 4043279 AB - 1. The major pathways of ethoxyquin (EQ) metabolism in both the rat and mouse are O-deethylation and conjugation to endogenous substrates. 2. The two major EQ-derived metabolites excreted in rat urine were in the form of sulphate conjugates, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate, and 1,2,3,4-tetrahydro-3,6-dihydroxy-4-methylene-2,2-dimethylquinoline sulphate. The latter apparently arises from an intramolecular rearrangement of the 3,4-epoxide of ethoxyquin. 3. Mouse urine contained one major glucuronide, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline glucuronide as well as one major sulphate conjugate, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate. 4. EQ-derived radioactivity was excreted in rat bile, mainly as GSH conjugates, with little unchanged EQ present. Two of the biliary metabolites are glutathione conjugates of ethoxyquin 3,4-epoxide; the third appears to be a conjugate of either ethoxyquin 7,8-epoxide or 2,2,4-trimethylquinol-6-one. JF - Xenobiotica AU - Burka, L T AU - Sanders, J M AU - Matthews, H B AD - Chemistry Branch, Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 597 EP - 611 VL - 26 IS - 6 SN - 0049-8254, 0049-8254 KW - metabolism KW - rats KW - mice KW - ethoxyquin KW - Toxicology Abstracts KW - feeds KW - antioxidants KW - preservatives KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15913314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica&rft.atitle=Comparative+metabolism+and+disposition+of+ethoxyquin+in+rat+and+mouse.+II.+Metabolism&rft.au=Burka%2C+L+T%3BSanders%2C+J+M%3BMatthews%2C+H+B&rft.aulast=Burka&rft.aufirst=L&rft.date=1996-06-01&rft.volume=26&rft.issue=6&rft.spage=597&rft.isbn=&rft.btitle=&rft.title=Xenobiotica&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - feeds; preservatives; antioxidants ER - TY - JOUR T1 - The role of the environment in Parkinson's disease AN - 15907816; 4041890 AB - Thirty leading scientists in the field of Parkinson's disease research attended a conference, "The Role of the Environment in Parkinson's Disease," 17-19 September 1995, sponsored and hosted by the National Institute of Environmental Health Sciences. Parkinson's disease investigators working in various basic and clinical disciplines presented and evaluated current scientific findings concerning the etiology of the disease and charted the most fruitful courses for future research. The role of the environment was highlighted, but considerable attention was given to pathological neurochemistry and genetic issues in the etiopathogenesis of Parkinson's disease. The conference was opened by Annette Kirshner, program administrator at NIEHS and chair of the conference, who framed the context of the discussions to take place. Terri Damstra, acting deputy director of NIEHS, welcomed attendees to the institute and reaffirmed the importance of the work to NIEHS. She emphasized that in Parkinson's disease the potential roles of environmental exposure to one or more agents, genetic susceptibility to such exposures, and the factor of time or aging are likely to play roles in the etiology of the neurodegenerative process. Formal presentations were divided into three sessions: environmental and genetic risk factors, neurotoxins and mechanisms of neuronal injury, and biological markers of Parkinson's disease. Summaries of each of these sessions follow. Environmental and Genetic Risk Factors The relative roles of environmental, endogenous neurochemical and genetic factors in the etiology of Parkinson's disease is currently unclear. For example, the prevalence of Parkinson's disease in a community could be due to a differential distribution of a hypothetical environmental toxicant or be more frequent where a heritable defect is common. Twin studies in the 1980s seemed to discount a significant genetic role in Parkinson's disease when the degree of concordance between monozygotic and dizygotic pairs was found to be similar. An environmental cause of the disease was favored when it was shown that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) could enter the brain and be metabolized to 1-methyl-4-phenylpyridinium ion (MPP super(+)), which could specifically destroy nigral neurons to produce a human condition that closely mimicked Parkinson's disease. Moreover, the fact that the amyotrophic lateral sclerosis /Parkinson's disease/dementia complex could develop in Guamanians decades after their migration from the island strengthened the idea that a long latent period after exposure to an environmental toxicant could be present before a degenerative disorder was fully manifest. JF - Environmental Health Perspectives AU - Gorrell, J M AU - DiMonte, D AU - Graham, D AD - A.G. Kirshner, MD 3-03, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 652 EP - 654 VL - 104 IS - 6 SN - 0091-6765, 0091-6765 KW - environmental factors KW - etiology KW - pathology KW - neurochemistry KW - risk factors KW - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - MPTP KW - Toxicology Abstracts; Genetics Abstracts KW - Parkinson's disease KW - conferences KW - genetic factors KW - X 24240:Miscellaneous KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15907816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=The+role+of+the+environment+in+Parkinson%27s+disease&rft.au=Gorrell%2C+J+M%3BDiMonte%2C+D%3BGraham%2C+D&rft.aulast=Gorrell&rft.aufirst=J&rft.date=1996-06-01&rft.volume=104&rft.issue=6&rft.spage=652&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Parkinson's disease; conferences; genetic factors ER - TY - JOUR T1 - A fluorogenic assay of endogenous phosphatase for assessment of cell adhesion AN - 15861365; 4021566 AB - Assays of cell adhesion generally require prelabeling of cells with radioactive or fluorescent probes. A new fluorogenic phosphatase assay requiring no prelabeling has been developed to quantitate cell number, which can thus serve as the basis for quantitating cell adhesion or migration. The assay uses the non-fluorescent substrate 3,6-fluorescein diphosphate (FDP) whose dephosphorylation generates fluorescein. The fluorescence generated is linear with incubation time and cell number until substrate becomes limiting; the assay easily quantitates cells over a range from 10 super(3) to 10 super(6) for a variety of cell types, including resting T cells. It is as sensitive as the super(51)Cr assay, but has the many advantages of a non-radioactive assay, making more convenient the removal of nonadherent cells by simple 1 x g sedimentation. Unlike most other non-radioactive assays, it requires no pre-incubation; this: (1) reduces cell manipulation; (2) eliminates problems of spontaneous release; and (3) avoids potential dye toxicity. This technique of cell quantitation has been adopted as standard in our laboratory for routine adhesion and migration assays. JF - Journal of Immunological Methods AU - Tolosa, E AU - Shaw, S AD - Exptl. Immun. Branch, NCI, Natl. Institutes Health, Bldg. 10 Rm. 4B17, 10 Cent. Dr., MSC 1360, Bethesda, MD 20892-1360, USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 165 EP - 172 VL - 192 IS - 1-2 SN - 0022-1759, 0022-1759 KW - 3,6-fluorescein diphosphate KW - phosphatase KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - fluorescence KW - cell adhesion KW - W3 33240:Immunology KW - F 06721:Immunofluorescence KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15861365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=A+fluorogenic+assay+of+endogenous+phosphatase+for+assessment+of+cell+adhesion&rft.au=Tolosa%2C+E%3BShaw%2C+S&rft.aulast=Tolosa&rft.aufirst=E&rft.date=1996-06-01&rft.volume=192&rft.issue=1-2&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - fluorescence; cell adhesion ER - TY - JOUR T1 - Immediate inflammatory responses to adenovirus-mediated gene transfer in rat salivary glands AN - 15824315; 4007688 AB - Although replication-deficient adenoviruses can efficiently transfer genes to the salivary glands, the current vectors precipitate an immediate, transient decrease in salivary function. To study the cause of this salivary hypofunction, 10 super(6)-10 super(10) plaque-forming units (pfu) of the vector AdCMV beta gal were delivered by retrograde ductal infusion to the submandibular glands (SMGs) of rats. Microscopic analysis of infected glands showed a dose-related, rapidly developing inflammatory response, which at the highest amount of virus was characterized by a predominantly neutrophil-containing infiltrate, focal necrosis, and edema. Moreover, the glands of nude rats developed similar morphologic changes to those of immunocompetent rats. After 3 days, the volume of stimulated saliva secreted from SMGs receiving AdCMV beta gal (6.75 X 10 super(9) pfu) was similar to 20% that of controls. UV-inactivated virus caused a similar decrease in saliva output. We evaluated to what extent the anti-inflammatory glucocorticoid, dexamethasone, could suppress inflammation and preserve salivary function. Three days after infusion with a high dose of AdCMV beta gal (6.75 X 10 super(9) pfu), the glands from dexamethasone-treated animals showed markedly less inflammation and no necrosis. Furthermore, there was no significant difference in the average amount of saliva secreted from the infected glands (105 plus or minus 17 mu l) compared to the control glands (123 plus or minus 18 mu l). In addition, dexamethasone extended the expression of beta -galactosidase in the SMGs. These results suggest that the adenovirus-mediated acute inflammation in rat SMG is responsible for diminished gland function and transgene expression. Furthermore, we demonstrate a useful role for glucocorticoids in controlling acute inflammation during experimental gene transfer with current adenovirus vectors. JF - Human Gene Therapy AU - Adesanya, M R AU - Redman, R S AU - Baum, B J AU - O'Connell, B C AD - Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bldg. 10, Rm. 1N113, Bethesda, MD 20892-1190 USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 1085 EP - 1093 VL - 7 IS - 9 SN - 1043-0342, 1043-0342 KW - glucocorticoids KW - rats KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - gene transfer KW - inflammation KW - adenovirus KW - salivary gland KW - G 07240:Immunogenetics KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15824315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Immediate+inflammatory+responses+to+adenovirus-mediated+gene+transfer+in+rat+salivary+glands&rft.au=Adesanya%2C+M+R%3BRedman%2C+R+S%3BBaum%2C+B+J%3BO%27Connell%2C+B+C&rft.aulast=Adesanya&rft.aufirst=M&rft.date=1996-06-01&rft.volume=7&rft.issue=9&rft.spage=1085&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene transfer; inflammation; salivary gland; adenovirus ER - TY - JOUR T1 - Viral interference during simultaneous transduction with two independent helper-free retroviral vectors AN - 15823455; 4007693 AB - The ability to stably transduce a single cell with two independent retroviral vectors would have distinct advantages for gene therapy. We determined that cells can be transduced with two distinct retroviral vectors and have quantitated transduction efficiencies in cells infected sequentially and simultaneously. Two amphotropic, helper virus-free, retroviral vectors, a murine Moloney sarcoma virus-based vector containing the nuclear beta -galactosidase and neomycin resistance genes (MMSVn beta -gal/neo super(R)) and a Harvey virus-derived vector containing the human multidrug resistance gene (HaMDR) were introduced into NIH-3T3 cells, pig keratinocytes, and primary pig fibroblasts simultaneously and sequentially. Analytical flow cytometry was utilized to determine retroviral transduction efficiency by assessing the percentage of cells transduced by either one or both retroviruses, in the absence of selection. Simultaneous retroviral transductions were infrequent events. In addition, transduction of previously infected cells (sequential transductions) occurred at lower than expected frequencies. Our data suggest that there is quantifiable viral interference in sequential retroviral transductions. This interference occurs by a mechanism that appears to be independent of the amphotropic retroviral receptor. Thus, such dual transductions will likely require in vitro selection or the use of a single retrovirus which contains both desired genes on the same genome. JF - Human Gene Therapy AU - Walker, P S AU - Hengge, U R AU - Udey, M C AU - Aksentijevich, I AU - Vogel, J C AD - Dermatology Branch, National Cancer Institute, NIH, Bldg. 10, 12N238, 10 Center Dr. MSC 1908, Bethesda, MD 20892-1908, USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 1131 EP - 1138 VL - 7 IS - 9 SN - 1043-0342, 1043-0342 KW - pigs KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - retrovirus KW - transduction KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15823455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Viral+interference+during+simultaneous+transduction+with+two+independent+helper-free+retroviral+vectors&rft.au=Walker%2C+P+S%3BHengge%2C+U+R%3BUdey%2C+M+C%3BAksentijevich%2C+I%3BVogel%2C+J+C&rft.aulast=Walker&rft.aufirst=P&rft.date=1996-06-01&rft.volume=7&rft.issue=9&rft.spage=1131&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - retrovirus; transduction ER - TY - JOUR T1 - In vitro and in vivo liposome-mediated gene transfer leads to human MDR1 expression in mouse bone marrow progenitor cells AN - 15823268; 4007691 AB - The ability to select bone marrow cells (BMC) expressing a selectable gene that confers resistance to anticancer drugs would be useful to protect bone marrow during chemotherapy. The human multidrug resistance (MDR1) gene encodes a 170-kD glycoprotein (P-gp), an ATP-dependent transmembrane efflux pump for many different cytotoxic drugs. In this work, we demonstrate efficient expression of the human MDR1 gene in mouse BMC after transfection with a liposomal delivery system (DLS-liposomes). The human MDR1 cDNA expression plasmid (pHaMDR1/A) was encapsulated in DLS-liposomes and delivered to mouse BMC using two approaches: (i) in vitro transfection of BMC followed by bone marrow transplantation and (ii) in vivo direct systemic gene transfer. After both the in vitro and the in vivo approaches, polymerase chain reaction (PCR) analysis confirmed that the human MDR1 gene was successfully transfected to bone marrow, spleen, and peripheral blood (PB) cells, with the human MDR1 gene detected in BMC for up to 30 days after bone marrow transplantation and 28 days after direct systemic administration. Efflux studies using rhodamine-123 demonstrated function of the MDR1 gene product in the in vitro-transfected BMC. Flow cytometry studies using the human MDR1-specific MRK16 monoclonal antibody confirmed the presence of P-gp in BMC after in vitro transfection, as well as in BMC from reconstituted or in vivo-transfected mice. Transgene expression in both lymphoid and myeloid subpopulations of BMC was demonstrated. Colony-forming units (CFU-Mix) were obtained after exposure of BMC to lethal doses of vincristine, demonstrating functional expression of the MDR1 gene in hematopoietic progenitor cells for up to 1 month. JF - Human Gene Therapy AU - Aksentijevich, I AU - Pastan, I AU - Lunardi-Iskandar, Y AU - Gallo, R C AU - Gottesman, M M AU - Thierry, A R AD - Laboratory of Cell Biology NCI, NIH, Building 37, Room 1B22 37 Convent Dr. MSC 4255 Bethesda, MD 20892-4255 USA Y1 - 1996/06// PY - 1996 DA - Jun 1996 SP - 1111 EP - 1122 VL - 7 IS - 9 SN - 1043-0342, 1043-0342 KW - MDR1 gene KW - mdr-1 gene KW - mice KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - gene transfer KW - liposomes KW - stem cells KW - chemotherapy KW - bone marrow KW - multidrug resistance KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15823268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=In+vitro+and+in+vivo+liposome-mediated+gene+transfer+leads+to+human+MDR1+expression+in+mouse+bone+marrow+progenitor+cells&rft.au=Aksentijevich%2C+I%3BPastan%2C+I%3BLunardi-Iskandar%2C+Y%3BGallo%2C+R+C%3BGottesman%2C+M+M%3BThierry%2C+A+R&rft.aulast=Aksentijevich&rft.aufirst=I&rft.date=1996-06-01&rft.volume=7&rft.issue=9&rft.spage=1111&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene transfer; liposomes; stem cells; chemotherapy; multidrug resistance; bone marrow ER - TY - JOUR T1 - Role of CAS, a human homologue to the yeast chromosome segregation gene CSE1, in toxin and tumor necrosis factor mediated apoptosis. AN - 78074094; 8639641 AB - We have previously isolated by expression/selection cloning plasmids containing human cDNAs that rendered MCF-7 breast cancer cells resistant to immunotoxins, Pseudomonas exotoxin (PE), and diphtheria toxin (DT) [Brinkmann et al. (1995) Mol. Med. 1, 206-216]. Here we describe that one of these resistant plasmids, which contains an antisense cDNA fragment homologous to the yeast chromosome segregation gene CSE1 [CAS; Brinkmann et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 10427-10431], reduces the intracellular content of the human CSE1 homologue CAS protein. CAS reduction confers resistance not only to the ADP-ribosylating toxins PE and DT, but also to tumor necrosis factor alpha and beta. The resistance was observed as reduced apoptosis. CAS antisense did not affect the cell death induced by staurosporine, cycloheximide, or etoposide. The observation that CAS antisense can interfere with apoptosis mediated by TNF and ADP-ribosylating toxins suggests that CAS may play a role in selected pathways of apoptosis. JF - Biochemistry AU - Brinkmann, U AU - Brinkmann, E AU - Gallo, M AU - Scherf, U AU - Pastan, I AD - Laboratory of Molecular Biology, DBS, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-4255, USA. Y1 - 1996/05/28/ PY - 1996 DA - 1996 May 28 SP - 6891 EP - 6899 VL - 35 IS - 21 SN - 0006-2960, 0006-2960 KW - Antibodies KW - 0 KW - Antigens, Polyomavirus Transforming KW - Bacterial Toxins KW - CSE1 protein, S cerevisiae KW - Cellular Apoptosis Susceptibility Protein KW - DNA, Antisense KW - DNA, Neoplasm KW - Diphtheria Toxin KW - Exotoxins KW - Fungal Proteins KW - Immunotoxins KW - Lymphotoxin-alpha KW - Nuclear Proteins KW - Nucleocytoplasmic Transport Proteins KW - Peptide Elongation Factor 2 KW - Peptide Elongation Factors KW - Proteins KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - Tumor Necrosis Factor-alpha KW - Virulence Factors KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Protein Biosynthesis KW - Peptide Elongation Factors -- metabolism KW - HeLa Cells KW - Humans KW - Breast Neoplasms KW - Drug Resistance, Neoplasm KW - Recombinant Fusion Proteins -- toxicity KW - Fungal Proteins -- genetics KW - Adenosine Diphosphate Ribose -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - DNA, Neoplasm -- drug effects KW - Fungal Proteins -- metabolism KW - Tumor Cells, Cultured KW - Transfection KW - Antigens, Polyomavirus Transforming -- biosynthesis KW - Antibodies -- pharmacology KW - DNA, Antisense -- pharmacology KW - Pseudomonas aeruginosa KW - Cell Line KW - Female KW - Gene Library KW - Genes, Fungal KW - Immunotoxins -- toxicity KW - Apoptosis -- physiology KW - Diphtheria Toxin -- toxicity KW - Proteins -- metabolism KW - Tumor Necrosis Factor-alpha -- toxicity KW - Lymphotoxin-alpha -- toxicity KW - Proteins -- antagonists & inhibitors KW - Apoptosis -- drug effects KW - Exotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78074094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Role+of+CAS%2C+a+human+homologue+to+the+yeast+chromosome+segregation+gene+CSE1%2C+in+toxin+and+tumor+necrosis+factor+mediated+apoptosis.&rft.au=Brinkmann%2C+U%3BBrinkmann%2C+E%3BGallo%2C+M%3BScherf%2C+U%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1996-05-28&rft.volume=35&rft.issue=21&rft.spage=6891&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-17 N1 - Date created - 1996-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of residues 99, 220, and 221 of human cytochrome P450 2C19 as key determinants of omeprazole activity. AN - 78041085; 8647857 AB - Human P450 2C19 is selective for 4'-hydroxylation of S-mephenytoin and 5-hydroxylation of omeprazole, while the structurally homologous P450 2C9 has low activity toward these substrates. To identify the critical amino acids that determine the specificity of human amino acids that determine the specificity of human P450 2C19, we constructed chimeras of p450 2C9 replacing various proposed substrate binding sites (SRS) with those of P450 2C19 and then replaced individual residues of P450 2C19 and then replaced individual residues of P450 2C9 by site-directed mutagenesis. The 339 NH2-terminal amino acid residues (SRS-1-SRS-4) and amino acids 160-383 (SRS-2-SRS-5) of P450 2C19 conferred omeprazole 5-hydroxylase activity to P450 2C9. In contract, the COOH terminus of P450 2C19 (residues 340-490 including SRS-5 and SRS-6), residues 228-339 (SRS-3 and SRS-4) and residues 292-383 (part of SRS-4 and SRS-5) conferred only modest increases in activity. A single mutation Ile99 --> His increased omeprazole 5-hydroxylase to approximately 51% of that of P450 2C19. A chimera spanning residues 160-227 of P450 2C19 also exhibited omeprazole 5-hydroxylase activity which was dramatically enhanced by the mutation Ile99 --> His. A combination of two mutations, Ile99 --> His and Ser200 --> Pro, converted P450 2C9 to an enzyme with a turnover number of omeprazole 5-hyrdroxylation, which resembled that of P450 /c19. Mutation of Pro221 --> Thr enhanced this activity. Residue 99 is within SRS-1, but amino acids 220 and 221 are in the F-G loop and outside any known SRS. Mutation of these three amino acids did not confer significant S-mephenytoin 4'-hydroxylase activity to P450 2C9, although chimeras containing SRS-1-SRS-4 and SRS-2-SRS-5 of P450 2C19 exhibited activity toward this substrate. Our results thus indicate that amino acids 99, 220, and 221 are key residues that determine the specificity of P450 2C19 for omeprazole. JF - The Journal of biological chemistry AU - Ibeanu, G C AU - Ghanayem, B I AU - Linko, P AU - Li, L AU - Pederson, L G AU - Goldstein, J A AD - NIEHS, National Institute of Health, Research Triangle Park, North Carolina 27709, USA Y1 - 1996/05/24/ PY - 1996 DA - 1996 May 24 SP - 12496 EP - 12501 VL - 271 IS - 21 SN - 0021-9258, 0021-9258 KW - Oligodeoxyribonucleotides KW - 0 KW - Recombinant Fusion Proteins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C19 protein, human KW - Cytochrome P-450 CYP2C19 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- chemistry KW - Mixed Function Oxygenases -- chemistry KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78041085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+residues+99%2C+220%2C+and+221+of+human+cytochrome+P450+2C19+as+key+determinants+of+omeprazole+activity.&rft.au=Ibeanu%2C+G+C%3BGhanayem%2C+B+I%3BLinko%2C+P%3BLi%2C+L%3BPederson%2C+L+G%3BGoldstein%2C+J+A&rft.aulast=Ibeanu&rft.aufirst=G&rft.date=1996-05-24&rft.volume=271&rft.issue=21&rft.spage=12496&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-22 N1 - Date created - 1996-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced expression of the eosinophil-derived neurotoxin ribonuclease (RNS2) gene requires interaction between the promoter and intron. AN - 78040920; 8647842 AB - The eosinophil-derived neurotoxin (EDN/RNS2) is a member of the mammalian ribonuclease gene family and is one of four proteins found in the large specific granules of human eosinophilic leukocytes. The gene encoding EDN consists of two exons, including a noncoding exon 1, separated by a single intron from the coding sequence in exon 2. We have identified a functional promoter of the EDN gene and shown that optimal expression depends on interaction between the promoter and one or more sequence elements found in the single intron. Cells of the clone 15 eosinophilic variant of the human promyelocytic HL-60 cell line were transfected with constructs that included the promoter region of the EDN gene alone, promoter with exon 1, and promoter with both exon 1 and the intron positioned 5' to the chloramphenicol acetyltransferase (CAT) reporter gene (constructs referred to as PrCAT, PrExCAT, and PrExIn CAT, respectively). Although reporter gene activity from either PrCAT or PrExCAT was only 2-3 fold higher than baseline (CAT alone), inclusion of the single intron (PrExInCAT) resulted in a 28-fold increase in reporter gene activity in uninduced clone 15 cells, and an 80-fold in activity when clone 15 cells were induced to differentiate toward eosinophils with butyric acid. The intron-mediated enhancer activity was reproduced in other human hematopoietic cell lines (K562, Jurkat, U937, and HL-60), but was not found in human 293 kidney cells, suggesting that the function of the enhancer element(s) may be tissue-specific. A significant portion of the observed enhancer activity resides in the first 60 base pairs the the intron, which includes consensus binding sites for both AP-1, and NF-ATp transcription factors, and a 15-base pair segment that is identical to a sequence found in the promoter of the gene encoding the neutrophil granule protein, lactoferrin. The noncoding exon 1/single intron/coding exon 2 genomic structure is a common feature among the mammalian ribonucleases; this finding suggests the possibility of a conserved mechanism of regulation in this gene family. JF - The Journal of biological chemistry AU - Tiffany, H L AU - Handen, J S AU - Rosenberg, H F AD - Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20893, USA. Y1 - 1996/05/24/ PY - 1996 DA - 1996 May 24 SP - 12387 EP - 12393 VL - 271 IS - 21 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - DNA, Complementary KW - Neurotoxins KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - RNASE2 protein, human KW - EC 3.1.27.5 KW - Ribonuclease, Pancreatic KW - Index Medicus KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Enhancer Elements, Genetic KW - Molecular Sequence Data KW - Cloning, Molecular KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Enzymologic KW - Neurotoxins -- genetics KW - Introns KW - Ribonuclease, Pancreatic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78040920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Enhanced+expression+of+the+eosinophil-derived+neurotoxin+ribonuclease+%28RNS2%29+gene+requires+interaction+between+the+promoter+and+intron.&rft.au=Tiffany%2C+H+L%3BHanden%2C+J+S%3BRosenberg%2C+H+F&rft.aulast=Tiffany&rft.aufirst=H&rft.date=1996-05-24&rft.volume=271&rft.issue=21&rft.spage=12387&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-22 N1 - Date created - 1996-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of CYP2E1 in the hepatotoxicity of acetaminophen. AN - 78034405; 8662637 AB - CYP2El, a cytochrome P-450 that is well conserved across mammalian species, metabolizes ethanol and many low molecular weight toxins and cancer suspect agents. The cyp2e1 gene was isolated, and a mouse line that lacks expression of CYP2E1 was generated by homologous recombination in embryonic stem cells. Animals deficient in expression of the enzyme were fertile, developed normally, and exhibited no obvious phenotypic abnormalities, thus indicating that CYP2E1 has no critical role in mammalian development and physiology in the absence of external stimuli. When cyp2el knockout mice were challenged with the common analgesic acetaminophen, they were found to be considerably less sensitive to its hepatotoxic effects than wild-type animals, indicating that this P-450 is the principal enzyme responsible for the metabolic conversion of the drug to its active hepatotoxic metabolite. JF - The Journal of biological chemistry AU - Lee, S S AU - Buters, J T AU - Pineau, T AU - Fernandez-Salguero, P AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/05/17/ PY - 1996 DA - 1996 May 17 SP - 12063 EP - 12067 VL - 271 IS - 20 SN - 0021-9258, 0021-9258 KW - Analgesics, Non-Narcotic KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Index Medicus KW - Animals KW - Mice, Inbred C57BL KW - Mice KW - Mice, Knockout KW - Oxidoreductases, N-Demethylating -- genetics KW - Liver -- drug effects KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- physiology KW - Analgesics, Non-Narcotic -- toxicity KW - Acetaminophen -- metabolism KW - Acetaminophen -- toxicity KW - Oxidoreductases, N-Demethylating -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78034405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Role+of+CYP2E1+in+the+hepatotoxicity+of+acetaminophen.&rft.au=Lee%2C+S+S%3BButers%2C+J+T%3BPineau%2C+T%3BFernandez-Salguero%2C+P%3BGonzalez%2C+F+J&rft.aulast=Lee&rft.aufirst=S&rft.date=1996-05-17&rft.volume=271&rft.issue=20&rft.spage=12063&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-29 N1 - Date created - 1996-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tissue-specific factors additively increase the probability of the all-or-none formation of a hypersensitive site. AN - 78050706; 8665857 AB - DNase I-hypersensitive sites lack a canonical nucleosome and have binding sites for various transcription factors. To understand how the hypersensitivity is generated and maintained, we studied the chicken erythroid-specific beta(A)/epsilon globin gene enhancer, a region where both tissue-specific and ubiquitous transcription factors can bind. Constructions containing mutations of this enhancer were stably introduced into a chicken erythroid cell line. We found that the hypersensitivity was determined primarily by the erythroid factors and that their binding additively increased the accessibility. The fraction of accessible sites in clonal cell lines was quantitated using restriction endonucleases; these data implied that the formation of each hypersensitive site was an all-or-none phenomenon. Use of DNase I and micrococcal nuclease probes further indicated that the size of the hypersensitive site was influenced by the binding of transcription factors which then determined the length of the nucleosome-free gap. Our data are consistent with a model in which hypersensitive sites are generated stochastically: mutations that reduce the number of bound factors reduce the probability that these factors will prevail over a nucleosome; thus, the fraction of sites in the population that are accessible is also diminished. JF - The EMBO journal AU - Boyes, J AU - Felsenfeld, G AD - Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892, USA. Y1 - 1996/05/15/ PY - 1996 DA - 1996 May 15 SP - 2496 EP - 2507 VL - 15 IS - 10 SN - 0261-4189, 0261-4189 KW - Biological Factors KW - 0 KW - Nucleosomes KW - Transcription Factors KW - Globins KW - 9004-22-2 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Animals KW - Nucleosomes -- physiology KW - Erythropoiesis -- genetics KW - Drug Resistance KW - Organ Specificity KW - Mice KW - Mutagenesis, Site-Directed KW - Transcription Factors -- pharmacology KW - Base Sequence KW - Chickens KW - DNA Footprinting KW - Genes -- drug effects KW - Molecular Sequence Data KW - Erythroid Precursor Cells -- cytology KW - Cell Line KW - Promoter Regions, Genetic -- drug effects KW - Deoxyribonuclease I -- metabolism KW - Globins -- genetics KW - Biological Factors -- pharmacology KW - Enhancer Elements, Genetic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78050706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Tissue-specific+factors+additively+increase+the+probability+of+the+all-or-none+formation+of+a+hypersensitive+site.&rft.au=Boyes%2C+J%3BFelsenfeld%2C+G&rft.aulast=Boyes&rft.aufirst=J&rft.date=1996-05-15&rft.volume=15&rft.issue=10&rft.spage=2496&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-06 N1 - Date created - 1996-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1993 May;13(5):2776-86 [7682653] Cell. 1992 Nov 27;71(5):853-64 [1423633] Mol Cell Biol. 1993 Jul;13(7):3990-8 [8321206] Nature. 1994 Feb 10;367(6463):525-32 [8107823] Bioessays. 1994 Mar;16(3):165-70 [8166669] Science. 1994 Jul 1;265(5168):53-60 [8016655] Nature. 1994 Aug 11;370(6489):481-5 [8047170] Trends Biochem Sci. 1994 Jun;19(6):240-4 [8073501] Genes Dev. 1994 May 15;8(10):1133-46 [7926719] Science. 1994 Dec 23;266(5193):2007-11 [7801129] EMBO J. 1995 Jan 3;14(1):106-16 [7828582] Trends Biochem Sci. 1995 Apr;20(4):143-6 [7770913] Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7125-9 [7624382] Cell. 1981 Nov;27(1 Pt 2):45-55 [6276024] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Cell. 1986 Oct 24;47(2):217-27 [3021334] Proc Natl Acad Sci U S A. 1987 Jul;84(14):4786-90 [3474625] Cell. 1987 Nov 20;51(4):613-22 [3677170] Mol Cell Biol. 1987 Oct;7(10):3822-5 [2824998] Proc Natl Acad Sci U S A. 1988 Aug;85(16):5819-23 [3045805] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6267-71 [3166139] Cell. 1988 Oct 21;55(2):211-9 [2844412] Annu Rev Biochem. 1988;57:159-97 [3052270] Genes Dev. 1988 Sep;2(9):1089-100 [2461328] J Biol Chem. 1988 Dec 25;263(36):19259-62 [3198625] Mol Cell Biol. 1988 Aug;8(8):3114-21 [2463472] Mol Cell Biol. 1990 Jun;10(6):2774-86 [2160585] Genes Dev. 1990 Oct;4(10):1637-49 [2249769] Nature. 1990 Dec 20-27;348(6303):749-52 [2175398] Genes Dev. 1989 Nov;3(11):1814-22 [2558048] Cell. 1991 Feb 8;64(3):533-44 [1991320] Blood. 1991 May 15;77(10):2272-84 [1709381] EMBO J. 1991 Sep;10(9):2569-76 [1678348] Nature. 1992 Jan 16;355(6357):219-24 [1731219] Nucleic Acids Res. 1992 Jan 25;20(2):273-8 [1311071] Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4811-5 [1317573] J Mol Biol. 1992 Jun 20;225(4):985-98 [1377279] Trends Genet. 1993 Apr;9(4):134-7 [8516848] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. AN - 78048906; 8675009 AB - The molecular pathway of p53-dependent apoptosis (programmed cell death) is poorly understood. Because p53 binds to the basal transcription-repair complex TFIIH and modulates its DNA helicase activities, we hypothesized that TFIIH DNA helicases XPB and XPD are members of the p53-mediated apoptotic pathway. Whereas transfer of a wild-type p53 expression vector by microinjection or retroviral infection into primary normal human fibroblasts resulted in apoptosis, primary fibroblasts from individuals with xeroderma pigmentosum (XP), who are deficient in DNA repair and have germ-line mutations in the XPB or XPD gene, but not in the XPA or XPC gene, have a deficiency in the apoptotic response. This deficiency can be rescued by transferring the wild-type XPB or XPD gene into the corresponding mutant cells. XP-D lymphocytes also have a decreased apoptotic response to DNA damage by adriamycin, indicating a physiologically relevant deficiency. The XP-B or XP-D mutant cells undergo a normal apoptotic response when microinjected with the Ich-L, and ICE genes. Analyses of p53 mutants and the effects of microinjected anti-p53 antibody, Pab421, indicate that the carboxyl terminus of p53 may be required for apoptosis. Direct microinjection of the p53 carboxy-terminal-derived peptide (amino acid residues 319-393) resulted in apoptosis of primary normal human fibroblasts. These results disclose a novel pathway of p53-induced apoptosis. JF - Genes & development AU - Wang, X W AU - Vermeulen, W AU - Coursen, J D AU - Gibson, M AU - Lupold, S E AU - Forrester, K AU - Xu, G AU - Elmore, L AU - Yeh, H AU - Hoeijmakers, J H AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/05/15/ PY - 1996 DA - 1996 May 15 SP - 1219 EP - 1232 VL - 10 IS - 10 SN - 0890-9369, 0890-9369 KW - DNA-Binding Proteins KW - 0 KW - Proteins KW - Trans-Activators KW - Transcription Factors KW - Transcription Factors, TFII KW - Tumor Suppressor Protein p53 KW - XPBC-ERCC-3 protein KW - 146045-44-5 KW - Transcription Factor TFIIH KW - 148710-81-0 KW - Caspase 2 KW - EC 3.4.22.- KW - Caspases KW - Cysteine Endopeptidases KW - Caspase 1 KW - EC 3.4.22.36 KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Trans-Activators -- metabolism KW - Gene Transfer Techniques KW - Transcription Factors -- metabolism KW - DNA Damage KW - Cells, Cultured KW - Humans KW - Cysteine Endopeptidases -- metabolism KW - Xeroderma Pigmentosum -- metabolism KW - Fibroblasts -- cytology KW - Apoptosis KW - DNA Helicases -- metabolism KW - DNA-Binding Proteins -- genetics KW - DNA Helicases -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78048906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=The+XPB+and+XPD+DNA+helicases+are+components+of+the+p53-mediated+apoptosis+pathway.&rft.au=Wang%2C+X+W%3BVermeulen%2C+W%3BCoursen%2C+J+D%3BGibson%2C+M%3BLupold%2C+S+E%3BForrester%2C+K%3BXu%2C+G%3BElmore%2C+L%3BYeh%2C+H%3BHoeijmakers%2C+J+H%3BHarris%2C+C+C&rft.aulast=Wang&rft.aufirst=X&rft.date=1996-05-15&rft.volume=10&rft.issue=10&rft.spage=1219&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-12 N1 - Date created - 1996-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Two serologic markers to monitor the engraftment, growth, and treatment response of human leukemias in severe combined immunodeficient mice. AN - 78036582; 8639792 AB - We have investigated human lactate dehydrogenase (LDH) isoenzymes and human nuclear matrix protein 41/7 (NMP 41/7) as potential serologic markers to monitor the course of human leukemia in severe combined immunodeficient (SCID) mice. Following the transplantation of 10(6) human acute lymphoblastic leukemia (ALL) Nalm-6 cells, human specific LDH isoenzymes were measurable in the serum of SCID mice as early as 7 days after transplantation, although serum total LDH increased in some animals as early as 5 days after transplantation. Human NMP 41/7 was measurable in all animals at day 15 after leukemia cell injection. Serum levels of total LDH, human specific LDH and NMP 41/7 increased progressively over time, reaching total LDH levels as high as 50,000 U/L at day 25 after transplantation. To determine whether the levels of LDH and NMP 41/7 in serum were a reflection of human tumor burden, we studied these serologic markers in SCID mice bearing measurable subcutaneous human neuroblastoma tumors, or compared the serum levels of these markers with the number of human leukemia CD10+ cells in the bone marrow of the SCID mice. The serum levels of total LDH, human specific LDH isoenzymes, and NMP 41/7 correlated well with tumor burden, and they drastically decreased or disappeared from serum after the human leukemia or neuroblastoma cells were selectively killed with a single intravenous (IV) injection of 1 to 3 micrograms diphtheria toxin (DT) (the cellular receptor for DT is present on human cells, but not on mouse cells). Paraplegic mice with central nervous system leukemia completely recovered after DT treatment. We conclude that measurements of serum levels of total LDH, human LDH isoenzymes, and NMP 41/7 are sensitive, quantitative, rapid, and easy to perform serologic methods useful to monitor the engraftment, progression, and treatment response of human leukemia in SCID mice. JF - Blood AU - Arguello, F AU - Sterry, J A AU - Zhao, Y Z AU - Alexander, M R AU - Shoemaker, R H AU - Cohen, H J AD - Division of Cancer Treatment, National Institutes of Health, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1996/05/15/ PY - 1996 DA - 1996 May 15 SP - 4325 EP - 4332 VL - 87 IS - 10 SN - 0006-4971, 0006-4971 KW - Antigens, Nuclear KW - 0 KW - Biomarkers, Tumor KW - Diphtheria Toxin KW - HBEGF protein, human KW - Hbegf protein, mouse KW - Heparin-binding EGF-like Growth Factor KW - Intercellular Signaling Peptides and Proteins KW - Isoenzymes KW - NUMA1 protein, human KW - Neoplasm Proteins KW - Nuclear Matrix-Associated Proteins KW - Nuclear Proteins KW - Numa1 protein, mouse KW - Protein Synthesis Inhibitors KW - Receptors, Cell Surface KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Abridged Index Medicus KW - Index Medicus KW - Sensitivity and Specificity KW - Neuroblastoma -- pathology KW - Animals KW - Paraneoplastic Syndromes -- etiology KW - Neuroblastoma -- blood KW - Severe Combined Immunodeficiency -- complications KW - Humans KW - Mice KW - Mice, Inbred BALB C KW - Paraplegia -- drug therapy KW - Meninges -- pathology KW - Paraplegia -- etiology KW - Neuroblastoma -- drug therapy KW - Graft Survival KW - Mice, Inbred C57BL KW - Diphtheria Toxin -- therapeutic use KW - Leukemic Infiltration KW - Protein Synthesis Inhibitors -- therapeutic use KW - Paraneoplastic Syndromes -- drug therapy KW - Species Specificity KW - Female KW - Receptors, Cell Surface -- drug effects KW - Nuclear Proteins -- blood KW - Neoplasm Transplantation KW - Isoenzymes -- blood KW - L-Lactate Dehydrogenase -- blood KW - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy KW - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma -- blood KW - Transplantation, Heterologous KW - Neoplasm Proteins -- blood KW - Mice, SCID -- blood KW - Biomarkers, Tumor -- blood KW - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78036582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Two+serologic+markers+to+monitor+the+engraftment%2C+growth%2C+and+treatment+response+of+human+leukemias+in+severe+combined+immunodeficient+mice.&rft.au=Arguello%2C+F%3BSterry%2C+J+A%3BZhao%2C+Y+Z%3BAlexander%2C+M+R%3BShoemaker%2C+R+H%3BCohen%2C+H+J&rft.aulast=Arguello&rft.aufirst=F&rft.date=1996-05-15&rft.volume=87&rft.issue=10&rft.spage=4325&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced engraftment of hematopoietic progenitor cells in mice treated with granulocyte colony-stimulating factor before low-dose irradiation: implications for gene therapy. AN - 78034796; 8639760 AB - Gene therapy for inherited disorders of blood cells will require both efficient methods for stable gene transfer and nonablative bone marrow conditioning regimens to allow engraftment of modified hematopoietic progenitor cells (HPCs). We have used a sensitive murine system for detecting HPC engraftment using congenic C57BL/6 mice that differ at the Ly5 locus, which encodes the leukocyte common antigen. The system relies on the ability of monoclonal antibodies with specificity for Ly5.1 and Ly5.2 (revised nomenclature: CD45.1 and CD45.2, respectively) to distinguish donor and recipient peripheral blood leukocytes after transplantation of purified Sca-1+ bone marrow-derived HPCs. No detectable engraftment occurred in nonirradiated recipient mice, even when as many as 2.0 x 10(6) SCa-1+HPCs were transplanted. However, in mice receiving total body irradiation (TBI), engraftment increased as a function of pretransplantation radiation dose, number of transplanted cells, and time after transplantation. Moreover, mice receiving either granulocyte colony-stimulating factor (G-CSF) or G-CSF+ stem cell factor before low-dose TBI (160 cGy) exhibited a marked increase in engraftment compared with mice receiving a vehicle control before low-dose TBI (18.9% and 20.6% v 5.6% at a 1 month, respectively; 29% and 35% v 15.1% at 4 months, respectively). Use of growth factor pretreatment even allowed TBI doses as low as 30, 70, or 120 cGy to achieve significant engraftment of donor progenitors (0.3%, 1.5%, and 6.8% at 1 month, respectively; 1.7%, 5.8%, and 13.9% at 4 months, respectively). All animals remained healthy during the observation periods. Thus, growth factor preconditioning of the recipient followed by low-dose TBI may provide an optimal balance between safety and efficacy in achieving required levels of engraftment for gene therapy of blood disorders. JF - Blood AU - Mardiney, M AU - Malech, H L AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886, USA. Y1 - 1996/05/15/ PY - 1996 DA - 1996 May 15 SP - 4049 EP - 4056 VL - 87 IS - 10 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Ly KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Abridged Index Medicus KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Bone Marrow Cells KW - Radiation Dosage KW - Animals KW - Antigens, Ly -- genetics KW - Mice, Inbred C57BL KW - Mice KW - Antibodies, Monoclonal -- immunology KW - Whole-Body Irradiation KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Hematopoietic Stem Cell Transplantation KW - Genetic Therapy -- methods KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - Radiation Chimera KW - Graft Survival -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78034796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Enhanced+engraftment+of+hematopoietic+progenitor+cells+in+mice+treated+with+granulocyte+colony-stimulating+factor+before+low-dose+irradiation%3A+implications+for+gene+therapy.&rft.au=Mardiney%2C+M%3BMalech%2C+H+L&rft.aulast=Mardiney&rft.aufirst=M&rft.date=1996-05-15&rft.volume=87&rft.issue=10&rft.spage=4049&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The impact of interindividual variation in NAT2 activity on benzidine urinary metabolites and urothelial DNA adducts in exposed workers. AN - 78016024; 8643532 AB - Several epidemiologic studies indicate that NAT2-related slow N-acetylation increases bladder cancer risk among workers exposed to aromatic amines, presumably because N-acetylation is important for the detoxification of these compounds. Previously, we showed that NAT2 polymorphisms did not influence bladder cancer risk among Chinese workers exposed exclusively to benzidine (BZ), suggesting that NAT2 N-acetylation is not a critical detoxifying pathway for this aromatic amine. To evaluate the biologic plausibility of this finding, we carried out a cross-sectional study of 33 workers exposed to BZ and 15 unexposed controls in Ahmedabad, India, to evaluate the presence of BZ-related DNA adducts in exfoliated urothelial cells, the excretion pattern of BZ metabolites, and the impact of NAT2 activity on these outcomes. Four DNA adducts were significantly elevated in exposed workers compared to controls; of these, the predominant adduct cochromatographed with a synthetic N-(3'- phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine standard and was the only adduct that was significantly associated with total BZ urinary metabolites (r = 0.68, P < 0.0001). To our knowledge this is the first report to show that BZ forms DNA adducts in exfoliated urothelial cells of exposed humans and that the predominant adduct formed is N-acetylated, supporting the concept that monofunctional acetylation is an activation, rather than a detoxification, step for BZ. However, because almost all BZ-related metabolites measured in the urine of exposed workers were acetylated among slow, as well as rapid, acetylators (mean +/- SD 95 +/- 1.9% vs. 97 +/- 1.6%, respectively) and NAT2 activity did not affect the levels of any DNA adduct measured, it is unlikely that interindividual variation in NAT2 function is relevant for BZ-associated bladder carcinogenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Rothman, N AU - Bhatnagar, V K AU - Hayes, R B AU - Zenser, T V AU - Kashyap, S K AU - Butler, M A AU - Bell, D A AU - Lakshmi, V AU - Jaeger, M AU - Kashyap, R AU - Hirvonen, A AU - Schulte, P A AU - Dosemeci, M AU - Hsu, F AU - Parikh, D J AU - Davis, B B AU - Talaska, G AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/05/14/ PY - 1996 DA - 1996 May 14 SP - 5084 EP - 5089 VL - 93 IS - 10 SN - 0027-8424, 0027-8424 KW - Benzidines KW - 0 KW - Carcinogens KW - DNA Adducts KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - NAT2 protein, human KW - Index Medicus KW - Phenotype KW - Occupational Exposure KW - Genetic Variation KW - Cross-Sectional Studies KW - Urinary Bladder Neoplasms -- etiology KW - Risk Factors KW - Humans KW - Urinary Bladder Neoplasms -- genetics KW - Adult KW - Urinary Bladder Neoplasms -- metabolism KW - Male KW - India KW - Urinary Bladder -- metabolism KW - Benzidines -- metabolism KW - Carcinogens -- metabolism KW - Carcinogens -- toxicity KW - Benzidines -- toxicity KW - Arylamine N-Acetyltransferase -- metabolism KW - DNA Adducts -- metabolism KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78016024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+impact+of+interindividual+variation+in+NAT2+activity+on+benzidine+urinary+metabolites+and+urothelial+DNA+adducts+in+exposed+workers.&rft.au=Rothman%2C+N%3BBhatnagar%2C+V+K%3BHayes%2C+R+B%3BZenser%2C+T+V%3BKashyap%2C+S+K%3BButler%2C+M+A%3BBell%2C+D+A%3BLakshmi%2C+V%3BJaeger%2C+M%3BKashyap%2C+R%3BHirvonen%2C+A%3BSchulte%2C+P+A%3BDosemeci%2C+M%3BHsu%2C+F%3BParikh%2C+D+J%3BDavis%2C+B+B%3BTalaska%2C+G&rft.aulast=Rothman&rft.aufirst=N&rft.date=1996-05-14&rft.volume=93&rft.issue=10&rft.spage=5084&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-18 N1 - Date created - 1996-07-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1982 Jul;42(7):2678-86 [7083160] Anal Biochem. 1996 Feb 15;234(2):183-9 [8714596] J Pharmacol Exp Ther. 1983 Dec;227(3):545-50 [6418878] Carcinogenesis. 1984 Mar;5(3):407-12 [6705145] Carcinogenesis. 1984 Nov;5(11):1499-503 [6488474] Proc Natl Acad Sci U S A. 1984 Nov;81(22):6943-7 [6594673] Carcinogenesis. 1985 Jul;6(7):959-65 [4017176] J Natl Cancer Inst. 1986 Jan;76(1):1-8 [3455732] Fed Proc. 1986 Sep;45(10):2465-70 [3091404] Carcinogenesis. 1987 Dec;8(12):1899-905 [3677313] Proc Natl Acad Sci U S A. 1988 May;85(10):3513-7 [3368462] Biochim Biophys Acta. 1988 Aug 3;948(1):37-66 [3293663] Arch Environ Health. 1988 Jul-Aug;43(4):269-72 [3415352] Cancer Res. 1989 Apr 15;49(8):1977-82 [2495173] Cancer Res. 1989 May 1;49(9):2448-54 [2784998] Carcinogenesis. 1990 Apr;11(4):639-46 [2323002] Anticancer Res. 1990 Jan-Feb;10(1):225-9 [2334132] Br J Ind Med. 1990 Aug;47(8):544-52 [2393635] Mol Pharmacol. 1991 Feb;39(2):184-91 [1996083] J Occup Med. 1967 Jun;9(6):277-85 [6026374] Arch Environ Health. 1973 Jul;27(1):1-7 [4709106] J Occup Med. 1990 Sep;32(9):917-8 [2074519] Annu Rev Pharmacol Toxicol. 1979;19:129-57 [378100] Environ Health Perspect. 1979 Apr;29:71-9 [510245] Carcinogenesis. 1981;2(8):747-52 [7285281] Nihon Eiseigaku Zasshi. 1990 Oct;45(4):909-18 [2089166] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5237-41 [1675794] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5350-4 [2052611] Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6333-7 [2068113] Am J Ind Med. 1992;21(4):481-9 [1580253] Cancer Res. 1992 Jul 15;52(14):3961-4 [1617672] Am J Hum Genet. 1993 Apr;52(4):827-34 [8460648] Carcinogenesis. 1993 Apr;14(4):675-8 [8472331] Cancer Epidemiol Biomarkers Prev. 1991 Nov-Dec;1(1):61-6 [1845172] Pharmacogenetics. 1992 Jun;2(3):116-27 [1306111] Carcinogenesis. 1993 Aug;14(8):1689-92 [8102597] Pharmacogenetics. 1993 Oct;3(5):250-5 [8287063] Carcinogenesis. 1994 Dec;15(12):2781-7 [8001235] Hum Mol Genet. 1995 Feb;4(2):231-6 [7757072] Pharmacogenetics. 1995 Feb;5(1):1-17 [7773298] Carcinogenesis. 1995 Jul;16(7):1565-71 [7614690] Cancer Res. 1995 Aug 15;55(16):3537-42 [7627961] Chem Res Toxicol. 1995 Jul-Aug;8(5):711-20 [7548754] Cancer Res. 1995 Nov 15;55(22):5226-9 [7585580] Cancer Res. 1995 Nov 15;55(22):5230-7 [7585581] Lancet. 1982 Oct 16;2(8303):842-5 [6126711] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. AN - 78007169; 8643547 AB - A second isoform of the human vesicular monoamine transporter (hVMAT) has been cloned from a pheochromocytoma cDNA library. The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2. Central, peripheral, and enteric neurons express only VMAT2. VMAT1 is expressed exclusively in neuroendocrine, including chromaffin and enterochromaffin, cells. VMAT1 and VMAT2 are coexpressed in all chromaffin cells of the adrenal medulla. VMAT2 alone is expressed in histamine-storing enterochromaffin-like cells of the oxyntic mucosa of the stomach. The transport characteristics and pharmacology of each VMAT isoform have been directly compared after expression in digitonin-permeabilized fibroblastic (CV-1) cells, providing information about substrate feature recognition by each transporter and the role of vesicular monoamine storage in the mechanism of action of psychopharmacologic and neurotoxic agents in human. Serotonin has a similar affinity for both transporters. Catecholamines exhibit a 3-fold higher affinity, and histamine exhibits a 30-fold higher affinity, for VMAT2. Reserpine and ketanserin are slightly more potent inhibitors of VMAT2-mediated transport than of VMAT1-mediated transport, whereas tetrabenazine binds to and inhibits only VMAT2. N-methyl-4-phenylpyridinium, phenylethylamine, amphetamine, and methylenedioxymethamphetamine are all more potent inhibitors of VMAT2 than of VMAT1, whereas fenfluramine is a more potent inhibitor of VMAT1-mediated monamine transport than of VMAT2-mediated monoamine transport. The unique distributions of hVMAT1 and hVMAT2 provide new markers for multiple neuroendocrine lineages, and examination of their transport properties provides mechanistic insights into the pharmacology and physiology of amine storage in cardiovascular, endocrine, and central nervous system function. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Erickson, J D AU - Schafer, M K AU - Bonner, T I AU - Eiden, L E AU - Weihe, E AD - Section on Molecular Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1996/05/14/ PY - 1996 DA - 1996 May 14 SP - 5166 EP - 5171 VL - 93 IS - 10 SN - 0027-8424, 0027-8424 KW - DNA, Complementary KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Neuropeptides KW - SLC18A1 protein, human KW - SLC18A2 protein, human KW - Vesicular Biogenic Amine Transport Proteins KW - Vesicular Monoamine Transport Proteins KW - Index Medicus KW - Antibody Specificity KW - Protein Structure, Secondary KW - DNA, Complementary -- genetics KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Tissue Distribution KW - Immunohistochemistry KW - Cloning, Molecular KW - Neurosecretory Systems -- metabolism KW - Membrane Glycoproteins -- immunology KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78007169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Distinct+pharmacological+properties+and+distribution+in+neurons+and+endocrine+cells+of+two+isoforms+of+the+human+vesicular+monoamine+transporter.&rft.au=Erickson%2C+J+D%3BSchafer%2C+M+K%3BBonner%2C+T+I%3BEiden%2C+L+E%3BWeihe%2C+E&rft.aulast=Erickson&rft.aufirst=J&rft.date=1996-05-14&rft.volume=93&rft.issue=10&rft.spage=5166&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-18 N1 - Date created - 1996-07-18 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U39905; GENBANK N1 - SuppNotes - Cited By: Brain Res. 1982 Mar 4;235(1):93-103 [6145488] Science. 1983 Feb 25;219(4587):979-80 [6823561] Science. 1985 Sep 6;229(4717):986-8 [4023719] Gut. 1985 Dec;26(12):1284-95 [2867954] J Biol Chem. 1986 Jun 15;261(17):7585-7 [3486869] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 [3095828] Digestion. 1986;35 Suppl 1:42-55 [3792671] Histochemistry. 1986;86(1):5-17 [2878908] Nature. 1987 Oct 29-Nov 4;329(6142):840-2 [3313052] Proc Natl Acad Sci U S A. 1987 Nov;84(22):8160-4 [2891137] Brain Res. 1988 Apr 12;446(1):165-8 [2897228] Mol Pharmacol. 1988 Jun;33(6):672-7 [3380081] J Pharmacol Exp Ther. 1988 Sep;246(3):822-8 [2458447] J Pharmacol Exp Ther. 1988 Nov;247(2):487-94 [3263494] Biochemistry. 1989 Feb 21;28(4):1692-7 [2719928] Neuron. 1990 Dec;5(6):797-808 [2268433] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1817-21 [1347426] Cell Tissue Res. 1992 Apr;268(1):109-16 [1499046] Cell. 1992 Aug 21;70(4):539-51 [1505023] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9730-3 [1357668] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10993-7 [1438304] Annu Rev Neurosci. 1993;16:129-58 [8460888] Gastroenterology. 1993 Apr;104(4):994-1006 [7681798] FEBS Lett. 1993 Nov 29;335(1):27-32 [7902299] J Neurochem. 1993 Dec;61(6):2314-7 [8245983] Mol Pharmacol. 1993 Dec;44(6):1227-31 [7903417] FEBS Lett. 1994 Jan 24;338(1):16-22 [8307150] J Biol Chem. 1994 Mar 11;269(10):7231-7 [8125935] FEBS Lett. 1994 Mar 28;342(1):97-102 [8143858] FEBS Lett. 1994 Apr 11;342(3):225-9 [8150075] J Pharmacol Exp Ther. 1994 May;269(2):792-8 [7514223] Peptides. 1994;15(2):263-79 [8008631] Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26 [7912402] Physiol Rev. 1995 Apr;75(2):369-92 [7724667] J Mol Neurosci. 1994 Fall;5(3):149-64 [7654518] J Neurosci. 1995 Sep;15(9):6179-88 [7666200] J Mol Neurosci. 1995;6(4):277-87 [8860238] Science. 1971 Aug 13;173(3997):598-606 [4397955] Psychiatry Res. 1979 Dec;1(3):249-54 [298352] Biochem Pharmacol. 1980 Nov 15;29(22):3045-50 [6109535] Neurology. 1981 Aug;31(8):1051-4 [6455607] Proc Natl Acad Sci U S A. 1985 Apr;82(7):2173-7 [3872460] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factor expression in human cancer cell lines. AN - 78020581; 8626706 AB - The insulin-like growth factors (IGFs), IGF-I and IGF-II, are potent mitogens for human lung and other epithelial cancer cell lines. Previous studies in defined medium lacking added IGF or insulin suggest that an IGF-related ligand can act as an autocrine growth factor for many cancer cell lines through action via the type I IGF receptor (IGF-R). Analysis of RNA isolated from human lung and breast cancer cell lines by reverse transcription of mRNA and polymerase chain reaction reveal that IGF-I and IGF-II mRNAs were co-expressed with IGF-R in the majority of cell lines. IGF-I mRNA was detected in 11/12 small cell lung cancer cell lines (SCLC), 13/14 nonsmall cell lung cancer (NSCLC) cell lines, and 1/2 breast cancer cell lines. IGF-II mRNA was detected in 8/10 SCLC, 11/12 NSCLC cell lines, and 2/2 breast lines. All cell lines expressed IGF-R. For analysis of IGF peptide secretion, cell lines were adapted to growth in serum/hormone-free culture medium (R0), and to avoid interference by IGF-binding proteins, secreted IGF peptides were isolated under acidic conditions and analyzed by Western blotting. Based upon measurement of the sensitivity of the anti-IGF antibodies for detection of recombinant human IGFs, IGF peptides accumulated in conditioned medium at greater than picomolar concentrations should have been readily detected. In three cell lines (two lung and one breast) secreted IGF immunoreactivity was detected as three molecular mass species of 23, 14, and 6 kDa. Isolation and NH2-terminal sequencing of each of these species definitively identified them as differentially processed forms of the IGF-II prohormone. Despite the high frequency of IGF-I gene expression detected by reverse transcription-polymerase chain reaction analysis, only one lung cancer cell line, NCI-N417d, was found that unequivocally secreted IGF-I peptide. This direct sequence determination unambiguously identifies IGF-II as the predominant IGF involved in the autocrine growth stimulation of human lung and breast epithelial tumor cell lines and supports a growing body of literature that implicates IGF-II/IGF-R autocrine loops as a common growth mechanism in epithelial carcinogenesis. JF - The Journal of biological chemistry AU - Quinn, K A AU - Treston, A M AU - Unsworth, E J AU - Miller, M J AU - Vos, M AU - Grimley, C AU - Battey, J AU - Mulshine, J L AU - Cuttitta, F AD - Biomarkers and Prevention Research Branch, NCI, National Institutes of Health, Rockville, Maryland 20850, USA. Y1 - 1996/05/10/ PY - 1996 DA - 1996 May 10 SP - 11477 EP - 11483 VL - 271 IS - 19 SN - 0021-9258, 0021-9258 KW - Culture Media, Conditioned KW - 0 KW - DNA Primers KW - RNA, Messenger KW - RNA, Neoplasm KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Humans KW - RNA, Messenger -- analysis KW - Breast Neoplasms KW - Transcription, Genetic KW - Amino Acid Sequence KW - RNA, Neoplasm -- analysis KW - RNA, Messenger -- biosynthesis KW - Chromatography, High Pressure Liquid KW - Carcinoma, Small Cell KW - Polymerase Chain Reaction KW - Base Sequence KW - Blotting, Western KW - Tumor Cells, Cultured KW - Lung Neoplasms KW - Molecular Sequence Data KW - Adenocarcinoma KW - Carcinoma, Non-Small-Cell Lung KW - Female KW - Insulin-Like Growth Factor I -- biosynthesis KW - Insulin-Like Growth Factor II -- analysis KW - Insulin-Like Growth Factor II -- biosynthesis KW - Gene Expression KW - Insulin-Like Growth Factor I -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78020581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Insulin-like+growth+factor+expression+in+human+cancer+cell+lines.&rft.au=Quinn%2C+K+A%3BTreston%2C+A+M%3BUnsworth%2C+E+J%3BMiller%2C+M+J%3BVos%2C+M%3BGrimley%2C+C%3BBattey%2C+J%3BMulshine%2C+J+L%3BCuttitta%2C+F&rft.aulast=Quinn&rft.aufirst=K&rft.date=1996-05-10&rft.volume=271&rft.issue=19&rft.spage=11477&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-27 N1 - Date created - 1996-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential mu opiate receptor phosphorylation and desensitization induced by agonists and phorbol esters. AN - 78017144; 8626702 AB - mu opiate receptors, the principal sites for opiate analgesia and reward, can display compensatory responses to opiate agonist drug administration. Agonist-induced K+ channel responses mediated by these receptors desensitize when examined in Xenopus oocyte expression systems. Mechanisms underlying such processes could include phosphorylation events similar to those reported to desensitize other G-protein-linked receptors. We used C-terminally directed anti-mu receptor antibodies to immunoprecipitate a phosphoprotein with size appropriate for the mu receptor from stably expressing Chinese hamster ovary cells. Phosphorylation of this mu opiate receptor protein was enhanced approximately 5-fold by treatment with the mu agonist morphine. The time course and dose-response relationships between mu receptor phosphorylation and agonist-induced desensitization display interesting parallels. Phosphorylation of mu opiate receptor protein is also enhanced approximately 5-fold by treatment with the protein kinase C activator phorbol 12-myristate 13-acetate. The protein kinase inhibitor staurosporine blocked the effect of phorbol 12-myristate 13-acetate on mu receptor phosphorylation. However, staurosporine failed to block morphine-induced phosphorylation. These observations suggest that several biochemical pathways can lead to mu receptor phosphorylation events that may include mechanisms involved in mu receptor desensitization. JF - The Journal of biological chemistry AU - Zhang, L AU - Yu, Y AU - Mackin, S AU - Weight, F F AU - Uhl, G R AU - Wang, J B AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-8205, USA. Y1 - 1996/05/10/ PY - 1996 DA - 1996 May 10 SP - 11449 EP - 11454 VL - 271 IS - 19 SN - 0021-9258, 0021-9258 KW - Analgesics KW - 0 KW - Enkephalins KW - Phosphoproteins KW - Potassium Channels KW - Receptors, Opioid, mu KW - Recombinant Proteins KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- KW - 100929-53-1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Analgesics -- pharmacology KW - Oocytes -- physiology KW - Xenopus laevis KW - Patch-Clamp Techniques KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - CHO Cells KW - Membrane Potentials -- drug effects KW - Phosphoproteins -- isolation & purification KW - Female KW - Phosphoproteins -- metabolism KW - Cricetinae KW - Receptors, Opioid, mu -- physiology KW - Enkephalins -- pharmacology KW - Receptors, Opioid, mu -- agonists KW - Receptors, Opioid, mu -- biosynthesis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Potassium Channels -- physiology KW - Potassium Channels -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78017144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Differential+mu+opiate+receptor+phosphorylation+and+desensitization+induced+by+agonists+and+phorbol+esters.&rft.au=Zhang%2C+L%3BYu%2C+Y%3BMackin%2C+S%3BWeight%2C+F+F%3BUhl%2C+G+R%3BWang%2C+J+B&rft.aulast=Zhang&rft.aufirst=L&rft.date=1996-05-10&rft.volume=271&rft.issue=19&rft.spage=11449&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-27 N1 - Date created - 1996-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced growth capacity of hepatocytes from c-myc and c-myc/TGF-alpha transgenic mice in primary culture. AN - 78017273; 8630075 AB - We have previously shown that coexpression of c-myc and TGF-alpha in the liver results in accelerated replicative senescence and promotes tumor development in young adult transgenic mice. Here we describe the characteristics of hepatocyte proliferation in primary cultures established from 10-week-old control, c-myc and c-myc/TGF-alpha transgenic mice. A variety of cellular and functional changes occurred in the transgenic livers at this age including enhanced polypoidization and impairment of hepatic functions. Control mouse hepatocytes demonstrated a high level of DNA synthesis in serum-free medium with a maximum at day three in culture at which time 70% of the cells were in S phase. In contrast, DNA synthesis peaked one day later and was reduced by 50% in the cultured c-myc and c-myc/TGF-alpha hepatocytes. Also, higher frequency of apoptosis was observed in the transgenic hepatocytes. However, in hepatocytes isolated from c-myc/TGF-alpha mice, which show early appearance of preneoplastic lesions in vivo, the DNA synthesis continued for 6 days in culture in contrast to a sharp decrease in the labeling index of control and c-myc hepatocytes after 3-4 days in culture. The results suggest that proliferative features of the transgenic hepatocytes in vitro reflect the general properties of these cells in vivo and thus may provide a model for studies on senescence and transformation of hepatocytes. JF - Biochemical and biophysical research communications AU - Kao, C Y AU - Factor, V M AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/05/06/ PY - 1996 DA - 1996 May 06 SP - 64 EP - 70 VL - 222 IS - 1 SN - 0006-291X, 0006-291X KW - RNA, Messenger KW - 0 KW - Transforming Growth Factor alpha KW - Index Medicus KW - Animals KW - Cells, Cultured KW - Gene Expression KW - Mice KW - RNA, Messenger -- genetics KW - Ploidies KW - Mice, Transgenic KW - Cell Division KW - Liver -- cytology KW - Transforming Growth Factor alpha -- genetics KW - Genes, myc KW - Cell Aging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78017273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Reduced+growth+capacity+of+hepatocytes+from+c-myc+and+c-myc%2FTGF-alpha+transgenic+mice+in+primary+culture.&rft.au=Kao%2C+C+Y%3BFactor%2C+V+M%3BThorgeirsson%2C+S+S&rft.aulast=Kao&rft.aufirst=C&rft.date=1996-05-06&rft.volume=222&rft.issue=1&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integrin alpha v beta 5-dependent serine phosphorylation of paxillin in cultured human macrophages adherent to vitronectin. AN - 78033589; 8631923 AB - The macrophage colony-stimulating factor (M-CSF) is able to induce the expression of the alpha v beta 5 integrin receptor on the surface of cultured human macrophages (De Nichilo, M. O., and Burns, G. F. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2517-2521). In the present study, we establish that the adhesion of M-CSF-treated macrophages to vitronectin is mediated by the integrin alpha v beta 5, and show by indirect immunofluorescence analysis that alpha v beta 5 and the cytoskeletal protein paxillin localize to focal contacts upon adhesion to vitronectin. Immunoprecipitation and Western blot analysis revealed that M-CSF-treated macrophages do not express focal adhesion kinase (FAK), thereby providing direct evidence for integrin-dependent localization of paxillin to focal contacts in the absence of FAK expression. Investigation of paxillin phosphorylation by two-dimensional phosphoamino acid analysis indicates that paxillin is 99% phosphorylated on serine residue(s) in response to vitronectin adhesion, and only 1% phosphorylated on tyrosine. Stimulation of protein kinase C (PKC) activity with the phorbol ester phorbol 12-myristate 13-acetate enhances paxillin phosphorylation, while two selective inhibitors of PKC, GF109203X and chelerythrine chloride, effectively block the phosphorylation of paxillin induced in response to vitronectin adhesion. Taken together, these data demonstrate that in M-CSF-treated macrophages adherent to vitronectin, paxillin localizes to focal contacts in the absence of FAK expression and is predominantly phosphorylated on serine residue(s) in a PKC-dependent manner. JF - The Journal of biological chemistry AU - De Nichilo, M O AU - Yamada, K M AD - Laboratory of Developmental Biology, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA. mnichilo@yoda.nidr.nih.gov Y1 - 1996/05/03/ PY - 1996 DA - 1996 May 03 SP - 11016 EP - 11022 VL - 271 IS - 18 SN - 0021-9258, 0021-9258 KW - Cell Adhesion Molecules KW - 0 KW - Cytoskeletal Proteins KW - Integrins KW - PXN protein, human KW - Paxillin KW - Phosphoproteins KW - Receptors, Vitronectin KW - Vitronectin KW - integrin alphaVbeta5 KW - Serine KW - 452VLY9402 KW - Macrophage Colony-Stimulating Factor KW - 81627-83-0 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Focal Adhesion Kinase 1 KW - EC 2.7.10.2 KW - Focal Adhesion Protein-Tyrosine Kinases KW - PTK2 protein, human KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Enzyme Activation KW - Humans KW - Macrophage Colony-Stimulating Factor -- pharmacology KW - Protein-Tyrosine Kinases -- metabolism KW - Protein Binding KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Phosphorylation KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Adhesion Molecules -- metabolism KW - Cell Adhesion KW - Macrophages -- cytology KW - Vitronectin -- metabolism KW - Macrophages -- drug effects KW - Integrins -- metabolism KW - Cytoskeletal Proteins -- metabolism KW - Serine -- metabolism KW - Phosphoproteins -- metabolism KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78033589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Integrin+alpha+v+beta+5-dependent+serine+phosphorylation+of+paxillin+in+cultured+human+macrophages+adherent+to+vitronectin.&rft.au=De+Nichilo%2C+M+O%3BYamada%2C+K+M&rft.aulast=De+Nichilo&rft.aufirst=M&rft.date=1996-05-03&rft.volume=271&rft.issue=18&rft.spage=11016&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-01 N1 - Date created - 1996-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single nucleotide positions have proximal and distal influence on UV mutation hotspots and coldspots. AN - 78006963; 8627623 AB - Base substitution mutation frequency is influenced by the sequence context surrounding lesions in the DNA. We have been studying ultraviolet mutagenesis in human repair-deficient cells in the supF marker gene carried in a shuttle vector plasmid. There are prominent hotspots, on opposite strands, at the 5' TC sites in the eight base palindrome 5' CTTCGAAG. Recently, we developed a reporter system which permits sequence manipulation in the vicinity of mutational hotspots. We have used the system to characterize the influence of individual positions in the palindrome on the frequency of mutagenesis at the two UV hotspots. In this paper we have determined the contribution of bases at the second and third positions in the palindrome. Changes in bases that were in the primer template duplex when the replication complex encountered the photoproducts at one of the hotspot sites significantly increased or decreased the probability of mutations at the site. We also observed modulation of hotspot activity at other sites as a function of single base changes as much as 80 bases away from the hotspots. In these instances, the site of the changed base was in the unreplicated template ahead of the primer terminus when the polymerase encountered the relevant photoproduct. Our results indicate that sequence context has both proximal and distal consequences for mutagenesis. JF - Journal of molecular biology AU - Levy, D D AU - Magee, A D AU - Seidman, M M AD - Laboratory of Molecular Carcinogenesis, NCI, NIH Bethesda, MD 20892, USA. Y1 - 1996/05/03/ PY - 1996 DA - 1996 May 03 SP - 251 EP - 260 VL - 258 IS - 2 SN - 0022-2836, 0022-2836 KW - Nucleotides KW - 0 KW - supF tRNA KW - DNA KW - 9007-49-2 KW - RNA, Transfer KW - 9014-25-9 KW - Index Medicus KW - Base Sequence KW - Base Composition KW - Humans KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Cell Line KW - Ultraviolet Rays KW - RNA, Transfer -- genetics KW - Mutagenesis KW - Genes, Suppressor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78006963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Single+nucleotide+positions+have+proximal+and+distal+influence+on+UV+mutation+hotspots+and+coldspots.&rft.au=Levy%2C+D+D%3BMagee%2C+A+D%3BSeidman%2C+M+M&rft.aulast=Levy&rft.aufirst=D&rft.date=1996-05-03&rft.volume=258&rft.issue=2&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Noise reduction in PET attenuation correction by maximum likelihood histogram sharpening of attenuation images. AN - 85276528; pmid-8965146 AB - A new method for PET transmission data processing was developed and found to reduce transmission noise in 18F-FDG cardiac emission images. This method is based on a model that describes the measured attenuation image histogram as some unknown true underlying histogram, blurred by noise. METHODS: Emission data from an elliptical phantom (cardiac insert) and three humans were reconstructed using transmission data of varying duration with varying levels of smoothing. Biases and noise levels (cardiac sector analysis) were evaluated for the phantom (simulated replicates) and human emission images. RESULTS: The estimated attenuation histograms typically displayed three distinct peaks corresponding to air, lung and soft tissue without a priori assumptions of the underlying mu values. This method effectively sharpened the histogram peaks and performed well for the phantom and human data. For intermediate transmission noise levels, biases in the phantom sector values were <4%. The human sector results were more variable but consistent with the phantom results. Noise reduction (approximately 30%) was demonstrated across all smooth levels for the phantom data. CONCLUSION: This histogram sharpening method introduces only small bias in the cardiac sector values while achieving an increase in effective transmission scan time of 50-100%. Alternatively, histogram sharpening permits less transmission data smoothing without increased noise. JF - Journal of Nuclear Medicine AU - Price, J C AU - Bacharach, S L AU - Freedman, N AU - Carson, R E AD - PET Department, National Institutes of Health, Bethesda, Maryland, USA. PY - 1996 SP - 786 EP - 794 VL - 37 IS - 5 SN - 0161-5505, 0161-5505 KW - Coronary Disease KW - Heart KW - Models, Cardiovascular KW - Phantoms, Imaging KW - Artifacts KW - Fludeoxyglucose F 18 KW - Human KW - Fluorine Radioisotopes KW - Deoxyglucose KW - Tomography, Emission-Computed KW - Image Processing, Computer-Assisted KW - Algorithms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85276528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Nuclear+Medicine&rft.atitle=Noise+reduction+in+PET+attenuation+correction+by+maximum+likelihood+histogram+sharpening+of+attenuation+images.&rft.au=Price%2C+J+C%3BBacharach%2C+S+L%3BFreedman%2C+N%3BCarson%2C+R+E&rft.aulast=Price&rft.aufirst=J&rft.date=1996-05-01&rft.volume=37&rft.issue=5&rft.spage=786&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Ethics education in neurology residency programs: results of a survey. AN - 85244958; pmid-8628507 JF - Neurology AU - Wichman, A AU - Foa, R AD - Office of Human Subjects Research, National Institutes of Health, Bethesda, MD 20892-1154, USA. PY - 1996 SP - 1481 EP - 1483 VL - 46 IS - 5 SN - 0028-3878, 0028-3878 KW - United States KW - Questionnaires KW - Human KW - Ethics Committees, Clinical KW - Ethics Consultation KW - Accreditation KW - Neurology KW - Ethics, Medical KW - Internship and Residency KW - Education, Medical, Graduate UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85244958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Ethics+education+in+neurology+residency+programs%3A+results+of+a+survey.&rft.au=Wichman%2C+A%3BFoa%2C+R&rft.aulast=Wichman&rft.aufirst=A&rft.date=1996-05-01&rft.volume=46&rft.issue=5&rft.spage=1481&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Evolution of directional preferences in the supplementary eye field during acquisition of conditional oculomotor associations. AN - 85223601; pmid-8622136 AB - We assessed the preferred directions (PDs) of supplementary eye field (SEF) neurons during conditional visuomotor learning. Monkeys learned to select one of four saccadic eye movements in response to a foveal instruction stimulus (IS). ISs were either familiar or novel. Each familiar IS reliably evoked one saccade: 7 degrees left, right, up, or down form the central fixation point. Novel ISs initially triggered virtually random responses among those four possibilities, but the monkeys ultimately learned to select the instructed saccade. As reported previously, activity rates on novel IS trials significantly changed during learning. Some of these cells (learning-dependent) also have significant modulation on familiar IS trials, but others (learning-selective) lack such activity. Of the former, the familiar IS activity can be either directionally selective or omnidirectional. For most neurons, PDs were apparent during all phases of learning, but they were rarely constant. Only infrequently did a neuron's PD for novel ISs closely match that for familiar ISs throughout the learning process. In directional learning-dependent cells, the PD usually reoriented near the end of learning to resemble that for familiar IS trials. In omnidirectional cells, initially evident PDs dissipated with learning, even as the cell became more strongly modulated. Learning-selective cells typically began with significant PDs, but became unmodulated as learning progressed. Our findings show a pervasive lability in SEF PDs that may reflect a flexible and rapid remapping between inputs and responses within the premotor cortical network. JF - The Journal of Neuroscience AU - Chen, L L AU - Wise, S P AD - Laboratory of Neurophysiology, National Institute of Mental Health, Poolesville, Maryland, 20837, USA. PY - 1996 SP - 3067 EP - 3081 VL - 16 IS - 9 SN - 0270-6474, 0270-6474 KW - Frontal Lobe KW - Learning KW - Photic Stimulation KW - Neurons KW - Animal KW - Macaca mulatta KW - Oculomotor Muscles KW - Saccades KW - Behavior, Animal KW - Male KW - Conditioning (Psychology) KW - Ocular Physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85223601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Neuroscience&rft.atitle=Evolution+of+directional+preferences+in+the+supplementary+eye+field+during+acquisition+of+conditional+oculomotor+associations.&rft.au=Chen%2C+L+L%3BWise%2C+S+P&rft.aulast=Chen&rft.aufirst=L&rft.date=1996-05-01&rft.volume=16&rft.issue=9&rft.spage=3067&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - News from the National Institute on Deafness and other Communication Disorders. AN - 85199817; pmid-8817031 JF - The American Journal of Otology AU - Snow, J B AD - National Institute on Deafness and other Communication Disorders, Bethesda, Maryland 20892, USA. PY - 1996 SP - 493 EP - 495 VL - 17 IS - 3 SN - 0192-9763, 0192-9763 KW - Chromosomes, Human, Pair 17 KW - Deafness KW - Hair Cells KW - Human KW - Chromosomes, Human, Pair 9 KW - Research KW - Cochlear Implants KW - Tinnitus KW - Chromosomes, Human, Pair 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85199817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Otology&rft.atitle=News+from+the+National+Institute+on+Deafness+and+other+Communication+Disorders.&rft.au=Snow%2C+J+B&rft.aulast=Snow&rft.aufirst=J&rft.date=1996-05-01&rft.volume=17&rft.issue=3&rft.spage=493&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Otology&rft.issn=01929763&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Evolution of research otolaryngology--head and neck surgery over the past century. AN - 85193754; pmid-8628076 JF - The Laryngoscope AU - Snow, J B AD - National Institute on Deafness and other Communication Disorders, Bethesda, Maryland 20892, USA. PY - 1996 SP - 529 EP - 531 VL - 106 IS - 5 Pt 1 SN - 0023-852X, 0023-852X KW - Human KW - History of Medicine, 20th Cent. KW - Research KW - Otolaryngology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85193754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Laryngoscope&rft.atitle=Evolution+of+research+otolaryngology--head+and+neck+surgery+over+the+past+century.&rft.au=Snow%2C+J+B&rft.aulast=Snow&rft.aufirst=J&rft.date=1996-05-01&rft.volume=106&rft.issue=5+Pt+1&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Confocal Laser Scanning Microscopy of Oncogene Localization in Rainbow Trout Cell Lines Derived from Normal and Tumor Tissue* super(1) AN - 807258390; 13645721 AB - We examined the localization and expression of the nuclear oncoprotein c-myc and the cytoplasmic membrane-associated oncoprotein c-ras in rainbow trout cell lines derived from both normal and tumor tissue in order to question whether c-myc and ras oncoprotein immunostaining was increased in cells derived from tumors compared to cells derived from normal tissue. Cell lines examined were derived from normal rainbow trout gonadal cells (RTG-2), a rainbow trout hepatoma (RTH-149), and a rainbow trout mesothelioma (RTM). Protein products of c-ras and c-myc were visualized in these 3 cell lines by employing fluorescein-labeled anti-mouse pan-ras and c-myc antibodies. The RTG-2 cells were used in this study as normal, control cells, and they exhibited little pan-ras and c-myc staining. The RTH-149 cell line (a tumorigenic cell line) exhibited positive pan-ras staining in regions of the membrane and cell cytoplasm. Localization of c-myc staining to perinuclear regions was punctate in RTH-149 cells. RTM cells (also a tumorigenic cell line) displayed a ras staining localization similar to the pattern seen in RTH-149 cells. RTM cells exhibit a diffuse perinuclear staining and, thus, display a more ubiquitous localization of c-myc than RTH-149 cells. Northern blot analysis indicated that c-myc expression was highest in RTM cells, whereas RTG-2 cells and RTH-149 cells expressed similar lower levels of c-myc expression. We were unable to detect significant ras expression in any of the cell lines by Northern blot analysis. In summary, the cell line derived from normal tissue, the RTG-2 cells, displayed little ras and c-myc immunostaining, whereas the cell lines derived from tumorigenic tissue, RTH and RTM cells, displayed increased immunostaining for c-myc and ras proteins. JF - Toxicologic Pathology AU - Carter, Charleata A AU - Ellington, William W AU - Van Beneden, Rebecca J AD - Laboratory of Experimental Pathology, P.O. Box 12233, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 339 EP - 345 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 3 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality KW - Ras protein KW - Pathology KW - Oncorhynchus mykiss KW - Tumors KW - Staining KW - RAS KW - Hepatoma KW - Antibodies KW - Oncogenes KW - Cytoplasm KW - Confocal microscopy KW - Microscopy KW - mesothelioma KW - Lasers KW - Tumours KW - c-Myc protein KW - X 24390:Radioactive Materials KW - Q5 08503:Characteristics, behavior and fate KW - B 26610:Guanine nucleotide-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/807258390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Confocal+Laser+Scanning+Microscopy+of+Oncogene+Localization+in+Rainbow+Trout+Cell+Lines+Derived+from+Normal+and+Tumor+Tissue*+super%281%29&rft.au=Carter%2C+Charleata+A%3BEllington%2C+William+W%3BVan+Beneden%2C+Rebecca+J&rft.aulast=Carter&rft.aufirst=Charleata&rft.date=1996-05-01&rft.volume=24&rft.issue=3&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339602400310 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Number of references - 38 N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Antibodies; Pathology; Cytoplasm; Microscopy; Lasers; Staining; Tumours; RAS; Ras protein; Hepatoma; Oncogenes; Confocal microscopy; mesothelioma; Tumors; c-Myc protein; Oncorhynchus mykiss DO - http://dx.doi.org/10.1177/019262339602400310 ER - TY - JOUR T1 - Studies on the mechanism of action of 1-beta-D-arabinofuranosyl-5-azacytosine (fazarabine) in mammalian lymphoblasts. AN - 78749498; 9414404 AB - Fazarabine has shown activity in the panel of 60 cultured human tumor lines of the National Cancer Institute. COMPARE analyses relating correlation coefficients of other anticancer drugs with those of fazarabine suggest that this agent operates through a similar mode of action to that of cytarabine. Studies have been carried out both in culture and in vivo to examine the mechanism of action of fazarabine in P388 murine and Molt-4 human lymphoblasts. Authentic fazarabine nucleotide standards were prepared by chemical and enzymatic methods and characterized on HPLC by comparison to related pyrimidine nucleoside-5'-phosphates as well as by enzymatic digestion. Fazarabine inhibited the incorporation of labeled thymidine into DNA without influencing the synthesis of RNA or protein. Deoxycytidine overcomes this inhibition of DNA synthesis and also prevents the cytotoxicity of the drug to lymphoblasts, probably by competing for fazarabine uptake and metabolism. Fazarabine was rapidly phosphorylated in both cell lines; in P388 cells it was incorporated into DNA, where it continued to undergo the same type of ring opening and degradation as the free nucleoside. Alkaline elution studies demonstrated that exposure to the agent resulted in the formation of alkaline labile sites. Fazarabine also inhibited the methylation of deoxycytidine residues in DNA, but this effect was less pronounced than that produced by 5-azacytidine. Taken together, these studies suggest that fazarabine probably acts by arresting the synthesis and/or altering the structural integrity or functional competence of DNA. JF - Journal of experimental therapeutics & oncology AU - Barchi, J J AU - Cooney, D A AU - Ahluwalia, G S AU - Gharehbaghi, K AU - Covey, J M AU - Hochman, I AU - Paull, K D AU - Jayaram, H N AD - Laboratory of Medicinal Chemistry, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 191 EP - 203 VL - 1 IS - 3 SN - 1359-4117, 1359-4117 KW - Antimetabolites, Antineoplastic KW - 0 KW - DNA, Neoplasm KW - Deoxycytidine KW - 0W860991D6 KW - fazarabine KW - 5V71D8JOKK KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Tumor Cells, Cultured KW - Phosphorylation KW - Leukemia P388 -- drug therapy KW - Cell Survival -- drug effects KW - Humans KW - DNA, Neoplasm -- genetics KW - Mice KW - Deoxycytidine -- pharmacology KW - DNA, Neoplasm -- biosynthesis KW - Azacitidine -- therapeutic use KW - Azacitidine -- metabolism KW - Azacitidine -- analogs & derivatives KW - Lymphocytes -- metabolism KW - Azacitidine -- antagonists & inhibitors KW - Antimetabolites, Antineoplastic -- metabolism KW - Lymphocytes -- drug effects KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78749498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+therapeutics+%26+oncology&rft.atitle=Studies+on+the+mechanism+of+action+of+1-beta-D-arabinofuranosyl-5-azacytosine+%28fazarabine%29+in+mammalian+lymphoblasts.&rft.au=Barchi%2C+J+J%3BCooney%2C+D+A%3BAhluwalia%2C+G+S%3BGharehbaghi%2C+K%3BCovey%2C+J+M%3BHochman%2C+I%3BPaull%2C+K+D%3BJayaram%2C+H+N&rft.aulast=Barchi&rft.aufirst=J&rft.date=1996-05-01&rft.volume=1&rft.issue=3&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+therapeutics+%26+oncology&rft.issn=13594117&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-30 N1 - Date created - 1998-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potential clinical applications of interleukin-12. AN - 78739591; 9372079 AB - Interleukin-12 is a central modulatory cytokine with potent effects on the development and differentiation of the cellular immune response. Because of its biologic activities, interleukin-12 could either mediate or contribute to the control of a large range of critical world-wide pathologic conditions, including infectious diseases and cancer. Its potential efficacy has been demonstrated in several animal models of intracellular pathogens and tumors, as well as in vitro in some human pathologies. As an adjuvant, interleukin-12 appears to be useful for inducing a protective immune response in different animal models. However, its potential toxicity and complex regulation indicate that clinical trials must proceed with caution. Thus its prophylactic and therapeutic value may reside in our ability to minimize toxicity and simultaneously deliver this cytokine to immunologically relevant sites. JF - Current opinion in hematology AU - Chougnet, C AU - Shearer, G M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 216 EP - 222 VL - 3 IS - 3 SN - 1065-6251, 1065-6251 KW - Adjuvants, Immunologic KW - 0 KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Animals KW - Humans KW - Adjuvants, Immunologic -- pharmacology KW - Adjuvants, Immunologic -- therapeutic use KW - Immune System -- drug effects KW - Interleukin-12 -- pharmacology KW - Interleukin-12 -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78739591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+hematology&rft.atitle=Potential+clinical+applications+of+interleukin-12.&rft.au=Chougnet%2C+C%3BShearer%2C+G+M&rft.aulast=Chougnet&rft.aufirst=C&rft.date=1996-05-01&rft.volume=3&rft.issue=3&rft.spage=216&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+hematology&rft.issn=10656251&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-09 N1 - Date created - 1997-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asthma among the famous. James Anderson (1738-1809). AN - 78720970; 9091238 JF - Allergy and asthma proceedings AU - Cohen, S G AD - National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. PY - 1996 SP - 165 EP - 167 VL - 17 IS - 3 SN - 1088-5412, 1088-5412 KW - Index Medicus KW - History of medicine KW - Anderson KW - Humans KW - History, 18th Century KW - History, 19th Century KW - United Kingdom KW - Male KW - Plants, Toxic KW - Asthma -- drug therapy KW - Datura stramonium KW - Plants, Medicinal KW - Asthma -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78720970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Allergy+and+asthma+proceedings&rft.atitle=Asthma+among+the+famous.+James+Anderson+%281738-1809%29.&rft.au=Cohen%2C+S+G&rft.aulast=Cohen&rft.aufirst=S&rft.date=1996-05-01&rft.volume=17&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Allergy+and+asthma+proceedings&rft.issn=10885412&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-09 N1 - Date created - 1997-04-09 N1 - Date revised - 2017-01-13 N1 - People - Anderson N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Anderson ER - TY - CONF T1 - Workshop overview. National Toxicology Program Studies: principles of dose selection and applications to mechanistic based risk assessment. AN - 78605539; 8998945 AB - A workshop entitled "NTP Studies: Principles of Dose Selection and Applications to Mechanistic Based Risk Assessment" was held at the 34th Annual Meeting of the Society of Toxicology in Baltimore, Maryland. The purpose of the workshop was to provide an overview of factors currently considered important in the selection of doses for NTP studies, to describe some of the confounding factors that can result from the indiscriminate use of bioassay data in quantitative risk assessment, and to suggest ways in which information from mechanistic studies or studies of biomarkers of exposure or effect might be used to better advantage in risk assessment. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Bucher, J R AU - Portier, C J AU - Goodman, J I AU - Faustman, E M AU - Lucier, G W Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1 EP - 8 VL - 31 IS - 1 KW - Biomarkers KW - 0 KW - Index Medicus KW - Toxicology -- standards KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78605539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Workshop+overview.+National+Toxicology+Program+Studies%3A+principles+of+dose+selection+and+applications+to+mechanistic+based+risk+assessment.&rft.au=Bucher%2C+J+R%3BPortier%2C+C+J%3BGoodman%2C+J+I%3BFaustman%2C+E+M%3BLucier%2C+G+W&rft.aulast=Bucher&rft.aufirst=J&rft.date=1996-05-01&rft.volume=31&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-17 N1 - Date created - 1997-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stochastic simulation of a multistage model of carcinogenesis. AN - 78557563; 8935954 AB - Stochastic mathematical models of carcinogenesis have been used to quantify cancer risks for about 40 years. As more detailed data of the cancer process are obtained, mathematical models try to incorporate this information and as a result become more complex and sometimes analytically and numerically intractable. Simulation studies have become an important tool for examining the operating characteristics of the models of interest. The many quantities one can examine using this tool include bias in parameter estimates, adequacy of approximation methods, and the appropriateness of large sample generalizations to small studies. This manuscript describes a general method of stochastic simulation that may be carried out for arbitrarily complicated stochastic models of carcinogenesis. JF - Mathematical biosciences AU - Sherman, C D AU - Portier, C J AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 35 EP - 50 VL - 134 IS - 1 SN - 0025-5564, 0025-5564 KW - Index Medicus KW - Computer Simulation KW - Kinetics KW - Humans KW - Cell Transformation, Neoplastic KW - Mathematics KW - Cell Division KW - Cocarcinogenesis KW - Stochastic Processes KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78557563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mathematical+biosciences&rft.atitle=Stochastic+simulation+of+a+multistage+model+of+carcinogenesis.&rft.au=Sherman%2C+C+D%3BPortier%2C+C+J&rft.aulast=Sherman&rft.aufirst=C&rft.date=1996-05-01&rft.volume=134&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Mathematical+biosciences&rft.issn=00255564&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-02 N1 - Date created - 1997-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxicology: clinical consequences. AN - 78413997; 8843569 JF - Toxicology and industrial health AU - Luster, M I AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. PY - 1996 SP - 533 EP - 535 VL - 12 IS - 3-4 SN - 0748-2337, 0748-2337 KW - Immunosuppressive Agents KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Occupational Exposure KW - Humans KW - Drug-Related Side Effects and Adverse Reactions KW - Environmental Exposure KW - CD4-CD8 Ratio -- drug effects KW - Autoimmune Diseases -- chemically induced KW - Immune System -- drug effects KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78413997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+industrial+health&rft.atitle=Immunotoxicology%3A+clinical+consequences.&rft.au=Luster%2C+M+I&rft.aulast=Luster&rft.aufirst=M&rft.date=1996-05-01&rft.volume=12&rft.issue=3-4&rft.spage=533&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+industrial+health&rft.issn=07482337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-20 N1 - Date created - 1996-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of mianserin on symptoms of delirium in the aged: an open trial study. AN - 78413272; 8843489 AB - 1. The authors administered the tetracyclic antidepressant mianserin to aged patients with delirium to examine its efficacy in delirium. 2. The subjects were 62 consecutive aged patients with delirium, diagnosed according to DSM-IV. 3. The patients' symptoms of delirium were assessed once a week over the 4-week study period using the Delirium Rating Scale. 4. It was found that mianserin was effective, especially in treating behavioral and sleep-wake disturbance and that it was almost free from undesirable side-effects. It appears to be particularly useful for elderly patients with delirium, who easily develop extrapyramidal side-effects when given antipsychotic drugs. These properties of mianserin are worthy of further study. JF - Progress in neuro-psychopharmacology & biological psychiatry AU - Uchiyama, M AU - Tanaka, K AU - Isse, K AU - Toru, M AD - Department of Psychophysiology, National Institute of Mental Health, NCNP, Ichikawa, Japan. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 651 EP - 656 VL - 20 IS - 4 SN - 0278-5846, 0278-5846 KW - Antidepressive Agents, Second-Generation KW - 0 KW - Mianserin KW - 250PJI13LM KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Aged, 80 and over KW - Humans KW - Aged KW - Male KW - Female KW - Mianserin -- therapeutic use KW - Mianserin -- adverse effects KW - Antidepressive Agents, Second-Generation -- adverse effects KW - Antidepressive Agents, Second-Generation -- therapeutic use KW - Delirium -- psychology KW - Antidepressive Agents, Second-Generation -- administration & dosage KW - Mianserin -- administration & dosage KW - Delirium -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78413272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.atitle=Efficacy+of+mianserin+on+symptoms+of+delirium+in+the+aged%3A+an+open+trial+study.&rft.au=Uchiyama%2C+M%3BTanaka%2C+K%3BIsse%2C+K%3BToru%2C+M&rft.aulast=Uchiyama&rft.aufirst=M&rft.date=1996-05-01&rft.volume=20&rft.issue=4&rft.spage=651&rft.isbn=&rft.btitle=&rft.title=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.issn=02785846&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-03 N1 - Date created - 1997-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Liver tumorigenesis by Helicobacter hepaticus: considerations of mechanism. AN - 78319108; 8797029 AB - A new animal model for the causation of liver tumors via a bacterial infection presented itself fortuitously in the form of a new species, Helicobacter hepaticus. This species of Helicobacter colonizes the hepatic bile canaliculi in susceptible strains of mice, resulting in hepatitis and hepatocellular and hepatocholangiolar adenomas and carcinomas. The mechanism by which this infection leads to cancer is unknown. Tests with Helicobacter hepaticus have revealed thus far that the bacteria do not secrete a mutagen which is capable of detection by the Ames Assay. Measurement of oxidatively damaged bases in the liver DNA of hepaticus infected mice have shown accumulation of 8-oxodeoxyguanosine with disease progression. Other promutagenic DNA lesions, 7-methylguanine and O6-methylguanine, indicative of nitrosation of endogenous amines by nitric oxide, were not detected. Analysis of carcinomas and adenomas taken from H. hepaticus infected A/JCr mice revealed no mutations in ras oncogenes or in exons 5-8 of the p53 gene. These preliminary results indicate that a non-genotoxic tumor promotion mechanism, possibly implemented by reactive oxygen species from the immune response, is more likely than a genotoxic mechanism. JF - In vivo (Athens, Greece) AU - Canella, K A AU - Diwan, B A AU - Gorelick, P L AU - Donovan, P J AU - Sipowicz, M A AU - Kasprzak, K S AU - Weghorst, C M AU - Snyderwine, E G AU - Davis, C D AU - Keefer, L K AU - Kyrtopoulos, S A AU - Hecht, S S AU - Wang, M AU - Anderson, L M AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. PY - 1996 SP - 285 EP - 292 VL - 10 IS - 3 SN - 0258-851X, 0258-851X KW - Carcinogens KW - 0 KW - DNA Adducts KW - Index Medicus KW - Animals KW - DNA Damage KW - Oxidative Stress KW - Carcinogens -- toxicity KW - Mice KW - Mutation KW - Alkylation KW - Liver Neoplasms -- microbiology KW - Helicobacter Infections -- complications KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78319108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Liver+tumorigenesis+by+Helicobacter+hepaticus%3A+considerations+of+mechanism.&rft.au=Canella%2C+K+A%3BDiwan%2C+B+A%3BGorelick%2C+P+L%3BDonovan%2C+P+J%3BSipowicz%2C+M+A%3BKasprzak%2C+K+S%3BWeghorst%2C+C+M%3BSnyderwine%2C+E+G%3BDavis%2C+C+D%3BKeefer%2C+L+K%3BKyrtopoulos%2C+S+A%3BHecht%2C+S+S%3BWang%2C+M%3BAnderson%2C+L+M%3BRice%2C+J+M&rft.aulast=Canella&rft.aufirst=K&rft.date=1996-05-01&rft.volume=10&rft.issue=3&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indicators of genetic and environmental influences in drug abusing individuals. AN - 78314807; 8793306 AB - To assess relative contribution of genetic and environmental influences in individual cases of drug abuse/dependence, separate scales were constructed from DIS (version III) drug symptom items. Using data from 38 MZ and 35 DZ male twin pairs, items with significant MZ/DZ differences in probandwise concordance were assigned to a genetic scale whereas items without significant MZ/DZ differences were assigned to an environmental scale. As expected, significant differences were found between MZ and DZ twins in intraclass correlations for the genetic but not environmental scale. Genetic scores on drug and alcohol scales were correlated (r = 0.40), whereas environmental scales were not. When scores on the genetic scales were compared, the correlation between drug and alcohol scores within individuals was similar to that across MZ twins, both of which were higher than the correlation across DZ twins. These results suggest (1) relative contribution of genetic and environmental influences in individual cases of drug dependence can be assessed, and (2) common genetic mechanisms may be involved in alcohol and drug dependence. JF - Drug and alcohol dependence AU - Johnson, E O AU - van den Bree, M B AU - Uhl, G R AU - Pickens, R W AD - Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 17 EP - 23 VL - 41 IS - 1 SN - 0376-8716, 0376-8716 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Twins, Dizygotic -- genetics KW - Risk Factors KW - Humans KW - Adult KW - Twins, Dizygotic -- psychology KW - Middle Aged KW - Personality Development KW - Twins, Monozygotic -- genetics KW - Personality Assessment KW - Adolescent KW - Male KW - Twins, Monozygotic -- psychology KW - Alcoholism -- rehabilitation KW - Diseases in Twins -- psychology KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- psychology KW - Alcoholism -- genetics KW - Diseases in Twins -- genetics KW - Alcoholism -- psychology KW - Substance-Related Disorders -- genetics KW - Social Environment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78314807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Indicators+of+genetic+and+environmental+influences+in+drug+abusing+individuals.&rft.au=Johnson%2C+E+O%3Bvan+den+Bree%2C+M+B%3BUhl%2C+G+R%3BPickens%2C+R+W&rft.aulast=Johnson&rft.aufirst=E&rft.date=1996-05-01&rft.volume=41&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitrosamines, alcohol, and gastrointestinal tract cancer: recent epidemiology and experimentation. AN - 78314722; 8797028 AB - Recent epidemiological and experimental data continues to implicate nitrosamines in causation of gastrointestinal cancers. The evidence is strong for pharynx, esophagus, and stomach, and more problematic for liver, pancreas, and colorectum. Substantial levels of the promutagenic DNA adduct, Ob-methylguanine, in DNA from these organs in patas monkeys after a low dose of N-nitrosodimethylamine confirms the capacity for activation of environmental nitrosamines in these primate tissues. Alcohol is both an independent and a tobacco-interactive risk factor, influencing cancer incidence for oropharynx and esophagus strongly, and for stomach, colorectum, and liver more moderately. In a tabulation of experimental effects of ethanol potentially related to cancer-enhancing effects, toxicokinetic inhibition of hepatic first-pass clearance of nitrosamines is quantitatively greatest, and may be a major part of the mechanism of alcohol's effect on cancer risk for oropharnx, esophagus, and colon. Other operative mechanisms supported by experimental data are induction of activating enzymes, inhibition of DNA repair, and tumor promotion. JF - In vivo (Athens, Greece) AU - Chhabra, S K AU - Souliotis, V L AU - Kyrtopoulos, S A AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. PY - 1996 SP - 265 EP - 284 VL - 10 IS - 3 SN - 0258-851X, 0258-851X KW - Carcinogens KW - 0 KW - Nitrosamines KW - Index Medicus KW - Mouth Neoplasms -- chemically induced KW - Animals KW - Drug Interactions KW - Nasopharyngeal Neoplasms -- chemically induced KW - Risk Factors KW - Humans KW - Gastrointestinal Neoplasms -- chemically induced KW - Gastrointestinal Neoplasms -- epidemiology KW - Nitrosamines -- adverse effects KW - Alcohol Drinking -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78314722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Nitrosamines%2C+alcohol%2C+and+gastrointestinal+tract+cancer%3A+recent+epidemiology+and+experimentation.&rft.au=Chhabra%2C+S+K%3BSouliotis%2C+V+L%3BKyrtopoulos%2C+S+A%3BAnderson%2C+L+M&rft.aulast=Chhabra&rft.aufirst=S&rft.date=1996-05-01&rft.volume=10&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of antioxidants in the nitric oxide-elicited inhibition of dopamine uptake in cultured mesencephalic neurons. Insights into potential mechanisms of nitric oxide-mediated neurotoxicity. AN - 78304382; 8792343 AB - Under aerobic conditions the addition of (C2N5)2N(N[O]NO)-.Na+(DEA/NO), S-nitroso-N-acetyl penicillamine and nitric oxide (NO)-saturated buffer, but not S-nitroso-L-glutathione, to dopamine solutions resulted in dopamine o-semiquinone formation that was dependent on the formation of a NO/oxygen intermediate. High pressure liquid chromatography (HPLC) electrochemical analysis of dopamine demonstrated that the DEA/NO-induced oxidation of dopamine was abrogated in the presence of the antioxidants, ascorbate and glutathione. NO spontaneously released from DEA/NO decreased [3H]dopamine accumulation in primary cultures of mesencephalic neurons in a dose-dependent fashion. In contrast, [3H] gamma-aminobutyric acid uptake by mesencephalic neurons tested under the same conditions was unchanged. When DEA/NO was added to incubation buffer that contained [3H]dopamine and the antioxidant, ascorbate or glutathione, [3H]dopamine uptake was also inhibited. These data excluded that oxidation of extracellular [3H]dopamine by the intermediates of the NO/O2 reaction could have caused this decrease. Instead, NO may have acted directly on a not yet identified target operative in the regulation of dopamine storage and release. Analysis of the rate constants for the NO reaction with ascorbate, glutathione and dopamine revealed that dopamine quinone formation was delayed by the presence of antioxidants. Since the formation of NO as well as neurotransmitter release are activated during ischemia reperfusion injury, it is possible that prolonged NO exposure could deplete antioxidants and facilitate the oxidation of dopamine and thereby cause neurotoxicity. JF - Neurochemistry international AU - Cook, J A AU - Wink, D A AU - Blount, V AU - Krishna, M C AU - Hanbauer, I AD - Radiation Biology Branch, National Cancer Institute, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA. PY - 1996 SP - 609 EP - 617 VL - 28 IS - 5-6 SN - 0197-0186, 0197-0186 KW - Antioxidants KW - 0 KW - Neuroprotective Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Female KW - Mesencephalon -- metabolism KW - Antioxidants -- metabolism KW - Neurons -- metabolism KW - Neuroprotective Agents -- metabolism KW - Dopamine -- metabolism KW - Nitric Oxide -- physiology KW - Mesencephalon -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78304382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemistry+international&rft.atitle=Role+of+antioxidants+in+the+nitric+oxide-elicited+inhibition+of+dopamine+uptake+in+cultured+mesencephalic+neurons.+Insights+into+potential+mechanisms+of+nitric+oxide-mediated+neurotoxicity.&rft.au=Cook%2C+J+A%3BWink%2C+D+A%3BBlount%2C+V%3BKrishna%2C+M+C%3BHanbauer%2C+I&rft.aulast=Cook&rft.aufirst=J&rft.date=1996-05-01&rft.volume=28&rft.issue=5-6&rft.spage=609&rft.isbn=&rft.btitle=&rft.title=Neurochemistry+international&rft.issn=01970186&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-30 N1 - Date created - 1996-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology, and cancer risk assessment. AN - 78283624; 8781359 AB - Carcinogenesis is a multistage process involving the inappropriate activation of normal cellular genes to become oncogenes, e.g., ras, and the inactivation of other cellular genes called tumor suppressor genes. p53 is the prototypic tumor suppressor gene that is well suited as a molecular link between the causes of cancer, i.e., carcinogenic chemical and physical agents and certain viruses, and the development of clinical cancer. The p53 tumor suppressor gene is mutated in the majority of human cancers. Genetic analysis of human cancer is providing clues to the etiology of these diverse tumors and to the functions of the p53 gene. Some of the mutations in the p53 gene reflect endogenous causes of cancer, whereas others are characteristic of carcinogens found in our environment. In geographic areas where hepatitis B virus and a dietary chemical carcinogen, aflatoxin B1, are risk factors of liver cancer, a molecular signature of the chemical carcinogen is found in the mutated p53 gene. A different molecular signature in the p53 gene is found in skin cancer caused by sunlight. Because mutations in the p53 gene can occur in precancerous lesions in the lung, breast, esophagus, and colon, molecular analysis of the p53 gene in exfoliated cells found in either body fluids or tissue biopsies may identify individuals at increased cancer risk. p53 mutations in tumors generally indicate a poorer prognosis. In summary, the recent history of p53 investigations is a paradigm in cancer research, illustrating both the convergence of previously parallel lines of basic, clinical, and epidemiologic investigation and the rapid translation of research findings from the laboratory to the clinic. JF - Environmental health perspectives AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. harris@dc37a.nci.nih.gov Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 435 EP - 439 VL - 104 Suppl 3 SN - 0091-6765, 0091-6765 KW - DNA Adducts KW - 0 KW - Index Medicus KW - Animals KW - DNA Repair KW - Humans KW - Genetic Predisposition to Disease KW - Mutation KW - Risk Assessment KW - Genes, p53 -- genetics KW - Neoplasms -- epidemiology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78283624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=p53+tumor+suppressor+gene%3A+at+the+crossroads+of+molecular+carcinogenesis%2C+molecular+epidemiology%2C+and+cancer+risk+assessment.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1996-05-01&rft.volume=104+Suppl+3&rft.issue=&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3 [5279523] Science. 1991 Nov 22;254(5035):1138-46 [1659741] Science. 1990 Sep 14;249(4974):1288-90 [1697983] Nature. 1992 Mar 19;356(6366):215-21 [1552940] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030-4 [1557408] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5413-7 [1608950] Cell. 1992 Aug 21;70(4):523-6 [1505019] Cell. 1992 Sep 18;70(6):923-35 [1356076] Cell. 1992 Sep 18;70(6):937-48 [1525830] Prog Clin Biol Res. 1992;376:1-30 [1528915] Cell. 1992 Nov 13;71(4):543-6 [1423612] Cell. 1992 Nov 13;71(4):587-97 [1423616] Cell. 1992 Dec 24;71(7):1073-80 [1473145] Science. 1993 Apr 2;260(5104):37-8 [8465198] Science. 1993 Apr 2;260(5104):53-8 [8465200] Science. 1993 Apr 2;260(5104):58-63 [8465201] Nature. 1993 Apr 29;362(6423):847-9 [8479522] Nature. 1993 Apr 29;362(6423):849-52 [8479523] Nat Genet. 1993 May;4(1):42-6 [8099841] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8586-90 [8397412] N Engl J Med. 1993 Oct 28;329(18):1318-27 [8413413] Cancer Res. 1993 Nov 15;53(22):5377-81 [8221675] Lancet. 1993 Dec 18-25;342(8886-8887):1520-1 [7902903] Science. 1994 Mar 11;263(5152):1436-8 [8128225] Cancer Res. 1994 Apr 15;54(8):2064-8 [8174105] Science. 1994 Jul 15;265(5170):346-55 [8023157] Cancer Res. 1994 Sep 15;54(18):4855-78 [8069852] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9700-4 [7937876] Science. 1995 Jun 23;268(5218):1749-53 [7792600] Nat Genet. 1995 Jun;10(2):188-95 [7663514] Science. 1990 Nov 30;250(4985):1233-8 [1978757] Cell. 1991 Jan 25;64(2):235-48 [1988146] Nature. 1991 Apr 4;350(6317):427-8 [1849234] Nature. 1991 Apr 4;350(6317):429-31 [1672732] Nature. 1991 Jun 6;351(6326):453-6 [2046748] Science. 1991 Jul 5;253(5015):49-53 [1905840] Cancer Res. 1991 Sep 15;51(18 Suppl):5023s-5044s [1884379] Carcinogenesis. 1991 Nov;12(11):1983-92 [1934282] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124-8 [1946433] Science. 1991 Nov 15;254(5034):1001-3 [1948068] Mol Cell Biol. 1989 Sep;9(9):3982-91 [2476668] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of protein kinase C alpha in nerve growth factor-induced arachidonic acid release from PC12 cells. AN - 78282257; 8780012 AB - Nerve growth factor (NGF) increases arachidonic acid (AA) release by PC12 pheochromocytoma cells. To explore the role of protein kinase C (PKC) in this action of NGF, PKC was down-regulated by long-term treatment of the cells with phorbol 12-myristate 13-acetate (PMA). Such prolonged exposure to PMA (1 microM) resulted in the inhibition of NGF-induced AA release. Moreover, pretreatment of PC12 cells with the protein kinase inhibitor staurosporine or with calphostin C, a specific inhibitor of PKC, also blocks the increase of AA release induced by NGF. These data, as well as that PMA alone can induce AA release in PC12 cells, suggest that PKC is necessary for NGF-induced AA release. Immunoblot analysis of whole cell lysates by using antibodies against various PKC isoforms revealed that our PC12 cells contained PKCs alpha, delta, epsilon, and zeta. PMA down-regulation depleted PKCs alpha, delta, and epsilon, and partially depleted zeta. To see which isoform was involved in NGF-induced AA release, an isoform-specific PKC inhibitor was used. GO 6976, a compound that inhibits PKCs alpha and beta specifically, blocked NGF-induced AA release. In addition, thymeleatoxin, a specific activator of PKCs alpha, beta, and gamma, induced AA release from PC12 cells in amounts comparable with those seen with NGF. Taken together, these data suggest that PKC alpha plays a role in NGF-induced AA release. JF - Journal of neurochemistry AU - Zheng, W H AU - Fink, D W AU - Guroff, G AD - Section on Growth Factors, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1868 EP - 1875 VL - 66 IS - 5 SN - 0022-3042, 0022-3042 KW - Isoenzymes KW - 0 KW - Nerve Growth Factors KW - Arachidonic Acid KW - 27YG812J1I KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Animals KW - Enzyme Activation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Kinase C -- antagonists & inhibitors KW - PC12 Cells -- metabolism KW - Isoenzymes -- physiology KW - Nerve Growth Factors -- pharmacology KW - PC12 Cells -- drug effects KW - Protein Kinase C -- physiology KW - Arachidonic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78282257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Role+of+protein+kinase+C+alpha+in+nerve+growth+factor-induced+arachidonic+acid+release+from+PC12+cells.&rft.au=Zheng%2C+W+H%3BFink%2C+D+W%3BGuroff%2C+G&rft.aulast=Zheng&rft.aufirst=W&rft.date=1996-05-01&rft.volume=66&rft.issue=5&rft.spage=1868&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-14 N1 - Date created - 1997-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Confocal laser scanning microscopy of oncogene localization in rainbow trout cell lines derived from normal and tumor tissue. AN - 78234361; 8736390 AB - We examined the localization and expression of the nuclear oncoprotein c-myc and the cytoplasmic membrane-associated oncoprotein c-ras in rainbow trout cell lines derived from both normal and tumor tissue in order to question whether c-myc and ras oncoprotein immunostaining was increased in cells derived from tumors compared to cells derived from normal tissue. Cell lines examined were derived from normal rainbow trout gonadal cells (RTG-2), a rainbow trout hepatoma (RTH-149), and a rainbow trout mesothelioma (RTM). Protein products of c-ras and c-myc were visualized in these 3 cell lines by employing fluorescein-labeled anti-mouse pan-ras and c-myc antibodies. The RTG-2 cells were used in this study as normal, control cells, and they exhibited little pan-ras and c-myc staining. The RTH-149 cell line (a tumorigenic cell line) exhibited positive pan-ras staining in regions of the membrane and cell cytoplasm. Localization of c-myc staining to perinuclear regions was punctate in RTH-149 cells. RTM cells (also a tumorigenic cell line) displayed a ras staining localization similar to the pattern seen in RTH-149 cells. RTM cells exhibit a diffuse perinuclear staining and, thus, display a more ubiquitous localization of c-myc than RTH-149 cells. Northern blot analysis indicated that c-myc expression was highest in RTM cells, whereas RTG-2 cells and RTH-149 cells expressed similar lower levels of c-myc expression. We were unable to detect significant ras expression in any of the cell lines by Northern blot analysis. In summary, the cell line derived from normal tissue, the RTG-2 cells, displayed little ras and c-myc immunostaining, whereas the cell lines derived from tumorigenic tissue, RTH and RTM cells, displayed increased immunostaining for c-myc and ras proteins. JF - Toxicologic pathology AU - Carter, C A AU - Ellington, W W AU - Van Beneden, R J AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1996 SP - 339 EP - 345 VL - 24 IS - 3 SN - 0192-6233, 0192-6233 KW - Phosphorus Radioisotopes KW - 0 KW - Proto-Oncogene Proteins c-myc KW - RNA, Messenger KW - RNA, Neoplasm KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Proto-Oncogene Proteins c-myc -- biosynthesis KW - Microscopy, Confocal KW - Animals KW - Blotting, Northern KW - Tumor Cells, Cultured KW - Gonads -- cytology KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Immunohistochemistry KW - RNA, Messenger -- biosynthesis KW - Cell Line KW - Liver Neoplasms, Experimental -- metabolism KW - Oncorhynchus mykiss -- genetics KW - Liver Neoplasms, Experimental -- chemically induced KW - Neoplasms -- veterinary KW - Fish Diseases -- metabolism KW - Neoplasms -- pathology KW - Fish Diseases -- pathology KW - Genes, ras -- genetics KW - Liver Neoplasms, Experimental -- pathology KW - Mesothelioma -- metabolism KW - Mesothelioma -- veterinary KW - Mesothelioma -- pathology KW - Oncorhynchus mykiss -- metabolism KW - Genes, myc -- genetics KW - Fish Diseases -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78234361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Confocal+laser+scanning+microscopy+of+oncogene+localization+in+rainbow+trout+cell+lines+derived+from+normal+and+tumor+tissue.&rft.au=Carter%2C+C+A%3BEllington%2C+W+W%3BVan+Beneden%2C+R+J&rft.aulast=Carter&rft.aufirst=C&rft.date=1996-05-01&rft.volume=24&rft.issue=3&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Idazoxan and response to typical neuroleptics in treatment-resistant schizophrenia. Comparison with the atypical neuroleptic, clozapine. AN - 78215462; 8733795 AB - We investigated whether antagonism of alpha 2 adrenergic receptors would augment treatment response in schizophrenia, by administering idazoxan, an alpha 2 antagonist drug, to treatment-resistant patients on typical neuroleptics. Seventeen hospitalised treatment-resistant patients with DSM-III-R schizophrenia or schizoaffective disorder were studied on typical neuroleptic treatment, on treatment with idazoxan plus typical neuroleptic, and after discontinuation of idazoxan, in fixed, non-random order, and under double-blind, placebo-controlled conditions. The addition of idazoxan to fluphenazine treatment resulted in significant reductions of global psychosis and total, positive and negative symptoms on the Brief Psychiatric Rating Scale, compared to neuroleptic treatment alone. Symptom improvement significantly correlated with idazoxan-induced changes in indices of noradrenergic function. In a subgroup of patients, idazoxan plus typical neuroleptic treatment compared favourably with clozapine treatment, when both were compared to typical neuroleptic treatment alone. The antagonism of alpha 2 receptors augmented therapeutic response to typical neuroleptic treatment in treatment-resistant patients with schizophrenia. This antagonism may contribute to clozapine's superior antipsychotic effects. JF - The British journal of psychiatry : the journal of mental science AU - Litman, R E AU - Su, T P AU - Potter, W Z AU - Hong, W W AU - Pickar, D AD - National Institute of Mental Health, Experimental Therapeutics Branch, Bethesda MD 20892-1380, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 571 EP - 579 VL - 168 IS - 5 SN - 0007-1250, 0007-1250 KW - Adrenergic alpha-Antagonists KW - 0 KW - Antipsychotic Agents KW - Dioxanes KW - Imidazoles KW - Clozapine KW - J60AR2IKIC KW - Fluphenazine KW - S79426A41Z KW - Idazoxan KW - Y310PA316B KW - Index Medicus KW - Drug Therapy, Combination KW - Psychiatric Status Rating Scales KW - Fluphenazine -- adverse effects KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Fluphenazine -- administration & dosage KW - Male KW - Female KW - Antipsychotic Agents -- administration & dosage KW - Clozapine -- administration & dosage KW - Dioxanes -- administration & dosage KW - Imidazoles -- administration & dosage KW - Schizophrenia -- diagnosis KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Adrenergic alpha-Antagonists -- administration & dosage KW - Clozapine -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Imidazoles -- adverse effects KW - Dioxanes -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78215462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.atitle=Idazoxan+and+response+to+typical+neuroleptics+in+treatment-resistant+schizophrenia.+Comparison+with+the+atypical+neuroleptic%2C+clozapine.&rft.au=Litman%2C+R+E%3BSu%2C+T+P%3BPotter%2C+W+Z%3BHong%2C+W+W%3BPickar%2C+D&rft.aulast=Litman&rft.aufirst=R&rft.date=1996-05-01&rft.volume=168&rft.issue=5&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+psychiatry+%3A+the+journal+of+mental+science&rft.issn=00071250&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-17 N1 - Date created - 1996-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific depletion of alloreactivity against haplotype mismatched related individuals by a recombinant immunotoxin: a new approach to graft-versus-host disease prophylaxis in haploidentical bone marrow transplantation. AN - 78198556; 8733700 AB - Haploidentical bone marrow transplantation (BMT) is associated with a high risk of severe graft-versus-host disease (GVHD). While pan-T cell depletion of the graft is the most effective means of preventing severe GVHD, it is associated with delayed recovery of T cell function leading to fatal infections. We used two related Pseudomonas exotoxin-based immunotoxins, anti-Tac(Fv)-PE38 and anti-Tac(Fv)-PE38KDEL, that both target the IL-2 receptor on activated T cells, to specifically deplete alloreactive lymphocytes against haploidentical stimulators. The functional capacity of the remaining lymphocytes was tested in proliferative assays against the original haploidentical stimulator and pooled cells from other mismatched donors (third party). We varied the recombinant toxin concentration and schedule to determine the optimum conditions for selective depletion. In 10 experiments, the mean residual reactivity after depletion was 7.6 +/- 1.4% against the haploidentical stimulator and 64.2 +/- 5% against the third party, expressed as a percentage of the undepleted response to the same stimulators. Depletion was shown to be specific for mixed lymphocyte culture (MLC)-activated lymphocytes. The immunotoxin did not affect CFU-GM growth of normal BM cells. This selective depletion of haploidentical alloreactivity could be used to prevent GVHD while conserving immune recovery following haploidentical BMT. JF - Bone marrow transplantation AU - Mavroudis, D A AU - Jiang, Y Z AU - Hensel, N AU - Lewalle, P AU - Couriel, D AU - Kreitman, R J AU - Pastan, I AU - Barrett, A J AD - Bone Marrow Transplantation Unit, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 793 EP - 799 VL - 17 IS - 5 SN - 0268-3369, 0268-3369 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Lymphocyte Activation KW - Exotoxins -- pharmacology KW - Recombinant Proteins -- pharmacology KW - Haplotypes KW - Humans KW - Lymphocyte Culture Test, Mixed KW - In Vitro Techniques KW - Bacterial Toxins -- pharmacology KW - Colony-Forming Units Assay KW - T-Lymphocytes -- immunology KW - Receptors, Interleukin-2 -- immunology KW - Bone Marrow Transplantation -- methods KW - Bone Marrow Transplantation -- immunology KW - Bone Marrow Transplantation -- adverse effects KW - Lymphocyte Depletion -- methods KW - Immunotoxins -- pharmacology KW - Graft vs Host Disease -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78198556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bone+marrow+transplantation&rft.atitle=Specific+depletion+of+alloreactivity+against+haplotype+mismatched+related+individuals+by+a+recombinant+immunotoxin%3A+a+new+approach+to+graft-versus-host+disease+prophylaxis+in+haploidentical+bone+marrow+transplantation.&rft.au=Mavroudis%2C+D+A%3BJiang%2C+Y+Z%3BHensel%2C+N%3BLewalle%2C+P%3BCouriel%2C+D%3BKreitman%2C+R+J%3BPastan%2C+I%3BBarrett%2C+A+J&rft.aulast=Mavroudis&rft.aufirst=D&rft.date=1996-05-01&rft.volume=17&rft.issue=5&rft.spage=793&rft.isbn=&rft.btitle=&rft.title=Bone+marrow+transplantation&rft.issn=02683369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-06 N1 - Date created - 1996-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of genes amplified in human cancers by microdissection mediated cDNA capture. AN - 78193754; 8733125 AB - It has been increasingly recognized that homogeneously staining regions (hsr) in human cancers may be complex structures composed of large amplified DNA domains containing multiple genes. It is therefore important to devise strategies for the rapid isolation of cDNAs expressed from these structures. Using a procedure we term microdissection mediated cDNA capture, we recovered hsr specific cDNAs from two different human tumors. The glioblastoma cell line TX3868 and the human sarcoma cell line OsA-CL carry hsrs containing amplified sequences from chromosome 12q13-15. We recovered 17 hsr specific cDNAs following microdissection of these hsrs which had been previously hybridized in situ with linkered cDNA. Northern blot analysis with these cDNAs revealed hybridization to distinct transcripts in OsA-CL RNA and TX3868 RNA. None of the OsA-CL cDNA clones showed cross hybridization with the TX3868 cDNAs suggesting that despite their coincident band localization on 12q, the OsA-CL and TX3868 amplification units do not completely overlap. These results significantly increase the number of amplified genes assigned to the 12q13-15 amplicon illustrating both the complexity of hsrs derived from this region and the utility of microdissection mediated cDNA capture to gain rapid access to cDNAs transcribed from amplified genes. JF - Human molecular genetics AU - Gracia, E AU - Fischer, U AU - elKahloun, A AU - Trent, J M AU - Meese, E AU - Meltzer, P S AD - Laboratory of Cancer Genetics, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 595 EP - 600 VL - 5 IS - 5 SN - 0964-6906, 0964-6906 KW - DNA, Complementary KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Polymerase Chain Reaction KW - Glioblastoma -- genetics KW - Base Sequence KW - Blotting, Northern KW - Tumor Cells, Cultured KW - Blotting, Southern KW - Humans KW - Molecular Sequence Data KW - In Situ Hybridization, Fluorescence KW - Electrophoresis, Agar Gel KW - Osteosarcoma -- genetics KW - Nucleic Acid Hybridization KW - Mutagenesis, Insertional KW - DNA, Neoplasm -- analysis KW - Neoplasms -- genetics KW - DNA, Complementary -- analysis KW - Gene Amplification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78193754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Isolation+of+genes+amplified+in+human+cancers+by+microdissection+mediated+cDNA+capture.&rft.au=Gracia%2C+E%3BFischer%2C+U%3BelKahloun%2C+A%3BTrent%2C+J+M%3BMeese%2C+E%3BMeltzer%2C+P+S&rft.aulast=Gracia&rft.aufirst=E&rft.date=1996-05-01&rft.volume=5&rft.issue=5&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-04 N1 - Date created - 1997-06-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U46847; GENBANK; U47340; U46845; U46846; U47345; U47346; U47347; U47341; U47342; U47343; U47344 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective changes in laminin adhesion and alpha 6 beta 4 integrin regulation are associated with the initial steps in keratinocyte maturation. AN - 78190152; 8732671 AB - In skin, the distribution of integrins is compartmentalized. Whereas the alpha 6 beta 4 integrin complex is polarized to the basal portion of proliferating cells in the basal layer juxtaposed to the basement membrane, alpha 3 beta 1 integrin receptors are localized on the cell surface surrounding basal and suprabasal cells, suggesting beta 1 integrins mediate both cell-matrix and cell-cell interactions. As initiation of maturation in skin is associated with the detachment of cells from the basement membrane, the early loss of alpha 6 beta 4, but not alpha 3 beta 1, integrin expression could be a determining factor in the transition from the proliferating to a differentiating keratinocyte. We have studied the regulation of adhesion potential and integrin expression during differentiation of mouse basal keratinocytes culture in 0.05 mM Ca2+ medium and induced to differentiate in 0.12 mM Ca2+ medium. Within 12-24 h after elevation of Ca2+, a selective loss of the alpha 6 beta 4 integrin complex is associated with the induction of the spinous cell marker keratin 1. This early differentiation phenotype coincides with loss of cell attachment mediated by alpha 6 beta 4 to laminins 1 and 5 but not a fibronectin or collagen IV. Selective loss of attachment to laminin is also detected in spinous cells isolated from newborn epidermis in vivo. The loss of alpha 6 and beta 4 protein expression is a consequence of transcriptional and posttranscriptional events, including reduction in mRNA transcripts, reduced synthesis of the alpha 6 protein, and enhanced processing of the alpha 6 and beta 4 chains as determined by Western blots and pulse-chase experiments in metabolically labeled keratinocytes. Selective processing of the beta 4 intracellular domain is detected before loss of beta 4 from the cell surface in basal keratinocytes, and this process is accelerated during differentiation. Whereas early keratinocyte maturation is linked to the selective loss of the alpha 6 beta 4 complex, loss of both beta 1 and beta 4 integrin mRNA and protein occurs as cells proceed to later stages in the differentiation program as induced by 0.5 mM Ca2+ or suspension culture. These conditions are characterized by accelerated expression of transglutaminase; reduced keratin 1 protein; loss of adhesion to fibronectin, laminin 1, laminin 5, and collagen IV; and rapid cell death. Contributing to the down-regulation of beta 1 integrins during terminal differentiation is a selective sensitivity of alpha 3 beta 1 but not alpha 6 beta 4 to down-regulation by transforming growth factors beta 1 and beta 2, factors that are also expressed differentially in normal skin. This study indicates that down-regulation of the alpha 6 beta 4 but not beta 1 integrins occurs during the initial steps of keratinocyte differentiation and is associated with detachment from the laminin matrix. Such changes could contribute an important signal to initiate the process of terminal keratinocyte differentiation. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Tennenbaum, T AU - Li, L AU - Belanger, A J AU - De Luca, L M AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 615 EP - 628 VL - 7 IS - 5 SN - 1044-9523, 1044-9523 KW - Antigens, Neoplasm KW - 0 KW - Antigens, Surface KW - Culture Media KW - Integrin alpha3beta1 KW - Integrin alpha6beta4 KW - Integrins KW - Laminin KW - RNA, Messenger KW - Receptors, Laminin KW - Keratins KW - 68238-35-7 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Space life sciences KW - Keratins -- metabolism KW - Animals KW - Immunoblotting KW - Extracellular Matrix -- physiology KW - Cell Adhesion -- physiology KW - Mice KW - Calcium -- pharmacology KW - Mice, Inbred BALB C KW - Blotting, Western KW - Down-Regulation -- physiology KW - RNA, Messenger -- metabolism KW - Cell Differentiation -- physiology KW - Kinetics KW - Receptors, Laminin -- metabolism KW - Antigens, Neoplasm -- metabolism KW - Antigens, Neoplasm -- genetics KW - Receptors, Laminin -- genetics KW - Cell Differentiation -- drug effects KW - Laminin -- metabolism KW - Keratinocytes -- chemistry KW - Keratinocytes -- cytology KW - Keratinocytes -- metabolism KW - Antigens, Surface -- metabolism KW - Integrins -- metabolism KW - Integrins -- genetics KW - Antigens, Surface -- biosynthesis KW - Antigens, Surface -- genetics KW - Integrins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78190152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Selective+changes+in+laminin+adhesion+and+alpha+6+beta+4+integrin+regulation+are+associated+with+the+initial+steps+in+keratinocyte+maturation.&rft.au=Tennenbaum%2C+T%3BLi%2C+L%3BBelanger%2C+A+J%3BDe+Luca%2C+L+M%3BYuspa%2C+S+H&rft.aulast=Tennenbaum&rft.aufirst=T&rft.date=1996-05-01&rft.volume=7&rft.issue=5&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-31 N1 - Date created - 1996-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A negative tyrosine aminotransferase gene element that blocks glucocorticoid modulatory element-regulated modulation of glucocorticoid-induced gene expression. AN - 78187503; 8732678 AB - Tyrosine aminotransferase (TAT) is the prototypic steroid-inducible gene. Recently, we have found that the modulation of TAT induction properties is reproduced by a novel cis-acting TAT gene element, the glucocorticoid modulatory element (GME). This GME lies about 1 kb upstream of the glucocorticoid response elements (GREs) of the TAT gene and binds a heterooligomer of two recently defined proteins. We now report the existence of an additional TAT gene element between the GME and the GREs that blocks the action of the GME and thus prevents the left shift in the glucocorticoid dose-response curve caused by the GME. This negative element has the properties of a silencer because its activity is relatively position- and orientation-independent. The interaction appears to be stoichiometric in that the effects of a single negative element can be overcome by a second GME. This negative element also has an intrinsic inhibitory activity in the absence of the GME. The majority of the negative element activity could be elicited by a 56-bp sequence between -3105 and -3050 bp of the TAT gene. Multiple, clustered mutations of this sequence reduced, but did not eliminate, the negative activity. Further efforts to restrict the negative element were unsuccessful, suggesting that multiple sequences are required for full activity. High affinity, sequence-specific binding of a trans-acting factor(s) was observed in gel shift assays. This binding was half-maximally competed by a 4.4-fold excess of nonradioactive probe and was very stable once formed (delta H [symbol: see text] dissoc. = 32 kcal/mol), suggesting that low concentrations of a high affinity binding protein(s) exist in nuclear extracts. Further support for this conclusion came from the observation that cotransfection of a plasmid containing multiple copies of the 56-bp negative element was able to relieve the negation of GME activity in a GME-56-bp-GRE reporter construct. These data directly support the role of a trans-acting factor(s) in binding to the 56-bp negative element and blocking GME activity. Collectively, these data suggest that glucocorticoid induction of TAT gene expression is subject to multiple levels of control by several new cis-acting elements and thus is much more complex than previously appreciated. JF - Molecular endocrinology (Baltimore, Md.) AU - Collier, C D AU - Oshima, H AU - Simons, S S AD - Steroid Hormones Section, National Institute of Diabetes and Digestive and Kidney Diseases@Laboratory of Molecular and Cellular Biology, National Institute of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 463 EP - 476 VL - 10 IS - 5 SN - 0888-8809, 0888-8809 KW - Glucocorticoids KW - 0 KW - Oligodeoxyribonucleotides KW - Trans-Activators KW - Dexamethasone KW - 7S5I7G3JQL KW - DNA KW - 9007-49-2 KW - Tyrosine Transaminase KW - EC 2.6.1.5 KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - Thermodynamics KW - Transfection KW - Oligodeoxyribonucleotides -- chemistry KW - Dexamethasone -- pharmacology KW - Binding, Competitive KW - Molecular Sequence Data KW - DNA -- chemistry KW - Repetitive Sequences, Nucleic Acid KW - Cell Line KW - Mutagenesis KW - Binding Sites KW - Trans-Activators -- metabolism KW - Tyrosine Transaminase -- genetics KW - Gene Expression Regulation -- drug effects KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78187503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=A+negative+tyrosine+aminotransferase+gene+element+that+blocks+glucocorticoid+modulatory+element-regulated+modulation+of+glucocorticoid-induced+gene+expression.&rft.au=Collier%2C+C+D%3BOshima%2C+H%3BSimons%2C+S+S&rft.aulast=Collier&rft.aufirst=C&rft.date=1996-05-01&rft.volume=10&rft.issue=5&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of the putative dopamine D1 agonist and D2 antagonist FCE 23884 on Parkinson's disease. AN - 78175163; 8723141 AB - The ergoline derivative FCE 23,884 acts as a dopamine D1 agonist in untreated parkinsonian animals and as a D2 antagonist in animals whose dopamine system is intact or levodopa treated. To evaluate whether this dual action might benefit patients with Parkinson's disease (PD) who have developed levodopa-induced dyskinesias, the motor effects of FCE 23,884 were examined in seven such individuals using a double-blind, placebo-controlled design. At doses up to the maximum tolerated dose (3.5 +/- 0.5 mg), FCE 23,884 monotherapy did not affect parkinsonian severity. On the other hand, coadministration of FCE 23,884 with a mildly dyskinetic dose of levodopa, infused intravenously under steady-state conditions, reduced the antiparkinson response by 54 +/- 19% and tended to diminish dyskinesia severity. The results thus fail to suggest any useful role for FCE 23,884 in the symptomatic treatment of PD. Although D2 receptor blockade provided by FCE 23,884 antagonizes both the antiparkinson and dyskinesigenic responses to levodopa, the degree of D1 receptor stimulation appears insufficient to ameliorate parkinsonian symptomatology. JF - Movement disorders : official journal of the Movement Disorder Society AU - Metman, L V AU - Blanchet, P J AU - de Jong, D AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 257 EP - 260 VL - 11 IS - 3 SN - 0885-3185, 0885-3185 KW - Antiparkinson Agents KW - 0 KW - Dopamine Agonists KW - Dopamine Antagonists KW - Dopamine D2 Receptor Antagonists KW - Ergolines KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - FCE 23884 KW - 107052-56-2 KW - Levodopa KW - 46627O600J KW - Carbidopa KW - MNX7R8C5VO KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Carbidopa -- adverse effects KW - Aged KW - Receptors, Dopamine D2 -- physiology KW - Drug Therapy, Combination KW - Treatment Outcome KW - Neurologic Examination -- drug effects KW - Levodopa -- therapeutic use KW - Carbidopa -- therapeutic use KW - Middle Aged KW - Levodopa -- adverse effects KW - Female KW - Male KW - Antiparkinson Agents -- adverse effects KW - Dopamine Antagonists -- therapeutic use KW - Antiparkinson Agents -- therapeutic use KW - Receptors, Dopamine D1 -- drug effects KW - Ergolines -- adverse effects KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- drug therapy KW - Dopamine Agonists -- therapeutic use KW - Receptors, Dopamine D1 -- physiology KW - Dopamine Antagonists -- adverse effects KW - Dopamine Agonists -- administration & dosage KW - Ergolines -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78175163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Effect+of+the+putative+dopamine+D1+agonist+and+D2+antagonist+FCE+23884+on+Parkinson%27s+disease.&rft.au=Metman%2C+L+V%3BBlanchet%2C+P+J%3Bde+Jong%2C+D%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Metman&rft.aufirst=L&rft.date=1996-05-01&rft.volume=11&rft.issue=3&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-07 N1 - Date created - 1996-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of PCR-based approaches to molecular epidemiologic analysis of Clostridium difficile. AN - 78145261; 8727893 AB - Representative isolates of the 10 serogroups of Clostridium difficile and 39 clinical isolates (30 toxigenic and 9 nontoxigenic), including 5 isolates from a confirmed nosocomial outbreak, were analyzed by using two previously described arbitrary-primer PCR (AP-PCR) molecular typing methodologies (AP-PG05 and AP-ARB11) and PCR ribotyping. The two AP-PCR methods investigated gave comparable results; AP-PG05 and AP-ARB11 identified 8 and 7 groups among the serogroup isolates and classified the clinical isolates into 21 and 20 distinct groups, respectively. PCR ribotyping also identified 8 unique groups among the serogroup isolates but classified the clinical isolates into 23 groups. In addition, when results obtained by the PCR methods were compared with typing data generated by pulsed-field gel electrophoresis (PFGE), PCR ribotyping and PFGE were found to be in agreement for 83% (29 of 35) of isolates typeable by both techniques while AP-PG05 was in agreement with PFGE for 60% (20 of 33) and AP-ARB11 was in agreement with PFGE for only 44% (17 of 36). These results indicate that PCR ribotyping is a more discriminatory approach than AP-PCR for typing C. difficile and, furthermore, that this technique generates results that are in higher concordance with those obtained by using an established method for differentiating isolates of this organism on a molecular level than are results generated by using AP-PCR. JF - Journal of clinical microbiology AU - Collier, M C AU - Stock, F AU - DeGirolami, P C AU - Samore, M H AU - Cartwright, C P AD - Clinical Pathology Department Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1153 EP - 1157 VL - 34 IS - 5 SN - 0095-1137, 0095-1137 KW - DNA Primers KW - 0 KW - Index Medicus KW - DNA Primers -- genetics KW - Enterocolitis, Pseudomembranous -- epidemiology KW - Humans KW - Serotyping KW - Bacterial Typing Techniques KW - Disease Outbreaks KW - Enterocolitis, Pseudomembranous -- microbiology KW - Evaluation Studies as Topic KW - Base Sequence KW - Molecular Epidemiology KW - Molecular Sequence Data KW - Electrophoresis, Gel, Pulsed-Field KW - Cross Infection -- epidemiology KW - Cross Infection -- microbiology KW - Clostridium difficile -- isolation & purification KW - Polymerase Chain Reaction -- statistics & numerical data KW - Polymerase Chain Reaction -- methods KW - Clostridium difficile -- classification KW - Clostridium difficile -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78145261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+microbiology&rft.atitle=Comparison+of+PCR-based+approaches+to+molecular+epidemiologic+analysis+of+Clostridium+difficile.&rft.au=Collier%2C+M+C%3BStock%2C+F%3BDeGirolami%2C+P+C%3BSamore%2C+M+H%3BCartwright%2C+C+P&rft.aulast=Collier&rft.aufirst=M&rft.date=1996-05-01&rft.volume=34&rft.issue=5&rft.spage=1153&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Clin Microbiol. 1988 Mar;26(3):426-8 [2833528] J Clin Microbiol. 1995 Sep;33(9):2233-9 [7494007] Clin Microbiol Rev. 1988 Jan;1(1):1-18 [3144429] N Engl J Med. 1989 Jan 26;320(4):204-10 [2911306] J Clin Microbiol. 1992 Apr;30(4):967-73 [1572985] FEMS Microbiol Lett. 1992 Apr 1;71(1):5-9 [1624110] Clin Infect Dis. 1992 Oct;15(4):573-81 [1420669] J Clin Microbiol. 1993 Apr;31(4):982-5 [8463406] Clin Infect Dis. 1993 Aug;17(2):153-62; quiz 163-4 [8399860] Eur J Clin Microbiol Infect Dis. 1993 Oct;12(10):794-5 [8307056] J Gen Microbiol. 1993 Dec;139(12):3089-97 [7510324] J Infect Dis. 1994 Mar;169(3):661-4 [8158046] Clin Microbiol Rev. 1994 Apr;7(2):174-84 [8055466] J Clin Microbiol. 1994 Jun;32(6):1591-3 [7741841] J Clin Microbiol. 1994 Aug;32(8):1963-9 [7989550] J Clin Microbiol. 1994 Sep;32(9):2067-70 [7814526] J Clin Microbiol. 1995 Jan;33(1):184-7 [7699038] J Infect Dis. 1988 Oct;158(4):731-6 [2844914] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inverse dose-rate effect for mutation induction by gamma-rays in human lymphoblasts. AN - 78083611; 8648243 AB - In order to define further the effects of differences in recombinational proficiency on cell survival and mutation by ionizing radiation, we exposed the syngenic cell lines TK6 and WTK1 to continuous low dose-rate gamma-irradiation. We previously demonstrated that acute X-ray exposure results in lower survival and lower mutation induction at both the thymidine kinase (tk) and the hypoxanthine-guanine phosphoribosyltransferase (hprt) loci in TK6 cells compared with WTK1 cells. These differences were attributed in part to reduced levels of recombination in the TK6 line relative to WTK1. Using a low dose rate 137Cs irradiator, we exposed asynchronous growing populations of these cells to gamma-rays at 14.3, 6.7 and 2.7 cGy/h. Both cell lines exhibited a dose-rate effect on survival. Compared with acute doses, the low dose-rates also protected against mutation induction at the hrpt locus in WTK1, but protection was inversely related to dose-rate. There was also a slight inverse dose-rate effect in TK6, with mutation induction at the lowest dose-rate exceeding that at acute exposures. JF - International journal of radiation biology AU - Amundson, S A AU - Chen, D J AD - National Cancer Institute, National Institudes of Health, Bethesda, MD 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 555 EP - 563 VL - 69 IS - 5 SN - 0955-3002, 0955-3002 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Index Medicus KW - Space life sciences KW - Non-programmatic KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Gamma Rays KW - Cells, Cultured KW - Humans KW - Lymphocytes -- radiation effects KW - Dose-Response Relationship, Radiation KW - Cell Survival -- radiation effects KW - Cell Cycle KW - Thymidine Kinase -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78083611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+biology&rft.atitle=Inverse+dose-rate+effect+for+mutation+induction+by+gamma-rays+in+human+lymphoblasts.&rft.au=Amundson%2C+S+A%3BChen%2C+D+J&rft.aulast=Amundson&rft.aufirst=S&rft.date=1996-05-01&rft.volume=69&rft.issue=5&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+biology&rft.issn=09553002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-19 N1 - Date created - 1996-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and expression of a second human natural killer cell granule tryptase, HNK-Tryp-2/granzyme 3. AN - 78074845; 8656064 AB - Cytotoxic lymphocytes possess a number of serine proteases (granzymes) usually localized in cytoplasmic granules. To date, the DNA sequences of four human granzymes have been reported. A fifth human granzyme (granzyme 3) has been biochemically purified and its N-terminal amino acid sequence has been reported. This enzyme was described as possessing tryptase activity, cleaving synthetic substrates after arginine or lysine. We recently cloned a rat granzyme tryptase (RNK-Tryp-2), and used this cDNA to screen human cDNA libraries. Isolation of cDNA fragments of a human gene could be overlapped to provide a complete cDNA sequence, which we designated HNK-Tryp-2. The N-terminal amino acid sequence deduced from HNK-Tryp-2 was identical to that reported for granzyme 3. This gene appears to be a single copy gene that is expressed in isolated natural killer cells and T cells as well as in tissues containing these cells. JF - Journal of leukocyte biology AU - Sayers, T J AU - Lloyd, A R AU - McVicar, D W AU - O'Connor, M D AU - Kelly, J M AU - Carter, C R AU - Wiltrout, T A AU - Wiltrout, R H AU - Smyth, M J AD - Biological Carcinogenesis and Developmental Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Developmental Center, Maryland 21702, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 763 EP - 768 VL - 59 IS - 5 SN - 0741-5400, 0741-5400 KW - DNA, Complementary KW - 0 KW - GZMK protein, human KW - EC 3.4.21.- KW - Granzymes KW - Serine Endopeptidases KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Blotting, Southern KW - Humans KW - Molecular Sequence Data KW - DNA, Complementary -- isolation & purification KW - Mice KW - Amino Acid Sequence KW - Cloning, Molecular KW - Serine Endopeptidases -- genetics KW - Serine Endopeptidases -- chemistry KW - Killer Cells, Natural -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78074845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Cloning+and+expression+of+a+second+human+natural+killer+cell+granule+tryptase%2C+HNK-Tryp-2%2Fgranzyme+3.&rft.au=Sayers%2C+T+J%3BLloyd%2C+A+R%3BMcVicar%2C+D+W%3BO%27Connor%2C+M+D%3BKelly%2C+J+M%3BCarter%2C+C+R%3BWiltrout%2C+T+A%3BWiltrout%2C+R+H%3BSmyth%2C+M+J&rft.aulast=Sayers&rft.aufirst=T&rft.date=1996-05-01&rft.volume=59&rft.issue=5&rft.spage=763&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-01 N1 - Date created - 1996-08-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U35237; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-12 inhibits endotoxin-induced inflammation in the eye. AN - 78070584; 8647191 AB - Interleukin-12 (IL-12) is a heterodimeric cytokine that induces interferon (IFN)-gamma production and an increased generation of Th1 cells. Both IL-12 and IL-12 antagonists are being studied for the treatment of allergic reactions, autoimmune disease and malignancy. The goal of the present experiments was to examine the importance of IL-12 in endotoxin-induced ocular inflammation. The number of inflammatory cells infiltrating eyes with endotoxin-induced uveitis (EIU) was significantly increased in animals treated with intraperitoneal anti-IL-12 antibody when compared to control animals, but there was no difference in infiltrating inflammatory cells in the eyes of animals treated with IL-12 when compared to controls. In contrast, intraocular injection of IL-12 significantly inhibited the development of endotoxin-induced intraocular inflammation. The infiltrating inflammatory cells were reduced in the eyes of animals receiving intraocular IL-12 when compared to controls. Cytokine analysis of the aqueous humor obtained from eyes with EIU showed increased levels of IFN-gamma and decreased levels of IL-6 in eyes receiving intraocular IL-12. These data show that IL-12 has an inhibitory effect on endotoxin-induced inflammation in the eye and suggest that IL-12 can have an immunoregulatory function in some forms of inflammatory disease. JF - European journal of immunology AU - Whitcup, S M AU - Rizzo, L V AU - Lai, J C AU - Hayashi, S AU - Gazzinelli, R AU - Chan, C C AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 995 EP - 999 VL - 26 IS - 5 SN - 0014-2980, 0014-2980 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Antibodies, Monoclonal KW - Bacterial Toxins KW - Cytokines KW - Endotoxins KW - Recombinant Proteins KW - salmonella toxin KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Cytokines -- analysis KW - Animals KW - Recombinant Proteins -- pharmacology KW - Aqueous Humor -- chemistry KW - Mice, Inbred C3H KW - Mice KW - Antibodies, Monoclonal -- pharmacology KW - Eye -- drug effects KW - Salmonella typhimurium -- immunology KW - Female KW - Uveitis -- prevention & control KW - Interleukin-12 -- immunology KW - Uveitis -- pathology KW - Anti-Inflammatory Agents, Non-Steroidal -- immunology KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Bacterial Toxins -- toxicity KW - Interleukin-12 -- therapeutic use KW - Uveitis -- etiology KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78070584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+immunology&rft.atitle=IL-12+inhibits+endotoxin-induced+inflammation+in+the+eye.&rft.au=Whitcup%2C+S+M%3BRizzo%2C+L+V%3BLai%2C+J+C%3BHayashi%2C+S%3BGazzinelli%2C+R%3BChan%2C+C+C&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1996-05-01&rft.volume=26&rft.issue=5&rft.spage=995&rft.isbn=&rft.btitle=&rft.title=European+journal+of+immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-25 N1 - Date created - 1996-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of hepatic and renal P4502E1 of neonatal rats exposed translactationally to ethanol. AN - 78070380; 8655096 AB - The effect of maternal ethanol intake during lactation on neonatal cytochrome P4502E1 was investigated in Sprague-Dawley rats. Dams were exposed to 15% (v/v) ethanol in drinking water from day 1 of lactation to 4, 7 or 14 days postpartum. Significant (P < 0.01) enhancement of both hepatic and renal N-nitrosodimethylamine (NDMA) demethylase, an activity of P4502E1, was observed in lactating mothers given ethanol in drinking water. Demethylase activity also significantly increased (P < 0.01) in the 7- and 14-day livers of both female and male pups and in the 7- and 14-day female and 14-day male kidneys exposed to ethanol through the transmammary route. Cytochrome P4502E1 protein content, assayed by immunoblotting, increased in the maternal liver and kidney of all groups consuming ethanol. Neonatal P4502E1 protein content increased in the 7- and 14-day livers of both sexes and 14-day female kidneys exposed translactationally to ethanol. No effect of ethanol on enzyme activity or protein content of P4502E1 was observed in the liver or kidney of 4-day-old neonates. These results demonstrate the translactational effect of ethanol on neonatal P4502E1 enzyme, which is involved in the metabolism of many low molecular weight xenobiotics, and indicate the possibility of alterations occurring in the kinetics of neonatal drug and xenobiotic metabolism and also in processes connected with perinatal carcinogenesis. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Chhabra, S K AU - Perella, C AU - Anderson, L M AD - Perinatal Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 469 EP - 476 VL - 34 IS - 5 SN - 0278-6915, 0278-6915 KW - Ethanol KW - 3K9958V90M KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Alcohol Drinking -- adverse effects KW - Oxidoreductases, N-Demethylating -- metabolism KW - Male KW - Female KW - Maternal Exposure -- adverse effects KW - Lactation -- drug effects KW - Liver -- enzymology KW - Liver -- drug effects KW - Kidney -- enzymology KW - Kidney -- drug effects KW - Ethanol -- toxicity KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Cytochrome P-450 Enzyme System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78070380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Induction+of+hepatic+and+renal+P4502E1+of+neonatal+rats+exposed+translactationally+to+ethanol.&rft.au=Chhabra%2C+S+K%3BPerella%2C+C%3BAnderson%2C+L+M&rft.aulast=Chhabra&rft.aufirst=S&rft.date=1996-05-01&rft.volume=34&rft.issue=5&rft.spage=469&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-30 N1 - Date created - 1996-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Qualitative and quantitative contributions of the T cell receptor zeta chain to mature T cell apoptosis. AN - 78062195; 8642321 AB - Engagement of the T cell receptor (TCR) of mature T lymphocytes can lead either to activation/proliferation responses or programmed cell death. To understand the molecular regulation of these two fundamentally different outcomes of TCR signaling, we investigated the participation of various components of the TCR-CD3 complex. We found that the TCR-zeta chain, while not absolutely required, was especially effective at promoting mature T cell apoptosis compared with the CD3 epsilon, gamma, or delta chains. We also carried out mutagenesis to address the role of the immunoreceptor tyrosine-based activation motifs (ITAMs) that are the principal signaling components found three times in the TCR-zeta chain and once in each of the CD3 epsilon, gamma, or delta chains. We found that the ability of the TCR-zeta chain to promote apoptosis results both from a quantitative effect of the presence of multiple ITAMs as well as qualitatively different contributions made by individual ITAMs. Apoptosis induced by single chain chimeras revealed that the first zeta ITAM stimulated greater apoptosis than the third zeta ITAM, and the second zeta ITAM was unable to trigger apoptosis. Because microheterogeneity in the amino acid sequence of the various ITAM motifs found in the TCR-zeta and CD3 chains predicts interactions with distinct src-homology-2-domain signaling proteins, our results suggest the possibility that individual ITAM motifs might play unique roles in TCR responses by engaging specific signaling pathways. JF - The Journal of experimental medicine AU - Combadière, B AU - Freedman, M AU - Chen, L AU - Shores, E W AU - Love, P AU - Lenardo, M J AD - Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 2109 EP - 2117 VL - 183 IS - 5 SN - 0022-1007, 0022-1007 KW - DNA Primers KW - 0 KW - Membrane Proteins KW - Receptor-CD3 Complex, Antigen, T-Cell KW - Receptors, Antigen, T-Cell KW - Recombinant Fusion Proteins KW - antigen T cell receptor, zeta chain KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Clone Cells KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Genetic Variation KW - Recombinant Fusion Proteins -- immunology KW - DNA -- analysis KW - Amino Acid Sequence KW - Mice KW - Lymphocyte Activation KW - Polymerase Chain Reaction KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Signal Transduction KW - Membrane Proteins -- immunology KW - Membrane Proteins -- biosynthesis KW - Apoptosis -- immunology KW - Receptors, Antigen, T-Cell -- immunology KW - Receptors, Antigen, T-Cell -- biosynthesis KW - T-Lymphocytes -- drug effects KW - Receptor-CD3 Complex, Antigen, T-Cell -- immunology KW - T-Lymphocytes -- immunology KW - Receptor-CD3 Complex, Antigen, T-Cell -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78062195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Qualitative+and+quantitative+contributions+of+the+T+cell+receptor+zeta+chain+to+mature+T+cell+apoptosis.&rft.au=Combadi%C3%A8re%2C+B%3BFreedman%2C+M%3BChen%2C+L%3BShores%2C+E+W%3BLove%2C+P%3BLenardo%2C+M+J&rft.aulast=Combadi%C3%A8re&rft.aufirst=B&rft.date=1996-05-01&rft.volume=183&rft.issue=5&rft.spage=2109&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-18 N1 - Date created - 1996-07-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374-8 [2950524] Science. 1993 Aug 13;261(5123):918-21 [7688481] Cell. 1988 Jan 15;52(1):85-95 [3278811] Annu Rev Immunol. 1988;6:629-62 [3289580] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] Nature. 1989 Jan 12;337(6203):181-4 [2521375] Nature. 1989 Mar 30;338(6214):383-4 [2927501] Eur J Immunol. 1993 Sep;23(9):2257-62 [8103746] Cell. 1994 Jan 28;76(2):263-74 [8293463] Cell. 1994 Feb 25;76(4):593-6 [8124703] Mol Cell Biol. 1994 Apr;14(4):2777-85 [7511210] Curr Opin Genet Dev. 1994 Aug;4(4):581-6 [7950327] Science. 1994 Nov 11;266(5187):1047-50 [7526464] J Biol Chem. 1994 Dec 30;269(52):32828-34 [7806507] J Exp Med. 1995 Jan 1;181(1):375-80 [7528772] J Exp Med. 1995 Feb 1;181(2):781-6 [7530763] Cell Immunol. 1995 Jan;160(1):71-8 [7531119] Immunity. 1994 Aug;1(5):365-71 [7533645] Immunol Today. 1995 Feb;16(2):110 [7888063] Clin Immunol Immunopathol. 1989 Sep;52(3):447-59 [2547539] Annu Rev Immunol. 1990;8:139-67 [2188661] Immunity. 1995 Apr;2(4):401-11 [7719942] Curr Opin Genet Dev. 1995 Feb;5(1):97-104 [7749333] Int Rev Immunol. 1995;13(2):115-34 [8789425] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358-62 [2190221] Science. 1990 Dec 21;250(4988):1720-3 [2125367] Cell. 1991 Feb 8;64(3):511-20 [1671341] Cell. 1991 Mar 8;64(5):891-901 [1705867] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2151-5 [1826050] Cell. 1991 Apr 19;65(2):281-91 [2015626] Nature. 1991 Oct 31;353(6347):858-61 [1944559] Cell. 1992 Jan 10;68(1):83-95 [1531041] Cell. 1992 Mar 6;68(5):889-97 [1547489] Science. 1992 Jan 3;255(5040):79-82 [1532456] Annu Rev Immunol. 1992;10:267-93 [1590988] J Biol Chem. 1992 Jul 5;267(19):13656-60 [1535630] Cell. 1992 Aug 21;70(4):585-93 [1505025] J Biol Chem. 1992 Dec 15;267(35):24913-6 [1459994] Semin Immunol. 1992 Dec;4(6):379-88 [1286165] Cell. 1993 Mar 12;72(5):767-78 [7680959] J Exp Med. 1993 Apr 1;177(4):1093-103 [8459204] Eur J Immunol. 1993 Jul;23(7):1552-60 [8325332] Mol Cell Biol. 1988 Jan;8(1):466-72 [2827008] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of growth in vitro and tumorigenicity in vivo of human carcinoma cell lines by transfected p16INK4. AN - 78046331; 8634094 AB - The function of p16INK4 as a putative tumor suppressor gene was examined by investigating its ability to inhibit the growth of cancer cell lines in vitro and tumor formation in vivo. A p16INK4 cDNA expression vector was transfected into five human cancer cell lines that varied in their p16INK4 and retinoblastoma (Rb) status. Suppression of colony-forming efficiency was seen in four cell lines. Of two cell lines wild type for p16INK4 but null for Rb protein expression, one (Hep 3B) showed inhibition of colony formation, whereas the other (Saos-2) did not. This observation may demonstrate involvement of p16INK4 independent of Rb. The transfected p16INK4 gene was frequently selected against and lost during continued growth in vitro. When compared to the colon carcinoma cell line (DLD-1),p16INK4-transfected DLD-1 clone 1 cells were less tumorigenic in athymic nude mice. Tumors arising from p16INK4-transfected DLD-1 clones, which were growth suppressed in vitro, either lost the integrated exogenous p16INK4 or expressed reduced amounts of p16INK4 protein. Therefore, p16INK4 was also selected against during tumor formation in vivo. These data are consistent with the hypothesis that p16INK4 is a tumor suppressor gene. JF - Molecular carcinogenesis AU - Spillare, E A AU - Okamoto, A AU - Hagiwara, K AU - Demetrick, D J AU - Serrano, M AU - Beach, D AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 53 EP - 60 VL - 16 IS - 1 SN - 0899-1987, 0899-1987 KW - Carrier Proteins KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - DNA Primers KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Base Sequence KW - Transfection KW - Humans KW - Molecular Sequence Data KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - DNA Primers -- chemistry KW - Cell Division KW - Tumor Cells, Cultured -- cytology KW - Carrier Proteins -- metabolism KW - Genes, Tumor Suppressor UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78046331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Suppression+of+growth+in+vitro+and+tumorigenicity+in+vivo+of+human+carcinoma+cell+lines+by+transfected+p16INK4.&rft.au=Spillare%2C+E+A%3BOkamoto%2C+A%3BHagiwara%2C+K%3BDemetrick%2C+D+J%3BSerrano%2C+M%3BBeach%2C+D%3BHarris%2C+C+C&rft.aulast=Spillare&rft.aufirst=E&rft.date=1996-05-01&rft.volume=16&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-10 N1 - Date created - 1996-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diabetic-like retinopathy ameliorated with the aldose reductase inhibitor WAY-121,509. AN - 78046187; 8631629 AB - To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), in preventing the retinopathy that develops in the galactose-fed rat model of diabetic ocular complications. Sprague-Dawley rats were randomized into treatment and duration groups and fed diets with either 50% starch of 50% galactose with or without WAY-121,509 (25 mg/kg body weight per day). Progression of cataracts was monitored by slit-lamp biomicroscopy. After duration of 4, 8, 16, and 24 months, levels of plasma glucose and glycated hemoglobin, as well as erythrocyte and retinal galactose and galactitol, were measured in rats in each group. Retinal vasculatures of the 24-month rats were isolated by elastase digestion and analyzed by computer-assisted morphometry. Mature, diabetic-like cataracts developed within 5 weeks in all the galactose-fed, untreated rats, but only nonprogressive anterior cortical opacities were present in lenses of 85% of the ARI-treated galactosemic animals after 3 months. Plasma glucose remained the same in all groups. Erythrocyte and retinal galactose and glycated (galactosylated) hemoglobin were elevated with galactosemia and were unaffected by ARI treatment. Erythrocyte and retinal galactitol levels were decreased by 91% and 95%, respectively, with inhibitor treatment. At 24 months, capillary length, width, density, the number of microaneurysms, and the percent of capillary length involved in intraretinal microvascular abnormalities, expressed as hypercellular channels with diameters > 20 microns, were significantly increased by galactosemia and were attenuated in the galactose-fed, ARI-treated group. A dose of WAY-121,509 sufficient to reduce retinal polyol levels by 95% ameliorated the development of galactose-induced cataracts and diabetic-like retinopathy but was insufficient to prevent early lens opacifications or all the diabetic-like retinal microangiopathies. JF - Investigative ophthalmology & visual science AU - Robinson, W G AU - Laver, N M AU - Jacot, J L AU - Glover, J P AU - Basso, M D AU - Blouin, P AU - Hohman, T C AD - National Eye Institute, Bethesda, Maryland 20892-2740, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1149 EP - 1156 VL - 37 IS - 6 SN - 0146-0404, 0146-0404 KW - Blood Glucose KW - 0 KW - Hemoglobin A, Glycosylated KW - Polymers KW - WAY 121-509 KW - polyol KW - Galactitol KW - 113ZQ1Y7DD KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Retina -- metabolism KW - Animals KW - Blood Glucose -- metabolism KW - Random Allocation KW - Cataract -- chemically induced KW - Lens, Crystalline -- physiopathology KW - Cataract -- physiopathology KW - Erythrocytes -- metabolism KW - Galactitol -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Hemoglobin A, Glycosylated -- metabolism KW - Cataract -- prevention & control KW - Lens, Crystalline -- drug effects KW - Retinal Vessels -- drug effects KW - Polymers -- metabolism KW - Image Processing, Computer-Assisted KW - Female KW - Retinal Vessels -- pathology KW - Aldehyde Reductase -- therapeutic use KW - Diabetic Retinopathy -- pathology KW - Aldehyde Reductase -- administration & dosage KW - Diabetic Retinopathy -- chemically induced KW - Aldehyde Reductase -- antagonists & inhibitors KW - Diabetic Retinopathy -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78046187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=Diabetic-like+retinopathy+ameliorated+with+the+aldose+reductase+inhibitor+WAY-121%2C509.&rft.au=Robinson%2C+W+G%3BLaver%2C+N+M%3BJacot%2C+J+L%3BGlover%2C+J+P%3BBasso%2C+M+D%3BBlouin%2C+P%3BHohman%2C+T+C&rft.aulast=Robinson&rft.aufirst=W&rft.date=1996-05-01&rft.volume=37&rft.issue=6&rft.spage=1149&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-01 N1 - Date created - 1996-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural flexibility and functional versatility of mammalian P450 enzymes. AN - 78044863; 8635685 AB - P450 enzymes have evolved into a large superfamily that displays great diversity in substrate and product specificities by fixing the natural amino acid substitutions with high frequency. Site-directed mutagenesis has been used to correlate the substitutions with the diverse specificities in various P450s. As a result, the common residues that determine the specificities of various mammalian P450s have been identified and aligned to the corresponding residues in the substrate-heme pocket of the 3-dimensional structures of bacterial P450s. The substrate-heme pocket appears to be structurally variable so that only a minor substitution (Ala -> -> Val, for example) at the critical positions is enough to define the altered specificity. Thus, the structural variability of the P450s provides the inherent versatility in acquiring a novel activity. Recent mutational studies indicate that the side chain size is the major determining factor of specificity, outweighing other factors such as polarity. Further understanding of the paradoxical characteristics observed may provide us with the underlying principles that determine P450 activities, and may lead to the ability to predict P450 activities based on the types of key amino acid residues. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Negishi, M AU - Uno, T AU - Darden, T A AU - Sueyoshi, T AU - Pedersen, L G AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709 USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 683 EP - 689 VL - 10 IS - 7 SN - 0892-6638, 0892-6638 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Molecular KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - Cytochrome P-450 Enzyme System -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78044863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Structural+flexibility+and+functional+versatility+of+mammalian+P450+enzymes.&rft.au=Negishi%2C+M%3BUno%2C+T%3BDarden%2C+T+A%3BSueyoshi%2C+T%3BPedersen%2C+L+G&rft.aulast=Negishi&rft.aufirst=M&rft.date=1996-05-01&rft.volume=10&rft.issue=7&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-10 N1 - Date created - 1996-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico. AN - 78043281; 8640905 AB - The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC). The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGGarg-->AGTser missense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation. We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population. Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly. The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA. Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antiserum (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg-->AGTser mutations were found. Serum antibodies recognizing p53 protein were found in one of 18 patients. Positive serology for HBV and/or HCV was found in 12 of 20 cases. The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin. These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico. JF - Carcinogenesis AU - Soini, Y AU - Chia, S C AU - Bennett, W P AU - Groopman, J D AU - Wang, J S AU - DeBenedetti, V M AU - Cawley, H AU - Welsh, J A AU - Hansen, C AU - Bergasa, N V AU - Jones, E A AU - DiBisceglie, A M AU - Trivers, G E AU - Sandoval, C A AU - Calderon, I E AU - Munoz Espinosa, L E AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1007 EP - 1012 VL - 17 IS - 5 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Codon KW - Serum Albumin KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Serum Albumin -- metabolism KW - Animals KW - Hepatitis C -- complications KW - Humans KW - Aged KW - Rabbits KW - Base Sequence KW - Hepatitis B -- complications KW - Adult KW - Molecular Sequence Data KW - Middle Aged KW - Female KW - Male KW - Aflatoxin B1 -- metabolism KW - Genes, p53 KW - Carcinoma, Hepatocellular -- etiology KW - Carcinoma, Hepatocellular -- genetics KW - Carcinogens -- toxicity KW - Aflatoxin B1 -- toxicity KW - Liver Neoplasms -- etiology KW - Mutation KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78043281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=An+aflatoxin-associated+mutational+hotspot+at+codon+249+in+the+p53+tumor+suppressor+gene+occurs+in+hepatocellular+carcinomas+from+Mexico.&rft.au=Soini%2C+Y%3BChia%2C+S+C%3BBennett%2C+W+P%3BGroopman%2C+J+D%3BWang%2C+J+S%3BDeBenedetti%2C+V+M%3BCawley%2C+H%3BWelsh%2C+J+A%3BHansen%2C+C%3BBergasa%2C+N+V%3BJones%2C+E+A%3BDiBisceglie%2C+A+M%3BTrivers%2C+G+E%3BSandoval%2C+C+A%3BCalderon%2C+I+E%3BMunoz+Espinosa%2C+L+E%3BHarris%2C+C+C&rft.aulast=Soini&rft.aufirst=Y&rft.date=1996-05-01&rft.volume=17&rft.issue=5&rft.spage=1007&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-17 N1 - Date created - 1996-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of transforming growth factor alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met and acidic fibroblast growth factor/fibroblast growth factor receptors during hepatocarcinogenesis. AN - 78042795; 8640940 AB - It is widely believed that abnormal production of polypeptide growth factors, together with other molecular alterations, play an important role in neoplastic development. Transforming growth factor alpha (TGFalpha), hepatocyte growth factor (HGF) and acidic fibroblast growth factor (aFGF) are the three major growth factors that contribute to liver regeneration occurring via both hepatocyte replication and oval cell proliferation. It is not clear, however, whether and to what extent these growth factors are also involved in hepatocarcinogenesis. In the present study, the gene expression of TGFalpha, HGF and aFGF and their corresponding receptors was examined by Northern blotting and in situ hybridization during hepatocarcinogenesis induced by the Solt-Farber protocol. All three growth factor/receptor systems, TGFalpha/epidermal growth factor receptor (EGFR), HGF/c-met and aFGF/FGF receptors (flg and bek) were significantly elevated at early time points when oval cells were proliferating. Their respective expression decreased after 1 month and remained at a low level until the development of liver tumors. In all hepatocellular carcinomas (HCC) examined, the transcripts of TGFalpha and aFGF were highly expressed, while those of HGF were low. With regard to the receptor expression in the tumors, EGFR was present at varying levels, c-met was expressed at higher levels and flg increased significantly, whereas bek remained at low levels. These data suggest that TGFalpha and aFGF are the major growth factors involved in the progression of HCC, and that the signal of aFGF is mainly transduced by the receptor flg in HCC. Furthermore, HCC cells were phenotypically very similar to oval cells with regard to the gene expression of growth factor/receptor systems. These results, along with the finding that all the HCC cells are positive for the oval cell antigen OV6, and that cytokeratin 19 is heavily expressed in both tumor and oval cells, strongly suggest that at least some of the HCC induced by the Solt-Farber protocol may be derived from oval cells. JF - Carcinogenesis AU - Hu, Z AU - Evarts, R P AU - Fujio, K AU - Omori, N AU - Omori, M AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 931 EP - 938 VL - 17 IS - 5 SN - 0143-3334, 0143-3334 KW - Receptors, Fibroblast Growth Factor KW - 0 KW - Transforming Growth Factor alpha KW - Fibroblast Growth Factor 1 KW - 104781-85-3 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Receptor, Epidermal Growth Factor KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - In Situ Hybridization KW - Immunohistochemistry KW - Male KW - Hepatocyte Growth Factor -- analysis KW - Receptor Protein-Tyrosine Kinases -- analysis KW - Transforming Growth Factor alpha -- analysis KW - Fibroblast Growth Factor 1 -- analysis KW - Receptor, Epidermal Growth Factor -- analysis KW - Liver Neoplasms, Experimental -- chemistry KW - Receptors, Fibroblast Growth Factor -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78042795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Expression+of+transforming+growth+factor+alpha%2Fepidermal+growth+factor+receptor%2C+hepatocyte+growth+factor%2Fc-met+and+acidic+fibroblast+growth+factor%2Ffibroblast+growth+factor+receptors+during+hepatocarcinogenesis.&rft.au=Hu%2C+Z%3BEvarts%2C+R+P%3BFujio%2C+K%3BOmori%2C+N%3BOmori%2C+M%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Hu&rft.aufirst=Z&rft.date=1996-05-01&rft.volume=17&rft.issue=5&rft.spage=931&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-17 N1 - Date created - 1996-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel DNA damage-inducible transcript, gadd7, inhibits cell growth, but lacks a protein product. AN - 78041645; 8649973 AB - gadd7 cDNA was isolated from Chinese hamster ovary (CHO) cells on the basis of increased levels of RNA following treatment with UV radiation. The transcript for gadd7, as well as for four other gadd genes, was found to increase rapidly and coordinately following several different types of DNA damage and more slowly following other stresses that elicit growth arrest. Agents that induce gadd7 RNA include alkylating agents, such as methyl methanesulfonate (MMS), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and mechlorethamine HCl (HN2), oxidizing agents, such as hydrogen peroxide, and growth arrest signals, such as medium depletion (starvation). Since growth arrest is a cellular consequence of many types of DNA damage in normal cells, it was thought that gadd7 may play a role in the cellular response to DNA damage. Indeed, overexpression of gadd7 led to a decrease in cell growth. Interestingly, gadd7 cDNA does not contain an appreciable open reading frame and does not appear to encode a protein product, but instead may function at the RNA level. JF - Nucleic acids research AU - Hollander, M C AU - Alamo, I AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, Division of Basic Science, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 1589 EP - 1593 VL - 24 IS - 9 SN - 0305-1048, 0305-1048 KW - Alkylating Agents KW - 0 KW - Culture Media KW - DNA, Complementary KW - Oxidants KW - RNA, Messenger KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Oxidants -- pharmacology KW - Humans KW - Alkylating Agents -- pharmacology KW - Hydrogen Peroxide -- pharmacology KW - Amino Acid Sequence KW - Methyl Methanesulfonate -- pharmacology KW - Cloning, Molecular KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Mesocricetus KW - CHO Cells KW - Gene Expression Regulation -- drug effects KW - Gene Dosage KW - Open Reading Frames -- genetics KW - Cell Line KW - Cricetinae KW - DNA Damage KW - RNA, Messenger -- physiology KW - Cell Division -- physiology KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78041645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=A+novel+DNA+damage-inducible+transcript%2C+gadd7%2C+inhibits+cell+growth%2C+but+lacks+a+protein+product.&rft.au=Hollander%2C+M+C%3BAlamo%2C+I%3BFornace%2C+A+J&rft.aulast=Hollander&rft.aufirst=M&rft.date=1996-05-01&rft.volume=24&rft.issue=9&rft.spage=1589&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-25 N1 - Date created - 1996-07-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U26834; GENBANK N1 - SuppNotes - Cited By: Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] Science. 1994 Nov 25;266(5189):1376-80 [7973727] Nucleic Acids Res. 1986 Jul 25;14(14):5793-811 [2426659] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4298-302 [3035577] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] J Mol Biol. 1987 Aug 20;196(4):947-50 [3681984] Nature. 1988 Jan 21;331(6153):280-3 [2447506] Mol Cell Biol. 1988 May;8(5):2195-203 [3133554] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8800-4 [3194391] J Cell Biol. 1989 Jun;108(6):2045-57 [2500443] Mol Cell Biol. 1989 Oct;9(10):4196-203 [2573827] Mol Cell Biol. 1990 Jan;10(1):28-36 [1688465] Biotechniques. 1990 Aug;9(2):174-9 [2205249] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] Genes Dev. 1992 Mar;6(3):439-53 [1547942] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3266-70 [1314384] Cell. 1992 Oct 30;71(3):515-26 [1423610] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11026-30 [1438308] Genes Chromosomes Cancer. 1992 Nov;5(4):278-85 [1283316] Nature. 1993 Apr 22;362(6422):747-9 [8385745] J Biol Chem. 1993 Nov 15;268(32):24385-93 [8226988] Mol Cell Biol. 1994 Mar;14(3):1743-51 [8114708] Mol Cell Biol. 1994 Apr;14(4):2361-71 [8139541] Eur J Hum Genet. 1993;1(2):109-13 [8055321] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sustained cocaine abstinence in methadone maintenance patients through voucher-based reinforcement therapy. AN - 78037213; 8624184 AB - Chronic cocaine abuse remains a serious and costly public health problem. This study assessed the effectiveness of a voucher-based reinforcement contingency in producing sustained cocaine abstinence. A randomized controlled trial compared voucher-based reinforcement of cocaine abstinence to noncontingent voucher presentation. Patients were selected from 52 consecutively admitted injecting heroin abusers in a methadone maintenance treatment program. Patients with heavy cocaine use during baseline period (N = 37) participated. Except where otherwise indicated, the term cocaine abuse is used in this article in a generic sense and not according to the DSM-III-R definition. Patients exposed to abstinence reinforcement received a voucher for each cocaine-free urine sample (ie, negative for benzoylecgonine) provided three times per week throughout a 12-week period; the vouchers had monetary values that increased as the number of consecutive cocaine-free urine samples increased. Control patients received noncontingent vouchers that were matched in pattern and amount to the vouchers received by patients in the abstinence reinforcement group. Patients receiving vouchers for cocaine-free urine samples achieved significantly more weeks of cocaine abstinence (P = .007) and significantly longer durations of sustained cocaine abstinence (P = .001) than controls. Nine patients (47%) receiving vouchers for cocaine-free urine samples achieved between 7 and 12 weeks of sustained cocaine abstinence; only one control patient (6%) achieved more than 2 weeks of sustained abstinence. Among patients receiving vouchers for cocaine-free urine samples, those who achieved sustained abstinence ( > or = 5 weeks) had significantly lower concentrations of benzoylecgonine in baseline urine samples than those who did not achieve sustained abstinence (P < or = .01). Patients receiving voucher reinforcement rated the overall treatment quality significantly higher than controls (P = .002). Voucher-based reinforcement contingencies can produce sustained cocaine abstinence in injecting polydrug abusers. JF - Archives of general psychiatry AU - Silverman, K AU - Higgins, S T AU - Brooner, R K AU - Montoya, I D AU - Cone, E J AU - Schuster, C R AU - Preston, K L AD - Addiction Research Center, Intramural Research Program of the National Institute on Drug Abuse, Baltimore, Md, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 409 EP - 415 VL - 53 IS - 5 SN - 0003-990X, 0003-990X KW - Cocaine KW - I5Y540LHVR KW - Methadone KW - UC6VBE7V1Z KW - Abridged Index Medicus KW - Index Medicus KW - Combined Modality Therapy KW - Substance Abuse, Intravenous -- rehabilitation KW - Substance Abuse Detection KW - Humans KW - Adult KW - Treatment Outcome KW - Substance Abuse, Intravenous -- therapy KW - Male KW - Female KW - Substance Abuse, Intravenous -- psychology KW - Substance-Related Disorders -- therapy KW - Methadone -- therapeutic use KW - Token Economy KW - Behavior Therapy KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78037213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Sustained+cocaine+abstinence+in+methadone+maintenance+patients+through+voucher-based+reinforcement+therapy.&rft.au=Silverman%2C+K%3BHiggins%2C+S+T%3BBrooner%2C+R+K%3BMontoya%2C+I+D%3BCone%2C+E+J%3BSchuster%2C+C+R%3BPreston%2C+K+L&rft.aulast=Silverman&rft.aufirst=K&rft.date=1996-05-01&rft.volume=53&rft.issue=5&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Platelet binding of IgG from patients with heparin-induced thrombocytopenia. AN - 78033388; 8621980 AB - Although heparin induces immune-mediated thrombocytopenia, it has been difficult to demonstrate heparin specificity of the putative immunoglobin. Recently, however, a body of data has indicated that platelet factor 4 (PF4) is required for heparin-induced thrombocytopenia (HIT) antibody to bind to heparin. Using viable platelets in a physiologic buffer, we have now documented specific and reversible platelet binding of iodine 125-labeled IgG from 5 patients with HIT and binding of 125I-labeled F(ab')2 from 2 of them. The binding requires the presence of both heparin and PF4 in a molar ratio of approximately 1:1. We have also shown that platelet activation increases HIT antibody binding. Our data suggest that the F(ab')2 domain of HIT antibody binds to heparin-PF4 complexes that accumulate on the platelet surface when equimolar concentrations of heparin and PF4 are present. JF - The Journal of laboratory and clinical medicine AU - Horne, M K AU - Alkins, B R AD - Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 435 EP - 442 VL - 127 IS - 5 SN - 0022-2143, 0022-2143 KW - Immunoglobulin Fab Fragments KW - 0 KW - Immunoglobulin G KW - Iodine Radioisotopes KW - Platelet Factor 4 KW - 37270-94-3 KW - Heparin KW - 9005-49-6 KW - Abridged Index Medicus KW - Index Medicus KW - Immunoglobulin Fab Fragments -- blood KW - Platelet Factor 4 -- metabolism KW - Humans KW - Platelet Activation KW - Platelet Factor 4 -- immunology KW - Immunoglobulin G -- blood KW - Blood Platelets -- immunology KW - Heparin -- administration & dosage KW - Thrombocytopenia -- immunology KW - Thrombocytopenia -- chemically induced KW - Heparin -- therapeutic use KW - Blood Platelets -- metabolism KW - Heparin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78033388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+laboratory+and+clinical+medicine&rft.atitle=Platelet+binding+of+IgG+from+patients+with+heparin-induced+thrombocytopenia.&rft.au=Horne%2C+M+K%3BAlkins%2C+B+R&rft.aulast=Horne&rft.aufirst=M&rft.date=1996-05-01&rft.volume=127&rft.issue=5&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+laboratory+and+clinical+medicine&rft.issn=00222143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-18 N1 - Date created - 1996-06-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Lab Clin Med. 1996 May;127(5):418-9 [8621977] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of hepatic aneuploidy in vivo by tamoxifen, toremifene and idoxifene in female Sprague-Dawley rats. AN - 78025405; 8640912 AB - Since tamoxifen is efficacious for the prevention of second primary breast neoplasms in humans and has a low reported incidence of acute side effects, several structurally related compounds have been developed for the treatment of breast cancer including toremifene and idoxifene. We have compared the karyotypic alterations that occur after a single per os administration of 35 mg/kg of tamoxifen, toremifene or idoxifene to female Sprague-Dawley rats. One day following treatment, the rats were sacrificed and the hepatocytes isolated and cultured. After 47 h in culture, colcemid was added for 3 h prior to harvest of the hepatocytes for karyotypic evaluation. At least 100 metaphase spreads were examined for each of five rats per treatment. Toremifene resulted in aneuploidy in 50 +/- 7% of the cells examined and idoxifene induced a 57 +/- 4% aneuploidy compared with the 85 +/- 7% level induced by tamoxifen. Since the level of aneuploidy in solvent-treated rats was 3 +/- 3 %, the induction of aneuploidy in at least 50% of the cells from rats treated with tamoxifen, toremifene or idoxifene was highly significant. Analysis of electron micrographs of cultures treated with these antiestrogens demonstrated a range of phenotypes including multipolar spindles in toremifene-treated rats and condensed chromosomes in the presence of an intact nuclear envelope in occasional idoxifene-treated rat hepatocytes. The exclusion of chromosomes from the spindle apparatus and the lagging of some chromosomes on the metaphase plate correlate with the high rate of induction of aneuploidy in the rat liver as determined by karyotypic analysis of hepatocytes from rats treated with these triphenylethylenes. JF - Carcinogenesis AU - Sargent, L M AU - Dragan, Y P AU - Sattler, C AU - Bahnub, N AU - Sattler, G AU - Martin, P AU - Cisneros, A AU - Mann, J AU - Thorgeirsson, S AU - Jordan, V C AU - Pitot, H C AD - National Cancer Institute, Laboratory of Experimental Carcinogenesis, Bethesda, MD, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1051 EP - 1056 VL - 17 IS - 5 SN - 0143-3334, 0143-3334 KW - Antineoplastic Agents, Hormonal KW - 0 KW - DNA Adducts KW - Estrogen Antagonists KW - Tamoxifen KW - 094ZI81Y45 KW - idoxifene KW - 456UXE9867 KW - Toremifene KW - 7NFE54O27T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - DNA Adducts -- analysis KW - Female KW - Toremifene -- toxicity KW - Tamoxifen -- toxicity KW - Liver -- ultrastructure KW - Estrogen Antagonists -- toxicity KW - Aneuploidy KW - Liver -- drug effects KW - Tamoxifen -- analogs & derivatives KW - Antineoplastic Agents, Hormonal -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78025405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Induction+of+hepatic+aneuploidy+in+vivo+by+tamoxifen%2C+toremifene+and+idoxifene+in+female+Sprague-Dawley+rats.&rft.au=Sargent%2C+L+M%3BDragan%2C+Y+P%3BSattler%2C+C%3BBahnub%2C+N%3BSattler%2C+G%3BMartin%2C+P%3BCisneros%2C+A%3BMann%2C+J%3BThorgeirsson%2C+S%3BJordan%2C+V+C%3BPitot%2C+H+C&rft.aulast=Sargent&rft.aufirst=L&rft.date=1996-05-01&rft.volume=17&rft.issue=5&rft.spage=1051&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-17 N1 - Date created - 1996-07-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Carcinogenesis 1996 Jun;17(6):1393 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic silicosis, cirrhosis, and liver tumors in mice and hamsters: studies of transforming growth factor beta expression. AN - 78024919; 8621163 AB - Hepatic silicosis, cirrhosis, liver cell adenoma, and carcinomas developed in nude mice (NCr-Nu) given quartz by the subcutaneous and intraperitoneal routes. Syrian golden hamsters (15:16 EHS:cr) given quartz by both routes developed extensive fibrosis and cirrhosis and had higher morbidity and mortality rates after 3 months. Crystalline silica (quartz) induces fibrosis, adenomas, and carcinomas in the lungs of Fisher 344 rats, but certain strains of mice and hamsters are resistant to quartz-induced pulmonary carcinogenesis. Pulmonary fibrosis, however, is minimal in mice and absent in hamsters who received quartz intratracheally. To determine whether species differences are due to organ-specific rather than species-specific factors, susceptibility of the liver to quartz toxicity was investigated in nude mice and hamsters. The present study shows that the differential manifestations of quartz toxicity by these rodent species are dependent on factors that are organ-specific rather than host-specific. At 3 months, hepatocytes in mice were immunostained with intracellular transforming growth factor (TGF) beta 1 (LC 1-30) but not with TGF-beta 1 latency-associated peptide (LAP) protein (266-278); at 12 months, hepatocytes were immunostained with TGF-beta 1 LAP (266-278) but not with TGF-beta 1 (LC1-30). The hepatocytes of hamsters at 3 months showed immunoreactivities to TGF-beta 1 LAP (266-278) and TGF-beta 1 (LC1-30); immunostaining to TGF-beta 1 (LC1-30) was detected in nonparenchymal cells. Extracellular TGF-beta 1 (CC1-30) was detected in the silicotic granulomas and fibrous tissue in livers of both species. Quartz-induced liver carcinoma did not express TGF-beta 1 LAP (266-278) and LC (1-30) proteins, but these were detected in the cells of the adenoma in the same liver. Control animals showed no hepatic lesions nor immunoreactivity to TGF-beta 1. The spatial and temporal patterns of expression of TGF-beta 1, TGF-beta 2, TGF-beta receptor type II messenger RNAs (mRNAs), and TGF-beta 1 proteins in the different hepatic lesions suggests that TGF-beta isoforms may play a role in the pathogenesis of quartz-induced fibrosis, cirrhosis, liver cell adenoma, and carcinoma. JF - Hepatology (Baltimore, Md.) AU - Williams, A O AU - Knapton, A D AD - Laboratory of Experimental Pathology, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1268 EP - 1275 VL - 23 IS - 5 SN - 0270-9139, 0270-9139 KW - RNA, Messenger KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Quartz KW - 14808-60-7 KW - Index Medicus KW - Receptors, Transforming Growth Factor beta -- genetics KW - Adenoma, Liver Cell -- metabolism KW - Animals KW - Liver -- pathology KW - Blotting, Northern KW - Chemical and Drug Induced Liver Injury KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Liver -- metabolism KW - Mice, Nude KW - Mice KW - Adenoma, Liver Cell -- chemically induced KW - Quartz -- toxicity KW - RNA, Messenger -- metabolism KW - Mesocricetus KW - Microscopy, Electron KW - Adenoma, Liver Cell -- pathology KW - Microscopy, Immunoelectron KW - Immunohistochemistry KW - Female KW - Male KW - Cricetinae KW - Liver Cirrhosis, Experimental -- chemically induced KW - Silicosis -- metabolism KW - Silicosis -- pathology KW - Liver Neoplasms, Experimental -- metabolism KW - Liver Neoplasms, Experimental -- chemically induced KW - Liver Cirrhosis, Experimental -- metabolism KW - Liver Diseases -- metabolism KW - Liver Neoplasms, Experimental -- pathology KW - Liver Diseases -- pathology KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Liver Cirrhosis, Experimental -- pathology KW - Silicosis -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78024919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Hepatic+silicosis%2C+cirrhosis%2C+and+liver+tumors+in+mice+and+hamsters%3A+studies+of+transforming+growth+factor+beta+expression.&rft.au=Williams%2C+A+O%3BKnapton%2C+A+D&rft.aulast=Williams&rft.aufirst=A&rft.date=1996-05-01&rft.volume=23&rft.issue=5&rft.spage=1268&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-19 N1 - Date created - 1996-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A lysine residue of the cannabinoid receptor is critical for receptor recognition by several agonists but not WIN55212-2. AN - 78018557; 8622639 AB - Lys192 in the third transmembrane domain of the human CB1 cannabinoid receptor was converted to an alanine to study its role in receptor recognition and activation by agonists. HU-210, CP-55940, WIN55212-2, and anandamide, four cannabinoid agonists with distinct chemical structures, were used to characterize the wild-type and the mutant receptors. In human embryonal kidney 293 cells stably expressing the wild-type receptor, specific binding to [3H]WIN55212-2 and inhibition of cAMP accumulation by cannabinoid agonists were demonstrated, with different ligands exhibiting the expected rank orders of potency and stereoselectivity in competition binding and functional assays. In cells expressing the mutant receptor, the binding affinity of the receptor for [3H]WIN55212-2 was only slightly affected (the Kd for the mutant receptor was twice that of the wild-type), and the ability of WIN55212-2 to inhibit cAMP accumulation was unchanged. However, HU-210, CP-55940, and anandamide were unable to compete for [3H]WIN55212-2 binding to the mutant receptor. In addition, the potencies of HU-210, CP-55940, and anandamide in inhibiting cAMP accumulation were reduced by > 100-fold. These results demonstrate that Lys192 is critical for receptor binding by HU-210, CP-55940, and anandamide. Because Lys192 is not important for receptor binding and activation by WIN55212-2, WIN55212-2 must interact with the cannabinoid receptor through at least one point of interaction that is distinct from those of the three other agonists. JF - Molecular pharmacology AU - Song, Z H AU - Bonner, T I AD - Laboratory of Cell Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. zhsong@codon.nih.gov Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 891 EP - 896 VL - 49 IS - 5 SN - 0026-895X, 0026-895X KW - Benzoxazines KW - 0 KW - DNA Primers KW - Ligands KW - Morpholines KW - Naphthalenes KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Win 55212-2 KW - 5H31GI9502 KW - Cyclic AMP KW - E0399OZS9N KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Cyclic AMP -- metabolism KW - Radioligand Assay KW - Cell Line KW - Structure-Activity Relationship KW - DNA Primers -- chemistry KW - Naphthalenes -- chemistry KW - Receptors, Drug -- agonists KW - Lysine -- chemistry KW - Morpholines -- chemistry KW - Receptors, Drug -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78018557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=A+lysine+residue+of+the+cannabinoid+receptor+is+critical+for+receptor+recognition+by+several+agonists+but+not+WIN55212-2.&rft.au=Song%2C+Z+H%3BBonner%2C+T+I&rft.aulast=Song&rft.aufirst=Z&rft.date=1996-05-01&rft.volume=49&rft.issue=5&rft.spage=891&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-19 N1 - Date created - 1996-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor. AN - 78018461; 8611693 AB - Stem cell factor (SCF) is a hematopoietic growth factor that interacts with the receptor tyrosine kinase, c-kit. We have found that SCF-stimulates rapid and transient tyrosine phosphorylation of JAK2 in human and murine cell lines, as well as in normal human progenitor cells. JAK2 and c-kit were associated in unstimulated cells with further recruitment of JAK2 to the c-kit receptor complex after SCF stimulation. Treatment of cells with JAK2 antisense oligonucleotides resulted in a 46% decrease in SCF-induced proliferation. These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway. JF - Blood AU - Weiler, S R AU - Mou, S AU - DeBerry, C S AU - Keller, J R AU - Ruscetti, F W AU - Ferris, D K AU - Longo, D L AU - Linnekin, D AD - Division of Cancer Treatment, and Biological Carcinogenesis and Development Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 3688 EP - 3693 VL - 87 IS - 9 SN - 0006-4971, 0006-4971 KW - Proto-Oncogene Proteins KW - 0 KW - Stem Cell Factor KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-kit KW - JAK2 protein, human KW - EC 2.7.10.2 KW - Jak2 protein, mouse KW - Janus Kinase 2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Mice KW - Cell Line KW - Phosphorylation -- drug effects KW - Proto-Oncogene Proteins c-kit -- metabolism KW - Stem Cell Factor -- pharmacology KW - Signal Transduction -- drug effects KW - Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78018461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=JAK2+is+associated+with+the+c-kit+proto-oncogene+product+and+is+phosphorylated+in+response+to+stem+cell+factor.&rft.au=Weiler%2C+S+R%3BMou%2C+S%3BDeBerry%2C+C+S%3BKeller%2C+J+R%3BRuscetti%2C+F+W%3BFerris%2C+D+K%3BLongo%2C+D+L%3BLinnekin%2C+D&rft.aulast=Weiler&rft.aufirst=S&rft.date=1996-05-01&rft.volume=87&rft.issue=9&rft.spage=3688&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-06 N1 - Date created - 1996-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phylogenetic history of LINE-1 among arvicolid rodents. AN - 78016440; 8676737 AB - The extent of restriction fragment sharing among arvicolid rodents was examined following Southern blotting with a reverse transcriptase region probe from long interspersed nuclear element 1 (LINE-1 or L1). DNAs from 30 species belonging to nine genera were digested with 11 restriction endonucleases. Following hybridization discrete bands were scored with respect to their presence or absence and intensity, and both within- and between-species comparisons were conducted. Intraspecific analyses revealed low but detectable levels of variation. Interspecific comparisons revealed three groups of bands: those present in all 30 species (6 out of a total of 248 bands), those phylogenetically informative in two or more species (130 out of 248), and those unique to a single species (114 out of 248). A multistate data matrix consisting of species by codes representing the intensities of informative bands was analyzed by maximum parsimony. Further, distance values between species were converted to rates using estimated fossil divergence times. Both the parsimony and rate analyses revealed differences between species in the extent of band sharing and in the intensities of common bands, indicating that the amplification and movement of LINE elements has occurred in episodic bursts during the history of this group. Systematic interpretations of the evolutionary trees were concordant with those previously obtained using other data sets, suggesting that although the amplification of repetitive sequences may occur episodically in this taxonomic group, there do appear to be some constraints. JF - Molecular biology and evolution AU - Modi, W S AD - Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick, Maryland 21702-1201, USA. modi@fcrfv2.ncifcrf.gov Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 633 EP - 641 VL - 13 IS - 5 SN - 0737-4038, 0737-4038 KW - Index Medicus KW - Animals KW - Blotting, Southern KW - Biological Evolution KW - Genetic Variation -- genetics KW - Species Specificity KW - Gene Amplification KW - Phylogeny KW - Polymorphism, Restriction Fragment Length KW - Repetitive Sequences, Nucleic Acid -- genetics KW - Arvicolinae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78016440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+and+evolution&rft.atitle=Phylogenetic+history+of+LINE-1+among+arvicolid+rodents.&rft.au=Modi%2C+W+S&rft.aulast=Modi&rft.aufirst=W&rft.date=1996-05-01&rft.volume=13&rft.issue=5&rft.spage=633&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+and+evolution&rft.issn=07374038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-15 N1 - Date created - 1996-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ahr locus phenotype in congenic mice influences hepatic and pulmonary DNA adduct levels of 2-amino-3-methylimidazo[4,5-f]quinoline in the absence of cytochrome P450 induction. AN - 78016386; 8622637 AB - The potent food mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) undergoes metabolic N-hydroxylation by cytochromes P450, including cytochrome P450 1A2, followed by generation of an unstable ester catalyzed by acetyltransferases; promutagenic DNA adducts result. Genetic polymorphisms in these enzymes have been implicated in human cancer risk related to arylamine exposure. We investigated the effects of Ahr locus and acetylator polymorphisms on 32P-postlabeled IQ/DNA adducts in lungs and livers of female C57BL/6 mice congenic for slow acetylation and/or Ahr-nonresponsiveness; some groups were pretreated with beta-naphthoflavone (beta NF), a cytochrome P450 1A inducer. Total adducts in lung were doubled by beta NF pretreatment in Ahr-responsive mice only and consisted of < or = 30% adduct 2 and < or = 60% adduct 3. In contrast, in Ahr-nonresponsive mice, adducts 2 and 3 were each < or= 7% of the total. Livers of noninduced Ahr-responsive mice formed 6-18-fold more adducts than those of nonresponsive mice. This striking difference was not due to altered levels of cyp1a-2, as indicated by specific enzyme assays and immunoblotting, and was not accompanied by a comparable increase in the ability of liver preparations to activate IQ to a mutagen in the Ames test. Pretreatment of responsive mice with beta NF to induce cyp1a-1 and cyp1a-2 led to a reduction in liver adduct levels. Acetylation phenotype also had a significant effect in Ahr-responsive mice, with 3-fold more adducts in slow than in rapid acetylators. These results indicate that in uninduced mice, the normal Ah receptor facilitates formation of IQ/DNA adducts in liver and alters the profile of adducts in lung, via an unknown mechanism, whereas the Ah receptor-dependent enzyme induction reduces adducts in liver, probably due to increased detoxification, but increases them in lung. JF - Molecular pharmacology AU - Nerurkar, P V AU - Schut, H A AU - Anderson, L M AU - Riggs, C W AU - Fornwald, L W AU - Davis, C D AU - Snyderwine, E G AU - Thorgeirsson, S S AU - Weber, W W AU - Rice, J M AU - Levy, G N AD - Laboratory of Comparative Carcinogenesis, Frederick Cancer Research and Development Center, National Cancer Institute, National Institutes of Health, Maryland 21702, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 874 EP - 881 VL - 49 IS - 5 SN - 0026-895X, 0026-895X KW - DNA Adducts KW - 0 KW - DNA-(2-amino-3-methylimidazo(4,5-f)quinoline) adduct KW - Quinolines KW - Receptors, Aryl Hydrocarbon KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Phenotype KW - Mice, Inbred Strains KW - Animals KW - Acetylation KW - Enzyme Induction KW - Mice KW - Female KW - Quinolines -- metabolism KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Lung -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78016386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Ahr+locus+phenotype+in+congenic+mice+influences+hepatic+and+pulmonary+DNA+adduct+levels+of+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline+in+the+absence+of+cytochrome+P450+induction.&rft.au=Nerurkar%2C+P+V%3BSchut%2C+H+A%3BAnderson%2C+L+M%3BRiggs%2C+C+W%3BFornwald%2C+L+W%3BDavis%2C+C+D%3BSnyderwine%2C+E+G%3BThorgeirsson%2C+S+S%3BWeber%2C+W+W%3BRice%2C+J+M%3BLevy%2C+G+N&rft.aulast=Nerurkar&rft.aufirst=P&rft.date=1996-05-01&rft.volume=49&rft.issue=5&rft.spage=874&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-19 N1 - Date created - 1996-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetic evidence of the occurrence of breast cancer as an integral tumor in patients with the hereditary nonpolyposis colorectal carcinoma syndrome. AN - 78014110; 8646682 AB - The hereditary nonpolyposis colorectal carcinoma (HNPCC) syndrome is an autosomal dominant genetic disorder caused by the inheritance of a mutation in one of a family of genes encoding DNA mismatch repair (MMR) proteins. HNPCC manifests as genetic instability in linked tumors. Clinically, the syndrome is characterized by early onset malignancies, primarily of the colon and endometrium, with an increased incidence of tumors at other gastrointestinal sites, upper urologic tract, ovary, and pancreas as well. However, the inclusion of breast cancer as an integral tumor of this syndrome is controversial. Mutation screening of MMR genes was carried out by single strand conformation polymorphism (SSCP) and sequencing analyses of genomic DNA prepared from normal lymphocytes. Expression analysis was performed by SSCP. Sequence analyses of cDNA was prepared from breast tumor tissue and normal lymphocytes. Genetic instability was assessed by comparing the electrophoretic mobility of polymerase chain reaction (PCR) products using multiple microsatellite markers. A 4-bp frameshift mutation in the hMLH1 gene was found to segregate with disease in the germlines of the affected members of a large kindred HNPCC. Expression of only the mutant allele was observed in the breast cancer tissue of one family member, however both alleles were observed in her normal tissue. This breast cancer exhibited widespread microsatellite instability, as did breast cancers obtained from several other HNPCC kindreds. These data indicate that breast cancer may result from the inheritance of a mutant MMR gene, and that breast cancer may occur as an integral tumor in the HNPCC syndrome. JF - Cancer AU - Risinger, J I AU - Barrett, J C AU - Watson, P AU - Lynch, H T AU - Boyd, J AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Chapel Hill, North Carolina, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 1836 EP - 1843 VL - 77 IS - 9 SN - 0008-543X, 0008-543X KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Carrier Proteins KW - DNA-Binding Proteins KW - MLH1 protein, human KW - Neoplasm Proteins KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - MSH2 protein, human KW - EC 3.6.1.3 KW - MutL Protein Homolog 1 KW - MutS Homolog 2 Protein KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Aged KW - Gene Expression Regulation, Neoplastic KW - Alleles KW - Adult KW - Neoplasm Proteins -- genetics KW - Endometrial Neoplasms -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Adolescent KW - Male KW - Colonic Neoplasms -- genetics KW - Microsatellite Repeats -- genetics KW - Age of Onset KW - Genes, Dominant -- genetics KW - Sequence Analysis, DNA KW - Polymorphism, Single-Stranded Conformational KW - Frameshift Mutation -- genetics KW - DNA Repair -- genetics KW - Molecular Biology KW - Mutation -- genetics KW - Middle Aged KW - Female KW - Breast Neoplasms -- genetics KW - Breast Neoplasms, Male -- genetics KW - Colorectal Neoplasms, Hereditary Nonpolyposis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78014110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Molecular+genetic+evidence+of+the+occurrence+of+breast+cancer+as+an+integral+tumor+in+patients+with+the+hereditary+nonpolyposis+colorectal+carcinoma+syndrome.&rft.au=Risinger%2C+J+I%3BBarrett%2C+J+C%3BWatson%2C+P%3BLynch%2C+H+T%3BBoyd%2C+J&rft.aulast=Risinger&rft.aufirst=J&rft.date=1996-05-01&rft.volume=77&rft.issue=9&rft.spage=1836&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-22 N1 - Date created - 1996-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of cyclosporin A on the synthesis, excretion, and metabolism of endothelin in the rat. AN - 78011466; 8621208 AB - Increasing evidence suggests that endothelin, a potent vasoconstrictor, is implicated in cyclosporin A (CsA)-induced nephrotoxicity. Increased levels of urinary and circulating endothelin have been described in CsA-treated humans and animals. The exact mechanisms by which CsA induces these increases are still unknown, and no data indicate whether these elevated levels reflect increased synthesis or decreased clearance of endothelin. In the present study, we investigated the effects of CsA administration (50 mg/kg per day i.p. for 6 days) to rats on plasma and urinary levels of endothelin; expression of endothelin-1 (ET-1), ET-3, and endothelin-converting enzyme in renal tissue; clearance of infused 125I-ET-1; and degradation of 125I-ET-1 by recombinant neutral endopeptidase. Rats given CsA for 6 days developed severe renal insufficiency, as shown by a 74% decrease in creatinine clearance rate (Ccr) (P < .006). Ccr was remarkably improved in CsA-treated rats that received bosentan, the combined antagonist of both endothelin A and endothelin B receptors. Urinary excretion of endothelin increased from an undetectable level to 31.7 +/- 6.0 pg/24 h (P < .001), and plasma levels of endothelin were unchanged (2.8 +/- 0.2 to 3.1 +/- 0.2 pg/mL). Reverse transcription followed by quantitative polymerase chain reaction revealed that ET-1 mRNA in the renal medulla increased by 59% (P < .006), whereas the expression of both ET-3 and endothelin-converting enzyme was unchanged. In other rats, neither acute nor chronic treatment with CsA affected either the clearance of 125I-ET-1 from the blood or the renal and pulmonary uptake of the peptide. Moreover, CsA did not affect the degradation of 125I-ET-1 by highly purified recombinant neutral endopeptidase, a well-known endothelinase. Taken together, these data suggest that the elevated urinary endothelin levels obtained after CsA treatment originate from the kidney and reflect increased renal synthesis of ET-1. Moreover, the production of endothelin appears to be regulated at the mRNA transcription level, and expressions of ET-1 and ET-3 are regulated independently. JF - Hypertension (Dallas, Tex. : 1979) AU - Abassi, Z A AU - Pieruzzi, F AU - Nakhoul, F AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1754, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1140 EP - 1148 VL - 27 IS - 5 SN - 0194-911X, 0194-911X KW - Endothelins KW - 0 KW - Molecular Probes KW - Recombinant Proteins KW - Sulfonamides KW - Cyclosporine KW - 83HN0GTJ6D KW - Creatinine KW - AYI8EX34EU KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Neprilysin KW - EC 3.4.24.11 KW - Endothelin-Converting Enzymes KW - EC 3.4.24.71 KW - bosentan KW - Q326023R30 KW - Index Medicus KW - Animals KW - Neprilysin -- metabolism KW - Aspartic Acid Endopeptidases -- metabolism KW - Metalloendopeptidases -- genetics KW - Rats KW - Molecular Probes -- genetics KW - Rats, Sprague-Dawley KW - Aspartic Acid Endopeptidases -- genetics KW - Base Sequence KW - Creatinine -- metabolism KW - Sulfonamides -- pharmacology KW - Molecular Sequence Data KW - Metalloendopeptidases -- metabolism KW - Male KW - Kidney -- metabolism KW - Endothelins -- metabolism KW - Cyclosporine -- pharmacology KW - Endothelins -- genetics KW - Kidney -- drug effects KW - Endothelins -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78011466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.atitle=Effects+of+cyclosporin+A+on+the+synthesis%2C+excretion%2C+and+metabolism+of+endothelin+in+the+rat.&rft.au=Abassi%2C+Z+A%3BPieruzzi%2C+F%3BNakhoul%2C+F%3BKeiser%2C+H+R&rft.aulast=Abassi&rft.aufirst=Z&rft.date=1996-05-01&rft.volume=27&rft.issue=5&rft.spage=1140&rft.isbn=&rft.btitle=&rft.title=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.issn=0194911X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-14 N1 - Date created - 1996-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study. AN - 78010225; 8622076 AB - To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen--vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Kalamazoo, MI) (VATH)--in patients with stage II node-positive breast carcinoma. Nine hundred forty-five women were treated with a 6-week induction course of CMFVP. They were then randomized to receive one of two consolidation CMFVP regimens: 6-week courses or 2-week courses. Following completion of CMFVP consolidation, patients were again randomized to either continue the CMFVP regimen or to receive six escalating doses of VATH. Among all patients, with a median follow-up time of 11.5 years, there is no statistically significant difference in disease-free survival (DFS) between the two consolidation CMFVP regimens. VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040). For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positive lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years). This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-positive patients. Chemotherapy with crossover to escalating doses of VATH following CMFVP was well tolerated and effective. Inauguration of VATH as a treatment intensification at the eighth month produced a major increase in relapse-free and overall survival. The observation that sensitivity to VATH is retained so long after mastectomy raises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of cross-over designs in future trials to postoperative adjuvant chemotherapy regimens. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Perloff, M AU - Norton, L AU - Korzun, A H AU - Wood, W C AU - Carey, R W AU - Gottlieb, A AU - Aust, J C AU - Bank, A AU - Silver, R T AU - Saleh, F AU - Canellos, G P AU - Perry, M C AU - Weiss, R B AU - Holland, J F AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7329, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1589 EP - 1598 VL - 14 IS - 5 SN - 0732-183X, 0732-183X KW - Vincristine KW - 5J49Q6B70F KW - Vinblastine KW - 5V9KLZ54CY KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Thiotepa KW - 905Z5W3GKH KW - Fluoxymesterone KW - 9JU12S4YFY KW - Fluorouracil KW - U3P01618RT KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Probability KW - Fluoxymesterone -- administration & dosage KW - Humans KW - Vincristine -- administration & dosage KW - Aged KW - Doxorubicin -- administration & dosage KW - Postoperative Period KW - Fluorouracil -- administration & dosage KW - Adult KW - Vinblastine -- administration & dosage KW - Thiotepa -- administration & dosage KW - Follow-Up Studies KW - Middle Aged KW - Methotrexate -- administration & dosage KW - Prednisone -- administration & dosage KW - Chemotherapy, Adjuvant KW - Female KW - Survival Analysis KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- surgery KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78010225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Postsurgical+adjuvant+chemotherapy+of+stage+II+breast+carcinoma+with+or+without+crossover+to+a+non-cross-resistant+regimen%3A+a+Cancer+and+Leukemia+Group+B+study.&rft.au=Perloff%2C+M%3BNorton%2C+L%3BKorzun%2C+A+H%3BWood%2C+W+C%3BCarey%2C+R+W%3BGottlieb%2C+A%3BAust%2C+J+C%3BBank%2C+A%3BSilver%2C+R+T%3BSaleh%2C+F%3BCanellos%2C+G+P%3BPerry%2C+M+C%3BWeiss%2C+R+B%3BHolland%2C+J+F&rft.aulast=Perloff&rft.aufirst=M&rft.date=1996-05-01&rft.volume=14&rft.issue=5&rft.spage=1589&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-18 N1 - Date created - 1996-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coexpression of stem cell factor and c-kit in embryonic and adult liver. AN - 78008868; 8612701 AB - Stem cell factor and its receptor c-kit constitute an important signal transduction system implicated in survival, proliferation, and differentiation of stem cells in hematopoiesis, gametogenesis, and melanogenesis. In the present study we used both immunocytochemical methods and Western analysis to demonstrate the presence of this cytokine/receptor system in both embryonic and adult rat liver. Stem cell factor was present in the ductular cells around the portal vein during the late embryonic stage of the liver. In the adult liver both bile ducts and bile ductules were positive for stem cell factor and c-kit. When the activation of the liver stem cell compartment was induced by combining administration of acetylaminofluorene and partial hepatectomy, both stem cell factor and c-kit were expressed in the infiltrating oval cell population, but absent in the newly formed basophilic hepatocytes. Activation of oval cell proliferation following administration Of D-galactosamine also produced a similar but less prominent increase in the level of the stem cell factor. Our data suggest that the stem cell factor/c-kit signal transduction system is involved in the development of bile ducts and that it may also be an important member of the growth factor/receptor systems associated with the biology of liver stem cells. JF - Experimental cell research AU - Fujio, K AU - Hu, Z AU - Evarts, R P AU - Marsden, E R AU - Niu, C H AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 243 EP - 250 VL - 224 IS - 2 SN - 0014-4827, 0014-4827 KW - Stem Cell Factor KW - 0 KW - Proto-Oncogene Proteins c-kit KW - EC 2.7.10.1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Blotting, Western KW - Age Factors KW - Stem Cells -- chemistry KW - Biliary Tract -- cytology KW - Epithelium -- metabolism KW - Stem Cells -- metabolism KW - Immunohistochemistry KW - Male KW - Female KW - Epithelium -- chemistry KW - Pregnancy KW - Liver -- cytology KW - Proto-Oncogene Proteins c-kit -- biosynthesis KW - Liver -- metabolism KW - Proto-Oncogene Proteins c-kit -- analysis KW - Stem Cell Factor -- biosynthesis KW - Liver -- embryology KW - Stem Cell Factor -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78008868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Coexpression+of+stem+cell+factor+and+c-kit+in+embryonic+and+adult+liver.&rft.au=Fujio%2C+K%3BHu%2C+Z%3BEvarts%2C+R+P%3BMarsden%2C+E+R%3BNiu%2C+C+H%3BThorgeirsson%2C+S+S&rft.aulast=Fujio&rft.aufirst=K&rft.date=1996-05-01&rft.volume=224&rft.issue=2&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-31 N1 - Date created - 1996-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deletions and insertions in the p53 tumor suppressor gene in human cancers: confirmation of the DNA polymerase slippage/misalignment model. AN - 78008711; 8616861 AB - We analyzed all published deletions and insertions in the p53 gene to assess the relevance of mutagenesis models. Almost all deletions and insertions can be explained by one or more of the following DNA sequence features: monotonic base runs, adjacent or nonadjacent repeats of short tandem sequences, palindromes, and runs of purines or pyrimidines (homocopolymer runs). Increased length of monotonic runs correlates positively with increased frequency of events. Complex frameshift mutations can be explained by the formation of quasi-palindromes, with mismatch excision and replication using one strand of the palindrome as a template. Deletions and insertions in the p53 tumor suppressor gene may reflect both spontaneous and carcinogen-induced mutagenesis. JF - Cancer research AU - Greenblatt, M S AU - Grollman, A P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 2130 EP - 2136 VL - 56 IS - 9 SN - 0008-5472, 0008-5472 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Mutagenesis, Insertional KW - Gene Deletion KW - Genes, Tumor Suppressor KW - Models, Genetic KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78008711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Deletions+and+insertions+in+the+p53+tumor+suppressor+gene+in+human+cancers%3A+confirmation+of+the+DNA+polymerase+slippage%2Fmisalignment+model.&rft.au=Greenblatt%2C+M+S%3BGrollman%2C+A+P%3BHarris%2C+C+C&rft.aulast=Greenblatt&rft.aufirst=M&rft.date=1996-05-01&rft.volume=56&rft.issue=9&rft.spage=2130&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-12 N1 - Date created - 1996-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. AN - 78007808; 8619541 AB - Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor have been reported to potentiate the antiparkinsonian action of levodopa and reverse levodopa-induced motor fluctuations in animal models of Parkinson's disease. To evaluate the effect of NMDA receptor blockade on dyskinesias complicating the response to long-term levodopa therapy, we studied the selective antagonist LY235959 in six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. Drugs were administered subcutaneously, LY235959 at doses of 0.5, 1.0, 3.0, and 5.0 mg/kg and levodopa/benserazide at doses that produced moderate dyskinesias while almost totally reversing parkinsonian signs. Compared with vehicle control injections, LY235959 (3.0 mg/kg) abolished oral dyskinesias and diminished choreic dyskinesias by 68% (p < 0.01). Lower doses had smaller effects, although still significant, on oral dyskinesias (55% reduction at 1.0 mg/kg, p < 0.05). The highest LY235959 dose (5.0 mg/kg) prolonged oral dyskinesia suppression, but tended to increase dystonia severity. LY235959 had no effect on motor function when given alone and did not reduce the antiparkinsonian response to levodopa. These findings suggest that NMDA receptor blockade may ameliorate the dyskinetic complications of long-term levodopa therapy, without diminishing the beneficial effects on parkinsonian signs. JF - Annals of neurology AU - Papa, S M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 574 EP - 578 VL - 39 IS - 5 SN - 0364-5134, 0364-5134 KW - Antiparkinson Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Isoquinolines KW - Receptors, N-Methyl-D-Aspartate KW - LY 235959 KW - 137433-06-8 KW - Levodopa KW - 46627O600J KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Chorea -- chemically induced KW - Dystonia -- drug therapy KW - Behavior, Animal -- drug effects KW - Chorea -- drug therapy KW - Isoquinolines -- pharmacology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Dystonia -- chemically induced KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Macaca mulatta KW - Antiparkinson Agents -- pharmacology KW - Male KW - Female KW - Levodopa -- pharmacology KW - Dyskinesia, Drug-Induced -- drug therapy KW - Parkinson Disease, Secondary -- drug therapy KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78007808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+neurology&rft.atitle=Levodopa-induced+dyskinesias+improved+by+a+glutamate+antagonist+in+Parkinsonian+monkeys.&rft.au=Papa%2C+S+M%3BChase%2C+T+N&rft.aulast=Papa&rft.aufirst=S&rft.date=1996-05-01&rft.volume=39&rft.issue=5&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-13 N1 - Date created - 1996-06-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Neurol. 1996 May;39(5):557-8 [8619538] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ploidy and karyotypic alterations associated with early events in the development of hepatocarcinogenesis in transgenic mice harboring c-myc and transforming growth factor alpha transgenes. AN - 78003405; 8616862 AB - The cooperation of the c-myc oncogene with the growth factor transforming growth factor (TGF)-alpha in development of liver tumors in transgenic mice has been demonstrated previously. In this study, we analyzed the ploidy and karyotype of c-myc, TGF-alpha, parental control, and the double transgenic c-myc/TGF-alpha hepatocytes at 3 weeks of age when the liver is histologically normal and at 10 weeks when the c-myc/TGF-alpha liver is dysplastic and contains basophilic foci. Eighty % of the 10-week hepatocytes were aneuploid, and 32% had chromosomal breakage. Statistically significant breakage was observed in six different chromosomes. Breakage at band A5 and at the border of bands C4/5 of chromosome 1 was observed. Fragile sets on chromosome 4 were most frequent in the middle of the chromosome at bands C2 and C6. Chromosome 6 was fragile at band F2. The region of chromosome 7 at bands B5 and D3 was frequently broken and involved in translocations. Chromosome 12 was broken at bands D1 and D3. The breakage sites on chromosomes 1, 4, 7, and 12 correspond to sites of tumor susceptibility genes in the mouse. Although there was no consistent change in copy number, recurrent translocations between chromosomes 1, 4, 7, 12 and 19 were also observed. These studies demonstrate that the development of dysplasia and basophilic foci in the liver is correlated with aneuploidy and chromosome breakage. The specific fragile sites indicate genetic regions that are altered during early stages of hepatocarcinogenesis. Due to the conservation of genetic linkage groups between mice and humans, the identification of genetic alterations in the mouse during hepatocarcinogenesis may provide critical information about tumor susceptibility genes that are important in the early development of human hepatocellular carcinoma. JF - Cancer research AU - Sargent, L M AU - Sanderson, N D AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 2137 EP - 2142 VL - 56 IS - 9 SN - 0008-5472, 0008-5472 KW - Transforming Growth Factor alpha KW - 0 KW - Index Medicus KW - Karyotyping KW - Animals KW - Gene Transfer Techniques KW - Chromosome Banding KW - Humans KW - Mice KW - Ploidies KW - Mice, Transgenic KW - Cell Division -- genetics KW - Gene Expression Regulation, Neoplastic KW - Liver Neoplasms, Experimental -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Liver Neoplasms, Experimental -- pathology KW - Genes, myc UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78003405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Ploidy+and+karyotypic+alterations+associated+with+early+events+in+the+development+of+hepatocarcinogenesis+in+transgenic+mice+harboring+c-myc+and+transforming+growth+factor+alpha+transgenes.&rft.au=Sargent%2C+L+M%3BSanderson%2C+N+D%3BThorgeirsson%2C+S+S&rft.aulast=Sargent&rft.aufirst=L&rft.date=1996-05-01&rft.volume=56&rft.issue=9&rft.spage=2137&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-12 N1 - Date created - 1996-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of endogenous IL-1 beta and IL-1 receptor antagonist results in opposing effects on HIV expression in chronically infected monocytic cells. AN - 78003142; 8617979 AB - A proportion of HIV-infected individuals experience episodes of localized or systemic bacterial infections caused by Gram-negative bacteria. Many of the clinical side effects of these infections are associated with the production of proinflammatory cytokines, which are induced primarily by LPS, a constituent of the bacterial cell wall of Gram-negative bacteria. The present study examines the mechanisms involved in LPS-mediated induction of HIV expression in U1 cells, a promonocytic cell line chronically infected with HIV. Stimulation of U1 cells by LPS alone induced minimal levels of HIV expression, which was significantly enhanced by granulocyte-macrophage colony-stimulating factor (GM-CSF). Costimulation of U1 cells with LPS plus GM-CSF resulted in the accumulation of steady-state levels of HIV RNA; however, only a weak induction of HIV long terminal repeat-driven transcription, which was not associated with the activation of the cellular transcription factor nuclear factor-kappa B, was noted. Costimulation of cells with LPS plus GM-CSF induced the production of proinflammatory cytokines, IL-8, IL-1 beta and IL-6, but not TNF-alpha. IL-1 receptor antagonist (ra) inhibited LPS enhancement of HIV expression in GM-CSF-stimulated cells, suggesting that endogenous IL-1 was involved in LPS-mediated viral production. In this regard, anti-inflammatory cytokines inhibited LPS plus GM-CSF-stimulated HIV expression, and this effect closely correlated with inhibition of IL-1 beta release and, in particular, with up-regulation of endogenous IL-1ra production. Thus, the balance between an endogenously produced viral inducer (IL-1 beta ) and an inhibitor (IL-1ra) may represent an important pathway leading to modulation of HIV expression from monocytic cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Goletti, D AU - Kinter, A L AU - Hardy, E C AU - Poli, G AU - Fauci, A S AD - National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 3501 EP - 3508 VL - 156 IS - 9 SN - 0022-1767, 0022-1767 KW - Antiviral Agents KW - 0 KW - Cytokines KW - IL1RN protein, human KW - Interleukin 1 Receptor Antagonist Protein KW - Interleukin-1 KW - Lipopolysaccharides KW - NF-kappa B KW - RNA, Viral KW - Sialoglycoproteins KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Cytokines -- pharmacology KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Cytokines -- secretion KW - HIV Long Terminal Repeat -- physiology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Base Sequence KW - Virus Activation -- drug effects KW - Antiviral Agents -- pharmacology KW - Molecular Sequence Data KW - Virus Activation -- genetics KW - Binding Sites -- genetics KW - Drug Synergism KW - RNA, Viral -- metabolism KW - Cell Line KW - NF-kappa B -- metabolism KW - HIV -- drug effects KW - Interleukin-1 -- pharmacology KW - HIV -- physiology KW - Sialoglycoproteins -- pharmacology KW - Interleukin-1 -- metabolism KW - Sialoglycoproteins -- metabolism KW - Monocytes -- metabolism KW - Monocytes -- drug effects KW - Monocytes -- virology KW - HIV -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78003142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Modulation+of+endogenous+IL-1+beta+and+IL-1+receptor+antagonist+results+in+opposing+effects+on+HIV+expression+in+chronically+infected+monocytic+cells.&rft.au=Goletti%2C+D%3BKinter%2C+A+L%3BHardy%2C+E+C%3BPoli%2C+G%3BFauci%2C+A+S&rft.aulast=Goletti&rft.aufirst=D&rft.date=1996-05-01&rft.volume=156&rft.issue=9&rft.spage=3501&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-13 N1 - Date created - 1996-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of dose histories for U.S. nuclear power plant workers, based on records held by a major dosimetry service company and on the NRC REIRS database. AN - 78002422; 8690574 AB - In order to conduct valid epidemiological studies of nuclear power plant workers, good information on the workers' radiation dose histories is essential. Dose records held by a major dosimetry service company and on the Nuclear Regulatory Commission's Radiation Exposure Information and Recording System have been compared for a sample of 99 workers. About half of the workers in the sample had no records on the Radiation Exposure Information and Recording System, since they had not terminated employment at a Nuclear Regulatory Commission-licensed facility; accordingly, their career doses (as recorded by the service company) were generally higher than those for workers on the Radiation Exposure Information and Recording System. For nearly half of the workers with records on both databases, the total dose recorded for terminated employments at nuclear power plants differed by at least a factor of 5 between the databases. In absolute terms, these differences were of the order of 100 mSv or more. An approach that utilized both the Radiation Exposure Information and Recording System and the dosimetry service company's records might be of value in constructing dose histories for a large epidemiological study. However, the comparisons presented here support the initiatives of the Nuclear Regulatory Commission to request licensees to report voluntarily career doses for current employees. These data are essential if a large and valid epidemiological study of nuclear plant workers is to be conducted in the foreseeable future. JF - Health physics AU - Muirhead, C R AU - Boice, J D AU - Raddatz, C T AU - Yoder, R C AD - Radiation Epidemiology Branch, National Cancer Institute, Rockville, MD 20852, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 645 EP - 650 VL - 70 IS - 5 SN - 0017-9078, 0017-9078 KW - Index Medicus KW - United States KW - Information Systems KW - Humans KW - National Academy of Sciences (U.S.) KW - Occupational Exposure KW - Radiation Dosage KW - Power Plants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78002422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+physics&rft.atitle=Comparison+of+dose+histories+for+U.S.+nuclear+power+plant+workers%2C+based+on+records+held+by+a+major+dosimetry+service+company+and+on+the+NRC+REIRS+database.&rft.au=Muirhead%2C+C+R%3BBoice%2C+J+D%3BRaddatz%2C+C+T%3BYoder%2C+R+C&rft.aulast=Muirhead&rft.aufirst=C&rft.date=1996-05-01&rft.volume=70&rft.issue=5&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Health+physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-23 N1 - Date created - 1996-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The bryostatins inhibit growth of B16/F10 melanoma cells in vitro through a protein kinase C-independent mechanism: dissociation of activities using 26-epi-bryostatin 1. AN - 78001752; 8616857 AB - Bryostatin 1 is a potential cancer chemotherapeutic agent in Phase II clinical trials, with positive responses observed for malignant melanoma, among other tumors. The bryostatins are known to be potent ligands for protein kinase C (PKC), functioning as partial antagonists. In the present study, we explore the mechanism by which the bryostatins inhibit growth to B16/F10 mouse melanoma cells in vitro. Three experimental approaches suggest that the growth inhibition is independent of PKC. First, we characterized in detail the translocation and down-regulation of the PKC isozymes alpha, delta, and epsilon in response to phorbol ester and bryostatin 1 in these cells. Although the dose-response curves obtained for the translocation-activation of PKC isozymes showed good correlation with the growth-enhancing activity of phorbol 12-myristate 13-acetate, for no PKC isozyme was there a good correlation with the growth-inhibitory activity of bryostatin 1. Second, inhibition PKC, inhibited the growth of the B16/F10 melanoma cell lines with potency similar to that of bryostatin 1. We confirmed here that 26-epi-bryostatin 1 showed 60-fold reduced affinity for PKC and 30-60-fold reduced potency to translocate and downregulate PKC isozymes compared with bryostatin 1. We presumed that the principal toxicity of bryostatin 1 reflects its interaction with PKC, and we would thus predict that epi-bryostatin 1 would be less toxic. Indeed, we found at least 10-fold reduced toxicity of 26-epi-bryostatin 1 in C57BL/6 mice compared with bryostatin 1. We conclude that the growth inhibition of the bryostatins, at least in this system, does not result from interaction with PKC. As exemplified by 26-epi-bryostatin 1, this insight permits the design of analogues with comparable growth inhibition to bryostatin 1 but with reduced toxicity. JF - Cancer research AU - Szallasi, Z AU - Du, L AU - Levine, R AU - Lewin, N E AU - Nguyen, P N AU - Williams, M D AU - Pettit, G R AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 2105 EP - 2111 VL - 56 IS - 9 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Bryostatins KW - Lactones KW - Macrolides KW - bryostatin 1 KW - 37O2X55Y9E KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Cell Division -- drug effects KW - Mice KW - Protein Kinase C -- metabolism KW - Melanoma, Experimental -- metabolism KW - Lactones -- therapeutic use KW - Signal Transduction -- drug effects KW - Melanoma, Experimental -- drug therapy KW - Melanoma, Experimental -- pathology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Lactones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78001752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+bryostatins+inhibit+growth+of+B16%2FF10+melanoma+cells+in+vitro+through+a+protein+kinase+C-independent+mechanism%3A+dissociation+of+activities+using+26-epi-bryostatin+1.&rft.au=Szallasi%2C+Z%3BDu%2C+L%3BLevine%2C+R%3BLewin%2C+N+E%3BNguyen%2C+P+N%3BWilliams%2C+M+D%3BPettit%2C+G+R%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1996-05-01&rft.volume=56&rft.issue=9&rft.spage=2105&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-12 N1 - Date created - 1996-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. AN - 77999340; 8616842 AB - Angiogenesis is essential for the growth and metastasis of solid tumors. In this study, we examined gene expression of vascular endothelial growth factor (VEGF); its receptor, flt-1; basic fibroblast growth factor; and transforming growth factors (TGFs) alpha and beta in 18 paired cases of human breast carcinomas and the adjacent nonneoplastic tissues. In all of the paired cases, VEGF expression was markedly increased in the carcinomas. In contrast, an insignificant difference was observed in the expression of flt-1, basic fibroblast growth factor, TGF-alpha, and TGF-beta between the malignant breast tissue and the nonneoplastic counterpart. Immunostaining showed variable VEGF positivity of the malignant cells, whereas the nonneoplastic breast epithelial cells were negative. The findings of this study suggest that VEGF is an important angiogenic factor in human breast cancer. JF - Cancer research AU - Yoshiji, H AU - Gomez, D E AU - Shibuya, M AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 2013 EP - 2016 VL - 56 IS - 9 SN - 0008-5472, 0008-5472 KW - Angiogenesis Inducing Agents KW - 0 KW - Endothelial Growth Factors KW - Lymphokines KW - Receptors, Growth Factor KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptors, Vascular Endothelial Growth Factor KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Humans KW - Immunohistochemistry KW - Breast Neoplasms -- genetics KW - Endothelial Growth Factors -- biosynthesis KW - Receptors, Growth Factor -- biosynthesis KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Endothelial Growth Factors -- genetics KW - Neovascularization, Pathologic -- metabolism KW - Breast Neoplasms -- metabolism KW - Receptors, Growth Factor -- genetics KW - Lymphokines -- biosynthesis KW - Lymphokines -- genetics KW - Angiogenesis Inducing Agents -- biosynthesis KW - Angiogenesis Inducing Agents -- genetics KW - Breast Neoplasms -- blood supply KW - Receptor Protein-Tyrosine Kinases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77999340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Expression+of+vascular+endothelial+growth+factor%2C+its+receptor%2C+and+other+angiogenic+factors+in+human+breast+cancer.&rft.au=Yoshiji%2C+H%3BGomez%2C+D+E%3BShibuya%2C+M%3BThorgeirsson%2C+U+P&rft.aulast=Yoshiji&rft.aufirst=H&rft.date=1996-05-01&rft.volume=56&rft.issue=9&rft.spage=2013&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-12 N1 - Date created - 1996-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peptide growth factor cross-talk with the estrogen receptor requires the A/B domain and occurs independently of protein kinase C or estradiol. AN - 77994227; 8612509 AB - Modulation of steroid receptor-dependent transcription by extra- cellular ligands represents a novel mechanism of steroid receptor regulation. We have assessed the effects of epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulin-like growth factor I (IGF-I) on transcription from consensus estrogen response elements (ERE) in estrogen receptor (ER)-positive BG-1 human ovarian adenocarcinoma calls. EGF, TGF alpha, IGF-I, and estradiol (E2) enhanced transcription in a dose-dependent manner using either a strong or a minimal promoter, and ICI 164,384, a specific ER antagonist, inhibited these responses. Combinations of E2 with TGF alpha or IGF-I induced synergistic activation of transcription from an ERE, whereas as additive response was observed with combinations of IGF-I and TGF alpha of EGF. Tetradecanoyl 12-phorbol 13-acetate (TPA), a protein kinase C (PKC) activator, stimulated ERE-mediated transcription, and this effect was inhibited by ICI 164,384. Bisindolylmaleimide, a relatively specific inhibitor of PKC, completely antagonized TPA-induced transcription, but did not affect the response to TGF alpha, IGF-I, or E2. The combination of TPA with E2 in transcriptional synergism was inhibited by ICI 164,384; conversely, the combination of TPA with either TGF alpha of IGF-I elicited a response only equal to the maximal TPA response. Thus, peptide growth factors elicit ER-dependent transcription independently of PFC; however, there may be a common mechanistic component, as saturation of response was observed. Finally, activation of ERE-dependent transcription in Chinese hamster ovary cells by IGF-I was observed in the presence of a mutant receptor that lacks estrogen-binding activity. The effect of both IGF-I and E2 were dependent on the ability of the ER to bind to DNA. IGF-I elicited only weak transcriptional activation in the presence of a deletion mutant that lacked the entire A/B domain; however, synergism between IGF-I and E2 was observed with this mutant. Therefore, ligand-independent activation of ER-dependent transcription by IGF-I is predominantly mediated through activation function I by a mechanism distinct from that of E2. JF - Endocrinology AU - Ignar-Trowbridge, D M AU - Pimentel, M AU - Parker, M G AU - McLachlan, J A AU - Korach, K S AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 1735 EP - 1744 VL - 137 IS - 5 SN - 0013-7227, 0013-7227 KW - Receptors, Estrogen KW - 0 KW - Transforming Growth Factor alpha KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Estradiol KW - 4TI98Z838E KW - Epidermal Growth Factor KW - 62229-50-9 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Cell Division -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - CHO Cells KW - Transcription, Genetic KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Cricetinae KW - Binding Sites KW - Protein Kinase C -- metabolism KW - Estradiol -- pharmacology KW - Transforming Growth Factor alpha -- pharmacology KW - Receptors, Estrogen -- metabolism KW - Epidermal Growth Factor -- pharmacology KW - Insulin-Like Growth Factor I -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77994227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Peptide+growth+factor+cross-talk+with+the+estrogen+receptor+requires+the+A%2FB+domain+and+occurs+independently+of+protein+kinase+C+or+estradiol.&rft.au=Ignar-Trowbridge%2C+D+M%3BPimentel%2C+M%3BParker%2C+M+G%3BMcLachlan%2C+J+A%3BKorach%2C+K+S&rft.aulast=Ignar-Trowbridge&rft.aufirst=D&rft.date=1996-05-01&rft.volume=137&rft.issue=5&rft.spage=1735&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-05 N1 - Date created - 1996-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of the adhesion of a human breast carcinoma cell line to type IV collagen and vitronectin: roles for lipoxygenase and protein kinase C. AN - 77993400; 8616873 AB - We have investigated the regulation of adhesion of metastatic human breast carcinoma cells to various protein substrates in the presence or absence of the protein kinase C (PKC) activator, 12-tetradecanoyl phorbol 13-acetate (TPA) or calcium ionophore A23187 (A23187). Both TPA and A23187 dramatically enhanced MDA-MB-435 cell adhesion to type IV collagen (collagen IV), vitronectin, and, to some extent, fibronectin and laminin. Adhesion to BSA and polylysine were not affected. TPA and A23187 induced substantial dose-dependent effects that were apparent after 30- and 60-min incubations, respectively, whereas a phorbol ester, which does not activate PKC, had no effect. A23187, but not TPA, induced a release of arachidonic acid (AA) from MDA-MB-435 cells. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, prevented A23187 and exogenous AA, but not TPA, from stimulating cell adhesion to collagen IV. In contrast, the increase in adhesion to vitronectin induced by A23187 and AA was, at best, only partially inhibited by nordihydroguaiaretic acid treatment. Calphostin C, a PKC inhibitor, blocked the stimulation of adhesion by A23187, exogenous AA, and TPA to both collagen IV and vitronectin. Together, these results suggest that calcium mobilization activates the release of AA and its metabolism through a lipoxygenase pathway leading to a rapid increase of MDA-MB-435 cell adhesion to collagen IV, whereas other mechanisms regulate adhesion to vitronectin. Finally, PKC activation, occurring downstream from calcium mobilization or the AA effects, is a key event involved in the regulation of adhesion to both proteins. JF - Cancer research AU - Palmantier, R AU - Roberts, J D AU - Glasgow, W C AU - Eling, T AU - Olden, K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/05/01/ PY - 1996 DA - 1996 May 01 SP - 2206 EP - 2212 VL - 56 IS - 9 SN - 0008-5472, 0008-5472 KW - Vitronectin KW - 0 KW - Collagen KW - 9007-34-5 KW - Lipoxygenase KW - EC 1.13.11.12 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Humans KW - Neoplasm Metastasis KW - Female KW - Cell Adhesion KW - Protein Kinase C -- metabolism KW - Lipoxygenase -- metabolism KW - Vitronectin -- metabolism KW - Carcinoma -- pathology KW - Breast Neoplasms -- pathology KW - Collagen -- metabolism KW - Breast Neoplasms -- metabolism KW - Carcinoma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77993400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Regulation+of+the+adhesion+of+a+human+breast+carcinoma+cell+line+to+type+IV+collagen+and+vitronectin%3A+roles+for+lipoxygenase+and+protein+kinase+C.&rft.au=Palmantier%2C+R%3BRoberts%2C+J+D%3BGlasgow%2C+W+C%3BEling%2C+T%3BOlden%2C+K&rft.aulast=Palmantier&rft.aufirst=R&rft.date=1996-05-01&rft.volume=56&rft.issue=9&rft.spage=2206&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-12 N1 - Date created - 1996-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strand specificity of mutagenic bypass replication of DNA containing psoralen monoadducts in a human cell extract. AN - 77992029; 8628322 AB - Psoralens are mutagenic compounds of vegetable origin that are used as photosensitizing agents in the treatment of various skin diseases, blood cell cancer, and autoimmune disorders. To study the mechanism of mutagenicity of psoralens in humans, we examined the efficiency and fidelity of simian virus 40 origin-dependent replication in a human cell extract of M13mp2 DNA randomly treated with the psoralen derivative 4'-hydroxymethyl-4,5',8-trimethyl psoralen plus UVA irradiation. Replication of DNA treated with variable amounts of 4'-hydroxymethyl-4,5',8-trimethyl psoralen and a fixed UVA fluence was inhibited in a concentration-dependent manner. However, covalently closed monomer-length circular replication products were observed. Product analysis by renaturing agarose gel electrophoresis after cross-linking with 250- to 280-nm UV light indicated that approximately 1 of 9 psoralen monoadducts was bypassed during in vitro replication. Introduction of product DNA into Escherichia coli to score replication errors in the lacZalpha reporter gene demonstrated that replication of the damaged DNA was more mutagenic than was replication of undamaged DNA. Sequence analysis of lacZ mutants revealed that damage-dependent replication errors were predominantly T.A-->C.G transitions, transversions at C.G base pairs, and deletions of single A.T base pairs, the last occurring most frequently in homopolymeric runs. A comparison of error specificities with two substrates having the replication origin asymmetrically placed on opposite sides of the mutational target suggests that the lagging-strand replication apparatus is less accurate than the leading-strand replication apparatus for psoralen monoadduct-dependent deletion errors. A model is proposed based on the preferential loopout of the monoadducted base from the strand that templates retrograde discontinuous synthesis. JF - Molecular and cellular biology AU - Thomas, D C AU - Svoboda, D L AU - Vos, J M AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 2537 EP - 2544 VL - 16 IS - 5 SN - 0270-7306, 0270-7306 KW - DNA Adducts KW - 0 KW - DNA, Viral KW - hydroxymethyltrioxsalen KW - 3I2U5ZBX3W KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Trioxsalen KW - Y6UY8OV51T KW - Index Medicus KW - Genes, Bacterial KW - Escherichia coli -- metabolism KW - Base Sequence KW - Base Composition KW - HeLa Cells KW - Dose-Response Relationship, Drug KW - Humans KW - Simian virus 40 KW - Molecular Sequence Data KW - Bacteriophage M13 KW - beta-Galactosidase -- biosynthesis KW - DNA, Viral -- biosynthesis KW - Ultraviolet Rays KW - DNA Replication -- radiation effects KW - DNA Damage KW - Trioxsalen -- pharmacology KW - Trioxsalen -- analogs & derivatives KW - DNA Replication -- drug effects KW - Sequence Deletion KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77992029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Strand+specificity+of+mutagenic+bypass+replication+of+DNA+containing+psoralen+monoadducts+in+a+human+cell+extract.&rft.au=Thomas%2C+D+C%3BSvoboda%2C+D+L%3BVos%2C+J+M%3BKunkel%2C+T+A&rft.aulast=Thomas&rft.aufirst=D&rft.date=1996-05-01&rft.volume=16&rft.issue=5&rft.spage=2537&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Genet. 1975;9:245-84 [55095] Cell. 1995 Jul 14;82(1):9-12 [7606789] Mutat Res. 1983 Aug;118(3):191-204 [6877268] N Engl J Med. 1984 May 3;310(18):1156-61 [6709010] Mol Cell Biol. 1985 Jun;5(6):1238-46 [2993858] J Mol Biol. 1985 Aug 20;184(4):725-34 [3900419] Nucleic Acids Res. 1987 Jun 25;15(12):4957-71 [3299260] Cell. 1987 Aug 28;50(5):789-99 [3621344] Carcinogenesis. 1987 Dec;8(12):1923-7 [3677315] J Biol Chem. 1988 Mar 25;263(9):4450-9 [2831231] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7064-8 [3174620] Mol Cell Biol. 1989 Mar;9(3):1277-83 [2725498] Mol Cell Biol. 1989 Jul;9(7):2897-905 [2779552] N Engl J Med. 1990 Apr 19;322(16):1093-7 [2320078] J Cell Biochem. 1990 Jun;43(2):173-83 [2380262] J Mol Biol. 1991 Jan 20;217(2):217-22 [1992158] Mol Cell Biol. 1991 Apr;11(4):1927-34 [2005888] Mol Cell Biol. 1991 Apr;11(4):2245-52 [2005908] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3465-9 [1901658] Nucleic Acids Res. 1991 May 11;19(9):2411-5 [1674998] Mutat Res. 1991 Nov;251(1):143-55 [1944372] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124-8 [1946433] J Photochem Photobiol B. 1991 Jul;10(1-2):165-71 [1955944] Biochemistry. 1991 Dec 24;30(51):11751-9 [1751492] J Photochem Photobiol B. 1992 Jan;12(1):37-55 [1542088] Bioessays. 1992 May;14(5):303-8 [1637361] Curr Opin Cell Biol. 1992 Jun;4(3):385-95 [1497911] J Photochem Photobiol B. 1992 Jun 30;14(1-2):3-22 [1432383] Mol Cell Biol. 1993 Jan;13(1):533-42 [8417349] Mol Cell Biol. 1993 Feb;13(2):1002-12 [8423773] EMBO J. 1993 Feb;12(2):397-402 [8440233] Biochemistry. 1993 Apr 20;32(15):4083-9 [8385995] Photochem Photobiol. 1993 Jan;57(1):163-74 [8389052] Mutat Res. 1993 Aug;294(2):167-77 [7687009] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7744-8 [8356079] Mutagenesis. 1993 Jul;8(4):355-61 [8377656] Biochemistry. 1993 Nov 2;32(43):11476-82 [8218213] J Biol Chem. 1994 Jan 21;269(3):1711-7 [8294419] Carcinogenesis. 1994 Feb;15(2):201-7 [8313509] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6830-4 [8041704] Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7752-6 [8052656] Cell. 1994 Sep 9;78(5):725-8 [8087839] Cytogenet Cell Genet. 1983;35(2):100-3 [6851666] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Common core sequences are found in skeletal muscle slow- and fast-fiber-type-specific regulatory elements. AN - 77989387; 8628309 AB - The molecular mechanisms generating muscle diversity during development are unknown. The phenotypic properties of slow- and fast-twitch myofibers are determined by the selective transcription of genes coding for contractile proteins and metabolic enzymes in these muscles, properties that fail to develop in cultured muscle. Using transgenic mice, we have identified regulatory elements in the evolutionarily related troponin slow (TnIs) and fast (TnIf) genes that confer specific transcription in either slow or fast muscles. Analysis of serial deletions of the rat TnIs upstream region revealed that sequences between kb -0.95 and -0.5 are necessary to confer slow-fiber-specific transcription; the -0.5-kb fragment containing the basal promoter was inactive in five transgenic mouse lines tested. We identified a 128-bp regulatory element residing at kb -0.8 that, when linked to the -0.5-kb TnIs promoter, specifically confers transcription to slow-twitch muscles. To identify sequences directing fast-fiber-specific transcription, we generated transgenic mice harboring a construct containing the TnIs kb -0.5 promoter fused to a 144-bp enhancer derived from the quail TnIf gene. Mice harboring the TnIf/TnIs chimera construct expressed the transgene in fast but not in slow muscles, indicating that these regulatory elements are sufficient to confer fiber-type-specific transcription. Alignment of rat TnIs and quail TnIf regulatory sequences indicates that there is a conserved spatial organization of core elements, namely, an E box, a CCAC box, a MEF-2-like sequence, and a previously uncharacterized motif. The core elements were shown to bind their cognate factors by electrophoretic mobility shift assays, and their mutation demonstrated that the TnIs CCAC and E boxes are necessary for transgene expression. Our results suggest that the interaction of closely related transcriptional protein-DNA complexes is utilized to specify fiber type diversity. JF - Molecular and cellular biology AU - Nakayama, M AU - Stauffer, J AU - Cheng, J AU - Banerjee-Basu, S AU - Wawrousek, E AU - Buonanno, A AD - Unit on Molecular Neurobiology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 2408 EP - 2417 VL - 16 IS - 5 SN - 0270-7306, 0270-7306 KW - DNA Primers KW - 0 KW - Troponin KW - Troponin I KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Space life sciences KW - Animals KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Sequence Homology, Nucleic Acid KW - Biological Evolution KW - Mice KW - Mice, Transgenic KW - Mutagenesis, Site-Directed KW - Rats KW - Polymerase Chain Reaction KW - Base Sequence KW - Conserved Sequence KW - Restriction Mapping KW - Molecular Sequence Data KW - Muscle Fibers, Fast-Twitch -- metabolism KW - Regulatory Sequences, Nucleic Acid KW - Promoter Regions, Genetic KW - Troponin -- genetics KW - Point Mutation KW - Muscle Fibers, Slow-Twitch -- metabolism KW - Transcription, Genetic KW - Troponin -- biosynthesis KW - Muscle, Skeletal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77989387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Common+core+sequences+are+found+in+skeletal+muscle+slow-+and+fast-fiber-type-specific+regulatory+elements.&rft.au=Nakayama%2C+M%3BStauffer%2C+J%3BCheng%2C+J%3BBanerjee-Basu%2C+S%3BWawrousek%2C+E%3BBuonanno%2C+A&rft.aulast=Nakayama&rft.aufirst=M&rft.date=1996-05-01&rft.volume=16&rft.issue=5&rft.spage=2408&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U49920; GENBANK N1 - SuppNotes - Cited By: EMBO J. 1989 Mar;8(3):701-9 [2721498] Mol Cell Biol. 1988 Dec;8(12):5072-9 [3244349] Genes Dev. 1989 May;3(5):628-40 [2473006] Cell. 1989 Aug 11;58(3):537-44 [2503252] J Biol Chem. 1989 Aug 15;264(23):13896-901 [2760049] Mol Cell Biol. 1989 Jun;9(6):2396-413 [2761536] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7780-4 [2813357] Mol Cell Biol. 1989 Nov;9(11):5022-33 [2601707] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1089-93 [2300571] EMBO J. 1990 Mar;9(3):821-31 [2311584] Genes Dev. 1989 Dec;3(12B):2050-61 [2560751] Nature. 1990 Mar 15;344(6263):260-2 [2156167] Curr Opin Cell Biol. 1989 Dec;1(6):1094-101 [2699798] J Biol Chem. 1990 Aug 15;265(23):13974-80 [2380199] Genes Dev. 1990 Oct;4(10):1811-22 [2123467] J Biol Chem. 1990 Dec 5;265(34):21247-53 [2250022] Genes Dev. 1990 Sep;4(9):1454-61 [2253873] Mol Cell Biol. 1991 Jan;11(1):267-80 [1846022] Science. 1991 Feb 15;251(4995):761-6 [1846704] Rev Physiol Biochem Pharmacol. 1990;116:1-76 [2149884] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5847-51 [2062862] J Cell Biol. 1991 Oct;115(2):423-34 [1717485] Mol Cell Biol. 1991 Oct;11(10):5090-100 [1922033] Genes Dev. 1991 Dec;5(12A):2327-41 [1748287] Mol Cell Biol. 1992 Mar;12(3):1031-42 [1312219] Trends Genet. 1992 Apr;8(4):144-8 [1321521] Mol Cell Biol. 1992 Sep;12(9):3665-77 [1324403] Genes Dev. 1992 Sep;6(9):1783-98 [1516833] Mol Cell Biol. 1992 Nov;12(11):5024-32 [1406677] J Histochem Cytochem. 1993 May;41(5):733-43 [8468455] Curr Opin Genet Dev. 1993 Apr;3(2):265-74 [8389217] Circ Res. 1993 Aug;73(2):360-6 [8330378] Nature. 1993 Aug 5;364(6437):501-6 [8393145] Mol Cell Biol. 1993 Oct;13(10):6469-78 [8413246] Mol Cell Biol. 1993 Nov;13(11):7019-28 [8413291] Development. 1993 Aug;118(4):1137-47 [8269844] Mol Cell Biol. 1994 Mar;14(3):1870-85 [8114720] J Biol Chem. 1994 Apr 8;269(14):10651-9 [8144655] Development. 1993 Nov;119(3):691-701 [8187638] J Biol Chem. 1994 Jun 17;269(24):16740-5 [8206996] Mol Cell Biol. 1994 Jul;14(7):4596-605 [8007964] Mol Cell Biol. 1994 Oct;14(10):6797-808 [7935397] J Cell Biol. 1995 Apr;129(2):383-96 [7721942] Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6185-9 [7597099] Development. 1994 Jul;120(7):1799-804 [7924987] Methods Enzymol. 1983;101:582-98 [6888276] Proc Natl Acad Sci U S A. 1985 Dec;82(23):8080-4 [3865218] Annu Rev Biophys Biophys Chem. 1987;16:535-59 [2954560] Nucleic Acids Res. 1987 Jul 10;15(13):5490 [3037497] Dev Biol. 1987 Sep;123(1):1-9 [3305110] Mol Cell Biol. 1987 Sep;7(9):3065-75 [3670306] Cell. 1987 Dec 24;51(6):987-1000 [3690668] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6404-8 [3413104] Cell. 1989 Feb 24;56(4):607-17 [2537150] Mol Cell Biol. 1989 Apr;9(4):1397-405 [2725509] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro infection of primary and retrovirus-infected human leukocytes by human foamy virus. AN - 77987486; 8627751 AB - The infectivity of human foamy virus (HFV) was examined in primary and cultured human leukocytes. Cell-free infectious viral stocks of HFV were prepared from the human kidney cell line 293 transfected with an infectious molecular clone of HFV. HFV productively infects a variety of human myeloid and lymphoid cell lines. In addition, primary cell cultures enriched for human CD4+, monocytes and brain-derived microglial cells, were readily infected by HFV. Interestingly, while infected primary CD4+ lymphocytes and microglial cells showed marked cytopathology characteristic of foamy virus, HFV-infected monocyte-derived macrophages failed to show any cytopathology. In addition, marked cytotoxicity due to HFV infection was seen in both human T-cell leukemia virus type 1- and human immunodeficiency virus type 1-infected T-cell lines and in human immunodeficiency virus type 1-infected monocytoid cell lines. Thus, HFV infection produces differential cytopathology in a wide host range of primary human leukocytes and hematopoietic cell lines. JF - Journal of virology AU - Mikovits, J A AU - Hoffman, P M AU - Rethwilm, A AU - Ruscetti, F W AD - Biological Carcinogenesis Development Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 2774 EP - 2780 VL - 70 IS - 5 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - DNA, Viral KW - Gene Products, gag KW - Index Medicus KW - AIDS/HIV KW - Cell Nucleus -- virology KW - Humans KW - Proviruses -- physiology KW - Polymerase Chain Reaction KW - DNA, Viral -- biosynthesis KW - Base Sequence KW - Cells, Cultured KW - DNA, Viral -- analysis KW - Kinetics KW - Molecular Sequence Data KW - Kidney KW - Cell Nucleus -- physiology KW - Gene Products, gag -- biosynthesis KW - Cell Line KW - Virus Replication KW - Retroviridae -- pathogenicity KW - Spumavirus -- pathogenicity KW - Retroviridae -- physiology KW - Spumavirus -- physiology KW - Leukocytes -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77987486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=In+vitro+infection+of+primary+and+retrovirus-infected+human+leukocytes+by+human+foamy+virus.&rft.au=Mikovits%2C+J+A%3BHoffman%2C+P+M%3BRethwilm%2C+A%3BRuscetti%2C+F+W&rft.aulast=Mikovits&rft.aufirst=J&rft.date=1996-05-01&rft.volume=70&rft.issue=5&rft.spage=2774&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1993 Nov;67(11):6618-24 [8411364] J Med Virol. 1984;14(3):247-54 [6502141] J Virol. 1994 Aug;68(8):4946-54 [8035493] AIDS Res Hum Retroviruses. 1994 May;10(5):601-5 [7917521] J Virol. 1994 Nov;68(11):7124-30 [7933094] J Virol. 1995 Mar;69(3):1907-12 [7853532] AIDS Res Hum Retroviruses. 1995 Jan;11(1):161-70 [7734189] Virology. 1995 Jun 20;210(1):167-78 [7793069] Trends Microbiol. 1995 May;3(5):173-8 [7627455] Curr Top Microbiol Immunol. 1995;193:1-24 [7648870] Immunol Today. 1995 Dec;16(12):574-80 [8579750] J Immunol. 1986 May 15;136(10):3619-24 [2422259] Arch Virol. 1987;92(1-2):183-6 [2432853] Gene. 1987;59(1):19-28 [2830164] Nature. 1988 Jun 9;333(6173):497-8 [2836735] Nucleic Acids Res. 1990 Feb 25;18(4):733-8 [1690391] J Exp Med. 1990 May 1;171(5):1705-20 [2332735] Science. 1990 Aug 3;249(4968):549-53 [2200125] J Virol. 1991 Feb;65(2):727-35 [1846194] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):941-5 [1846970] J Virol. 1991 May;65(5):2589-94 [1850032] Science. 1991 Aug 2;253(5019):555-7 [1650034] J Virol. 1991 Nov;65(11):6353-7 [1656100] J Virol. 1991 Dec;65(12):7012-5 [1658392] J Exp Med. 1991 Dec 1;174(6):1477-82 [1720811] J Virol. 1992 May;66(5):3236-40 [1313928] J Virol. 1992 Jun;66(6):3946-9 [1316494] EMBO J. 1992 Aug;11(8):3053-8 [1322294] J Clin Invest. 1992 Oct;90(4):1486-91 [1401081] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11784-8 [1465399] Virology. 1993 Feb;192(2):663-6 [8380669] Am J Pathol. 1993 Apr;142(4):1061-71 [8386440] J Virol. 1993 Sep;67(9):5411-8 [8394455] Intervirology. 1993;35(1-4):196-207 [8407246] J Virol. 1996 Feb;70(2):1250-4 [8551590] Mol Cell Biol. 1987 Aug;7(8):2745-52 [3670292] Nature. 1967 Nov 4;216(5114):446-9 [4964401] J Natl Cancer Inst. 1971 Feb;46(2):299-307 [4329955] Proc Soc Exp Biol Med. 1971 Sep;137(4):1318-23 [5003008] Bacteriol Rev. 1975 Sep;39(3):169-85 [51620] Science. 1978 Jun 9;200(4346):1153-4 [306682] Blood. 1980 Aug;56(2):265-73 [6967340] J Med Virol. 1981;7(1):67-73 [6264025] J Immunol Methods. 1983 Sep 16;62(3):353-63 [6350465] Virology. 1994 Jun;201(2):187-99 [8184531] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A unique transactivation sequence motif is found in the carboxyl-terminal domain of the single-strand-binding protein FBP. AN - 77987371; 8628294 AB - The far-upstream element-binding protein (FBP) is one of several recently described factors which bind to a single strand of DNA in the 5' region of the c-myc gene. Although cotransfection of FBP increases expression from a far-upstream element-bearing c-myc promoter reporter, the mechanism of this stimulation is heretofore unknown. Can a single-strand-binding protein function as a classical transactivator, or are these proteins restricted to stabilizing or altering the conformation of DNA in an architectural role? Using chimeric GAL4-FBP fusion proteins we have shown that the carboxyl-terminal region (residues 448 to 644) is a potent transcriptional activation domain. This region contains three copies of a unique amino acid sequence motif containing tyrosine diads. Analysis of deletion mutants demonstrated that a single tyrosine motif alone (residues 609 to 644) was capable of activating transcription. The activation property of the C-terminal domain is repressed by the N-terminal 107 amino acids of FBP. These results show that FBP contains a transactivation domain which can function alone, suggesting that FBP contributes directly to c-myc transcription while bound to a single-strand site. Furthermore, activation is mediated by a new motif which can be negatively regulated by a repression domain of FBP. JF - Molecular and cellular biology AU - Duncan, R AU - Collins, I AU - Tomonaga, T AU - Zhang, T AU - Levens, D AD - Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 2274 EP - 2282 VL - 16 IS - 5 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - GAL4 protein, S cerevisiae KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Tyrosine KW - 42HK56048U KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Protein Structure, Secondary KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - HeLa Cells KW - Humans KW - Fungal Proteins -- biosynthesis KW - Amino Acid Sequence KW - Plasmids KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Transfection KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - TATA Box KW - Cell Line KW - DNA-Binding Proteins -- chemistry KW - DNA-Binding Proteins -- biosynthesis KW - Transcriptional Activation KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77987371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=A+unique+transactivation+sequence+motif+is+found+in+the+carboxyl-terminal+domain+of+the+single-strand-binding+protein+FBP.&rft.au=Duncan%2C+R%3BCollins%2C+I%3BTomonaga%2C+T%3BZhang%2C+T%3BLevens%2C+D&rft.aulast=Duncan&rft.aufirst=R&rft.date=1996-05-01&rft.volume=16&rft.issue=5&rft.spage=2274&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Trends Genet. 1995 Feb;11(2):69-74 [7716810] Nature. 1988 Oct 20;335(6192):683-9 [3050531] Cell. 1988 Dec 2;55(5):887-98 [3142690] Nature. 1989 Mar 2;338(6210):39-44 [2521923] Cell. 1989 Aug 25;58(4):741-53 [2504497] Nucleic Acids Res. 1989 Sep 25;17(18):7539 [2798115] J Mol Biol. 1989 Oct 5;209(3):423-32 [2511324] Nature. 1990 May 24;345(6273):361-4 [2160609] J Biol Chem. 1990 Oct 25;265(30):18538-45 [2211718] Nucleic Acids Res. 1992 May 11;20(9):2241-7 [1594443] Annu Rev Biochem. 1992;61:809-60 [1497324] Oncogene. 1995 Jun 1;10(11):2229-38 [7784068] Genes Dev. 1995 Jun 1;9(11):1354-65 [7797075] Mol Cell Biol. 1995 Aug;15(8):4309-18 [7623825] Genes Dev. 1995 Aug 15;9(16):1992-2006 [7649480] Annu Rev Cell Dev Biol. 1995;11:441-69 [8689565] Cell. 1987 May 8;49(3):295-7 [2882858] Genes Dev. 1993 Jul;7(7B):1341-53 [8330738] Mol Cell Biol. 1993 Aug;13(8):4640-7 [8336707] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):192-6 [8278363] Genes Dev. 1994 Feb 15;8(4):465-80 [8125259] Nature. 1994 Mar 10;368(6467):163-6 [8139661] Cell. 1994 Apr 8;77(1):5-8 [8156597] Science. 1994 May 20;264(5162):1100-1 [8178167] Science. 1994 Jun 3;264(5164):1415-21 [8197455] J Biol Chem. 1995 Mar 3;270(9):4875-81 [7876260] Annu Rev Cell Biol. 1994;10:405-55 [7888182] J Biol Chem. 1995 Apr 7;270(14):8241-8 [7713931] Nature. 1988 Oct 6;335(6190):563-4 [3047590] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinction of mutagenic carcinogens from a mutagenic noncarcinogen in the big blue transgenic mouse. AN - 21253398; 11701745 AB - The aromatic amines 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT) are structural isomers that have been extensively studied for their mutagenic and carcinogenic characteristics. Both compounds are rapidly absorbed after oral administration and are equally mutagenic in the Ames test; however, 2,4-DAT is a potent hepatocarcinogen, whereas 2,6-DAT does not produce an increased incidence of tumors in rats or mice at similar doses. The Big Blue transgenic B6C3F1 mouse carries multiple copies of the lacl mutational target gene. Our studies were designed to determine whether the Big Blue system could be used to detect differences in the vivo mutagenic activity between the carcinogen-noncarcinogen pair 2,4-DAT and 2,6-DAT and to determine whether the in vivo mutagenesis assay results correspond to the rodent carcinogen bioassay results. Male B6C3F1 transgenic mice were exposed to 2,4-DAT or 2,6-DAT at 0 or 1,000 ppm in the diet for 30 and 90 days or to dimethylnitrosamine as a positive control. Mutant frequencies were nearly identical for all three groups at 30 days, while at 90 days the mutant frequency for the hepatocarcinogen 2,4-DAT (12.1 +/- 1.4 x 10(-5)) was significantly higher (p & 0.01) as compared to both age-matched (spontaneous) controls (5.7 +/- 2.9 x 10(-5)) and the 2,6-DAT-exposed group (5.7 +/- 2.4 x 10(-5)). Results from this study demonstrate that the Big Blue transgenic mutation assay can distinguish differences in vivo between the mutagenic responses of hepatic carcinogens ad a noncarcinogen; is sensitive to mutagens through subchronic dietary exposure; and yields a differential response depending upon the length of time mice are exposed to a mutagen. JF - Environmental Health Perspectives AU - Cunningham, M L AU - Hayward, J J AU - Shane, B S AU - Tindall, K R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA., cunning1@niehs.nih.gov Y1 - 1996/05// PY - 1996 DA - May 1996 SP - 683 EP - 686 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 104 IS - Suppl 3 SN - 0091-6765, 0091-6765 KW - Biotechnology and Bioengineering Abstracts; Environment Abstracts KW - Mutagens KW - AMES test KW - 2,6-Diaminotoluene KW - Mutant frequency KW - Carcinogens KW - Mutants KW - Isomers KW - Mutagenesis KW - Rats KW - amines KW - Carcinogenicity KW - 2,4-Diaminotoluene KW - Diets KW - Oral administration KW - Mice KW - Tumors KW - Ames test KW - Transgenic mice KW - Liver KW - Dimethylnitrosamine KW - Mutation KW - rodents KW - Aromatics KW - W 30925:Genetic Engineering KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21253398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Distinction+of+mutagenic+carcinogens+from+a+mutagenic+noncarcinogen+in+the+big+blue+transgenic+mouse.&rft.au=Cunningham%2C+M+L%3BHayward%2C+J+J%3BShane%2C+B+S%3BTindall%2C+K+R&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1996-05-01&rft.volume=104&rft.issue=Suppl+3&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Diets; Mutagens; Oral administration; 2,6-Diaminotoluene; Mutant frequency; Carcinogens; Tumors; Transgenic mice; Ames test; Mutagenesis; Isomers; amines; 2,4-Diaminotoluene; Dimethylnitrosamine; Liver; Mutation; Aromatics; Rats; Carcinogenicity; AMES test; Mice; rodents; Mutants ER - TY - JOUR T1 - Transforming Growth Factor-beta Receptors: Role in Physiology and Disease. AN - 1859358192; 11725095 AB - Transforming growth factor-beta (TGF-beta) plays a pivotal role in numerous vital cellular activities, most significantly the regulation of cellular proliferation and differentiation and synthesis of extracellular matrix components. Its ubiquitous presence in different tissues and strict conservation of nucleotide sequence down through the most primitive vertebrate organism underscore the essential nature of this family of molecules. The effects of TGF-beta are mediated by a family of dedicated receptors, the TGF-beta types I, II, and III receptors. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors or their cognate ligands. The coding sequence of the human type II receptor appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. There are now substantial data suggesting that TGF-beta type II receptor should be considered a tumor suppressor gene. High levels of mutation in the TGF-beta type II receptor gene have been observed in a wide variety of primarily epithelial malignancies, including colon, gastric, and hepatic cancer. It appears likely that mutation of the TGF-beta type II receptor gene represents a very critical step in the pathway of carcinogenesis. Copyright 1996 S. Karger AG, Basel JF - Journal of biomedical science AU - Kim, D.H. AU - Kim, S.-J. AD - Laboratory of Chemoprevention, National Cancer Institute, NIH, Bethesda, Md., USA. PY - 1996 SP - 143 EP - 158 VL - 3 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859358192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biomedical+science&rft.atitle=Transforming+Growth+Factor-beta+Receptors%3A+Role+in+Physiology+and+Disease.&rft.au=Kim%2C+D.H.%3BKim%2C+S.-J.&rft.aulast=Kim&rft.aufirst=D.H.&rft.date=1996-05-01&rft.volume=3&rft.issue=3&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomedical+science&rft.issn=1423-0127&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2001-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in the RNA binding sites of iron regulatory proteins and potential target diversity. AN - 78013429; 8633068 AB - Posttranscriptional regulation of genes of mammalian iron metabolism is mediated by the interaction of iron regulatory proteins (IRPs) with RNA stem-loop sequence elements known as iron-responsive elements (IREs). There are two identified IRPs, IRP1 and IRP2, each of which binds consensus IREs present in eukaryotic transcripts with equal affinity. Site-directed mutagenesis of IRP1 and IRP2 reveals that, although the binding affinities for consensus IREs are indistinguishable, the contributions of arginine residues in the active-site cleft to the binding affinity are different in the two RNA binding sites. Furthermore, although each IRP binds the consensus IRE with high affinity, each IRP also binds a unique alternative ligand, which was identified in an in vitro systematic evolution of ligands by exponential enrichment procedure. Differences in the two binding sites may be important in the function of the IRE-IRP regulatory system. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Butt, J AU - Kim, H Y AU - Basilion, J P AU - Cohen, S AU - Iwai, K AU - Philpott, C C AU - Altschul, S AU - Klausner, R D AU - Rouault, T A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/04/30/ PY - 1996 DA - 1996 Apr 30 SP - 4345 EP - 4349 VL - 93 IS - 9 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Iron-Regulatory Proteins KW - Iron-Sulfur Proteins KW - RNA, Messenger KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Iron Regulatory Protein 1 KW - EC 4.2.1.3 KW - Iron Regulatory Protein 2 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Amino Acid Sequence KW - Nucleic Acid Conformation KW - Binding Sites KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Alternative Splicing KW - Kinetics KW - Binding, Competitive KW - Cercopithecus aethiops KW - Point Mutation KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Consensus Sequence KW - Cell Line KW - Iron-Sulfur Proteins -- chemistry KW - RNA-Binding Proteins -- biosynthesis KW - RNA-Binding Proteins -- metabolism KW - RNA, Messenger -- metabolism KW - RNA, Messenger -- chemistry KW - Iron-Sulfur Proteins -- biosynthesis KW - RNA-Binding Proteins -- chemistry KW - Iron-Sulfur Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78013429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Differences+in+the+RNA+binding+sites+of+iron+regulatory+proteins+and+potential+target+diversity.&rft.au=Butt%2C+J%3BKim%2C+H+Y%3BBasilion%2C+J+P%3BCohen%2C+S%3BIwai%2C+K%3BPhilpott%2C+C+C%3BAltschul%2C+S%3BKlausner%2C+R+D%3BRouault%2C+T+A&rft.aulast=Butt&rft.aufirst=J&rft.date=1996-04-30&rft.volume=93&rft.issue=9&rft.spage=4345&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-01 N1 - Date created - 1996-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):574-8 [8290565] EMBO J. 1995 Nov 1;14(21):5350-7 [7489724] J Biol Chem. 1992 Sep 15;267(26):19005-10 [1527027] Biometals. 1992 Autumn;5(3):131-40 [1421965] Cell. 1993 Jan 15;72(1):19-28 [8380757] J Mol Biol. 1972 Dec 30;72(3):671-90 [4573844] Nucleic Acids Res. 1987 Nov 11;15(21):8783-98 [3684574] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8478-82 [3479802] Science. 1987 Dec 11;238(4833):1570-3 [3685996] EMBO J. 1989 Dec 1;8(12):3693-9 [2583116] Mol Cell Biol. 1989 Nov;9(11):5055-61 [2601708] J Biol Chem. 1990 Feb 15;265(5):2814-21 [2303429] J Biol Chem. 1990 Apr 25;265(12):7000-8 [2324109] Nucleic Acids Res. 1990 Apr 11;18(7):1819-24 [2336358] Science. 1990 Aug 3;249(4968):505-10 [2200121] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):688-92 [1992460] EMBO J. 1991 Jul;10(7):1891-902 [2050125] EMBO J. 1991 Jul;10(7):1903-9 [2050126] Biochemistry. 1992 Mar 17;31(10):2735-48 [1547214] J Biol Chem. 1992 Apr 15;267(11):7895-903 [1313811] Nucleic Acids Res. 1993 Jul 1;21(13):2963-5 [8332518] Nucleic Acids Res. 1993 Sep 25;21(19):4627-31 [8233801] Blood Rev. 1993 Dec;7(4):251-8 [8130687] EMBO J. 1994 Apr 15;13(8):1969-80 [7909515] Arch Biochem Biophys. 1994 Jun;311(2):517-22 [8203918] J Biol Chem. 1994 Jul 1;269(26):17481-9 [8021254] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7321-5 [8041788] EMBO J. 1994 Aug 15;13(16):3882-91 [8070415] J Biol Chem. 1994 Sep 30;269(39):24252-60 [7523370] J Biol Chem. 1994 Dec 9;269(49):30904-10 [7983023] Biochem J. 1994 Nov 15;304 ( Pt 1):1-11 [7998919] J Biol Chem. 1995 Mar 10;270(10):4983-6 [7890603] EMBO J. 1995 Jun 15;14(12):2917-24 [7796817] J Biol Chem. 1995 Jun 30;270(26):15451-4 [7541043] J Biol Chem. 1995 Sep 15;270(37):21645-51 [7665579] J Biol Chem. 1992 Aug 15;267(23):16531-7 [1644834] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced RNA expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in human breast cancer. AN - 78012298; 8608981 AB - Tissue inhibitor of metalloproteinases-1 (TIMP-1) is known to have at least 2 distinct types of activity, i.e., as a regulator of collagenolytic activity, and erythroid potentiating activity (EPA). In this study, we examined the expression of TIMP-1 in human mammary carcinomas, non-malignant breast tissues and benign breast tumors. A total of 53 samples were subjected to Northern-blot analysis, including 23 of primary breast cancer, 26 of non-malignant breast tissues, and 4 benign tumors. Of the 53 samples, 10 were paired malignant and non-malignant breast-tissue samples from the same patient. TIMP-1 RNA expression was significantly higher in the malignant tumor tissues than in the non-malignant counterpart. Similar differences were observed in the level of TIMP-1 protein expression in the paired breast samples examined. Moreover, breast-cancer cell lines secreted larger amounts of TIMP-1 in vitro than non-neoplastic breast epithelial lines. The up-regulation of TIMP-1 expression in breast cancer may suggest that TIMP-1 has an additional role to that of metalloproteinase inhibitor. JF - International journal of cancer AU - Yoshiji, H AU - Gomez, D E AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA. Y1 - 1996/04/22/ PY - 1996 DA - 1996 Apr 22 SP - 131 EP - 134 VL - 69 IS - 2 SN - 0020-7136, 0020-7136 KW - Glycoproteins KW - 0 KW - Neoplasm Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Tissue Inhibitor of Metalloproteinases KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Tumor Cells, Cultured KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - RNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - Neoplasm Proteins -- metabolism KW - Breast -- metabolism KW - Breast Neoplasms -- genetics KW - Glycoproteins -- metabolism KW - Glycoproteins -- genetics KW - Carcinoma, Lobular -- genetics KW - Carcinoma, Ductal, Breast -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78012298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Enhanced+RNA+expression+of+tissue+inhibitor+of+metalloproteinases-1+%28TIMP-1%29+in+human+breast+cancer.&rft.au=Yoshiji%2C+H%3BGomez%2C+D+E%3BThorgeirsson%2C+U+P&rft.aulast=Yoshiji&rft.aufirst=H&rft.date=1996-04-22&rft.volume=69&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-29 N1 - Date created - 1996-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human T-cell leukemia virus type I tax masks c-Myc function through a cAMP-dependent pathway. AN - 78015155; 8621651 AB - Human T-cell leukemia virus type I Tax is a pleiotropic gene regulator that functions through CREB/ATF- and NF-kappaB-mediated pathways. In most contexts, Tax is a potent gene activator. Here, we describe an unexpected finding of Myc repression by Tax. In cells that overexpress human T-cell leukemia virus type I Tax, the detection of c-Myc protein in the nucleus by a monoclonal antibody was masked. Tax prevented immunological visualization of a Myc epitope contained within amino acids 45-104, resulting in interference with Myc function in transcription and in anchorage-independent cell growth. Tax did not affect steady-state protein levels since detection of c-Myc with other antibodies was unperturbed. Four observations suggest that this Tax-Myc interaction is mediated through CREB/ATF signal transduction. 1) Tax point mutants, selectively defective for activation of CREB/ATF but not NF-kappaB, failed to mask c-Myc; 2) masking of Myc was abolished when Tax-expressing cells were treated with protein kinase inhibitor H-9; 3) Tax-specific shielding of Myc is absent in cells (B1R) that are genetically defective for cAMP signaling; and 4) forskolin treatment of cells mimicked Tax in masking the Myc epitope. Considered collectively, these findings suggest a regulation of Myc function at the level of localized protein conformation. JF - The Journal of biological chemistry AU - Semmes, O J AU - Barret, J F AU - Dang, C V AU - Jeang, K T AD - Molecular Virology Section, Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1996/04/19/ PY - 1996 DA - 1996 Apr 19 SP - 9730 EP - 9738 VL - 271 IS - 16 SN - 0021-9258, 0021-9258 KW - Cyclic AMP Response Element-Binding Protein KW - 0 KW - Epitopes KW - Gene Products, tax KW - Proto-Oncogene Proteins c-myc KW - Recombinant Proteins KW - Cyclic AMP KW - E0399OZS9N KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Genes, myc KW - HeLa Cells KW - Humans KW - Plasmids KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Mutagenesis KW - Cloning, Molecular KW - Rats KW - Epitopes -- analysis KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - Transfection KW - Recombinant Proteins -- metabolism KW - Restriction Mapping KW - Escherichia coli KW - Signal Transduction KW - Cell Line KW - Sequence Deletion KW - Protein Conformation KW - Cell Division KW - Proto-Oncogene Proteins c-myc -- biosynthesis KW - Gene Products, tax -- metabolism KW - Cyclic AMP -- metabolism KW - Human T-lymphotropic virus 1 -- metabolism KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Proto-Oncogene Proteins c-myc -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78015155?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Human+T-cell+leukemia+virus+type+I+tax+masks+c-Myc+function+through+a+cAMP-dependent+pathway.&rft.au=Semmes%2C+O+J%3BBarret%2C+J+F%3BDang%2C+C+V%3BJeang%2C+K+T&rft.aulast=Semmes&rft.aufirst=O&rft.date=1996-04-19&rft.volume=271&rft.issue=16&rft.spage=9730&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-18 N1 - Date created - 1996-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity. AN - 77991373; 8632481 AB - A number of biochemical properties differ dramatically among homologues within the pancreatic ribonuclease superfamily. Human pancreatic ribonuclease (hRNase) has high enzyme activity, extreme sensitivity to ribonuclease inhibitor (RI) and is non-toxic, whereas a homologous RNase from frog eggs, called onconase, has much lower enzyme activity, is not sensitive to RI and is cytotoxic to cancer cell lines and animals. To explore the structural basis of these differences among members in the RNAse family we synthesized genes for onconase, hRNase, a mutant onconase (K9Q) and onconase-hRNase N-terminal hybrids and expressed the proteins in Escherichia coli with final yields of 10 to 50 mg per liter of culture after purification. A recombinant version of onconase with an N-terminal methionine instead of the native pyroglutamyl residue had decreased cytotoxicity and enzyme activity. Cleavage of the recombinant onconase Met-1 residue, and cyclization of the Gln1 residue to reform the pyroglutamyl N terminus, reconstituted cytotoxicity and enzyme activity. Thus a unique role of the pyroglutamyl residue in the active site of amphibian RNases is indicated. Replacement of one to nine residues of onconase with the homologous residues of hRNase increased the enzymatic activity against most of the substrates tested with a simultaneous shift in the enzyme specificity from high preference for poly(U) to slight preference for poly(C). Cytotoxicity of the chimera decreased, dissociating cytotoxicity from enzymatic activity. The molecular basis for the low binding affinity of onconase for RI has been examined experimentally with the recombinant RNases and by fitting onconase and RNase A structures to the coordinates from the recently published RNase A-RI complex. JF - Journal of molecular biology AU - Boix, E AU - Wu, Y AU - Vasandani, V M AU - Saxena, S K AU - Ardelt, W AU - Ladner, J AU - Youle, R J AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/04/19/ PY - 1996 DA - 1996 Apr 19 SP - 992 EP - 1007 VL - 257 IS - 5 SN - 0022-2836, 0022-2836 KW - Egg Proteins KW - 0 KW - Enzyme Inhibitors KW - Placental Hormones KW - Recombinant Fusion Proteins KW - placental ribonuclease inhibitor KW - 120178-77-0 KW - RNA KW - 63231-63-0 KW - Ribonucleases KW - EC 3.1.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Pyrrolidonecarboxylic Acid KW - SZB83O1W42 KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Rana pipiens KW - Osmolar Concentration KW - Animals KW - Humans KW - Recombinant Fusion Proteins -- isolation & purification KW - Amino Acid Sequence KW - Pyrrolidonecarboxylic Acid -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - Tumor Cells, Cultured KW - RNA -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Pyrrolidonecarboxylic Acid -- chemistry KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Ribonuclease, Pancreatic -- antagonists & inhibitors KW - Ribonucleases -- antagonists & inhibitors KW - Ribonucleases -- chemistry KW - Ribonucleases -- metabolism KW - Ribonuclease, Pancreatic -- metabolism KW - Egg Proteins -- antagonists & inhibitors KW - Ribonuclease, Pancreatic -- pharmacology KW - Cell Survival -- drug effects KW - Ribonucleases -- pharmacology KW - Placental Hormones -- pharmacology KW - Egg Proteins -- chemistry KW - Egg Proteins -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Egg Proteins -- pharmacology KW - Ribonuclease, Pancreatic -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77991373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Role+of+the+N+terminus+in+RNase+A+homologues%3A+differences+in+catalytic+activity%2C+ribonuclease+inhibitor+interaction+and+cytotoxicity.&rft.au=Boix%2C+E%3BWu%2C+Y%3BVasandani%2C+V+M%3BSaxena%2C+S+K%3BArdelt%2C+W%3BLadner%2C+J%3BYoule%2C+R+J&rft.aulast=Boix&rft.aufirst=E&rft.date=1996-04-19&rft.volume=257&rft.issue=5&rft.spage=992&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-28 N1 - Date created - 1996-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased incidence of spontaneous mammary gland neoplasms in female F344 rats treated with amphetamine, methylphenidate, or codeine. AN - 77978636; 8603383 AB - Three drugs that affect the neuroendocrine system (amphetamine, methylphenidate, and codeine) caused decreases in body weights and in the incidence of spontaneously occurring mammary gland neoplasms in the female F344/N rat in 2-year carcinogenicity studies. Using a mathematical model that relates body weight changes to the incidence of mammary gland neoplasms, we find that the decrease in mammary gland tumours seen in female rats cannot be fully explained by body weight decreases relative to control animals. Further, the observed decreases in body weight in treated female rats were not a function of differences in feed consumption between treated and control groups. These pharmaceuticals are thought to affect the biologic system through interaction with membrane receptors. This interaction and/or subsequent cell signaling events may play a role in the observed decrease in spontaneously occurring mammary gland neoplasms in the female rat treated with amphetamine, methylphenidate, or codeine. JF - Cancer letters AU - Dunnick, J K AU - Elwell, M R AU - Haseman, J K AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/04/19/ PY - 1996 DA - 1996 Apr 19 SP - 77 EP - 83 VL - 102 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Analgesics, Opioid KW - 0 KW - Anticarcinogenic Agents KW - Central Nervous System Stimulants KW - Methylphenidate KW - 207ZZ9QZ49 KW - Amphetamine KW - CK833KGX7E KW - Codeine KW - Q830PW7520 KW - Index Medicus KW - Rats KW - Mice, Inbred Strains KW - Animals KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Carcinogenicity Tests KW - Body Weight -- physiology KW - Mice KW - Male KW - Female KW - Anticarcinogenic Agents -- therapeutic use KW - Codeine -- therapeutic use KW - Analgesics, Opioid -- therapeutic use KW - Methylphenidate -- therapeutic use KW - Central Nervous System Stimulants -- therapeutic use KW - Amphetamine -- therapeutic use KW - Mammary Neoplasms, Experimental -- etiology KW - Mammary Neoplasms, Experimental -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77978636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Decreased+incidence+of+spontaneous+mammary+gland+neoplasms+in+female+F344+rats+treated+with+amphetamine%2C+methylphenidate%2C+or+codeine.&rft.au=Dunnick%2C+J+K%3BElwell%2C+M+R%3BHaseman%2C+J+K&rft.aulast=Dunnick&rft.aufirst=J&rft.date=1996-04-19&rft.volume=102&rft.issue=1-2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-16 N1 - Date created - 1996-05-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Lett 1996 Jul 19;105(1):121-2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide and septic shock. AN - 77996949; 8609688 JF - JAMA AU - Cobb, J P AU - Danner, R L AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/04/17/ PY - 1996 DA - 1996 Apr 17 SP - 1192 EP - 1196 VL - 275 IS - 15 SN - 0098-7484, 0098-7484 KW - Enzyme Inhibitors KW - 0 KW - Isoenzymes KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Hypotension -- etiology KW - Multiple Organ Failure -- physiopathology KW - Vascular Resistance -- drug effects KW - Mice KW - Hypotension -- physiopathology KW - Child, Preschool KW - Mice, Knockout KW - Multiple Organ Failure -- etiology KW - Adult KW - Dogs KW - Blood Pressure -- drug effects KW - Female KW - Male KW - Hemodynamics -- drug effects KW - Nitric Oxide -- adverse effects KW - Enzyme Inhibitors -- therapeutic use KW - Nitric Oxide -- antagonists & inhibitors KW - Shock, Septic -- drug therapy KW - Nitric Oxide -- physiology KW - Isoenzymes -- antagonists & inhibitors KW - Isoenzymes -- physiology KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Nitric Oxide Synthase -- physiology KW - Enzyme Inhibitors -- pharmacology KW - Shock, Septic -- diagnosis KW - Shock, Septic -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77996949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Nitric+oxide+and+septic+shock.&rft.au=Cobb%2C+J+P%3BDanner%2C+R+L&rft.aulast=Cobb&rft.aufirst=J&rft.date=1996-04-17&rft.volume=275&rft.issue=15&rft.spage=1192&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-28 N1 - Date created - 1996-05-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1996 Sep 11;276(10):781-2 [8769583] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of BRCA1 mutations in women with early-onset ovarian cancer by use of the protein truncation test. AN - 77994583; 8606385 JF - Journal of the National Cancer Institute AU - Lancaster, J M AU - Cochran, C J AU - Brownlee, H A AU - Evans, A C AU - Berchuck, A AU - Futreal, P A AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1996/04/17/ PY - 1996 DA - 1996 Apr 17 SP - 552 EP - 554 VL - 88 IS - 8 SN - 0027-8874, 0027-8874 KW - BRCA1 Protein KW - 0 KW - DNA, Neoplasm KW - Neoplasm Proteins KW - Transcription Factors KW - Index Medicus KW - DNA, Neoplasm -- chemistry KW - Humans KW - Middle Aged KW - Female KW - Ovarian Neoplasms -- genetics KW - Neoplasm Proteins -- genetics KW - Transcription Factors -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77994583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Detection+of+BRCA1+mutations+in+women+with+early-onset+ovarian+cancer+by+use+of+the+protein+truncation+test.&rft.au=Lancaster%2C+J+M%3BCochran%2C+C+J%3BBrownlee%2C+H+A%3BEvans%2C+A+C%3BBerchuck%2C+A%3BFutreal%2C+P+A%3BWiseman%2C+R+W&rft.aulast=Lancaster&rft.aufirst=J&rft.date=1996-04-17&rft.volume=88&rft.issue=8&rft.spage=552&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-21 N1 - Date created - 1996-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. AN - 78005064; 8623000 AB - Determinants of the recommended dietary allowance (RDA) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration, bioavailability, urinary excretion, cell concentration, and potential adverse effects. Because current data are inadequate, an in-hospital depletion-repletion study was conducted. Seven healthy volunteers were hospitalized for 4-6 months and consumed a diet containing <5 mg of vitamin C daily. Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg. Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics. The steep portion of the curve occurred between the 30- and 100-mg daily dose, the current RDA of 60 mg daily was on the lower third of the curve, the first dose beyond the sigmoid portion of the curve was 200 mg daily, and complete plasma saturation occurred at 1000 mg daily. Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Levine, M AU - Conry-Cantilena, C AU - Wang, Y AU - Welch, R W AU - Washko, P W AU - Dhariwal, K R AU - Park, J B AU - Lazarev, A AU - Graumlich, J F AU - King, J AU - Cantilena, L R AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USA. Y1 - 1996/04/16/ PY - 1996 DA - 1996 Apr 16 SP - 3704 EP - 3709 VL - 93 IS - 8 SN - 0027-8424, 0027-8424 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - United States KW - Humans KW - Safety KW - National Institutes of Health (U.S.) KW - Adult KW - Male KW - Biological Availability KW - Nutritional Requirements KW - Ascorbic Acid -- administration & dosage KW - Nutrition Policy KW - Ascorbic Acid -- adverse effects KW - Ascorbic Acid -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78005064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Vitamin+C+pharmacokinetics+in+healthy+volunteers%3A+evidence+for+a+recommended+dietary+allowance.&rft.au=Levine%2C+M%3BConry-Cantilena%2C+C%3BWang%2C+Y%3BWelch%2C+R+W%3BWashko%2C+P+W%3BDhariwal%2C+K+R%3BPark%2C+J+B%3BLazarev%2C+A%3BGraumlich%2C+J+F%3BKing%2C+J%3BCantilena%2C+L+R&rft.aulast=Levine&rft.aufirst=M&rft.date=1996-04-16&rft.volume=93&rft.issue=8&rft.spage=3704&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-18 N1 - Date created - 1996-06-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Clin Nutr. 1987 Aug;46(2):290-4 [3618533] J Biol Chem. 1986 Jun 5;261(16):7347-56 [3711090] J Biol Chem. 1989 Sep 15;264(26):15404-9 [2768269] J Biol Chem. 1989 Nov 15;264(32):18996-9002 [2681206] Anal Biochem. 1989 Sep;181(2):276-82 [2817392] Clin Chem. 1989 Dec;35(12):2330-3 [2591053] J Biol Chem. 1990 Feb 15;265(5):2584-7 [2303417] Am J Clin Nutr. 1990 May;51(5):837-45 [2333842] Atherosclerosis. 1990 Jun;82(3):185-91 [2375783] Lancet. 1991 Jan 5;337(8732):1-5 [1670647] Anal Biochem. 1990 Aug 15;189(1):18-23 [2278385] J Nutr. 1991 Feb;121(2):170-6 [1995787] J Biol Chem. 1991 Mar 25;266(9):5384-7 [1825997] Biochem J. 1991 Mar 15;274 ( Pt 3):739-44 [2012602] Am J Clin Nutr. 1991 Oct;54(4):712-6 [1897478] J Nutr. 1992 May;122(5):1111-8 [1564563] J Urol. 1992 May;147(5):1215-8 [1569652] Epidemiology. 1992 May;3(3):194-202 [1591317] Anal Biochem. 1992 Jul;204(1):1-14 [1514674] J Am Diet Assoc. 1992 Nov;92(11):1352-7 [1430720] Carcinogenesis. 1992 Dec;13(12):2277-80 [1473234] Clin Investig. 1993 Jan;71(1):3-6 [8453256] N Engl J Med. 1993 May 20;328(20):1450-6 [8479464] World Rev Nutr Diet. 1993;72:114-27 [8506699] Biochem J. 1993 Sep 1;294 ( Pt 2):505-10 [8373364] J Urol. 1994 Apr;151(4):834-7 [8126804] Eur J Clin Nutr. 1994 Feb;48(2):118-27 [8194493] N Engl J Med. 1994 Jul 21;331(3):141-7 [8008027] Nutr Rev. 1994 Aug;52(8 Pt 1):266-70 [7970289] Am J Clin Nutr. 1966 Dec;19(6):371-8 [5954013] Am J Clin Nutr. 1969 May;22(5):535-48 [4977512] Am J Clin Nutr. 1969 May;22(5):549-58 [4891320] Am J Clin Nutr. 1971 Apr;24(4):432-43 [5090631] Am J Clin Nutr. 1971 Apr;24(4):444-54 [5090632] Eur J Pharmacol. 1972 Jul;19(1):140-2 [5048660] Ann Intern Med. 1976 Apr;84(4):385-8 [1259282] Am J Clin Nutr. 1979 Mar;32(3):530-9 [420145] Clin Pharmacol Ther. 1981 Mar;29(3):318-21 [7471601] Am J Clin Nutr. 1982 Aug;36(2):332-9 [7102589] Blood. 1984 Sep;64(3):721-6 [6466873] Am J Public Health. 1986 Mar;76(3):287-9 [3484909] N Engl J Med. 1986 Apr 3;314(14):892-902 [3513016] Am J Clin Nutr. 1987 Nov;46(5):818-26 [3673928] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complete nucleotide sequences of the domestic cat (Felis catus) mitochondrial genome and a transposed mtDNA tandem repeat (Numt) in the nuclear genome. AN - 78174348; 8660972 AB - The complete 17,009-bp mitochondrial genome of the domestic cat, Felis catus, has been sequenced and conforms largely to the typical organization of previously characterized mammalian mtDNAs. Codon usage and base composition also followed canonical vertebrate patterns, except for an unusual ATC (non-AUG) codon initiating the NADH dehydrogenase subunit 2 (ND2) gene. Two distinct repetitive motifs at opposite ends of the control region contribute to the relatively large size (1559 bp) of this carnivore mtDNA. Alignment of the feline mtDNA genome to a homologous 7946-bp nuclear mtDNA tandem repeat DNA sequence in the cat, Numt, indicates simple repeat motifs associated with insertion/deletion mutations. Overall DNA sequence divergence between Numt and cytoplasmic mtDNA sequence was only 5.1%. Substitutions predominate at the third codon position of homologous feline protein genes. Phylogenetic analysis of mitochondrial gene sequences confirms the recent transfer of the cytoplasmic mtDNA sequences to the domestic cat nucleus and recapitulates evolutionary relationships between mammal species. JF - Genomics AU - Lopez, J V AU - Cevario, S AU - O'Brien, S J AD - Biological Carcinogenesis and Development Program, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, Maryland, USA. Y1 - 1996/04/15/ PY - 1996 DA - 1996 Apr 15 SP - 229 EP - 246 VL - 33 IS - 2 SN - 0888-7543, 0888-7543 KW - DNA Transposable Elements KW - 0 KW - DNA, Mitochondrial KW - Index Medicus KW - Phylogeny KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Mitochondria KW - Amino Acid Sequence KW - Cell Nucleus KW - Repetitive Sequences, Nucleic Acid KW - Nucleic Acid Conformation KW - Genome KW - Cats -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78174348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Complete+nucleotide+sequences+of+the+domestic+cat+%28Felis+catus%29+mitochondrial+genome+and+a+transposed+mtDNA+tandem+repeat+%28Numt%29+in+the+nuclear+genome.&rft.au=Lopez%2C+J+V%3BCevario%2C+S%3BO%27Brien%2C+S+J&rft.aulast=Lopez&rft.aufirst=J&rft.date=1996-04-15&rft.volume=33&rft.issue=2&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-22 N1 - Date created - 1997-01-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U20754; GENBANK; U20753 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of a truncated Int3 gene in developing secretory mammary epithelium specifically retards lobular differentiation resulting in tumorigenesis. AN - 77976160; 8620493 AB - Insertional mutation of the Int3 gene, a member of the Notch gene family, is frequently associated with primary mouse mammary tumors induced by the mouse mammary tumor virus (MMTV). A major consequence of these mutations is the production of a shortened 2.4-kb tumor specific Int3 RNA transcript that encodes the entire intracellular domain of the Int3 protein. Previous studies have demonstrated that mammary gland development and function was severely impaired in transgenic mice expressing the truncated Int3 gene product from the MMTV viral promoter. Both mammary ductal growth and secretory lobule development were curtailed in these mice. These results were attributed to a gain of function modification of the Int3 gene, which led to a restriction of cell fate selection in the affected mammary epithelial cells. To confirm and extend these findings, truncated Int3 was expressed from the whey acidic protein (WAP) promoter, the activity of which, unlike that of the MMTV long terminal repeat, is restricted to the secretory mammary epithelial population. In transgenic mice carrying the WAP/Int3 construct, mammary ductal growth was unaffected in virgin females, but growth and differentiation of secretory lobules during gestation was profoundly inhibited. Coincidental with the block in lobular secretory differentiation, mammary dysplasia and tumorigenesis occurred in all breeding females by 25 weeks of age. In nonbreeding WAP/Int3 females, mammary tumor incidence also reached 100%, but only after 70 weeks. The WAP/Int3 mammary tumors were highly malignant, and most tumor-bearing females, irrespective of breeding history, developed metastatic lung lesions. These results suggest that WAP promotor-targeted Int3 function is associated with mammary secretory cell differentiation and maintenance in this transgenic model. Consistent with the conclusion that WAP-driven truncated Int3 expression influenced only lobular differentiation and not ductal growth and extension during mammary gland development, transplants of WAP/Int3 gland into nontransgenic mammary fat pads produced complete mammary ductal outgrowths in virgin FVB/N mice but failed to develop secretory lobules when the females were impregnated. JF - Cancer research AU - Gallahan, D AU - Jhappan, C AU - Robinson, G AU - Hennighausen, L AU - Sharp, R AU - Kordon, E AU - Callahan, R AU - Merlino, G AU - Smith, G H AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996/04/15/ PY - 1996 DA - 1996 Apr 15 SP - 1775 EP - 1785 VL - 56 IS - 8 SN - 0008-5472, 0008-5472 KW - DNA Primers KW - 0 KW - Milk Proteins KW - Proto-Oncogene Proteins KW - Receptors, Cell Surface KW - Receptors, Notch KW - Recombinant Proteins KW - whey acidic proteins KW - Notch4 protein, mouse KW - 146991-60-8 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Milk Proteins -- biosynthesis KW - Mammary Tumor Virus, Mouse KW - Cell Differentiation KW - Transcription, Genetic KW - Mice KW - Mice, Transgenic KW - Precancerous Conditions -- pathology KW - Pregnancy KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Promoter Regions, Genetic KW - Precancerous Conditions -- genetics KW - Base Sequence KW - Epithelial Cells KW - Milk Proteins -- genetics KW - Epithelium -- physiology KW - Molecular Sequence Data KW - Epithelium -- pathology KW - Mutagenesis, Insertional KW - Female KW - Proto-Oncogene Proteins -- biosynthesis KW - Mammary Glands, Animal -- cytology KW - Mammary Glands, Animal -- physiology KW - Mammary Glands, Animal -- pathology KW - Gene Expression KW - Mammary Neoplasms, Experimental -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Mammary Neoplasms, Experimental -- prevention & control KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77976160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Expression+of+a+truncated+Int3+gene+in+developing+secretory+mammary+epithelium+specifically+retards+lobular+differentiation+resulting+in+tumorigenesis.&rft.au=Gallahan%2C+D%3BJhappan%2C+C%3BRobinson%2C+G%3BHennighausen%2C+L%3BSharp%2C+R%3BKordon%2C+E%3BCallahan%2C+R%3BMerlino%2C+G%3BSmith%2C+G+H&rft.aulast=Gallahan&rft.aufirst=D&rft.date=1996-04-15&rft.volume=56&rft.issue=8&rft.spage=1775&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-14 N1 - Date created - 1996-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Familial alcoholism in manic-depressive (bipolar) disease. AN - 78187286; 8723047 AB - A previous analysis found a relatively high rate of alcoholism in a cohort of bipolar I subjects, and a trend for increased rates of alcoholism in relatives of subjects with both bipolar I disorder and alcoholism, compared to relatives of subjects with bipolar I disorder and no alcoholism. The sample of subjects with bipolar I disorder has been enlarged through continued follow-up, permitting new analyses to address the association and heritability of bipolar I disorder with alcoholism. Probands with bipolar I disorder were followed for 10 years as part of the NIMH Collaborative Depression Study. The rate of alcoholism in relatives of probands with both bipolar I disorder and alcoholism was compared to the rate of alcoholism in relatives of probands with bipolar disorder and no alcoholism. The prevalence of alcoholism in relatives of subjects with bipolar I disorder was compared to the rate of alcoholism in relatives of control subjects. Relatives of probands with bipolar I disorder showed a higher rate of alcoholism than relatives of controls. Relatives of probands with bipolar I disorder and alcoholism showed a higher rate of alcoholism than relatives of probands with bipolar I disorder without alcoholism. These data suggest that familial alcoholism may contribute to a vulnerability to bipolar I disorder, and that there is a shared heritability for the two disorders. JF - American journal of medical genetics AU - Winokur, G AU - Coryell, W AU - Endicott, J AU - Keller, M AU - Akiskal, H AU - Solomon, D AD - National Institute of Mental Health Collaborative Program on the Psychobiology of Depression, Clinical Studies, Washington, DC, USA. Y1 - 1996/04/09/ PY - 1996 DA - 1996 Apr 09 SP - 197 EP - 201 VL - 67 IS - 2 SN - 0148-7299, 0148-7299 KW - Index Medicus KW - Age of Onset KW - Humans KW - Adult KW - Retrospective Studies KW - Follow-Up Studies KW - Longitudinal Studies KW - Male KW - Female KW - Bipolar Disorder -- genetics KW - Alcoholism -- genetics KW - Alcoholism -- complications KW - Bipolar Disorder -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78187286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=Familial+alcoholism+in+manic-depressive+%28bipolar%29+disease.&rft.au=Winokur%2C+G%3BCoryell%2C+W%3BEndicott%2C+J%3BKeller%2C+M%3BAkiskal%2C+H%3BSolomon%2C+D&rft.aulast=Winokur&rft.aufirst=G&rft.date=1996-04-09&rft.volume=67&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of delta-opioid receptors in mediating the aversive stimulus effects of morphine withdrawal in the rat. AN - 78180104; 8741160 AB - An unbiased place preference conditioning procedure was used to examine the role of delta-opioid receptors in mediating the aversive effects of opioid withdrawal. Rats were implanted s.c. with two pellets each containing placebo or 75 mg morphine. Single-trial conditioning sessions with saline and the opioid receptor antagonists naloxone (0.001-1.0 mg/kg, s.c.), naltrindole (0.01-3.0 mg/kg, s.c.) or naltriben (0.01-3.0 mg/kg, s.c.) commenced 4 days later. During these conditioning sessions, physical signs of withdrawal were also quantified. Tests of conditioning were conducted on day 5. Naloxone in doses of 0.01-1.0 mg/kg produced significant conditioned place aversions in morphine-implanted animals. A dose of 0.01 mg/kg produced few physical withdrawal signs whereas higher doses resulted in marked wet dog shakes, body weight loss ptosis and diarrhea. No such effects were observed in control (placebo-implanted) animals. Administration of the selective delta-opioid receptor antagonists naltrindole and naltriben produced dose-related place aversions in morphine-implanted animals. The magnitude of these effects did not differ from that observed with naloxone. The minimum effective doses of naltrindole and naltriben were 0.1 mg/kg. Doses of 0.1-1.0 mg/kg produced few, if any, somatic signs of withdrawal whereas higher doses of these antagonists only produced diarrhea and wet-dog shakes. Other withdrawal signs were absent. In contrast to the opioid receptor antagonists tested, the dopamine D1 receptor antagonist SCH23390 failed to produced conditioned place aversions or physical signs of withdrawal in morphine-pelleted animals. These data demonstrate that the selective blockade of either delta- or mu-opioid receptors is sufficient to induce conditioned aversive effects in morphine-dependent animals. They also indicate that physical symptoms associated with precipitated morphine withdrawal differ depending upon the opioid receptor antagonist employed. JF - European journal of pharmacology AU - Funada, M AU - Schutz, C G AU - Shippenberg, T S AD - Clinical Pharmacology Branch, National Institute on Drug Abuse, National Institute of Health, Baltimore, MD 21224, USA. Y1 - 1996/04/04/ PY - 1996 DA - 1996 Apr 04 SP - 17 EP - 24 VL - 300 IS - 1-2 SN - 0014-2999, 0014-2999 KW - Narcotic Antagonists KW - 0 KW - Receptors, Opioid, delta KW - naltrindole benzofuran KW - 111555-58-9 KW - Naloxone KW - 36B82AMQ7N KW - Naltrexone KW - 5S6W795CQM KW - Morphine KW - 76I7G6D29C KW - naltrindole KW - G167Z38QA4 KW - Index Medicus KW - Rats KW - Naloxone -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Male KW - Receptors, Opioid, delta -- antagonists & inhibitors KW - Substance Withdrawal Syndrome -- physiopathology KW - Morphine -- adverse effects KW - Naltrexone -- analogs & derivatives KW - Naltrexone -- pharmacology KW - Receptors, Opioid, delta -- physiology KW - Narcotic Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78180104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Role+of+delta-opioid+receptors+in+mediating+the+aversive+stimulus+effects+of+morphine+withdrawal+in+the+rat.&rft.au=Funada%2C+M%3BSchutz%2C+C+G%3BShippenberg%2C+T+S&rft.aulast=Funada&rft.aufirst=M&rft.date=1996-04-04&rft.volume=300&rft.issue=1-2&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-17 N1 - Date created - 1996-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The secondary leukemias: challenges and research directions. AN - 77966151; 8618232 AB - Acute myelogenous leukemia (AML) arising following exposure to genotoxic agents has been recognized as a distinctive entity for more than 40 years. Secondary, or therapy-related, AML accounts for 10%-20% of all AML cases. This review addresses four overarching areas of investigation focused on secondary AMLs: 1) dissection of the molecular structure of the induced genetic lesions and identification of the functional consequences of these changes, thereby providing clues to the pathogenesis of secondary AML and potentially serving as a basis for innovative therapeutic interventions; 2) identification and characterization of mechanisms of DNA damage and the orderly repair of such damage; 3) identification and application of accurate biomarkers of leukemogenesis for the purpose of risk prediction and quantification, potentially allowing recognition of patients especially susceptible to the leukemogenic effects of chemotherapy (for genetic or acquired reasons) and allowing their treatment for cancer to be modified on the basis of this susceptibility; and 4) design and implementation of longitudinal clinical and genetic monitoring of high-risk populations (i.e., individuals under-going cytotoxic therapies for primary cancers). This review of the literature relating to these areas builds upon these themes and attempts to synthesize these seemingly disparate areas of research so that they can be more effectively utilized together to address the problem of secondary AML. Ultimately, the evaluation of these areas will improve our understanding of de novo leukemia and will serve as a springboard for the development of new concepts of therapy and prevention. JF - Journal of the National Cancer Institute AU - Smith, M A AU - McCaffrey, R P AU - Karp, J E AD - National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/04/03/ PY - 1996 DA - 1996 Apr 03 SP - 407 EP - 418 VL - 88 IS - 7 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Alkylating KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Index Medicus KW - Animals KW - DNA Repair KW - DNA Damage KW - Risk Factors KW - Humans KW - DNA Topoisomerases, Type II -- metabolism KW - Prognosis KW - Incidence KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Neoplasms -- drug therapy KW - Neoplasms, Second Primary -- epidemiology KW - Neoplasms, Second Primary -- etiology KW - Leukemia, Myeloid, Acute -- genetics KW - Leukemia, Myeloid, Acute -- epidemiology KW - Neoplasms, Second Primary -- genetics KW - Leukemia, Myeloid, Acute -- etiology KW - Leukemia, Myeloid, Acute -- chemically induced KW - Neoplasms, Second Primary -- chemically induced KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77966151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=The+secondary+leukemias%3A+challenges+and+research+directions.&rft.au=Smith%2C+M+A%3BMcCaffrey%2C+R+P%3BKarp%2C+J+E&rft.aulast=Smith&rft.aufirst=M&rft.date=1996-04-03&rft.volume=88&rft.issue=7&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-07 N1 - Date created - 1996-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ultrastructural localization of G-protein GS in the lateral wall of the guinea pig cochlear duct. AN - 85242846; pmid-8735072 AB - Immunocytochemical localization of a GTP-binding protein, Gs, in the various cells of the lateral wall of guinea pig cochlear duct was investigated using a post-embedding immunogold method with antibody raised against a synthetic decapeptide (RMHLRQYELL) encoding the C-terminus of the alpha-subunit of Gs. In the stria vascularis, labeling was observed on the basolateral membrane infoldings of marginal cells, on the juxtaposed membrane of intermediate cells, and on the cell membrane of basal cell. In contrast, no significant labeling was observed on the luminal membrane of marginal cells. Immunoreactivity also was detected on the cell membranes of various other cells. These include spiral prominence epithelial cells, fibrocytes of spiral ligament, external sulcus cells, and epithelial and mesothelial cells of Reissner's membrane. Adenylylcyclase has been functionally implicated in some of the cell types with membranes labeled in this study. The significance of these findings is briefly discussed. JF - Hearing Research AU - Mizuta, K AU - Iwasa, K H AU - Simonds, W F AU - Tachibana, M AD - Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892, USA. PY - 1996 SP - 111 EP - 119 VL - 93 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Guinea Pigs KW - Animal KW - Stria Vascularis KW - Adenylate Cyclase KW - Epithelium KW - GTP-Binding Proteins KW - Peptides KW - Spiral Ganglion KW - Immunohistochemistry KW - Female KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85242846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hearing+Research&rft.atitle=Ultrastructural+localization+of+G-protein+GS+in+the+lateral+wall+of+the+guinea+pig+cochlear+duct.&rft.au=Mizuta%2C+K%3BIwasa%2C+K+H%3BSimonds%2C+W+F%3BTachibana%2C+M&rft.aulast=Mizuta&rft.aufirst=K&rft.date=1996-04-01&rft.volume=93&rft.issue=1-2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Hearing+Research&rft.issn=03785955&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Laryngeal muscle activity during speech breaks in adductor spasmodic dysphonia. AN - 85189159; pmid-8614226 AB - To determine the laryngeal muscle activation abnormalities that are associated with speech symptoms in adductor spasmodic dysphonia (ADSD), electromyographic measures of extrinsic and intrinsic laryngeal muscles during speech compared 1) muscle activity when ADSD patients had breaks in words with when they produced the same words without breaks; and 2) muscle activity in ADSD patients during speech without voice breaks with normal control producing phonetically similar words. Simultaneous electromyographic recordings were made from the thyroarytenoid (TA), cricothyroid (CT), sternothyroid (ST), thyrohyoid (TH) and the posterior cricoarytenoid (PCA) muscles during speech testing in 11 ADSD patients and 10 control subjects. Speech breaks were identified and mean muscle activity measured starting 100 ms preceding a voice break and for the remainder of the word. Mean muscle activity level was significantly greater on break than non break words in ADSD patients only for the thyroarytenoid muscle (p<.001). No significant differences were found between the ADSD and control subjects during non break words for any of the laryngeal muscles studied. The results demonstrated that 1) only the thyroarytenoid, of the muscles tested, was affected in ADSD, 2) that muscle activation abnormalities were spasmodic, only appearing when symptoms occurred and 3) no imbalances of muscle tone were evident when speech disruptions did not appear. JF - The Laryngoscope AU - Nash, E A AU - Ludlow, C L AD - Voice and Speech Section, National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892-1416, USA. PY - 1996 SP - 484 EP - 489 VL - 106 IS - 4 SN - 0023-852X, 0023-852X KW - Spasm KW - Analysis of Variance KW - Muscle Tonus KW - Laryngeal Muscles KW - Human KW - Electromyography KW - Aged KW - Comparative Study KW - Adult KW - Electrodes KW - Middle Age KW - Voice Disorders KW - Speech KW - Male KW - Female KW - Statistics, Nonparametric UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85189159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Laryngoscope&rft.atitle=Laryngeal+muscle+activity+during+speech+breaks+in+adductor+spasmodic+dysphonia.&rft.au=Nash%2C+E+A%3BLudlow%2C+C+L&rft.aulast=Nash&rft.aufirst=E&rft.date=1996-04-01&rft.volume=106&rft.issue=4&rft.spage=484&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Differential regulation of integrins and extracellular matrix binding in epidermal differentiation and squamous tumor progression. AN - 78770649; 9627711 AB - Cell surface receptors of the integrin family regulate physiological and pathological processes in skin, including proliferation, differentiation, and malignant transformation. In skin, integrins are compartmentalized. While alpha 6 beta 4 is restricted to the basal surface of basal cells, beta 1 integrins are expressed in basal and suprabasal layers. In vivo and in Ca(2+)-induced differentiation of mouse keratinocytes in vitro, the loss of attachment to laminin via alpha 6 beta 4 integrin is an early event associated with initiation of spinous differentiation. The restricted expression of alpha 6 beta 4 to the basal cells in normal skin is disrupted early in the development of squamous cancer, where benign papillomas at high risk for malignant progression express alpha 6 beta 4 suprabasally in an expanded proliferative compartment. The aberrant suprabasal alpha 6 beta 4 is associated with reduced keratin 1 expression and upregulation of keratin 13, keratin 8, and gamma-glutamyltranspeptidase. During malignant conversion, the increase in alpha 6 beta 4 protein and mRNA is associated with novel expression of an alternatively spliced form of the alpha 6 subunit, alpha 6B. The induction of alpha 6B both in vivo and in vitro is particularly high in malignant cells produced by transduction of both v-fos and v-rasHa oncogenes into normal keratinocytes where it was associated with increased attachment to laminin. Furthermore, binding to laminin is increased by introduction of alpha 6B into a papilloma cell line. These results establish a link between squamous tumor progression and the upregulation of the alpha 6 beta 4 integrin and suggest that expression of alpha 6B could be functionally relevant to interaction of tumor cells with the laminin matrix during malignant conversion. JF - The journal of investigative dermatology. Symposium proceedings AU - Tennenbaum, T AU - Belanger, A J AU - Quaranta, V AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute National Institutes of Health, bethesda, Maryland 20892-4355, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 157 EP - 161 VL - 1 IS - 2 SN - 1087-0024, 1087-0024 KW - Antigens, Surface KW - 0 KW - Integrin alpha6beta4 KW - Integrins KW - Laminin KW - Index Medicus KW - Animals KW - Humans KW - Cell Differentiation KW - Mice KW - Laminin -- metabolism KW - Skin Neoplasms -- etiology KW - Epidermis -- cytology KW - Epidermis -- metabolism KW - Antigens, Surface -- metabolism KW - Integrins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78770649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.atitle=Differential+regulation+of+integrins+and+extracellular+matrix+binding+in+epidermal+differentiation+and+squamous+tumor+progression.&rft.au=Tennenbaum%2C+T%3BBelanger%2C+A+J%3BQuaranta%2C+V%3BYuspa%2C+S+H&rft.aulast=Tennenbaum&rft.aufirst=T&rft.date=1996-04-01&rft.volume=1&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.issn=10870024&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of cisplatin cytotoxicity by 9-aminocamptothecin. AN - 78770493; 9816219 AB - Camptothecin (CPT) derivatives are presently in ongoing Phase I/II clinical trials. The interactions between 9-aminocamptothecin (9AC) and cisplatin (CDDP) have been studied in the IGROV-1 human ovarian cancer cell line used in the National Cancer Institute Drug Discovery Anticancer Screen. One-h simultaneous treatment with 9AC and CDDP produced synergistic cytotoxicity. Under these conditions, 9AC delayed the reversal of CDDP-induced DNA interstrand cross-links (ISCs) without modifying the maximum ISC frequency at 6 h after drug treatment. CDDP did not affect the amount and the kinetics of reversion of 9AC-induced DNA single-strand breaks. Simultaneous treatment with CDDP and 9AC prolonged the DNA synthesis inhibition produced by each drug alone. Consistently, flow cytometry analyses showed enhanced S-phase arrest in cells treated with the CDDP-9AC combination. The DNA polymerase inhibitor aphidicolin also increased the residual CDDP-induced ISCs. These results suggest that prolonged inhibition of DNA synthesis by CPTs potentiate the cytotoxicity of CDDP by inhibiting the reversal of CDDP-induced DNA damage. Therefore, the combination of CPTs and CDDP appears to be worthwhile in cancer chemotherapy. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Goldwasser, F AU - Valenti, M AU - Torres, R AU - Kohn, K W AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Science, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 687 EP - 693 VL - 2 IS - 4 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - DNA, Single-Stranded KW - Aphidicolin KW - 38966-21-1 KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - DNA KW - 9007-49-2 KW - Cisplatin KW - Q20Q21Q62J KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Aphidicolin -- pharmacology KW - S Phase -- drug effects KW - DNA, Single-Stranded -- drug effects KW - Tumor Cells, Cultured KW - DNA Damage KW - Humans KW - Drug Synergism KW - DNA -- biosynthesis KW - Female KW - Camptothecin -- pharmacology KW - Cisplatin -- pharmacology KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78770493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Potentiation+of+cisplatin+cytotoxicity+by+9-aminocamptothecin.&rft.au=Goldwasser%2C+F%3BValenti%2C+M%3BTorres%2C+R%3BKohn%2C+K+W%3BPommier%2C+Y&rft.aulast=Goldwasser&rft.aufirst=F&rft.date=1996-04-01&rft.volume=2&rft.issue=4&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53: at the crossroads of molecular carcinogenesis and molecular epidemiology. AN - 78767420; 9627703 AB - The p53 tumor suppressor gene is frequently mutated in human cancer, including squamous cell carcinoma and basal cell carcinoma of the skin, but is rarely mutated in skin melanoma. The p53 mutation spectrum provides insight into both the etiology of human cancer and the functional regions of the encoded protein that lead to clonal expansion of the p53 mutant cell. JF - The journal of investigative dermatology. Symposium proceedings AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 115 EP - 118 VL - 1 IS - 2 SN - 1087-0024, 1087-0024 KW - Index Medicus KW - Animals KW - Genes, Tumor Suppressor KW - Humans KW - Genetic Predisposition to Disease KW - Mutation KW - Genes, p53 -- physiology KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78767420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.atitle=p53%3A+at+the+crossroads+of+molecular+carcinogenesis+and+molecular+epidemiology.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1996-04-01&rft.volume=1&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.issn=10870024&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multistage carcinogenesis in the skin. AN - 78750404; 9627709 AB - The multistage evolution of squamous cell cancer on mouse skin has provided a model to dissect the biological and genetic changes that contribute to specific stages of carcinogenesis. Keratinocyte cell culture models have been developed that reproduce the genetic and epigenetic events in multistage skin carcinogenesis, and these provide insights into the biochemistry of the process. When the v-rasHa oncogene is transduced into normal mouse keratinocytes, the resultant papilloma phenotype is characterized by a high rate of cell proliferation, an aberrant program of differentiation marker expression, and resistance to terminal differentiation. These changes are attributed to differential effects on isoforms of protein kinase C coupled to activation of the epidermal growth factor receptor. Premalignant progression requires additional genetic changes in the v-rasHa-transduced cells. The acquisition of these changes is suppressed by transforming growth factor beta (TGF beta), and the absence of TGF beta in premalignant tumors indicates a high risk for malignant progression. Keratinocytes that are genetically null for the TGF beta 1 gene rapidly progress to squamous cell carcinomas when transduced with the v-rasHa oncogene. In culture, TGF beta 1 null keratinocytes exhibit a high rate of gene amplification that can be suppressed by concentrations of exogenous TGF beta well below those required to inhibit proliferation. This model is well-suited to identifying critical genetic changes that contribute to premalignant progression. JF - The journal of investigative dermatology. Symposium proceedings AU - Yuspa, S H AU - Dlugosz, A A AU - Denning, M F AU - Glick, A B AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4355, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 147 EP - 150 VL - 1 IS - 2 SN - 1087-0024, 1087-0024 KW - RNA, Messenger KW - 0 KW - Transforming Growth Factor beta KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Papilloma -- etiology KW - Precancerous Conditions -- etiology KW - Humans KW - RNA, Messenger -- analysis KW - Calcium -- physiology KW - Mice KW - Transforming Growth Factor beta -- genetics KW - Skin Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78750404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.atitle=Multistage+carcinogenesis+in+the+skin.&rft.au=Yuspa%2C+S+H%3BDlugosz%2C+A+A%3BDenning%2C+M+F%3BGlick%2C+A+B&rft.aulast=Yuspa&rft.aufirst=S&rft.date=1996-04-01&rft.volume=1&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.issn=10870024&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lessons learned from xeroderma pigmentosum. AN - 78555349; 8934754 JF - Photochemistry and photobiology AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, NCI, Bethesda, MD, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 420 EP - 422 VL - 63 IS - 4 SN - 0031-8655, 0031-8655 KW - Isotretinoin KW - EH28UP18IF KW - Index Medicus KW - Immunotherapy KW - Humans KW - Isotretinoin -- pharmacology KW - In Vitro Techniques KW - Ultraviolet Rays -- adverse effects KW - Mutation KW - Skin Neoplasms -- etiology KW - Skin Neoplasms -- therapy KW - Xeroderma Pigmentosum -- complications KW - Skin Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78555349?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Photochemistry+and+photobiology&rft.atitle=Lessons+learned+from+xeroderma+pigmentosum.&rft.au=Kraemer%2C+K+H&rft.aulast=Kraemer&rft.aufirst=K&rft.date=1996-04-01&rft.volume=63&rft.issue=4&rft.spage=420&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+photobiology&rft.issn=00318655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-31 N1 - Date created - 1996-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of the DNA incorporation in human MOLT-4 cells of two 2'-beta-fluoronucleosides, 2'-beta-fluoro-2',3'-dideoxyadenosine and fialuridine. AN - 78499247; 8901088 AB - Incorporation of 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ddA), a recently developed anti-HIV agent, into the cellular DNA of human MOLT-4 cells has been compared with the DNA incorporation seen with fialuridine (FIAU; 1-[2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl]-5-iodouracil), a potent anti-hepatitis B (anti-HBV) nucleoside analogue recently found to cause severe hepatic toxicity in human subjects. At equimolar concentrations (10 microM), incorporation of F-ddA was less than 1% of that for FIAU, a difference attributable to the lack of a 3'-hydroxyl group in the former compound and a consequent inability of F-ddA, unlike FIAU, to form DNA internucleotide linkages. JF - Journal of pharmaceutical sciences AU - Ahluwalia, G S AU - Driscoll, J S AU - Ford, H AU - Johns, D G AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 454 EP - 455 VL - 85 IS - 4 SN - 0022-3549, 0022-3549 KW - Antiviral Agents KW - 0 KW - 2-fluoro-2',3'-dideoxyadenosine KW - 114849-59-1 KW - Arabinofuranosyluracil KW - 3083-77-0 KW - Dideoxyadenosine KW - 4Q86AH641A KW - fialuridine KW - 53T7IN77LC KW - DNA KW - 9007-49-2 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Cell Line KW - Dideoxyadenosine -- metabolism KW - DNA -- metabolism KW - Arabinofuranosyluracil -- analogs & derivatives KW - Antiviral Agents -- metabolism KW - Arabinofuranosyluracil -- metabolism KW - Dideoxyadenosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78499247?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pharmaceutical+sciences&rft.atitle=Comparison+of+the+DNA+incorporation+in+human+MOLT-4+cells+of+two+2%27-beta-fluoronucleosides%2C+2%27-beta-fluoro-2%27%2C3%27-dideoxyadenosine+and+fialuridine.&rft.au=Ahluwalia%2C+G+S%3BDriscoll%2C+J+S%3BFord%2C+H%3BJohns%2C+D+G&rft.aulast=Ahluwalia&rft.aufirst=G&rft.date=1996-04-01&rft.volume=85&rft.issue=4&rft.spage=454&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmaceutical+sciences&rft.issn=00223549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-13 N1 - Date created - 1997-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-response analysis in risk assessment: evaluation of behavioral specificity. AN - 78434397; 9182046 AB - Several methods of quantitative risk assessment that have been described recently are particularly applicable to neurotoxic end points. These methods can be broadly divided into two types of approaches based on their treatment of dose-response data to estimate risks. Benchmark approaches estimate risks using variability in response to a fixed dose level in comparison with background control variability. Probabilistic approaches estimate risks using the variability in the dose to produce a small effect in the sample population. The current report seeks to extend the development of probabilistic approaches for neurotoxic end points. Because behavioral data are often used to assess therapeutic efficacy as well as toxicity (unwanted effects), this analysis focused on the relative risks of producing these effects with the same agent. The therapeutic potential of GBR 12909 was determined by its ability to decrease cocaine-maintained responding in monkeys. The effects of this agent were also assessed in the same monkeys using food-maintained responding to provide an indication of behavioral toxicity. GBR 12909 decreased both behaviors, with complete decreases on drug-seeking behavior occurring at doses that had minimal effects on food-maintained responding. The difference in the estimates of doses to decrease drug-seeking and food-maintained behavior suggested that specific therapeutic effects could be obtained in the absence of unwanted side effects for a definable proportion of the population. These results also suggest that multiple behavioral end points can be useful for identifying specific effects of chemicals for the purposes' of risk assessment. JF - Environmental health perspectives AU - Glowa, J R AD - Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. G7W@cu.nih.gov Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 391 EP - 396 VL - 104 Suppl 2 SN - 0091-6765, 0091-6765 KW - Neurotoxins KW - 0 KW - Piperazines KW - vanoxerine KW - 90X28IKH43 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Probability KW - Animals KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Piperazines -- therapeutic use KW - Macaca mulatta KW - Cocaine -- pharmacology KW - Risk Assessment KW - Behavior, Animal -- drug effects KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78434397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Dose-response+analysis+in+risk+assessment%3A+evaluation+of+behavioral+specificity.&rft.au=Glowa%2C+J+R&rft.aulast=Glowa&rft.aufirst=J&rft.date=1996-04-01&rft.volume=104+Suppl+2&rft.issue=&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-10 N1 - Date created - 1997-06-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Pharmacol Exp Ther. 1976 Mar;196(3):605-15 [1263115] Lab Anim Sci. 1994 Oct;44(5):491-4 [7844959] J Clin Psychiatry. 1983 May;44(5 Pt 2):202-5 [6406458] Fundam Appl Toxicol. 1984 Oct;4(5):854-71 [6510615] J Environ Pathol Toxicol Oncol. 1986 May-Aug;6(5-6):153-68 [3783437] Science. 1987 Sep 4;237(4819):1219-23 [2820058] Environ Health Perspect. 1987 Dec;76:155-61 [3447892] Science. 1988 Nov 4;242(4879):715-23 [2903550] Regul Toxicol Pharmacol. 1988 Dec;8(4):471-86 [3222488] Trends Pharmacol Sci. 1988 Feb;9(2):59-62 [3072731] J Pharmacol Exp Ther. 1989 Oct;251(1):150-5 [2529365] Neurotoxicology. 1990 Summer;11(2):237-56 [2234543] Int Clin Psychopharmacol. 1990 Oct;5(4):237-51 [2150527] Neurosci Biobehav Rev. 1991 Spring;15(1):153-8 [2052190] Br J Addict. 1991 Dec;86(12):1549-58 [1786486] J Neurosci. 1992 Jul;12(7):2439-50 [1319476] Science. 1978 Aug 11;201(4355):534-5 [96531] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Associations between drug use and behavioral repertoire in urban youths. AN - 78425863; 8857378 AB - Converging with psycho-social research findings, animal and human laboratory studies indicate that behavioral alternatives are important determinants of drug-taking. To investigate associations between how early adolescents spend their time, i.e. their behavioral repertoire and drug use (use of marijuana, crack/cocaine or inhalants), we analyzed data from an epidemiological sample of 1516 urban middle-school students who had completed private interviews in spring 1993. The interview included a 36-item questionnaire to assess how frequently the youth engaged in different activities; history of drug-taking was assessed separately. Multiple logistic regression was used to estimate associations between drug use and each of seven behavioral domains as well as sex, age and racial-ethnic status. Youths spending a great deal of time working for pay and assuming other adult-like roles were more likely to have initiated drug use (estimated odds ratio, OR = 3.49; p = 0.002). Those who spent much time in religious activities were less likely (OR = 0.2, p <0.001). An exploratory search for interactions disclosed other associations that merit attention in future research. These results corroborate evidence on the potential etiological significance of behavioral repertoire in relation to risk of drug use. JF - Addiction (Abingdon, England) AU - Johanson, C E AU - Duffy, F F AU - Anthony, J C AD - Etiology Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 523 EP - 534 VL - 91 IS - 4 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Humans KW - Surveys and Questionnaires KW - Child KW - Adolescent KW - Male KW - Female KW - Adolescent Behavior KW - Substance-Related Disorders KW - Urban Population UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78425863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Associations+between+drug+use+and+behavioral+repertoire+in+urban+youths.&rft.au=Johanson%2C+C+E%3BDuffy%2C+F+F%3BAnthony%2C+J+C&rft.aulast=Johanson&rft.aufirst=C&rft.date=1996-04-01&rft.volume=91&rft.issue=4&rft.spage=523&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-14 N1 - Date created - 1997-01-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Addiction 1996 Nov;91(11):1731-3 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Human tumor necrosis factor mutants: preparation and some properties]. TT - Mutanty faktora nekroza opukholeĭ cheloveka: poluchenie i nekotorye svoĭstva. AN - 78227914; 8768260 AB - Using polymerase chain reaction, a number of mutant genes encoding human tumor necrosis factor (TNF-alpha) with amino acid substitutions and a deletion were obtained. The mutant proteins (muteins) contained point mutations R32H, A33S, F144L, I118M, and I118A; double mutation R32H-F144L; and deletion of four amino acid residues 67-70. The mutant genes were expressed in E. coli under the control of constitutive promoters. A simple purification method for the muteins was developed and their physicochemical properties were studied. All the muteins obtained, except F144L and I118A, were shown by CD and cross-linking to from a spatial structure similar to that of the native TNF-alpha. The collection of muteins was characterized by their biological activity. Mutants R32H and A33S exerted a decreased cytotoxicity against murine fibroblast cell line L929, whereas point mutant F144L and double mutant R32H-F144L were essentially inactive. JF - Bioorganicheskaia khimiia AU - Shingarova, L N AU - Sagaĭdak, L N AU - Turetskaia, R L AU - Nedospasov, S A AU - Esipov, D S AU - Korobko, V G AD - National Cancer Institute, Frederick, MD, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 243 EP - 251 VL - 22 IS - 4 SN - 0132-3423, 0132-3423 KW - DNA Primers KW - 0 KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Humans KW - Point Mutation KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Plasmids KW - Cell Line KW - Sequence Deletion KW - Mutagenesis KW - Cloning, Molecular KW - Tumor Necrosis Factor-alpha -- physiology KW - Tumor Necrosis Factor-alpha -- isolation & purification KW - Tumor Necrosis Factor-alpha -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78227914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganicheskaia+khimiia&rft.atitle=%5BHuman+tumor+necrosis+factor+mutants%3A+preparation+and+some+properties%5D.&rft.au=Shingarova%2C+L+N%3BSaga%C4%ADdak%2C+L+N%3BTuretskaia%2C+R+L%3BNedospasov%2C+S+A%3BEsipov%2C+D+S%3BKorobko%2C+V+G&rft.aulast=Shingarova&rft.aufirst=L&rft.date=1996-04-01&rft.volume=22&rft.issue=4&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Bioorganicheskaia+khimiia&rft.issn=01323423&rft_id=info:doi/ LA - Russian DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-26 N1 - Date created - 1996-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-induced reversion of progression phenotype is accompanied by reversion of AP-1 phenotype in JB6 cells. AN - 78222537; 8727048 AB - Transformed JB6 cells can be stably reverted to nontransformed phenotype by AP-1 inhibiting gluccorticoid fluocinolone (FA) and cAMP elevator forskolin (FN), yielding stable revertants of promotion resistant (P-) and promotion sensitive (P+) phenotypes. AP-1 activity of nontransformed P- and P+ revertant clones was decreased under a variety of experimental conditions compared with their transformed counterparts. Moreover, AP-1 activity in P+ cells under anchorage-independent conditions was induced by 12-0-tetradecanoyl-phorbol-13-acetate (TPA) while AP-1 activity in the reverted P- cells was not induced, just as observed for the original P+ and P- variants. Taken together these data suggest that changes in AP-1 activity may be one key mediator not only of forward progression but also of reversion of tumor cells to nontransformed phenotype. In addition, the higher transfection efficiency of the new reverted P- and P+ cells renders them useful for studying the role of transcription factors in tumor promotion. JF - In vitro cellular & developmental biology. Animal AU - Lavrovsky, V AU - Dong, Z AU - Ma, W Y AU - Colburn, N AD - Laboratory of Viral Carcinogenesis, NCI-FCRDC, Frederick, Maryland 21702-1201, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 234 EP - 237 VL - 32 IS - 4 SN - 1071-2690, 1071-2690 KW - Glucocorticoids KW - 0 KW - Transcription Factor AP-1 KW - Fluocinolone Acetonide KW - 0CD5FD6S2M KW - Colforsin KW - 1F7A44V6OU KW - Epidermal Growth Factor KW - 62229-50-9 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Phenotype KW - Animals KW - 3T3 Cells KW - Transfection KW - Cell Division -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Epidermal Growth Factor -- pharmacology KW - Cell Line KW - Clone Cells -- drug effects KW - Colforsin -- pharmacology KW - Transcription Factor AP-1 -- antagonists & inhibitors KW - Transcription Factor AP-1 -- metabolism KW - Fluocinolone Acetonide -- pharmacology KW - Cell Transformation, Neoplastic -- drug effects KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78222537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vitro+cellular+%26+developmental+biology.+Animal&rft.atitle=Drug-induced+reversion+of+progression+phenotype+is+accompanied+by+reversion+of+AP-1+phenotype+in+JB6+cells.&rft.au=Lavrovsky%2C+V%3BDong%2C+Z%3BMa%2C+W+Y%3BColburn%2C+N&rft.aulast=Lavrovsky&rft.aufirst=V&rft.date=1996-04-01&rft.volume=32&rft.issue=4&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=In+vitro+cellular+%26+developmental+biology.+Animal&rft.issn=10712690&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-15 N1 - Date created - 1996-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oncogenic retroviruses of cattle, chickens and turkeys: potential infectivity and oncogenicity for humans. AN - 78191046; 8733164 AB - Reticuloendotheliosis virus naturally infects and cause lymphoid leukosis in chickens and turkeys. We investigated whether it can infect/transfect a variety of human cells in vitro. Successful infection and transfection were achieved with limited replication of virus. These findings, together with the knowledge that other oncogenic retroviruses of chickens and cattle, viz. The avian leukosis/sarcoma viruses and bovine leukemia virus show similar infectivity/oncogencity in vitro for humans, and the recent demonstration of antibodies to avian leukosis/sarcoma virus and reticuloendotheliosis virus in human sera, suggest that these viruses may have a role in the etiology of certain cancers in humans. There is now urgent need to investigate this, particularly because recent epidemiological studies consistently demonstrate excess of cancers in groups occupationally exposed to these viruses. JF - Medical hypotheses AU - Johnson, E S AU - Griswold, C M AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 354 EP - 356 VL - 46 IS - 4 SN - 0306-9877, 0306-9877 KW - Index Medicus KW - Animals KW - Cattle -- virology KW - HeLa Cells KW - Chickens -- virology KW - Humans KW - Reticuloendotheliosis virus -- pathogenicity KW - Occupational Diseases -- etiology KW - Cell Transformation, Viral KW - Turkeys -- virology KW - Retroviridae -- pathogenicity KW - Tumor Virus Infections -- etiology KW - Retroviridae Infections -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78191046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+hypotheses&rft.atitle=Oncogenic+retroviruses+of+cattle%2C+chickens+and+turkeys%3A+potential+infectivity+and+oncogenicity+for+humans.&rft.au=Johnson%2C+E+S%3BGriswold%2C+C+M&rft.aulast=Johnson&rft.aufirst=E&rft.date=1996-04-01&rft.volume=46&rft.issue=4&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Medical+hypotheses&rft.issn=03069877&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-06 N1 - Date created - 1996-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins for central nervous system malignancy. AN - 78186216; 8740561 AB - Current therapy for primary brain tumors, metastatic brain tumors and leptomeningeal carcinomatosus is inadequate. Monoclonal antibodies and certain biological ligands such as transferrin and epidermal growth factor bind selectively to tumors but in and of themselves have little therapeutic activity. Linking these binding moieties to protein toxins yields new molecules, called immunotoxins, that display enormous cell-type specific toxicity in vitro and could be valuable agents for treatment of CNS cancer. This review discusses our development of immunotoxins to treat brain tumors after systemic, intrathecal and intratumoral injection. JF - Seminars in cancer biology AU - Youle, R J AD - Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1414, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 65 EP - 70 VL - 7 IS - 2 SN - 1044-579X, 1044-579X KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Index Medicus KW - Injections, Intralesional KW - Brain Neoplasms -- therapy KW - Purkinje Cells -- drug effects KW - Meningeal Neoplasms -- drug therapy KW - Injections, Spinal KW - Humans KW - Brain Neoplasms -- secondary KW - Blood-Brain Barrier KW - Antibodies, Monoclonal -- therapeutic use KW - Immunotoxins -- immunology KW - Central Nervous System Neoplasms -- drug therapy KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78186216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+cancer+biology&rft.atitle=Immunotoxins+for+central+nervous+system+malignancy.&rft.au=Youle%2C+R+J&rft.aulast=Youle&rft.aufirst=R&rft.date=1996-04-01&rft.volume=7&rft.issue=2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Seminars+in+cancer+biology&rft.issn=1044579X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-23 N1 - Date created - 1996-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Agricultural Health Study. AN - 78185804; 8732939 AB - The Agricultural Health Study, a large prospective cohort study has been initiated in North Carolina and Iowa. The objectives of this study are to: 1) identify and quantify cancer risks among men, women, whites, and minorities associated with direct exposure to pesticides and other agricultural agents; 2) evaluate noncancer health risks including neurotoxicity reproductive effects, immunologic effects, nonmalignant respiratory disease, kidney disease, and growth and development among children; 3) evaluate disease risks among spouses and children of farmers that may arise from direct contact with pesticides and agricultural chemicals used in the home lawns and gardens, and from indirect contact, such as spray drift, laundering work clothes, or contaminated food or water; 4) assess current and past occupational and nonoccupational agricultural exposures using periodic interviews and environmental and biologic monitoring; 5) study the relationship between agricultural exposures, biomarkers of exposure, biologic effect, and genetic susceptibility factors relevant to carcinogenesis; and 6) identify and quantify cancer and other disease risks associated with lifestyle factors such as diet, cooking practices, physical activity, smoking and alcohol consumption, and hair dye use. In the first year of a 3-year enrollment period, 26,235 people have been enrolled in the study, including 19,776 registered pesticide applicators and 6,459 spouses of registered farmer applicators. It is estimated that when the total cohort is assembled in 1997 it will include approximately 75,000 adult study subjects. Farmers, the largest group of registered pesticide applicators comprise 77% of the target population enrolled in the study. This experience compares favorably with enrollment rates of previous prospective studies. JF - Environmental health perspectives AU - Alavanja, M C AU - Sandler, D P AU - McMaster, S B AU - Zahm, S H AU - McDonnell, C J AU - Lynch, C F AU - Pennybacker, M AU - Rothman, N AU - Dosemeci, M AU - Bond, A E AU - Blair, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 362 EP - 369 VL - 104 IS - 4 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Pesticides KW - Index Medicus KW - Occupational Exposure KW - Humans KW - Child KW - Iowa KW - Cross-Sectional Studies KW - Prospective Studies KW - Risk Factors KW - Adult KW - Cohort Studies KW - North Carolina KW - Surveys and Questionnaires KW - Middle Aged KW - Female KW - Male KW - Neoplasms -- etiology KW - Agriculture KW - Occupational Health KW - Pesticides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78185804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=The+Agricultural+Health+Study.&rft.au=Alavanja%2C+M+C%3BSandler%2C+D+P%3BMcMaster%2C+S+B%3BZahm%2C+S+H%3BMcDonnell%2C+C+J%3BLynch%2C+C+F%3BPennybacker%2C+M%3BRothman%2C+N%3BDosemeci%2C+M%3BBond%2C+A+E%3BBlair%2C+A&rft.aulast=Alavanja&rft.aufirst=M&rft.date=1996-04-01&rft.volume=104&rft.issue=4&rft.spage=362&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1992 Dec 16;84(24):1866-74 [1460670] Scand J Work Environ Health. 1992 Aug;18(4):209-15 [1411362] Am J Epidemiol. 1993 Feb 1;137(3):270-80 [8452135] J Occup Med. 1993 Jun;35(6):557-61 [8331434] Arch Environ Contam Toxicol. 1994 Jan;26(1):47-59 [8110023] Cancer Causes Control. 1994 Jul;5(4):310-8 [8080942] J Occup Med. 1994 Nov;36(11):1247-50 [7532217] Eur J Cancer Prev. 1995 Feb;4(1):81-90 [7728101] Neuroepidemiology. 1992;11(4-6):267-76 [1337947] Arch Intern Med. 1971 Dec;128(6):920-8 [5132450] Pestic Monit J. 1974 Dec;8(3):209-12 [4142653] J Natl Cancer Inst. 1977 Sep;59(3):851-3 [197245] J Natl Cancer Inst. 1981 Jun;66(6):1191-308 [7017215] Med J Aust. 1982 Mar 20;1(6):253-6 [7087848] J Natl Cancer Inst. 1982 Aug;69(2):333-7 [6287075] Scand J Work Environ Health. 1985 Dec;11(6):397-407 [3912986] Arch Environ Health. 1987 Jul-Aug;42(4):204-12 [3662607] Am J Ind Med. 1988;14(2):167-76 [3207102] Arch Environ Health. 1989 Mar-Apr;44(2):94-101 [2930251] Int J Epidemiol. 1989 Mar;18(1):146-51 [2722358] Br J Ind Med. 1989 Nov;46(11):809-14 [2590647] J Natl Cancer Inst. 1990 Apr 4;82(7):575-82 [2313734] J Natl Cancer Inst. 1990 May 16;82(10):840-8 [2332902] Am J Ind Med. 1990;18(2):133-48 [2206046] Occup Med. 1991 Jul-Sep;6(3):335-54 [1835166] Rev Environ Contam Toxicol. 1992;126:1-85 [1598424] Erratum In: Environ Health Perspect.1996 Jul;104(7):683 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Liver tumors and possible preneoplastic lesions, induced by a food-derived heterocyclic amine in cynomolgus monkeys; a study of histology and cytokeratin expression. AN - 78176557; 8740838 AB - A food-derived mutagenic heterocyclic aromatic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), is a potent hepatocarcinogen in cynomolgus monkeys. In an ongoing carcinogenesis study, 34 out of 40 monkeys dosed with IQ have developed malignant liver tumors. The histology and cytokeratin expression was examined in a total of 94 tumors and non-neoplastic lesions obtained from 34 cases. The majority of the tumors were classified as hepatocellular carcinoma. In some cases, a striking difference in the histological features between individual tumor nodules was suggestive of a multicentric origin. Intrahepatic vascular invasion was seen in 14 (41.2%) and metastases in 6 (17.6%) of the hepatocellular carcinoma cases. There was no evidence of regenerative hyperplasia or fibrosis in the parenchyma of the tumor-bearing livers. Clear-cell foci composed of glycogen-rich hepatocytes were the only macroscopic lesions detected prior to gross tumor development. Other liver lesions included dysplastic hepatocyte foci and areas of proliferating bile ductular like (oval) cells, located around the periportal areas and along the portal tracts. Expression of bile duct type cytokeratin 7 was observed in a few of the oval cells and non-malignant hepatocytes, as well as in some of the hepatocellular carcinoma nodules. This aberrant cytokeratin expression raises questions concerning the histogenesis of the IQ-induced hepatocellular carcinoma. JF - Liver AU - Thorgeirsson, U P AU - Gomez, D E AU - Lindsay, C K AU - Sinha, C C AU - Adamson, R H AD - Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 71 EP - 83 VL - 16 IS - 2 SN - 0106-9543, 0106-9543 KW - Carcinogens KW - 0 KW - Mutagens KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Food KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Precancerous Conditions -- metabolism KW - Precancerous Conditions -- pathology KW - Neovascularization, Pathologic -- pathology KW - Bile Ducts, Intrahepatic -- pathology KW - Precancerous Conditions -- chemically induced KW - Neoplasm Metastasis KW - Macaca mulatta KW - Immunohistochemistry KW - Quinolines -- toxicity KW - Keratins -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- metabolism KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms, Experimental -- chemically induced KW - Carcinoma, Hepatocellular -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78176557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver&rft.atitle=Liver+tumors+and+possible+preneoplastic+lesions%2C+induced+by+a+food-derived+heterocyclic+amine+in+cynomolgus+monkeys%3B+a+study+of+histology+and+cytokeratin+expression.&rft.au=Thorgeirsson%2C+U+P%3BGomez%2C+D+E%3BLindsay%2C+C+K%3BSinha%2C+C+C%3BAdamson%2C+R+H&rft.aulast=Thorgeirsson&rft.aufirst=U&rft.date=1996-04-01&rft.volume=16&rft.issue=2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Liver&rft.issn=01069543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-21 N1 - Date created - 1996-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The practice of causal inference in cancer epidemiology. AN - 78160709; 8722223 AB - Causal inference is an important link between the practice of cancer epidemiology and effective cancer prevention. Although many papers and epidemiology textbooks have vigorously debated theoretical issues in causal inference, almost no attention has been paid to the issue of how causal inference is practiced. In this paper, we review two series of review papers published between 1985 and 1994 to find answers to the following questions: which studies and prior review papers were cited, which causal criteria were used, and what causal conclusions and public health recommendations ensued. Fourteen published reviews on alcohol and breast cancer and 6 published reviews on vasectomy and prostate cancer were examined. For both series of reviews, nearly all available published studies were cited except for ecological studies and prior reviews. Sources of causal criteria were often not provided. When they appeared, all citations were either the 1964 Surgeon General's report or works of Austin Bradford Hill. Reviews often excluded and sometimes altered criteria without giving reasons for these changes. The criteria of consistency and strength of association were almost always used accompanied by dose-response and biological plausibility in a majority of reviews. The criterion of temporality, considered by many methodologists to be a necessary causal condition, was infrequently used. Confounding and bias were often added considerations. Public health recommendations were not discussed in nearly one-half of the reviews. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Weed, D L AU - Gorelic, L S AD - Preventive Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 303 EP - 311 VL - 5 IS - 4 SN - 1055-9965, 1055-9965 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Causality KW - Ethanol -- adverse effects KW - Vasectomy -- adverse effects KW - Epidemiologic Methods KW - Risk Factors KW - Humans KW - Retrospective Studies KW - Incidence KW - Male KW - Female KW - Prostatic Neoplasms -- etiology KW - Prostatic Neoplasms -- epidemiology KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78160709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=The+practice+of+causal+inference+in+cancer+epidemiology.&rft.au=Weed%2C+D+L%3BGorelic%2C+L+S&rft.aulast=Weed&rft.aufirst=D&rft.date=1996-04-01&rft.volume=5&rft.issue=4&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-25 N1 - Date created - 1996-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intervention research: a model from the National Cancer Institute's Smoking and Tobacco Control Program. AN - 78148664; 8728133 AB - Recognizing that the scientific method is as critical to cancer control as it is to basic laboratory research, the National Cancer Institute (NCI) established a well-defined, systematic strategy for attaining its cancer control goals and objectives. This strategy, operationalized in the early 1980s as a five-phase process, emphasized cancer control as a research science rather than a demonstration science. The five phases of NCI's cancer control research strategy progress from hypothesis development, to methods development, to controlled intervention trials, to defined population studies, and finally to demonstration and implementation programs. This research base provides the foundation for nationwide prevention and health services programs. The application of this five-phase approach to NCI's efforts to reduce morbidity and mortality attributable to tobacco use is described, and some of the challenges that faced the Institute in this process are identified. These experiences provide an important framework for other disciplines faced with the challenge of translating science into practice. JF - American journal of industrial medicine AU - Alciati, M H AD - Public Health Agency Section, National Cancer Institute, Rockville, MD, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 324 EP - 328 VL - 29 IS - 4 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Controlled Clinical Trials as Topic KW - Humans KW - Occupational Diseases -- prevention & control KW - Preventive Health Services KW - Preventive Medicine KW - Organizational Objectives KW - Neoplasms -- prevention & control KW - Research KW - United States -- epidemiology KW - Smoking -- mortality KW - Plants, Toxic KW - Smoking Cessation KW - National Institutes of Health (U.S.) KW - Tobacco KW - Smoking -- adverse effects KW - Smoking -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78148664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Intervention+research%3A+a+model+from+the+National+Cancer+Institute%27s+Smoking+and+Tobacco+Control+Program.&rft.au=Alciati%2C+M+H&rft.aulast=Alciati&rft.aufirst=M&rft.date=1996-04-01&rft.volume=29&rft.issue=4&rft.spage=324&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of NF-kB-like transcription factors in brain areas susceptible to kainate toxicity. AN - 78144984; 8721671 AB - Administration of kainate (KA), a glutamate receptor agonist, to rats causes neuronal damage in the CA1/CA3 fields of the hippocampus and in the pyriform/ entorhinal cortex. Reactive gliosis also occurs and activated astrocytes upregulate their expression of a large number of molecules. Since NF-kB transcription factors are involved in cellular responses to diverse pathogenic stimuli and have been shown to be induced in astrocytes in vitro in response to cytokines and growth factors, we investigated their possible involvement in the changes in gene expression subsequent to KA-induced lesions. Immunoreactivity to the p65 subunit of NF-kB was markedly increased in non-neuronal cells 2 days after KA administration (8 mg/kg i.p.) in the areas of selective neuronal degeneration. This increase was not observed 3 h or 1 day after injection, but was still present 7-10 days after KA injection. By gel mobility-shift assay, a protein complex binding to the kB consensus sequence was found to be induced by 2 days after KA, which correlated with immunohistochemical findings. This NF-kB-protein complex seemed to be localized in reactive astrocytes, as indicated by the morphological similarity of NF-kB-positive cells and reactive astrocytes stained with glial fibrillary acidic protein (GFAP) antibody, and the parallelism between the time course of NF-kB induction and appearance of gliosis after KA treatment. Double immunocytochemistry experiments demonstrated the colocalization of NF-kB positive cells and reactive astrocytes. Our results suggest that activated NF-kB in astrocytes participates in delayed and long-term responses of glia to injury. JF - Glia AU - Pérez-Otano, I AU - McMillian, M K AU - Chen, J AU - Bing, G AU - Hong, J S AU - Pennypacker, K R AD - Neuropharmacology Section, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 306 EP - 315 VL - 16 IS - 4 SN - 0894-1491, 0894-1491 KW - Excitatory Amino Acid Agonists KW - 0 KW - Glial Fibrillary Acidic Protein KW - NF-kappa B KW - Oligonucleotide Probes KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Nerve Degeneration -- drug effects KW - Animals KW - Glial Fibrillary Acidic Protein -- metabolism KW - Macrophage Activation -- physiology KW - Cytoplasm -- drug effects KW - Biotransformation -- drug effects KW - Hippocampus -- drug effects KW - Macrophage Activation -- drug effects KW - Rats KW - Gliosis -- pathology KW - Rats, Inbred F344 KW - Base Sequence KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Hippocampus -- pathology KW - Microglia -- drug effects KW - Immunohistochemistry KW - Male KW - Microglia -- metabolism KW - NF-kappa B -- biosynthesis KW - Brain Chemistry -- drug effects KW - Brain -- anatomy & histology KW - Excitatory Amino Acid Agonists -- toxicity KW - Kainic Acid -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78144984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glia&rft.atitle=Induction+of+NF-kB-like+transcription+factors+in+brain+areas+susceptible+to+kainate+toxicity.&rft.au=P%C3%A9rez-Otano%2C+I%3BMcMillian%2C+M+K%3BChen%2C+J%3BBing%2C+G%3BHong%2C+J+S%3BPennypacker%2C+K+R&rft.aulast=P%C3%A9rez-Otano&rft.aufirst=I&rft.date=1996-04-01&rft.volume=16&rft.issue=4&rft.spage=306&rft.isbn=&rft.btitle=&rft.title=Glia&rft.issn=08941491&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-17 N1 - Date created - 1996-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toward an alcohol treatment model: a comparison of treated and untreated respondents with DSM-IV alcohol use disorders in the general population. AN - 78140092; 8730232 AB - The purpose of this study was to compare characteristics of person with alcohol use disorders who sought alcohol treatment with those who did not using data from a nationally representative sample of the United States. Applying an organizing framework from the larger literature on service utilization, a logistic regression analysis was conducted to examine the interaction among factors influencing treatment. The results identified unemployment status and lower educational level as barriers to alcohol treatment, but the impact of these factors differed depending on whether the respondent had previous experience with alcohol treatment. The major findings of this study are discussed in terms of consumer satisfaction, minimizing barriers to alcohol treatment services, and the need to examine individual determinants of alcohol treatment within the larger context of organizational and sociopolitical factors. JF - Alcoholism, clinical and experimental research AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 372 EP - 378 VL - 20 IS - 2 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Educational Status KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Unemployment -- psychology KW - Longitudinal Studies KW - Adolescent KW - Psychometrics KW - Male KW - Health Services Accessibility KW - Female KW - Social Environment KW - Alcoholism -- rehabilitation KW - Patient Acceptance of Health Care KW - Alcoholism -- diagnosis KW - Alcoholism -- classification KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78140092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Toward+an+alcohol+treatment+model%3A+a+comparison+of+treated+and+untreated+respondents+with+DSM-IV+alcohol+use+disorders+in+the+general+population.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1996-04-01&rft.volume=20&rft.issue=2&rft.spage=372&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Excretion and identification of methacrylonitrile metabolites in the bile of male F344 rats. AN - 78138029; 8801052 AB - Methacrylonitrile (MAN) is structurally similar to the known carcinogen acrylonitrile (AN), has similar industrial uses, and is occasionally used as its replacement. In contrast to AN, minimal information is available on the toxicity, carcinogenicity, or metabolism of MAN. Earlier work in this laboratory demonstrated that, in rats, MAN is primarily eliminated in the expired air as unchanged MAN, acetone, and CO2. Two mercapturic acids were identified in the urine of rats and mice treated with MAN. In the present work, the common bile duct of anesthetized rats was cannulated. The animals received a single gavage dose of 58 mg/kg 2-[14C]MAN. Bile was collected before and after MAN administration. Bile flow and MAN-derived radioactivity were determined at each time point. MAN had a minimal effect on bile flow and 4 to 6% of the administered MAN dose was excreted in the bile within 6 hr after dosing. HPLC analysis of bile showed two major metabolites, which were identified as 1-(S-glutathionyl)-2-propanone and 1-(S-glutathionyl)-2-cyanopropane by using NMR spectra and chemical synthesis. The ratio of the two metabolites in MAN-treated rats was approximately 2:1. Pretreatment of rats with sodium phenobarbital caused minimal quantitative or qualitative changes in the biliary excretion of MAN metabolites. In contrast, pretreatment of rats with beta-diethylaminoethyl diphenylpropylacetate before MAN administration resulted in a significant decrease in the ratio of 1-(S-glutathionyl)-2-propanone to 1-(S-glutathionyl)-2-cyanopropane (1:2). These data, especially the identification of 1-(S-glutathionyl)-2-propanone, indirectly demonstrated that MAN is metabolized via an epoxide intermediate (1-cyano-1-methyloxirane). Modulation of MAN metabolism by the P450 modulators suggested that this metabolic pathway is catalyzed via the cytochrome P450 enzymes. This work also confirms that MAN undergoes direct reaction with reduced glutathione via a Michael addition. Because of earlier work demonstrated that AN undergoes similar metabolism, MAN might have a qualitative toxicity profile similar to that of acryonitrile. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Ghanayem, B I AU - Burka, L T AD - National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 390 EP - 394 VL - 24 IS - 4 SN - 0090-9556, 0090-9556 KW - Methacrylates KW - 0 KW - Nitriles KW - methacrylonitrile KW - 04S4K38612 KW - Proadifen KW - A510CA4CBT KW - Acrylonitrile KW - MP1U0D42PE KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Proadifen -- pharmacology KW - Phenobarbital -- pharmacology KW - Acrylonitrile -- metabolism KW - Time Factors KW - Male KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Bile -- chemistry KW - Nitriles -- metabolism KW - Methacrylates -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78138029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Excretion+and+identification+of+methacrylonitrile+metabolites+in+the+bile+of+male+F344+rats.&rft.au=Ghanayem%2C+B+I%3BBurka%2C+L+T&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=1996-04-01&rft.volume=24&rft.issue=4&rft.spage=390&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-30 N1 - Date created - 1996-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors. AN - 78126558; 8703849 AB - Comparative genomic hybridization was used to screen the DNA extracted from histologically defined tissue sections from consecutive stages of colorectal carcinogenesis for chromosomal aberrations. No aberrations were detected in normal epithelium (n = 14). Gain of chromosome 7 occurred as a single event in low-grade adenomas (n = 14). In high-grade adenomas (n = 12), and overrepresentation of chromosomes 7 and 20 was present in 30% of the cases analyzed. The transition to colon carcinomas (n = 16) was characterized by the emergence of multiple chromosomal aberrations. Chromosomes 1, 13, and 20 and chromosome arms 7p and 8q were frequently gained, whereas chromosome 4 and chromosome arms 8p and 18q were recurrently underrepresented. The same tissue sections that were used for CGH were analyzed by means of DNA-ploidy measurements and immunohistochemical staining to quantify proliferative activity and p21/WAF-1 and TP53 expression. We observed that crude aneuploidy and increased proliferative activity are early events in colorectal carcinogenesis, followed by TP53 overexpression and the acquisition of recurrent chromosomal gains and losses during the progression from high-grade adenomas to invasive carcinomas. JF - Genes, chromosomes & cancer AU - Ried, T AU - Knutzen, R AU - Steinbeck, R AU - Blegen, H AU - Schröck, E AU - Heselmeyer, K AU - du Manoir, S AU - Auer, G AD - Diagnostic Development Branch, National Center for Human Genome Research, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 234 EP - 245 VL - 15 IS - 4 SN - 1045-2257, 1045-2257 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Karyotyping KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Nucleic Acid Hybridization KW - Male KW - Female KW - Chromosome Deletion KW - Colorectal Neoplasms -- pathology KW - Chromosome Aberrations KW - Colorectal Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78126558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Comparative+genomic+hybridization+reveals+a+specific+pattern+of+chromosomal+gains+and+losses+during+the+genesis+of+colorectal+tumors.&rft.au=Ried%2C+T%3BKnutzen%2C+R%3BSteinbeck%2C+R%3BBlegen%2C+H%3BSchr%C3%B6ck%2C+E%3BHeselmeyer%2C+K%3Bdu+Manoir%2C+S%3BAuer%2C+G&rft.aulast=Ried&rft.aufirst=T&rft.date=1996-04-01&rft.volume=15&rft.issue=4&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-11 N1 - Date created - 1996-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement. AN - 78108548; 8666950 AB - Rearrangement of the immunoglobulin (Ig) and T cell receptor (TCR) gene loci allows for the generation of B and T lymphocytes with antigen-specific receptors. Complete rearrangement and expression of the TCR-beta chain enables immature thymocytes to differentiate from the CD4-CD8- to the CD4+CD8+ stage mice in which rearrangement is impaired, such as severe combined immunodeficient (SCID) mice or recombinase activating gene-deficient (RAG-/-) mice, lack mature B and T lymphocytes. Thymocytes from these mice are arrested at the CD4-CD8- stage of T cell development. We previously observed that thymocytes from RAG-2-/- mice exposed to gamma radiation differentiate from CD4-CD8- into CD4+CD8+ without TCR-beta chain rearrangement. We now report that irradiated RAG-2-/- thymocytes undergo direct somatic mutations at the p53 gene locus, and that p53 inactivation is associated with maturation of RAG2-/- thymocytes to the CD4+CD8+ stage. Generation of RAG2-/- and p53-/- double-deficient mice revealed that, in the absence of TCR-beta chain rearrangement, loss of p53 function is sufficient for CD4-CD8- thymocytes to differentiate into the CD4+CD8+ stage of T cell development. Our data provide evidence for a novel p53 mediated checkpoint in early thymocyte development that regulates the transition of CD4-CD8- into CD4+CD8+ thymocytes. JF - The Journal of experimental medicine AU - Jiang, D AU - Lenardo, M J AU - Zúñiga-Pflücker, J C AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. Y1 - 1996/04/01/ PY - 1996 DA - 1996 Apr 01 SP - 1923 EP - 1928 VL - 183 IS - 4 SN - 0022-1007, 0022-1007 KW - Immunoglobulin A KW - 0 KW - Immunoglobulin G KW - Immunoglobulin M KW - Receptors, Antigen, T-Cell, gamma-delta KW - Tetanus Toxoid KW - Cholera Toxin KW - 9012-63-9 KW - Index Medicus KW - Peyer's Patches -- immunology KW - Animals KW - Peyer's Patches -- cytology KW - Mice KW - Vaccination KW - Jejunum -- cytology KW - Mice, Mutant Strains KW - Cholera Toxin -- immunology KW - Mice, Inbred C57BL KW - Jejunum -- immunology KW - Immunoglobulin M -- biosynthesis KW - Ileum -- cytology KW - Immunoglobulin G -- biosynthesis KW - Immunohistochemistry KW - Ileum -- immunology KW - Tetanus Toxoid -- immunology KW - Intestinal Mucosa -- cytology KW - Intestinal Mucosa -- immunology KW - Intestine, Small -- cytology KW - Receptors, Antigen, T-Cell, gamma-delta -- genetics KW - Intestine, Small -- immunology KW - Immunoglobulin A -- biosynthesis KW - Receptors, Antigen, T-Cell, gamma-delta -- deficiency KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78108548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=p53+prevents+maturation+to+the+CD4%2BCD8%2B+stage+of+thymocyte+differentiation+in+the+absence+of+T+cell+receptor+rearrangement.&rft.au=Jiang%2C+D%3BLenardo%2C+M+J%3BZ%C3%BA%C3%B1iga-Pfl%C3%BCcker%2C+J+C&rft.aulast=Jiang&rft.aufirst=D&rft.date=1996-04-01&rft.volume=183&rft.issue=4&rft.spage=1923&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-05 N1 - Date created - 1996-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1983 Feb 10;301(5900):527-30 [6823332] Cell. 1992 Mar 6;68(5):869-77 [1547488] J Immunol. 1990 May 15;144(10):3736-40 [2110211] Semin Immunol. 1991 May;3(3):167-75 [1909594] Semin Immunol. 1990 Jan;2(1):35-44 [2151796] Nature. 1992 May 14;357(6374):161-4 [1579166] Cancer Res. 1992 Jul 1;52(13):3791-5 [1617648] Cell. 1992 Aug 21;70(4):523-6 [1505019] Nature. 1992 Nov 19;360(6401):225-31 [1359428] Oncol Res. 1992;4(8-9):349-57 [1486218] Science. 1993 Feb 5;259(5096):822-5 [8430336] EMBO J. 1993 Apr;12(4):1671-80 [8385609] Nature. 1993 Apr 29;362(6423):847-9 [8479522] Cell. 1993 Aug 27;74(4):609-19 [8358790] J Exp Med. 1993 Oct 1;178(4):1139-49 [8376926] Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11401-5 [8248261] Immunol Today. 1993 Nov;14(11):547-53 [7903854] Nature. 1994 May 26;369(6478):321-3 [8183370] Oncogene. 1994 Jun;9(6):1799-805 [8183579] J Exp Med. 1994 Oct 1;180(4):1517-21 [7931082] Cell. 1994 Oct 21;79(2):189-92 [7954787] Science. 1994 Nov 18;266(5188):1208-12 [7973703] Cell. 1995 Jan 27;80(2):293-9 [7834749] Immunity. 1994 Jun;1(3):197-205 [7889408] Immunity. 1994 Jul;1(4):261-7 [7889413] Immunity. 1995 Aug;3(2):215-22 [7648394] Cell. 1992 Mar 6;68(5):855-67 [1547487] Mol Cell Biol. 1989 Sep;9(9):3982-91 [2476668] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The dual roles of nutrients as antioxidants and prooxidants: their effects on tumor cell growth. AN - 78076675; 8642460 AB - The development of a beneficial or a detrimental cellular response by a nutrient will depend on the nutrient's antioxidant or prooxidant characteristics, which in turn are a product of the cellular oxygen environment. Nutrients such as carotenoids, tocopherols or ascorbate derivatives will demonstrate an antioxidant or prooxidant characteristic depending on the redox potential of the individual molecule and the inorganic chemistry of the cell. Nutrients acting as chemopreventives, inhibit the continual growth of transformed clones of cells through their prooxidant activity. In contrast, when an antioxidant activity occurs in transformed cells an enhanced growth may result. In addition, when an inappropriate prooxidant activity develops in normal cells, the reactive oxygen metabolites generated could damage the DNA and cellular membranes. The cellular response is usually a loss of normal regulatory function and activity, depressing cellular integrity. Therefore, the labile redox character of each nutrient must be considered in terms of the extracellular and intracellular microoxygen environment. To predict if a specific nutrient will have a beneficial or detrimental effect on a particular tissue or cell, it is important to identify markers that will characterize the biologic activities of each nutrient and elucidate a possible mechanism of action for that nutrient. In various tissues chemopreventive agents derived from nutrients have been shown in laboratory animal studies and in some human intervention trials to inhibit the growth and development of premalignant or malignant lesions. Examples of these tissues include oral tissues, esophagus, gastric cardia and lung tissues. Recently, some clinical studies demonstrated no reduction in the incidence of premalignant change, but, to the contrary, statistical evidence indicated an increase in cancer development. In general, the results of clinical intervention trials remains equivocal. The use of chemopreventive agents without considering their pharmacologic, oxygen-responsive characteristics will produce unwanted iatrogenic side effects or further cloud evidence of these nutrients' biologic activities. JF - The Journal of nutrition AU - Schwartz, J L AD - National Institutes of Health, Molecular Epidemiology Biologic Indicators Branch, Bethesda, MD 20889, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 1221S EP - 7S VL - 126 IS - 4 Suppl SN - 0022-3166, 0022-3166 KW - Antioxidants KW - 0 KW - Oxidants KW - Retinoids KW - Vitamin E KW - 1406-18-4 KW - Carotenoids KW - 36-88-4 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Humans KW - Carotenoids -- toxicity KW - Retinoids -- toxicity KW - Oxidants -- pharmacology KW - Antioxidants -- pharmacology KW - Vitamin E -- toxicity KW - Vitamin E -- pharmacology KW - Neoplasms -- prevention & control KW - Retinoids -- pharmacology KW - Ascorbic Acid -- toxicity KW - Carotenoids -- pharmacology KW - Ascorbic Acid -- pharmacology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78076675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=The+dual+roles+of+nutrients+as+antioxidants+and+prooxidants%3A+their+effects+on+tumor+cell+growth.&rft.au=Schwartz%2C+J+L&rft.aulast=Schwartz&rft.aufirst=J&rft.date=1996-04-01&rft.volume=126&rft.issue=4+Suppl&rft.spage=1221S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I crossover study of paclitaxel with r-verapamil in patients with metastatic breast cancer. AN - 78072349; 8648372 AB - We conducted a phase I crossover study of escalating doses of both paclitaxel (Taxol; Bristol-Myers, Squibb, Princeton, NJ) and r-verapamil, the less cardiotoxic stereoisomer, in heavily pretreated patients with metastatic breast cancer. Twenty-nine patients refractory to paclitaxel by 3-hour infusion were treated orally with r-verapamil every 4 hours starting 24 hours before the same-dose 3-hour paclitaxel infusion and continuing for a total of 12 doses. Once the maximum-tolerated dose (MTD) of the combination was determined, seven additional patients who had not been treated with either drug were evaluated to determine whether the addition of r-verapamil altered the pharmacokinetics of paclitaxel. Consenting patients had tumor biopsies for P-glycoprotein (Pgp) expression before receiving paclitaxel and after becoming refractory to paclitaxel therapy. The MTD of the combination was 225 mg/m2 of r-verapamil every 4 hours with paclitaxel 200 mg/m2 by 3-hour infusion. Dose-limiting hypotension and bradycardia were observed in three of five patients treated at 250 mg/m2 r-verapamil. Fourteen patients received 32 cycles of r-verapamil at the MTD as outpatient therapy without developing cardiac toxicity. The median peak and trough serum verapamil concentrations at the MTD were 5.1 micromol/L (range, 1.9 to 6.3), respectively, which are within the range necessary for in vitro modulation of Pgp-mediated multidrug resistance (MDR). Increased serum verapamil concentrations and cardiac toxicity were observed more frequently in patients with elevated hepatic transaminases and bilirubin levels. Hematologic toxicity from combined paclitaxel and r-verapamil was significantly worse compared with the previous cycle of paclitxel without r-verapamil. In the pharmacokinetic analysis, r-verapamil delayed mean paclitaxel clearance and increased mean peak paclitaxel concentrations. r-Verapamil at 225 mg/m2 orally every 4 hours can be given safely with paclitaxel 200 mg/m2 by 3-hour infusion as outpatient therapy and is associated with serum levels considered active for Pgp inhibition. The addition of r-verapamil significantly alters the toxicity and pharmacokinetics of paclitaxel. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Tolcher, A W AU - Cowan, K H AU - Solomon, D AU - Ognibene, F AU - Goldspiel, B AU - Chang, R AU - Noone, M H AU - Denicoff, A M AU - Barnes, C S AU - Gossard, M R AU - Fetsch, P A AU - Berg, S L AU - Balis, F M AU - Venzon, D J AU - O'Shaughnessy, J A AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 1173 EP - 1184 VL - 14 IS - 4 SN - 0732-183X, 0732-183X KW - Antibodies, Monoclonal KW - 0 KW - Antineoplastic Agents, Phytogenic KW - P-Glycoprotein KW - Verapamil KW - CJ0O37KU29 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Humans KW - Aged KW - Biopsy KW - Drug Resistance, Neoplasm KW - P-Glycoprotein -- biosynthesis KW - Drug Therapy, Combination KW - Gene Expression Regulation, Neoplastic KW - P-Glycoprotein -- drug effects KW - Adult KW - Treatment Outcome KW - Cross-Over Studies KW - Middle Aged KW - Immunohistochemistry KW - Female KW - Paclitaxel -- administration & dosage KW - Breast Neoplasms -- drug therapy KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Verapamil -- blood KW - Breast Neoplasms -- pathology KW - Paclitaxel -- pharmacokinetics KW - Breast Neoplasms -- metabolism KW - Verapamil -- pharmacology KW - Verapamil -- therapeutic use KW - Breast Neoplasms -- blood KW - Antineoplastic Agents, Phytogenic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78072349?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+crossover+study+of+paclitaxel+with+r-verapamil+in+patients+with+metastatic+breast+cancer.&rft.au=Tolcher%2C+A+W%3BCowan%2C+K+H%3BSolomon%2C+D%3BOgnibene%2C+F%3BGoldspiel%2C+B%3BChang%2C+R%3BNoone%2C+M+H%3BDenicoff%2C+A+M%3BBarnes%2C+C+S%3BGossard%2C+M+R%3BFetsch%2C+P+A%3BBerg%2C+S+L%3BBalis%2C+F+M%3BVenzon%2C+D+J%3BO%27Shaughnessy%2C+J+A&rft.aulast=Tolcher&rft.aufirst=A&rft.date=1996-04-01&rft.volume=14&rft.issue=4&rft.spage=1173&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-25 N1 - Date created - 1996-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients. AN - 78063831; 8648379 AB - To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 microg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 microg/m2/h with G-CSF. Without G-CSF, two of eight patients who received 47 microg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 microg/m2/h (with a platelet count or = 25 microg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicities of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia ( r = .85). The recommended phase II dose of 9-AC given by 72-hour infusion every 2 weeks is 35 microg/m2/h without G-CSF or 47 microg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Dahut, W AU - Harold, N AU - Takimoto, C AU - Allegra, C AU - Chen, A AU - Hamilton, J M AU - Arbuck, S AU - Sorensen, M AU - Grollman, F AU - Nakashima, H AU - Lieberman, R AU - Liang, M AU - Corse, W AU - Grem, J AD - National Cancer Institute-Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, MD, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 1236 EP - 1244 VL - 14 IS - 4 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Humans KW - Adult KW - Treatment Outcome KW - Neutropenia -- chemically induced KW - Aged KW - Middle Aged KW - Neutropenia -- therapy KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Camptothecin -- pharmacology KW - Antineoplastic Agents -- administration & dosage KW - Camptothecin -- pharmacokinetics KW - Antineoplastic Agents -- pharmacokinetics KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- adverse effects KW - Antineoplastic Agents -- pharmacology KW - Camptothecin -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78063831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+and+pharmacologic+study+of+9-aminocamptothecin+given+by+72-hour+infusion+in+adult+cancer+patients.&rft.au=Dahut%2C+W%3BHarold%2C+N%3BTakimoto%2C+C%3BAllegra%2C+C%3BChen%2C+A%3BHamilton%2C+J+M%3BArbuck%2C+S%3BSorensen%2C+M%3BGrollman%2C+F%3BNakashima%2C+H%3BLieberman%2C+R%3BLiang%2C+M%3BCorse%2C+W%3BGrem%2C+J&rft.aulast=Dahut&rft.aufirst=W&rft.date=1996-04-01&rft.volume=14&rft.issue=4&rft.spage=1236&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-25 N1 - Date created - 1996-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thapsigargin, a weak skin tumor promoter, alters the growth and differentiation of mouse keratinocytes in culture. AN - 78025815; 8625480 AB - Thapsigargin (Tg), applied twice weekly to the backs of CD-1 mice initiated with 7,12-dimethylbenz[a]anthracene, promoted papillomas on the skin of approximately 50% of the mice. Tg alone induced papillomas in 10% of the mice. Although Tg and 12-O-tetradecanoylphorbol-13-acetate (TPA) are synergistic in a keratinocyte co-culture assay for promotion, skin tumor promotion by TPA was inhibited by co-treatment with Tg. Treatment of cultured keratinocytes with non-toxic doses of Tg increased the level of intracellular free Ca(2+)-induced stratification. Tg blocked expression of the spinous layer differentiation marker keratin 1 (K1), while inducing cornification, a marker of differentiation in the granular layer/stratum corneum. In medium with 1.4 mM Ca2+, Tg prolonged keratinocyte proliferation and selected foci of monolayer cells. A Tg-independent cell line, TK-1, was developed from a single dish in which foci continued to expand after Tg removal. Grafting TK-1 cells on to the backs of nude mice as part of a reconstituted skin resulted in the development of dysplastic papillomas with a high rate of progression to squamous cell carcinomas. JF - Carcinogenesis AU - Lowry, D T AU - Li, L AU - Hennings, H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 699 EP - 706 VL - 17 IS - 4 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Terpenes KW - Thapsigargin KW - 67526-95-8 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Tetradecanoylphorbol Acetate -- toxicity KW - Animals KW - Skin -- metabolism KW - Skin -- pathology KW - Cell Division -- drug effects KW - Mice KW - Calcium -- metabolism KW - Phenotype KW - Hyperplasia KW - Skin -- drug effects KW - Cells, Cultured KW - Cell Differentiation -- drug effects KW - Drug Synergism KW - Female KW - Terpenes -- toxicity KW - Skin Neoplasms -- chemically induced KW - Keratinocytes -- drug effects KW - Carcinogens -- toxicity KW - Skin Neoplasms -- pathology KW - Keratinocytes -- cytology KW - Skin Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78025815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Thapsigargin%2C+a+weak+skin+tumor+promoter%2C+alters+the+growth+and+differentiation+of+mouse+keratinocytes+in+culture.&rft.au=Lowry%2C+D+T%3BLi%2C+L%3BHennings%2C+H&rft.aulast=Lowry&rft.aufirst=D&rft.date=1996-04-01&rft.volume=17&rft.issue=4&rft.spage=699&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the fusion peptide of the human immunodeficiency virus type 1: identification of critical glycine residues. AN - 78020691; 8615045 AB - The ability of human immunodeficiency virus type 1 (HIV-1) to fuse its membrane with the membrane of the target cell is a function of a approximately 23-amino-acid amino-terminal segment of the gp41 subunit of the envelope glycoprotein complex, known as the fusion peptide. The sequence of the fusion peptide is highly conserved among different variants of HIV-1 and is also very similar to that of HIV-2 and SIV. The fusion peptide is very hydrophobic and has a high content of glycine and alanine residues. Representation of the fusion peptide of HIV-1 as an alpha-helix predicts that most glycine residues would be found on one face of the alpha-helix. To assess the importance of the glycine residues for the fusogenic activity of the envelope glycoprotein complex, we mutagenized each glycine residue in the fusion peptide individually to a valine residue. The mutant envelope constructs were tested for their ability to induce syncytia (cell/cell fusion) and to mediate infection (virus/cell fusion) of CD4-positive cells. The results of our analyses show that two glycine residues (G10 and G13) located within the sequence FLGFLG in the middle of the fusion peptide are critical for syncytium formation and for the establishment of a productive infection, whereas other glycine residues (G3, G5, and G20) are more permissive to substitutions. Mutation of each of the two phenylalanines (F8 and F11) of the FLGFLG sequence to valine also decreased fusion, although to a lesser extent than mutation of G10 and G13. These observations demonstrate that G10 and G13 are critical elements of the fusion peptide and suggest that, in addition to hydrophobicity, the exact amino acid composition and structure of the fusion peptide are critical for function. JF - Virology AU - Delahunty, M D AU - Rhee, I AU - Freed, E O AU - Bonifacino, J S AD - Cell Biology and Metabolism Branch, National Institutes of Health, Bethesda, Maryland, 20892, USA. Y1 - 1996/04/01/ PY - 1996 DA - 1996 Apr 01 SP - 94 EP - 102 VL - 218 IS - 1 SN - 0042-6822, 0042-6822 KW - HIV Envelope Protein gp41 KW - 0 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - AIDS/HIV KW - HeLa Cells KW - Humans KW - Glycine -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Giant Cells -- virology KW - Mutagenesis KW - Binding Sites KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - HIV-1 -- pathogenicity KW - HIV Envelope Protein gp41 -- metabolism KW - HIV Envelope Protein gp41 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78020691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Mutational+analysis+of+the+fusion+peptide+of+the+human+immunodeficiency+virus+type+1%3A+identification+of+critical+glycine+residues.&rft.au=Delahunty%2C+M+D%3BRhee%2C+I%3BFreed%2C+E+O%3BBonifacino%2C+J+S&rft.aulast=Delahunty&rft.aufirst=M&rft.date=1996-04-01&rft.volume=218&rft.issue=1&rft.spage=94&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-05 N1 - Date created - 1996-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distribution of 7-alkyl-2'-deoxyguanosine adduct levels in human lung. AN - 78011242; 8625485 AB - Human lung tissue is frequently studied as a target organ for DNA damage from carcinogen-DNA adducts. In order to assess the distribution of carcinogen-DNA adducts in human lung, we measured 7-methyl-2'-deoxyguanosine-3'-monophosphate (7-methyl-dGp), 7-ethyl-2'-deoxyguanosine-3'-monophosphate (7-ethyl-dGp) and 4-hydroxy-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts in different lobes. The first two result from exposure to N-nitrosamines, including tobacco-specific nitrosamines, and the latter only from tobacco-specific nitrosamines. Using a chemically-specific 32P-postlabeling assay for 7-alkyl-2'-deoxyguanosines, adducts were measured in eight separate lung segments of ten autopsy donors. 7-Methyl-dGp levels were detected in all eighty samples (range from 0.3 to 11.5 adducts/10(7) dGp; mean 2.5 +/- 2.3 adducts/10(7) dGp). 7-Ethyl-dGp were detected in all but five of the samples (range from <0.1 to 7.1 adducts/10(7) dGp; mean 1.6 +/- 1.7 adducts/10(7) dGp). 7-Methyl-dGp levels were approximately 1.5-fold higher than 7-ethyl-dGp levels, and they were positively correlated with each other in most individuals. There was no consistent pattern of adduct distribution in the different lobar segments. Most individuals, especially those with the lowest levels, had similar levels among the lobes, while those with the highest levels had a widely variable pattern ranging as much as ten-fold. Moreover 7-methyl-dGp and 7-ethyl-dGp levels in all people showed a highly significant inter-individual variation (P = 0.0001). The levels of 7-alkyl-2'-deoxyguanosine among individuals could not be explained by differences in tobacco exposure (measured by serum cotinine), onset of death, gender, age, race, blood ethanol, or ventilation and perfusion variability. In an effort to corroborate 7-alkyl-2'-deoxyguanosine adducts variability among lobes or individuals, we sought to determine a correlation with HPB-releasing DNA adducts as an independent marker of tobacco exposure. However, this tobacco- specific carcinogen-DNA adduct could not be detected in four individuals tested (detection limit: 0.3 adducts per 10(7) dGp). Based upon the lack of 7-alkyl-2'-deoxyguanosine discernible adduct patterns, no conclusions could be drawn regarding a potential relationship to lobar cancer incidence. The results indicate that in studies of carcinogen-DNA adducts, such as 7-alkyl-dGp in human lungs, for most individuals a random lung sample would be representative of other parts of the lungs. Some individuals however might be misclassified due to highly variable 7-alkyl-dGp levels. JF - Carcinogenesis AU - Blömeke, B AU - Greenblatt, M J AU - Doan, V D AU - Bowman, E D AU - Murphy, S E AU - Chen, C C AU - Kato, S AU - Shields, P G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 741 EP - 748 VL - 17 IS - 4 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Humans KW - Adult KW - Carcinogens -- toxicity KW - Aged KW - Middle Aged KW - Male KW - Female KW - Deoxyguanosine -- metabolism KW - Lung -- metabolism KW - DNA Adducts -- metabolism KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78011242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Distribution+of+7-alkyl-2%27-deoxyguanosine+adduct+levels+in+human+lung.&rft.au=Bl%C3%B6meke%2C+B%3BGreenblatt%2C+M+J%3BDoan%2C+V+D%3BBowman%2C+E+D%3BMurphy%2C+S+E%3BChen%2C+C+C%3BKato%2C+S%3BShields%2C+P+G&rft.aulast=Bl%C3%B6meke&rft.aufirst=B&rft.date=1996-04-01&rft.volume=17&rft.issue=4&rft.spage=741&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histological evaluation of the canine retinal vasculature following chronic systemic administration of basic fibroblast growth factor. AN - 78010249; 8621333 AB - The purpose of the present study was to determine if prolonged systemic arterial administration of basic fibroblast growth factor (bFGF) at a dose sufficient to enhance collateral vessel formation in the ischaemic hearts of dogs would produce retinal neovascularisation in these same animals. Adult dogs (15-25 kg) were subjected to gradual occlusion of a coronary artery and randomised to receive 1 of 3 treatments via an indwelling left atrial catheter: (1) bFGF 1.74 mg/d, 5 d/wk for 63 d (n = 7); (2) bFGF 1.74 mg/d, 5 d/wk, for 35 d followed by physiological saline, 5 d/wk, for 28 d (n = 10); or (3) physiological saline, 5 d/wk, for 63 d (n = 10). After 63 d the retinal vasculatures from these dogs were isolated and examined for capillary varicosity, neovascularisation and other histopathological signs of angiopathy. All data were collected under masked conditions. The results suggest that chronic, systemic arterial administration of bFGF stimulates neovascularisation in the ischemic myocardium, but has no significant structural or vasoproliferative effect on the nonischaemic retina of the same animal. JF - Journal of anatomy AU - Jacot, J L AU - Laver, N M AU - Glover, J P AU - Lazarous, D F AU - Unger, E F AU - Robison, W G AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 349 EP - 354 VL - 188 ( Pt 2) SN - 0021-8782, 0021-8782 KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Index Medicus KW - Animals KW - Infusions, Intra-Arterial KW - Capillaries -- anatomy & histology KW - Coronary Disease -- pathology KW - Random Allocation KW - Dose-Response Relationship, Drug KW - Neovascularization, Pathologic -- chemically induced KW - Dogs KW - Male KW - Female KW - Coronary Vessels -- anatomy & histology KW - Fibroblast Growth Factor 2 -- pharmacology KW - Retinal Neovascularization -- chemically induced KW - Retinal Vessels -- anatomy & histology KW - Retinal Vessels -- drug effects KW - Fibroblast Growth Factor 2 -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78010249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+anatomy&rft.atitle=Histological+evaluation+of+the+canine+retinal+vasculature+following+chronic+systemic+administration+of+basic+fibroblast+growth+factor.&rft.au=Jacot%2C+J+L%3BLaver%2C+N+M%3BGlover%2C+J+P%3BLazarous%2C+D+F%3BUnger%2C+E+F%3BRobison%2C+W+G&rft.aulast=Jacot&rft.aufirst=J&rft.date=1996-04-01&rft.volume=188+%28+Pt+2%29&rft.issue=&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=Journal+of+anatomy&rft.issn=00218782&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Physiol. 1994 Apr;266(4 Pt 2):H1588-95 [8184938] Int Ophthalmol. 1993 Aug;17(4):195-9 [8112966] Circulation. 1995 Jan 1;91(1):145-53 [7805195] Circulation. 1974 Oct;50(4):831-7 [4425386] Am J Ophthalmol. 1978 Mar;85(3):287-301 [580695] Am J Cardiol. 1984 Mar 1;53(6):694-9 [6702615] Diabetes. 1987 Jul;36(7):808-12 [3556280] N Engl J Med. 1987 Nov 26;317(22):1390-8 [3317040] Diabetes Metab Rev. 1988 Jun;4(4):291-322 [3292173] Dev Biol. 1989 Jul;134(1):201-5 [2731647] J Cell Physiol. 1989 Jun;139(3):570-9 [2738102] J Cell Biol. 1989 Aug;109(2):811-22 [2760113] Invest Ophthalmol Vis Sci. 1990 Jul;31(7):1238-44 [2365555] Cancer Metastasis Rev. 1990 Nov;9(3):227-38 [2292137] Arch Ophthalmol. 1991 Jul;109(7):1005-11 [2064554] Arch Ophthalmol. 1992 Sep;110(9):1295-302 [1520120] N Engl J Med. 1992 Dec 24;327(26):1825-31 [1448120] Growth Factors. 1993;8(1):61-75 [7680568] Invest Ophthalmol Vis Sci. 1993 May;34(6):2097-104 [8491560] Curr Eye Res. 1994 Mar;13(3):183-95 [7514965] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased corpus callosum size among alcoholic women. AN - 78009594; 8929159 AB - Although females appear to be more sensitive to the hepatic consequences of alcoholism, it is not clear if women are more sensitive to the effects of excessive alcohol consumption on the brain than men. We compared the cross-sectional area of the corpus callosum in a group of 14 hospitalized alcoholic women and 13 hospitalized alcoholic men with a group of nine nonalcoholic women and 10 nonalcoholic men. All subjects were between the ages of 30 and 50 years. The cross-sectional areas of the corpus callosum and the inner table of the skull were measured on midsagittal T1-weighted magnetic resonance images. Females had smaller intracranial areas than males, but there was no difference in intracranial area between the alcoholics and nonalcoholics. The corpus callosum area was significantly smaller among the alcoholic women compared with either the control women or the alcoholic men. Alcoholic men did not differ from control men in the corpus callosum area. These results did not change when the corpus callosum area was adjusted for intracranial area by analysis of covariance. When the corpus callosum was divided into four segments of equal length, the reduction in area was not localized to any particular region. These results suggest an increased sensitivity to alcohol-induced brain damage among alcoholic women compared with alcoholic men. JF - Archives of neurology AU - Hommer, D AU - Momenan, R AU - Rawlings, R AU - Ragan, P AU - Williams, W AU - Rio, D AU - Eckardt, M AD - Laboratory of Clinical Studies, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 359 EP - 363 VL - 53 IS - 4 SN - 0003-9942, 0003-9942 KW - Abridged Index Medicus KW - Index Medicus KW - Magnetic Resonance Imaging KW - Reference Values KW - Analysis of Variance KW - Humans KW - Adult KW - Aged KW - Male KW - Female KW - Corpus Callosum -- pathology KW - Alcoholism -- pathology KW - Sex Characteristics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78009594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+neurology&rft.atitle=Decreased+corpus+callosum+size+among+alcoholic+women.&rft.au=Hommer%2C+D%3BMomenan%2C+R%3BRawlings%2C+R%3BRagan%2C+P%3BWilliams%2C+W%3BRio%2C+D%3BEckardt%2C+M&rft.aulast=Hommer&rft.aufirst=D&rft.date=1996-04-01&rft.volume=53&rft.issue=4&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=Archives+of+neurology&rft.issn=00039942&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-13 N1 - Date created - 1996-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - O6-ethylguanine and O6-benzylguanine incorporated site-specifically in codon 12 of the rat H-ras gene induce semi-targeted as well as targeted mutations in Rat4 cells. AN - 78009037; 8625500 AB - To examine the miscoding properties of modified guanine residues bearing increasingly bulky O6-substituents, Rat4 cells, grown in the presence of O6-benzylguanine to deplete the DNA repair protein O6-alkylguanine-DNA alkyltransferase, were transfected with plasmids carrying H-ras genes in which O6-methyl, O6-ethyl- and O6-benzylguanine were substituted for the first, second or both the first and second guanine residues of codon 12 (GGA). DNA from isolated transformed colonies was amplified by PCR and directly sequenced by high-temperature manual and automated methods. The results show that O6-ethylguanine and O6-benzylguanine induced semi-targeted as well as targeted mutations, in contrast to O6-methylguanine, which induced only targeted mutations. When incorporated in place of the first guanine of H-ras codon 12, the targeted mutations induced by all these modified guanines were exclusively G-->A transitions. When incorporated at the second position of codon 12, O6-benzylguanine induced G-->A, G-->T and G-->C mutations. O6-Ethylguanine at the second position induced chiefly G-->A transitions, and O6-methylguanine induced G-->A transitions exclusively. Semi-targeted mutations were strictly G-->A at the base 3' to a position 1 adduct or 5' to a position 2 adduct. The mechanism for induction of targeted mutations probably involves decreasing preference to thymidine incorporation opposite an O6-modified guanine as the size of the O6-substituent increases, while the mechanism for non-targeted mutations may be related to abasic site formation or to translesion synthesis which might be made error-prone by obstructive DNA lesions in this context. JF - Carcinogenesis AU - Bishop, R E AU - Pauly, G T AU - Moschel, R C AD - Carcinogen-Modified Nucleic Acid Chemistry Section, NCI-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 849 EP - 856 VL - 17 IS - 4 SN - 0143-3334, 0143-3334 KW - Codon KW - 0 KW - O(6)-benzylguanine KW - 01KC87F8FE KW - 6-ethylguanine KW - 51866-19-4 KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Rats KW - Clone Cells KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Mutation KW - Cell Line KW - Genes, ras KW - Guanine -- analogs & derivatives KW - Guanine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78009037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=O6-ethylguanine+and+O6-benzylguanine+incorporated+site-specifically+in+codon+12+of+the+rat+H-ras+gene+induce+semi-targeted+as+well+as+targeted+mutations+in+Rat4+cells.&rft.au=Bishop%2C+R+E%3BPauly%2C+G+T%3BMoschel%2C+R+C&rft.aulast=Bishop&rft.aufirst=R&rft.date=1996-04-01&rft.volume=17&rft.issue=4&rft.spage=849&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic activation of the potent carcinogen dibenzo[a,h]anthracene by cDNA-expressed human cytochromes P450. AN - 78006923; 8638931 AB - The metabolic activation of the potent carcinogen dibenzo[a,h]anthracene (DB[a,h]A) was investigated with recombinant human cytochrome P450 enzymes 1A2, 2B6, 2C8, 2C9, 2E1, 3A3, 3A4, and 3A5 expressed in hepatoma G2 cells and with 14 different human liver microsomes. Three dihydrodiols, three phenols, and one diphenol were formed and separated by high-performance liquid chromatography and identified by UV absorption and mass spectra. Of all P450s tested, 1A2 and 2C9 were the most active and 2B6 was moderately active in the rate of total DB[a,h]A metabolism (2.5- to 12-fold greater activity than that for other P450s). The trans-3,4-dihydrodiol, generally recognized as a precursor of the ultimate carcinogenic 3,4-diol-1,2-epoxides, was produced most actively by 2C9, then 1A2 and 2B6. The values of enzymatic kinetics (K(m) and V(max)) indicated that 2C9 had the highest catalytic efficiency (V(max)/K(m) = 9.7) in the formation of 3,4-dihydrodiol, in contrast to 1A2 (5.9) and 2B6 (4.4). 1A2 had the highest activity toward production of the 1,2-dihydrodiol, which is considered to be a weakly carcinogenic metabolite. Although specific activities of human liver microsomes in overall metabolism of DB[a,h]A markedly differed between individuals, metabolic patterns were observed similar to that generated from 1A2. Since human 1A1, a predominant enzyme for metabolism of polycyclic aromatic hydrocarbons, is not significantly expressed in the liver, hepatic microsomal 2C9, 1A2, and 2B6 all probably contribute to the metabolic activation of DB[a,h]A. JF - Archives of biochemistry and biophysics AU - Shou, M AU - Krausz, K W AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/04/01/ PY - 1996 DA - 1996 Apr 01 SP - 201 EP - 207 VL - 328 IS - 1 SN - 0003-9861, 0003-9861 KW - Benz(a)Anthracenes KW - 0 KW - Carcinogens KW - Isoenzymes KW - Recombinant Proteins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - 1,2,5,6-dibenzanthracene KW - T30ELH3D5X KW - Index Medicus KW - Recombinant Proteins -- metabolism KW - Biotransformation KW - Microsomes, Liver -- metabolism KW - Kinetics KW - Humans KW - Substrate Specificity KW - Carcinogens -- pharmacology KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Benz(a)Anthracenes -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78006923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Metabolic+activation+of+the+potent+carcinogen+dibenzo%5Ba%2Ch%5Danthracene+by+cDNA-expressed+human+cytochromes+P450.&rft.au=Shou%2C+M%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Shou&rft.aufirst=M&rft.date=1996-04-01&rft.volume=328&rft.issue=1&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-10 N1 - Date created - 1996-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo expression of inducible nitric oxide synthase in cerebellar neurons. AN - 77999303; 8627305 AB - In the CNS, nitric oxide (NO) functions as both neuromodulator and neurotoxic agent. In vivo neuronal expression of NO synthase (NOS) has been attributed to constitutive NOS--both the neuronal and the endothelial types. The other class of NOS--the inducible NOS (iNOS)--is known to mediate toxic effects of NO in various tissues. In this study, we show for the first time that direct intracerebellar injection of endotoxin and cytokine (lipopolysaccharide and interferon-gamma) induced in vivo neuronal expression of the iNOS gene, as demonstrated by fluorescent in situ hybridization and immunohistochemical staining analyzed by confocal laser-scanning microscopy. This raises the possibility that neuronal iNOS might contribute significantly to the vulnerability of the brain to various insults. JF - Journal of neurochemistry AU - Minc-Golomb, D AU - Yadid, G AU - Tsarfaty, I AU - Resau, J H AU - Schwartz, J P AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 1504 EP - 1509 VL - 66 IS - 4 SN - 0022-3042, 0022-3042 KW - Lipopolysaccharides KW - 0 KW - RNA, Messenger KW - Interferon-gamma KW - 82115-62-6 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Rats KW - Microscopy, Confocal KW - Gene Expression -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Transcription, Genetic -- drug effects KW - Lipopolysaccharides -- pharmacology KW - RNA, Messenger -- analysis KW - In Situ Hybridization, Fluorescence KW - Interferon-gamma -- pharmacology KW - Microinjections KW - Immunohistochemistry KW - Male KW - Cerebellum -- cytology KW - Nitric Oxide Synthase -- genetics KW - Neurons -- enzymology KW - Nitric Oxide Synthase -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77999303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=In+vivo+expression+of+inducible+nitric+oxide+synthase+in+cerebellar+neurons.&rft.au=Minc-Golomb%2C+D%3BYadid%2C+G%3BTsarfaty%2C+I%3BResau%2C+J+H%3BSchwartz%2C+J+P&rft.aulast=Minc-Golomb&rft.aufirst=D&rft.date=1996-04-01&rft.volume=66&rft.issue=4&rft.spage=1504&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-25 N1 - Date created - 1996-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extracellular ATP inhibits adrenergic agonist-induced hypertrophy of neonatal cardiac myocytes. AN - 77995619; 8635209 AB - We have previously shown that extracellular ATP, like norepinephrine (NE) and many other hypertrophy-inducing agents, increases expression of the immediate-early genes c-fos and junB in cultured neonatal cardiac myocytes but that the intracellular signaling pathways activated by ATP and responsible for these changes differ from those stimulated by NE. Furthermore, whereas NE increases incorporation of [14C]phenylalanine (14C-Phe) and cell size in neonatal cardiomyocytes, ATP does not. Since ATP is coreleased with NE from sympathetic nerve endings in the heart, we investigated whether ATP could modulate cardiac hypertrophy induced by adrenergic agonists, such as NE. We report in the present study that extracellular ATP inhibited the increase in incorporation of 14C-Phe into cellular protein and the increase in cell size in neonatal rat cardiac myocytes that was induced by NE, phenylephrine (PE), basic fibroblast growth factor, or endothelin-1. This inhibition was dose dependent, occurred predominantly through P2 purinergic receptors, and was observed even when cells were treated with ATP for as little as 1 hour before the addition of the hypertrophy-inducing agent. ATP also selectively affected changes in gene expression associated with hypertrophy. It prevented PE-stimulated increases in atrial natriuretic factor and myosin light chain-2 mRNA levels, while appearing to augment basal and PE-stimulated skeletal alpha-actin mRNA levels. ATP alone increased sarcoplasmic reticulum Ca2+-ATPase mRNA levels but had no effect when added with PE. ATP did not significantly affect the level of the constitutively expressed mRNA for GAPDH. Neither the PE-stimulated increase in immediate-early gene expression nor the initial induction of mitogen-activated protein kinase activity by PE was inhibited by ATP. These results demonstrate that extracellular ATP can inhibit hypertrophic growth of neonatal cardiac myocytes and differentially alter the changes in gene expression that accompany hypertrophy. JF - Circulation research AU - Zheng, J S AU - Boluyt, M O AU - Long, X AU - O'Neill, L AU - Lakatta, E G AU - Crow, M T AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 525 EP - 535 VL - 78 IS - 4 SN - 0009-7330, 0009-7330 KW - Adrenergic Agonists KW - 0 KW - Adrenergic Antagonists KW - Carbon Radioisotopes KW - Molecular Probes KW - Phenylephrine KW - 1WS297W6MV KW - Phenylalanine KW - 47E5O17Y3R KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Protein Kinases KW - EC 2.7.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Phenylalanine -- metabolism KW - Phenylalanine -- pharmacology KW - Protein-Tyrosine Kinases -- metabolism KW - Myocardium -- metabolism KW - Chromatography, High Pressure Liquid KW - Cell Size -- drug effects KW - Rats KW - Protein Kinases -- metabolism KW - Myocardium -- cytology KW - Animals, Newborn KW - Molecular Probes -- genetics KW - Protein Kinases -- drug effects KW - Cells, Cultured KW - Rats, Wistar KW - Molecular Sequence Data KW - Heart Ventricles KW - Phenylephrine -- pharmacology KW - Adenosine Triphosphate -- physiology KW - Adrenergic Antagonists -- pharmacology KW - Extracellular Space -- chemistry KW - Cardiomegaly -- chemically induced KW - Genes, fos KW - Cardiomegaly -- genetics KW - Cardiomegaly -- prevention & control KW - Adenosine Triphosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77995619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation+research&rft.atitle=Extracellular+ATP+inhibits+adrenergic+agonist-induced+hypertrophy+of+neonatal+cardiac+myocytes.&rft.au=Zheng%2C+J+S%3BBoluyt%2C+M+O%3BLong%2C+X%3BO%27Neill%2C+L%3BLakatta%2C+E+G%3BCrow%2C+M+T&rft.aulast=Zheng&rft.aufirst=J&rft.date=1996-04-01&rft.volume=78&rft.issue=4&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Circulation+research&rft.issn=00097330&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-11 N1 - Date created - 1996-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of wild-type and mutant adeno-associated virus (AAV) Rep proteins on AAV hairpin DNA. AN - 77987649; 8642672 AB - Both the Rep68 and Rep78 proteins of adeno-associated virus type 2 (AAV) bind to AAV terminal repeat hairpin DNA and can mediate site-specific nicking in vitro at the terminal resolution site (trs) within the terminal repeats. To define the regions of the Rep proteins required for these functions, a series of truncated Rep78 derivatives was created. Wild-type and mutant proteins were synthesized by in vitro translation and analyzed for AAV hairpin DNA binding, trs endonuclease activity, and interaction on hairpin DNA. Amino-terminal deletion mutants which lacked the first 29 or 79 amino acid residues of Rep78 did not bind hairpin DNA, which is consistent with our previous identification of a DNA-binding domain in this region. Progressive truncation of the carboxyl-terminal region of Rep78 did not eliminate hairpin DNA binding until the deletion reached amino acid 443. The electrophoretic mobility of the Rep-specific protein-DNA complexes was inversely related to the molecular weight of the Rep derivative. Analysis of the C-terminal deletion mutants by the trs endonuclease assay identified a region (amino acids 467 to 476) that is essential for nicking but is not necessary for DNA binding. When endonuclease-positive, truncated Rep proteins that bound hairpin DNA were mixed with full-length Rep78 or Rep68 protein in electrophoretic mobility shift assays, a smear of protein-DNA complexes was observed. This smear migrated at an intermediate position with respect to the bands generated by the proteins individually. An antibody recognizing only the full-length protein produced a novel supershift band when included in a mixed binding assay containing Rep68 and a truncated Rep mutant. These experiments suggest that the Rep proteins can form hetero-oligomers on the AAV hairpin DNA. JF - Journal of virology AU - Weitzman, M D AU - Kyöstiö, S R AU - Carter, B J AU - Owens, R A AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 2440 EP - 2448 VL - 70 IS - 4 SN - 0022-538X, 0022-538X KW - DNA-Binding Proteins KW - 0 KW - Viral Proteins KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - DNA KW - 9007-49-2 KW - Endonucleases KW - EC 3.1.- KW - Index Medicus KW - Endonucleases -- metabolism KW - Terminator Regions, Genetic KW - Humans KW - Protein Binding KW - Nucleic Acid Conformation KW - Sequence Deletion KW - Mutagenesis KW - Viral Proteins -- genetics KW - Dependovirus -- metabolism KW - DNA -- metabolism KW - Dependovirus -- genetics KW - DNA-Binding Proteins -- genetics KW - Viral Proteins -- metabolism KW - DNA -- chemistry KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77987649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Interaction+of+wild-type+and+mutant+adeno-associated+virus+%28AAV%29+Rep+proteins+on+AAV+hairpin+DNA.&rft.au=Weitzman%2C+M+D%3BKy%C3%B6sti%C3%B6%2C+S+R%3BCarter%2C+B+J%3BOwens%2C+R+A&rft.aulast=Weitzman&rft.aufirst=M&rft.date=1996-04-01&rft.volume=70&rft.issue=4&rft.spage=2440&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-18 N1 - Date created - 1996-07-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1991 Jan;65(1):396-404 [1845899] J Virol. 1990 Dec;64(12):6204-13 [2173787] Virology. 1991 Sep;184(1):14-22 [1651588] J Virol. 1992 Feb;66(2):1119-28 [1309894] J Virol. 1992 Feb;66(2):1236-40 [1309900] J Biol Chem. 1992 Apr 15;267(11):7596-610 [1313807] Science. 1992 Apr 17;256(5055):350-5 [1533057] Mol Cell Biol. 1992 May;12(5):2331-8 [1314954] J Virol. 1992 Jul;66(7):4050-7 [1318396] J Virol. 1992 Jul;66(7):4209-19 [1318402] J Virol. 1992 Oct;66(10):6058-69 [1326656] J Virol. 1992 Nov;66(11):6361-9 [1404595] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8923-7 [1409587] Genes Dev. 1992 Nov;6(11):2221-32 [1330829] J Virol. 1993 Feb;67(2):997-1005 [8380475] J Virol. 1993 Jul;67(7):4442-7 [8389942] Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):942-6 [8302872] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5808-12 [8016070] J Virol. 1994 Aug;68(8):4998-5006 [8035499] Virology. 1995 Jan 10;206(1):254-62 [7831779] Virology. 1995 Jan 10;206(1):448-56 [7831800] J Virol. 1995 Nov;69(11):6787-96 [7474090] Virology. 1973 Apr;52(2):456-67 [4705382] Proc Natl Acad Sci U S A. 1976 Mar;73(3):742-6 [1062784] Virology. 1977 May 15;78(2):488-99 [867815] J Gen Virol. 1977 Jul;36(1):59-74 [886304] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] J Virol. 1983 Feb;45(2):555-64 [6300419] Gene. 1984 Jun;28(3):351-9 [6235151] J Virol. 1984 Aug;51(2):329-39 [6086948] J Virol. 1984 Sep;51(3):611-9 [6088786] J Virol. 1984 Sep;51(3):768-75 [6088799] J Mol Biol. 1984 Oct 15;179(1):1-20 [6094825] Proc Natl Acad Sci U S A. 1984 Nov;81(22):6973-7 [6095264] EMBO J. 1985 Nov;4(11):2933-9 [2998767] J Virol. 1986 Dec;60(3):823-32 [3023672] J Virol. 1987 Feb;61(2):436-45 [3027373] J Gen Virol. 1987 Mar;68 ( Pt 3):885-93 [3819702] Virology. 1987 Nov;161(1):18-28 [2823460] EMBO J. 1987 Sep;6(9):2781-4 [3678204] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9396-400 [2849101] Nature. 1989 Apr 20;338(6217):658-62 [2539565] J Virol. 1989 Jul;63(7):3034-9 [2542611] J Virol. 1989 Jul;63(7):3095-104 [2542617] Virology. 1989 Jul;171(1):239-47 [2545030] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5698-702 [2569737] J Virol. 1989 Nov;63(11):4777-86 [2552152] Virology. 1989 Nov;173(1):120-8 [2554565] Cell. 1990 Jan 12;60(1):105-13 [2153052] Cell. 1990 Jan 26;60(2):181-4 [2153460] J Virol. 1990 Apr;64(4):1764-70 [2157057] Cell. 1990 May 4;61(3):447-57 [2159383] Nucleic Acids Res. 1991 Feb 25;19(4):851-60 [1850126] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination therapy with didanosine and interferon-alpha in human immunodeficiency virus-infected patients: results of a phase I/II trial. AN - 77987066; 8603961 AB - A nonrandomized trial was undertaken to evaluate the combination of didanosine and interferon-alpha (INF-alpha) in human immunodeficiency virus (HIV)-infected patients. Thirty-six volunteers with >200 x 10(6) CD4 cells/L received didanosine (one 100-, 250-, or 375-mg sachet twice daily) for at least 6 weeks, following which IFN-alpha (1, 5, 10, or 15 MU/day) was begun. Didanosine (one 375-mg sachet twice daily) was substituted for zidovudine in 14 additional patients who had received IFN-alpha and zidovudine for 7-45 months. Thirty-five patients completed the 34-week study. Clinical or chemical pancreatitis was the most common (6 patients) dose-limiting toxicity. CD4 cell counts increased with didanosine but declined following the addition of IFN-alpha; CD4 cell percents tended to increase and remain elevated. Thus, combination therapy with didanosine and IFN-alpha can be safely administered to patients with HIV infection. The clinical benefit of this combination therapy will require further evaluation. JF - The Journal of infectious diseases AU - Kovacs, J A AU - Bechtel, C AU - Davey, R T AU - Falloon, J AU - Polis, M A AU - Walker, R E AU - Metcalf, J A AU - Davey, V AU - Piscitelli, S C AU - Baseler, M AU - Dewar, R AU - Salzman, N P AU - Masur, H AU - Lane, H C AD - National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 840 EP - 848 VL - 173 IS - 4 SN - 0022-1899, 0022-1899 KW - Antiviral Agents KW - 0 KW - HIV Core Protein p24 KW - Interferon-alpha KW - RNA, Viral KW - Reverse Transcriptase Inhibitors KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Humans KW - HIV-1 -- growth & development KW - HIV Core Protein p24 -- metabolism KW - CD4 Lymphocyte Count KW - RNA, Viral -- metabolism KW - Pancreatitis -- chemically induced KW - Male KW - Female KW - Antiviral Agents -- administration & dosage KW - Interferon-alpha -- adverse effects KW - Reverse Transcriptase Inhibitors -- administration & dosage KW - Interferon-alpha -- administration & dosage KW - HIV Infections -- drug therapy KW - Didanosine -- administration & dosage KW - Didanosine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77987066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Combination+therapy+with+didanosine+and+interferon-alpha+in+human+immunodeficiency+virus-infected+patients%3A+results+of+a+phase+I%2FII+trial.&rft.au=Kovacs%2C+J+A%3BBechtel%2C+C%3BDavey%2C+R+T%3BFalloon%2C+J%3BPolis%2C+M+A%3BWalker%2C+R+E%3BMetcalf%2C+J+A%3BDavey%2C+V%3BPiscitelli%2C+S+C%3BBaseler%2C+M%3BDewar%2C+R%3BSalzman%2C+N+P%3BMasur%2C+H%3BLane%2C+H+C&rft.aulast=Kovacs&rft.aufirst=J&rft.date=1996-04-01&rft.volume=173&rft.issue=4&rft.spage=840&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-16 N1 - Date created - 1996-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Live subgroup B respiratory syncytial virus vaccines that are attenuated, genetically stable, and immunogenic in rodents and nonhuman primates. AN - 77987016; 8603960 AB - Optimal immunization of neonates against disease caused by respiratory syncytial virus (RSV) probably will require multiple doses of a vaccine containing viruses of both subgroups A and B. Live subgroup B RSV mutants were generated containing multiple attenuating mutations, ts (temperature-sensitive) and non-ts (host range), that were introduced by prolonged passage in cell culture or by chemical mutagenesis. The cold-passaged (cp)-52 mutant was restricted in replication compared to wild type virus in rodents and nonhuman primates. In addition, the attenuation phenotype of cp-52 was stable after prolonged replication in immunosuppressed rodents. One or two ts mutations were then introduced into the cp-52 mutant to generate additional candidate vaccine strains that were more attenuated in vivo than the cp-52 parental virus. Tests in humans are being done to determine if one or more of the RSV B-1 mutants exhibit a satisfactory balance between attenuation and immunogenicity. JF - The Journal of infectious diseases AU - Crowe, J E AU - Bui, P T AU - Firestone, C Y AU - Connors, M AU - Elkins, W R AU - Chanock, R M AU - Murphy, B R AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 829 EP - 839 VL - 173 IS - 4 SN - 0022-1899, 0022-1899 KW - Antibodies, Viral KW - 0 KW - Vaccines, Attenuated KW - Viral Vaccines KW - Abridged Index Medicus KW - Index Medicus KW - Virus Replication KW - Animals KW - Cercopithecus aethiops KW - Serotyping KW - Sigmodontinae KW - Mutagenesis KW - Antibodies, Viral -- biosynthesis KW - Respiratory Syncytial Viruses -- immunology KW - Vaccines, Attenuated -- immunology KW - Viral Vaccines -- immunology KW - Respiratory Syncytial Virus Infections -- prevention & control KW - Respiratory Syncytial Virus Infections -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77987016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Live+subgroup+B+respiratory+syncytial+virus+vaccines+that+are+attenuated%2C+genetically+stable%2C+and+immunogenic+in+rodents+and+nonhuman+primates.&rft.au=Crowe%2C+J+E%3BBui%2C+P+T%3BFirestone%2C+C+Y%3BConnors%2C+M%3BElkins%2C+W+R%3BChanock%2C+R+M%3BMurphy%2C+B+R&rft.aulast=Crowe&rft.aufirst=J&rft.date=1996-04-01&rft.volume=173&rft.issue=4&rft.spage=829&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-16 N1 - Date created - 1996-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic analysis of the zinc finger in the Moloney murine leukemia virus nucleocapsid domain: replacement of zinc-coordinating residues with other zinc-coordinating residues yields noninfectious particles containing genomic RNA. AN - 77986666; 8642691 AB - The effect of changing zinc (Zn2+)-coordinating residues in the nucleocapsid protein of Moloney murine leukemia virus was investigated by introducing a His-34-to-Cys or Cys-39-to-His mutation into the putative Zn2+ finger. Mutant virions contained normal levels of properly processed Gag and Env proteins and wild-type levels of full-length viral RNA. However, the specific infectivity of the mutants was approximately 4 x 10(-4) that of wild-type particles. They were probably noninfectious because of the inability of the particles to synthesize cDNA transcripts, since full-length viral DNA could not be detected in Hirt supernatants of NIH 3T3 cells infected with the CCCC or CCHH virus. These mutants will provide an extremely valuable tool for analysis of the role of retroviral Zn2+ fingers in infection processes, independent of viral RNA recognition and packaging. JF - Journal of virology AU - Gorelick, R J AU - Chabot, D J AU - Ott, D E AU - Gagliardi, T D AU - Rein, A AU - Henderson, L E AU - Arthur, L O AD - AIDS Vaccine Program, SAIC-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 2593 EP - 2597 VL - 70 IS - 4 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - RNA, Viral KW - Viral Core Proteins KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Virus Replication -- genetics KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Virus Replication -- physiology KW - RNA, Viral -- metabolism KW - Cell Line KW - Zinc Fingers -- physiology KW - Moloney murine leukemia virus -- pathogenicity KW - Zinc -- physiology KW - Zinc Fingers -- genetics KW - Capsid -- genetics KW - Viral Core Proteins -- genetics KW - Moloney murine leukemia virus -- physiology KW - Viral Core Proteins -- physiology KW - Moloney murine leukemia virus -- genetics KW - Capsid -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77986666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Genetic+analysis+of+the+zinc+finger+in+the+Moloney+murine+leukemia+virus+nucleocapsid+domain%3A+replacement+of+zinc-coordinating+residues+with+other+zinc-coordinating+residues+yields+noninfectious+particles+containing+genomic+RNA.&rft.au=Gorelick%2C+R+J%3BChabot%2C+D+J%3BOtt%2C+D+E%3BGagliardi%2C+T+D%3BRein%2C+A%3BHenderson%2C+L+E%3BArthur%2C+L+O&rft.aulast=Gorelick&rft.aufirst=R&rft.date=1996-04-01&rft.volume=70&rft.issue=4&rft.spage=2593&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-18 N1 - Date created - 1996-07-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Protein Eng. 1991 Aug;4(6):695-700 [1658777] Adv Inorg Biochem. 1990;8:199-248 [2119553] J Virol. 1992 Oct;66(10):6107-16 [1326661] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10041-5 [1332027] Nature. 1993 Feb 4;361(6411):473-5 [8429889] Protein Sci. 1992 May;1(5):563-74 [1304355] J Virol. 1993 Jul;67(7):4027-36 [8510214] J Virol. 1993 Sep;67(9):5443-9 [8350405] J Virol. 1994 Feb;68(2):757-65 [8289379] J Virol. 1994 Aug;68(8):5013-8 [8035501] J Virol. 1994 Sep;68(9):5969-81 [8057473] J Biol Chem. 1994 Sep 2;269(35):21948-50 [8071314] Biochemistry. 1994 Oct 4;33(39):11707-16 [7918387] J Biol Chem. 1994 Dec 16;269(50):31491-5 [7989315] Science. 1995 Nov 17;270(5239):1194-7 [7502043] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] Nature. 1971 Feb 19;229(5286):564-6 [4925356] J Gen Virol. 1971 Nov;13(2):245-52 [4333712] Virology. 1973 Apr;52(2):456-67 [4705382] J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] Nature. 1981 Oct 15-21;293(5833):543-8 [6169994] Virology. 1982 Jul 15;120(1):251-7 [6285602] J Virol. 1988 May;62(5):1590-7 [2451755] J Virol. 1988 May;62(5):1808-9 [3357211] J Virol. 1988 Sep;62(9):3328-33 [2841485] EMBO J. 1988 Jun;7(6):1777-83 [2458920] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8420-4 [3141927] J Virol. 1990 May;64(5):1920-6 [2109098] J Virol. 1990 Jul;64(7):3207-11 [2191147] J Virol. 1990 Oct;64(10):4978-87 [2168981] J Virol. 1990 Oct;64(10):5076-92 [1697912] J Virol. 1992 Feb;66(2):840-7 [1731111] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of benztropine on behavioral and toxic effects of cocaine: comparison with atropine and the selective dopamine uptake inhibitor 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-propyl)-piperazine. AN - 77984323; 8613919 AB - Behavioral effects of cocaine that are relevant to its abuse have been associated with pharmacological actions at the dopamine uptake carrier. Benztropine (Cogentin) is an antiparkinson agent that has limited abuse despite its ability to block dopamine uptake, and has been suggested as a candidate for the treatment of cocaine dependence. Preclinical studies were conducted to assess the behavioral and toxic effects of benztropine alone and in conjunction with cocaine. Because of the mixed pharmacology of benztropine which includes antimuscarinic as well as dopaminergic actions, results obtained from parallel experiments with atropine and the selective dopamine uptake inhibitor, GBR 12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-propyl)-piperazine), were performed. All of the drugs stimulated locomotor activity of mice, but atropine and benztropine had much lower efficacy. Nonstimulatory doses of GBR 12935 enhanced the locomotor stimulant effects of cocaine, whereas benztropine and atropine did not share this effect. GBR 12935, benztropine and cocaine increased fixed-interval responding, whereas atropine decreased fixed-interval response rates in rats. Only GBR 12935 and cocaine increased responding during timeout periods. GBR 12935, but not benztropine or atropine, fully reproduced the discriminative stimulus effects of cocaine (10 mg/kg). GBR 12935 and atropine augmented the discriminative stimulus effects of lower cocaine doses in rats. Only GBR 12935 and cocaine had convulsant effects and only GBR 12935 significantly enhanced the convulsant effects of cocaine in mice. These results document a behavioral and toxicity profile for benztropine distinct from that of classical dopamine uptake blockers. The data underscore further the potential of benztropine as a candidate for clinical evaluation in the treatment of cocaine dependence. JF - The Journal of pharmacology and experimental therapeutics AU - Acri, J B AU - Siedleck, B K AU - Witkin, J M AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 198 EP - 206 VL - 277 IS - 1 SN - 0022-3565, 0022-3565 KW - Dopamine Uptake Inhibitors KW - 0 KW - Piperazines KW - Benztropine KW - 1NHL2J4X8K KW - Atropine KW - 7C0697DR9I KW - 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine KW - 9J9974WIBA KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Seizures -- chemically induced KW - Rats KW - Discrimination Learning -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Motor Activity -- drug effects KW - Mice KW - Male KW - Behavior, Animal -- drug effects KW - Cocaine -- toxicity KW - Benztropine -- pharmacology KW - Piperazines -- pharmacology KW - Atropine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77984323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Effects+of+benztropine+on+behavioral+and+toxic+effects+of+cocaine%3A+comparison+with+atropine+and+the+selective+dopamine+uptake+inhibitor+1-%5B2-%28diphenylmethoxy%29ethyl%5D-4-%283-phenyl-propyl%29-piperazine.&rft.au=Acri%2C+J+B%3BSiedleck%2C+B+K%3BWitkin%2C+J+M&rft.aulast=Acri&rft.aufirst=J&rft.date=1996-04-01&rft.volume=277&rft.issue=1&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-06 N1 - Date created - 1996-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutamate residues in the second extracellular loop of the human A2a adenosine receptor are required for ligand recognition. AN - 77977519; 8609897 AB - The A2a adenosine receptor, a member of the G protein-coupled receptor family, is important in the regulation of dopaminergic pathways of the brain and in platelet and cardiovascular functions. In this study, the role of extracellular loops in ligand binding to the human A2a receptor was explored through site-directed mutagenesis. Four glutamate/aspartate residues (Glu151, Glu161, Glu169, and Asp170) in the second extracellular loop (E2) and a cysteine residue (Cys262) in the third extracellular loop (E3) were individually replaced with alanine and other amino acids. A proline residue (Pro173) in E2 was mutated to arginine, the homologous amino acid in A3 receptors. The binding properties of the resultant mutant receptors were determined in transfected COS-7 cells. The mutant receptors were tagged at their amino terminus with a hemagglutinin epitope, thus allowing their detection in the plasma membrane with immunological techniques. High affinity specific binding of [3H]2-[4-[(2-carboxyethyl)phenyl]ethyl-amino]-5'-N-ethylcarboxamidoad eno sine (15 nM) and [3H]8-[4-[[[[2-aminoethyl)-amino]carbonyl]methyl]oxy]phenyl]-1,3- dipropylxanthine (4nM), an A2a agonist and antagonist, respectively, was not observed with four of the mutant receptors, E151A, E151Q, E151D, and E169A, although they were well expressed at the cell surface. The E151A and E169A mutant receptors showed nearly full stimulation of adenylyl cyclase at approximately 10(3)-fold higher concentrations of 2-[4-[(2-carboxyethyl)phenyl]ethyl-amino]-5'-N-ethylcarboxamidoadenosine . The E161A mutant receptor showed as increase in affinity for the nonxanthine adenosine antagonist 9-chloro-2-(furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine(6 fold) but not for other ligands. An E169Q mutant gained affinity (5-22 fold) for adenosine derivatives (agonists) substituted at N6 but not at C2 or C5' positions. Mutant receptors D170K and P173R were similar to wild-type receptors in binding of both agonist and antagonist radioligands. A C262G mutant also resembled the wild-type receptor in radioligand binding, indicating that a potential disulfide bridge with another cysteine residue in proximity is not required for the structural integrity of the receptor. Our data suggest that certain amino acids in the second extracellular loop may be directly or indirectly involved in ligand binding. JF - Molecular pharmacology AU - Kim, J AU - Jiang, Q AU - Glashofer, M AU - Yehle, S AU - Wess, J AU - Jacobson, K A AD - Molecular Recognition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 683 EP - 691 VL - 49 IS - 4 SN - 0026-895X, 0026-895X KW - Ligands KW - 0 KW - Phenethylamines KW - Receptors, Purinergic P1 KW - 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine KW - 120225-54-9 KW - Glutamic Acid KW - 3KX376GY7L KW - Magnesium KW - I38ZP9992A KW - Adenosine KW - K72T3FS567 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Adenosine -- analogs & derivatives KW - Humans KW - Amino Acid Sequence KW - Calcium -- pharmacology KW - Structure-Activity Relationship KW - Binding Sites KW - Phenethylamines -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Magnesium -- pharmacology KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Adenosine -- metabolism KW - Receptors, Purinergic P1 -- chemistry KW - Receptors, Purinergic P1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77977519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Glutamate+residues+in+the+second+extracellular+loop+of+the+human+A2a+adenosine+receptor+are+required+for+ligand+recognition.&rft.au=Kim%2C+J%3BJiang%2C+Q%3BGlashofer%2C+M%3BYehle%2C+S%3BWess%2C+J%3BJacobson%2C+K+A&rft.aulast=Kim&rft.aufirst=J&rft.date=1996-04-01&rft.volume=49&rft.issue=4&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-30 N1 - Date created - 1996-05-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] Mol Pharmacol. 1983 May;23(3):576-84 [6306429] Mol Pharmacol. 1985 Jun;27(6):595-9 [2987658] Methods Enzymol. 1987;152:684-704 [3657593] J Biol Chem. 1989 Aug 15;264(23):13572-8 [2547766] Physiol Rev. 1990 Jul;70(3):761-845 [2194223] J Med Chem. 1992 Feb 7;35(3):407-22 [1738138] Mol Pharmacol. 1992 Feb;41(2):352-9 [1311411] J Mol Biol. 1992 May 5;225(1):155-75 [1583688] J Biol Chem. 1992 May 25;267(15):10764-70 [1587851] Med Res Rev. 1992 Sep;12(5):423-71 [1513184] Biochem Pharmacol. 1992 Dec 15;44(12):2365-70 [1472101] Pharmacol Biochem Behav. 1993 Aug;45(4):951-8 [8105493] J Biol Chem. 1994 Jan 28;269(4):2373-6 [8300561] J Biol Chem. 1994 Jan 28;269(4):2863-9 [8300621] J Med Chem. 1994 Mar 4;37(5):636-46 [8126704] J Biol Chem. 1994 Jul 1;269(26):17531-6 [7912696] J Biol Chem. 1994 Jul 8;269(27):18016-20 [8027060] J Biol Chem. 1994 Aug 5;269(31):19738-44 [8051054] J Biol Chem. 1994 Sep 9;269(36):22636-41 [7915716] Prog Neuropsychopharmacol Biol Psychiatry. 1994 May;18(3):545-53 [8078988] Eur J Pharmacol. 1994 Jun 15;268(1):95-104 [7925617] J Biol Chem. 1994 Oct 7;269(40):24621-6 [7929134] J Biol Chem. 1994 Oct 7;269(40):24692-8 [7929142] J Biol Chem. 1994 Nov 11;269(45):27900-6 [7961722] Mol Pharmacol. 1995 Jan;47(1):88-98 [7838137] Structure. 1995 Jan 15;3(1):7-11 [7743133] Neuron. 1995 May;14(5):889-92 [7538310] EMBO J. 1995 May 15;14(10):2176-82 [7774575] J Biol Chem. 1995 Jun 9;270(23):13987-97 [7775460] J Biol Chem. 1995 Jul 28;270(30):18000-6 [7629108] Life Sci. 1995;56(11-12):915-22 [10188793] J Pharmacol Exp Ther. 1989 Dec;251(3):888-93 [2600819] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenovirus-mediated gene transfer of ornithine aminotransferase in cultured human retinal pigment epithelium. AN - 77971393; 8603861 AB - To evaluate the efficacy of adenovirus mediated transfer of ornithine delta-aminotransferase (OAT) into human retinal pigment epithelial (RPE) cells. Adenovirus-mediated gene transfer into primary cultures of human RPE was evaluated by measurement of enzyme activity in whole cell extracts and by Western blot analysis. To assess mitochondrial integrity, succinate dehydrogenase activity was measured in transduced RPE cells. Expression of adenovirus early genes was evaluated using reverse transcription-polymerase chain reaction. OAT activity, which was 65 nmol/mg.hour in untransduced cells, could be increased to levels in excess of 20,000 nmol/mg.hour using an adenovirus vector carrying the OAT cDNA. There was, however, a significant reduction in succinate dehydrogenase activity associated with OAT activity greater than 12,000 nmol/mg.hour. Transduced human RPE displayed an altered morphology that appears to be a response to the vector because similar changes could be induced by an adenovirus vector that does not carry the OAT cDNA. Adenovirus early gene expression was detected in transduced RPE. This study represents a first step in the development of intraocular gene replacement therapy for the treatment of gyrate atrophy. The authors demonstrate that adenovirus is an efficient vehicle for the delivery of OAT into human RPE and that RPE will tolerate greater than a 150-fold increase in OAT-specific activity. Evidence for disruption of mitochondria when OAT activity exceeds 12,000 nmol/mg.hour and vector-induced toxicity indicate that more controlled transgene expression and refinement of the vector systems is needed. JF - Investigative ophthalmology & visual science AU - Sullivan, D M AU - Chung, D C AU - Anglade, E AU - Nussenblatt, R B AU - Csaky, K G AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20895, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 766 EP - 774 VL - 37 IS - 5 SN - 0146-0404, 0146-0404 KW - DNA Primers KW - 0 KW - Succinate Dehydrogenase KW - EC 1.3.99.1 KW - Ornithine-Oxo-Acid Transaminase KW - EC 2.6.1.13 KW - Index Medicus KW - Defective Viruses -- genetics KW - Gene Expression Regulation, Viral KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Mitochondria -- enzymology KW - Polymerase Chain Reaction KW - Base Sequence KW - Blotting, Western KW - Gene Expression Regulation, Enzymologic KW - Cells, Cultured KW - Genetic Vectors KW - Molecular Sequence Data KW - Succinate Dehydrogenase -- metabolism KW - DNA Primers -- chemistry KW - Ornithine-Oxo-Acid Transaminase -- metabolism KW - Gene Transfer Techniques KW - Adenoviruses, Human -- genetics KW - Pigment Epithelium of Eye -- virology KW - Ornithine-Oxo-Acid Transaminase -- genetics KW - Pigment Epithelium of Eye -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77971393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=Adenovirus-mediated+gene+transfer+of+ornithine+aminotransferase+in+cultured+human+retinal+pigment+epithelium.&rft.au=Sullivan%2C+D+M%3BChung%2C+D+C%3BAnglade%2C+E%3BNussenblatt%2C+R+B%3BCsaky%2C+K+G&rft.aulast=Sullivan&rft.aufirst=D&rft.date=1996-04-01&rft.volume=37&rft.issue=5&rft.spage=766&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-16 N1 - Date created - 1996-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraocular levels of methotrexate after intravenous administration. AN - 77970870; 8604740 AB - To determine if adequate intraocular levels of methotrexate are achieved after intravenous administration. After intravenous administration, methotrexate levels were determined in the serum, the anterior chamber, and the cerebrospinal fluids of a patient with recurrent ocular lymphoma. A fluorescence polarization immunoassay was used to make the determinations. At seven hours into a 24-hour intravenous infusion, methotrexate was at cytotoxic level in all samples. At 74 hours, cytotoxic levels were present only in the aqueous humor. Sustained cytotoxic ocular methotrexate levels are achievable after systemic administration. JF - American journal of ophthalmology AU - de Smet, M D AU - Stark-Vancs, V AU - Kohler, D R AU - Smith, J AU - Wittes, R AU - Nussenblatt, R B AD - Clinical Immunology Section, National Eye Institute, Bethesda, MD 20892-1858, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 442 EP - 444 VL - 121 IS - 4 SN - 0002-9394, 0002-9394 KW - Antimetabolites, Antineoplastic KW - 0 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Lymphoma, Non-Hodgkin -- metabolism KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Fluorescence Polarization Immunoassay KW - Infusions, Intravenous KW - Humans KW - Anterior Chamber -- metabolism KW - Eye Neoplasms -- drug therapy KW - Cerebrospinal Fluid -- metabolism KW - Middle Aged KW - Eye Neoplasms -- metabolism KW - Female KW - Biological Availability KW - Aqueous Humor -- metabolism KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Methotrexate -- pharmacokinetics KW - Methotrexate -- therapeutic use KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Methotrexate -- administration & dosage KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77970870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+ophthalmology&rft.atitle=Intraocular+levels+of+methotrexate+after+intravenous+administration.&rft.au=de+Smet%2C+M+D%3BStark-Vancs%2C+V%3BKohler%2C+D+R%3BSmith%2C+J%3BWittes%2C+R%3BNussenblatt%2C+R+B&rft.aulast=de+Smet&rft.aufirst=M&rft.date=1996-04-01&rft.volume=121&rft.issue=4&rft.spage=442&rft.isbn=&rft.btitle=&rft.title=American+journal+of+ophthalmology&rft.issn=00029394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-13 N1 - Date created - 1996-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glycoprotein hormone alpha-subunit functions synergistically with progesterone to stimulate differentiation of cultured human endometrial stromal cells to decidualized cells: a novel role for free alpha-subunit in reproduction. AN - 77970690; 8625908 AB - Glycoprotein hormone-free alpha subunit is secreted by the pituitary throughout the menstrual cycle and by the placenta during pregnancy. We showed previously that free alpha subunit stimulated PRL secretion from term pregnancy decidual cells, suggesting a function for free alpha in pregnancy. However, no role has been ascribed to free alpha in the normal menstrual cycle. Using an in vitro model, we examined the role of alpha subunit in regulating human endometrial stromal cell differentiation (decidualization). PRL and insulin-like growth factor binding protein-1 (IGFBP-1), specific decidual secretory products, were used as markers of decidualization. We found that alpha subunit acted synergistically with progesterone (P) to induce more rapid decidualization with higher output (2- to 6-fold) of PRL and IGFBP-1, compared with P alone (P < 0.01). The effect of alpha was dose dependent, with stimulatory activity starting at 0.05 ng/ml and reaching maximal levels at 1-2 ng/ml. These levels correspond to serum concentrations of free alpha found during the luteal phase of the menstrual cycle when endometrial decidualization occurs in vivo. These findings demonstrate new biological activity for alpha subunit in the regulation of human endometrial decidualization and indicate that free alpha plays a role in human reproduction. Furthermore, demonstration of potential bioactivities of free alpha subunit has important implications for understanding normal endocrine function and various pathological conditions. JF - Endocrinology AU - Moy, E AU - Kimzey, L M AU - Nelson, L M AU - Blithe, D L AD - Unit on Glycobiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 1332 EP - 1339 VL - 137 IS - 4 SN - 0013-7227, 0013-7227 KW - Chorionic Gonadotropin KW - 0 KW - Glycoprotein Hormones, alpha Subunit KW - Insulin-Like Growth Factor Binding Protein 1 KW - Progesterone KW - 4G7DS2Q64Y KW - Prolactin KW - 9002-62-4 KW - Abridged Index Medicus KW - Index Medicus KW - Prolactin -- biosynthesis KW - Insulin-Like Growth Factor Binding Protein 1 -- biosynthesis KW - Reproduction -- physiology KW - Chorionic Gonadotropin -- pharmacology KW - Cells, Cultured KW - Humans KW - Adult KW - Middle Aged KW - Drug Synergism KW - Cell Differentiation -- drug effects KW - Female KW - Pregnancy KW - Glycoprotein Hormones, alpha Subunit -- physiology KW - Decidua -- cytology KW - Progesterone -- pharmacology KW - Glycoprotein Hormones, alpha Subunit -- pharmacology KW - Endometrium -- cytology KW - Stromal Cells -- cytology KW - Endometrium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77970690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Glycoprotein+hormone+alpha-subunit+functions+synergistically+with+progesterone+to+stimulate+differentiation+of+cultured+human+endometrial+stromal+cells+to+decidualized+cells%3A+a+novel+role+for+free+alpha-subunit+in+reproduction.&rft.au=Moy%2C+E%3BKimzey%2C+L+M%3BNelson%2C+L+M%3BBlithe%2C+D+L&rft.aulast=Moy&rft.aufirst=E&rft.date=1996-04-01&rft.volume=137&rft.issue=4&rft.spage=1332&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaginal clear cell adenocarcinoma in the United States. AN - 77959276; 8626097 AB - We elected to examine available information from several sources to approximate the annual number of cases of vaginal adenocarcinoma in the United States for recent years. Data were obtained from the Registry of Hormonal Transplacental Carcinogenesis, the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute, the National Cancer Databank of the American College of Surgeons Commission on Cancer, and a survey of gynecologic oncologists practicing in the United States. In 1990 a total of 33 new cases and 11 recurrences were reported, while in 1991 23 new cases and 8 recurrences were reported. Neither SEER nor the Registry appear to provide adequate surveillance for this rare disease. Phase III clinical trials are not feasible, given the small number of patients. Statistically effective phase II one-armed studies to investigate new agents in the treatment of advanced or recurrent vaginal clear cell cancer may be possible. Effective mobilization of patients and physicians will be required for such trials to be completed in a timely manner. JF - Gynecologic oncology AU - Trimble, E L AU - Rubinstein, L V AU - Menck, H R AU - Hankey, B F AU - Kosary, C AU - Giusti, R M AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 113 EP - 115 VL - 61 IS - 1 SN - 0090-8258, 0090-8258 KW - Index Medicus KW - Registries KW - Gynecology KW - Humans KW - SEER Program KW - Incidence KW - Medical Oncology KW - Data Collection KW - Neoplasm Recurrence, Local KW - United States -- epidemiology KW - Female KW - Adenocarcinoma, Clear Cell -- epidemiology KW - Vaginal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77959276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Vaginal+clear+cell+adenocarcinoma+in+the+United+States.&rft.au=Trimble%2C+E+L%3BRubinstein%2C+L+V%3BMenck%2C+H+R%3BHankey%2C+B+F%3BKosary%2C+C%3BGiusti%2C+R+M&rft.aulast=Trimble&rft.aufirst=E&rft.date=1996-04-01&rft.volume=61&rft.issue=1&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of Molecular Approaches to Early Lung Cancer Detection. AN - 1859322606; 10717164 AB - Lung cancer has been particularly recalcitrant to standard therapeutic interventions. Improvement in the outcome for this disease requires the ability to identify the disease while it is still localized in the airways. Usually, radiation therapy to eliminate this disease fails because of progression of the cancer outside the radiation treatment ports. This is a failure of the diagnostic modalities to detect the extent of the cancer, not a failure of the radiation. With new epithelial-directed diagnostics, the ability to detect the premetastatic phase of lung cancer is emerging. Evolution of the screening infrastructure will be required to allow percolation of this technology out to the medical community, so that a benefit in cancer mortality reduction can be achieved. Some development issues will have to be resolved. Considering our fragmentary understanding of pulmonary carcinogenesis, the heterogeneity of lung cancer suggests that a panel of biomarkers instead of a single marker will be required to clarify the status of an individual's epithelium. However, the data output from multiplexed bioassays performed on large clinical populations will require better integration of information technology to optimize analysis and reporting of test results. An important new area for outcomes research is the systematic analysis of population screening approaches. With population sampling algorithms, selective screening. This type of research requires careful clinical validation. Finally, the general acceptance of population-based screening will be determined by the availability of effective interventions to complement the new diagnostic tools. New measures to prevent the progression of early cancer will be discussed. JF - Seminars in radiation oncology AU - Mulshine AU - Scott AU - Zhou AU - Avis AU - Vos AU - Miller AU - Szabo AU - Martinez AU - Treston AU - Cuttitta AU - Tockman AD - Biomarkers and Prevention Research Branch, National Cancer Institute, Rockville, MD, USA Y1 - 1996/04// PY - 1996 DA - April 1996 SP - 72 EP - 75 VL - 6 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859322606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+radiation+oncology&rft.atitle=Development+of+Molecular+Approaches+to+Early+Lung+Cancer+Detection.&rft.au=Mulshine%3BScott%3BZhou%3BAvis%3BVos%3BMiller%3BSzabo%3BMartinez%3BTreston%3BCuttitta%3BTockman&rft.aulast=Mulshine&rft.aufirst=&rft.date=1996-04-01&rft.volume=6&rft.issue=2&rft.spage=72&rft.isbn=&rft.btitle=&rft.title=Seminars+in+radiation+oncology&rft.issn=1532-9461&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2000-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxol-induced apoptosis and phosphorylation of Bcl-2 protein involves c-Raf-1 and represents a novel c-Raf-1 signal transduction pathway AN - 15852703; 4020316 AB - c-Raf-1 (Raf-1) is a central component of signal transduction pathways stimulated by various growth factors, protein kinase C, and other protein kinases. Raf-1 activation is thought to be initiated at the plasma membrane after its recruitment by Ras. Raf-1 activation is associated primarily with proliferation and cell survival, but it has also been implicated in apoptosis. Raf-1 has also been shown to form complexes with both R-Ras and Bcl-2, raising the possibility that this component of cellular Raf-1 plays a role in apoptosis. Recently, taxol was reported to induce Bcl-2 phosphorylation and inactivation. We have previously demonstrated Raf-1 activation following taxol in MCF7 cells. We now present evidence that taxol fails to stimulate either apoptosis or phosphorylation of Bcl-2 in the absence of Raf-1. Moreover, Raf-1 activation by taxol coincided with Bcl-2 phosphorylation, showing similar dose and time dependence. Thus, our data support a role for a distinct subcellular component of Raf-1, which is taxol but not phorbol myristate acetate sensitive, in mediating an apoptotic pathway involving Bcl-2. (DBO) JF - Cancer Research AU - Blagosklonny, M V AU - Schulte, T AU - Nguyen, Phuongmai AU - Trepel, J AU - Neckers, L M AD - Clinical Pharmacology Branch, National Cancer Institute, NIH, Building 10, 12N226, Bethesda, MD 20892, USA Y1 - 1996/04// PY - 1996 DA - Apr 1996 SP - 1851 EP - 1854 VL - 56 IS - 8 SN - 0008-5472, 0008-5472 KW - taxol KW - Bcl-2 protein KW - c-Raf-1 protein KW - paclitaxel KW - Toxicology Abstracts KW - apoptosis KW - antineoplastic drugs KW - signal transduction KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15852703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Taxol-induced+apoptosis+and+phosphorylation+of+Bcl-2+protein+involves+c-Raf-1+and+represents+a+novel+c-Raf-1+signal+transduction+pathway&rft.au=Blagosklonny%2C+M+V%3BSchulte%2C+T%3BNguyen%2C+Phuongmai%3BTrepel%2C+J%3BNeckers%2C+L+M&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=1996-04-01&rft.volume=56&rft.issue=8&rft.spage=1851&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - apoptosis; signal transduction; antineoplastic drugs ER - TY - JOUR T1 - A soluble active mutant of HIV-1 integrase: involvement of both the core and carboxyl-terminal domains in multimerization. AN - 78010461; 8631811 AB - Structural studies of human immunodeficiency virus type 1 (HIV-1) integrase have been impeded by the low solubility of the protein. By systematic replacement of hydrophobic residues, we previously identified a single amino acid change (F185K) that dramatically improved the solubility of the catalytic domain of HIV-1 integrase and enabled the structure to be determined by x-ray crystallography. We have introduced the same mutation into full-length HIV-1 integrase. The resulting recombinant protein is soluble and fully active in vitro, whereas, HIV-1 carrying the mutation is replication-defective due to improper virus assembly. Analysis of the recombinant protein by gel filtration and sedimentation equilibrium demonstrate a dimer-tetramer self-association. We find that the regions involved in multimerization map to both the catalytic core and carboxyl-terminal domains. The dramatically improved solubility of this protein make it a good candidate for structural studies. JF - The Journal of biological chemistry AU - Jenkins, T M AU - Engelman, A AU - Ghirlando, R AU - Craigie, R AD - Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0560, USA. Y1 - 1996/03/29/ PY - 1996 DA - 1996 Mar 29 SP - 7712 EP - 7718 VL - 271 IS - 13 SN - 0021-9258, 0021-9258 KW - Macromolecular Substances KW - 0 KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Solubility KW - Recombinant Proteins -- biosynthesis KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Amino Acid Sequence KW - Virus Integration KW - Ultracentrifugation KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Point Mutation KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - HIV-1 -- genetics KW - DNA Nucleotidyltransferases -- biosynthesis KW - HIV-1 -- enzymology KW - HIV-1 -- physiology KW - DNA Nucleotidyltransferases -- chemistry KW - DNA Nucleotidyltransferases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78010461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=A+soluble+active+mutant+of+HIV-1+integrase%3A+involvement+of+both+the+core+and+carboxyl-terminal+domains+in+multimerization.&rft.au=Jenkins%2C+T+M%3BEngelman%2C+A%3BGhirlando%2C+R%3BCraigie%2C+R&rft.aulast=Jenkins&rft.aufirst=T&rft.date=1996-03-29&rft.volume=271&rft.issue=13&rft.spage=7712&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-03 N1 - Date created - 1996-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-nitrosodimethylamine-derived O(6)-methylguanine in DNA of monkey gastrointestinal and urogenital organs and enhancement by ethanol. AN - 77973591; 8608956 AB - N-nitrosodimethylamine (NDMA) is a human cancer initiator suspect. Ethanol, a cancer risk factor, may synergize with nitrosamines by suppressing hepatic clearance, to increase internal exposure. A limitation to these hypotheses is lack of activation of NDMA by many rodent tissues. However, systemtic primate studies are lacking. Patas monkeys were utilized to investigate NDMA activation by primate tissues in vivo, generating the promutagenic DNA lesion 0(6)-methylguanine (0(6)-meG). Adult monkeys received 0. 1 mg/kg NDMA by gavage, in some cases preceded by ethanol. Four hours after NDMA only, 0(6)-meG was detected in DNA from all tissues. Levels were highest in gastric mucosa and liver and were only about 50% lower in DNA from white blood cells, esophagus, ovary, pancreas, urinary bladder and uterus. With ethanol co-exposure, amounts of 0(6)-meG increased at least 2-fold in all tissues except liver. The largest effect was in esophagus (17-fold increase), followed by ovary, large intestine, urinary bladder, spleen and cerebellum (9- to 13-fold increases), and uterus, cerebrum and brain stem (7- to 8-fold increases). Alkylguanine alkyltransferase activities varied over a 30-fold range and were highest in liver and stomach. Thus primate tissues, especially those of the gastrointestinal and urogenital organs, are sensitive targets for DNA adduct damage due to NDMA, and ethanol co-exposure leads to striking increases in adducts. Our data support epidemiology implicating nitrosamines in causation of cancers of stomach and other organs, and alcohol as enhancing internal exposure to nitrosamines. JF - International journal of cancer AU - Anderson, L M AU - Souliotis, V L AU - Chhabra, S K AU - Moskal, T J AU - Harbaugh, S D AU - Kyrtopoulos, S A AD - Laboratory of Comparative Carcinogenesis, NCI, Frederick, MD, USA. Y1 - 1996/03/28/ PY - 1996 DA - 1996 Mar 28 SP - 130 EP - 134 VL - 66 IS - 1 SN - 0020-7136, 0020-7136 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Nitroso Compounds KW - 4-nitrosodimethylaniline KW - 138-89-6 KW - Ethanol KW - 3K9958V90M KW - Methyltransferases KW - EC 2.1.1.- KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Index Medicus KW - Animals KW - Urogenital System -- metabolism KW - Digestive System -- metabolism KW - Ethanol -- administration & dosage KW - Methyltransferases -- metabolism KW - Erythrocebus patas KW - Male KW - Female KW - Alkylation KW - DNA Damage KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77973591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=N-nitrosodimethylamine-derived+O%286%29-methylguanine+in+DNA+of+monkey+gastrointestinal+and+urogenital+organs+and+enhancement+by+ethanol.&rft.au=Anderson%2C+L+M%3BSouliotis%2C+V+L%3BChhabra%2C+S+K%3BMoskal%2C+T+J%3BHarbaugh%2C+S+D%3BKyrtopoulos%2C+S+A&rft.aulast=Anderson&rft.aufirst=L&rft.date=1996-03-28&rft.volume=66&rft.issue=1&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-29 N1 - Date created - 1996-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Orphan nuclear receptor RZRbeta: cyclic AMP regulates expression in the pineal gland. AN - 77998617; 8607878 AB - The nuclear orphan receptor RZRbeta is highly expressed in the rat pineal gland. Recent studies proposed that melatonin, the pineal hormone which regulates a wide variety of circadian-linked phenomena, may be the natural ligand of this receptor. These provocative reports prompted us to learn more about RZRbeta and how it might function in circadian physiology. Here we confirm high expression of this receptor in the pineal gland, and report that pineal RZRbeta expression exhibits a strong daily rhythm. Expression is under photoneural regulation and involves an adrenergic --> cAMP mechanism. JF - Biochemical and biophysical research communications AU - Baler, R AU - Coon, S AU - Klein, D C AD - Laboratory of Developmental Neurobiology, National Institute of Child and Human Development, National Institutes of Health, Bethesda, Maryland 20892 USA. Y1 - 1996/03/27/ PY - 1996 DA - 1996 Mar 27 SP - 975 EP - 978 VL - 220 IS - 3 SN - 0006-291X, 0006-291X KW - DNA Primers KW - 0 KW - RNA, Messenger KW - Receptors, Cell Surface KW - Receptors, Melatonin KW - Colforsin KW - 1F7A44V6OU KW - Dibutyryl Cyclic GMP KW - 32266-35-6 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Bucladesine KW - 63X7MBT2LQ KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Vasoactive Intestinal Peptide -- pharmacology KW - Animals KW - Cell Nucleus -- metabolism KW - Norepinephrine -- pharmacology KW - RNA, Messenger -- analysis KW - Cholera Toxin -- pharmacology KW - Bucladesine -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Dibutyryl Cyclic GMP -- pharmacology KW - Rats KW - Polymerase Chain Reaction KW - Rats, Sprague-Dawley KW - Base Sequence KW - Colforsin -- pharmacology KW - Kinetics KW - Molecular Sequence Data KW - Time Factors KW - Organ Culture Techniques KW - Male KW - Gene Expression -- drug effects KW - Pineal Gland -- metabolism KW - Cyclic AMP -- metabolism KW - Pineal Gland -- drug effects KW - Gene Expression -- physiology KW - Receptors, Cell Surface -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77998617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Orphan+nuclear+receptor+RZRbeta%3A+cyclic+AMP+regulates+expression+in+the+pineal+gland.&rft.au=Baler%2C+R%3BCoon%2C+S%3BKlein%2C+D+C&rft.aulast=Baler&rft.aufirst=R&rft.date=1996-03-27&rft.volume=220&rft.issue=3&rft.spage=975&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-20 N1 - Date created - 1996-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cdk2 binding domain of p27Kip correlates with the inhibition of the kinase activity of cdk2/cyclin complexes. AN - 77977145; 8607829 AB - The cyclin-dependent kinase inhibitor p27Kip binds to cyclin/cyclin-dependent kinases and preferentially inhibits the catalytic activity of cdk2 and cdk4. The cdk2 binding domain of p27Kip was determined using a series of N-terminal truncated and point mutations of GST-p27Kip. The binding domain was contained within amino acid residues 53-85. The inhibition of the catalytic activity of preformed functional cdk2/cyclin complexes by P27KiP was also associated with the binding domain. JF - Biochemical and biophysical research communications AU - Kwon, T K AU - Buchholz, M A AU - Nordin, A A AD - Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1996/03/27/ PY - 1996 DA - 1996 Mar 27 SP - 703 EP - 709 VL - 220 IS - 3 SN - 0006-291X, 0006-291X KW - Cdkn1b protein, mouse KW - 0 KW - Cell Cycle Proteins KW - Cyclins KW - DNA Primers KW - Microtubule-Associated Proteins KW - Recombinant Fusion Proteins KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - Cdk2 protein, mouse KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Recombinant Fusion Proteins -- isolation & purification KW - Amino Acid Sequence KW - Mice KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Kinetics KW - Thymoma KW - Thymus Neoplasms KW - Molecular Sequence Data KW - Point Mutation KW - Recombinant Fusion Proteins -- pharmacology KW - Cell Line KW - Cyclin-Dependent Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- chemistry KW - Microtubule-Associated Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- isolation & purification KW - Cyclin-Dependent Kinases -- chemistry KW - Microtubule-Associated Proteins -- pharmacology KW - Cyclins -- antagonists & inhibitors KW - Cyclins -- metabolism KW - Microtubule-Associated Proteins -- isolation & purification KW - Cyclin-Dependent Kinases -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77977145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=The+cdk2+binding+domain+of+p27Kip+correlates+with+the+inhibition+of+the+kinase+activity+of+cdk2%2Fcyclin+complexes.&rft.au=Kwon%2C+T+K%3BBuchholz%2C+M+A%3BNordin%2C+A+A&rft.aulast=Kwon&rft.aufirst=T&rft.date=1996-03-27&rft.volume=220&rft.issue=3&rft.spage=703&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-20 N1 - Date created - 1996-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene. AN - 77976099; 8607787 AB - We describe a Japanese patient with male-limited precocious puberty who has a heterozygous thymine to cytosine (T to C) transition at nucleotide 1193; the mutation encodes a methionine to threonine substitution in residue 398 (M398T) of transmembrane helix 2 of the luteinizing hormone/choriogonadotropin receptor. Transfected into COS-7 cells, M398T exhibited constitutively high basal cAMP levels but retained an agonist-induced cAMP response. The constitutively higher cAMP levels caused by M398T are consistent with Leydig cell activation and precocious puberty in the patient. By comparison to wild type receptor, M398T transfectants have significantly lower agonist-induced inositol phosphate (IP) levels at > 10(-10) M hCG concentrations and a higher apparent affinity for binding hCG. These data suggest that the M398T substitution alters Gq coupling and phospholipase-C activation, as well as Gs, coupling and adenylyl cyclase activity, and changes the conformation of the extracellular domain of the receptor. JF - Biochemical and biophysical research communications AU - Yano, K AU - Kohn, L D AU - Saji, M AU - Kataoka, N AU - Okuno, A AU - Cutler, G B AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/27/ PY - 1996 DA - 1996 Mar 27 SP - 1036 EP - 1042 VL - 220 IS - 3 SN - 0006-291X, 0006-291X KW - Chorionic Gonadotropin KW - 0 KW - DNA Primers KW - Inositol Phosphates KW - Receptors, LH KW - Recombinant Proteins KW - Cytosine KW - 8J337D1HZY KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - Pedigree KW - Animals KW - Models, Structural KW - Sex Characteristics KW - Inositol Phosphates -- metabolism KW - Humans KW - Cell Membrane -- ultrastructure KW - Mutagenesis, Site-Directed KW - Heterozygote Detection KW - Chorionic Gonadotropin -- pharmacology KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Male KW - Amino Acid Sequence KW - Child, Preschool KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Cercopithecus aethiops KW - Cell Membrane -- metabolism KW - Female KW - Cell Line KW - Japan KW - Protein Structure, Secondary KW - Receptors, LH -- chemistry KW - Receptors, LH -- genetics KW - Point Mutation KW - Receptors, LH -- metabolism KW - Puberty, Precocious -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77976099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=A+case+of+male-limited+precocious+puberty+caused+by+a+point+mutation+in+the+second+transmembrane+domain+of+the+luteinizing+hormone+choriogonadotropin+receptor+gene.&rft.au=Yano%2C+K%3BKohn%2C+L+D%3BSaji%2C+M%3BKataoka%2C+N%3BOkuno%2C+A%3BCutler%2C+G+B&rft.aulast=Yano&rft.aufirst=K&rft.date=1996-03-27&rft.volume=220&rft.issue=3&rft.spage=1036&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-20 N1 - Date created - 1996-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. AN - 77967328; 8596932 AB - For some time it has been thought that antigenic challenge in neonatal life is a tolerogenic rather than immunogenic event. Reexamination of the classic neonatal tolerance experiments of Billingham, Brent, and Medawar showed that tolerance is not an intrinsic property of the newborn immune system, but that the nature of the antigen-presenting cell determines whether the outcome is neonatal tolerance or immunization. JF - Science (New York, N.Y.) AU - Ridge, J P AU - Fuchs, E J AU - Matzinger, P AD - Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/03/22/ PY - 1996 DA - 1996 Mar 22 SP - 1723 EP - 1726 VL - 271 IS - 5256 SN - 0036-8075, 0036-8075 KW - H-Y Antigen KW - 0 KW - Index Medicus KW - Cytotoxicity, Immunologic KW - Animals KW - Self Tolerance KW - Mice, Inbred C57BL KW - H-Y Antigen -- immunology KW - Cytotoxicity Tests, Immunologic KW - Mice KW - B-Lymphocytes -- immunology KW - Male KW - Female KW - Animals, Newborn -- immunology KW - Dendritic Cells -- immunology KW - Immune Tolerance KW - T-Lymphocytes -- immunology KW - Immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77967328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Neonatal+tolerance+revisited%3A+turning+on+newborn+T+cells+with+dendritic+cells.&rft.au=Ridge%2C+J+P%3BFuchs%2C+E+J%3BMatzinger%2C+P&rft.aulast=Ridge&rft.aufirst=J&rft.date=1996-03-22&rft.volume=271&rft.issue=5256&rft.spage=1723&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-17 N1 - Date created - 1996-04-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Science. 1996 Aug 9;273(5276):722-3 [8701318] Science. 1996 Sep 13;273(5281):1479-80 [8801631] Science. 1996 Jun 7;272(5267):1408 [8633223] Science. 1996 Jun 7;272(5267):1405-8 [8633222] Science. 1996 Mar 22;271(5256):1665-7 [8596923] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of Epstein-Barr virus nuclear antigen-1 in targeted therapy of EBV-associated neoplasia. AN - 78079795; 8845390 AB - To target expression of toxic genes to Epstein-Barr virus (EBV)-associated tumor cells, we have developed an EBV-driven enzyme prodrug system (EDEPS) that takes advantage of the trans-activating properties of EBNA1, a latent protein expressed in all EBV-containing cells, to direct expression of cytosine deaminase (CD) at high levels in those cells only. Plasmids were constructed in which the CD gene or a luciferase reporter gene were cloned downstream of the herpes simplex virus thymidine kinase (tk) promoter and the family of repeats (FR) sequence from the oriP region of EBV. Analysis of luciferase activity after transient transfection into a panel of EBV-negative or -positive human cell lines showed that the presence of the FR element enhanced transcription from the tk promoter in all EBV-positive cell lines, whereas transcription from tk was repressed in all EBV-negative cell lines, including B, T, and fibroblast cell lines. In clonogenicity assays following transfection with the CD vector, the presence of 5-fluorocytosine (5-FC) in the culture medium completely abolished cell growth in EBV-positive cell lines, but did not affect the growth of EBV-negative cell lines. This vector system should have wide applicability in that it allows targeted expression of any gene of interest to tumors that carry EBV, irrespective of the role EBV plays in their pathogenesis. JF - Human gene therapy AU - Judde, J G AU - Spangler, G AU - Magrath, I AU - Bhatia, K AD - Lymphoma Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/03/20/ PY - 1996 DA - 1996 Mar 20 SP - 647 EP - 653 VL - 7 IS - 5 SN - 1043-0342, 1043-0342 KW - Antigens, Viral KW - 0 KW - DNA-Binding Proteins KW - Epstein-Barr Virus Nuclear Antigens KW - Prodrugs KW - Trans-Activators KW - Flucytosine KW - D83282DT06 KW - Luciferases KW - EC 1.13.12.- KW - Nucleoside Deaminases KW - EC 3.5.4.- KW - Cytosine Deaminase KW - EC 3.5.4.1 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Cell Survival -- genetics KW - Gene Transfer Techniques KW - Humans KW - Luciferases -- metabolism KW - Base Sequence KW - Tumor Cells, Cultured KW - Transfection KW - Fluorouracil -- toxicity KW - Genetic Vectors KW - Molecular Sequence Data KW - Genes, Reporter KW - Flucytosine -- metabolism KW - Fluorouracil -- metabolism KW - Gene Expression Regulation KW - Prodrugs -- metabolism KW - Nucleoside Deaminases -- genetics KW - Neoplasms -- virology KW - Herpesvirus 4, Human -- genetics KW - Trans-Activators -- therapeutic use KW - Nucleoside Deaminases -- metabolism KW - Genetic Therapy -- methods KW - DNA-Binding Proteins -- therapeutic use KW - Neoplasms -- therapy KW - Herpesvirus 4, Human -- immunology KW - Antigens, Viral -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78079795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Use+of+Epstein-Barr+virus+nuclear+antigen-1+in+targeted+therapy+of+EBV-associated+neoplasia.&rft.au=Judde%2C+J+G%3BSpangler%2C+G%3BMagrath%2C+I%3BBhatia%2C+K&rft.aulast=Judde&rft.aufirst=J&rft.date=1996-03-20&rft.volume=7&rft.issue=5&rft.spage=647&rft.isbn=&rft.btitle=&rft.title=Human+gene+therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein-protein interaction: a genetic selection for compensating mutations at the barnase-barstar interface. AN - 78015744; 8637875 AB - Barnase and barstar are trivial names of the extracellular RNase and its intracellular inhibitor produced by Bacillus amyloliquefaciens. Inhibition involves the formation of a very tight one-to-one complex of the two proteins. With the crystallographic solution of the structure of the barnase-barstar complex and the development of methods for measuring the free energy of binding, the pair can be used to study protein-protein recognition in detail. In this report, we describe the isolation of suppressor mutations in barstar that compensate for the loss in interaction energy caused by a mutation in barnase. Our suppressor search is based on in vivo selection for barstar variants that are able to protect host cells against the RNAse activity of those barnase mutants not properly inhibited by wild-type barstar. This approach utilizes a plasmid system in which barnase expression is tightly controlled to keep the mutant barnase gene silent. When expression of barnase is turned on, failure to form a complex between the mutant barnase and barstar has a lethal effect on host cells unless overcome by substitution of the wild-type barstar by a functional suppressor derivative. A set of barstar suppressors has been identified for barnase mutants with substitutions in two amino acid positions (residues 102 and 59), which are critically involved in both RNase activity and barstar binding. The mutations selected as suppressors could not have been predicted on the basis of the known protein structures. The single barstar mutation with the highest information content for inhibition of barnase (H102K) has the substitution Y30W. The reduction in binding caused by the R59E mutation in barnase can be partly reversed by changing Glu-76 of barstar, which forms a salt bridge with the Arg-59 in the wild-type complex, to arginine, thus completing an interchange of the two charges. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Jucovic, M AU - Hartley, R W AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/03/19/ PY - 1996 DA - 1996 Mar 19 SP - 2343 EP - 2347 VL - 93 IS - 6 SN - 0027-8424, 0027-8424 KW - Bacterial Proteins KW - 0 KW - Enzyme Inhibitors KW - Macromolecular Substances KW - barstar protein, Bacillus amyloliquefaciens KW - 37328-61-3 KW - Ribonucleases KW - EC 3.1.- KW - Bacillus amyloliquefaciens ribonuclease KW - EC 3.1.4.- KW - Index Medicus KW - Models, Molecular KW - Kinetics KW - Enzyme Inhibitors -- chemistry KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Genes, Suppressor KW - Structure-Activity Relationship KW - Mutagenesis KW - Ribonucleases -- antagonists & inhibitors KW - Bacterial Proteins -- chemistry KW - Ribonucleases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78015744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Protein-protein+interaction%3A+a+genetic+selection+for+compensating+mutations+at+the+barnase-barstar+interface.&rft.au=Jucovic%2C+M%3BHartley%2C+R+W&rft.aulast=Jucovic&rft.aufirst=M&rft.date=1996-03-19&rft.volume=93&rft.issue=6&rft.spage=2343&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-10 N1 - Date created - 1996-07-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gene. 1980 Feb;8(3):279-300 [6244215] Structure. 1993 Nov 15;1(3):165-76 [16100951] Gene. 1987;53(1):11-9 [3297926] Gene. 1987;56(1):145-51 [2960590] J Mol Biol. 1988 Aug 20;202(4):913-5 [3050134] Science. 1990 Mar 16;247(4948):1306-10 [2315699] Biotechniques. 1990 Feb;8(2):178-83 [2180450] Biotechniques. 1990 Jan;8(1):28-30 [2182075] Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10880-4 [1961758] Biochemistry. 1992 Mar 17;31(10):2728-34 [1547213] J Mol Biol. 1992 Apr 5;224(3):847-59 [1569561] J Mol Biol. 1992 Jun 5;225(3):585-9 [1602471] Proteins. 1992 Sep;14(1):29-44 [1329081] Biochemistry. 1993 May 18;32(19):5145-50 [8494892] Biochemistry. 1993 Jun 15;32(23):5978-84 [8507637] Biochemistry. 1993 Oct 19;32(41):11195-203 [8218183] Biochemistry. 1994 Aug 2;33(30):8878-89 [8043575] Protein Sci. 1994 Sep;3(9):1409-17 [7833803] Protein Eng. 1995 May;8(5):497-9 [8532672] Biochemistry. 1963 Jul-Aug;2:787-93 [14075115] Gene. 1985;40(1):163-8 [3005124] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase expression by wild-type p53. AN - 78004408; 8637893 AB - The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage from exogenous chemical and physical mutagens. Therefore, we hypothesized that p53 performs a similar role in response to putative endogenous mutagens, such as nitric oxide (NO). We report here that exposure of human cells to NO generated from an NO donor or from overexpression of inducible nitric oxide synthase (NOS2) results in p53 protein accumulation. In addition, expression of wild-type (WT) p53 in a variety of human tumor cell lines, as well as murine fibroblasts, results in down-regulation of NOS2 expression through inhibition of the NOS2 promoter. These data are consistent with the hypothesis of a negative feedback loop in which endogenous NO-induced DNA damage results in WT p53 accumulation and provides a novel mechanism by which p53 safeguards against DNA damage through p53-mediated transrepression of NOS2 gene expression, thus reducing the potential for NO-induced DNA damage. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Forrester, K AU - Ambs, S AU - Lupold, S E AU - Kapust, R B AU - Spillare, E A AU - Weinberg, W C AU - Felley-Bosco, E AU - Wang, X W AU - Geller, D A AU - Tzeng, E AU - Billiar, T R AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/03/19/ PY - 1996 DA - 1996 Mar 19 SP - 2442 EP - 2447 VL - 93 IS - 6 SN - 0027-8424, 0027-8424 KW - Repressor Proteins KW - 0 KW - Tumor Suppressor Protein p53 KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - DNA Damage KW - Humans KW - Mice KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Enzymologic KW - Tumor Cells, Cultured KW - Down-Regulation KW - Cells, Cultured KW - Colon -- enzymology KW - Repressor Proteins -- physiology KW - Enzyme Induction KW - Tumor Suppressor Protein p53 -- physiology KW - Nitric Oxide -- physiology KW - Nitric Oxide Synthase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78004408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Nitric+oxide-induced+p53+accumulation+and+regulation+of+inducible+nitric+oxide+synthase+expression+by+wild-type+p53.&rft.au=Forrester%2C+K%3BAmbs%2C+S%3BLupold%2C+S+E%3BKapust%2C+R+B%3BSpillare%2C+E+A%3BWeinberg%2C+W+C%3BFelley-Bosco%2C+E%3BWang%2C+X+W%3BGeller%2C+D+A%3BTzeng%2C+E%3BBilliar%2C+T+R%3BHarris%2C+C+C&rft.aulast=Forrester&rft.aufirst=K&rft.date=1996-03-19&rft.volume=93&rft.issue=6&rft.spage=2442&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-10 N1 - Date created - 1996-07-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Carcinogenesis. 1990 Jan;11(1):37-41 [2295126] Nat Genet. 1992 Apr;1(1):45-9 [1301998] Science. 1990 Aug 24;249(4971):912-5 [2144057] Pharmacol Rev. 1991 Jun;43(2):109-42 [1852778] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979-83 [1946467] Science. 1991 Nov 15;254(5034):1001-3 [1948068] Chem Res Toxicol. 1988 Sep-Oct;1(5):249-57 [2979740] Mutat Res. 1992 Mar;281(3):193-202 [1371842] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030-4 [1557408] Mol Cell Biol. 1992 Jun;12(6):2866-71 [1588974] Nature. 1992 Jul 2;358(6381):15-6 [1614522] J Virol. 1992 Aug;66(8):4757-62 [1352831] Nature. 1993 May 20;363(6426):281-3 [8387645] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11771-5 [8524846] Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1054-9 [8577713] J Biol Chem. 1994 Mar 4;269(9):6765-72 [7509810] J Exp Med. 1993 Jun 1;177(6):1779-84 [7684434] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5123-7 [7685115] Lancet. 1993 Aug 7;342(8867):338-40 [7687730] Am J Respir Cell Mol Biol. 1993 Oct;9(4):371-7 [7691109] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9730-4 [7692452] Biochemistry. 1993 Nov 2;32(43):11600-5 [7692964] J Biol Chem. 1993 Nov 15;268(32):24385-93 [8226988] Cell. 1993 Nov 19;75(4):765-78 [8242748] Cancer Res. 1994 Mar 1;54(5):1169-74 [8118801] Cancer Res. 1994 Mar 1;54(5):1352-4 [7509718] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2230-4 [8134379] Cancer Res. 1994 May 1;54(9):2462-7 [8162595] Cancer Res. 1994 Jun 15;54(12):3131-5 [8205530] Cancer Res. 1994 Sep 15;54(18):4855-78 [8069852] Cancer Res. 1994 Nov 1;54(21):5584-92 [7923201] Cell. 1994 Sep 23;78(6):915-8 [7522969] EMBO J. 1994 Oct 17;13(20):4816-22 [7957050] FEBS Lett. 1994 Nov 21;355(1):23-6 [7525358] Carcinogenesis. 1994 Dec;15(12):2875-7 [8001249] Mol Cell Biol. 1995 Jan;15(1):227-34 [7799929] Cancer Res. 1995 Feb 15;55(4):727-30 [7531613] J Biol Chem. 1995 May 5;270(18):10625-30 [7537735] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5258-65 [7777494] Oncogene. 1995 Jun 15;10(12):2271-9 [7784075] Br J Cancer. 1995 Jul;72(1):41-4 [7541238] Nat Genet. 1995 Jun;10(2):188-95 [7663514] J Immunol. 1995 Sep 15;155(6):2858-65 [7673702] Cell. 1992 Aug 21;70(4):523-6 [1505019] FASEB J. 1992 Sep;6(12):3051-64 [1381691] Cell. 1992 Nov 13;71(4):587-97 [1423616] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028-32 [1465435] Science. 1993 Jan 1;259(5091):84-7 [8418500] Oncogene. 1993 Feb;8(2):307-18 [8426740] Diabetes. 1993 Mar;42(3):496-500 [8432420] Lancet. 1993 Feb 20;341(8843):465-6 [8094492] Oncogene. 1993 Mar;8(3):589-97 [8382357] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3491-5 [7682706] Nature. 1993 Apr 29;362(6423):847-9 [8479522] Nature. 1993 Apr 29;362(6423):849-52 [8479523] Biotechniques. 1988 May;6(5):454-8 [2908509] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple SH3 domain interactions regulate NADPH oxidase assembly in whole cells. AN - 78024834; 8635453 AB - Src homology 3 (SH3) domains mediate specific protein-protein interactions crucial for signal transduction and protein subcellular localization. Upon phagocyte stimulation, two SH3 domain-containing cytosolic components of the NADPH oxidase, p47phox and p67phox, are recruited to the membrane where they interact with flavocytochrome b558 to form an activated microbicidal oxidase. Deletion analysis of p47phox and p67phox in transfected K562 cells demonstrated multiple SH3-mediated interactions between p47phox and the transmembrane flavocytochrome b558 and also between the cytosolic components themselves. The core region of p47phox (residues 151-284), spanning both SH3 domains, was required for flavocytochrome-dependent translocation and oxidase activity in whole cells. Furthermore, translocation of p67phox occurred through interactions of its N-terminal domain (residues 1-246) with p47phox SH3 domains. Both of these interactions were promoted by PMA activation of cells and were influenced by the presence of other domains in both cytosolic factors. Deletion analysis also revealed a third SH3 domain-mediated interaction involving the C-termini of both cytosolic factors, which also promoted p67phox membrane translocation. These data provide evidence for a central role for p47phox in regulation of oxidase assembly through several SH3 domain interactions. JF - The EMBO journal AU - de Mendez, I AU - Adams, A G AU - Sokolic, R A AU - Malech, H L AU - Leto, T L AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/03/15/ PY - 1996 DA - 1996 Mar 15 SP - 1211 EP - 1220 VL - 15 IS - 6 SN - 0261-4189, 0261-4189 KW - Cytochrome b Group KW - 0 KW - Phosphoproteins KW - neutrophil cytosol factor 67K KW - cytochrome b558 KW - 9064-78-2 KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - Index Medicus KW - Cytosol -- metabolism KW - Cytochrome b Group -- metabolism KW - Transfection KW - Cells, Cultured KW - Molecular Sequence Data KW - Membranes -- metabolism KW - Biological Transport KW - Amino Acid Sequence KW - Mutagenesis KW - Phosphoproteins -- genetics KW - NADH, NADPH Oxidoreductases -- genetics KW - Gene Expression Regulation, Enzymologic KW - NADH, NADPH Oxidoreductases -- biosynthesis KW - src Homology Domains KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78024834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Multiple+SH3+domain+interactions+regulate+NADPH+oxidase+assembly+in+whole+cells.&rft.au=de+Mendez%2C+I%3BAdams%2C+A+G%3BSokolic%2C+R+A%3BMalech%2C+H+L%3BLeto%2C+T+L&rft.aulast=de+Mendez&rft.aufirst=I&rft.date=1996-03-15&rft.volume=15&rft.issue=6&rft.spage=1211&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-11 N1 - Date created - 1996-07-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1995 May 12;270(19):11216-21 [7744754] J Biol Chem. 1994 Jun 10;269(23):16326-32 [8206939] J Biol Chem. 1987 Apr 25;262(12):5563-9 [3571224] Science. 1989 Jul 28;245(4916):409-12 [2547247] Proc Natl Acad Sci U S A. 1989 Sep;86(18):7195-9 [2550933] J Biol Chem. 1990 May 25;265(15):8745-50 [2160466] J Biol Chem. 1990 Nov 15;265(32):19910-5 [2246268] Blood. 1994 Jul 1;84(1):53-8 [7517218] Science. 1994 Jul 22;265(5171):531-3 [8036496] J Biol Chem. 1994 Sep 2;269(35):22405-11 [8071369] Prog Biophys Mol Biol. 1994;61(3):283-97 [8073124] EMBO J. 1994 Sep 1;13(17):4011-21 [7521298] J Biol Chem. 1994 Sep 23;269(38):23431-6 [8089108] Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10650-4 [7938008] J Exp Med. 1994 Dec 1;180(6):2329-34 [7964505] Nature. 1994 Nov 24;372(6504):375-9 [7802869] Science. 1994 Nov 18;266(5188):1241-7 [7526465] Cell. 1995 Jan 27;80(2):237-48 [7834743] Blood. 1995 Feb 15;85(4):1104-10 [7849298] Nature. 1995 Feb 16;373(6515):573-80 [7531822] J Biol Chem. 1995 Mar 17;270(11):5695-7 [7890694] J Biol Chem. 1995 May 5;270(18):10800-5 [7537740] J Clin Invest. 1991 Jan;87(1):352-6 [1985107] J Biol Chem. 1991 Oct 15;266(29):19812-8 [1918085] Nucleic Acids Res. 1992 Mar 25;20(6):1293-9 [1313966] Science. 1992 Jun 5;256(5062):1459-62 [1318579] J Biol Chem. 1992 Aug 25;267(24):16767-70 [1512217] Science. 1993 Feb 19;259(5098):1157-61 [8438166] Oncogene. 1993 Jul;8(7):1943-56 [8510937] EMBO J. 1993 Jul;12(7):2625-34 [7687537] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7446-50 [8395049] Cell. 1993 Oct 8;75(1):25-36 [8402898] Biochem J. 1993 Dec 1;296 ( Pt 2):367-71 [8257426] Biochem J. 1993 Dec 15;296 ( Pt 3):557-61 [8280052] Cell. 1994 Mar 11;76(5):933-45 [7510218] J Clin Invest. 1994 May;93(5):2120-6 [8182143] J Biol Chem. 1994 May 13;269(19):13752-5 [8188650] Curr Opin Genet Dev. 1994 Feb;4(1):15-24 [8193535] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5345-9 [8202490] Blood. 1996 Jan 1;87(1):42-50 [8547675] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospective, randomized trial of 5-fluorouracil, leucovorin, doxorubicin, and cyclophosphamide chemotherapy in combination with the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein (PIXY321) versus GM-CSF in patients with advanced breast cancer. AN - 78014853; 8630380 AB - We conducted a prospective randomized trial to evaluate the ability of the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein, PIXY321, to ameliorate cumulative thrombocytopenia after multiple cycles of 5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide (FLAC) chemotherapy compared with GM-CSF in patients with advanced breast cancer. Fifty-three patients were randomized to receive either PIXY321. 375 microg/m2 twice a day subcutaneously, or GM-CSF, 250 microg/m2 daily subcutaneously after FLAC chemotherapy. PIXY321 was less well tolerated than GM-CSF, with more patients developing chills and local skin reactions and more patients stopping PIXY321 due to intolerance. While no difference in the neutrophil nadirs was seen with the two cytokines, the duration of the absolute neutrophil count less than 1,000/muL for all cycles was significantly longer with PIXY321 than with GM-CSF. Fifty percent of patients treated with multiple cycles of FLAC chemotherapy on both study arms developed dose-limiting thrombocytopenia. No differences in platelet nadirs, duration of thrombocytopenia, or need for platelet transfusions were observed with PIXY321 versus GM-CSF. The average delivered doses of FLAC chemotherapy were somewhat higher in the GM-CSF study arm. PIXY321 was not superior to GM-CSF in ameliorating the cumulative thrombocytopenia observed with multiple cycles of FLAC chemotherapy and was less well tolerated. JF - Blood AU - O'Shaughnessy, J A AU - Tolcher, A AU - Riseberg, D AU - Venzon, D AU - Zujewski, J AU - Noone, M AU - Gossard, M AU - Danforth, D AU - Jacobson, J AU - Chang, V AU - Goldspiel, B AU - Keegan, P AU - Giusti, R AU - Cowan, K H AD - Medicine Branch, Biostatistics and Data Management Section, National Cancer Institute and Clinical Center, National Institutes of Health, Bethesda, MD USA. Y1 - 1996/03/15/ PY - 1996 DA - 1996 Mar 15 SP - 2205 EP - 2211 VL - 87 IS - 6 SN - 0006-4971, 0006-4971 KW - Immunologic Factors KW - 0 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Fluorouracil -- adverse effects KW - Doxorubicin -- adverse effects KW - Prospective Studies KW - Combined Modality Therapy KW - Leucovorin -- administration & dosage KW - Humans KW - Treatment Outcome KW - Leucovorin -- adverse effects KW - Middle Aged KW - Doxorubicin -- administration & dosage KW - Platelet Transfusion KW - Female KW - Cyclophosphamide -- adverse effects KW - Breast Neoplasms -- drug therapy KW - Thrombocytopenia -- therapy KW - Breast Neoplasms -- pathology KW - Immunologic Factors -- therapeutic use KW - Thrombocytopenia -- chemically induced KW - Neutropenia -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Neutropenia -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78014853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Prospective%2C+randomized+trial+of+5-fluorouracil%2C+leucovorin%2C+doxorubicin%2C+and+cyclophosphamide+chemotherapy+in+combination+with+the+interleukin-3%2Fgranulocyte-macrophage+colony-stimulating+factor+%28GM-CSF%29+fusion+protein+%28PIXY321%29+versus+GM-CSF+in+patients+with+advanced+breast+cancer.&rft.au=O%27Shaughnessy%2C+J+A%3BTolcher%2C+A%3BRiseberg%2C+D%3BVenzon%2C+D%3BZujewski%2C+J%3BNoone%2C+M%3BGossard%2C+M%3BDanforth%2C+D%3BJacobson%2C+J%3BChang%2C+V%3BGoldspiel%2C+B%3BKeegan%2C+P%3BGiusti%2C+R%3BCowan%2C+K+H&rft.aulast=O%27Shaughnessy&rft.aufirst=J&rft.date=1996-03-15&rft.volume=87&rft.issue=6&rft.spage=2205&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-02 N1 - Date created - 1996-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid down-regulation of fibronectin and retinoic acid receptor alpha proteins in NIH-3T3 cells. Blocks of this response by ras transformation. AN - 78014128; 8626453 AB - All-trans-retinoic acid (RA) markedly reduced the level of intracellular fibronectin (FN) in a time- and concentration-dependent fashion in NIH-3T3 cells, but not in NIH-3T3 cells transformed by an activated Ha-ras oncogene. Pulse/chase experiments indicated that RA affects FN biosynthesis rather than its turnover rate. Steady state levels of FN transcripts did not change after treatment of the cells with RA for various times or concentrations, suggesting that RA acts at the translational level. Similar effects were observed in other fibroblasts. In NIH-3T3 cells, RA had distinct effects on different receptors; it down-modulated retinoic acid receptor (RAR) a protein and transcript levels, it up-regulated RAR beta transcripts, and it had no effect on RAR gamma. Transformation of NIH-3T3 cells with an activated Ha-ras oncogene down-modulated RAR expression and abolished responsiveness to RA. We identified the retinoid signal transduction pathways responsible for the effects of RA on FN and RAR alpha proteins by the use of the retinoid X receptor-selective compound, SR11237, by stable over-expression of a truncated form of the RAR alpha gene, RAR alpha 403 with strong RAR dominant negative activity, and by overexpression of RAR alpha. We conclude that: 1) RA-dependent FN down-modulation is mediated by RARs, 2) retinoid X receptors mediate the observed reduction of RAR alpha by RA, and 3) the block of RA responsiveness in Ha-ras cells cannot be overcome by overexpression of RAR alpha. These studies have defined fibronectin and RAR alpha as targets of RA in fibroblast cells and have shown that oncogenic transformation renders the cells resistant to RA action. JF - The Journal of biological chemistry AU - Scita, G AU - Darwiche, N AU - Greenwald, E AU - Rosenberg, M AU - Politi, K AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/15/ PY - 1996 DA - 1996 Mar 15 SP - 6502 EP - 6508 VL - 271 IS - 11 SN - 0021-9258, 0021-9258 KW - Fibronectins KW - 0 KW - Rara protein, mouse KW - Receptors, Retinoic Acid KW - Retinoic Acid Receptor alpha KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Protein Biosynthesis -- drug effects KW - Animals KW - 3T3 Cells KW - Down-Regulation KW - Transformation, Genetic KW - Gene Expression KW - Mice KW - Signal Transduction KW - Cell Transformation, Neoplastic KW - Receptors, Retinoic Acid -- metabolism KW - Receptors, Retinoic Acid -- genetics KW - Tretinoin -- pharmacology KW - Fibronectins -- metabolism KW - Fibronectins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78014128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Retinoic+acid+down-regulation+of+fibronectin+and+retinoic+acid+receptor+alpha+proteins+in+NIH-3T3+cells.+Blocks+of+this+response+by+ras+transformation.&rft.au=Scita%2C+G%3BDarwiche%2C+N%3BGreenwald%2C+E%3BRosenberg%2C+M%3BPoliti%2C+K%3BDe+Luca%2C+L+M&rft.aulast=Scita&rft.aufirst=G&rft.date=1996-03-15&rft.volume=271&rft.issue=11&rft.spage=6502&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ligand-toxin hybrids directed to the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein exhibit lower toxicity than native Pseudomonas exotoxin. AN - 78004777; 8626399 AB - Pseudomonas exotoxin (PE) binds the heavy chain of the alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP). To understand the significance of this interaction, novel toxin-derived gene fusions were constructed with two ligands that also bind this receptor. A 39-kDa cellular protein, termed RAP, binds LRP with high affinity and often co-purifies with it. Two RAP toxins were constructed, one with PE and one with diphtheria toxin (DT). RAP, which replaced the toxins binding domains, was combined with each of the corresponding translocating and ADP-ribosylating domains. Both RAP-toxins bound LRP with an apparent higher affinity than native PE. Despite this, RAP-PE and DT-RAP were less toxic than native PE. Apparently, RAP-toxin molecules bound and entered cells but used a pathway that afforded only low efficiency of toxin transport to the cytosol. This was evident because co-internalization with adenovirus increased the toxicity of RAP-toxins by 10-fold. We speculate that the high affinity of RAP binding may not allow the toxin's translocating and ADP-ribosylating domains to reach the cytosol but rather causes the toxin to take another pathway, possibly one that leads to lysosomes. To test this hypothesis, additional RAP-PE fusions were constructed. N-terminal or C-terminal fragments of RAP were joined to PE to produce two novel fusion proteins which were likely to have reduced affinity for LRP. Both of these shorter fusion proteins exhibited greater toxicity than full-length RAP-PE. A second ligand-toxin gene fusion was constructed between plasminogen activator inhibitor type 1 and DT. DT-plasminogen activator inhibitor type 1 formed a complex with tissue-type plasminogen activator and inhibited its proteolytic activity. However, like the RAP-toxins, this hybrid was less toxic for cells than native PE. JF - The Journal of biological chemistry AU - Zdanovsky, A G AU - Zdanovskaia, M V AU - Strickland, D AU - FitzGerald, D J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/15/ PY - 1996 DA - 1996 Mar 15 SP - 6122 EP - 6128 VL - 271 IS - 11 SN - 0021-9258, 0021-9258 KW - Bacterial Toxins KW - 0 KW - Carrier Proteins KW - Exotoxins KW - Glycoproteins KW - LDL-Receptor Related Protein-Associated Protein KW - Ligands KW - Low Density Lipoprotein Receptor-Related Protein-1 KW - Receptors, Immunologic KW - Receptors, LDL KW - Recombinant Proteins KW - Virulence Factors KW - alpha-Macroglobulins KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Pseudomonas -- genetics KW - Animals KW - Carrier Proteins -- chemistry KW - Plasmids -- genetics KW - Glycoproteins -- chemistry KW - Carrier Proteins -- genetics KW - Humans KW - Carrier Proteins -- pharmacology KW - Recombinant Proteins -- genetics KW - Glycoproteins -- genetics KW - Cloning, Molecular KW - Recombinant Proteins -- toxicity KW - Base Sequence KW - Glycoproteins -- pharmacology KW - In Vitro Techniques KW - Molecular Sequence Data KW - Cell Line KW - Bacterial Toxins -- genetics KW - Receptors, Immunologic -- drug effects KW - Exotoxins -- genetics KW - alpha-Macroglobulins -- metabolism KW - Receptors, Immunologic -- metabolism KW - Exotoxins -- toxicity KW - Bacterial Toxins -- toxicity KW - Receptors, LDL -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78004777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Ligand-toxin+hybrids+directed+to+the+alpha+2-macroglobulin+receptor%2Flow+density+lipoprotein+receptor-related+protein+exhibit+lower+toxicity+than+native+Pseudomonas+exotoxin.&rft.au=Zdanovsky%2C+A+G%3BZdanovskaia%2C+M+V%3BStrickland%2C+D%3BFitzGerald%2C+D+J&rft.aulast=Zdanovsky&rft.aufirst=A&rft.date=1996-03-15&rft.volume=271&rft.issue=11&rft.spage=6122&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation. AN - 77997313; 8626452 AB - Mitogen-activated protein (MAP) kinases can be grouped into three structural families, ERK, JNK, and p38, which are thought to carry out unique functions within cells. We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implicated in the in vivo inactivation of ERK or of ERK and JNK, respectively. Here we characterize a new MAP kinase phosphatase, MKP-2, that is induced in human peripheral blood T cells with phorbol 12-myristate 13-acetate and is expressed in a variety of nonhematopoietic tissues as well. We show that the in vivo substrate specificities of individual phosphatases are unique. PAC1, MKP-2, and MKP-1 recognize ERK and p38, ERK and JNK, and ERK, p38, and JNK, respectively. Thus, individual MAP kinase phosphatases can differentially regulate the potential for cross-talk between the various MAP kinase pathways. A hyperactive allele of ERK2 (D319N), analogous to the Drosophila sevenmaker gain-of-function mutation, has significantly reduced sensitivity to all three MAP kinase phosphatases in vivo. JF - The Journal of biological chemistry AU - Chu, Y AU - Solski, P A AU - Khosravi-Far, R AU - Der, C J AU - Kelly, K AD - Labortory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/15/ PY - 1996 DA - 1996 Mar 15 SP - 6497 EP - 6501 VL - 271 IS - 11 SN - 0021-9258, 0021-9258 KW - Cell Cycle Proteins KW - 0 KW - Drosophila Proteins KW - Immediate-Early Proteins KW - RNA, Messenger KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 1 KW - Mitogen-Activated Protein Kinases KW - Mitogen-Activated Protein Kinase Phosphatases KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - Protein Phosphatase 1 KW - Protein Phosphatase 2 KW - DUSP1 protein, human KW - EC 3.1.3.48 KW - DUSP2 protein, human KW - DUSP4 protein, human KW - Dmel-MKP protein, Drosophila KW - Dual Specificity Phosphatase 1 KW - Dual Specificity Phosphatase 2 KW - Dual-Specificity Phosphatases KW - Dusp1 protein, mouse KW - Dusp2 protein, mouse KW - Protein Tyrosine Phosphatases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - HeLa Cells KW - Humans KW - Mice KW - Tissue Distribution KW - RNA, Messenger -- genetics KW - T-Lymphocytes -- enzymology KW - RNA, Messenger -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Induction KW - T-Lymphocytes -- drug effects KW - Substrate Specificity KW - Mutation KW - Cell Line KW - Female KW - Male KW - Protein Tyrosine Phosphatases -- biosynthesis KW - Calcium-Calmodulin-Dependent Protein Kinases -- genetics KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Immediate-Early Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77997313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+mitogen-activated+protein+kinase+phosphatases+PAC1%2C+MKP-1%2C+and+MKP-2+have+unique+substrate+specificities+and+reduced+activity+in+vivo+toward+the+ERK2+sevenmaker+mutation.&rft.au=Chu%2C+Y%3BSolski%2C+P+A%3BKhosravi-Far%2C+R%3BDer%2C+C+J%3BKelly%2C+K&rft.aulast=Chu&rft.aufirst=Y&rft.date=1996-03-15&rft.volume=271&rft.issue=11&rft.spage=6497&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U48807; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanisms involved in muscarinic acetylcholine receptor-mediated G protein activation studied by insertion mutagenesis. AN - 77994935; 8626406 AB - We have recently shown that a four-amino acid epitope (VTIL) on the m2 muscarinic receptor (corresponding to Val385, Thr386, Ile389, and Leu390) is essential for Gi/o coupling specificity and Gi/o activation (Liu, J., Conklin, B. R., Blin, N., Yun, J., and Wess, J. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 11642-11646). Because this sequence element is thought to be located at the junction between the third intracellular loop and the sixth transmembrane helix (TM VI), we speculated that agonist binding to the m2 receptor protein results in conformational changes that enable the VTIL motif to interact with Gi/o proteins. To test the hypothesis that such structural changes might involve a relative movement of TM VI toward the cytoplasm, we created a series of mutant m2 muscarinic receptors in which one to four extra Ala residues were inserted into TM VI immediately after Leu390. Based on the geometry of an alpha-helix, such mutations are predicted to "push" the VTIL sequence away from the lipid bilayer. Consistent with our working hypothesis, second messenger assays with transfected COS-7 cells showed that all mutant m2 receptors containing extra Ala residues C-terminal of Leu390 could activate the proper G proteins even in the absence of agonist. However, replacement of the VTIL motif in such constitutively active m2 receptors with the corresponding m3 muscarinic receptor sequence (AALS) or deletion of Ala391 from the wild type m2 receptor completely abolished G protein coupling. Interestingly, introduction of extra Ala residues C-terminal of the AALS motif in the m3 muscarinic receptor completely abolished functional activity. Mutant m2 and m3 receptors that contained extra Ala residues immediately N-terminal of the VTIL and AALS motif, respectively, displayed wild type-like coupling properties. Our data are consistent with a model in which agonist binding to the m2 muscarinic receptor leads to a relative movement of TM VI toward the cytoplasm, thus enabling the adjacent VTIL sequence to interact with the C terminus of Galpha(i/o) subunits. JF - The Journal of biological chemistry AU - Liu, J AU - Blin, N AU - Conklin, B R AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/15/ PY - 1996 DA - 1996 Mar 15 SP - 6172 EP - 6178 VL - 271 IS - 11 SN - 0021-9258, 0021-9258 KW - Receptors, Muscarinic KW - 0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Rats KW - Animals KW - Protein Structure, Secondary KW - Kinetics KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Models, Biological KW - Mutagenesis, Insertional KW - Cell Line KW - Binding Sites KW - Receptors, Muscarinic -- genetics KW - GTP-Binding Proteins -- metabolism KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77994935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Molecular+mechanisms+involved+in+muscarinic+acetylcholine+receptor-mediated+G+protein+activation+studied+by+insertion+mutagenesis.&rft.au=Liu%2C+J%3BBlin%2C+N%3BConklin%2C+B+R%3BWess%2C+J&rft.aulast=Liu&rft.aufirst=J&rft.date=1996-03-15&rft.volume=271&rft.issue=11&rft.spage=6172&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular localization of guidance cues in the establishment of retinotectal topography. AN - 77977578; 8604052 AB - Topographic projections of the nervous system are essential to numerous brain functions. They arise during development as a result of encounters between projecting growth cones and particular target cells. Cellular localization of guidance cues can indicate the sequential processes involved in establishment of such topography. The map formed by retinal ganglion cells on their target nuclei has served widely as a model system to investigate mechanisms underlying the highly precise and stereotypic connectivity of the nervous system. To investigate cellular localization of guidance cues in the developing retinotectal system, a three-compartment chamber was created to delimit areas where cultured embryonic chick retinal ganglion axons and tectal cells encounter one another and guidance behavior could be readily assessed. Whereas explants from nasal retinae extended fibers across their natural target population, fibers from temporal regions of retinae failed to invade areas of growing posterior tectal cells. This preservation of relevant guidance information on living cell populations enabled an evaluation of retinal ganglion cell growth cone behavior after encounter with individual tectal cells. Posterior tectal neurons appeared selectively repulsive for temporal retinal ganglion cell growth cones, causing growth cone collapse and retraction. On the contrary, neuroepithelial cells from all regions of the tectum attenuated retinal ganglion axon extension, without inducing sudden retraction. Nasal growth cones traversed or tracked more often along neuroepithelial cells from their natural target area, potentially indicating a second set of guidance cues possibly localized to posterior glia. Together, these differential interactions suggest that development of retinotectal topography critically depends on cell-specific cues, which are distributed selectively on particular populations of target cells. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Davenport, R W AU - Thies, E AU - Nelson, P G AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/15/ PY - 1996 DA - 1996 Mar 15 SP - 2074 EP - 2085 VL - 16 IS - 6 SN - 0270-6474, 0270-6474 KW - Tetrodotoxin KW - 4368-28-9 KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - Phosphatidylinositol Diacylglycerol-Lyase KW - EC 4.6.1.13 KW - Index Medicus KW - Animals KW - Age Factors KW - Chick Embryo KW - Cells, Cultured -- cytology KW - Neurites -- physiology KW - Neurons -- ultrastructure KW - Epithelial Cells KW - Cell Movement -- physiology KW - Retinal Ganglion Cells -- cytology KW - Neurons -- cytology KW - Cell Movement -- drug effects KW - Cell Communication -- physiology KW - Cells, Cultured -- physiology KW - Tetrodotoxin -- pharmacology KW - Afferent Pathways KW - Phosphoric Diester Hydrolases -- pharmacology KW - Retina -- cytology KW - Superior Colliculi -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77977578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Cellular+localization+of+guidance+cues+in+the+establishment+of+retinotectal+topography.&rft.au=Davenport%2C+R+W%3BThies%2C+E%3BNelson%2C+P+G&rft.aulast=Davenport&rft.aufirst=R&rft.date=1996-03-15&rft.volume=16&rft.issue=6&rft.spage=2074&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-15 N1 - Date created - 1996-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of the epidermal growth factor receptor signal transduction pathway stimulates tyrosine phosphorylation of protein kinase C delta. AN - 78042077; 8621384 AB - The expression of an oncogenic rasHa gene in epidermal keratinocytes stimulates the tyrosine phosphorylation of protein kinase C delta and inhibits its enzymatic activity (Denning, M. F., Dlugosz, A. A., Howett, M. K., and Yuspa, S. H. (1993) J. Biol. Chem. 268, 26079-26081). Keratinocytes expressing an activated rasHa gene secrete transforming growth factor alpha (TGFalpha) and have an altered response to differentiation signals involving protein kinase C (PKC). Because the neoplastic phenotype of v-rasHa expressing keratinocytes can be partially mimicked in vitro by chronic treatment with TGF alpha and the G protein activator aluminum fluoride (AlF4-), we determined if TGF alpha or AlF4- could induce tyrosine phosphorylation of PKCdelta. Treatment of primary keratinocyte cultures for 4 days with TGFalpha induced tyrosine phosphorylation of PKCdelta, whereas AlF4- only slightly stimulated PKCdelta tyrosine phosphorylation. The PKCdelta that was tyrosine-phosphorylated in response to TGFalpha had reduced activity compared with the nontyrosine-phosphorylated PKCdelta. Treatment of keratinocytes expressing a normal epidermal growth factor receptor (EGFR) with TGFalpha or epidermal growth factor for 5 min induced PKCdelta tyrosine phosphorylation. This acute epidermal growth factor treatment did not induce tyrosine phosphorylation of PKCdelta in keratinocytes isolated from waved-2 mice that have a defective epidermal growth factor receptor. In addition, the level of PKCdelta tyrosine phosphorylation in v-rasHa-transduced keratinocytes from EGFR null mice was substantially lower than in v-rasHa transduced wild type cells, suggesting that activation of the EGFR is important for PKC delta tyrosine phosphorylation in ras transformation. However, purified EGFR did not phosphorylate recombinant PKC delta in vitro, whereas members of the Src family (c-Src, c-Fyn) and membrane preparations from keratinocytes did. Furthermore, clearing c-Src or c-Fyn from keratinocyte membrane lysates decreased PKCdelta tyrosine phosphorylation, and c-Src and c-Fyn isolated from keratinocytes treated with TGFalpha had increased kinase activity. Acute or chronic treatment with TGFalpha did not induce significant PKCdelta translocation in contrast to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, which induced both translocation and tyrosine phosphorylation of PKCdelta. This suggests that TGFalpha-induced tyrosine phosphorylation of PKC delta results from the activation of a tyrosine kinase rather than physical association of PKCdelta with a membrane-anchored tyrosine kinase. Taken together, these results indicate that PKCdelta activity is inhibited by tyrosine phosphorylation in response to EGFR-mediated signaling and activation of a member of the Src kinase family may be the proximal tyrosine kinase acting on PKCdelta in keratinocytes. JF - The Journal of biological chemistry AU - Denning, M F AU - Dlugosz, A A AU - Threadgill, D W AU - Magnuson, T AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/03/08/ PY - 1996 DA - 1996 Mar 08 SP - 5325 EP - 5331 VL - 271 IS - 10 SN - 0021-9258, 0021-9258 KW - Aluminum Compounds KW - 0 KW - Isoenzymes KW - Proto-Oncogene Proteins KW - Recombinant Proteins KW - Transforming Growth Factor alpha KW - tetrafluoroaluminate KW - 21340-02-3 KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Epidermal Growth Factor KW - 62229-50-9 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, Epidermal Growth Factor KW - Fyn protein, mouse KW - EC 2.7.10.2 KW - Proto-Oncogene Proteins c-fyn KW - Proto-Oncogene Proteins pp60(c-src) KW - Protein Kinase C KW - EC 2.7.11.13 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Fluorides KW - Q80VPU408O KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Spodoptera KW - Gene Expression KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins pp60(c-src) -- biosynthesis KW - Mice, Inbred BALB C KW - Mutagenesis KW - Proto-Oncogene Proteins -- biosynthesis KW - Alleles KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Transforming Growth Factor alpha -- pharmacology KW - Aluminum Compounds -- pharmacology KW - Tyrosine -- metabolism KW - Proto-Oncogene Proteins pp60(c-src) -- metabolism KW - Fluorides -- pharmacology KW - Mice KW - Epidermal Growth Factor -- pharmacology KW - Protein-Tyrosine Kinases -- metabolism KW - Animals, Newborn KW - Mice, Mutant Strains KW - Transfection KW - GTP-Binding Proteins -- metabolism KW - Cell Transformation, Neoplastic KW - Cell Line KW - Protein Kinase C -- metabolism KW - Genes, ras KW - Keratinocytes -- drug effects KW - Phosphotyrosine -- metabolism KW - Receptor, Epidermal Growth Factor -- physiology KW - Keratinocytes -- metabolism KW - Signal Transduction KW - Isoenzymes -- metabolism KW - Receptor, Epidermal Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78042077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation+of+the+epidermal+growth+factor+receptor+signal+transduction+pathway+stimulates+tyrosine+phosphorylation+of+protein+kinase+C+delta.&rft.au=Denning%2C+M+F%3BDlugosz%2C+A+A%3BThreadgill%2C+D+W%3BMagnuson%2C+T%3BYuspa%2C+S+H&rft.aulast=Denning&rft.aufirst=M&rft.date=1996-03-08&rft.volume=271&rft.issue=10&rft.spage=5325&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TrkC isoforms with inserts in the kinase domain show impaired signaling responses. AN - 78039906; 8621434 AB - The genetic locus for the TrkC/neurotrophin 3 (NT-3) receptor tyrosine kinase encodes multiple isoforms including receptors with inserts in the catalytic domain. This study examines the signaling capabilities of TrkC and related kinase insert isoforms TrkC14 and TrkC25. We show that in PC12 cells expressing both TrkC and TrkA/nerve growth factor (NGF) receptors, different morphological changes occur upon addition of NGF or NT-3. NT-3-treated cells exhibit longer neurites and larger cell bodies as compared to NGF-treated cells. Both TrkC and TrkA mediate qualitatively similar increases in the tyrosine phosphorylation of phospholipase C (PLC)-gamma1, Shc, SNT, and MAPK and the transcription of the c-fos, c-jun, NGFI-A, and NGFI-B immediate early genes. However, the TrkC kinase insert forms fail to stimulate these events. Furthermore, TrkC14 and TrkC25 have only a low intrinsic tyrosine kinase activity, and insertion of the TrkC14 kinase insert into TrkA at an equivalent position results in a dramatic reduction of the kinase activity and signaling capabilities of TrkA. The TrkC14 and -25 isoforms may fail to transmit signals due to their low intrinsic kinase activity and failure to activate and/or tyrosine phosphorylate targets shown to be involved in neurotrophin signal transduction pathways. JF - The Journal of biological chemistry AU - Tsoulfas, P AU - Stephens, R M AU - Kaplan, D R AU - Parada, L F AD - Molecular Embryology Section, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, National Institutes of Health, Frederick, Maryland 21702-1201, USA. Y1 - 1996/03/08/ PY - 1996 DA - 1996 Mar 08 SP - 5691 EP - 5697 VL - 271 IS - 10 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Nerve Growth Factors KW - Neurotrophin 3 KW - Receptors, Nerve Growth Factor KW - Recombinant Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, trkA KW - Receptor, trkC KW - Index Medicus KW - Animals KW - Nerve Growth Factors -- pharmacology KW - Humans KW - Phosphotyrosine -- metabolism KW - Cell Differentiation KW - Transcription, Genetic KW - Rats KW - Transfection KW - Recombinant Proteins -- metabolism KW - Phosphotyrosine -- analysis KW - Kinetics KW - Receptor, trkA -- metabolism KW - Genes, fos KW - Time Factors KW - Signal Transduction KW - Mutagenesis, Insertional KW - Genes, jun KW - PC12 Cells KW - Gene Expression -- drug effects KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Neurites -- physiology KW - Receptors, Nerve Growth Factor -- metabolism KW - Isoenzymes -- metabolism KW - Genes, Immediate-Early UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78039906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=TrkC+isoforms+with+inserts+in+the+kinase+domain+show+impaired+signaling+responses.&rft.au=Tsoulfas%2C+P%3BStephens%2C+R+M%3BKaplan%2C+D+R%3BParada%2C+L+F&rft.aulast=Tsoulfas&rft.aufirst=P&rft.date=1996-03-08&rft.volume=271&rft.issue=10&rft.spage=5691&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen-related receptor, hERR1, modulates estrogen receptor-mediated response of human lactoferrin gene promoter. AN - 78037308; 8621448 AB - We have shown previously that estrogen-stimulated transcription from the human lactoferrin gene in RL95-2 endometrium carcinoma cells is mediated through an imperfect estrogen response element (ERE) at the 5 -flanking region of the gene. Upstream from the ERE, a DNA sequence (-418 to -378, FP1) was selectively protected from DNase I digestion by nuclear extracts from endometrial and mammary gland cell lines. In this report, using the electrophoresis mobility shift assay, site-directed mutagenesis, and DNA methylation interference analyses, we show that three different nuclear proteins bind to the FP1 region (C1, C2, and C3 sites). The nuclear receptor, COUP-TF, binds to the C2 site. Mutations in the C1 binding region abolish C1 complex formation and reduce estrogen-dependent transcription from the lactoferrin ERE. When the imperfect ERE of the lactoferrin gene is converted to a perfect palindromic structure, the enhancing effect of the C1 binding element for estrogen responsiveness was abolished. We isolated a complementary DNA (cDNA) clone from an RL95-2 expression library that encodes the C1 site-binding protein. The encoded polypeptide maintains 99% amino acid identity with the previously described orphan nuclear receptor hERR1. A 2.2-kilobase mRNA was detected in RL95-2 cells by the newly isolated cDNA but not by the first 180 base pair of the published hERR1 sequence. By Western analysis, a major 42-kDa protein is detected in the RL95-2 nuclear extract with antibody generated against GST-hERR1 fusion protein. Finally, we show that the hERR1 interacts with the human estrogen receptor through protein-protein contacts. JF - The Journal of biological chemistry AU - Yang, N AU - Shigeta, H AU - Shi, H AU - Teng, C T AD - Gene Regulation Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/03/08/ PY - 1996 DA - 1996 Mar 08 SP - 5795 EP - 5804 VL - 271 IS - 10 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - DNA, Complementary KW - DNA, Neoplasm KW - DNA-Binding Proteins KW - ERRalpha estrogen-related receptor KW - Nuclear Proteins KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Estrogen KW - Recombinant Proteins KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Recombinant Proteins -- biosynthesis KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Humans KW - Breast KW - Transcription, Genetic KW - Amino Acid Sequence KW - Carcinoma, Endometrioid KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - Tumor Cells, Cultured KW - Transfection KW - Glutathione Transferase -- biosynthesis KW - Molecular Sequence Data KW - Nuclear Proteins -- metabolism KW - Methylation KW - DNA, Neoplasm -- metabolism KW - Mutagenesis, Insertional KW - Cell Line KW - Female KW - Gene Library KW - Promoter Regions, Genetic KW - Receptors, Estrogen -- isolation & purification KW - Lactoferrin -- genetics KW - Lactoferrin -- biosynthesis KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- isolation & purification KW - Gene Expression KW - Receptors, Estrogen -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78037308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Estrogen-related+receptor%2C+hERR1%2C+modulates+estrogen+receptor-mediated+response+of+human+lactoferrin+gene+promoter.&rft.au=Yang%2C+N%3BShigeta%2C+H%3BShi%2C+H%3BTeng%2C+C+T&rft.aulast=Yang&rft.aufirst=N&rft.date=1996-03-08&rft.volume=271&rft.issue=10&rft.spage=5795&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L38487; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding. AN - 78034914; 8621442 AB - The functional importance of cysteine residues in the extracellular domain and the extracellular loops (EL1 and EL2) to hormone binding of the rat luteinizing hormone receptor (LHR) was investigated. For this purpose, cysteines in the seven-transmembrane holoreceptor (Form A) and its hormone-binding splice variant (Form B) were replaced by serine residues, and mutant receptors were expressed in COS1 and/or insect cells. Within the extracellular domain, individual replacement of all four cysteines from Exon 1 abolished hormone binding activity, and replacement of Cys-109 and Cys-134 from exons 5 and 6 caused a 75% decrease in both cell surface and total cellular solubilized LHR hormone binding activity. Mutations of Cys-257 and -258 (Exon 9), Cys-321 and -331, and Cys-417 and -492 of EL1 and EL2, respectively (Exon 11), showed no surface hormone binding activity on intact cells, but exhibited wild type levels of total hormone binding activity when recovered from detergent-solubilized cellular extracts. This finding indicated that expression of high affinity LHR binding activity at the cell surface is independent of the acquisition of the high affinity binding conformation. Other cysteine residues, including Cys-282 (exon 10), and Cys-314 (exon 11) were not essential for hormone binding activity or plasma membrane insertion. This study demonstrates that the functional hormone binding domain utilizes all cysteines N-terminal to exon 7 and localizes the binding site to this N-terminal region of the extracellular domain. JF - The Journal of biological chemistry AU - Zhang, R AU - Buczko, E AU - Dufau, M L AD - Section on Molecular Endocrinology, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/08/ PY - 1996 DA - 1996 Mar 08 SP - 5755 EP - 5760 VL - 271 IS - 10 SN - 0021-9258, 0021-9258 KW - Chorionic Gonadotropin KW - 0 KW - Receptors, LH KW - Recombinant Proteins KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Genetic Variation KW - Spodoptera KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Amino Acid Sequence KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Blotting, Western KW - Transfection KW - Recombinant Proteins -- metabolism KW - Alternative Splicing KW - Kinetics KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Cell Membrane -- metabolism KW - Cell Line KW - Female KW - Ovary -- metabolism KW - Protein Structure, Secondary KW - Receptors, LH -- chemistry KW - Exons KW - Chorionic Gonadotropin -- metabolism KW - Receptors, LH -- genetics KW - Receptors, LH -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78034914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Requirement+of+cysteine+residues+in+exons+1-6+of+the+extracellular+domain+of+the+luteinizing+hormone+receptor+for+gonadotropin+binding.&rft.au=Zhang%2C+R%3BBuczko%2C+E%3BDufau%2C+M+L&rft.aulast=Zhang&rft.aufirst=R&rft.date=1996-03-08&rft.volume=271&rft.issue=10&rft.spage=5755&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. AN - 78199959; 8700864 AB - While most effects of dopamine in the brain are mediated by the D1 and D2 receptor subtypes, other members of this G protein-coupled receptor family have potentially important functions. D3 receptors belong to the D2-like subclass of dopamine receptors, activation of which inhibits adenylyl cyclase. Using targeted mutagenesis in mouse embryonic stem cells, we have generated mice lacking functional D3 receptors. A premature chain-termination mutation was introduced in the D3 receptor gene after residue Arg-148 in the second intracellular loop of the predicted protein sequence. Binding of the dopamine antagonist [125I]iodosulpride to D3 receptors was absent in mice homozygous for the mutation and greatly reduced in heterozygous mice. Behavioral analysis of mutant mice showed that this mutation is associated with hyperactivity in an exploratory test. Homozygous mice lacking D3 receptors display increased locomotor activity and rearing behavior. Mice heterozygous for the D3 receptor mutation show similar, albeit less pronounced, behavioral alterations. Our findings indicate that D3 receptors play an inhibitory role in the control of certain behaviors. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Accili, D AU - Fishburn, C S AU - Drago, J AU - Steiner, H AU - Lachowicz, J E AU - Park, B H AU - Gauda, E B AU - Lee, E J AU - Cool, M H AU - Sibley, D R AU - Gerfen, C R AU - Westphal, H AU - Fuchs, S AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. Y1 - 1996/03/05/ PY - 1996 DA - 1996 Mar 05 SP - 1945 EP - 1949 VL - 93 IS - 5 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Drd3 protein, mouse KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - Index Medicus KW - Animals KW - Base Sequence KW - Motor Activity KW - Molecular Sequence Data KW - Behavior, Animal -- physiology KW - Mice KW - Amino Acid Sequence KW - Brain -- physiology KW - Mice, Knockout KW - DNA Primers -- chemistry KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78199959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=A+targeted+mutation+of+the+D3+dopamine+receptor+gene+is+associated+with+hyperactivity+in+mice.&rft.au=Accili%2C+D%3BFishburn%2C+C+S%3BDrago%2C+J%3BSteiner%2C+H%3BLachowicz%2C+J+E%3BPark%2C+B+H%3BGauda%2C+E+B%3BLee%2C+E+J%3BCool%2C+M+H%3BSibley%2C+D+R%3BGerfen%2C+C+R%3BWestphal%2C+H%3BFuchs%2C+S&rft.aulast=Accili&rft.aufirst=D&rft.date=1996-03-05&rft.volume=93&rft.issue=5&rft.spage=1945&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-05 N1 - Date created - 1996-09-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1990 Sep 13;347(6289):146-51 [1975644] Nat Genet. 1996 Jan;12(1):106-9 [8528241] Trends Pharmacol Sci. 1992 Feb;13(2):61-9 [1561715] Brain Res. 1991 Nov 15;564(2):203-19 [1839781] Synapse. 1992 Jun;11(2):146-54 [1385664] Eur J Pharmacol. 1992 Apr 10;225(4):331-7 [1354163] Eye (Lond). 1992;6 ( Pt 1):1-10 [1358680] J Biol Chem. 1993 Mar 15;268(8):5872-8 [8449953] Annu Rev Neurosci. 1993;16:299-321 [8460895] Brain Res Mol Brain Res. 1993 Apr;18(1-2):187-92 [8097550] Science. 1993 Jun 18;260(5115):1814-6 [8099761] Neuropharmacology. 1993 May;32(5):509-10 [8321432] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8942-6 [8415635] Eur J Neurosci. 1993 Feb 1;5(2):145-53 [8261096] Br J Psychiatry Suppl. 1993 Dec;(22):31-8 [7906523] J Neural Transm Gen Sect. 1993;94(1):11-9 [8129881] Trends Pharmacol Sci. 1994 Feb;15(2):46-7 [8165723] Trends Pharmacol Sci. 1994 Jun;15(6):173-4 [7916508] Cell. 1994 Nov 18;79(4):729-42 [7954836] Eur J Pharmacol. 1994 Jul 15;268(2):129-39 [7957635] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12564-8 [7809078] J Neurochem. 1995 Feb;64(2):482-6 [7830039] Eur J Pharmacol. 1994 Oct 3;263(3):235-43 [7843260] J Neural Transm Gen Sect. 1994;95(1):71-4 [7857588] Neuroscience. 1995 Apr;65(3):731-45 [7609872] Neuroscience. 1995 Apr;65(3):747-56 [7609873] Nature. 1995 Oct 5;377(6548):424-8 [7566118] Trends Pharmacol Sci. 1995 Aug;16(8):270-5 [7482988] Biochem Pharmacol. 1992 Feb 18;43(4):659-66 [1347215] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation. AN - 78198400; 8700888 AB - One of the earliest events induced by interleukin 2 (IL-2) is tyrosine phosphorylation of cellular proteins, including the IL-2 receptor beta chain (IL-2Rbeta). Simultaneous mutation of three tyrosines (Y338, Y392, and Y510) in the IL-2Rbeta cytoplasmic domain abrogated IL-2-induced proliferation, whereas mutation of only Y338 or of Y392 and Y510 inhibited proliferation only partially. While Y392 and Y510 were critical for IL-2-induced activation of signal transducers and activators of transcription (STAT proteins), Y338 was required for Shc-IL-2Rbeta association and for IL-2-induced tyrosine phosphorylation of Shc. Thus, activation of both Jak-STAT and Shc-coupled signaling pathways requires specific IL-2Rbeta tyrosines that together act in concert to mediate maximal proliferation. In COS-7 cells, overexpression of Jak1 augmented phosphorylation of Y338 as well as Y392 and Y510, suggesting that the role for this Jak kinase may extend beyond the Jak-STAT pathway. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Friedmann, M C AU - Migone, T S AU - Russell, S M AU - Leonard, W J AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA. Y1 - 1996/03/05/ PY - 1996 DA - 1996 Mar 05 SP - 2077 EP - 2082 VL - 93 IS - 5 SN - 0027-8424, 0027-8424 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - DNA-Binding Proteins KW - Proteins KW - Receptors, Interleukin-2 KW - SHC1 protein, human KW - STAT1 Transcription Factor KW - STAT1 protein, human KW - Shc Signaling Adaptor Proteins KW - Shc1 protein, mouse KW - Src Homology 2 Domain-Containing, Transforming Protein 1 KW - Stat1 protein, mouse KW - Trans-Activators KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - JAK1 protein, human KW - EC 2.7.10.2 KW - Jak1 protein, mouse KW - Janus Kinase 1 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Phosphotyrosine -- chemistry KW - Humans KW - Amino Acid Sequence KW - Mice KW - Receptor Aggregation KW - Protein-Tyrosine Kinases -- metabolism KW - Proteins -- metabolism KW - Protein Binding KW - Tyrosine -- chemistry KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Cells, Cultured KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - DNA-Binding Proteins -- metabolism KW - Lymphocyte Activation KW - Receptors, Interleukin-2 -- physiology KW - T-Lymphocytes -- physiology KW - Receptors, Interleukin-2 -- chemistry KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78198400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Different+interleukin+2+receptor+beta-chain+tyrosines+couple+to+at+least+two+signaling+pathways+and+synergistically+mediate+interleukin+2-induced+proliferation.&rft.au=Friedmann%2C+M+C%3BMigone%2C+T+S%3BRussell%2C+S+M%3BLeonard%2C+W+J&rft.aulast=Friedmann&rft.aufirst=M&rft.date=1996-03-05&rft.volume=93&rft.issue=5&rft.spage=2077&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-05 N1 - Date created - 1996-09-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1988 Jan;8(1):466-72 [2827008] Science. 1993 Dec 17;262(5141):1874-7 [8266076] J Biol Chem. 1990 Feb 25;265(6):3561-7 [2303462] J Exp Med. 1990 Mar 1;171(3):637-44 [2106566] Cell Regul. 1991 Jan;2(1):73-85 [2007186] Nature. 1994 Jul 14;370(6485):153-7 [8022486] EMBO J. 1994 Jun 15;13(12):2822-30 [8026467] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6850-4 [8041708] Immunol Rev. 1994 Apr;138:61-86 [8070818] Science. 1994 Nov 11;266(5187):1039-42 [7973657] Science. 1994 Nov 11;266(5187):1042-5 [7973658] Science. 1994 Nov 11;266(5187):1045-7 [7973659] EMBO J. 1994 Dec 1;13(23):5605-15 [7988557] Science. 1993 Dec 17;262(5141):1877-80 [8266077] Science. 1993 Dec 17;262(5141):1880-3 [8266078] J Biol Chem. 1994 Jan 21;269(3):1599-602 [8294403] Science. 1994 Mar 11;263(5152):1453-4 [8128231] Nature. 1994 May 26;369(6478):330-3 [8183373] Nature. 1994 May 26;369(6478):333-6 [7514277] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4940-4 [8197161] Nature. 1994 Jul 14;370(6485):151-3 [8022485] Eur J Immunol. 1994 Dec;24(12):3082-6 [7528668] Cell. 1995 Jan 27;80(2):213-23 [7834741] Trends Biochem Sci. 1995 Feb;20(2):59-64 [7701563] Science. 1995 Apr 14;268(5208):251-5 [7716517] Immunol Today. 1995 Mar;16(3):159-64 [7718090] Int Immunol. 1995 Jan;7(1):115-20 [7718508] Immunity. 1995 Apr;2(4):321-9 [7719937] Immunity. 1995 Apr;2(4):331-9 [7719938] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5482-6 [7777534] Science. 1995 Jul 7;269(5220):79-81 [7604283] Science. 1995 Jul 7;269(5220):81-3 [7541555] Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7192-6 [7543676] J Biol Chem. 1995 Sep 15;270(37):21729-37 [7665592] Science. 1995 Sep 29;269(5232):1875-7 [7569929] Science. 1995 Nov 3;270(5237):797-800 [7481768] Annu Rev Med. 1996;47:229-39 [8712778] Cell. 1991 Jun 14;65(6):973-82 [1646080] Science. 1991 Jun 14;252(5012):1523-8 [2047859] J Biol Chem. 1991 Aug 5;266(22):14167-70 [1713578] Eur J Immunol. 1992 Mar;22(3):817-21 [1547824] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2789-93 [1557384] Science. 1992 Jul 17;257(5068):379-82 [1631559] J Biol Chem. 1992 Dec 15;267(35):25423-7 [1460037] Cell. 1993 Apr 9;73(1):147-57 [8462096] J Immunol. 1993 Jul 15;151(2):1075-85 [8335891] J Biol Chem. 1993 Aug 25;268(24):17659-61 [7688728] J Biol Chem. 1993 Oct 25;268(30):22733-6 [8226783] J Immunol. 1989 Oct 15;143(8):2530-3 [2477446] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ARD1, a 64-kDa bifunctional protein containing an 18-kDa GTP-binding ADP-ribosylation factor domain and a 46-kDa GTPase-activating domain. AN - 78198358; 8700863 AB - The alpha subunits of the heterotrimeric guanine nucleotide-binding proteins (G proteins) hydrolyze GTP at a rate significantly higher than do most members of the Ras family of approximatelly 20-kDa GTP-binding proteins, which depend on a GTPase-activating protein (GAP) for acceleration of GTP hydrolysis. It has been demonstrated that an inserted domain in the G-protein alpha subunit, not present in the much smaller Ras-like proteins, is responsible for this difference [Markby, D. W., Onrust, R. & Bourne, H. R. (1993) Science 262, 1895-1900]. We report here that ARD1, a 64-kDa protein with an 18-kDa carboxyl-terminal ADP-ribosylation factor (ARF) domain, exhibited significant GTPase activity, whereas the ARF domain, expressed as a recombinant protein in Escherichia coli, did not. Addition of the 46-kDa amino-terminal extension (similarly synthesized in E. coli) to the GTP-binding ARF-domain of ARD1 enhanced GTPase activity and inhibited GDP dissociation. The kinetic properties of mixtures of the ARF and non-ARF domains were similar to those of an intact recombinant ARD1. Physical association of the two proteins was demonstrated directly by gel filtration and by using the immobilized non-ARF domain. Thus, like the alpha subunits of heterotrimeric G proteins, ARD1 appears to consist of two domains that interact to regulate the biological activity of the protein. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Vitale, N AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/03/05/ PY - 1996 DA - 1996 Mar 05 SP - 1941 EP - 1944 VL - 93 IS - 5 SN - 0027-8424, 0027-8424 KW - DNA, Complementary KW - 0 KW - GTPase-Activating Proteins KW - Proteins KW - Recombinant Proteins KW - ras GTPase-Activating Proteins KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - DNA, Complementary -- genetics KW - Recombinant Proteins -- chemistry KW - Structure-Activity Relationship KW - Cholera Toxin -- metabolism KW - Cell-Free System KW - Proteins -- chemistry KW - GTP-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78198358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=ARD1%2C+a+64-kDa+bifunctional+protein+containing+an+18-kDa+GTP-binding+ADP-ribosylation+factor+domain+and+a+46-kDa+GTPase-activating+domain.&rft.au=Vitale%2C+N%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Vitale&rft.aufirst=N&rft.date=1996-03-05&rft.volume=93&rft.issue=5&rft.spage=1941&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-05 N1 - Date created - 1996-09-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3063-6 [8159707] J Biol Chem. 1994 Apr 8;269(14):10758-63 [8144664] J Biol Chem. 1995 Jun 16;270(24):14809-15 [7782347] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Anal Biochem. 1976 May 7;72:248-54 [942051] Nature. 1978 Feb 9;271(5645):501 [622185] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5139-42 [3110784] J Biol Chem. 1988 Feb 5;263(4):1768-72 [3123477] Nature. 1991 Jan 10;349(6305):117-27 [1898771] Nature. 1991 May 30;351(6325):400-2 [1903516] Annu Rev Biochem. 1991;60:349-400 [1909108] Cell. 1992 Aug 7;70(3):401-10 [1643658] J Biol Chem. 1993 Apr 25;268(12):8801-7 [8473324] Nature. 1993 Dec 16;366(6456):628-9 [8259206] Nature. 1993 Dec 16;366(6456):654-63 [8259210] Science. 1993 Dec 17;262(5141):1895-901 [8266082] J Biol Chem. 1995 May 26;270(21):12327-30 [7759471] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxin containing a disulfide-stabilized Fv directed at erbB2 that does not require proteolytic activation. AN - 77974383; 8608123 AB - PE35/e23(dsFv)KDEL is a recombinant immunotoxin composed of a recombinant form of Pseudomonas exotoxin that does not need proteolytic activation and a disulfide-stabilized Fv fragment of the anti-erbB2 monoclonal antibody e23. In this molecule, the variable heavy (V H) domain is inserted near the carboxyl terminus of PE at position 607 and the variable light (V L) domain is connected to the V H domain by a disulfide bond engineered into the framework region. The disulfide bond forms between cysteines introduced at position 44 of V H and position 99 of V L [Reiter et al. (1994) J. Biol. Chem. 269, 18327-18331]. In contrast to other PE-derived Fv fusion proteins, this type of recombinant toxin does not need proteolytic activation of the toxin domain. PE35/e23(dsFv)KDEL is very cytotoxic toward erbB2 antigen-expressing N87 cells (IC50 = 0.8 ng/mL) despite the fact that it binds to the erbB2 protein only 25% as well as e23(dsFv)PE38KDEL, in which the dsFv moiety is located at the amino terminus of the toxin. The lower binding affinity is probably due to interference by domain III of PE with the amino terminus of e23(V H), possibly where the antigen binding sites are located. Nevertheless, the specificity of immunotoxin is still retained, and it is very stable at 37 degrees C. Because of its small size, stability, and activity without proteolytic processing, this immunotoxin may be advantageous for tumor treatment. PE35/e23(dsFv)KDEL was also used to gain information about whether reduction of the disulfide bonds connecting V H and V L occur in the endoplasmic reticulum (ER) or in a proximal compartment. To do this, we switched the ER retention sequence KDEL from the toxin--V H subunit to the V L subunit. Our results suggest that reduction of the disulfide bond connecting the dsFv heterodimer occurs before the immunotoxin reaches the ER, where translocation to the cytosol appears to occur. JF - Biochemistry AU - Kuan, C T AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/03/05/ PY - 1996 DA - 1996 Mar 05 SP - 2872 EP - 2877 VL - 35 IS - 9 SN - 0006-2960, 0006-2960 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - DNA Primers KW - Disulfides KW - Exotoxins KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Protein Synthesis Inhibitors KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence KW - Plasmids KW - Disulfides -- metabolism KW - Polymerase Chain Reaction KW - Protein Synthesis Inhibitors -- toxicity KW - Base Sequence KW - Disulfides -- chemistry KW - Bacterial Toxins -- metabolism KW - Cell Survival -- drug effects KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Binding, Competitive KW - Receptor, ErbB-2 -- immunology KW - Molecular Sequence Data KW - Bacterial Toxins -- chemistry KW - Recombinant Proteins -- chemistry KW - Mutagenesis, Insertional KW - Cell Line KW - Immunotoxins -- chemistry KW - Immunotoxins -- toxicity KW - Endopeptidases -- metabolism KW - Exotoxins -- metabolism KW - Exotoxins -- toxicity KW - Exotoxins -- chemistry KW - Immunotoxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77974383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Recombinant+immunotoxin+containing+a+disulfide-stabilized+Fv+directed+at+erbB2+that+does+not+require+proteolytic+activation.&rft.au=Kuan%2C+C+T%3BPastan%2C+I&rft.aulast=Kuan&rft.aufirst=C&rft.date=1996-03-05&rft.volume=35&rft.issue=9&rft.spage=2872&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-28 N1 - Date created - 1996-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cortical stimulation elicits regional distinctions in auditory and visual naming. AN - 85245448; pmid-8598182 AB - We used electrical stimulation mapping to compare performance on auditory and visual naming tasks in inferotemporal, lateral temporal, frontal, and parietal cortex in 8 temporal lobe epilepsy (TLE) patients with subdural electrodes placed for preoperative language localization. Performance on auditory responsive naming (ARN) and visual confrontation naming (VCN) was best during stimulation of parietal cortex and was equally impaired during stimulation of inferotemporal and frontal cortex. In contrast, ARN performance was significantly poorer than VCN performance during stimulation of anterior and posterior lateral temporal cortex. In most patients, stimulation of inferotemporal cortex at relatively low stimulus intensities (< or = 5 mA) during either ARN or VCN elicited reproducible errors in which patients could describe, gesture, spell, or draw, but not name, in response to auditory or visual cues. Inferotemporal and frontal cortex appear to be multimodality language regions distinct from lateral temporal cortex. JF - Epilepsia AU - Malow, B A AU - Blaxton, T A AU - Sato, S AU - Bookheimer, S Y AU - Kufta, C V AU - Figlozzi, C M AU - Theodore, W H AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. PY - 1996 SP - 245 EP - 252 VL - 37 IS - 3 SN - 0013-9580, 0013-9580 KW - Verbal Behavior KW - Age of Onset KW - Electrodes, Implanted KW - Human KW - Electric Stimulation KW - Parietal Lobe KW - Frontal Lobe KW - Temporal Lobe KW - Adult KW - Middle Age KW - Speech KW - Male KW - Female KW - Epilepsy, Temporal Lobe KW - Brain Mapping KW - Visual Perception KW - Auditory Perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85245448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=Cortical+stimulation+elicits+regional+distinctions+in+auditory+and+visual+naming.&rft.au=Malow%2C+B+A%3BBlaxton%2C+T+A%3BSato%2C+S%3BBookheimer%2C+S+Y%3BKufta%2C+C+V%3BFiglozzi%2C+C+M%3BTheodore%2C+W+H&rft.aulast=Malow&rft.aufirst=B&rft.date=1996-03-01&rft.volume=37&rft.issue=3&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=00139580&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Antagonists have a greater selectivity for muscarinic receptor subtypes in intact cerebellar granule cells than in membranes. AN - 85229836; pmid-8724972 AB - A comparison of muscarinic acetylcholine receptor (mAChR) antagonist binding properties was made between intact cerebellar granule cell cultures and membranes prepared from these cells. [3H]quinuclidinyl benzylate (QNB) binding displacement by four mAChR antagonists was measured and the selectivities for m2- or m3-mAChRs estimated by curve fitting. For each antagonist, the preparation of membranes caused a subtype selective decrease in receptor affinity, as compared to intact cell binding. The m2-selective antagonists had lower affinities in membranes for m2- but not for m3-mAChR, while the m3-selective antagonists had lower affinities for m3- but not for m2-mAChR. As a result, the m2-mAChR selectivity of AF-DX 116 and methoctramine in membranes was 66- and 1.7-fold less than in intact cells, and the m3-mAChR selectivity of 4-DAMP and pFHHSiD was 2.4- and 3.9-fold less in membranes than in intact cells. The m3-mAChR selectivity of 4-DAMP in intact cells was unaffected by cytoskeletal depolymerization with cytochalasins and colchicine. We suggest that the changes in selectivity seen with cell disruption may be due to a loss of cellular factors which regulate receptor properties. Antagonists binding to receptors on intact cells may cause subtype-specific changes in the interaction of the mAChR with these factors. These data suggest that mAChR antagonist binding selectivity needs to be re-examined in intact cell systems. JF - Brain Research AU - Saunders, P A AU - Hough, C J AU - Chuang, D M AD - Section on Molecular Neurobiology, National Institutes of Mental Health, National Institutes of Health, Bethesda, MD 20892-1272, USA. PY - 1996 SP - 29 EP - 35 VL - 713 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Rats KW - Muscarinic Antagonists KW - Rats, Sprague-Dawley KW - Piperidines KW - Receptors, Muscarinic KW - Cells, Cultured KW - Dose-Response Relationship, Drug KW - Quinuclidinyl Benzilate KW - Binding, Competitive KW - Cell Membrane KW - Cerebellum KW - Animal KW - Time Factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85229836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+Research&rft.atitle=Antagonists+have+a+greater+selectivity+for+muscarinic+receptor+subtypes+in+intact+cerebellar+granule+cells+than+in+membranes.&rft.au=Saunders%2C+P+A%3BHough%2C+C+J%3BChuang%2C+D+M&rft.aulast=Saunders&rft.aufirst=P&rft.date=1996-03-01&rft.volume=713&rft.issue=1-2&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Correlates of response to IL-2 therapy in patients treated for metastatic renal cancer and melanoma. AN - 78774631; 9166506 AB - We evaluated the characteristics of patients with metastatic renal cancer or metastatic melanoma prior to and during treatment with bolus intravenous interleukin-2 to define prognostic indicators of subsequent response to therapy. A consecutive series of 509 patients with progressive metastatic cancer were treated with intravenous interleukin-2 from September 1985 to July 1993. Pretreatment demographic characteristics, treatment history, results of laboratory tests, and metastatic sites of disease were evaluated. The amount of interleukin-2 administered, toxicity, and changes in laboratory test results were recorded for the first course of therapy. Subsequent objective response to therapy and survival were determined and used to evaluate pretreatment and treatment characteristics that acted as prognostic indicators of response. At the end of the study, 22.6% of patients with renal cancer and 16.3% of patients with melanoma experienced an objective response to interleukin-2 therapy. Patients with renal cancer responded more frequently if they had not previously failed other immunotherapies. Also, renal cancer patients who achieved an objective response had a more profound thrombocytopenia during the first cycle of therapy. Patients with melanoma responded more frequently to interleukin-2 therapy when metastases were confined to subcutaneous tissue. In addition, responding patients with melanoma received more interleukin-2 in their first course and exhibited a more profound lymphocytosis 7 to 11 days after initiating therapy than did nonresponders. Renal cancer and melanoma displayed separate prognostic indicators with respect to response from interleukin-2 therapy. Although significant correlates to response were identified, there was much variability and a reliable predictive model of response to therapy could not be formulated based on these results. JF - The cancer journal from Scientific American AU - Royal, R E AU - Steinberg, S M AU - Krouse, R S AU - Heywood, G AU - White, D E AU - Hwu, P AU - Marincola, F M AU - Parkinson, D R AU - Schwartzentruber, D J AU - Topalian, S L AU - Yang, J C AU - Rosenberg, S A AD - Surgery Branch and Biostatistics and Data Management Section, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA. PY - 1996 SP - 91 EP - 98 VL - 2 IS - 2 SN - 1081-4442, 1081-4442 KW - Interleukin-2 KW - 0 KW - Recombinant Proteins KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Neoplasm Metastasis -- drug therapy KW - Lymphocytosis -- chemically induced KW - Humans KW - Treatment Outcome KW - Prognosis KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Drug Resistance, Neoplasm KW - Recombinant Proteins -- therapeutic use KW - Male KW - Female KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- drug therapy KW - Melanoma -- pathology KW - Interleukin-2 -- therapeutic use KW - Immunotherapy KW - Melanoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78774631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+cancer+journal+from+Scientific+American&rft.atitle=Correlates+of+response+to+IL-2+therapy+in+patients+treated+for+metastatic+renal+cancer+and+melanoma.&rft.au=Royal%2C+R+E%3BSteinberg%2C+S+M%3BKrouse%2C+R+S%3BHeywood%2C+G%3BWhite%2C+D+E%3BHwu%2C+P%3BMarincola%2C+F+M%3BParkinson%2C+D+R%3BSchwartzentruber%2C+D+J%3BTopalian%2C+S+L%3BYang%2C+J+C%3BRosenberg%2C+S+A&rft.aulast=Royal&rft.aufirst=R&rft.date=1996-03-01&rft.volume=2&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-10-25 N1 - Date created - 2006-09-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer J Sci Am. 1996 Mar-Apr;2(2):73-5 [9166502] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. AN - 78765591; 9816193 AB - Patients with decreased dihydropyrimidine dehydrogenase (DPD) activity are at increased risk for experiencing serious adverse reactions following 5-fluorouracil (5-FU)-based chemotherapy. Symptoms include severe and potentially life-threatening gastrointestinal toxicity, myelosuppression, and neurological toxicity. In the present study, we describe a 50-year-old Caucasian man who developed severe encephalopathy during his second cycle of 5-FU chemotherapy. The patient remained in a comatose state for 4 days but then showed dramatic improvement in his neurological status following continuous i.v. infusion of thymidine at 8 g/m2/day. Laboratory studies revealed the patient to be severely DPD deficient, as demonstrated by DPD enzyme activity from peripheral blood mononuclear cells being below the lower limit of the 95th percentile of a control population and by Western immunoblot analysis showing undetectable levels of DPD protein. Additional studies revealed a significant defect in pyrimidine catabolism with a 3.3- and 365-fold increase in the levels of uracil in plasma and urine, respectively, compared to normal subjects. Family studies suggest that the inheritance pattern of this syndrome is complex and most consistent with an autosomal recessive trait. This study demonstrates that cancer patients with DPD deficiency are at increased risk for developing severe neurological toxicity secondary to 5-FU chemotherapy, and that infusional thymidine should be considered as a potential rescue agent against this particular host toxicity. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Takimoto, C H AU - Lu, Z H AU - Zhang, R AU - Liang, M D AU - Larson, L V AU - Cantilena, L R AU - Grem, J L AU - Allegra, C J AU - Diasio, R B AU - Chu, E AD - National Cancer Institute-Navy Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20889-5105, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 477 EP - 481 VL - 2 IS - 3 SN - 1078-0432, 1078-0432 KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Humans KW - Middle Aged KW - Male KW - Fluorouracil -- adverse effects KW - Brain Diseases -- chemically induced KW - Oxidoreductases -- deficiency KW - Fluorouracil -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78765591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Severe+neurotoxicity+following+5-fluorouracil-based+chemotherapy+in+a+patient+with+dihydropyrimidine+dehydrogenase+deficiency.&rft.au=Takimoto%2C+C+H%3BLu%2C+Z+H%3BZhang%2C+R%3BLiang%2C+M+D%3BLarson%2C+L+V%3BCantilena%2C+L+R%3BGrem%2C+J+L%3BAllegra%2C+C+J%3BDiasio%2C+R+B%3BChu%2C+E&rft.aulast=Takimoto&rft.aufirst=C&rft.date=1996-03-01&rft.volume=2&rft.issue=3&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. AN - 78761508; 9816194 AB - Lovastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (the major regulatory enzyme of the mevalonate pathway of cholesterol synthesis), displays antitumor activity in experimental models. We therefore conducted a Phase I trial to characterize the tolerability of lovastatin administered at progressively higher doses to cancer patients. From January 1992 to July 1994, 88 patients with solid tumors (median age, 57 +/- 14 years) were treated p.o. with 7-day courses of lovastatin given monthly at doses ranging from 2 to 45 mg/kg/day. The inhibitory effects of lovastatin were monitored through serum concentrations of cholesterol and ubiquinone, two end products of the mevalonate pathway. Concentrations of lovastatin and its active metabolites were also determined, by bioassay, in the serum of selected patients. Cyclical treatment with lovastatin markedly inhibited the mevalonate pathway, evidenced by reductions in both cholesterol and ubiquinone concentrations, by up to 43 and 49% of pretreatment values, respectively. The effect was transient, however, and its magnitude appeared to be dose independent. Drug concentrations reached up to 3.9 micrometer and were in the range associated with antiproliferative activity in vitro. Myopathy was the dose-limiting toxicity. Other toxicities included nausea, diarrhea, and fatigue. Treatment with ubiquinone was associated with reversal of lovastatin-induced myopathy, and its prophylactic administration prevented the development of this toxicity in a cohort of 56 patients. One minor response was documented in a patient with recurrent high-grade glioma. Lovastatin given p.o. at a dose of 25 mg/kg daily for 7 consecutive days is well tolerated. The occurrence of myopathy, the dose-limiting toxicity, can be prevented by ubiquinone supplementation. To improve on the transient inhibitory activity of this dosing regimen on the mevalonate pathway, alternative schedules based on uninterrupted administration of lovastatin should also be studied. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Thibault, A AU - Samid, D AU - Tompkins, A C AU - Figg, W D AU - Cooper, M R AU - Hohl, R J AU - Trepel, J AU - Liang, B AU - Patronas, N AU - Venzon, D J AU - Reed, E AU - Myers, C E AD - Clinical Pharmacology Branch and Biometrics Section, National Cancer Institute, Warren Magnussen Clinical Center, NIH, Bethesda, Maryland 20892-1576, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 483 EP - 491 VL - 2 IS - 3 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors KW - Ubiquinone KW - 1339-63-5 KW - Lovastatin KW - 9LHU78OQFD KW - Index Medicus KW - Ubiquinone -- blood KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Lovastatin -- adverse effects KW - Neoplasms -- drug therapy KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- adverse effects KW - Neoplasms -- blood KW - Lovastatin -- pharmacology KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78761508?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+I+study+of+lovastatin%2C+an+inhibitor+of+the+mevalonate+pathway%2C+in+patients+with+cancer.&rft.au=Thibault%2C+A%3BSamid%2C+D%3BTompkins%2C+A+C%3BFigg%2C+W+D%3BCooper%2C+M+R%3BHohl%2C+R+J%3BTrepel%2C+J%3BLiang%2C+B%3BPatronas%2C+N%3BVenzon%2C+D+J%3BReed%2C+E%3BMyers%2C+C+E&rft.aulast=Thibault&rft.aufirst=A&rft.date=1996-03-01&rft.volume=2&rft.issue=3&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An update on air pollution. AN - 78756752; 9363127 AB - Air pollution is associated with adverse health effects. Much of the recent literature, which is the focus of this review, has concentrated on identifying individuals at risk and on the health effects of mixed pollutants. For indoor air, new analyses continue to support the notion that the risk of residential radon exposure is low and that environmental tobacco smoke may cause respiratory symptoms and dysfunction in adults, especially asthmatic adults, as well as in children. For outdoor air, the long-term effects of ozone exposure remain unclear, despite evidence of inflammation and small airway dysfunction after acute exposure. Ozone may increase the sensitivity of asthmatic patients to allergens. Increased morbidity in association with increasing particulate matter levels gives coherence to the argument that the relationship between particulate matter and mortality is causal. However, other investigators note the tight associations among outdoor pollutants and consider particulate matter a marker of air pollution levels. JF - Current opinion in pulmonary medicine AU - Weinmann, G G AD - Division of Lung Diseases, National Heart, Lung, and Blood Institute, Bethesda, MD 20892-7952, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 121 EP - 128 VL - 2 IS - 2 SN - 1070-5287, 1070-5287 KW - Air Pollutants KW - 0 KW - Air Pollutants, Radioactive KW - Allergens KW - Tobacco Smoke Pollution KW - Ozone KW - 66H7ZZK23N KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Allergens -- immunology KW - Causality KW - Lung Diseases -- etiology KW - Humans KW - Respiration Disorders -- etiology KW - Air Pollutants, Radioactive -- adverse effects KW - Child KW - Radon -- adverse effects KW - Longitudinal Studies KW - Immunization KW - Ozone -- adverse effects KW - Asthma -- complications KW - Air Pollution, Indoor -- adverse effects KW - Risk Factors KW - Adult KW - Air Pollutants, Radioactive -- analysis KW - Tobacco Smoke Pollution -- adverse effects KW - Environmental Exposure KW - Allergens -- adverse effects KW - Air Pollution -- adverse effects KW - Air Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78756752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+pulmonary+medicine&rft.atitle=An+update+on+air+pollution.&rft.au=Weinmann%2C+G+G&rft.aulast=Weinmann&rft.aufirst=G&rft.date=1996-03-01&rft.volume=2&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+pulmonary+medicine&rft.issn=10705287&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-02 N1 - Date created - 1997-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inflammatory responses to carrageenan injection in LEW/N and F344/N rats: LEW/N rats show sex- and age-dependent changes in inflammatory reactions. AN - 78584065; 8945724 AB - We studied the inflammatory responses of LEW/N and F344/N inbred rat strains after peripheral injection of carrageenan. The inflammatory responses were assessed in terms of volume, relative and total white blood cell counts of the exudates. Moreover, in both strains, blood CD4, CD8, CD25, naive CD4 (CD4/CD45RC) cell and B (CD45R) cell counts and plasma corticosterone levels, constituents of systemic inflammatory responses to carrageenan were evaluated. In general, LEW/N rats are highly responsive to challenge with carrageenan, whereas F344 rats are not. The strong local inflammatory responses to carrageenan are primarily exhibited by female LEW/N rats. The intensity of local inflammatory responses of LEW/N rats changes with the rat age, the highest exhibited by LEW/N rats up to 3 months of age, thereafter the carrageenan-induced inflammatory responses decline. Our results indicate that peripheral injection of carrageenan induces strong systemic immune component. After carrageenan injection, increases in CD8 and naive CD4 blood lymphocytes are seen. Although the carrageenan challenge does not change CD4 blood lymphocytes in both LEW/N and F344/N rat strains, LEW/N rats exhibit higher levels of CD4 cells than F344/N rats. Additionally, LEW/N rats demonstrated lower levels of B cells and higher naive CD4 lymphocytes. Carrageenan challenges induce significant increases in plasma corticosterone response in F344/N rats, as well as increases in LEW/N rats 1 h after injection. Our data stress the importance of rat age and gender in experiments studying inflammatory responses. JF - Neuroimmunomodulation AU - Misiewicz, B AU - Zelazowska, E AU - Raybourne, R B AU - Cizza, G AU - Sternberg, E M AD - Clinical Neuroendocrinology Branch, National Institute of Mental Health, Bethesda, MD 20892, USA. PY - 1996 SP - 93 EP - 101 VL - 3 IS - 2-3 SN - 1021-7401, 1021-7401 KW - Carrageenan KW - 9000-07-1 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Lymphocyte Count KW - Animals KW - Rats, Inbred Lew KW - Rats, Inbred F344 KW - Age Factors KW - Corticosterone -- blood KW - Injections, Subcutaneous KW - Lymphocyte Subsets KW - Male KW - Female KW - Inflammation -- physiopathology KW - Carrageenan -- toxicity KW - Inflammation -- chemically induced KW - Inflammation -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78584065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroimmunomodulation&rft.atitle=Inflammatory+responses+to+carrageenan+injection+in+LEW%2FN+and+F344%2FN+rats%3A+LEW%2FN+rats+show+sex-+and+age-dependent+changes+in+inflammatory+reactions.&rft.au=Misiewicz%2C+B%3BZelazowska%2C+E%3BRaybourne%2C+R+B%3BCizza%2C+G%3BSternberg%2C+E+M&rft.aulast=Misiewicz&rft.aufirst=B&rft.date=1996-03-01&rft.volume=3&rft.issue=2-3&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Neuroimmunomodulation&rft.issn=10217401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-19 N1 - Date created - 1997-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of patients with high grade non-Hodgkin's lymphomas and central nervous system involvement: is radiation an essential component of therapy? AN - 78513855; 8907276 AB - We have retrospectively examined the outcome of 41 patients with high grade non-Hodgkin's lymphomas (NHL) and central nervous system (CNS) involvement who were treated with and without radiation at a single institution. Group I consisted of 25 patients with CNS involvement at presentation and Group II, of 16 with CNS involvement at first relapse. All 41 had systemic disease at diagnosis and received systemic and intrathecal chemotherapy. Response to therapy did not differ whether patients received concomitant radiation or no CNS radiation. Thirteen of 16 non-irradiated (81%) and 8 of 9 irradiated Group I patients (89%) achieved complete responses. Three of 4 non-irradiated (75%) and 7 of 12 irradiated (58%) Group II patients achieved complete responses. CNS relapse patterns were similar whether or not patients were irradiated, and regardless of radiation dose. Most patients (18) failed systemically; there were few (6) isolated CNS relapses. Survival was not improved by the addition of radiation. Of the 15 patients who achieved long term survival, 13 remained disease-free throughout their clinical course: 7 of these 13 patients (all Group I) did not receive CNS radiation and 6 (4 Group I, 2 Group II) did. In this series, in which 44% of patients who presented with CNS disease and 13% of those who relapsed with CNS became long term disease-free survivors, there was no discernable benefit from radiation, but increased toxicity was observed. JF - Leukemia & lymphoma AU - Magrath, I T AU - Haddy, T B AU - Adde, M A AD - Pediatric Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 99 EP - 105 VL - 21 IS - 1-2 SN - 1042-8194, 1042-8194 KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Adult KW - Retrospective Studies KW - Middle Aged KW - Child KW - Adolescent KW - Child, Preschool KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Non-Hodgkin -- radiotherapy KW - Central Nervous System Neoplasms -- radiotherapy KW - Central Nervous System Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78513855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+%26+lymphoma&rft.atitle=Treatment+of+patients+with+high+grade+non-Hodgkin%27s+lymphomas+and+central+nervous+system+involvement%3A+is+radiation+an+essential+component+of+therapy%3F&rft.au=Magrath%2C+I+T%3BHaddy%2C+T+B%3BAdde%2C+M+A&rft.aulast=Magrath&rft.aufirst=I&rft.date=1996-03-01&rft.volume=21&rft.issue=1-2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Leukemia+%26+lymphoma&rft.issn=10428194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-25 N1 - Date created - 1997-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of maternal drug use during pregnancy with maternal HIV culture positivity and perinatal HIV transmission. AN - 78463519; 8882667 AB - To evaluate the relationship of drug use with maternal HIV culture positivity at delivery and perinatal HIV transmission. Multicenter prospective cohort study. Obstetric and pediatric clinics in five cities in the United States. Five hundred and thirty HIV-infected pregnant women and their infants. Multivariate logistic regression was used to evaluate the association of 'hard drug' use (one or more of the following: cocaine, heroin/opiates, methadone, injecting drug use) assessed by self-report and urine toxicology with positive maternal HIV culture at delivery and perinatal HIV transmission. Forty-two per cent of women used hard drugs during pregnancy. Increased probability of a positive maternal delivery HIV culture was significantly associated with prenatal hard drug use [odds ratio (OR), 3.08] and maternal cocaine use (OR, 2.98) among HIV-infected women with > 29% CD4+ lymphocytes. After adjusting for maternal culture positivity at delivery, CD4+ lymphocyte percentage and gestational age, significantly greater transmission risk was observed with hard drug use among women with membrane rupture > 4 h. On the basis of self-report and urine toxicology, overall maternal hard drug use and cocaine use in the WITS cohort were associated with maternal HIV culture positivity at delivery, and maternal hard drug use was associated with perinatal transmission. JF - AIDS (London, England) AU - Rodriguez, E M AU - Mofenson, L M AU - Chang, B H AU - Rich, K C AU - Fowler, M G AU - Smeriglio, V AU - Landesman, S AU - Fox, H E AU - Diaz, C AU - Green, K AU - Hanson, I C AD - Health Resources Services Administration, National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD 20857, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 273 EP - 282 VL - 10 IS - 3 SN - 0269-9370, 0269-9370 KW - Heroin KW - 70D95007SX KW - Cocaine KW - I5Y540LHVR KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Infant, Newborn KW - Alcohol Drinking KW - Marijuana Smoking KW - Pregnancy KW - Infant KW - Smoking KW - Prospective Studies KW - Cohort Studies KW - Female KW - Infectious Disease Transmission, Vertical KW - HIV Infections -- transmission KW - HIV Infections -- complications KW - HIV-1 -- isolation & purification KW - Pregnancy Complications, Infectious KW - Substance-Related Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78463519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+%28London%2C+England%29&rft.atitle=Association+of+maternal+drug+use+during+pregnancy+with+maternal+HIV+culture+positivity+and+perinatal+HIV+transmission.&rft.au=Rodriguez%2C+E+M%3BMofenson%2C+L+M%3BChang%2C+B+H%3BRich%2C+K+C%3BFowler%2C+M+G%3BSmeriglio%2C+V%3BLandesman%2C+S%3BFox%2C+H+E%3BDiaz%2C+C%3BGreen%2C+K%3BHanson%2C+I+C&rft.aulast=Rodriguez&rft.aufirst=E&rft.date=1996-03-01&rft.volume=10&rft.issue=3&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=AIDS+%28London%2C+England%29&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-11 N1 - Date created - 1996-12-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: AIDS. 1997 Jun;11(7):941-2 [9189229] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of acute and chronic haloperidol treatment on dopamine release mediated by the medial forebrain bundle in the striatum and nucleus accumbens. AN - 78439376; 8866705 AB - The delayed therapeutic effects of neuroleptics have been attributed to D2-mediated depolarization inactivation (DI) of mesolimbic dopaminergic neurons and concomitant reduction in dopamine release. Several studies have suggested, however, that DI may not reduce dopamine release and have hypothesized that this is due to increased impulse independent release. To examine the mechanisms that modulate dopamine release during DI, tetrodotoxin (TTX) was infused into the left medial forebrain bundle (MFB) of Sprague Dawley rats. Three-methoxytyramine (3-MT) levels 10 minutes after pargyline (75 mg/kg) were used as a measure of dopamine release. A dose response study showed that infusions of 10(-5) mol/L and 10(-4) mol/L TTX reduced 3-MT levels on the infused side by 70% in the striatum and 50% to 60% in the nucleus accumbens. In a time course study, 10(-5) mol/L TTX reduced striatal 3-MT at 30, 90, and 120 minutes. After intraperitoneal injections of haloperidol (0.4 mg/kg) for 1 or 21 days, TTX infusions again reduced 3-MT levels by approximately 70% in the striatum and 53% to 59% in the nucleus accumbens on the infused side. Acute and chronic haloperidol treatment did not alter the percent of TTX-induced reductions. These data suggest that dopaminergic neuronal impulse flow modulates similar amounts of total transmitter release after both acute and chronic haloperidol treatment. The results do not support the notion that DI mediates the antipsychotic effects of neuroleptics by markedly reducing total basal dopamine release or increasing impulse independent release. Alternatively, DI could reduce psychotic symptoms by changing the responsiveness of the dopamine system to external stimuli or by reducing synaptic dopamine levels that have been hypothesized to be elevated in psychotic patients. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Egan, M F AU - Chrapusta, S J AU - Karoum, F AU - Wyatt, R J AD - Neuropsychiatry Branch, National Institute of Mental Health Neuroscience Research Center at St. Elizabeth, Washington, DC 20032, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 211 EP - 223 VL - 14 IS - 3 SN - 0893-133X, 0893-133X KW - Tetrodotoxin KW - 4368-28-9 KW - Haloperidol KW - J6292F8L3D KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Tetrodotoxin -- pharmacology KW - Time Factors KW - Male KW - Dopamine -- secretion KW - Nucleus Accumbens -- drug effects KW - Haloperidol -- pharmacology KW - Dopamine -- metabolism KW - Corpus Striatum -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78439376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=The+effects+of+acute+and+chronic+haloperidol+treatment+on+dopamine+release+mediated+by+the+medial+forebrain+bundle+in+the+striatum+and+nucleus+accumbens.&rft.au=Egan%2C+M+F%3BChrapusta%2C+S+J%3BKaroum%2C+F%3BWyatt%2C+R+J&rft.aulast=Egan&rft.aufirst=M&rft.date=1996-03-01&rft.volume=14&rft.issue=3&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumors of the bladder, kidney, and intestine of F344 rats and liver of B6C3F1 mice administered o-nitroanisole in feed. AN - 78386930; 8812201 AB - o-Nitroanisole, a mutagenic intermediate used in the manufacture of azo dyes, was administered in feed for 2 years at concentrations of 0, 222, 666, or 2000 ppm to groups of 60 male and 60 female F344 rats. No significant increase in neoplasms occurred in these groups of rats. Additional (stop exposure) groups of 60 male and 60 female F344 rats received diets containing 0, 6000, or 18,000 ppm for 27 weeks followed by maintenance on control diets for up to an additional 77 weeks. Survival of the stop exposure groups was reduced because of the development of chemical related neoplasms of the urinary bladder. After 13, 28, 40, and 65 weeks on study, 10 rats per group were necropsied and evaluated for the presence of chemical associated lesions. Hyperplasia of the epithelium of the urinary bladder was significantly increased at all interim evaluations. A transitional cell carcinoma was observed at the 13-week evaluation in one male rat that received 18,000 ppm and thereafter transitional cell neoplasms of the bladder were present in male and female rats at each interim evaluation. Adenomatous polyps of the large intestine were significantly increased in groups that received 6000 or 18,000 ppm. In addition carcinomas of the large intestine were present in four males and two females that received 18,000 ppm. Hyperplasia of the transitional epithelium of the renal pelvis was significantly increased in groups of rats that received 6000 or 18,000 ppm and transitional cell papillomas were observed in three males and one female that received 18,000 ppm. Transitional cell carcinomas of the kidney occurred in one male that received 6000 ppm and six males and one female that received 18,000. Groups of 60 male and 60 female B6C3F1 mice received dietary concentrations of 0, 666, 2000, or 6000 ppm o-nitroanisole for 2 years. No stop exposure study was conducted with mice. The only neoplastic response observed in mice was in the liver of males; hepatocellular adenomas or carcinomas were increased in groups of male mice that received 2000 or 6000 ppm. No increase in neoplasms associated with chemical exposure occurred in female mice. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Irwin, R D AU - Chhabra, R AU - Eustis, S AU - Pinter, A AU - Prejean, J D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 12233, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 1 EP - 12 VL - 30 IS - 1 SN - 0272-0590, 0272-0590 KW - Anisoles KW - 0 KW - Carcinogens KW - 2-nitroanisole KW - ZRE7HLZ17K KW - Index Medicus KW - Animals KW - Kidney Neoplasms -- pathology KW - Urinary Bladder Neoplasms -- pathology KW - Kidney Neoplasms -- chemically induced KW - Kidney Diseases -- mortality KW - Kidney Neoplasms -- mortality KW - Rats KW - Animal Feed KW - Liver Neoplasms -- pathology KW - Rats, Inbred F344 KW - Intestinal Neoplasms -- chemically induced KW - Male KW - Kidney Diseases -- chemically induced KW - Urinary Bladder Neoplasms -- chemically induced KW - Kidney Diseases -- pathology KW - Drug Administration Schedule KW - Intestinal Neoplasms -- pathology KW - Liver Neoplasms -- mortality KW - Intestinal Neoplasms -- mortality KW - Liver Neoplasms -- chemically induced KW - Mice KW - Body Weight -- drug effects KW - Carcinogenicity Tests KW - Mice, Inbred C57BL KW - Urinary Bladder Neoplasms -- mortality KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- mortality KW - Anisoles -- administration & dosage KW - Neoplasms, Experimental -- pathology KW - Anisoles -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78386930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Tumors+of+the+bladder%2C+kidney%2C+and+intestine+of+F344+rats+and+liver+of+B6C3F1+mice+administered+o-nitroanisole+in+feed.&rft.au=Irwin%2C+R+D%3BChhabra%2C+R%3BEustis%2C+S%3BPinter%2C+A%3BPrejean%2C+J+D&rft.aulast=Irwin&rft.aufirst=R&rft.date=1996-03-01&rft.volume=30&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity of delta 9-tetrahydrocannabinol in Fischer rats and B6C3F1 mice. AN - 78384441; 8812248 AB - delta 9-Tetrahydrocannabinol (delta 9-THC) was studied for potential carcinogenicity in rodents because it is the principal psychoactive ingredient in marihuana and it has potential medicinal uses. delta 9-THC in corn oil was administered by gavage to groups of male and female Fischer rats and B6C3F1 mice at 0, 5, 15, 50, 150, or 500 mg/kg, 5 days a week for 13 weeks and for 13-week plus a 9-week recovery period, and to groups of rats at 0, 12.5, or 50 mg/kg and mice at 0, 125, 250, or 500 mg/kg, 5 times a week for 2 years. In all studies, mean body weights of dosed male and female rats and mice were lower than controls but feed consumptions were similar. Convulsions and hyperactivity were observed in dosed rats and mice; the onset and frequency were dose related. Serum FSH and LH levels in all dosed male rats and corticosterone levels in 25 mg/kg female rats were significantly higher than controls at 15 months in the 2-year studies. delta 9-THC administration for 13 weeks induced testicular atrophy and uterine and ovarian hypoplasia; the lesions persisted in a 9-week recovery period. In the 2-year studies, survival of dosed rats was higher than controls; that of mice was similar to controls. Incidences of testicular interstitial cell, pancreas and pituitary gland adenomas in male rats, mammary gland fibroadenoma and uterus stromal polyp in female rats, and hepatocellular adenoma/carcinoma in male and female mice were reduced in a dose-related manner. Decreased tumor incidences may be at least in part due to reduced body weights of dosed animals. Incidences of thyroid gland follicular cell hyperplasia were increased in all dosed groups of male and female mice, and follicular cell adenomas were significantly increased in the 125 mg/kg group of males, but there was no evidence of a dose-related trend in proliferative lesions of the thyroid. There was no evidence that delta 9-THC was carcinogenic in rats or mice. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Chan, P C AU - Sills, R C AU - Braun, A G AU - Haseman, J K AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 109 EP - 117 VL - 30 IS - 1 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - Dronabinol KW - 7J8897W37S KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Mice, Inbred C57BL KW - Carcinogens -- toxicity KW - Carcinogenicity Tests KW - Mice KW - Carcinogens -- analysis KW - Male KW - Female KW - Dronabinol -- analysis KW - Dronabinol -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78384441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Toxicity+and+carcinogenicity+of+delta+9-tetrahydrocannabinol+in+Fischer+rats+and+B6C3F1+mice.&rft.au=Chan%2C+P+C%3BSills%2C+R+C%3BBraun%2C+A+G%3BHaseman%2C+J+K%3BBucher%2C+J+R&rft.aulast=Chan&rft.aufirst=P&rft.date=1996-03-01&rft.volume=30&rft.issue=1&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality of lead smelter workers with the glucose-6-phosphate dehydrogenase-deficient phenotype. AN - 78383589; 8833623 AB - The mortality experience of 1345 male workers in a lead and zinc smelting plant was followed from 1973 to 1991. Information on the erythrocyte glucose-6-phosphate dehydrogenase (G6PD) phenotype was available for 1,222 (90.9%) cohort members, which provided the opportunity to compare the mortality experience of G6PD-deficient subjects to wild-type-G6PD coworkers with similar exposure to lead. A significant decrease in mortality was observed among the total cohort as well as among the subcohort of production and maintenance workers. Most deaths (27 of 31) and all cancer deaths occurred among production and maintenance workers. Lung cancer mortality was lower than expected. Two deaths from stomach cancer were observed versus 0.6 expected. Mortality from all causes and cancer mortality were lower among production and maintenance workers with the G6PD-deficient phenotype compared to coworkers with the wild-type phenotype. Although the low statistical power of this study prevents conclusive inference, lead smelter workers with the G6PD-deficient phenotype did not suffer adverse health outcomes in terms of mortality from all causes and cancer mortality compared to coworkers with the wild-type G6PD. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Cocco, P AU - Carta, P AU - Flore, C AU - Congia, P AU - Manca, M B AU - Saba, G AU - Salis, S AD - Istituto di Medicina del Lavoro, Universita di Cagliari, Italy. pierluic@epndce.nci.nih.gov Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 223 EP - 225 VL - 5 IS - 3 SN - 1055-9965, 1055-9965 KW - Lead KW - 2P299V784P KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Occupational Exposure KW - Healthy Worker Effect KW - Neoplasms -- mortality KW - Humans KW - Outcome Assessment (Health Care) KW - Occupational Diseases -- mortality KW - Phenotype KW - Cardiovascular Diseases -- mortality KW - Erythrocytes -- enzymology KW - Stomach Neoplasms -- mortality KW - Adult KW - Cohort Studies KW - Follow-Up Studies KW - Lung Neoplasms -- mortality KW - Italy -- epidemiology KW - Male KW - Glucosephosphate Dehydrogenase Deficiency -- genetics KW - Chemical Industry KW - Glucosephosphate Dehydrogenase Deficiency -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78383589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Mortality+of+lead+smelter+workers+with+the+glucose-6-phosphate+dehydrogenase-deficient+phenotype.&rft.au=Cocco%2C+P%3BCarta%2C+P%3BFlore%2C+C%3BCongia%2C+P%3BManca%2C+M+B%3BSaba%2C+G%3BSalis%2C+S&rft.aulast=Cocco&rft.aufirst=P&rft.date=1996-03-01&rft.volume=5&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-29 N1 - Date created - 1997-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thirteen-week inhalation toxicity of 2- and 4-chloronitrobenzene in F344/N rats and B6C3F1 mice. AN - 78379404; 8812232 AB - Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice to 2- and 4-chloronitrobenzene (CNB) by whole-body inhalation 6 hr/day, 5 days/week, for 13 weeks. Animals were evaluated for clinical chemistry (rats), hematology (rats), histopathology, and body/organ weights. Exposure concentrations were 0, 1.1, 2.3, 4.5, 9, and 18 ppm for 2-CNB and 0, 1.5, 3, 6, 12, and 24 ppm for 4-CNB. All rats in the 2-CNB study survived until the end of the study. Two male mice in the 18-ppm group in the 2-CNB study, however, died during Week 12; no deaths attributable to 4-CNB exposure occurred in rats or mice. In both studies, the mean body weight gains of exposed animals were similar to those of the respective controls. In rats, inhalation exposure to 2- or 4-CNB resulted in methemoglobinemia leading to a regenerative anemia and a variety of tissue changes secondary to the oxidative erythrocyte injury. In the 2-CNB study, methemoglobinemia resulted in a normocytic, normochromic, responsive anemia, whereas with 4-CNB, the methemoglobinemia was more severe and resulted in a macrocytic, hyperchromic, responsive anemia. Alterations of erythrocyte morphology were observed in both studies; changes included Heinz bodies, poikilocytes, and polychromasia. In rats, both isomers caused increases in serum activities of alanine aminotransferase and sorbitol dehydrogenase and increased bile acid concentrations. Microscopic liver changes included hemosiderin deposition in Kupffer cells (rats and mice exposed to 4-CNB), hepatocytomegaly (mice), and cytoplasmic basophilia (rats). Hepatocellular necrosis and chronic inflammation observed in mice were rather specific to the 2-CNB isomer, as only slight evidence of focal necrosis in the liver was observed in mice exposed to 4-CNB. Splenic lesions included hemosiderin accumulation capsular fibrosis, and increased hematopoietic cell proliferation. Increased bone marrow hemosiderin and hematopoietic cell proliferation and kidney tubule hemosiderin deposition were also observed. Other findings, attributed to chemical exposure but not to the hematotoxicity, were described. Lesions included hyaline droplet nephropathy and degeneration of the testis in male rats exposed to 4-CNB, inflammation of the harderian gland in rats exposed to 4-CNB, hyperplasia of the nasal cavity epithelium in rats exposed to 2-CNB, and hyperplasia of the forestomach epithelium in mice exposed to 4-CNB; these lesions have not been described previously in studies with these chemicals. Based on the exposure concentrations evaluated, A no-observed-adverse-effect level (NOAEL) for histopathological injury in mice was 4.5 ppm for 2-chloronitrobenzene and 6 ppm for 4-chloronitrobenzene; a NOAEL was not determined for rats. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Travlos, G S AU - Mahler, J AU - Ragan, H A AU - Chou, B J AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 75 EP - 92 VL - 30 IS - 1 SN - 0272-0590, 0272-0590 KW - Nitrobenzenes KW - 0 KW - 2-chloronitrobenzene KW - 88-73-3 KW - 4-chloronitrobenzene KW - CVL66U249D KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Kidney -- pathology KW - Kidney -- drug effects KW - Spleen -- pathology KW - Mice KW - Rats KW - Rats, Inbred F344 KW - No-Observed-Adverse-Effect Level KW - Liver -- drug effects KW - Mice, Inbred C57BL KW - Methemoglobinemia -- chemically induced KW - Spleen -- drug effects KW - Administration, Inhalation KW - Blood Cell Count -- drug effects KW - Female KW - Male KW - Organ Size -- drug effects KW - Nitrobenzenes -- toxicity KW - Nitrobenzenes -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78379404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Thirteen-week+inhalation+toxicity+of+2-+and+4-chloronitrobenzene+in+F344%2FN+rats+and+B6C3F1+mice.&rft.au=Travlos%2C+G+S%3BMahler%2C+J%3BRagan%2C+H+A%3BChou%2C+B+J%3BBucher%2C+J+R&rft.aulast=Travlos&rft.aufirst=G&rft.date=1996-03-01&rft.volume=30&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risks of non-Hodgkin's lymphoma, multiple myeloma, and leukemia associated with common medications. AN - 78375017; 8834551 AB - We utilized data from two Kaiser Permanente medical care programs to evaluate risks of hematopoietic and lymphoproliferative (HLP) malignancies after use of 14 common medications. The subjects were adult cases of non-Hodgkin's lymphoma (NHL) (N = 94), multiple myeloma (N = 159), and leukemia (N = 257) and individually matched controls (N = 695). Abstractors reviewed medical records and recorded medication notations. Using a minimum 5-year exposure lag between first notation and malignancy diagnosis, the risk of NHL was greater among plan members who were prescribed amphetamines [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.1-4.8], lidocaine (OR = 2.6; 95% CI = 1.2-5.5), and meprobamate (OR = 2.1; 95% CI = 1.03-4.3). The risk of NHL rose with increasing number of medical record notations for amphetamines; however, there was no association with number of notations for lidocaine or meprobamate. The odds ratio for total leukemia was decreased among patients who took chloramphenicol (OR = 0.4; 95% CI = 0.2-0.97). JF - Epidemiology (Cambridge, Mass.) AU - Doody, M M AU - Linet, M S AU - Glass, A G AU - Curtis, R E AU - Pottern, L M AU - Rush, B B AU - Boice, J D AU - Fraumeni, J F AU - Friedman, G D AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 131 EP - 139 VL - 7 IS - 2 SN - 1044-3983, 1044-3983 KW - Amphetamines KW - 0 KW - Chloramphenicol KW - 66974FR9Q1 KW - Lidocaine KW - 98PI200987 KW - Meprobamate KW - 9I7LNY769Q KW - Index Medicus KW - Lidocaine -- administration & dosage KW - Health Maintenance Organizations -- statistics & numerical data KW - Odds Ratio KW - Chloramphenicol -- adverse effects KW - Humans KW - Aged KW - Amphetamines -- adverse effects KW - Chloramphenicol -- administration & dosage KW - Meprobamate -- administration & dosage KW - Risk KW - Amphetamines -- administration & dosage KW - Meprobamate -- adverse effects KW - Lidocaine -- adverse effects KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Middle Aged KW - California -- epidemiology KW - Male KW - Female KW - Drug Prescriptions -- statistics & numerical data KW - Multiple Myeloma -- chemically induced KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Leukemia -- chemically induced KW - Leukemia -- epidemiology KW - Drug-Related Side Effects and Adverse Reactions KW - Multiple Myeloma -- epidemiology KW - Lymphoma, Non-Hodgkin -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78375017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Risks+of+non-Hodgkin%27s+lymphoma%2C+multiple+myeloma%2C+and+leukemia+associated+with+common+medications.&rft.au=Doody%2C+M+M%3BLinet%2C+M+S%3BGlass%2C+A+G%3BCurtis%2C+R+E%3BPottern%2C+L+M%3BRush%2C+B+B%3BBoice%2C+J+D%3BFraumeni%2C+J+F%3BFriedman%2C+G+D&rft.aulast=Doody&rft.aufirst=M&rft.date=1996-03-01&rft.volume=7&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Childhood exposure to magnetic fields: residential area measurements compared to personal dosimetry. AN - 78372370; 8834554 AB - We examined the relation between area measurements of residential magnetic fields and personal dosimetry measurements among 64 control children age 2-14 years from the National Cancer Institute-Children's Cancer Group's nine-state case-control study of childhood leukemia. During a typical weekday, an activity diary was completed, and a 24-hour measurement was obtained in each child's bedroom. According to the activity diaries, children spent more than 40% of the 24 hours in their bedrooms, and 68% of their time at home. We found that at-home personal dosimetry levels were highly correlated with total personal dosimetry levels in children under 9 years (Spearman correlation coefficient, R = 0.94), whereas the correlation was lower in older children (R = 0.59). For all children combined, bedroom 24-hour measurements correlated well with at-home personal dosimetry levels (R = 0.76). The 24-hour bedroom measurement was a useful predictor of both at-home and total personal dosimetry measurements. Particularly for younger children, our data suggest that in-home area measurements predict both current residential and current total magnetic field exposures. This information will be valuable for assessing the validity of exposure assessment in previous and ongoing studies and for developing measurement protocols for future studies. JF - Epidemiology (Cambridge, Mass.) AU - Friedman, D R AU - Hatch, E E AU - Tarone, R AU - Kaune, W T AU - Kleinerman, R A AU - Wacholder, S AU - Boice, J D AU - Linet, M S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7362, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 151 EP - 155 VL - 7 IS - 2 SN - 1044-3983, 1044-3983 KW - Index Medicus KW - Radiation Dosage KW - Humans KW - Child KW - Adolescent KW - United States -- epidemiology KW - Radiation Monitoring -- instrumentation KW - Male KW - Female KW - Child, Preschool KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Air Pollution, Indoor -- adverse effects KW - Electromagnetic Fields KW - Environmental Exposure -- adverse effects KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78372370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Childhood+exposure+to+magnetic+fields%3A+residential+area+measurements+compared+to+personal+dosimetry.&rft.au=Friedman%2C+D+R%3BHatch%2C+E+E%3BTarone%2C+R%3BKaune%2C+W+T%3BKleinerman%2C+R+A%3BWacholder%2C+S%3BBoice%2C+J+D%3BLinet%2C+M+S&rft.aulast=Friedman&rft.aufirst=D&rft.date=1996-03-01&rft.volume=7&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic cocaine exposure potentiates prolactin and head shake responses to 5-HT2 receptor stimulation in rats. AN - 78293867; 8783204 AB - The effect of repeated cocaine administration on serotonin2 (5-HT2) receptor function was examined in male rats. Rats were fitted with indwelling jugular catheters and subsequently received cocaine (15 mg/kg, i.p., b.i.d.) or saline for 7 days. Rats were challenged with the 5-HT2 agonist DOI (25, 100, 400 micrograms/kg, i.v.) or saline 42 hr and 8 days after cessation of chronic treatment. Serial blood samples were collected at various times after DOI challenge and analyzed for prolactin levels. DOI-induced head shakes and skin jerks were examined concurrently in the same subjects. After 42 hr of withdrawal, the stimulatory effects of DOI on prolactin release and shaking behavior were significantly enhanced in cocaine-treated rats. Conversely, the skin jerk response to DOI was not altered by prior cocaine exposure. After 8 days of withdrawal, the prolactin and head shake responses to DOI were still potentiated in cocaine-treated rats, but this effect was no longer statistically significant. The data indicate that chronic cocaine enhances the sensitivity of 5-HT2 receptor mechanisms. Our findings further suggest the possibility that altered 5-HT2 receptor function may be involved in the mood disturbances experienced by abstinent cocaine addicts. JF - Neuropharmacology AU - Baumann, M H AU - Rothman, R B AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore 21224, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 295 EP - 301 VL - 35 IS - 3 SN - 0028-3908, 0028-3908 KW - Amphetamines KW - 0 KW - Narcotics KW - Serotonin Receptor Agonists KW - Prolactin KW - 9002-62-4 KW - Cocaine KW - I5Y540LHVR KW - 4-iodo-2,5-dimethoxyphenylisopropylamine KW - OOM10GW9UE KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Male KW - Serotonin Receptor Agonists -- pharmacology KW - Prolactin -- blood KW - Substance Withdrawal Syndrome -- physiopathology KW - Amphetamines -- pharmacology KW - Narcotics -- adverse effects KW - Stereotyped Behavior -- drug effects KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78293867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Chronic+cocaine+exposure+potentiates+prolactin+and+head+shake+responses+to+5-HT2+receptor+stimulation+in+rats.&rft.au=Baumann%2C+M+H%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=1996-03-01&rft.volume=35&rft.issue=3&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-26 N1 - Date created - 1997-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Evaluation of the absorption of polycyclic aromatic hydrocarbons by analysing 1-hydroxypyrene in the urine of the workers in a factory of graphite electrodes]. TT - Valutazione dell'assorbimento di idrocarburi policiclici aromatici mediante dosaggio dell'1-OH-Pirene urinario nei lavoratori di una fabbrica di elettrodi di grafite. AN - 78293351; 8926919 AB - A group of 288 workers of a graphite electrode manufacturing plant (33 of whom were not classified as either exposed or non-exposed) participated in a biological monitoring programme of exposure to PAHs via determination of 1-hydroxypyrene in end-of-shift urine. A highly significant difference (p < 0.000001) was observed in the mean urinary values of the metabolite in the 132 subjects classified as exposed compared to the 123 not exposed, which was not influenced by by confounding factors. The maintenance workers group showed mean urinary levels of 1-hydroxypyrene similar to the production department workers who were exposed to pitch. Among the exposed the use of a mask with filters for organic fumes reduced absorption of PAHs and significantly reduced urinary excretion of 1-hydroxypyrene (p < 0.005). The test also proved to be sensitive in discriminating the subjects exposed to low doses of PAHs, as the results obtained in laboratory workers showed. After comparing their data with the proposals for Biological Limit Values for 1-hydroxypyrene, the authors stress the usefulness of this biological monitoring tool in exposure to PAHs for the assessment of cancer risk, as provided for by Law No. 626/94. JF - La Medicina del lavoro AU - Marchionna, G AU - Valenti, E AU - Paolemili, P AU - Ricci, R AD - U.O. Prevenzione e Sicurezza nei Luoghi di Lavoro, Dipartimento di Prevenzione USL n. 5, Narni Scalo, Terni. PY - 1996 SP - 162 EP - 170 VL - 87 IS - 2 SN - 0025-7818, 0025-7818 KW - Air Pollutants, Occupational KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - Pyrenes KW - Graphite KW - 7782-42-5 KW - 1-hydroxypyrene KW - N2H6O5V707 KW - Index Medicus KW - Humans KW - Electrodes KW - Absorption KW - Pyrenes -- analysis KW - Polycyclic Aromatic Hydrocarbons -- pharmacokinetics KW - Pyrenes -- metabolism KW - Air Pollutants, Occupational -- pharmacokinetics KW - Air Pollutants, Occupational -- urine KW - Polycyclic Aromatic Hydrocarbons -- urine KW - Occupational Exposure -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78293351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BEvaluation+of+the+absorption+of+polycyclic+aromatic+hydrocarbons+by+analysing+1-hydroxypyrene+in+the+urine+of+the+workers+in+a+factory+of+graphite+electrodes%5D.&rft.au=Marchionna%2C+G%3BValenti%2C+E%3BPaolemili%2C+P%3BRicci%2C+R&rft.aulast=Marchionna&rft.aufirst=G&rft.date=1996-03-01&rft.volume=87&rft.issue=2&rft.spage=162&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-18 N1 - Date created - 1996-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer; tumor neovasculature and the effect of tissue inhibitor of metalloproteinases-1 (TIMP-1) on angiogenesis. AN - 78248802; 8744792 AB - Microvessel density has been proposed as a prognostic factor in breast carcinoma. In paired samples of human breast carcinoma and the adjacent non-neoplastic tissue, proliferating microvessels were associated with in situ ductal and lobular carcinomas. In invasive carcinomas, the microvessels were located within the tumor stroma. Recombinant tissue inhibitor of metalloproteinases-1 (rTIMP-1) was produced in a baculovirus system to examine its effect on angiogenesis. When present as a molecule of 29 kDa, rTIMP-1 inhibited matrix metalloproteinase (MMP) activity. However, a 66 kDa aggregate of TIMP-1 did not block MMP activity, although it inhibited in vitro angiogenesis as the 29 kDa form did. Studies have been initiated to characterize the effects of overexpression of TIMP-1 on breast carcinoma cells. Preliminary findings show TIMP-1 mediated changes in morphology and downregulation of MMP activity. These findings suggest that the angiogenesis inhibitory activity of TIMP-1 is unrelated to its antimetalloproteinase activity and that TIMP-1 may affect cellular function in different ways. JF - In vivo (Athens, Greece) AU - Thorgeirsson, U P AU - Yoshiji, H AU - Sinha, C C AU - Gomez, D E AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 137 EP - 144 VL - 10 IS - 2 SN - 0258-851X, 0258-851X KW - Carcinogens KW - 0 KW - Culture Media, Conditioned KW - Glycoproteins KW - Matrix Metalloproteinase Inhibitors KW - Protease Inhibitors KW - Tissue Inhibitor of Metalloproteinases KW - Methylnitrosourea KW - 684-93-5 KW - Collagenases KW - EC 3.4.24.- KW - Gelatinases KW - Metalloendopeptidases KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Matrix Metalloproteinase 9 KW - EC 3.4.24.35 KW - Index Medicus KW - Metalloendopeptidases -- pharmacology KW - Animals KW - Carcinogens -- pharmacology KW - Endothelium, Vascular -- metabolism KW - Humans KW - Methylnitrosourea -- pharmacology KW - Gelatinases -- pharmacology KW - Molecular Weight KW - Rats KW - Blotting, Western KW - Tumor Cells, Cultured KW - Transfection KW - Female KW - Collagenases -- pharmacology KW - Protease Inhibitors -- pharmacology KW - Protease Inhibitors -- metabolism KW - Glycoproteins -- pharmacology KW - Breast Neoplasms -- pathology KW - Glycoproteins -- metabolism KW - Mammary Neoplasms, Experimental -- blood supply KW - Neovascularization, Pathologic KW - Breast Neoplasms -- blood supply KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78248802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Breast+cancer%3B+tumor+neovasculature+and+the+effect+of+tissue+inhibitor+of+metalloproteinases-1+%28TIMP-1%29+on+angiogenesis.&rft.au=Thorgeirsson%2C+U+P%3BYoshiji%2C+H%3BSinha%2C+C+C%3BGomez%2C+D+E&rft.aulast=Thorgeirsson&rft.aufirst=U&rft.date=1996-03-01&rft.volume=10&rft.issue=2&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-28 N1 - Date created - 1997-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary heterocyclic amines as potential human carcinogens: experimental data from nonhuman primates. AN - 78247817; 8744793 AB - During the cooking of meats, several highly potent mutagenic heterocyclic amines (HCAs) are produced. To date, 10 HCAs have been shown to be carcinogenic in rodents, and one HCA, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), has been shown to be a potent hepatocarcinogen in nonhuman primates. In this report, we discuss the role of metabolic activation and DNA adduct formation in the carcinogenicity of HCAs, especially in nonhuman primates. The potent hepatocarcinogenicity of IQ in cynomolgus monkeys appears to be associated with the in vivo metabolic activation of IQ and the formation of hepatic DNA adducts. Notably, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx), is poorly metabolically activated in monkeys and lacks the potency of IQ to induce hepatocellular carcinoma. Ongoing studies with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), indicate that PhlP is metabolically activated in monkeys and is a likely carcinogen in this species. We further compared human, rat, and cynomolgus monkey hepatic microsomes for their abilities to metabolically activate various HCAs to mutagens. Our in vitro results show that humans, relative to rats or cynomolgus monkeys, have a good capacity to metabolically activate the HCAs. These findings support the concept that humans are likely to be susceptible to the carcinogenic effects of HCAs. JF - In vivo (Athens, Greece) AU - Thorgeirsson, U P AU - Snyderwine, E G AU - Gomez, D E AU - Adamson, R H AD - Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 145 EP - 152 VL - 10 IS - 2 SN - 0258-851X, 0258-851X KW - Amines KW - 0 KW - Carcinogens KW - DNA Adducts KW - Heterocyclic Compounds KW - Hydroxylamines KW - Hydroxyquinolines KW - Imidazoles KW - Mutagens KW - Quinoxalines KW - 2-amino-3-methylimidazo(4,5-f)-quinoline 5-sulfate ester KW - 122719-40-8 KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Macaca fascicularis KW - Imidazoles -- pharmacology KW - Myocardium -- pathology KW - Hydroxyquinolines -- pharmacology KW - Humans KW - Myocardium -- ultrastructure KW - Mice KW - Hydroxylamines -- pharmacology KW - Mutagens -- pharmacology KW - Quinoxalines -- pharmacology KW - DNA Adducts -- metabolism KW - Heterocyclic Compounds -- metabolism KW - Carcinogens -- pharmacology KW - Carcinogens -- metabolism KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- metabolism KW - Heterocyclic Compounds -- pharmacology KW - Amines -- pharmacology KW - Amines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78247817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Dietary+heterocyclic+amines+as+potential+human+carcinogens%3A+experimental+data+from+nonhuman+primates.&rft.au=Thorgeirsson%2C+U+P%3BSnyderwine%2C+E+G%3BGomez%2C+D+E%3BAdamson%2C+R+H&rft.aulast=Thorgeirsson&rft.aufirst=U&rft.date=1996-03-01&rft.volume=10&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-28 N1 - Date created - 1997-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Racial comparison of p53 alterations in breast cancer: difference in prognostic value. AN - 78245358; 8744796 AB - A significant difference in breast cancer survival between blacks and whites has been observed in the United States. Biological variation between races has been suggested to explain the difference. We investigated the difference by comparing the prognostic value of p53 alterations (mutations and protein accumulation) between black and white breast cancer patients. Black, but not white, patients with p53 mutations had a significantly poorer survival than those without p53 mutations (p < 0.05). In contrast, white, but not black, patients having tumors with p53 protein accumulation tended to have a poorer survival than those without accumulation of p53 protein (p = 0.058). Among patients who died of breast cancer, blacks were often to have p53 mutations without protein accumulation, and whites frequently had p53 protein accumulation without mutations. The racial disparities in the associations of p53 alterations with breast cancer survival could have clinical implications in terms of treatment management. JF - In vivo (Athens, Greece) AU - Shiao, Y H AU - Chen, V W AU - Wu, X C AU - Scheer, W D AU - Lehmann, H P AU - Malcom, G T AU - Boudreau, D A AU - Ruiz, B AU - Correa, P AD - Laboratory of Comparative Carcinogenesis. NCI-FCRDC, NIH, Frederick, MD 21702, USA. PY - 1996 SP - 169 EP - 173 VL - 10 IS - 2 SN - 0258-851X, 0258-851X KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Humans KW - Prognosis KW - United States -- epidemiology KW - Tumor Suppressor Protein p53 -- metabolism KW - Mutation KW - Female KW - Breast Neoplasms -- mortality KW - Genes, p53 KW - African Continental Ancestry Group -- genetics KW - Breast Neoplasms -- ethnology KW - European Continental Ancestry Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78245358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Racial+comparison+of+p53+alterations+in+breast+cancer%3A+difference+in+prognostic+value.&rft.au=Shiao%2C+Y+H%3BChen%2C+V+W%3BWu%2C+X+C%3BScheer%2C+W+D%3BLehmann%2C+H+P%3BMalcom%2C+G+T%3BBoudreau%2C+D+A%3BRuiz%2C+B%3BCorrea%2C+P&rft.aulast=Shiao&rft.aufirst=Y&rft.date=1996-03-01&rft.volume=10&rft.issue=2&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-28 N1 - Date created - 1997-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol consumption and risk of colorectal cancer in a cohort of Finnish men. AN - 78220173; 8740734 AB - We investigated the association between self-reported alcohol ingestion and colorectal cancer in a cohort of male smokers in Finland. Among 27,109 men aged 50 to 69 years, 87 colon and 53 rectal cases were diagnosed during the five to eight years of follow-up. Among drinkers, colorectal cancer risk increased with the amount of alcohol consumed (P trend = 0.01) with risk increasing by 17 percent for each drink consumed. Both beer and spirits contributed to this increased risk. Further analyses revealed that the positive association with alcohol was primarily for colon cancer (P trend = 0.01). Interestingly, risk of colorectal cancer associated with drinking (cf self-reported abstinence) changed with follow-up time, suggesting an inverse association for alcohol early in follow-up, and a positive association after about three-and-a-half years of follow-up. Follow-up time did not modify the positive association with amount of alcohol among drinkers, however. Results also indicated that beta-carotene supplementation may attenuate the effect of alcohol on colorectal cancer risk among drinkers. In conclusion, this study supports a role for alcohol in colon carcinogenesis and suggests that similar studies should evaluate carefully the effects of lifetime drinking habits and recent abstinence. JF - Cancer causes & control : CCC AU - Glynn, S A AU - Albanes, D AU - Pietinen, P AU - Brown, C C AU - Rautalahti, M AU - Tangrea, J A AU - Taylor, P R AU - Virtamo, J AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 214 EP - 223 VL - 7 IS - 2 SN - 0957-5243, 0957-5243 KW - Antineoplastic Agents KW - 0 KW - beta Carotene KW - 01YAE03M7J KW - Carotenoids KW - 36-88-4 KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Time Factors KW - Finland -- epidemiology KW - Smoking -- epidemiology KW - Male KW - Antineoplastic Agents -- administration & dosage KW - Carotenoids -- administration & dosage KW - Colorectal Neoplasms -- epidemiology KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78220173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Alcohol+consumption+and+risk+of+colorectal+cancer+in+a+cohort+of+Finnish+men.&rft.au=Glynn%2C+S+A%3BAlbanes%2C+D%3BPietinen%2C+P%3BBrown%2C+C+C%3BRautalahti%2C+M%3BTangrea%2C+J+A%3BTaylor%2C+P+R%3BVirtamo%2C+J&rft.aulast=Glynn&rft.aufirst=S&rft.date=1996-03-01&rft.volume=7&rft.issue=2&rft.spage=214&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolutionary histories of highly repeated DNA families among the Artiodactyla (Mammalia). AN - 78216439; 8661995 AB - Six highly repeated DNA families were analyzed using Southern blotting and fluorescence in situ hybridization in a comparative study of 46 species of artiodactyls belonging to seven of the eight extant taxonomic families. Two of the repeats, the dispersed bovine-Pst family and the localized 1.715 component, were found to have the broadest taxonomic distributions, being present in all pecoran ruminants (Giraffidae, Cervidae, Antilocapridae, and Bovidae), indicating that these repeats may be 25-40 million years old. Different 1.715 restriction patterns were observed in different taxonomic families, indicating that independent concerted evolution events have homogenized different motifs in different lineages. The other four satellite arrays were restricted to the Bovini and sometimes to the related Boselaphini and Tragelaphini. Results reveal that among the two compound satellites studied, the two components of the 1.711a originated simultaneously, whereas the two components of the 1.711b originated at two different historical times, perhaps as many as 15 million years apart. Systematic conclusions support the monophyly of the infraorder Pecora, the monophyly of the subfamily Bovinae (containing the Boselaphini, Bovini, and Tragelaphini), an inability to resolve any interrelationships among the other tribes of bovids, paraphyly of the genus Bos with respect to Bison, and a lack of molecular variation among two morphologically and ecologically distinct subspecies of African buffaloes (Syncerus caffer cafer and S. c. nanus). Cytogenetically, a reduction in diploid chromosome numbers through centric fusion in derived karyotypes is accompanied by a loss of centromeric satellite DNA. The nilgai karyotype contains an apparent dicentric chromosome as evidenced by the sites of 1.715 hybridization. Telomeric sequences have been translocated to the centromeres without concomitant chromosomal rearrangement in Thompson's gazelle. JF - Journal of molecular evolution AU - Modi, W S AU - Gallagher, D S AU - Womack, J E AD - Biological Carcinogenesis and Development Program, SAIC Frederick, National Cancer Institute-FCRDC, Frederick, MD 21702-1201 USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 337 EP - 349 VL - 42 IS - 3 SN - 0022-2844, 0022-2844 KW - DNA, Satellite KW - 0 KW - Index Medicus KW - Phylogeny KW - Karyotyping KW - Animals KW - Base Sequence KW - Cells, Cultured KW - Blotting, Southern KW - Molecular Sequence Data KW - In Situ Hybridization, Fluorescence KW - Species Specificity KW - Fibroblasts KW - DNA, Satellite -- genetics KW - Repetitive Sequences, Nucleic Acid -- genetics KW - Artiodactyla -- genetics KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78216439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+evolution&rft.atitle=Evolutionary+histories+of+highly+repeated+DNA+families+among+the+Artiodactyla+%28Mammalia%29.&rft.au=Modi%2C+W+S%3BGallagher%2C+D+S%3BWomack%2C+J+E&rft.aulast=Modi&rft.aufirst=W&rft.date=1996-03-01&rft.volume=42&rft.issue=3&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-27 N1 - Date created - 1996-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A new reagent for the induction of T-cell depletion, anti-CD3-CRM9. AN - 78191827; 8732691 AB - We have developed a new reagent for inducing in vivo T-cell depletion and have tested this reagent in rhesus monkeys. The reagent is an anti-CD3 epsilon immunotoxin based on a diphtheria toxin binding-site mutant, CRM9. After administration to monkeys, T cells are depleted from both the blood and lymph node compartments to 30 days in old animals. The correlation between repopulation rate and age suggests that the repopulation is thymus dependent and that the repopulated T cells are probably naive T cells. This reagent should be a valuable tool in studying the role of memory T cells in rhesus models of autoimmune diseases and protocols of tolerance induction after organ transplantation. JF - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy AU - Neville, D M AU - Scharff, J AU - Hu, H Z AU - Rigaut, K AU - Shiloach, J AU - Slingerland, W AU - Jonker, M AD - Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4034, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 85 EP - 92 VL - 19 IS - 2 SN - 1067-5582, 1067-5582 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD3 KW - Antitoxins KW - Diphtheria Toxin KW - Immunotoxins KW - Indicators and Reagents KW - Index Medicus KW - Animals KW - Humans KW - Graft Survival -- immunology KW - Macaca mulatta KW - Protein Binding -- immunology KW - Antitoxins -- biosynthesis KW - Lymphocyte Activation -- drug effects KW - Antigens, CD3 -- immunology KW - Diphtheria Toxin -- immunology KW - Lymphocyte Depletion -- methods KW - T-Lymphocytes -- drug effects KW - Antibodies, Monoclonal -- pharmacology KW - Immunotoxins -- pharmacology KW - Diphtheria Toxin -- genetics KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78191827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=A+new+reagent+for+the+induction+of+T-cell+depletion%2C+anti-CD3-CRM9.&rft.au=Neville%2C+D+M%3BScharff%2C+J%3BHu%2C+H+Z%3BRigaut%2C+K%3BShiloach%2C+J%3BSlingerland%2C+W%3BJonker%2C+M&rft.aulast=Neville&rft.aufirst=D&rft.date=1996-03-01&rft.volume=19&rft.issue=2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-14 N1 - Date created - 1997-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuropathies in HIV infection. AN - 78186991; 8732208 AB - Peripheral neuropathies represent the most common neurological manifestation in patients infected with HIV infection occurring either early in the infection or during the course of the illness. They present as acute or chronic demyelinating neuropathies (Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy), mononeuritis multiplex, ganglioneuronitis, cytomegalovirus-related polyradiculoneuropathy, autonomic neuropathy or distal painful sensory neuropathy. They are multifactorial in aetiology. Their putative cause (viral, autoimmune, toxic, nutritional, co-infections) are often dictated by the stage of the underlying HIV disease. The virus, which is not found within ganglionic neurones or Schwann cells but only within the endoneurial macrophages, may generate a tissue-specific autoimmune attack by secretion of cytokines that promote trafficking of activated T cells and macrophages within the endoneurial parenchyma. The wide use of the neurotoxic antiretroviral nucleoside analogues ddC, ddI, d4T and 3TC, exacerbate or trigger subclinical neuropathy in many of these patients. JF - Bailliere's clinical neurology AU - Dalakas, M C AU - Cupler, E J AD - National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD 20892, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 199 EP - 218 VL - 5 IS - 1 SN - 0961-0421, 0961-0421 KW - Immunoglobulins KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Immunoglobulins -- administration & dosage KW - Demyelinating Diseases -- complications KW - Injections, Intravenous KW - Humans KW - Plasmapheresis KW - Immunoglobulins -- therapeutic use KW - Polyradiculoneuropathy -- drug therapy KW - Polyradiculoneuropathy -- complications KW - Polyradiculoneuropathy -- therapy KW - HIV Seropositivity -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78186991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+neurology&rft.atitle=Neuropathies+in+HIV+infection.&rft.au=Dalakas%2C+M+C%3BCupler%2C+E+J&rft.aulast=Dalakas&rft.aufirst=M&rft.date=1996-03-01&rft.volume=5&rft.issue=1&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+neurology&rft.issn=09610421&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-23 N1 - Date created - 1996-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of chronic beta-amyloid treatment on fatty acid incorporation into rat brain. AN - 78175950; 8744412 AB - The present study evaluated the effects of chronic A beta administration on radio-labeled plasma fatty acid incorporation in rat brain. A beta was chronically infused intraventricularly via an osmotic minipump, for 1 week, at a concentration of 460 microM. After the infusion, fatty acid incorporation was quantified using an in vivo method developed in this laboratory. Three radiolabeled fatty acids were separately infused IV in awake animals. Biochemical analyses of fatty acid incorporation and histology for A beta showed no differences between control (vehicle infusion only) and experimental groups. However, in vitro tests on the cytotoxicity of A beta showed that it caused significant cell death relative to controls (PC-12 cells). The lack of effect of infused A beta on radiolabeled fatty acid incorporation is discussed. JF - Neurobiology of aging AU - Brining, S K AU - Jones, C R AU - Chang, M C AD - National Institutes of Health, National Institute on Aging, Bethesda, MD 20892-1582, USA. PY - 1996 SP - 301 EP - 309 VL - 17 IS - 2 SN - 0197-4580, 0197-4580 KW - Amyloid beta-Peptides KW - 0 KW - Drug Implants KW - Fatty Acids KW - Lipids KW - Index Medicus KW - Lipids -- blood KW - Animals KW - Humans KW - Cell Death -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Brain -- pathology KW - Immunohistochemistry KW - Lipid Metabolism KW - Male KW - PC12 Cells KW - Amyloid beta-Peptides -- metabolism KW - Brain Chemistry -- drug effects KW - Amyloid beta-Peptides -- toxicity KW - Amyloid beta-Peptides -- administration & dosage KW - Fatty Acids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78175950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+aging&rft.atitle=Effects+of+chronic+beta-amyloid+treatment+on+fatty+acid+incorporation+into+rat+brain.&rft.au=Brining%2C+S+K%3BJones%2C+C+R%3BChang%2C+M+C&rft.aulast=Brining&rft.aufirst=S&rft.date=1996-03-01&rft.volume=17&rft.issue=2&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+aging&rft.issn=01974580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microwave treatment enhances the immunostaining of amyloid deposits in both the transmissible and non-transmissible brain amyloidoses. AN - 78167564; 8731388 AB - The immunolocalization of amyloid deposits containing either protease-resistant prion protein (PrP) or amyloid beta protein (A beta) in the brains of patients with transmissible or non-transmissible cerebral amyloidoses has been greatly facilitated by the pretreatment of tissue sections with concentrated formic acid. We have investigated whether microwave processing of formalin-fixed tissue sections would obviate the need for formic acid pretreatment. Exposure of brain sections to microwaves, even for periods as brief as 1 sec, greatly enhanced the immunostaining of PrP and A beta amyloid deposits in both the transmissible and non-transmissible brain amyloidoses. Microwaving for 1 min yielded staining intensities similar to that following pretreatment with concentrated formic acid for 10 min. Moreover, the combination of formic acid pretreatment and microwave processing resulted in an even more intense staining of amyloid deposits. Microwave processing, which is easy to perform and comparatively inexpensive, makes exposure to the potentially toxic fumes of formic acid unnecessary. JF - Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration AU - Liberski, P P AU - Yanagihara, R AU - Brown, P AU - Kordek, R AU - Kloszewska, I AU - Bratosiewicz, J AU - Gajdusek, D C AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 95 EP - 99 VL - 5 IS - 1 SN - 1055-8330, 1055-8330 KW - Amyloid beta-Peptides KW - 0 KW - Antibodies, Monoclonal KW - Prions KW - Index Medicus KW - Sensitivity and Specificity KW - Histological Techniques KW - Animals KW - Humans KW - Mice KW - Creutzfeldt-Jakob Syndrome -- pathology KW - Prions -- analysis KW - Microwaves KW - Gerstmann-Straussler-Scheinker Disease -- pathology KW - Brain -- pathology KW - Kuru -- pathology KW - Immunohistochemistry -- methods KW - Amyloid beta-Peptides -- analysis KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78167564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurodegeneration+%3A+a+journal+for+neurodegenerative+disorders%2C+neuroprotection%2C+and+neuroregeneration&rft.atitle=Microwave+treatment+enhances+the+immunostaining+of+amyloid+deposits+in+both+the+transmissible+and+non-transmissible+brain+amyloidoses.&rft.au=Liberski%2C+P+P%3BYanagihara%2C+R%3BBrown%2C+P%3BKordek%2C+R%3BKloszewska%2C+I%3BBratosiewicz%2C+J%3BGajdusek%2C+D+C&rft.aulast=Liberski&rft.aufirst=P&rft.date=1996-03-01&rft.volume=5&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Neurodegeneration+%3A+a+journal+for+neurodegenerative+disorders%2C+neuroprotection%2C+and+neuroregeneration&rft.issn=10558330&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-24 N1 - Date created - 1996-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Losses of arachidonic acid in rat liver after alcohol inhalation. AN - 78166438; 8729111 AB - This paper presents an animal model of alcoholism in which rats were exposed to alcohol by inhalation and were fed a diet that simulated the poor diet of some alcoholics. It is hypothesized that some of the pathophysiological effects of alcohol are related to its effects on essential fatty acid metabolism and composition of vital organs. A diet that contains no 20- and 22-carbon essential fatty acids and has low levels of 18-carbon essential fatty acids was used as a dietary challenge. Addition of a second metabolic challenge, i.e., alcohol, led to loss of tissue polyunsaturates, particularly liver arachidonate. A method of cycling alcohol inhalation for 12 h/d was also presented, which was also shown to lower liver arachidonic acid content. JF - Lipids AU - Salem, N AU - Reyzer, M AU - Karanian, J AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - S153 EP - S156 VL - 31 Suppl SN - 0024-4201, 0024-4201 KW - Dietary Fats, Unsaturated KW - 0 KW - Fatty Acids KW - Lipids KW - Olive Oil KW - Plant Oils KW - Arachidonic Acid KW - 27YG812J1I KW - Index Medicus KW - Rats KW - Lipids -- blood KW - Dietary Fats, Unsaturated -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Plant Oils -- pharmacology KW - Blood Platelets -- drug effects KW - Disease Models, Animal KW - Blood Platelets -- metabolism KW - Administration, Inhalation KW - Male KW - Fatty Acids -- analysis KW - Liver -- metabolism KW - Alcoholism -- metabolism KW - Arachidonic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78166438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lipids&rft.atitle=Losses+of+arachidonic+acid+in+rat+liver+after+alcohol+inhalation.&rft.au=Salem%2C+N%3BReyzer%2C+M%3BKaranian%2C+J&rft.aulast=Salem&rft.aufirst=N&rft.date=1996-03-01&rft.volume=31+Suppl&rft.issue=&rft.spage=S153&rft.isbn=&rft.btitle=&rft.title=Lipids&rft.issn=00244201&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-21 N1 - Date created - 1996-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Implications for risk assessment of suggested nongenotoxic mechanisms of chemical carcinogenesis. AN - 78140854; 8722116 AB - Nongenotoxic carcinogens are chemicals that induce neoplasia without it or its metabolites reacting directly with DNA. Chemicals classified as nongenotoxic carcinogens have been assumed to act as tumor promoters and exhibit threshold tumor dose-responses. This is in contrast to genotoxic carcinogens that are DNA reactive, act as tumor initiators, and are assumed to exhibit proportional responses at low doses. In this perspective, we examine the basic tenets and utility of this classification for evaluating human cancer risk. Two classes of so-called nongenotoxic chemical carcinogens selected for review include cytotoxic agents that induce regenerative hyperplasia (trihalomethanes and inducers of alpha 2-microglobulin nephropathy) and agents that act via receptor-mediated mechanisms (peroxisome proliferators and dioxin). Major conclusions of this review include: a) many chemicals considered to be nongenotoxic carcinogens actually possess certain genotoxic activities, and limiting evaluations of carcinogenicity to their nongenotoxic effects can be misleading; b) some nongenotoxic activities may cause oxidative DNA damage and thereby initiate carcinogenesis; c) although cell replication is involved in tumor development, cytotoxicity and mitogenesis do not reliably predict carcinogenesis; d) a threshold tumor response is not an inevitable result of a receptor-mediated mechanism. There are insufficient data on the chemicals reviewed here to justify treating their carcinogenic effects in animals as irrelevant for evaluating human risk. Research findings that characterize the multiple mechanisms of chemical carcinogenesis should be used quantitatively to clarify human dose-response relationships, leading to improved scientifically based public health decisions. Excessive reliance on oversimplified classification schemes that do not consider all potential contributing effects of a toxicant can obscure the actual causal relationships between exposure and cancer outcome. JF - Environmental health perspectives AU - Melnick, R L AU - Kohn, M C AU - Portier, C J AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 123 EP - 134 VL - 104 Suppl 1 SN - 0091-6765, 0091-6765 KW - Carcinogens, Environmental KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Index Medicus KW - Receptors, Aryl Hydrocarbon -- drug effects KW - Animals KW - Hyperplasia -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Humans KW - Carcinogenicity Tests KW - Risk Assessment KW - Carcinogens, Environmental -- adverse effects KW - Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78140854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Implications+for+risk+assessment+of+suggested+nongenotoxic+mechanisms+of+chemical+carcinogenesis.&rft.au=Melnick%2C+R+L%3BKohn%2C+M+C%3BPortier%2C+C+J&rft.aulast=Melnick&rft.aufirst=R&rft.date=1996-03-01&rft.volume=104+Suppl+1&rft.issue=&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-16 N1 - Date created - 1996-10-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nephron. 1981;28(3):133-40 [6170900] Food Cosmet Toxicol. 1981 Oct;19(5):567-76 [7030886] Cancer Res. 1982 Jan;42(1):259-66 [7053853] Annu Rev Pharmacol Toxicol. 1982;22:517-54 [6282188] Toxicol Lett. 1982 May;11(3-4):243-52 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[7681523] Mutat Res. 1993 Apr;286(2):135-44 [7681524] Carcinogenesis. 1993 Apr;14(4):611-8 [8472324] J Natl Cancer Inst. 1993 May 19;85(10):817-22 [8487327] Biochemistry. 1993 Jun 1;32(21):5598-604 [7684926] Biochimie. 1993;75(3-4):251-6 [8389594] Carcinogenesis. 1993 Jun;14(6):1229-31 [8099540] Toxicol Appl Pharmacol. 1993 May;120(1):138-54 [8511776] Cancer Res. 1993 Sep 1;53(17):3919-24 [8358718] Toxicol Ind Health. 1993 May-Jun;9(3):415-38 [8367884] Carcinogenesis. 1993 Sep;14(9):1885-93 [8403215] Risk Anal. 1993 Oct;13(5):565-72 [8259447] Cancer Res. 1994 Jan 1;54(1):62-8 [8261464] Carcinogenesis. 1993 Dec;14(12):2495-9 [8269617] Carcinogenesis. 1994 Jan;15(1):5-9 [8293548] Chem Res Toxicol. 1993 Nov-Dec;6(6):754-63 [8117913] Carcinogenesis. 1994 Mar;15(3):529-32 [8118938] Fundam Appl Toxicol. 1994 Jan;22(1):90-102 [8125218] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1558-62 [2922399] Carcinogenesis. 1989 Mar;10(3):513-9 [2924396] Toxicology. 1989 May 31;56(1):1-7 [2728002] Fundam Appl Toxicol. 1991 May;16(4):749-62 [1715830] Crit Rev Biochem Mol Biol. 1991;26(2):129-50 [1914494] Toxicol Appl Pharmacol. 1991 Oct;111(1):99-106 [1949040] Environ Health Perspect. 1991 Aug;94:231-5 [1954932] Environ Health Perspect. 1993 Dec;101 Suppl 5:149-51 [8013403] Environ Health Perspect. 1993 Dec;101 Suppl 5:3-7 [7912189] Cancer Res. 1994 Jul 15;54(14):3864-7 [8033108] Fundam Appl Toxicol. 1994 Apr;22(3):431-46 [8050638] Carcinogenesis. 1994 Oct;15(10):2087-94 [7955037] Eur J Biochem. 1994 Nov 1;225(3):967-74 [7957233] Toxicology. 1994 Nov-Dec;94(1-3):3-18 [7801327] Risk Anal. 1994 Dec;14(6):993-1000 [7846331] Hum Exp Toxicol. 1994 Nov;13 Suppl 2:S1-117 [7857698] Toxicol Appl Pharmacol. 1995 Jun;132(2):237-44 [7540335] Nature. 1967 May 6;214(5088):618-20 [4962427] Cancer Res. 1973 Nov;33(11):2701-5 [4748431] Exp Mol Pathol. 1976 Feb;24(1):13-22 [1253933] Drug Metab Dispos. 1977 Mar-Apr;5(2):198-204 [15814] Food Cosmet Toxicol. 1977 Apr;15(2):93-6 [873409] Nature. 1980 Jan 24;283(5745):397-8 [6766207] Mutat Res. 1980 Jan;77(1):55-63 [6767185] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential regulation of basal and kindling-induced TRH mRNA expression by thyroid hormone in the hypothalamic and limbic structures. AN - 78104679; 8677019 AB - It has previously been demonstrated that thyrotropin-releasing hormone (TRH) mRNA expression is dramatically increased in limbic structures including dentate gyrus granular layer, and pyriform, entorhinal and perirhinal cortices following amygdala kindling. Since thyroid hormone regulates TRH mRNA in the paraventricular nucleus of the hypothalamus (PVN), we investigated whether basal or kindling-induced TRH mRNA expression in limbic regions is also regulated by thyroid hormone. Hypo- and hyperthyroidism was induced by treating rats with 0.05% 6-n-propyl-2-thiouracil (PTU) (equivalent to approximately 30 mg/kg/day) or 0.9 microM 3,5,3'-triiodo-L-thyronine (T3) (equivalent to approximately 50 micrograms/kg/day), respectively, in their drinking water for 10 days before kindling and throughout the kindling procedure. Rats were sacrificed 4 h after their first stage 5 seizure. None of the thyroid hormone manipulations altered kindling development, or behavioral and electrographic after-discharge seizure durations. Pituitary TSH beta mRNA levels were significantly increased by PTU and suppressed by T3, but unaffected by kindling. In addition, in situ hybridization showed that PTU administration increased and T3 administration decreased TRH mRNA levels in the PVN, consistent with thyroid hormone's negative feedback effects. At the same time, kindling had no effect on TRH mRNA in the PVN. In contrast, kindling dramatically increased TRH mRNA in the dentate gyrus granular layer, and pyriform, entorhinal and perirhinal cortices, but thyroid hormone manipulations did not affect either basal or kindling-induced TRH mRNA expression in limbic structures. These findings demonstrate that TRH mRNA expression is differentially regulated in the hypothalamic PVN and limbic structures. JF - Neuroendocrinology AU - Kim, S Y AU - Post, R M AU - Rosen, J B AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Md., USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 297 EP - 304 VL - 63 IS - 3 SN - 0028-3835, 0028-3835 KW - RNA, Messenger KW - 0 KW - Triiodothyronine KW - 06LU7C9H1V KW - Thyrotropin-Releasing Hormone KW - 5Y5F15120W KW - Propylthiouracil KW - 721M9407IY KW - Thyrotropin KW - 9002-71-5 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Hypothyroidism -- metabolism KW - Hyperthyroidism -- metabolism KW - Hypothyroidism -- chemically induced KW - Hyperthyroidism -- chemically induced KW - Rats KW - Rats, Sprague-Dawley KW - Base Sequence KW - Thyrotropin -- genetics KW - Molecular Sequence Data KW - Amygdala -- physiology KW - Male KW - Triiodothyronine -- pharmacology KW - RNA, Messenger -- metabolism KW - Limbic System -- metabolism KW - Triiodothyronine -- blood KW - Kindling, Neurologic KW - Thyrotropin-Releasing Hormone -- genetics KW - Hypothalamus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78104679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroendocrinology&rft.atitle=Differential+regulation+of+basal+and+kindling-induced+TRH+mRNA+expression+by+thyroid+hormone+in+the+hypothalamic+and+limbic+structures.&rft.au=Kim%2C+S+Y%3BPost%2C+R+M%3BRosen%2C+J+B&rft.aulast=Kim&rft.aufirst=S&rft.date=1996-03-01&rft.volume=63&rft.issue=3&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Neuroendocrinology&rft.issn=00283835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-12 N1 - Date created - 1996-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of natural killer cells with MHC class II: reversal of HLA-DR1-mediated protection of K562 transfectant from natural killer cell-mediated cytolysis by brefeldin-A. AN - 78090677; 8778037 AB - Major histocompatibility complex (MHC) class I antigens on tumour cell surfaces have been shown to modulate target susceptibility to natural killer (NK) cell-mediated lysis in some, although not all, systems investigated. MHC class II expression may also affect NK cell function, but the mechanism by which MHC class II antigen regulates NK cell activity has not been fully examined. In this study we induced HLA-DR1 expression by gene transfection into the classic NK-sensitive K562 cell line to study the interaction of NK cells with MHC class II molecules and the effect of brefeldin-A (BFA), an endogenous antigen-processing pathway blocker, on NK-target cell interaction. We demonstrated that the expression of HLA-DR1 on the cell surface reduced K562 cell susceptibility to NK lysis by peripheral blood monuclear cells and a NK cell line. The effect was demonstrable in prolonged (8 hr) cytotoxicity assays and was blocked by pretreatment of target cells with anti-HLA-DR antibody. Treatment of K562 DR transfectant with BFA abrogated the resistance of K562 transfectant to NK-mediated cytolysis. These findings indicate that HLA class II molecules regulate NK cell function and target recognition, and suggest that endogenous peptides presented through MHC molecules are responsible for regulating NK cytolysis. JF - Immunology AU - Jiang, Y Z AU - Couriel, D AU - Mavroudis, D A AU - Lewalle, P AU - Malkovska, V AU - Hensel, N F AU - Dermime, S AU - Molldrem, J AU - Barrett, A J AD - Bone Marrow Transplantation Unit, National Institutes of Health, Bethesda, MD 20892-1652, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 481 EP - 486 VL - 87 IS - 3 SN - 0019-2805, 0019-2805 KW - Cyclopentanes KW - 0 KW - HLA-DR Antigens KW - Histocompatibility Antigens Class II KW - Protein Synthesis Inhibitors KW - Brefeldin A KW - 20350-15-6 KW - Index Medicus KW - HLA-DR Antigens -- immunology KW - Tumor Cells, Cultured -- immunology KW - Humans KW - Killer Cells, Lymphokine-Activated -- immunology KW - Cytotoxicity Tests, Immunologic KW - Cyclopentanes -- pharmacology KW - Protein Synthesis Inhibitors -- pharmacology KW - Histocompatibility Antigens Class II -- immunology KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78090677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology&rft.atitle=Interaction+of+natural+killer+cells+with+MHC+class+II%3A+reversal+of+HLA-DR1-mediated+protection+of+K562+transfectant+from+natural+killer+cell-mediated+cytolysis+by+brefeldin-A.&rft.au=Jiang%2C+Y+Z%3BCouriel%2C+D%3BMavroudis%2C+D+A%3BLewalle%2C+P%3BMalkovska%2C+V%3BHensel%2C+N+F%3BDermime%2C+S%3BMolldrem%2C+J%3BBarrett%2C+A+J&rft.aulast=Jiang&rft.aufirst=Y&rft.date=1996-03-01&rft.volume=87&rft.issue=3&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Immunology&rft.issn=00192805&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-16 N1 - Date created - 1996-09-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunol Rev. 1979;44:43-70 [761939] J Immunol. 1988 Jun 1;140(11):3712-6 [3259596] J Immunol. 1994 May 15;152(10):4852-60 [8176208] J Exp Med. 1994 Aug 1;180(2):537-43 [8046332] Immunology. 1994 Oct;83(2):240-4 [7835941] Science. 1995 Feb 17;267(5200):1016-8 [7863326] J Immunol. 1995 Mar 15;154(6):2631-41 [7876538] J Clin Invest. 1989 Jan;83(1):278-87 [2463268] J Immunol. 1989 Mar 15;142(6):2140-7 [2493507] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2361-4 [2784569] Eur J Immunol. 1989 Mar;19(3):447-51 [2707298] Nature. 1990 Jan 4;343(6253):74-6 [1967486] Immunol Today. 1990 Jul;11(7):237-44 [2201309] Hum Immunol. 1991 Aug;31(4):229-35 [1655683] Nature. 1991 Oct 17;353(6345):622-7 [1656276] J Immunol. 1992 Apr 1;148(7):2307-13 [1545133] Annu Rev Immunol. 1992;10:189-213 [1590985] Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8337-41 [1325654] J Exp Med. 1993 Aug 1;178(2):597-604 [8340759] Hum Immunol. 1993 Aug;37(4):264-70 [8300411] Science. 1985 Dec 20;230(4732):1398-401 [3906897] Annu Rev Immunol. 1986;4:651-80 [3518752] J Biol Chem. 1986 Aug 25;261(24):11398-403 [2426273] Proc Natl Acad Sci U S A. 1986 Aug;83(15):5688-92 [2426704] J Immunol. 1987 Mar 15;138(6):1657-9 [3819393] Nature. 1981 Aug 27;292(5826):848-50 [7266653] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of the mammalian stress response gene GADD153 by oxidative stress: role of AP-1 element. AN - 78079559; 8670069 AB - GADD153 is a CCAAT/enhancer-binding-protein-related gene that may function to control cellular growth in response to stress signals. In this study, a variety of oxidant treatments were shown to stimulate endogenous GADD153 mRNA expression and to transcriptionally activate a GADD153 promoter-reporter gene construct in transfected HeLa cells. Both commonalities and distinctions in the induction of GADD153 by H2O2 and the thiol-reactive compound arsenite were demonstrated. GADD153 mRNA induction by both H2O2 and arsenite was potentiated by GSH depletion, and completely inhibited by N-acetyl-cysteine. o-Phenanthroline and mannitol blocked GADD153 induction by H2O2, indicating that iron-generated hydroxyl radical mediates this induction. Concordantly, GSH peroxidase overexpression in WI38 cells attenuated GADD153 mRNA induction by H2O2. However, GADD153 induction by arsenite was only modestly reduced in the same cells, suggesting a lesser contribution of peroxides to gene activation by arsenite. We also demonstrated that oxidative stress participates in the induction of GADD153 by UVC (254 nm) irradiation. Finally, both promoter-deletion analysis and point mutation of the AP-1 site in an otherwise intact promoter support a significant role for AP-1 in transcriptional activation of GADD153 by UVC or oxidant treatment. Indeed, exposure of cells to oxidants or UVC stimulated binding of Fos and Jun to the GADD153 AP-1 element. Together, these results demonstrate that both free-radical generation and thiol modification can transcriptionally activate GADD153, and that AP-1 is critical to oxidative regulation of this gene. This study further supports a role for the GADD153 gene product in the cellular response to oxidant injury. JF - The Biochemical journal AU - Guyton, K Z AU - Xu, Q AU - Holbrook, N J AD - Section on Gene Expression and Aging, Gerontoloy Research Center, National Institute on Aging, Baltimore, MD 21224, USA. Y1 - 1996/03/01/ PY - 1996 DA - 1996 Mar 01 SP - 547 EP - 554 VL - 314 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Arsenites KW - 0 KW - CCAAT-Enhancer-Binding Proteins KW - DDIT3 protein, human KW - DNA-Binding Proteins KW - Oligodeoxyribonucleotides KW - Oxidants KW - RNA, Messenger KW - Sulfhydryl Compounds KW - Transcription Factor AP-1 KW - Transcription Factors KW - Transcription Factor CHOP KW - 147336-12-7 KW - Hydrogen Peroxide KW - BBX060AN9V KW - arsenite KW - N5509X556J KW - Index Medicus KW - Ultraviolet Rays KW - Arsenites -- pharmacology KW - Oxidants -- pharmacology KW - Sulfhydryl Compounds -- metabolism KW - HeLa Cells KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - RNA, Messenger -- genetics KW - Transcriptional Activation KW - Base Sequence KW - Promoter Regions, Genetic KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Transcription Factor AP-1 -- metabolism KW - Oxidative Stress KW - DNA-Binding Proteins -- genetics KW - Gene Expression Regulation KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78079559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Induction+of+the+mammalian+stress+response+gene+GADD153+by+oxidative+stress%3A+role+of+AP-1+element.&rft.au=Guyton%2C+K+Z%3BXu%2C+Q%3BHolbrook%2C+N+J&rft.aulast=Guyton&rft.aufirst=K&rft.date=1996-03-01&rft.volume=314+%28+Pt+2%29&rft.issue=&rft.spage=547&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-05 N1 - Date created - 1996-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1992 Oct 25;267(30):21894-900 [1400499] J Gerontol. 1956 Jul;11(3):298-300 [13332224] Cell. 1992 Dec 24;71(7):1081-91 [1473146] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] Mol Cell Biol. 1987 Jul;7(7):2610-3 [3475568] Photochem Photobiol. 1987 Aug;46(2):213-21 [3628510] Mol Cell Biol. 1989 Oct;9(10):4196-203 [2573827] Toxicol Appl Pharmacol. 1991 Apr;108(2):205-13 [2017750] Cell. 1991 Nov 29;67(5):837-9 [1659949] Cancer Res. 1992 Jan 1;52(1):5-10 [1727386] J Biol Chem. 1991 Dec 25;266(36):24398-403 [1761541] Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):668-72 [1731339] Pharmacol Ther. 1991;51(2):155-94 [1784629] J Biol Chem. 1992 Apr 25;267(12):8207-12 [1569075] J Biol Chem. 1992 Jun 5;267(16):11366-73 [1597467] Gene. 1992 Jul 15;116(2):259-67 [1339368] J Biol Chem. 1992 Jul 25;267(21):15097-104 [1340765] J Biol Chem. 1992 Oct 5;267(28):20465-70 [1400365] Science. 1993 Jan 15;259(5093):381-4 [7678352] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2965-9 [8385353] EMBO J. 1993 May;12(5):2005-15 [8491191] Mol Cell Biol. 1993 Aug;13(8):4736-44 [8336711] J Biol Chem. 1993 Dec 25;268(36):26904-10 [8262924] Biotechnology (N Y). 1994 Jan;12(1):37-40 [7764323] Chem Res Toxicol. 1993 Sep-Oct;6(5):598-602 [8292735] Genes Dev. 1994 Feb 15;8(4):453-64 [8125258] Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1672-6 [8127864] Mol Cell Biol. 1994 Apr;14(4):2361-71 [8139541] J Biol Chem. 1994 Jun 3;269(22):15488-92 [7515058] J Biol Chem. 1994 Jun 17;269(24):16638-42 [7515881] J Cell Biol. 1994 Aug;126(4):1079-88 [8051207] Mol Cell Biol. 1994 Sep;14(9):5997-6003 [8065332] J Biol Chem. 1994 Oct 21;269(42):26512-7 [7929374] Bioessays. 1994 Jul;16(7):497-502 [7945278] Mutat Res. 1992 Dec 16;284(2):215-21 [1281272] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Staurosporine induces a sequential program of mouse keratinocyte terminal differentiation through activation of PKC isozymes. AN - 78076702; 8648181 AB - Staurosporine (stsp) induces assembly of cornified envelopes in mouse keratinocyte cultures. To clarify whether this effect is the consequence of a coordinated differentiation program similar to that observed in epidermis, we assessed the expression of multiple differentiation-specific markers in stsp-treated keratinocytes. In medium containing 0.05 mM Ca2+, in which the basal cell phenotype is normally maintained, stsp induced dose-dependent increases in keratin 1, epidermal and keratinocyte transglutaminases, SPR-1, loricrin, and profilaggrin mRNA. Based on nuclear run-on analysis, stsp-mediated marker expression was found to be due at least in part to increased transcription. Since protein kinase C (PKC) activation is required for keratinocyte differentiation, we tested whether stsp influenced this signaling pathway. Stsp induced the translocation of multiple PKC isoforms from the cytosol to membrane and/or cytoskeletal fractions, inducing isozyme downregulation within 24 h. Moreover, AP-1 DNA binding activity was elevated in stsp-treated keratinocytes, consistent with the notion that this agent influences keratinocyte-specific gene expression via the PKC pathway. Stsp-mediated marker expression was inhibited by the PKC inhibitor GF 109203X. In cells pre-treated with bryostatin 1 to selectively down-modulate specific PKC isoforms, stsp-induced loricrin, filaggrin, and SPR-1 expression was suppressed when PKC alpha, epsilon, and/or delta were downregulated, suggesting that these isozymes may be necessary for marker expression in response to this agent. Thus, in addition to its effects on cornified envelope assembly, stsp induces a coordinate program of differentiation-specific keratinocyte gene expression that is mediated at least in part by the PKC signaling pathway. JF - The Journal of investigative dermatology AU - Stanwell, C AU - Denning, M F AU - Rutberg, S E AU - Cheng, C AU - Yuspa, S H AU - Dlugosz, A A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 482 EP - 489 VL - 106 IS - 3 SN - 0022-202X, 0022-202X KW - Alkaloids KW - 0 KW - DNA Primers KW - Enzyme Inhibitors KW - Isoenzymes KW - RNA, Messenger KW - Transcription Factor AP-1 KW - Transglutaminases KW - EC 2.3.2.13 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Transglutaminases -- genetics KW - Transcription Factor AP-1 -- metabolism KW - DNA Primers -- genetics KW - Calcium -- pharmacology KW - Mice KW - RNA, Messenger -- genetics KW - Biological Transport, Active -- drug effects KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Enzyme Activation -- drug effects KW - Molecular Sequence Data KW - Cell Differentiation -- drug effects KW - Down-Regulation -- drug effects KW - Signal Transduction KW - Protein Kinase C -- metabolism KW - Isoenzymes -- antagonists & inhibitors KW - Protein Kinase C -- antagonists & inhibitors KW - Keratinocytes -- enzymology KW - Keratinocytes -- drug effects KW - Keratinocytes -- cytology KW - Enzyme Inhibitors -- pharmacology KW - Alkaloids -- pharmacology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78076702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Staurosporine+induces+a+sequential+program+of+mouse+keratinocyte+terminal+differentiation+through+activation+of+PKC+isozymes.&rft.au=Stanwell%2C+C%3BDenning%2C+M+F%3BRutberg%2C+S+E%3BCheng%2C+C%3BYuspa%2C+S+H%3BDlugosz%2C+A+A&rft.aulast=Stanwell&rft.aufirst=C&rft.date=1996-03-01&rft.volume=106&rft.issue=3&rft.spage=482&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-25 N1 - Date created - 1996-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Utilization of an alternative open reading frame of a normal gene in generating a novel human cancer antigen. AN - 78056643; 8642255 AB - Tumor infiltrating lymphocytes (TILs) derived from tumor-bearing patients recognize tumor-associated antigens presented by major histocompatibility complex (MHC) class I molecules. The infusion of TIL586 along with interleukin (IL) 2 into an autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was recently isolated and shown to encode gp75. Here we report that an antigenic peptide, MSLQRQFLR, recognized by TIL586 was not derived from the normal gp75 protein. Instead, this nonamer peptide resulted from translation of an alternative open reading frame of the same gene. Thus, the gp75 gene encodes two completely different polypeptides, gp75 as an antigen recognized by immunoglobulin G antibodies in sera from a patient with cancer, and a 24-amino acid product as a tumor rejection antigen recognized by T cells. This represents the first demonstration that a human tumor rejection antigen can be generated from a normal cellular gene using an open reading frame other than that used to encode the normal protein. These findings revealed a novel mechanism for generating tumor antigens, which may be useful as vaccines to induce tumor-specific cell-mediated immunity against cancer. JF - The Journal of experimental medicine AU - Wang, R F AU - Parkhurst, M R AU - Kawakami, Y AU - Robbins, P F AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/03/01/ PY - 1996 DA - 1996 Mar 01 SP - 1131 EP - 1140 VL - 183 IS - 3 SN - 0022-1007, 0022-1007 KW - Antigens, Neoplasm KW - 0 KW - DNA Primers KW - Histocompatibility Antigens Class I KW - Interleukin-2 KW - Membrane Glycoproteins KW - Peptide Fragments KW - Proteins KW - Recombinant Proteins KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Oxidoreductases KW - EC 1.- KW - TYRP1 protein, human KW - EC 1.14.18.- KW - tyrosinase-related protein-1 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Amino Acid Sequence KW - Proteins -- genetics KW - Peptide Fragments -- chemical synthesis KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Cytotoxicity, Immunologic KW - Base Sequence KW - Granulocyte-Macrophage Colony-Stimulating Factor -- biosynthesis KW - Peptide Fragments -- chemistry KW - Tumor Cells, Cultured KW - Transfection KW - Peptide Fragments -- pharmacology KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Cell Line KW - Protein Biosynthesis KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Melanoma -- genetics KW - Alternative Splicing KW - Open Reading Frames KW - Interleukin-2 -- therapeutic use KW - Antigens, Neoplasm -- biosynthesis KW - Histocompatibility Antigens Class I -- immunology KW - Melanoma -- therapy KW - Antigens, Neoplasm -- genetics KW - Melanoma -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78056643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Utilization+of+an+alternative+open+reading+frame+of+a+normal+gene+in+generating+a+novel+human+cancer+antigen.&rft.au=Wang%2C+R+F%3BParkhurst%2C+M+R%3BKawakami%2C+Y%3BRobbins%2C+P+F%3BRosenberg%2C+S+A&rft.aulast=Wang&rft.aufirst=R&rft.date=1996-03-01&rft.volume=183&rft.issue=3&rft.spage=1131&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1983 Jun;43(6):2773-9 [6850592] Cancer J Sci Am. 1995 Jul-Aug;1(2):90-100 [9166458] Int J Cancer. 1983 Dec 15;32(6):717-21 [6197381] J Invest Dermatol. 1985 Aug;85(2):169-74 [3926906] J Invest Dermatol. 1988 Apr;90(4):459-66 [3280698] J Clin Oncol. 1988 May;6(5):839-53 [3259261] N Engl J Med. 1988 Dec 22;319(25):1676-80 [3264384] Immunogenetics. 1989;29(2):75-9 [2783681] J Cell Biol. 1989 Feb;108(2):229-41 [2645293] Proc Natl Acad Sci U S A. 1990 Jan;87(1):328-32 [2296589] J Exp Med. 1990 Apr 1;171(4):1375-80 [2324688] Cell. 1991 Nov 1;67(3):569-79 [1934061] Science. 1991 Dec 13;254(5038):1643-7 [1840703] Mol Cell Biol. 1992 Jan;12(1):207-19 [1729599] J Virol. 1993 Jun;67(6):3103-10 [8388490] J Exp Med. 1993 Aug 1;178(2):489-95 [8340755] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8219-23 [8367486] J Virol. 1994 Jan;68(1):170-6 [8254726] J Exp Med. 1994 Mar 1;179(3):1005-9 [8113668] J Exp Med. 1994 Mar 1;179(3):921-30 [8113684] Eur J Immunol. 1994 Mar;24(3):759-64 [8125142] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3487-9 [8170934] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] Science. 1994 Apr 29;264(5159):716-9 [7513441] Nature. 1994 Jun 2;369(6479):357 [8018207] Cancer Res. 1994 Jun 15;54(12):3124-6 [8205528] J Exp Med. 1994 Jul 1;180(1):1-4 [8006576] J Exp Med. 1994 Jul 1;180(1):347-52 [7516411] J Exp Med. 1994 Jul 1;180(1):35-42 [8006593] Annu Rev Immunol. 1994;12:337-65 [8011285] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 [8022805] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] Immunogenetics. 1994;40(3):238-41 [8039832] Nature. 1994 Oct 20;371(6499):662 [7935811] J Exp Med. 1995 Feb 1;181(2):799-804 [7836932] Biochimie. 1994;76(9):880-6 [7880905] Immunogenetics. 1995;41(4):178-228 [7890324] Immunity. 1995 Feb;2(2):167-75 [7895173] Cell. 1995 Dec 15;83(6):993-1000 [8521522] Proc Natl Acad Sci U S A. 1983 Aug;80(16):4879-83 [6308656] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Importance of low affinity Elf-1 sites in the regulation of lymphoid-specific inducible gene expression. AN - 78050455; 8642278 AB - Elf-1 is an Ets family transcription factor that regulates a number of inducible lymphoid-specific genes, including those encoding interleukin 3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and the IL-2 receptor (IL-2R) alpha chain. A minimal oligonucleotide spanning the IL-2R alpha Elf-1 site (-97/-84) bound Elf-1 poorly, but binding activity markedly increased when this oligonucleotide was multimerized or flanking sequences were added. This result is consistent with the requirement of accessory proteins for efficient Elf-1 binding, as has been demonstrated for the GM-CSF and IL-3 promoters. A binding site selection analysis revealed the optimal Elf-1 consensus motif to be A(A/t)(C/a)CCGGAAGT(A/S), which is similar to the consensus motif for the related Drosophila E74 protein. This minimal high affinity site could bind Elf-1 and functioned as a stronger transcription element than the -97/-84 IL-2R alpha oligonucleotide when cloned upstream of a heterologous promoter. In contrast, in the context of the IL-2R alpha promoter, conversion of the naturally occurring low affinity Elf-1 site to an optimal site decreased inducible activation of a reporter construct in Jurkat cells. This finding may be explained by the observation that another Ets family protein, ER GB/Fli-1, can efficiently bind only to the optimal site, and in this context, interferes with Elf-1 binding. Therefore, high affinity Elf-1 sites may lack sufficient binding specificity, whereas naturally occurring low affinity sites presumably favor the association of Elf-1 in the context of accessory proteins. These findings offer an explanation for the lack of optimal sites in any of the known Elf-1-regulated genes. JF - The Journal of experimental medicine AU - John, S AU - Marais, R AU - Child, R AU - Light, Y AU - Leonard, W J AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/01/ PY - 1996 DA - 1996 Mar 01 SP - 743 EP - 750 VL - 183 IS - 3 SN - 0022-1007, 0022-1007 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Interleukin-3 KW - Oligodeoxyribonucleotides KW - Receptors, Interleukin-2 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - HIV-1 -- genetics KW - Sequence Homology, Nucleic Acid KW - Interleukin-3 -- biosynthesis KW - Insects KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - HIV Long Terminal Repeat KW - Base Sequence KW - Granulocyte-Macrophage Colony-Stimulating Factor -- biosynthesis KW - Transfection KW - Molecular Sequence Data KW - HIV-2 -- genetics KW - Consensus Sequence KW - Drosophila KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - Lymphocytes -- immunology KW - Receptors, Interleukin-2 -- biosynthesis KW - Lymphocytes -- metabolism KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78050455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Importance+of+low+affinity+Elf-1+sites+in+the+regulation+of+lymphoid-specific+inducible+gene+expression.&rft.au=John%2C+S%3BMarais%2C+R%3BChild%2C+R%3BLight%2C+Y%3BLeonard%2C+W+J&rft.aulast=John&rft.aufirst=S&rft.date=1996-03-01&rft.volume=183&rft.issue=3&rft.spage=743&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1985 Dec;5(12):3610-6 [3915782] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] Nucleic Acids Res. 1990 Nov 11;18(21):6197-204 [2243767] Science. 1991 Aug 16;253(5021):762-8 [1876833] Nature. 1991 Dec 19-26;354(6354):531-4 [1722028] Mol Cell Biol. 1992 Jan;12(1):368-78 [1729611] Cell. 1992 Feb 7;68(3):597-612 [1339307] EMBO J. 1992 Jan;11(1):97-105 [1740119] J Biol Chem. 1994 Jul 8;269(27):18216-22 [7517940] Mol Cell Biol. 1994 Oct;14(10):6452-63 [7935370] Mol Cell Biol. 1995 Mar;15(3):1786-96 [7862168] Nucleic Acids Res. 1992 Feb 25;20(4):699-704 [1542566] Mol Cell Biol. 1992 Mar;12(3):1043-53 [1545787] J Exp Med. 1992 May 1;175(5):1391-9 [1569404] Genes Dev. 1992 Jun;6(6):975-90 [1592264] Trends Biochem Sci. 1992 Jul;17(7):251-6 [1502727] J Virol. 1992 Oct;66(10):5890-7 [1527846] EMBO J. 1992 Dec;11(12):4631-40 [1425594] Cell Growth Differ. 1992 Oct;3(10):705-13 [1445800] Eur J Biochem. 1993 Jan 15;211(1-2):7-18 [8425553] EMBO J. 1993 Mar;12(3):1169-78 [8458329] Nucleic Acids Res. 1992 Jan 25;20(2):376 [1311073] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1291-5 [1741383] Science. 1993 May 28;260(5112):1330-5 [8493578] J Virol. 1993 Sep;67(9):5522-8 [8350410] J Exp Med. 1993 Nov 1;178(5):1681-92 [8228815] Nucleic Acids Res. 1993 Nov 11;21(22):5184-91 [8255775] Mol Cell Biol. 1994 Jan;14(1):840-50 [8264651] Mol Cell Biol. 1994 Feb;14(2):1153-9 [8289796] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. AN - 78046478; 8642260 AB - A number of antigens recognized by tumor-reactive T cells have recently been identified. The antigens identified in mouse model systems appear, with one exception, to represent the products of mutated genes. In contrast, most of the antigens recognized by human tumor-reactive T cells reported to date appear to represent the products of non-mutated genes. Here we report the isolation of a cDNA clone encoding beta-catenin, which was shown to be recognized by the tumor-infiltrating lymphocyte (TIL) 1290, a HLA-A24 restricted melanoma-specific CTL line from patient 888. The cDNA clone, which was isolated from the autologous melanoma cDNA library, differed by a single base pair from the published beta-catenin sequence, resulting in a change from a serine to a phenylalanine residue at position 37. Normal tissues from this patient did not express the altered sequence, nor did 12 allogeneic melanomas, indicating that this represented a unique mutation in this patient's melanoma. A peptide corresponding to the sequence between amino acids 29 and 37 of the mutant gene product was identified as the T cell epitope recognized by TIL 1290. The observation that HLA-A24 binding peptides contain an aromatic or hydrophobic residue at position 9 suggested that the change at position 37 may have generated a peptide (SYLDSGIHF) which was capable of binding to HLA-A24, and a competitive binding assay confirmed this hypothesis. The beta-catenin protein has been shown previously to be involved in cell adhesion mediated through the cadherin family of cell surface adhesion molecules. The high frequency of mutations found in members of cellular adhesion complexes in a variety of cancers suggests that these molecules may play a role in development of the malignant phenotype. JF - The Journal of experimental medicine AU - Robbins, P F AU - El-Gamil, M AU - Li, Y F AU - Kawakami, Y AU - Loftus, D AU - Appella, E AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03/01/ PY - 1996 DA - 1996 Mar 01 SP - 1185 EP - 1192 VL - 183 IS - 3 SN - 0022-1007, 0022-1007 KW - CTNNB1 protein, human KW - 0 KW - Cadherins KW - Cytoskeletal Proteins KW - DNA Primers KW - DNA, Complementary KW - Peptides KW - Trans-Activators KW - beta Catenin KW - Index Medicus KW - Peptides -- chemical synthesis KW - Sequence Homology, Nucleic Acid KW - Humans KW - Organ Specificity KW - Amino Acid Sequence KW - Cloning, Molecular KW - Mutagenesis KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Kidney KW - Molecular Sequence Data KW - Peptides -- chemistry KW - Cadherins -- genetics KW - Cell Line KW - Sequence Deletion KW - Gene Library KW - Cytoskeletal Proteins -- biosynthesis KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Melanoma -- genetics KW - Point Mutation KW - Melanoma -- immunology KW - T-Lymphocytes -- immunology KW - Cytoskeletal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78046478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=A+mutated+beta-catenin+gene+encodes+a+melanoma-specific+antigen+recognized+by+tumor+infiltrating+lymphocytes.&rft.au=Robbins%2C+P+F%3BEl-Gamil%2C+M%3BLi%2C+Y+F%3BKawakami%2C+Y%3BLoftus%2C+D%3BAppella%2C+E%3BRosenberg%2C+S+A&rft.aulast=Robbins&rft.aufirst=P&rft.date=1996-03-01&rft.volume=183&rft.issue=3&rft.spage=1185&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - Z19054; GENBANK N1 - SuppNotes - Cited By: N Engl J Med. 1988 Dec 22;319(25):1676-80 [3264384] Science. 1995 Sep 1;269(5228):1281-4 [7652577] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] J Exp Med. 1991 Jun 1;173(6):1373-84 [1903428] Cell. 1991 Jul 12;66(1):107-19 [2070412] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124-8 [1946433] Science. 1991 Dec 13;254(5038):1643-7 [1840703] Immunogenetics. 1993;37(2):135-8 [8423052] Biochem Biophys Res Commun. 1993 Jun 30;193(3):897-904 [8323564] J Exp Med. 1993 Aug 1;178(2):489-95 [8340755] Curr Opin Cell Biol. 1993 Oct;5(5):797-805 [8240823] J Immunol. 1995 Nov 1;155(9):4307-12 [7594589] Science. 1993 Dec 10;262(5140):1734-7 [8259519] J Exp Med. 1994 Mar 1;179(3):921-30 [8113684] J Immunol. 1994 Apr 15;152(8):3913-24 [8144960] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] Cancer Res. 1994 Jun 15;54(12):3124-6 [8205528] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 [8022805] Cancer Res. 1994 Jul 15;54(14):3845-52 [8033105] J Cell Biol. 1994 Dec;127(5):1375-80 [7962096] J Immunol. 1995 Jan 15;154(2):685-93 [7529283] J Exp Med. 1995 Feb 1;181(2):799-804 [7836932] Mol Cell Biol. 1995 Mar;15(3):1175-81 [7862112] Immunity. 1995 Feb;2(2):167-75 [7895173] J Immunol. 1995 Jun 1;154(11):5944-50 [7751637] Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7976-80 [7644523] J Exp Med. 1995 Sep 1;182(3):689-98 [7544395] Cell. 1989 Jul 28;58(2):293-303 [2568889] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The chicken beta-globin gene promoter forms a novel "cinched" tetrahelical structure. AN - 78041876; 8617804 AB - We have previously shown that the G-rich sequence G16CG(GGT)2GG in the promoter region of the chicken beta-globin gene poses a formidable barrier to DNA synthesis in vitro (Woodford et al., 1994, J. Biol. Chem. 269, 27029-27035). The K+ requirement, template-strand specificity, template concentration independence, and involvement of Hoogsteen bonding suggested that the underlying basis of this new type of DNA synthesis arrest site might be an intrastrand tetrahelical structure. However, the arrest site lacks the four G-rich repeats that are a hallmark of previously described intramolecular tetraplexes and contains a number of noncanonical bases that would be expected to greatly destabilize such a structure. Here we report evidence for an unusual K+-dependent intrastrand "cinched" tetraplex. This structure has several unique features including the incorporation of bases other than guanine into the stem of the tetraplex, interaction between loop bases and bases in the flanking region, and base pairing between bases 3 and 5 of the tetrahelix-forming region to form a molecular "cinch." This finding extends the range of sequences capable of tetraplex formation as well as our appreciation of the conformational complexity of the chicken beta-globin promoter. JF - The Journal of biological chemistry AU - Howell, R M AU - Woodford, K J AU - Weitzmann, M N AU - Usdin, K AD - Section on Genomic Structure and Function, Laboratory of Biochemical Pharmacology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. Y1 - 1996/03/01/ PY - 1996 DA - 1996 Mar 01 SP - 5208 EP - 5214 VL - 271 IS - 9 SN - 0021-9258, 0021-9258 KW - Macromolecular Substances KW - 0 KW - Globins KW - 9004-22-2 KW - DNA KW - 9007-49-2 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Base Composition KW - Molecular Sequence Data KW - Potassium -- pharmacology KW - Plasmids KW - Promoter Regions, Genetic KW - Globins -- genetics KW - DNA -- chemistry KW - Repetitive Sequences, Nucleic Acid KW - Nucleic Acid Conformation KW - DNA -- biosynthesis KW - Chickens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78041876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+chicken+beta-globin+gene+promoter+forms+a+novel+%22cinched%22+tetrahelical+structure.&rft.au=Howell%2C+R+M%3BWoodford%2C+K+J%3BWeitzmann%2C+M+N%3BUsdin%2C+K&rft.aulast=Howell&rft.aufirst=R&rft.date=1996-03-01&rft.volume=271&rft.issue=9&rft.spage=5208&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-11 N1 - Date created - 1996-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of mdr1b gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro. AN - 78022076; 8631130 AB - Administration of 2-acetylaminofluorene (2-AAF) to rats increased mdr1b expression in Fischer, Wistar and Sprague-Dawley rat livers; however, the response was much smaller in Sprague-Dawley livers. To investigate the basis of this difference we further examined the regulation of the mdr1b gene in hepatocytes isolated from Fischer, Sprague-Dawley and Wistar rats. A time-dependent increase in basal expression of mdr1b but not mdr2 was observed in hepatocytes isolated from all three strains of rats. After 4 days in culture, a larger increase in mdr1b mRNA levels was observed in Fischer and Wistar rat hepatocytes (3.5- and 4.6-fold respectively) than Sprague-Dawley hepatocytes (2-fold). Treatment of primary hepatocytes with 2-AAF caused an induction of mdr1b expression that varied among the three strains. Notably, Sprague-Dawley hepatocytes were not responsive to 2-AAF. In contrast to the parent compound, the electrophilic metabolites N-hydroxy-2-acetylaminofluorene and N-acetoxy-2-acetylaminofluorene caused a dose-dependent induction of mdr1b expression in both Fischer and Sprague-Dawley hepatocytes, indicating that differences in the metabolic activation of 2-AAF between the strains may account for the differences in mdr1b by 2-AAF. Hepatocytes isolated from all three strains of rats showed an equivalent induction of mdr1b after treatment with cycloheximide. Nuclear run-on assays demonstrated that the increases in mdr1b expression with time in culture and after xenobiotic treatment were due to increased transcription. JF - Carcinogenesis AU - Hill, B A AU - Brown, P C AU - Preisegger, K H AU - Silverman, J A AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 451 EP - 457 VL - 17 IS - 3 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - P-Glycoprotein KW - Protein Synthesis Inhibitors KW - RNA, Messenger KW - Cycloheximide KW - 98600C0908 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - Index Medicus KW - Animals KW - 2-Acetylaminofluorene -- toxicity KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- metabolism KW - RNA, Messenger -- genetics KW - Rats KW - Protein Synthesis Inhibitors -- toxicity KW - Rats, Inbred F344 KW - Rats, Sprague-Dawley KW - RNA, Messenger -- metabolism KW - Cycloheximide -- toxicity KW - Rats, Wistar KW - Time Factors KW - Species Specificity KW - Male KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- metabolism KW - Liver -- drug effects KW - Liver -- metabolism KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78022076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Regulation+of+mdr1b+gene+expression+in+Fischer%2C+Wistar+and+Sprague-Dawley+rats+in+vivo+and+in+vitro.&rft.au=Hill%2C+B+A%3BBrown%2C+P+C%3BPreisegger%2C+K+H%3BSilverman%2C+J+A&rft.aulast=Hill&rft.aufirst=B&rft.date=1996-03-01&rft.volume=17&rft.issue=3&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-02 N1 - Date created - 1996-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine. AN - 78011661; 8622042 AB - We have observed a severe atypical neuropathy (SAN) in patients with small non-cleaved-cell (SNCL) and large-cell lymphoma (LCL) treated with intensive chemotherapy and hematopoietic colony-stimulating factors (CSFs). The present analysis was undertaken in an attempt to identify factors associated with the development of this syndrome. Fifty-four adult and pediatric patients consecutively treated according to the same chemotherapy protocol were included in the analysis. Low-risk patients received three cycles of cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate (CODOX-M) while in high-risk patients this drug combination was alternated with high-dose cytarabine (ara-C), etoposide, and ifosfamide (IVAC) for a total of four cycles. Twenty-eight patients received a CSF (granulocyte [G]- or granulocyte-macrophage [GM]-CSF), and 26 patients received no CSF. A statistical analysis, which included a logistic regression model, was undertaken to examine the importance of potential contributing factors to the development of SAN. SAN, which consisted of excruciating foot pain, usually associated with marked motor weakness, was observed in 12 patients. There was a highly significant association between the occurrence of this syndrome and the administration of CSFs, and an independent association with the cumulative dose of vincristine given in the first cycle of chemotherapy. Furthermore, the analysis suggested a synergistic effect between administration of the CSFs and vincristine in the genesis of this neuropathy. Our results indicate that CSFs can precipitate SAN when given in conjunction with vincristine. The development of SAN was associated most strongly with the cumulative dose of vincristine -- the size of individual doses and the number of doses given in cycle 1 were important to the extent that they influenced the cumulative dose. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Weintraub, M AU - Adde, M A AU - Venzon, D J AU - Shad, A T AU - Horak, I D AU - Neely, J E AU - Seibel, N L AU - Gootenberg, J AU - Arndt, C AU - Nieder, M L AU - Magrath, I T AD - Pediatric Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 935 EP - 940 VL - 14 IS - 3 SN - 0732-183X, 0732-183X KW - Cytarabine KW - 04079A1RDZ KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Ifosfamide KW - UM20QQM95Y KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Humans KW - Child KW - Doxorubicin -- administration & dosage KW - Cytarabine -- administration & dosage KW - Multivariate Analysis KW - Child, Preschool KW - Infant KW - Etoposide -- administration & dosage KW - Adult KW - Middle Aged KW - Adolescent KW - Methotrexate -- administration & dosage KW - Male KW - Female KW - Ifosfamide -- administration & dosage KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Vincristine -- adverse effects KW - Lymphoma, Large B-Cell, Diffuse -- drug therapy KW - Pain -- chemically induced KW - Vincristine -- administration & dosage KW - Foot Diseases -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Granulocyte-Macrophage Colony-Stimulating Factor -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Peripheral Nervous System Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78011661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Severe+atypical+neuropathy+associated+with+administration+of+hematopoietic+colony-stimulating+factors+and+vincristine.&rft.au=Weintraub%2C+M%3BAdde%2C+M+A%3BVenzon%2C+D+J%3BShad%2C+A+T%3BHorak%2C+I+D%3BNeely%2C+J+E%3BSeibel%2C+N+L%3BGootenberg%2C+J%3BArndt%2C+C%3BNieder%2C+M+L%3BMagrath%2C+I+T&rft.aulast=Weintraub&rft.aufirst=M&rft.date=1996-03-01&rft.volume=14&rft.issue=3&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early suppressive effects of chemotherapy and cytokine treatment on committed versus primitive haemopoietic progenitors in patient bone marrow. AN - 78005614; 8616014 AB - These studies investigated the effectiveness of in vivo administration of cytokines in ameliorating potential marrow damage induced by chemotherapy. Breast cancer patients received 5-fluorouracil, leucovorin, doxorubicin and cyclophosphamide (FLAC) followed by either GM-CSF, PIXY321, or no cytokine. Marrow was obtained before and after one or two cycles of FLAC once blood cell counts had recovered. Colony-forming units for granulocytes and macrophages (CFU-GM) were used to indicate the effect of therapy on recovery of committed progenitor cells responsible for early blood cell recovery. The frequency and number of CFU-GM in marrow obtained after FLAC + PIXY321 were significantly lower than in marrow obtained after FLAC+GM-CSF or FLAC without cytokine. CD34+ cell numbers were also reduced after FLAC + PIXY321. CFU-GM production in marrow long-term cultures (LTC) was used to assess the effect of therapy on primitive progenitors. After 5 weeks the number of CFU-GM in LTC of post-therapy marrow from all three treatment arms was < 15% of the number in pre-therapy LTC. Suppressive effects of FLAC on primitive progenitors were observed even when committed progenitors and CD34+ cells had recovered to pre-therapy levels. These results demonstrate that cytokine treatment did not ameliorate suppressive or toxic effects of FLAC on the functional integrity of the marrow. JF - British journal of haematology AU - Schwartz, G N AU - Hakim, F AU - Zujewski, J AU - Szabo, J M AU - Cepada, R AU - Riseberg, D AU - Warren, M K AU - Mackall, C L AU - Setzer, A AU - Noone, M AU - Cowan, K H AU - O'Shaughnessy, J AU - Gress, R E AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 537 EP - 547 VL - 92 IS - 3 SN - 0007-1048, 0007-1048 KW - Antigens, CD34 KW - 0 KW - Interleukin-3 KW - PIXY321 fusion protein, recombinant KW - Recombinant Fusion Proteins KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Bone Marrow -- pathology KW - Doxorubicin -- adverse effects KW - Humans KW - Granulocytes -- pathology KW - Leucovorin -- adverse effects KW - Cyclophosphamide -- adverse effects KW - Fluorouracil -- adverse effects KW - Macrophages -- pathology KW - Tumor Cells, Cultured KW - Breast Neoplasms -- pathology KW - Cohort Studies KW - Colony-Forming Units Assay KW - Hematopoietic Stem Cells -- pathology KW - Interleukin-3 -- pharmacology KW - Recombinant Fusion Proteins -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78005614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+haematology&rft.atitle=Early+suppressive+effects+of+chemotherapy+and+cytokine+treatment+on+committed+versus+primitive+haemopoietic+progenitors+in+patient+bone+marrow.&rft.au=Schwartz%2C+G+N%3BHakim%2C+F%3BZujewski%2C+J%3BSzabo%2C+J+M%3BCepada%2C+R%3BRiseberg%2C+D%3BWarren%2C+M+K%3BMackall%2C+C+L%3BSetzer%2C+A%3BNoone%2C+M%3BCowan%2C+K+H%3BO%27Shaughnessy%2C+J%3BGress%2C+R+E&rft.aulast=Schwartz&rft.aufirst=G&rft.date=1996-03-01&rft.volume=92&rft.issue=3&rft.spage=537&rft.isbn=&rft.btitle=&rft.title=British+journal+of+haematology&rft.issn=00071048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-10 N1 - Date created - 1996-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Compound 48/80-induced conjunctivitis in the mouse: kinetics, susceptibility, and mechanism. AN - 78001294; 8620098 AB - A mouse model of conjunctivitis has been developed by topical application of compound 48/80 (C48/80), an agent that triggers mast cell degranulation. We examined the responsiveness of C57BL/6, C3H/HeN, and ASW/J mouse strains to C48/80 stimulation, and of a mutant strain with mast cell depletion (WBB6F1/J and its sham control). Conjunctivae were collected and examined histopathologically at 15 min and 1,6,24,48 and 72 h after topical C48/80 administration. Conjunctival inflammation developed in all strains, although the severity varied. The conjunctivitis was characterized clinically by irritation, discharge, erythema, and chemosis. Pathology showed conjunctival infiltration with neutrophils, macrophages, CD4+ T lymphocytes, and a few eosinophils. Degranulation of mast cells and evacuation of goblet cells were also observed. Late-phase inflammatory reactions peaked 6-24 h after C48/80 administration and resolved by 48-72 h. WBB6F1/J mice had much less inflammation than their sham controls. In conclusion, topical C48/80 induced a conjunctival inflammatory response similar to allergen-induced conjunctivitis. The depletion of mast cells significantly reduced the inflammation. This model which consistently mimics the clinical signs and histopathological processes of allergic conjunctivitis in humans, is practical and reliable for the evaluation of new anti-allergic medications and for the investigation of conjunctival cellular responses in the allergic inflammatory cascade. JF - International archives of allergy and immunology AU - Li, Q AU - Luyo, D AU - Hikita, N AU - Whitcup, S M AU - Chan, C C AD - Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892-1858, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 277 EP - 285 VL - 109 IS - 3 SN - 1018-2438, 1018-2438 KW - p-Methoxy-N-methylphenethylamine KW - 4091-50-3 KW - Index Medicus KW - Animals KW - Mast Cells -- immunology KW - Disease Susceptibility KW - Cell Movement -- immunology KW - Disease Models, Animal KW - Mice KW - Cell Cycle -- immunology KW - Mice, Inbred A KW - Mice, Mutant Strains KW - Mast Cells -- pathology KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Female KW - p-Methoxy-N-methylphenethylamine -- toxicity KW - Conjunctivitis, Allergic -- pathology KW - Conjunctivitis, Allergic -- chemically induced KW - p-Methoxy-N-methylphenethylamine -- administration & dosage KW - Conjunctivitis, Allergic -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78001294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+archives+of+allergy+and+immunology&rft.atitle=Compound+48%2F80-induced+conjunctivitis+in+the+mouse%3A+kinetics%2C+susceptibility%2C+and+mechanism.&rft.au=Li%2C+Q%3BLuyo%2C+D%3BHikita%2C+N%3BWhitcup%2C+S+M%3BChan%2C+C+C&rft.aulast=Li&rft.aufirst=Q&rft.date=1996-03-01&rft.volume=109&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=International+archives+of+allergy+and+immunology&rft.issn=10182438&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-18 N1 - Date created - 1996-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. AN - 78001003; 8622041 AB - We have used identical treatment protocols for adults and children with small non-cleaved-cell lymphoma (SNCL) for many years and report here the results of two successive treatment regimens in these age groups. Seventy-two patients (39 adults and 33 children) were treated with protocol 77-04 between 1977 and 1985. All patients, except those with resected abdominal disease, received 15 cycles of a combination of cyclophosphamide (CTX), doxorubicin (ADR), prednisone (PRED), vincristine (VCR), high-dose methotrexate (MTX), and intrathecal (IT) therapy. Forty-one patients (20 adults and 21 children) were treated with protocol 89-C-41, which has been used since 1989. High-risk patients received four alternating cycles (with a total duration of 12 to 15 weeks) of an intensified version of protocol 77-04 without PRED (CODOX-M), and a new drug combination consisting of ifosfamide, etoposide, high-dose cytarabine (ara-C), and IT MTX (IVAC). Low-risk patients received three cycles of the CODOX-M regimen. High-risk patients were randomized to either receive or not receive granulocyte-macrophage colony-stimulating factor (GM-CSF). Event-free survival (EFS) in protocol 77-04 was 56% at 2 years and beyond. EFS in protocol 89-C-41 was 92% at 2 years and beyond. GM-CSF was associated with increased thrombocytopenia. Adults and children with SNCL have a similar prognosis when treated with the same chemotherapy. EFS in high-risk patients has been markedly improved by including IVAC in protocol 89-C-41, and excellent results can be achieved with only four cycles of therapy. In protocol 89-C-41, GM-CSF was not beneficial. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Magrath, I AU - Adde, M AU - Shad, A AU - Venzon, D AU - Seibel, N AU - Gootenberg, J AU - Neely, J AU - Arndt, C AU - Nieder, M AU - Jaffe, E AU - Wittes, R A AU - Horak, I D AD - Pediatric Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 925 EP - 934 VL - 14 IS - 3 SN - 0732-183X, 0732-183X KW - Cytarabine KW - 04079A1RDZ KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Ifosfamide KW - UM20QQM95Y KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Age Factors KW - Humans KW - Vincristine -- administration & dosage KW - Neutropenia -- chemically induced KW - Child KW - Doxorubicin -- administration & dosage KW - Cytarabine -- administration & dosage KW - Child, Preschool KW - Granulocyte-Macrophage Colony-Stimulating Factor -- administration & dosage KW - Etoposide -- administration & dosage KW - Adult KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Adolescent KW - Granulocyte-Macrophage Colony-Stimulating Factor -- adverse effects KW - Methotrexate -- administration & dosage KW - Prednisone -- administration & dosage KW - Male KW - Female KW - Survival Analysis KW - Ifosfamide -- administration & dosage KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Non-Hodgkin -- mortality KW - Lymphoma, Non-Hodgkin -- blood KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78001003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Adults+and+children+with+small+non-cleaved-cell+lymphoma+have+a+similar+excellent+outcome+when+treated+with+the+same+chemotherapy+regimen.&rft.au=Magrath%2C+I%3BAdde%2C+M%3BShad%2C+A%3BVenzon%2C+D%3BSeibel%2C+N%3BGootenberg%2C+J%3BNeely%2C+J%3BArndt%2C+C%3BNieder%2C+M%3BJaffe%2C+E%3BWittes%2C+R+A%3BHorak%2C+I+D&rft.aulast=Magrath&rft.aufirst=I&rft.date=1996-03-01&rft.volume=14&rft.issue=3&rft.spage=925&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy. AN - 78000910; 8622038 AB - To evaluate whether recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicities and supportive care requirements of an intensive combination chemoradiotherapy regimen in pediatric and young adult sarcoma patients. Thirty-seven newly diagnosed patients age 1 to 25 years were randomized to receive 18 cycles of chemotherapy alone or with GM-CSF beginning in cycle 3. GM-CSF (5 to 15 micrograms/kg/d subcutaneously) was begun 24 hours after the completion of chemotherapy and continued through day 19 of each cycle or until the absolute granulocyte count (AGC) was > or = 500/microliter on 2 consecutive days. GM-CSF reduced the median duration of grade 4 granulocytopenia from 9.0 days (range, 2 to 24) to 7.0 days (range, 1 to 21) (P 75,000/microliter, 16.0 days [range, 0 to 61] v 14.0 days [range, 0 to 38], P < .0001). GM-CSF does not produce clinically meaningful reductions in the degree or duration of severe granulocytopenia following intensive multiagent chemotherapy, but is associated with worsened thrombocytopenia. GM-CSF also does not reduce the need for hospitalization or the incidence of febrile neutropenia and infectious complications. We conclude that the costs and increased toxicities associated with the use of this agent are not justified by its minimal clinical benefit for regimens of this level of intensity. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wexler, L H AU - Weaver-McClure, L AU - Steinberg, S M AU - Jacobson, J AU - Jarosinski, P AU - Avila, N AU - Pizzo, P A AU - Horowitz, M E AD - Pediatric and Radiation Oncology Branches, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 901 EP - 910 VL - 14 IS - 3 SN - 0732-183X, 0732-183X KW - Anti-Bacterial Agents KW - 0 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Anti-Bacterial Agents -- therapeutic use KW - Disease-Free Survival KW - Humans KW - Child KW - Infection -- drug therapy KW - Infection -- epidemiology KW - Child, Preschool KW - Infant KW - Infection -- etiology KW - Prospective Studies KW - Adult KW - Adolescent KW - Hospitalization -- statistics & numerical data KW - Male KW - Female KW - Agranulocytosis -- complications KW - Thrombocytopenia -- therapy KW - Thrombocytopenia -- complications KW - Agranulocytosis -- prevention & control KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Sarcoma -- drug therapy KW - Agranulocytosis -- chemically induced KW - Bone Neoplasms -- blood KW - Bone Neoplasms -- drug therapy KW - Thrombocytopenia -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Granulocyte-Macrophage Colony-Stimulating Factor -- adverse effects KW - Thrombocytopenia -- prevention & control KW - Agranulocytosis -- therapy KW - Sarcoma -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78000910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Randomized+trial+of+recombinant+human+granulocyte-macrophage+colony-stimulating+factor+in+pediatric+patients+receiving+intensive+myelosuppressive+chemotherapy.&rft.au=Wexler%2C+L+H%3BWeaver-McClure%2C+L%3BSteinberg%2C+S+M%3BJacobson%2C+J%3BJarosinski%2C+P%3BAvila%2C+N%3BPizzo%2C+P+A%3BHorowitz%2C+M+E&rft.aulast=Wexler&rft.aufirst=L&rft.date=1996-03-01&rft.volume=14&rft.issue=3&rft.spage=901&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tamoxifen-associated eye disease. A review. AN - 77998756; 8622006 AB - The oral antiestrogen tamoxifen has demonstrated efficacy in the treatment of metastatic breast cancer and as adjuvant therapy in early-stage disease. Clinical trials of tamoxifen in chemoprevention of breast cancer among high-risk women have focused attention on potential adverse effects of long-term tamoxifen use, including the possibility of ocular toxicity. This review evaluates the published case reports, clinical series, and clinical trial data on ocular toxicities attributed to tamoxifen. Clinical issues of surveillance, differential diagnosis, and management of tamoxifen-related eye disease are discussed. National Library of Medicine online bibliographic services were used to identify case reports and clinical studies of ocular adverse effects that occurred in patients receiving tamoxifen published through the fall of 1994. The medical literature relevant to issues raised by the reports and studies was similarly identified and reviewed. Case reports and case series identify crystalline retinal deposits, macular edema, and corneal changes as potential tamoxifen ocular toxicities. Extensive retinal lesions and macular edema with visual impairment have been reported in a few patients receiving high-dose tamoxifen. Less extensive retinal changes may occur in patients receiving low doses for long periods, and isolated retinal crystals may be observed in patients without visual symptoms. Ocular toxicity is uncommon in the current clinical setting of long-term, low-dose tamoxifen use. Physicians should be aware of the potential for ocular toxicity among patients receiving the drug and should assure appropriate surveillance and prompt evaluation of visual complaints. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Nayfield, S G AU - Gorin, M B AD - Chemoprevention Branch, National Cancer Institute, Bethesda, MD, 20892, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 1018 EP - 1026 VL - 14 IS - 3 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Hormonal KW - 0 KW - Estrogen Antagonists KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Corneal Diseases -- chemically induced KW - Breast Neoplasms -- drug therapy KW - Aging -- physiology KW - Cross-Sectional Studies KW - Prospective Studies KW - Humans KW - Visual Acuity -- drug effects KW - Clinical Trials as Topic KW - Time Factors KW - Retinal Diseases -- chemically induced KW - Female KW - Estrogen Antagonists -- pharmacokinetics KW - Tamoxifen -- pharmacokinetics KW - Estrogen Antagonists -- adverse effects KW - Antineoplastic Agents, Hormonal -- pharmacokinetics KW - Eye Diseases -- chemically induced KW - Tamoxifen -- adverse effects KW - Antineoplastic Agents, Hormonal -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77998756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Tamoxifen-associated+eye+disease.+A+review.&rft.au=Nayfield%2C+S+G%3BGorin%2C+M+B&rft.aulast=Nayfield&rft.aufirst=S&rft.date=1996-03-01&rft.volume=14&rft.issue=3&rft.spage=1018&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early-onset alcoholics have lower cerebrospinal fluid 5-hydroxyindoleacetic acid levels than late-onset alcoholics. AN - 77995951; 8611057 AB - We investigated the interrelationships of age at onset of excessive alcohol consumption, family history of alcoholism, psychiatric comorbidity, and cerebrospinal fluid monoamine metabolite concentrations in abstinent, treatment-seeking alcoholics. We studied 131 recently abstinent alcoholics. Supervised abstinence was maintained on a research ward at the National Institutes of Health Clinical Center for a minimum of 3 weeks. All alcoholics received a low-monoamine diet for a minimum of 3 days before lumbar puncture. Lumbar punctures were performed in the morning after an overnight fast. Monamine metabolites and tryptophan in cerebrospinal fluid were quantified with liquid chromatography by means of electrochemical detection. Psychiatric diagnoses were established from blind-rated Schedule for Affective Disorders and Schizophrenia-Lifetime version interviews administered by a research social worker. Severity and age at onset of excessive alcohol consumption were documented with a structured lifetime drinking history questionnaire and with selected alcoholism screening questionnaires (CAGE and Michigan Alcoholism Screening Test). Family history of alcoholism was obtained from the probands. A majority of the treatment-seeking, primarily white male alcoholics had a lifetime history of psychiatric disorders other than alcoholism. None fulfilled criteria for antisocial personality disorder. Early-onset alcoholics (onset of excessive consumption before 25 years of age) had a more severe course of alcoholism and lower mean cerebrospinal fluid 5-hydroxyindoleacetic acid concentration than late-onset alcoholics. Patients who reported both parents to be alcoholics had particularly low mean cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan concentrations. Among treatment-seeking alcoholics, early age at onset is generally associated with a more severe course of alcoholism and lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentration. JF - Archives of general psychiatry AU - Fils-Aime, M L AU - Eckardt, M J AU - George, D T AU - Brown, G L AU - Mefford, I AU - Linnoila, M AD - Laboratory of Clinical Studies, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md. USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 211 EP - 216 VL - 53 IS - 3 SN - 0003-990X, 0003-990X KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Tryptophan KW - 8DUH1N11BX KW - Homovanillic Acid KW - X77S6GMS36 KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Homovanillic Acid -- cerebrospinal fluid KW - Psychiatric Status Rating Scales KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Age of Onset KW - Alcohol Drinking -- cerebrospinal fluid KW - Mental Disorders -- epidemiology KW - Humans KW - Adult KW - Tryptophan -- cerebrospinal fluid KW - Family KW - Male KW - Female KW - Comorbidity KW - Prevalence KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcoholism -- cerebrospinal fluid KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77995951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Early-onset+alcoholics+have+lower+cerebrospinal+fluid+5-hydroxyindoleacetic+acid+levels+than+late-onset+alcoholics.&rft.au=Fils-Aime%2C+M+L%3BEckardt%2C+M+J%3BGeorge%2C+D+T%3BBrown%2C+G+L%3BMefford%2C+I%3BLinnoila%2C+M&rft.aulast=Fils-Aime&rft.aufirst=M&rft.date=1996-03-01&rft.volume=53&rft.issue=3&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-28 N1 - Date created - 1996-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer. AN - 77993659; 8622023 AB - We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Fisherman, J S AU - Cowan, K H AU - Noone, M AU - Denicoff, A AU - Berg, S AU - Poplack, D AU - Balis, F AU - Venzon, D AU - McCabe, M AU - Goldspiel, B AU - Chow, C AU - Ognibene, F P AU - O'Shaughnessy, J AD - Medicine Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Clinical Center, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 774 EP - 782 VL - 14 IS - 3 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Doxorubicin KW - 80168379AG KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Doxorubicin -- pharmacokinetics KW - Disease-Free Survival KW - Doxorubicin -- adverse effects KW - Drug Administration Schedule KW - Paclitaxel -- pharmacokinetics KW - Humans KW - Heart -- drug effects KW - Aged KW - Doxorubicin -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Diarrhea -- chemically induced KW - Paclitaxel -- adverse effects KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Adult KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77993659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I%2FII+study+of+72-hour+infusional+paclitaxel+and+doxorubicin+with+granulocyte+colony-stimulating+factor+in+patients+with+metastatic+breast+cancer.&rft.au=Fisherman%2C+J+S%3BCowan%2C+K+H%3BNoone%2C+M%3BDenicoff%2C+A%3BBerg%2C+S%3BPoplack%2C+D%3BBalis%2C+F%3BVenzon%2C+D%3BMcCabe%2C+M%3BGoldspiel%2C+B%3BChow%2C+C%3BOgnibene%2C+F+P%3BO%27Shaughnessy%2C+J&rft.aulast=Fisherman&rft.aufirst=J&rft.date=1996-03-01&rft.volume=14&rft.issue=3&rft.spage=774&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of advanced solid tumors with immunotoxin LMB-1: an antibody linked to Pseudomonas exotoxin. AN - 77989971; 8612238 AB - Immunotoxin LMB-1 is composed of monoclonal antibody B3 chemically linked to PE38, a genetically engineered form of Pseudomonas exotoxin. B3 recognizes a carbohydrate antigen (Le(Y)) present on many human solid tumors. LMB-1 has excellent antitumor activity in nude mice bearing Le(Y)-positive tumors. We conducted a phase I study of 38 patients with solid tumors who failed conventional therapy and whose tumors expressed the Le(Y) antigen. Objective antitumor activity was observed in 5 patients, 18 had stable disease, 15 progressed. A complete remission was observed in a patient with metastatic breast cancer to supraclavicular nodes. A greater than 75% tumor reduction and resolution of all clinical symptoms lasting for more than six months was observed in a colon cancer patient with extensive retroperitoneal and cervical metastasis. Three patients (two colon, one breast cancer) had minor responses. The maximum tolerated dose of LMB-1 is 75 microgram/kg given intravenously three times every other day. The major toxicity is vascular leak syndrome manifested by hypoalbuminemia, fluid retention, hypotension and, in one case, pulmonary edema. Although immunotoxins have been evaluated in clinical studies for more than two decades, this is the first report of antitumor activity in epithelial tumors. JF - Nature medicine AU - Pai, L H AU - Wittes, R AU - Setser, A AU - Willingham, M C AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 350 EP - 353 VL - 2 IS - 3 SN - 1078-8956, 1078-8956 KW - Antibodies, Monoclonal KW - 0 KW - Exotoxins KW - Immunotoxins KW - Lewis Blood-Group System KW - Lewis Y antigen KW - Index Medicus KW - Animals KW - Humans KW - Tomography, X-Ray Computed KW - Aged KW - Mice KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use KW - Drug Tolerance KW - Adult KW - Middle Aged KW - Antibodies, Monoclonal -- adverse effects KW - Vascular Diseases -- etiology KW - Female KW - Male KW - Exotoxins -- administration & dosage KW - Neoplasms -- diagnostic imaging KW - Immunotoxins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Exotoxins -- adverse effects KW - Immunotoxins -- administration & dosage KW - Neoplasms -- therapy KW - Exotoxins -- therapeutic use KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77989971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+medicine&rft.atitle=Treatment+of+advanced+solid+tumors+with+immunotoxin+LMB-1%3A+an+antibody+linked+to+Pseudomonas+exotoxin.&rft.au=Pai%2C+L+H%3BWittes%2C+R%3BSetser%2C+A%3BWillingham%2C+M+C%3BPastan%2C+I&rft.aulast=Pai&rft.aufirst=L&rft.date=1996-03-01&rft.volume=2&rft.issue=3&rft.spage=350&rft.isbn=&rft.btitle=&rft.title=Nature+medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-05 N1 - Date created - 1996-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of epiroprim (Ro11-8958), a new dihydrofolate reductase inhibitor, in the treatment of acute Toxoplasma infection in mice. AN - 77987552; 8600759 AB - Toxoplasma gondii is a major cause of focal encephalitis in patients with acquired immunodeficiency syndrome. Epiroprim, an inhibitor of dihydrofolate reductase, was evaluated in vitro and in a mouse model of acute infection for activity against T. gondii. The 50% inhibitory concentration (IC50) of epiroprim for T. gondii dihydrofolate reductase was 0.9 micromole, similar to that of pyrimethamine, but epiroprim was 650-fold more selective than pyrimethamine for T. gondii compared with human dihydrofolate reductase. While intraperitoneally administered epiroprim (300 mg/kg/day for 14 days) alone was ineffective in mice acutely infected with the RH strain of T. gondii, 100% survival was seen when it was combined with orally administered sulfadiazine (375 mg/kg/day), which alone was also ineffective. Increases in survival were seen in combination with doses of sulfadiazine as low as 0.375 mg/kg/day. Orally administered epiroprim combined with dapsone also prolonged survival. Thus epiroprim is an active and potentially less toxic alternative pyrimethamine for the treatment of toxoplasmosis. JF - The American journal of tropical medicine and hygiene AU - Martinez, A AU - Allegra, C J AU - Kovacs, J A AD - Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 249 EP - 252 VL - 54 IS - 3 SN - 0002-9637, 0002-9637 KW - Anti-Infective Agents KW - 0 KW - Antiprotozoal Agents KW - Folic Acid Antagonists KW - Sulfadiazine KW - 0N7609K889 KW - Dapsone KW - 8W5C518302 KW - epiroprim KW - 9G69D95443 KW - Trimethoprim KW - AN164J8Y0X KW - Abridged Index Medicus KW - Index Medicus KW - Acute Disease KW - Administration, Oral KW - Injections, Intraperitoneal KW - Animals KW - Sulfadiazine -- therapeutic use KW - Anti-Infective Agents -- pharmacokinetics KW - Dapsone -- administration & dosage KW - Humans KW - Mice KW - Mice, Inbred BALB C KW - Drug Therapy, Combination KW - Anti-Infective Agents -- therapeutic use KW - Half-Life KW - Sulfadiazine -- administration & dosage KW - Injections, Subcutaneous KW - Anti-Infective Agents -- administration & dosage KW - Sulfadiazine -- pharmacokinetics KW - Dapsone -- therapeutic use KW - Trimethoprim -- analogs & derivatives KW - Folic Acid Antagonists -- therapeutic use KW - Trimethoprim -- pharmacokinetics KW - Antiprotozoal Agents -- pharmacokinetics KW - Folic Acid Antagonists -- administration & dosage KW - Antiprotozoal Agents -- administration & dosage KW - Trimethoprim -- administration & dosage KW - Toxoplasmosis, Animal -- drug therapy KW - Folic Acid Antagonists -- pharmacokinetics KW - Trimethoprim -- therapeutic use KW - Antiprotozoal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77987552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+tropical+medicine+and+hygiene&rft.atitle=Efficacy+of+epiroprim+%28Ro11-8958%29%2C+a+new+dihydrofolate+reductase+inhibitor%2C+in+the+treatment+of+acute+Toxoplasma+infection+in+mice.&rft.au=Martinez%2C+A%3BAllegra%2C+C+J%3BKovacs%2C+J+A&rft.aulast=Martinez&rft.aufirst=A&rft.date=1996-03-01&rft.volume=54&rft.issue=3&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+tropical+medicine+and+hygiene&rft.issn=00029637&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-29 N1 - Date created - 1996-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C, interleukin-1 beta, and corticosteroids regulate shedding of the type I, 55 kDa TNF receptor from human airway epithelial cells. AN - 77983237; 8845176 AB - Tumor necrosis factor (TNF) may contribute to the pathogenesis of inflammatory airway disorders via the regulation of inflammatory and cellular immune responses. Shed cell surface TNF receptors can act as soluble TNF binding proteins and modulate TNF biological activity. We report that normal human airway epithelial cells, as well as two human airway epithelial cell lines, shed soluble type I TNF receptors (sTNF-RI) in a concentration-dependent fashion following protein kinase C (PKC) activation by PMA. Interleukin (IL)-1beta also induced concentration-dependent sTNF-RI shedding from NCI-H292 cells, which could be inhibited by the PKC inhibitor calphostin C. Since corticosteroids are commonly utilized as antiinflammatory agents in airway disorders, the effect of dexamethasone on sTNF-RI release was assessed. Dexamethasone inhibited constitutive, as well as PMA- and IL-1beta-mediated sTNF-RI release from NCI-H292 cells in a concentration-dependent fashion. Furthermore, dexamethasone increased while PMA decreased total cellular 55 kDa TNF-RI protein as detected by immunoblotting. These changes in total cellular 55kDa TNF-RI protein did not appear to be mediated at the mRNA level, as assessed by ribonuclease protection assays. This suggests that sTNF-RI shedding represents a mechanism by which airway epithelial cells can actively participate in local cytokine networks and modulate TNF-mediated inflammation. Furthermore, since corticosteroids inhibit sTNF-RI release and are known to downregulate TNF synthesis, this may represent a mechanism by which equilibrium between TNF ligand and soluble binding protein is maintained in the airway microenvironment. JF - American journal of respiratory cell and molecular biology AU - Levine, S J AU - Logun, C AU - Chopra, D P AU - Rhim, J S AU - Shelhamer, J H AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 254 EP - 261 VL - 14 IS - 3 SN - 1044-1549, 1044-1549 KW - Antigens, CD KW - 0 KW - Enzyme Inhibitors KW - Interleukin-1 KW - Naphthalenes KW - RNA, Messenger KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Type I KW - Dexamethasone KW - 7S5I7G3JQL KW - Protein Kinase C KW - EC 2.7.11.13 KW - calphostin C KW - I271P23G24 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Naphthalenes -- pharmacology KW - Carcinoma, Mucoepidermoid KW - Enzyme Activation KW - Humans KW - Gene Expression KW - Trachea -- cytology KW - RNA, Messenger -- biosynthesis KW - Tumor Cells, Cultured KW - Bronchi -- cytology KW - Epithelial Cells KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Epithelium -- metabolism KW - Trachea -- metabolism KW - Bronchi -- metabolism KW - Cell Line KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Interleukin-1 -- pharmacology KW - Respiratory System -- metabolism KW - Dexamethasone -- pharmacology KW - Respiratory System -- cytology KW - Antigens, CD -- metabolism KW - Receptors, Tumor Necrosis Factor -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77983237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Protein+kinase+C%2C+interleukin-1+beta%2C+and+corticosteroids+regulate+shedding+of+the+type+I%2C+55+kDa+TNF+receptor+from+human+airway+epithelial+cells.&rft.au=Levine%2C+S+J%3BLogun%2C+C%3BChopra%2C+D+P%3BRhim%2C+J+S%3BShelhamer%2C+J+H&rft.aulast=Levine&rft.aufirst=S&rft.date=1996-03-01&rft.volume=14&rft.issue=3&rft.spage=254&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-23 N1 - Date created - 1996-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine. AN - 77981020; 8622028 AB - A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival. Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen. Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have had progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival time is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years. This combined modality regimen for patients with limited-stage small-cell lung cancer results in a 2-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Johnson, B E AU - Bridges, J D AU - Sobczeck, M AU - Gray, J AU - Linnoila, R I AU - Gazdar, A F AU - Hankins, L AU - Steinberg, S M AU - Edison, M AU - Frame, J N AU - Pass, H AU - Nesbitt, J AU - Holden, D AU - Mulshine, J L AU - Glatstein, E AU - Ihde, D C AD - National Cancer Institute-Navy Medical Oncology, National Naval Medical Center Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 806 EP - 813 VL - 14 IS - 3 SN - 0732-183X, 0732-183X KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Doxorubicin -- adverse effects KW - Vincristine -- adverse effects KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Aged KW - Doxorubicin -- administration & dosage KW - Cranial Irradiation KW - Brain Neoplasms -- secondary KW - Cause of Death KW - Cisplatin -- administration & dosage KW - Cyclophosphamide -- adverse effects KW - Etoposide -- administration & dosage KW - Radiotherapy Dosage KW - Adult KW - Brain Neoplasms -- prevention & control KW - Etoposide -- adverse effects KW - Middle Aged KW - Cisplatin -- adverse effects KW - Male KW - Female KW - Remission Induction KW - Carcinoma, Small Cell -- pathology KW - Lung Neoplasms -- radiotherapy KW - Carcinoma, Small Cell -- mortality KW - Lung Neoplasms -- drug therapy KW - Carcinoma, Small Cell -- secondary KW - Carcinoma, Small Cell -- radiotherapy KW - Lung Neoplasms -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Small Cell -- drug therapy KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77981020?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Patients+with+limited-stage+small-cell+lung+cancer+treated+with+concurrent+twice-daily+chest+radiotherapy+and+etoposide%2Fcisplatin+followed+by+cyclophosphamide%2C+doxorubicin%2C+and+vincristine.&rft.au=Johnson%2C+B+E%3BBridges%2C+J+D%3BSobczeck%2C+M%3BGray%2C+J%3BLinnoila%2C+R+I%3BGazdar%2C+A+F%3BHankins%2C+L%3BSteinberg%2C+S+M%3BEdison%2C+M%3BFrame%2C+J+N%3BPass%2C+H%3BNesbitt%2C+J%3BHolden%2C+D%3BMulshine%2C+J+L%3BGlatstein%2C+E%3BIhde%2C+D+C&rft.aulast=Johnson&rft.aufirst=B&rft.date=1996-03-01&rft.volume=14&rft.issue=3&rft.spage=806&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-20 N1 - Date created - 1996-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol research: at the cutting edge. AN - 77977006; 8611055 JF - Archives of general psychiatry AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 199 EP - 201 VL - 53 IS - 3 SN - 0003-990X, 0003-990X KW - Genetic Markers KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Disease Susceptibility KW - Age of Onset KW - Humans KW - Research KW - Alcoholism -- therapy KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77977006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Alcohol+research%3A+at+the+cutting+edge.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1996-03-01&rft.volume=53&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-28 N1 - Date created - 1996-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region. AN - 77973211; 8622688 AB - NotI linking clones, localized to the human chromosome 3p21.3 region and homozygously deleted in small cell lung cancer cell lines NCI-H740 and NCI-H1450, were used to search for a putative tumor suppressor gene(s). One of these clones, NL1G210, detected a 2.5-kb mRNA in all examined human tissues, expression being especially high in the heart and skeletal muscle. Two overlapping cDNA clones containing the entire open reading frame were isolated from a human heart cDNA library and fully characterized. Computer analysis and a search of the GenBank database to reveal high sequence identity of the product of this gene to serine-threonine kinases, especially to mitogen-activated protein kinase-activated protein kinase 2, a recently described substrate of mitogen-activated kinases. Sequence identitiy was 72% at the nucleotide level and 75% at the amino acid level, strongly suggesting that this protein is a serine-threonine kinase. Here we demonstrate that the new gene, referred to as 3pK (for chromosome 3p kinase), in fact encodes a mitogen-activated protein kinase-regulated protein serine-threonine kinase with a novel substrate specificity. JF - Molecular and cellular biology AU - Sithanandam, G AU - Latif, F AU - Duh, F M AU - Bernal, R AU - Smola, U AU - Li, H AU - Kuzmin, I AU - Wixler, V AU - Geil, L AU - Shrestha, S AD - Biological Carcinogenesis and Development Program, PRI/DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 868 EP - 876 VL - 16 IS - 3 SN - 0270-7306, 0270-7306 KW - DNA, Complementary KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - MAP-kinase-activated kinase 3 KW - EC 2.7.1.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Index Medicus KW - Base Sequence KW - DNA, Complementary -- genetics KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - DNA, Complementary -- isolation & purification KW - Amino Acid Sequence KW - Cloning, Molecular KW - Protein-Serine-Threonine Kinases -- isolation & purification KW - Genes, Tumor Suppressor KW - Lung Neoplasms -- genetics KW - Protein-Serine-Threonine Kinases -- genetics KW - Carcinoma, Small Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77973211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=3pK%2C+a+new+mitogen-activated+protein+kinase-activated+protein+kinase+located+in+the+small+cell+lung+cancer+tumor+suppressor+gene+region.&rft.au=Sithanandam%2C+G%3BLatif%2C+F%3BDuh%2C+F+M%3BBernal%2C+R%3BSmola%2C+U%3BLi%2C+H%3BKuzmin%2C+I%3BWixler%2C+V%3BGeil%2C+L%3BShrestha%2C+S&rft.aulast=Sithanandam&rft.aufirst=G&rft.date=1996-03-01&rft.volume=16&rft.issue=3&rft.spage=868&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-18 N1 - Date created - 1996-06-18 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U09578; GENBANK N1 - SuppNotes - Cited By: Genes Chromosomes Cancer. 1990 Jan;1(3):247-55 [2083219] FEBS Lett. 1995 May 8;364(2):229-33 [7750577] Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6142-6 [1712480] J Biol Chem. 1979 Jul 25;254(14):6211-4 [221492] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] Nature. 1987 Jun 25-Jul 1;327(6124):721-4 [2885753] J Mol Evol. 1987;25(4):351-60 [3118049] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1571-5 [2894030] Nature. 1988 Aug 25;334(6184):715-8 [2842685] Genomics. 1989 Jul;5(1):134-8 [2767683] Cytogenet Cell Genet. 1989;51(1-4):533-62 [2676383] Nature. 1990 Feb 15;343(6259):651-3 [2154696] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] Nucleic Acids Res. 1990 Nov 11;18(21):6319-24 [2243778] Nature. 1990 Nov 22;348(6299):302-8 [2123524] Cell. 1991 Jan 11;64(1):39-48 [1846090] Nature. 1991 Jan 17;349(6306):251-4 [1702878] Genes Chromosomes Cancer. 1990 Sep;2(3):231-8 [1981839] J Biol Chem. 1991 Aug 5;266(22):14721-4 [1860870] J Biol Chem. 1991 Aug 15;266(23):15180-4 [1907971] EMBO J. 1991 Nov;10(11):3297-309 [1655416] J Biol Chem. 1991 Nov 25;266(33):22159-63 [1939237] Trends Biochem Sci. 1991 Dec;16(12):478-81 [1664152] Genomics. 1991 Dec;11(4):1030-9 [1783374] Mol Cell Biol. 1992 Mar;12(3):915-27 [1545823] EMBO J. 1992 Jun;11(6):2123-9 [1318193] Nature. 1992 Jul 30;358(6385):414-7 [1322499] Nature. 1992 Jul 30;358(6385):417-21 [1322500] Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8205-9 [1381507] Genes Chromosomes Cancer. 1992 Sep;5(2):119-27 [1381947] EMBO J. 1992 Nov;11(11):3985-94 [1327754] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10877-81 [1438292] FEBS Lett. 1992 Nov 30;313(3):307-13 [1332886] J Biol Chem. 1993 Jan 25;268(3):1960-4 [8380583] Eur J Biochem. 1993 Mar 1;212(2):581-8 [8444194] Science. 1993 Mar 19;259(5102):1760-3 [7681220] Nature. 1993 May 6;363(6424):15-6 [8479530] Science. 1993 May 28;260(5112):1317-20 [8493574] Oncogene. 1993 Jul;8(7):1825-32 [8099726] Mol Cell Biol. 1993 Aug;13(8):4539-48 [8393135] FEBS Lett. 1993 Dec 20;336(1):143-7 [8262198] Oncogene. 1991 Apr;6(4):495-500 [2030909] Biochem J. 1993 Dec 15;296 ( Pt 3):843-9 [8280084] EMBO J. 1994 Jan 1;13(1):54-60 [7905823] J Biol Chem. 1994 Mar 4;269(9):7030-5 [8120067] Cell. 1994 Mar 11;76(5):933-45 [7510218] Science. 1994 Mar 18;263(5153):1625-9 [8128251] Cell. 1994 Mar 25;76(6):1025-37 [8137421] Nature. 1994 Mar 17;368(6468):258-61 [8145827] Nature. 1994 May 12;369(6476):156-60 [8177321] Biochem Biophys Res Commun. 1994 Apr 29;200(2):1118-24 [8179591] Cancer Res. 1994 Jun 1;54(11):3021-4 [7910519] Genomics. 1994 Jan 15;19(2):303-9 [8188261] Curr Opin Genet Dev. 1994 Feb;4(1):96-101 [8193547] Cancer Res. 1994 Jul 15;54(14):3710-3 [8033088] Cancer Res. 1994 Aug 1;54(15):4183-7 [8033151] Science. 1994 Sep 2;265(5177):1458-61 [8073291] Cell. 1994 Sep 23;78(6):1027-37 [7923353] Cell. 1994 Sep 23;78(6):1039-49 [7923354] Mol Cell Biol. 1994 Oct;14(10):6522-30 [7935374] Nature. 1994 Dec 22-29;372(6508):739-46 [7997261] Erratum In: Mol Cell Biol 1996 Apr;16(4):1880 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors. Giles F. Filley Lecture. AN - 77963074; 8598134 JF - Chest AU - Devereux, T R AU - Taylor, J A AU - Barrett, J C AD - The Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, NC 27709, USA. Y1 - 1996/03// PY - 1996 DA - March 1996 SP - 14S EP - 19S VL - 109 IS - 3 Suppl SN - 0012-3692, 0012-3692 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Chromosomes, Human, Pair 3 KW - Disease Susceptibility KW - Humans KW - Heterozygote KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Chromosomes, Human, Pair 9 KW - United States -- epidemiology KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Genes, p53 -- physiology KW - Lung Neoplasms -- genetics KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77963074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chest&rft.atitle=Molecular+mechanisms+of+lung+cancer.+Interaction+of+environmental+and+genetic+factors.+Giles+F.+Filley+Lecture.&rft.au=Devereux%2C+T+R%3BTaylor%2C+J+A%3BBarrett%2C+J+C&rft.aulast=Devereux&rft.aufirst=T&rft.date=1996-03-01&rft.volume=109&rft.issue=3+Suppl&rft.spage=14S&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-24 N1 - Date created - 1996-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. AN - 77958780; 8602705 AB - To describe the incidence of, clinical manifestations of, and risk factors for cyclophosphamide-induced urinary bladder toxicity in patients treated for nonmalignant disease. Retrospective analysis of patients followed at the National Institutes of Allergy and Infectious Diseases from 1967 to 1993. The Warren G. Magnuson Clinical Center of the National Institutes of Health (NIH). 145 patients who received cyclophosphamide for the treatment of Wegener granulomatosis and were followed for 0.5 to 27 years (median, 8.5 years), for a total of 1333 patient-years. Clinical characteristics, cystoscopic findings, results of cytologic examination of urine, surgical pathology, and total dose and duration of cyclophosphamide therapy were recorded and analyzed using a computer-based information retrieval system. Nonglomerular hematuria occurred in 73 of 145 patients treated with cyclophosphamide (50%). Sixty of the 73 patients with nonglomerular hematuria (82%) had cystoscopy at the NIH. Forty-two of the 60 patients (70%) who had cystoscopy had macroscopic changes consistent with cyclophosphamide-induced bladder injury. Seven patients (5%) developed transitional-cell carcinoma of the urinary bladder. In 6 of these 7 patients, the total cumulative cyclophosphamide dose exceeded 100 g, and the cumulative duration of cyclophosphamide therapy exceeded 2.7 years. Before they were given a diagnosis of bladder cancer, all 7 patients had had one or more episodes of microscopic or gross nonglomerular hematuria. In contrast, none of the 72 patients who had never had nonglomerular hematuria developed bladder cancer. Cox proportional hazards regression analysis showed that only microscopic nonglomerular hematuria was a significant risk factor for the development of bladder cancer (P < 0.01). Long-term oral cyclophosphamide therapy is associated with substantial urotoxicity, including the development of transitional-cell carcinoma of the urinary bladder. In this cohort of patients, the estimated incidence of bladder cancer after the first exposure to cyclophosphamide was 5% at 10 years and 16% at 15 years. Nonglomerular hematuria was a frequent manifestation of cyclophosphamide-induced cystitis, and it identified a subgroup of patients at high risk for the development of bladder cancer. JF - Annals of internal medicine AU - Talar-Williams, C AU - Hijazi, Y M AU - Walther, M M AU - Linehan, W M AU - Hallahan, C W AU - Lubensky, I AU - Kerr, G S AU - Hoffman, G S AU - Fauci, A S AU - Sneller, M C AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/03/01/ PY - 1996 DA - 1996 Mar 01 SP - 477 EP - 484 VL - 124 IS - 5 SN - 0003-4819, 0003-4819 KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Regression Analysis KW - Urine -- cytology KW - Hematuria -- chemically induced KW - Aged, 80 and over KW - Risk Factors KW - Humans KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Proportional Hazards Models KW - Cystitis -- chemically induced KW - Carcinoma, Transitional Cell -- chemically induced KW - Granulomatosis with Polyangiitis -- drug therapy KW - Urinary Bladder Neoplasms -- chemically induced KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77958780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Cyclophosphamide-induced+cystitis+and+bladder+cancer+in+patients+with+Wegener+granulomatosis.&rft.au=Talar-Williams%2C+C%3BHijazi%2C+Y+M%3BWalther%2C+M+M%3BLinehan%2C+W+M%3BHallahan%2C+C+W%3BLubensky%2C+I%3BKerr%2C+G+S%3BHoffman%2C+G+S%3BFauci%2C+A+S%3BSneller%2C+M+C&rft.aulast=Talar-Williams&rft.aufirst=C&rft.date=1996-03-01&rft.volume=124&rft.issue=5&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-06 N1 - Date created - 1996-05-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 1997 Jan 1;126(1):86 [8992929] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histopathology of Acetaminophen-Induced Liver Changes: Role of Interleukin 1a and Tumor Necrosis Factor a AN - 762278886; 13645701 AB - Administration of 500 mg/kg acetaminophen (APAP) to female B6C3F1 mice resulted in well-documented pathophysiological changes in the liver manifested as increased serum concentration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and serum sorbitol dehydrogenase), centrilobular congestion, and hepatocellular degeneration and necrosis. The role of proinflammatory cytokines, including tumor necrosis factor a (TNF-a) and interleukin 1a (IL-1a), on the hepatotoxicity of APAP was examined at 4,8, 12, and 24 hr following APAP administration. Neutralization of TNF-a or IL-1a with specific antibodies partially prevented the hepatotoxic effects of APAP at the 4- and 8-hr time points. In addition, prior administration of anti-TNF-a antibodies shortened the recovery time following APAP treatment. While IL-1 receptor antagonist (IL-1ra) had only a modest protective effect against APAP-induced liver damage, as determined by serum enzyme release, IL-1ra had no effect on the degree of hepatic congestion or necrosis at any of the time points examined. On the other hand, administration of antibodies against IL-1ra exacerbated APAP-induced liver toxicity. These results suggest that TNF-a and IL-1a play an important role in the degree of damage and recovery that the liver undergoes following APAP intoxication. JF - Toxicologic Pathology AU - Blazka, Mark E AU - Elwell, Michael R AU - Holladay, Steve D AU - Wilson, Ralph E AU - Luster, Michael I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709 Y1 - 1996/03// PY - 1996 DA - Mar 1996 SP - 181 EP - 189 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 2 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts; Immunology Abstracts KW - Intoxication KW - Aspartate aminotransferase KW - Interleukin 1 KW - Enzymes KW - Sorbitol KW - Toxicity KW - Alanine transaminase KW - Tumor necrosis factor-a KW - hepatotoxicity KW - Interleukin 1 receptor antagonist KW - dehydrogenase KW - Inflammation KW - L-Lactate dehydrogenase KW - Antibodies KW - Liver KW - Degeneration KW - Acetaminophen KW - X 24310:Pharmaceuticals KW - F 06955:Immunomodulation & Immunopharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762278886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Histopathology+of+Acetaminophen-Induced+Liver+Changes%3A+Role+of+Interleukin+1a+and+Tumor+Necrosis+Factor+a&rft.au=Blazka%2C+Mark+E%3BElwell%2C+Michael+R%3BHolladay%2C+Steve+D%3BWilson%2C+Ralph+E%3BLuster%2C+Michael+I&rft.aulast=Blazka&rft.aufirst=Mark&rft.date=1996-03-01&rft.volume=24&rft.issue=2&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339602400206 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Intoxication; Aspartate aminotransferase; Interleukin 1; Enzymes; Sorbitol; Toxicity; Tumor necrosis factor-a; Alanine transaminase; dehydrogenase; Interleukin 1 receptor antagonist; hepatotoxicity; L-Lactate dehydrogenase; Inflammation; Antibodies; Liver; Degeneration; Acetaminophen DO - http://dx.doi.org/10.1177/019262339602400206 ER - TY - JOUR T1 - Chemicals Associated with Decreases in the Incidence of Mononuclear Cell Leukemia in the Fischer Rat AN - 755138873; 13645707 AB - A significant treatment-related decrease in the incidence of mononuclear cell leukemia (MCL) was identified in Fischer-344/N rats for 20 chemicals tested in the National Toxicology Program's 2-yr carcinogenicity bioassay. Fourteen of the 20 chemicals caused decreases of MCL in both male and female rats; 6 of the 20 caused a significant decrease only in males and a marginal or no decrease in female rats. Seventeen of the chemicals associated with a decrease in MCL had a free aromatic amine or nitro functional groups that could be metabolized to free amines. With 1 exception, all 14 chemicals causing a decrease in MCL in both sexes produced spleen toxicity in the 13-wk studies. Reduced body weight and decreased survival, related either to toxicity or to an increase in other types of lethal neoplasms, did not contribute to the decreases in MCL observed in chemical exposure groups. Thirteen of the 20 chemicals were positive in Salmonella tests, and 15 were associated with increases in neoplasms at other sites in rats and/or mice, suggesting that different metabolites could be responsible for these varied biological effects. JF - Toxicologic Pathology AU - Elwell, Michael R AU - Dunnick, June K AU - Hailey, James R AU - Haseman, Joseph K AD - Experimental Toxicology Program, National Institute of Environmental Health Sciences Y1 - 1996/03// PY - 1996 DA - Mar 1996 SP - 238 EP - 245 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 2 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts; Immunology Abstracts KW - Leukocytes (mononuclear) KW - Survival KW - Spleen KW - Metabolites KW - Toxicity KW - Leukemia KW - amines KW - Body weight KW - Carcinogenicity KW - Salmonella KW - Aromatics KW - Sex KW - F 06955:Immunomodulation & Immunopharmacology KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755138873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Chemicals+Associated+with+Decreases+in+the+Incidence+of+Mononuclear+Cell+Leukemia+in+the+Fischer+Rat&rft.au=Elwell%2C+Michael+R%3BDunnick%2C+June+K%3BHailey%2C+James+R%3BHaseman%2C+Joseph+K&rft.aulast=Elwell&rft.aufirst=Michael&rft.date=1996-03-01&rft.volume=24&rft.issue=2&rft.spage=238&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339602400212 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Leukocytes (mononuclear); Leukemia; amines; Body weight; Carcinogenicity; Spleen; Survival; Metabolites; Toxicity; Aromatics; Sex; Salmonella DO - http://dx.doi.org/10.1177/019262339602400212 ER - TY - JOUR T1 - Clostridial neurotoxins and substrate proteolysis in intact neurons: Botulinum neurotoxin C acts on synaptosomal-associated protein of 25 kDa AN - 15800689; 3996022 AB - Clostridial neurotoxins are zinc endopeptidases that block neurotransmission and have been shown to cleave, in vitro, specific proteins involved in synaptic vesicle docking and/or fusion. We have used immunohistochemistry and immunoblotting to demonstrate alterations in toxin substrates in intact neurons under conditions of toxin-induced blockade of neurotransmitter release. Vesicle-associated membrane protein, which colocalizes with synaptophysin, is not detectable in tetanus toxin-blocked cultures. Syntaxin, also concentrated in synaptic sites, is cleaved by botulinum neurotoxin C. Similarly, the carboxyl terminus of the synaptosomal-associated protein of 25 kDa (SNAP-25) is not detectable in botulinum neurotoxin A-treated cultures. Unexpectedly, tetanus toxin exposure causes an increase in SNAP-25 immunofluorescence, reflecting increased accessibility of antibodies to antigenic sites rather than increased expression of the protein. Furthermore, botulinum neurotoxin C causes a marked loss of the carboxyl terminus of SNAP-25 when the toxin is added to living cultures, whereas it has no action on SNAP-25 in in vitro preparations. This study is the first to demonstrate in functioning neurons that the physiologic response to these toxins is correlated with the proteolysis of their respective substrates. Furthermore, the data demonstrate that botulinum neurotoxin C, in addition to cleaving syntaxin, exerts a secondary effect on SNAP-25. JF - Journal of Biological Chemistry AU - Williamson, L C AU - Halpern, J L AU - Montecucco, C AU - Brown, JE AU - Neale, E A AD - LDN, NICHD, Natl. Inst. Health, Bldg. 49, Rm. 5A38, Bethesda, MD 20892-4480, USA Y1 - 1996/03// PY - 1996 DA - Mar 1996 SP - 7694 EP - 7699 VL - 271 IS - 13 SN - 0021-9258, 0021-9258 KW - toxins KW - neurotoxin C KW - syntaxin KW - synaptosomal-associated protein KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts; CSA Neurosciences Abstracts KW - Clostridium botulinum KW - botulism KW - synaptic vesicles KW - X 24171:Microbial KW - N3 11070:Neurochemistry and cellular biology KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15800689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Clostridial+neurotoxins+and+substrate+proteolysis+in+intact+neurons%3A+Botulinum+neurotoxin+C+acts+on+synaptosomal-associated+protein+of+25+kDa&rft.au=Williamson%2C+L+C%3BHalpern%2C+J+L%3BMontecucco%2C+C%3BBrown%2C+JE%3BNeale%2C+E+A&rft.aulast=Williamson&rft.aufirst=L&rft.date=1996-03-01&rft.volume=271&rft.issue=13&rft.spage=7694&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Clostridium botulinum; toxins; synaptic vesicles; botulism ER - TY - JOUR T1 - Switching viral latency to viral lysis: A novel therapeutic approach for Epstein-Barr virus-associated neoplasia AN - 15792289; 3989600 AB - We describe an EBV-driven lytic system (LySED) that can be used to specifically target therapy to EBV-containing tumors. This system takes advantage of the transactivating properties of EBNA-1, a latency protein expressed in all EBV-containing cells, to drive the expression of Zta, a gene sufficient for inducing the EBV lytic cycle. Thus, EBV provides both the target and the executor for mediating tumor-specific cell death, markedly increasing the specificity of the system. Transfection of EBV-positive cell lines with the LySED construct resulted in a switch to lytic cycle and subsequent cell death, even in the presence of an inhibitor of EBV thymidine kinase (acyclovir) without an increase in virion production. In contrast, growth of EBV-negative B-cell lines was not affected. JF - Cancer Research AU - Gutierrez, MI AU - Judde, J-G AU - Magrath, I T AU - Bhatia, K G AD - Lymphoma Biology Section, Pediatric Branch, National Cancer Institute, NIH, Building 10, Room 13N240, 10 Center Drive, MSC 1928, Bethesda, MD 20892-1928, USA Y1 - 1996/03// PY - 1996 DA - Mar 1996 SP - 969 EP - 972 VL - 56 IS - 5 SN - 0008-5472, 0008-5472 KW - EBNA-1 protein KW - Zta gene KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Epstein-Barr virus KW - transfection KW - tumors KW - neoplasia KW - W3 33190:Therapy: Other KW - V 22114:Human oncogenic viruses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15792289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Switching+viral+latency+to+viral+lysis%3A+A+novel+therapeutic+approach+for+Epstein-Barr+virus-associated+neoplasia&rft.au=Gutierrez%2C+MI%3BJudde%2C+J-G%3BMagrath%2C+I+T%3BBhatia%2C+K+G&rft.aulast=Gutierrez&rft.aufirst=MI&rft.date=1996-03-01&rft.volume=56&rft.issue=5&rft.spage=969&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - transfection; tumors; neoplasia; Epstein-Barr virus ER - TY - JOUR T1 - Non-parametric two-sample tests for repeated ordinal responses. AN - 78072050; 8668869 AB - Consider data on two groups of clusters, where each cluster consists of many units that respond on an ordinal scale. We develop a Mann-Whitney type test to determine whether a typical response from the first group is larger (or smaller) than a typical response from the second group. JF - Statistics in medicine AU - Fay, M P AU - Gennings, C AD - National Cancer Institute, Biometry Branch, Bethesda, Maryland 20892-7354, USA. Y1 - 1996/02/28/ PY - 1996 DA - 1996 Feb 28 SP - 429 EP - 442 VL - 15 IS - 4 SN - 0277-6715, 0277-6715 KW - Cholesterol Esters KW - 0 KW - Lead KW - 2P299V784P KW - cholesteryl succinate KW - T3J4KS4201 KW - Index Medicus KW - Animals KW - Environmental Exposure -- statistics & numerical data KW - Salivation -- drug effects KW - Humans KW - Bayes Theorem KW - Child KW - Environmental Monitoring -- statistics & numerical data KW - Likelihood Functions KW - Lead -- blood KW - Population Surveillance KW - Child, Preschool KW - Rats KW - Cholesterol Esters -- pharmacology KW - Adolescent KW - Cluster Analysis KW - Data Interpretation, Statistical KW - Statistics, Nonparametric UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78072050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=Non-parametric+two-sample+tests+for+repeated+ordinal+responses.&rft.au=Fay%2C+M+P%3BGennings%2C+C&rft.aulast=Fay&rft.aufirst=M&rft.date=1996-02-28&rft.volume=15&rft.issue=4&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-06 N1 - Date created - 1996-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a minimum enhancer sequence for the type II collagen gene reveals several core sequence motifs in common with the link protein gene. AN - 78046212; 8626777 AB - The type II collagen gene (Col2a1) is expressed primarily in chondrocytes. Transcription of Col2a1 is mediated by cell-specific regulatory elements located within the promoter and first intron. Here, we map a minimal enhancer and identify elements that determine cartilage-specific Col2a1 expression by analyzing the activity of a series of chimeric genes consisting of rat Col2a1 first intron deletion mutants ligated to the chloramphenicol acetyltransferase reporter gene. We show that a 100-base pair (bp) segment within the first intron is the minimum size necessary for high level, cell type-specific expression of Col2a1. Sequence analysis of this 100-bp Col2a1 enhancer revealed several sequence motifs similar to motifs present within the regulatory region of the link protein gene, another cartilage gene. These motifs include an AT-rich element, a C1 motif and a C3 motif. Deletion of any of these elements reduced Col2a1 enhancer activity in chick embryo chondrocytes. We also tested enhancer-mediated activity in CFK2 cells which differentiate to a chondrogenic phenotype and begin to express type II collagen mRNA after extended culture. In stably transfected CFK2 cells, constructs containing the 100-bp enhancer were activated during the transition from prechondrogenic to chondrogenic cell populations and deletions within the enhancer strongly down-regulated activity. Chondrocyte-specific DNA-protein complexes were identified using nuclear extracts prepared from chick embryo chondrocytes and 32P-labeled oligonucleotides from these regions of the first intron. These results suggest that interaction of chondrocyte specific nuclear factors with multiple core elements from a small region within the first intron are important for cell-type specific Col2a1 enhancer activity. JF - The Journal of biological chemistry AU - Krebsbach, P H AU - Nakata, K AU - Bernier, S M AU - Hatano, O AU - Miyashita, T AU - Rhodes, C S AU - Yamada, Y AD - Laboratory of Developmental Biology, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/02/23/ PY - 1996 DA - 1996 Feb 23 SP - 4298 EP - 4303 VL - 271 IS - 8 SN - 0021-9258, 0021-9258 KW - Extracellular Matrix Proteins KW - 0 KW - Oligonucleotide Probes KW - Proteins KW - Proteoglycans KW - Recombinant Fusion Proteins KW - link protein KW - Collagen KW - 9007-34-5 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Protein Biosynthesis KW - Animals KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Sequence Homology, Nucleic Acid KW - Cell Nucleus -- metabolism KW - Chick Embryo KW - Extracellular Matrix Proteins -- biosynthesis KW - Mutagenesis KW - Rats KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - Transfection KW - Cartilage -- metabolism KW - Restriction Mapping KW - Extracellular Matrix Proteins -- genetics KW - Introns KW - Molecular Sequence Data KW - Sequence Deletion KW - Collagen -- genetics KW - Enhancer Elements, Genetic KW - Collagen -- biosynthesis KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78046212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+a+minimum+enhancer+sequence+for+the+type+II+collagen+gene+reveals+several+core+sequence+motifs+in+common+with+the+link+protein+gene.&rft.au=Krebsbach%2C+P+H%3BNakata%2C+K%3BBernier%2C+S+M%3BHatano%2C+O%3BMiyashita%2C+T%3BRhodes%2C+C+S%3BYamada%2C+Y&rft.aulast=Krebsbach&rft.aufirst=P&rft.date=1996-02-23&rft.volume=271&rft.issue=8&rft.spage=4298&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L48618; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. AN - 78044224; 8626753 AB - The mitogen-activated protein kinase (MAPK) family is comprised of key regulatory proteins that control the cellular response to both proliferation and stress signals. In this study we investigated the factors controlling MAPK activation by H2O2 and explored the impact of altering the pathways to kinase activation on cell survival following H2O2 exposure. Potent activation (10-20-fold) of extracellular signal-regulated protein kinase (ERK2) occurred within 10 min of H2O2 treatment, whereupon rapid inactivation ensued. H2O2 activated ERK2 in several cell types and also moderately activated (3-5-fold) both c-Jun N-terminal kinase and p38/RK/CSBP. Additionally, H2O2 increased the mRNA expression of MAPK-dependent genes c-jun, c-fos, and MAPK phosphatase-1. Suramin pretreatment completely inhibited H2O2 stimulation of ERK2, highlighting a role for growth factor receptors in this activation. Further, ERK2 activation by H2O2 was blocked by pretreatment with either N-acetyl-cysteine, o-phenanthroline, or mannitol, indicating that metal-catalyzed free radical formation mediates the initiation of signal transduction by H2O2. H2O2-stimulated activation of ERK2 was abolished in PC12 cells by inducible or constitutive expression of the dominant negative Ras-N-17 allele. Interestingly, PC12/Ras-N-17 cells were more sensitive than wild-type PC12 cells to H2O2 toxicity. Moreover, NIH 3T3 cells expressing constitutively active MAPK kinase (MEK, the immediate upstream regulator of ERK) were more resistant to H2O2 toxicity, while those expressing kinase-defective MEK were more sensitive, than cells expressing wild-type MEK. Taken together, these studies provide insight into mechanisms of MAPK regulation by H2O2 and suggest that ERK plays a critical role in cell survival following oxidant injury. JF - The Journal of biological chemistry AU - Guyton, K Z AU - Liu, Y AU - Gorospe, M AU - Xu, Q AU - Holbrook, N J AD - Section on Gene Expression and Aging, Gerontology Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1996/02/23/ PY - 1996 DA - 1996 Feb 23 SP - 4138 EP - 4142 VL - 271 IS - 8 SN - 0021-9258, 0021-9258 KW - Free Radicals KW - 0 KW - Phosphoproteins KW - Recombinant Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Luciferases KW - EC 1.13.12.- KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Gene Expression -- drug effects KW - Free Radicals -- analysis KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Luciferases -- analysis KW - Humans KW - Rats KW - Aorta -- drug effects KW - Phosphotyrosine -- analysis KW - Aorta -- cytology KW - Phosphoproteins -- isolation & purification KW - Genes, jun KW - Phosphoproteins -- metabolism KW - 3T3 Cells KW - Aorta -- physiology KW - Enzyme Activation KW - HeLa Cells KW - Mice KW - Free Radicals -- metabolism KW - Luciferases -- biosynthesis KW - Blotting, Western KW - Transfection KW - Cells, Cultured KW - Kinetics KW - Genes, fos KW - Recombinant Proteins -- analysis KW - PC12 Cells KW - Muscle, Smooth, Vascular -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Cell Survival -- drug effects KW - Hydrogen Peroxide -- pharmacology KW - Muscle, Smooth, Vascular -- drug effects KW - Muscle, Smooth, Vascular -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78044224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation+of+mitogen-activated+protein+kinase+by+H2O2.+Role+in+cell+survival+following+oxidant+injury.&rft.au=Guyton%2C+K+Z%3BLiu%2C+Y%3BGorospe%2C+M%3BXu%2C+Q%3BHolbrook%2C+N+J&rft.aulast=Guyton&rft.aufirst=K&rft.date=1996-02-23&rft.volume=271&rft.issue=8&rft.spage=4138&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relative susceptibilities of C57BL/6, (C57BL/6 x C3H/He)F1, and C3H/He mice to acute toxicity and carcinogenicity of nickel subsulfide. AN - 77982893; 8599172 AB - The aim of this study was to compare susceptibility of mice of different strains to the toxicity and carcinogenicity of nickel subsulfide (Ni3S2), a water insoluble compound suspected to damage cells through oxidative mechanisms. Groups of 30 male mice of each strain, C57BL/6 (C57BL), (C57BL x C3H/He)F1 (B6C3F1), and C3H/He (C3H), were injected with single doses of 0.5-10 mg of Ni3S2/site into the thigh muscle and observed for up to 78 weeks. The highest Ni3S2 dose was lethal within 1 week to C57BL (93%) > B6C3F1 (80%) > C3H (53%) mice. The most susceptible C57BL mice also had the most severe necrotic/inflammatory kidney damage, compared with that in the other mice. The final incidence of local sarcomas at the 5 mg Ni3S2 dose was: C3H (97%) > B6C3F1 (76%) > C57BL (40% of mice at risk, i.e. those surviving at least 25 week; P < 0.05 or better as compared to the incidence in C3H mice). The relatively highest acute toxicity of Ni3S2 in C57BL mice observed in the present study, concurred with the weakest antioxidant response to systemic water-soluble nickel(II), resulting in reduction in glutathione (GSH) level and increased lipid peroxidation (LPO) in their kidneys and livers, two main targets of acute nickel toxicity, reported by us previously (Toxicol. Lett. 1991, 57, 269; ibid. 1991, 58, 121). Ni3S2 deposited in the muscle, therefore, constitutes a source of soluble nickel that can reach and damage distant organs. THe strongest tumor response in C3H mice relative to other strains did, in turn, concur with the lowest base levels of GSH and highest LPO in their muscle, the target for Ni3S2 carcinogenesis. Thus, the acute toxicity and carcinogenicity of Ni3S2 and Ni3S2-derived soluble nickel(II) in mice seem to depend, at least in part, on antioxidant capacity of target organs, which varies among different strains. JF - Toxicology AU - Rodriguez, R E AU - Misra, M AU - Diwan, B A AU - Riggs, C W AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. kasprkaz@fcrfv2.ncifcrf.gov Y1 - 1996/02/22/ PY - 1996 DA - 1996 Feb 22 SP - 131 EP - 140 VL - 107 IS - 2 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - nickel subsulfide KW - 12035-72-2 KW - Nickel KW - 7OV03QG267 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Disease Susceptibility KW - Dose-Response Relationship, Drug KW - Injections, Intramuscular KW - Mice KW - Lipid Peroxidation KW - Sarcoma -- chemically induced KW - Survival Rate KW - Neoplasms -- chemically induced KW - Glutathione -- analysis KW - Carcinogenicity Tests KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Muscle Neoplasms -- chemically induced KW - Species Specificity KW - Male KW - Nickel -- administration & dosage KW - Kidney -- metabolism KW - Carcinogens -- administration & dosage KW - Liver -- drug effects KW - Kidney -- drug effects KW - Carcinogens -- toxicity KW - Liver -- metabolism KW - Nickel -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77982893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Relative+susceptibilities+of+C57BL%2F6%2C+%28C57BL%2F6+x+C3H%2FHe%29F1%2C+and+C3H%2FHe+mice+to+acute+toxicity+and+carcinogenicity+of+nickel+subsulfide.&rft.au=Rodriguez%2C+R+E%3BMisra%2C+M%3BDiwan%2C+B+A%3BRiggs%2C+C+W%3BKasprzak%2C+K+S&rft.aulast=Rodriguez&rft.aufirst=R&rft.date=1996-02-22&rft.volume=107&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-19 N1 - Date created - 1996-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metallothionein gene expression in testicular interstitial cells and liver of rats treated with cadmium. AN - 77960516; 8599171 AB - The rodent testes are generally more susceptible to cadmium (Cd)-induced toxicity than the liver. Cd induces predominantly testicular interstitial cell (TIC) tumors. In order to clarify the molecular mechanism underlying tissue differences in Cd sensitivity, we compared Cd-induced metallothionein (MT) gene expression, MT protein accumulation, and Cd retention in freshly isolated TICs and liver. Adult male Fischer rats received a s.c. injection of 4.0 micromol Cd/kg or vehicle and 24 h later tissues were sampled and TICs isolated. MT-I and MT-II mRNA levels were determined by slot-blot analysis followed by densitometry scanning, and MT was estimated by the Cd-heme method. Testicular lesions were not grossly or histologically observed in rats treated with 4 micromol Cd/kg. Both MT mRNA and MT (as determined by Cd-binding capacity) were constitutively present in TICs as well as the liver. TICs isolated from Cd-treated rats accumulated more Cd (4-fold), and had higher levels of MT-I (1.9-fold) and MT-II (1.4-fold) mRNAs over control, but contained less MT (30% decrease) than TICs isolated from control animals. Cd exposure substantially increased hepatic Cd content (6000-fold), MT (58-fold), and MT-I mRNA (5.3-fold), but did not increase MT-II mRNA. Thus, our findings indicate that, although low-dose Cd exposure results in increases of MT mRNA in TICs it does not enhance MT synthesis within these cells. The inability to induce the metal-detoxicating MT-protein, in response to Cd, might account for higher susceptibility of testes to Cd toxicity and carcinogenesis relative to liver. JF - Toxicology AU - McKenna, I M AU - Bare, R M AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1996/02/22/ PY - 1996 DA - 1996 Feb 22 SP - 121 EP - 130 VL - 107 IS - 2 SN - 0300-483X, 0300-483X KW - Oligonucleotide Probes KW - 0 KW - RNA, Messenger KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Molecular Sequence Data KW - Injections, Subcutaneous KW - RNA, Messenger -- genetics KW - Time Factors KW - Protein Binding KW - Male KW - Gene Expression -- drug effects KW - Cadmium -- administration & dosage KW - Metallothionein -- biosynthesis KW - Cadmium -- analysis KW - Metallothionein -- genetics KW - Liver -- metabolism KW - Leydig Cells -- drug effects KW - Liver -- chemistry KW - Cadmium -- metabolism KW - Leydig Cells -- metabolism KW - Leydig Cells -- chemistry KW - Liver -- drug effects KW - Cadmium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77960516?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Metallothionein+gene+expression+in+testicular+interstitial+cells+and+liver+of+rats+treated+with+cadmium.&rft.au=McKenna%2C+I+M%3BBare%2C+R+M%3BWaalkes%2C+M+P&rft.aulast=McKenna&rft.aufirst=I&rft.date=1996-02-22&rft.volume=107&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-19 N1 - Date created - 1996-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunocytochemical localization of the endogenous neuroexcitotoxin quinolinate in human peripheral blood monocytes/macrophages and the effect of human T-cell lymphotropic virus type I infection. AN - 78006037; 8643683 AB - Quinolinate (Quin), a metabolite in the kynurenine pathway of tryptophan degradation and a neurotoxin that appears to act through the N-methyl-D-aspartate receptor system, was localized in cultured human peripheral blood monocytes/macrophages (PBMOs) by using a recently developed immunocytochemical method. Quin immunoreactivity (Quin-IR) was increased in gamma interferon (IFN-gamma)-stimulated monocytes/macrophages (MOs). In addition, the precursors, tryptophan and kynurenine, significantly increased Quin-IR. Infection of MOs by human T-cell lymphotropic virus type I (HTLV-I) in vitro substantially increased both the number of Quin-IR cells and the intensity of Quin-IR. At the peak of the Quin-IR response, about 40% of the cells were Quin-IR positive. In contrast, only about 2-5% of the cells were positive for HTLV-I, as detected by both immunofluorescence for the HTLV-I antigens and PCR techniques for the HTLV-I Tax gene. These results suggest that HTLV-I-induced Quin production in MOs occurs by an indirect mechanism, perhaps via cytokines produced by the infection but not directly by the virus infection per se. The significance of these findings to the neuropathology of HTLV-I infection is discussed. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Venkateshan, C N AU - Narayanan, R AU - Espey, M G AU - Moffett, J R AU - Gajdusek, D C AU - Gibbs, C J AU - Namboodiri, M A AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/02/20/ PY - 1996 DA - 1996 Feb 20 SP - 1636 EP - 1641 VL - 93 IS - 4 SN - 0027-8424, 0027-8424 KW - DNA, Viral KW - 0 KW - Kynurenine KW - 343-65-7 KW - Interferon-gamma KW - 82115-62-6 KW - Tryptophan KW - 8DUH1N11BX KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - AIDS/HIV KW - Polymerase Chain Reaction KW - DNA, Viral -- analysis KW - Cells, Cultured KW - Humans KW - Proviruses -- isolation & purification KW - Proviruses -- genetics KW - Kynurenine -- metabolism KW - Interferon-gamma -- pharmacology KW - Tryptophan -- metabolism KW - Neuroimmunomodulation KW - Human T-lymphotropic virus 1 -- physiology KW - Human T-lymphotropic virus 1 -- genetics KW - Quinolinic Acid -- blood KW - Monocytes -- metabolism KW - Macrophages -- virology KW - Monocytes -- drug effects KW - Macrophages -- ultrastructure KW - Monocytes -- virology KW - Macrophages -- drug effects KW - Monocytes -- ultrastructure KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78006037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Immunocytochemical+localization+of+the+endogenous+neuroexcitotoxin+quinolinate+in+human+peripheral+blood+monocytes%2Fmacrophages+and+the+effect+of+human+T-cell+lymphotropic+virus+type+I+infection.&rft.au=Venkateshan%2C+C+N%3BNarayanan%2C+R%3BEspey%2C+M+G%3BMoffett%2C+J+R%3BGajdusek%2C+D+C%3BGibbs%2C+C+J%3BNamboodiri%2C+M+A&rft.aulast=Venkateshan&rft.aufirst=C&rft.date=1996-02-20&rft.volume=93&rft.issue=4&rft.spage=1636&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-17 N1 - Date created - 1996-07-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Pharmacol Rev. 1993 Sep;45(3):309-79 [8248282] Virology. 1993 Sep;196(1):25-33 [8356797] Intern Med. 1993 Aug;32(8):623-8 [8312659] Int Rev Cytol. 1994;149:99-143 [8119784] J Neuropathol Exp Neurol. 1994 Mar;53(2):165-75 [8120538] Brain Res Bull. 1994;33(5):513-6 [8186995] J Neuroimmunol. 1994 Oct;54(1-2):69-73 [7929805] Ann Neurol. 1994 Nov;36(5):787-90 [7979225] Cell Tissue Res. 1994 Dec;278(3):461-9 [7850857] J Leukoc Biol. 1995 Feb;57(2):199-206 [7852833] Trans R Soc Trop Med Hyg. 1994 Jul-Aug;88(4):410-1 [7570819] Proc Natl Acad Sci U S A. 1978 Aug;75(8):3998-4000 [279015] Proc Natl Acad Sci U S A. 1979 Aug;76(8):4084-6 [291064] Arch Biochem Biophys. 1981 Dec;212(2):629-37 [6976775] Cell Immunol. 1984 May;85(2):384-95 [6232003] Life Sci. 1984 Jul 2;35(1):19-32 [6234446] Biochem Biophys Res Commun. 1988 Apr 15;152(1):237-42 [3128977] Proc Natl Acad Sci U S A. 1989 Mar;86(6):2021-5 [2467295] Brain Res. 1989 Jan 9;476(2):384-7 [2522807] Biochim Biophys Acta. 1989 Jul 11;1012(2):140-7 [2500976] Biol Chem Hoppe Seyler. 1989 Sep;370(9):1063-9 [2482041] Ann Neurol. 1991 Feb;29(2):202-9 [1826418] Clin Exp Immunol. 1993 Oct;94(1):32-7 [8403513] Brain Res. 1993 Oct 1;623(2):337-40 [8221118] J Virol. 1991 Nov;65(11):6362-4 [1920639] J Clin Microbiol. 1992 Apr;30(4):905-10 [1572977] Biochem J. 1992 May 1;283 ( Pt 3):633-5 [1534219] Brain Res. 1992 Jan 20;570(1-2):237-50 [1535532] FASEB J. 1992 Aug;6(11):2977-89 [1322853] J Acquir Immune Defic Syndr. 1992;5(8):810-6 [1517966] Brain. 1992 Oct;115 ( Pt 5):1249-73 [1422788] J Virol Methods. 1992 Nov;40(2):163-73 [1452632] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11784-8 [1465399] AIDS Res Hum Retroviruses. 1992 Nov;8(11):1845-9 [1489573] Leuk Lymphoma. 1992 Sep;8(1-2):147-55 [1337297] J Histochem Cytochem. 1993 Apr;41(4):559-70 [8450195] Blood. 1993 Mar 15;81(6):1598-606 [8453107] Biochem J. 1993 Apr 1;291 ( Pt 1):11-4 [8471029] J Neuropathol Exp Neurol. 1994 Jan;53(1):72-7 [8301322] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of a Rrp1 transgene reduces the somatic mutation and recombination frequency induced by oxidative DNA damage in Drosophila melanogaster. AN - 78003498; 8643678 AB - Recombination repair protein 1 (Rrp1) includes a C-terminal region homologous to several DNA repair proteins, including Escherichia coli exonuclease III and human APE, that repair oxidative and alkylation damage to DNA. The nuclease activities of Rrp1 include apurinic/apyrimidinic endonuclease, 3'-phosphodiesterase, 3'-phosphatase, and 3'-exonuclease. As shown previously, the C-terminal nuclease region of Rrp1 is sufficient to repair oxidative- and alkylation-induced DNA damage in repair-deficient E. coli mutants. DNA strand-transfer and single-stranded DNA renaturation activities are associated with the unique N-terminal region of Rrp1, which suggests possible additional functions that include recombinational repair or homologous recombination. By using the Drosophila w/w+ mosaic eye system, which detects loss of heterozygosity as changes in eye pigmentation, somatic mutation and recombination frequencies were determined in transgenic flies overexpressing wild-type Rrp1 protein from a heat-shock-inducible transgene. A large decrease in mosaic clone frequency is observed when Rrp1 overexpression precedes treatment with gamma-rays, bleomycin, or paraquat. In contrast, Rrp1 overexpression does not alter the spot frequency after treatment with the alkylating agents methyl methanesulfonate or methyl nitrosourea. A reduction in mosaic clone frequency depends on the expression of the Rrp1 transgene and on the nature of the induced DNA damage. These data suggest a lesion-specific involvement of Rrp1 in the repair of oxidative DNA damage. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Szakmary, A AU - Huang, S M AU - Chang, D T AU - Beachy, P A AU - Sander, M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/02/20/ PY - 1996 DA - 1996 Feb 20 SP - 1607 EP - 1612 VL - 93 IS - 4 SN - 0027-8424, 0027-8424 KW - Alkylating Agents KW - 0 KW - Drosophila Proteins KW - Recombinant Fusion Proteins KW - Bleomycin KW - 11056-06-7 KW - Nucleotidyltransferases KW - EC 2.7.7.- KW - Rrp1 protein, Drosophila KW - Paraquat KW - PLG39H7695 KW - Index Medicus KW - Clone Cells KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Gamma Rays KW - Mosaicism -- genetics KW - Eye Color -- genetics KW - Larva -- radiation effects KW - Bleomycin -- toxicity KW - Animals, Genetically Modified KW - Paraquat -- toxicity KW - Mutagenesis KW - Hot Temperature KW - Gene Expression Regulation KW - Alkylating Agents -- toxicity KW - Male KW - Female KW - Larva -- drug effects KW - Nucleotidyltransferases -- biosynthesis KW - Drosophila melanogaster -- growth & development KW - DNA Damage KW - Drosophila melanogaster -- genetics KW - Transgenes KW - DNA Repair -- genetics KW - Nucleotidyltransferases -- genetics KW - Recombination, Genetic -- genetics KW - Oxidative Stress KW - Drosophila melanogaster -- drug effects KW - Mutation -- genetics KW - Drosophila melanogaster -- radiation effects KW - Nucleotidyltransferases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78003498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Overexpression+of+a+Rrp1+transgene+reduces+the+somatic+mutation+and+recombination+frequency+induced+by+oxidative+DNA+damage+in+Drosophila+melanogaster.&rft.au=Szakmary%2C+A%3BHuang%2C+S+M%3BChang%2C+D+T%3BBeachy%2C+P+A%3BSander%2C+M&rft.aulast=Szakmary&rft.aufirst=A&rft.date=1996-02-20&rft.volume=93&rft.issue=4&rft.spage=1607&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-17 N1 - Date created - 1996-07-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Biochem. 1988;57:29-67 [3052275] Microbiol Rev. 1988 Mar;52(1):70-102 [3280967] EMBO J. 1991 May;10(5):1075-81 [1708721] Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6780-4 [1713691] Nucleic Acids Res. 1991 Aug 25;19(16):4523-9 [1653418] Mutat Res. 1992 Dec 1;284(1):159-75 [1279388] J Biol Chem. 1993 Jan 25;268(3):2075-82 [7678415] Mutagenesis. 1993 Jan;8(1):57-81 [8450769] Biochemistry. 1993 Oct 26;32(42):11445-52 [7692963] Nucleic Acids Res. 1993 Oct 11;21(20):4788-95 [7694234] Mutat Res. 1994 Jul;315(1):55-63 [7517011] Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8165-9 [7520176] J Biol Chem. 1994 Dec 23;269(51):32685-92 [7798276] Nucleic Acids Res. 1994 Nov 25;22(23):4884-9 [7800476] Nucleic Acids Res. 1994 Nov 25;22(23):4943-6 [7800484] Biochemistry. 1995 Jan 31;34(4):1267-74 [7530050] Mutat Res. 1995 Apr;334(2):247-58 [7885379] Z Indukt Abstamm Vererbungsl. 1957;88(3):333-73 [13496909] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Mol Gen Genet. 1972;115(4):302-13 [4624405] Dev Biol. 1975 Feb;42(2):211-21 [1116643] Nature. 1976 Apr 1;260(5550):425-6 [815826] Genetics. 1977 Jun;86(2 Pt. 1):357-76 [407129] J Biol Chem. 1981 Aug 25;256(16):8608-15 [6167580] Annu Rev Biochem. 1982;51:61-87 [6287922] Science. 1982 Oct 22;218(4570):341-7 [6289435] Science. 1982 Oct 22;218(4570):348-53 [6289436] Environ Mutagen. 1984;6(2):153-88 [6423380] Genetics. 1985 Jul;110(3):441-51 [3926606] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7731-5 [2429316] J Bacteriol. 1986 Dec;168(3):1120-7 [2430946] Mutat Res. 1987 Oct;180(2):201-6 [3116420] Mutat Res. 1987 Oct;182(5):243-64 [3116423] Mutagenesis. 1987 May;2(3):161-71 [3325739] FASEB J. 1990 Nov;4(14):3239-44 [2172063] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The beneficial effects of dietary restriction: reduced oxidative damage and enhanced apoptosis. AN - 77999786; 8657188 AB - There is compelling evidence for the central role of oxidative damage in the aging process and for the participation of reactive oxygen species in tumor initiation and promotion. Caloric restriction (CR) or energy restriction retards age-associated increases in mitochondrial free-radical production and reduces the accumulation of oxidatively damaged cell components. CR has also been shown to slow down age-related declines in various repair capabilities, including some types of DNA repair. It is proposed that inhibitors of mitochondrial electron transport and/or uncouplers of oxidative phosphorylation (rotenone, amytal, amiodarone, valinomycin, etc.), when used at extremely low doses, could mimic the effects of CR in model systems. The objective is to lower mitochondrial free-radical production by decreasing the fraction of electron carriers in the reduced state. In addition to a variety of other effects, CR has been shown to increase the rate of apoptosis, particularly in preneoplastic cells, and in general, to promote elevated levels of free glucocorticoids (GCs). GCs are known to induce tissue-specific apoptosis and to upregulate gap-junction-mediated intercellular communication (GJIC). Tumor promoters like phorbol esters have the opposite effect, in that they inhibit both the process of apoptosis and GJIC. The enzyme poly (ADP-ribose) polymerase (PARP) is thought to play a central role in apoptosis, in a manner that has been highly conserved in evolution. There is good evidence that the apoptosis-associated Ca/Mg-dependent DNA endonuclease is maintained in a latent form by being poly (ADP-ribosylated). Apoptosis would require the removal of this polymer from the endonuclease, and, most likely, its removal from topoisomerase II and histone H1 as well. The role of poly (ADP-ribose) in apoptosis, carcinogenesis, and aging could be studied by the use of modulators of PARP activity (3-aminobenzamide, 3-nitrosobenzamide, 1% ethanol, etc.), inhibitors of poly ADP-ribose) glycohydrolase activity (ethacridine, 43 degrees C, etc.), and inhibitors of the PARP-specific protease (interleukin-1 beta converting enzyme (ICE)-like protease). Also, it would be of interest to determine if CR can decrease the half-life of poly (ADP-ribose), upregulate GJIC, and modulate the activities of PARP, the glycohydrolase, and the PARP-specific protease, factors potentially important in these processes. JF - Mutation research AU - Wachsman, J T AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/02/19/ PY - 1996 DA - 1996 Feb 19 SP - 25 EP - 34 VL - 350 IS - 1 SN - 0027-5107, 0027-5107 KW - Hormones KW - 0 KW - Reactive Oxygen Species KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Poly(ADP-ribose) Polymerases -- genetics KW - Humans KW - Aging KW - Mitochondria -- metabolism KW - Hormones -- metabolism KW - Neoplasms -- prevention & control KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Apoptosis KW - Oxidative Stress KW - Energy Intake UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77999786?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=The+beneficial+effects+of+dietary+restriction%3A+reduced+oxidative+damage+and+enhanced+apoptosis.&rft.au=Wachsman%2C+J+T&rft.aulast=Wachsman&rft.aufirst=J&rft.date=1996-02-19&rft.volume=350&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-26 N1 - Date created - 1996-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microsatellite instability and mismatch repair defects in cancer. AN - 77997159; 8657182 JF - Mutation research AU - Thomas, D C AU - Umar, A AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences Research, Triangle Park, North Carolina 27709, USA. Y1 - 1996/02/19/ PY - 1996 DA - 1996 Feb 19 SP - 201 EP - 205 VL - 350 IS - 1 SN - 0027-5107, 0027-5107 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Carcinogens KW - Carrier Proteins KW - MLH1 protein, human KW - Mutagens KW - Neoplasm Proteins KW - Nuclear Proteins KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - MutL Protein Homolog 1 KW - EC 3.6.1.3 KW - Index Medicus KW - Methylnitronitrosoguanidine -- toxicity KW - Humans KW - Carcinogens -- toxicity KW - Chromosomes, Human, Pair 3 -- genetics KW - Mutagens -- toxicity KW - Phenotype KW - Base Sequence KW - Tumor Cells, Cultured KW - Neoplasm Proteins -- genetics KW - Molecular Sequence Data KW - Neoplasm Proteins -- metabolism KW - Microsatellite Repeats KW - DNA Repair KW - Neoplasms -- genetics KW - DNA Replication KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77997159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Microsatellite+instability+and+mismatch+repair+defects+in+cancer.&rft.au=Thomas%2C+D+C%3BUmar%2C+A%3BKunkel%2C+T+A&rft.aulast=Thomas&rft.aufirst=D&rft.date=1996-02-19&rft.volume=350&rft.issue=1&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-26 N1 - Date created - 1996-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppressors of Escherichia coli mutT: antimutators for DNA replication errors. AN - 77995964; 8657178 AB - Previous studies in our laboratory used a papillation assay to identify a set of mutations in the E. coli dnaE gene that confer increased accuracy of DNA replication (antimutators). These antimutators were isolated as suppressors of the hugh mutability of a mismatch-repair-defective mutL strain, in which the majority of mutations represent uncorrected replication errors (mainly A.T --> G.C and G.C --> A.T transitions). In the present study, we have sought suppressors of the high mutability of a mutT mutator strain. mutT strains produce a high frequency of A.T --> C.G transversions due to their lack of the mutT-encoded 8-oxo-dGTPase, leading to a high frequency of A.(8-oxoG) mispairing errors. Following localized mutagenesis of the dnaE-dnaQ region of the chromosome, two strong suppressors of mutT mutability were obtained, both residing in the dnaE gene (dnaE940 and dnaE941). When subsequently tested in a mutL strain, these two alleles also proved antimutators in this background, dnaE941 being significantly stronger than the previously isolated antimutators. The results suggest that the DNA polymerase may use similar mechanisms to discriminate against A.(8-oxoG) transversion mispairs and A.C or T.G transition mispairs. The finding may also have significance for teh interpretation of the antimutator effect conferred by these dnaE alleles in a wild-type (mut+) background. JF - Mutation research AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/02/19/ PY - 1996 DA - 1996 Feb 19 SP - 17 EP - 23 VL - 350 IS - 1 SN - 0027-5107, 0027-5107 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Genetic Markers KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Pyrophosphatases KW - EC 3.6.1.- KW - mutT protein, E coli KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Phenotype KW - Genotype KW - Deoxyguanosine -- metabolism KW - Alleles KW - DNA Repair KW - Chromosomes, Bacterial -- genetics KW - Deoxyguanosine -- genetics KW - Deoxyguanosine -- analogs & derivatives KW - DNA Replication -- genetics KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- metabolism KW - Suppression, Genetic KW - Phosphoric Monoester Hydrolases -- genetics KW - Escherichia coli -- genetics KW - Phosphoric Monoester Hydrolases -- metabolism KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77995964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Suppressors+of+Escherichia+coli+mutT%3A+antimutators+for+DNA+replication+errors.&rft.au=Schaaper%2C+R+M&rft.aulast=Schaaper&rft.aufirst=R&rft.date=1996-02-19&rft.volume=350&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-26 N1 - Date created - 1996-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural flexibility and functional versatility of cytochrome P450 and rapid evolution. AN - 77993754; 8657195 AB - P450 represents a large group of heme-thiolate enzymes that exhibit remarkably diverse activities for the metabolism of numerous endogenous and exogenous chemicals. Recent site-directed mutagenesis studies indicate that a single mutation at any of the key residues can be enough to alter the substrate and/or product specificities in the P450 activities. Molecular modeling predicts that these key residues are located within the substrate heme pocket. Structural elements involved in diversifying P450 activity appear to correspond to the B' helix, the F helix and the F/G interhelical loop in the bacterial P450s. Structures represented by these regions are extremely variable despite the fact that the core of the P450 substrate pocket is well conserved. A mutation within these regions may result in a significant geometrical alteration of the pocket and lead to diversify the P450 activity. Phylogenetical analysis shows a relatively high rate of nonsynonymous substitution within these substrate binding regions. The functional versatility of P450 can thus be largely accounted for in terms of pocket change brought about by rapid mutations. JF - Mutation research AU - Negishi, M AU - Iwasaki, M AU - Juvonen, R O AU - Sueyoshi, T AU - Darden, T A AU - Pedersen, L G AD - Laboratory of Reproductive and Development Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/02/19/ PY - 1996 DA - 1996 Feb 19 SP - 43 EP - 50 VL - 350 IS - 1 SN - 0027-5107, 0027-5107 KW - Iron-Sulfur Proteins KW - 0 KW - Recombinant Proteins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP2A6 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Iron-Sulfur Proteins -- genetics KW - Mice KW - Structure-Activity Relationship KW - Binding Sites KW - Iron-Sulfur Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Mixed Function Oxygenases -- metabolism KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Mutation -- genetics KW - Recombinant Proteins -- chemistry KW - Mixed Function Oxygenases -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- chemistry KW - Steroid Hydroxylases -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Steroid Hydroxylases -- genetics KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77993754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Structural+flexibility+and+functional+versatility+of+cytochrome+P450+and+rapid+evolution.&rft.au=Negishi%2C+M%3BIwasaki%2C+M%3BJuvonen%2C+R+O%3BSueyoshi%2C+T%3BDarden%2C+T+A%3BPedersen%2C+L+G&rft.aulast=Negishi&rft.aufirst=M&rft.date=1996-02-19&rft.volume=350&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-26 N1 - Date created - 1996-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The antievolutionary component of antimutagenesis and anticarcinogenesis: where do mutation rates come from and where are they going? AN - 77992316; 8657196 JF - Mutation research AU - Drake, J W AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. Y1 - 1996/02/19/ PY - 1996 DA - 1996 Feb 19 SP - 5 EP - 8 VL - 350 IS - 1 SN - 0027-5107, 0027-5107 KW - Antimutagenic Agents KW - 0 KW - Carcinogens KW - Index Medicus KW - Animals KW - DNA Repair KW - DNA Damage KW - Humans KW - Escherichia coli -- genetics KW - Neoplasms -- prevention & control KW - Bacteriophage T4 -- genetics KW - RNA Viruses -- genetics KW - Mutation KW - Neoplasms -- etiology KW - Carcinogens -- metabolism KW - Biological Evolution KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77992316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=The+antievolutionary+component+of+antimutagenesis+and+anticarcinogenesis%3A+where+do+mutation+rates+come+from+and+where+are+they+going%3F&rft.au=Drake%2C+J+W&rft.aulast=Drake&rft.aufirst=J&rft.date=1996-02-19&rft.volume=350&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-26 N1 - Date created - 1996-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of National Toxicology Program rodent bioassay data for anticarcinogenic effects. AN - 77992312; 8657174 AB - We reanalyzed data from 218 two-year rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). These data were originally collected for the purpose of identifying potential human carcinogens. However, the objective of our analysis was to investigate the frequency of possible anticarcinogenic effects in these data, since recurring cases of chemical-associated tumor reductions have been noted in the course of these studies over time. Our analysis reveals that most (>90%) NTP-tested chemicals show at least one statistically significant (p<0.05) decrease in site-specific tumor incidence. Because of the large number of statistical comparisons made in a long-term bioassay, random variability can account for many of these tumor decreases. However, we found that certain tumors (predominantly those with a high spontaneous incidence) show chemically related decreases far more frequently than chance expectation. Many of these decreases, particularly those for pituitary and mammary gland tumors, adrenal pheochromocytoma and uterine polyps in rats and liver and lung tumors in mice, are associated with the reduced body weights frequently observed in the dosed groups. The chemically related decreased incidences of leukemia in rats appear to be related to spleen damage, i.e., chemically related splenic toxicity is evident for most chemicals showing decreased incidences of leukemia. While random variability, associations with body weight and splenic toxicity can account for most of the decreased tumor incidences observed in NTP studies, there are other tumor decreases that could not be totally explained by these factors. Further investigations of possible mechanisms of action are underway. These data are relevant to the concept of chemoprevention as well as to the task of using long-term laboratory animal studies to predict enhanced human environmental-cancer risk for regulatory purposes. JF - Mutation research AU - Haseman, J K AU - Johnson, F M AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/02/19/ PY - 1996 DA - 1996 Feb 19 SP - 131 EP - 141 VL - 350 IS - 1 SN - 0027-5107, 0027-5107 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - United States KW - Animals KW - Biological Assay KW - Mice KW - Body Weight KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - National Institutes of Health (U.S.) KW - Databases, Factual KW - Neoplasms -- prevention & control KW - Female KW - Toxicology KW - Anticarcinogenic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77992312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Analysis+of+National+Toxicology+Program+rodent+bioassay+data+for+anticarcinogenic+effects.&rft.au=Haseman%2C+J+K%3BJohnson%2C+F+M&rft.aulast=Haseman&rft.aufirst=J&rft.date=1996-02-19&rft.volume=350&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-26 N1 - Date created - 1996-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid metabolism and inhibition of cell proliferation: an unexpected liaison. AN - 78035426; 8630993 AB - The rationale for the use of all-trans-retinoic acid (RA) as an anticancer agent is based on its ability to inhibit growth and promote differentiation of some neoplastic cells. However, RA is not effective in all conditions of cell culture, and in some cases, it may stimulate cell growth. We used a serum-free culture system to study the effect of RA on cell proliferation. Following 2 days of RA exposure, 9 of a total of 15 cell lines showed an inhibition of cell growth (RA-sensitive), while 6 of 15 cell lines showed resistance to RA (RA-resistant cells). Metabolic studies and high-performance liquid chromatography analysis of the cell-associated and medium extracts from cells incubated with [3H]RA revealed that all nine RA-sensitive cells showed a very high activity to metabolize RA to polar metabolites found in the medium. In sharp contrast, RA-resistant cells retained about 60% of the original RA at 76 h. However, conditioned medium from the sensitive cells was without activity on the growth of sensitive and resistant cells. We conclude that a relationship exists between RA inhibition of cell growth and intracellular RA metabolism. These data may help design useful strategies in cancer therapy by retinoids and dispel the notion that RA itself is responsible for the inhibition of cell growth. JF - Cancer research AU - Takatsuka, J AU - Takahashi, N AU - de Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/02/15/ PY - 1996 DA - 1996 Feb 15 SP - 675 EP - 678 VL - 56 IS - 4 SN - 0008-5472, 0008-5472 KW - Culture Media, Serum-Free KW - 0 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Tumor Cells, Cultured KW - HL-60 Cells KW - Kinetics KW - Humans KW - Cell Differentiation KW - Mice KW - Cell Line, Transformed KW - Female KW - Chromatography, High Pressure Liquid KW - Cell Line KW - Tretinoin -- pharmacology KW - Tretinoin -- metabolism KW - Cell Division -- physiology KW - Cell Division -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78035426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Retinoic+acid+metabolism+and+inhibition+of+cell+proliferation%3A+an+unexpected+liaison.&rft.au=Takatsuka%2C+J%3BTakahashi%2C+N%3Bde+Luca%2C+L+M&rft.aulast=Takatsuka&rft.aufirst=J&rft.date=1996-02-15&rft.volume=56&rft.issue=4&rft.spage=675&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-03 N1 - Date created - 1996-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. AN - 78036872; 8621683 AB - Reports that interleukin-8 (IL-8) induces the infiltration of neutrophils followed by T-cells into injection sites led us to postulate that by stimulation of neutrophil degranulation IL-8 may cause the release of factors with chemoattractant activity for T-lymphocytes. Extracts of human neutrophil granules were chromatographed to isolate and purify T-lymphocyte chemoattractant factors. Two major peaks of T-cell chemotactic activity were purified by C18 reversed phase high pressure liquid chromatography (HPLC). The first peak was resolved further by C4 reversed phase HPLC and yielded an active fraction shown by NH2-terminal amino acid sequence analysis to contain defensins HNP-1, HNP-2, and HNP-3. Purified defensins HNP-1 and HNP-2 (kindly provided by Dr. R. I. Lehrer, UCLA) were also potent chemoattractants for human T-cells, while HNP-3 was inactive. The second peak of T-cell chemoattractant activity was also further purified to homogeneity by C4 reversed phase HPLC and identified by NH2-terminal sequence analysis as CAP37/azurocidin, a protein with sequence homology to serine proteases. 0.1 100 ng of defensins and 1.0 100 ng/ml CAP37 were able to stimulate in vitro T-cell chemotaxis. Neutrophil activating factors, i.e. IL-8, phorbol 12-myristate 13-acetate/ionomycin, and formylmethionylleucylphenylalanine each induced the release of CAP37 and defensins from neutrophil granules. Subcutaneous administration of defensins or CAP37/azurocidin into BALB/c mice resulted in a moderate neutrophil and mononuclear cell infiltrate by 4 h, which was greater by 24 h at the site of injection. Additionally, subcutaneous injection of defensins into chimeric huPBL-SCID mice resulted in significant infiltration by human CD3+ cells within 4 h. These results identify the antimicrobial proteins, CAP37/azurocidin and defensins HNP-1 and HNP-2, as potent neutrophil-derived chemoattractants for T-cells. These proteins represent primordial antimicrobial peptides which may have evolved into acute inflammatory cell-derived signals that mobilize immunocompetent T-cells and other inflammatory cells. JF - The Journal of biological chemistry AU - Chertov, O AU - Michiel, D F AU - Xu, L AU - Wang, J M AU - Tani, K AU - Murphy, W J AU - Longo, D L AU - Taub, D D AU - Oppenheim, J J AD - Laboratory of Molecular Immunoregulation, Biological Response Modifiers Program, Division of Cancer Treatment, NCI, National Institutes of Health, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1996/02/09/ PY - 1996 DA - 1996 Feb 09 SP - 2935 EP - 2940 VL - 271 IS - 6 SN - 0021-9258, 0021-9258 KW - Antimicrobial Cationic Peptides KW - 0 KW - Blood Proteins KW - Carrier Proteins KW - Defensins KW - Interleukin-8 KW - Peptide Fragments KW - alpha-Defensins KW - cationic antimicrobial protein CAP 37, human KW - human neutrophil peptide 1 KW - human neutrophil peptide 2 KW - human neutrophil peptide 3 KW - Ionomycin KW - 56092-81-0 KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Humans KW - Peptide Fragments -- isolation & purification KW - Cytoplasmic Granules -- physiology KW - Amino Acid Sequence KW - Ionomycin -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - Chromatography, High Pressure Liquid KW - N-Formylmethionine Leucyl-Phenylalanine -- pharmacology KW - Peptide Fragments -- chemistry KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice, SCID KW - Neutrophils -- drug effects KW - Blood Proteins -- physiology KW - Blood Proteins -- chemistry KW - T-Lymphocytes -- physiology KW - Neutrophils -- physiology KW - Chemotaxis, Leukocyte KW - Blood Proteins -- pharmacology KW - Interleukin-8 -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78036872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+defensin-1%2C+defensin-2%2C+and+CAP37%2Fazurocidin+as+T-cell+chemoattractant+proteins+released+from+interleukin-8-stimulated+neutrophils.&rft.au=Chertov%2C+O%3BMichiel%2C+D+F%3BXu%2C+L%3BWang%2C+J+M%3BTani%2C+K%3BMurphy%2C+W+J%3BLongo%2C+D+L%3BTaub%2C+D+D%3BOppenheim%2C+J+J&rft.aulast=Chertov&rft.aufirst=O&rft.date=1996-02-09&rft.volume=271&rft.issue=6&rft.spage=2935&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-19 N1 - Date created - 1996-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of epidermal growth factor receptor gene transcription by phorbol 12-myristate 13-acetate is mediated by activator protein 2. AN - 78030827; 8621697 AB - The response of the epidermal growth factor (EGF) receptor gene to phorbol 12-myristate 13-acetate (PMA) was analyzed using nuclei and nuclear extracts prepared from PMA-treated KB cells. Transient transfection assays and nuclear run-off experiments showed that PMA increased EGF receptor gene transcription. Cell-free transcription with promoter mutants revealed that the region of the promoter containing nucleotides -150 to -16 was sufficient for PMA inducibility. A promoter fragment containing nucleotides -167 to -105 showed increased binding of a factor present in extracts prepared from PMA-treated cells. When this factor was partially purified by column chromatography, it showed specific PMA-dependent binding to an EGF receptor promoter fragment. This binding was competed by an SV40 fragment containing binding sites for Sp1, AP1, and AP2. Purified AP2 was used in DNase I footprinting experiments to show that this factor can bind to the EGF receptor promoter. Oligonucleotides corresponding to the AP2 binding sites found in the EGF receptor promoter showed the ability to bind AP2 and compete for the binding of a factor induced by PMA treatment. The addition of AP2 to nuclear extract resulted in increased transcription from the EGF receptor promoter. These results demonstrate that AP2 can activate EGF receptor gene expression and may mediate the PMA response of this gene. JF - The Journal of biological chemistry AU - Johnson, A C AD - Laboratory of Molecular Biology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/02/09/ PY - 1996 DA - 1996 Feb 09 SP - 3033 EP - 3038 VL - 271 IS - 6 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - Transcription Factor AP-2 KW - Transcription Factors KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - KB Cells KW - Cell Nucleus -- metabolism KW - HeLa Cells KW - Humans KW - RNA, Messenger -- analysis KW - RNA, Messenger -- biosynthesis KW - Binding Sites KW - Base Sequence KW - Transfection KW - DNA Footprinting KW - Molecular Sequence Data KW - Transcription, Genetic -- drug effects KW - Promoter Regions, Genetic -- drug effects KW - Transcription Factors -- metabolism KW - Transcription Factors -- isolation & purification KW - Tetradecanoylphorbol Acetate -- pharmacology KW - DNA-Binding Proteins -- isolation & purification KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Receptor, Epidermal Growth Factor -- biosynthesis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78030827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation+of+epidermal+growth+factor+receptor+gene+transcription+by+phorbol+12-myristate+13-acetate+is+mediated+by+activator+protein+2.&rft.au=Johnson%2C+A+C&rft.aulast=Johnson&rft.aufirst=A&rft.date=1996-02-09&rft.volume=271&rft.issue=6&rft.spage=3033&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-19 N1 - Date created - 1996-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors for adrenal cancer: an exploratory study. AN - 77986886; 8621222 AB - Adrenal cancer is a heterogeneous group of neoplasms with unknown etiology. In search of risk factors, we conducted a case-control study based on data from the 1986 National Mortality Followback Survey, which included a questionnaire sent to the next of kin of almost 20,000 deceased adults (age > or = 25 year) in the United States. Information was obtained on a large number of items, including use of cigarettes, alcohol, oral contraceptives (OCs), height and weight and food consumption patterns. A total of 176 subjects who died of adrenal cancer (88 men and 88 women) and 352 controls (176 men and 176 women) who died of causes unrelated to smoking, drinking or OCs (for female controls) were included in the study. Although information on histologic type was not available, most cases were estimated from incidence surveys to be adrenocortical carcinoma, with a small percentage being malignant pheochromocytoma or neuroblastoma. An increased risk was associated with heavy smoking (> or = 25 cigarettes/day) among men (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.0-4.4) but not women. No clear association was seen for alcohol use, height and weight or food consumption patterns in either sex. Among women, increased risks were found for ever users of OCs (OR = 1.8, 95% CI 1.0-3.2) and especially those who used them before age 25 (OR = 2.5, 95% CI 1.2-5.5). When the analysis was restricted to subjects with spousal respondents, more pronounced risks were seen for ever users of OCs and for those who used OCs before age 25. Our findings suggest that cigarette smoking and use of OCs may increase the risk of adrenal cancer, but additional studies are needed with more detailed information on risk factors and histologic type of adrenal cancer. JF - International journal of cancer AU - Hsing, A W AU - Nam, J M AU - Co Chien, H T AU - McLaughlin, J K AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1996/02/08/ PY - 1996 DA - 1996 Feb 08 SP - 432 EP - 436 VL - 65 IS - 4 SN - 0020-7136, 0020-7136 KW - Contraceptives, Oral KW - 0 KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Male KW - Female KW - Contraceptives, Oral -- adverse effects KW - Adrenal Gland Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77986886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Risk+factors+for+adrenal+cancer%3A+an+exploratory+study.&rft.au=Hsing%2C+A+W%3BNam%2C+J+M%3BCo+Chien%2C+H+T%3BMcLaughlin%2C+J+K%3BFraumeni%2C+J+F&rft.aulast=Hsing&rft.aufirst=A&rft.date=1996-02-08&rft.volume=65&rft.issue=4&rft.spage=432&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-14 N1 - Date created - 1996-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catalytic activity of the mouse guanine nucleotide exchanger mSOS is activated by Fyn tyrosine protein kinase and the T-cell antigen receptor in T cells. AN - 77996623; 8577703 AB - mSOS, a guanine nucleotide exchange factor, is a positive regulator of Ras. Fyn tyrosine protein kinase is a potential mediator in T-cell antigen receptor signal transduction in subsets of T cells. We investigated the functional and physical interaction between mSOS and Fyn in T-cell hybridoma cells. Stimulation of the T-cell antigen receptor induced the activation of guanine nucleotide exchange activity in mSOS immunoprecipitates. Overexpression of Fyn mutants with an activated kinase mutation and with a Src homology 2 deletion mutation resulted in a stimulation and suppression of the mSOS activity, respectively. The complex formations of Fyn-Shc, Shc-Grb2, and Grb2-mSOS were detected in the activated Fyn-transformed cells, whereas the SH2 deletion mutant of Fyn failed to form a complex with mSOS. Moreover, tyrosine phosphorylation of Shc was induced by the overexpression of the activated Fyn. These findings support the idea that Fyn activates the activity of mSOS bound to Grb2 through tyrosine phosphorylation of Shc. Unlike the current prevailing model, Fyn-induced activation of Ras might involve the stimulation of the catalytic guanine nucleotide exchange activity of mSOS. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Li, B AU - Subleski, M AU - Fusaki, N AU - Yamamoto, T AU - Copeland, T AU - Princler, G L AU - Kung, H AU - Kamata, T AD - Biological Carcinogenesis and Development Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996/02/06/ PY - 1996 DA - 1996 Feb 06 SP - 1001 EP - 1005 VL - 93 IS - 3 SN - 0027-8424, 0027-8424 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Eukaryotic Initiation Factor-2 KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Guanine Nucleotide Exchange Factors KW - Proteins KW - Proto-Oncogene Proteins KW - Receptor-CD3 Complex, Antigen, T-Cell KW - Receptors, Antigen, T-Cell KW - Recombinant Proteins KW - ras Guanine Nucleotide Exchange Factors KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Fyn protein, mouse KW - EC 2.7.10.2 KW - Proto-Oncogene Proteins c-fyn KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Gene Expression KW - Mice KW - Protein Binding KW - src Homology Domains KW - Mutagenesis, Site-Directed KW - Transfection KW - Kinetics KW - Eukaryotic Initiation Factor-2 -- metabolism KW - Point Mutation KW - Sequence Deletion KW - Proto-Oncogene Proteins -- biosynthesis KW - Proteins -- isolation & purification KW - Receptors, Antigen, T-Cell -- metabolism KW - Proto-Oncogene Proteins -- isolation & purification KW - Receptor-CD3 Complex, Antigen, T-Cell -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - T-Lymphocytes, Helper-Inducer -- metabolism KW - T-Lymphocytes, Helper-Inducer -- immunology KW - Receptor-CD3 Complex, Antigen, T-Cell -- immunology KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77996623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Catalytic+activity+of+the+mouse+guanine+nucleotide+exchanger+mSOS+is+activated+by+Fyn+tyrosine+protein+kinase+and+the+T-cell+antigen+receptor+in+T+cells.&rft.au=Li%2C+B%3BSubleski%2C+M%3BFusaki%2C+N%3BYamamoto%2C+T%3BCopeland%2C+T%3BPrincler%2C+G+L%3BKung%2C+H%3BKamata%2C+T&rft.aulast=Li&rft.aufirst=B&rft.date=1996-02-06&rft.volume=93&rft.issue=3&rft.spage=1001&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-14 N1 - Date created - 1996-03-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1992 Sep 15;267(26):18259-62 [1526965] J Biol Chem. 1992 Mar 15;267(8):5155-61 [1347529] Cell. 1993 Apr 9;73(1):179-91 [8462098] Nature. 1993 May 6;363(6424):45-51 [8479536] Nature. 1993 May 6;363(6424):83-5 [8479540] Nature. 1993 May 6;363(6424):85-8 [8479541] Nature. 1993 May 6;363(6424):88-92 [8386805] J Biol Chem. 1993 May 5;268(13):9165-8 [8387483] Cell. 1993 May 7;73(3):611-20 [8490966] Science. 1993 Jun 25;260(5116):1950-2 [8391166] Science. 1993 Jun 25;260(5116):1953-5 [8316835] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8504-8 [8104337] Science. 1993 Nov 5;262(5135):902-5 [8235613] J Biol Chem. 1993 Dec 25;268(36):27413-9 [8262983] Science. 1994 Feb 25;263(5150):1136-9 [7509083] Neuron. 1994 Mar;12(3):691-705 [8155326] J Exp Med. 1992 Jun 1;175(6):1483-92 [1375262] Science. 1992 Jun 5;256(5062):1456-9 [1604323] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6511-5 [1631150] Cell. 1992 Sep 4;70(5):741-50 [1387588] Cell. 1992 Sep 4;70(5):751-63 [1516132] J Biol Chem. 1994 Aug 19;269(33):21165-76 [8063737] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8512-6 [8078913] Cell. 1994 Sep 23;78(6):949-61 [7923364] Int Immunol. 1994 Aug;6(8):1245-55 [7981151] Biochem Biophys Res Commun. 1995 Nov 2;216(1):110-8 [7488076] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358-62 [2190221] Nature. 1990 Aug 23;346(6286):719-23 [2201921] Cell. 1991 Mar 8;64(5):875-8 [1848158] Nature. 1991 Mar 7;350(6313):62-6 [1706070] Cell. 1991 Apr 19;65(2):281-91 [2015626] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8869-73 [1409579] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The wing of the enhancer-binding domain of Mu phage transposase is flexible and is essential for efficient transposition. AN - 77992368; 8577730 AB - A tetramer of the Mu transposase (MuA) pairs the recombination sites, cleaves the donor DNA, and joins these ends to a target DNA by strand transfer. Juxtaposition of the recombination sites is accomplished by the assembly of a stable synaptic complex of MuA protein and Mu DNA. This initial critical step is facilitated by the transient binding of the N-terminal domain of MuA to an enhancer DNA element within the Mu genome (called the internal activation sequence, IAS). Recently we solved the three-dimensional solution structure of the enhancer-binding domain of Mu phage transposase (residues 1-76, MuA76) and proposed a model for its interaction with the IAS element. Site-directed mutagenesis coupled with an in vitro transposition assay has been used to assess the validity of the model. We have identified five residues on the surface of MuA that are crucial for stable synaptic complex formation but dispensable for subsequent events in transposition. These mutations are located in the loop (wing) structure and recognition helix of the MuA76 domain of the transposase and do not seriously perturb the structure of the domain. Furthermore, in order to understand the dynamic behavior of the MuA76 domain prior to stable synaptic complex formation, we have measured heteronuclear 15N relaxation rates for the unbound MuA76 domain. In the DNA free state the backbone atoms of the helix-turn-helix motif are generally immobilized whereas the residues in the wing are highly flexible on the pico- to nanosecond time scale. Together these studies define the surface of MuA required for enhancement of transposition in vitro and suggest that a flexible loop in the MuA protein required for DNA recognition may become structurally ordered only upon DNA binding. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Clubb, R T AU - Mizuuchi, M AU - Huth, J R AU - Omichinski, J G AU - Savilahti, H AU - Mizuuchi, K AU - Clore, G M AU - Gronenborn, A M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institues of Health, Bethesda, MD 20892-0520, USA. Y1 - 1996/02/06/ PY - 1996 DA - 1996 Feb 06 SP - 1146 EP - 1150 VL - 93 IS - 3 SN - 0027-8424, 0027-8424 KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - Recombinant Proteins KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Transposases KW - Index Medicus KW - DNA-Binding Proteins -- chemistry KW - Models, Molecular KW - Computer Graphics KW - Binding Sites KW - Magnetic Resonance Spectroscopy KW - Mathematics KW - Mutagenesis, Site-Directed KW - Helix-Loop-Helix Motifs KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Restriction Mapping KW - Recombinant Proteins -- chemistry KW - DNA-Binding Proteins -- metabolism KW - Protein Structure, Secondary KW - DNA, Viral -- chemistry KW - Enhancer Elements, Genetic KW - Bacteriophage mu -- enzymology KW - DNA Nucleotidyltransferases -- chemistry KW - DNA, Viral -- metabolism KW - DNA Nucleotidyltransferases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77992368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+wing+of+the+enhancer-binding+domain+of+Mu+phage+transposase+is+flexible+and+is+essential+for+efficient+transposition.&rft.au=Clubb%2C+R+T%3BMizuuchi%2C+M%3BHuth%2C+J+R%3BOmichinski%2C+J+G%3BSavilahti%2C+H%3BMizuuchi%2C+K%3BClore%2C+G+M%3BGronenborn%2C+A+M&rft.aulast=Clubb&rft.aufirst=R&rft.date=1996-02-06&rft.volume=93&rft.issue=3&rft.spage=1146&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-14 N1 - Date created - 1996-03-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Biochem. 1992;61:1011-51 [1323232] Cell. 1992 Jul 24;70(2):303-11 [1322248] J Mol Biol. 1993 Mar 20;230(2):364-72 [8464050] Nature. 1993 Jul 29;364(6436):412-20 [8332212] Cell. 1993 Aug 27;74(4):723-33 [8395353] Protein Sci. 1994 Jan;3(1):15-21 [8142892] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6654-8 [7912831] Structure. 1994 Nov 15;2(11):1041-8 [7881904] Protein Sci. 1995 May;4(5):855-62 [7663341] Cell. 1985 Jul;41(3):867-76 [2988793] Cell. 1987 Apr 24;49(2):253-62 [3032448] Cell. 1987 Nov 6;51(3):493-501 [2822259] J Biol Chem. 1989 Apr 5;264(10):5586-92 [2647722] Nature. 1989 Apr 20;338(6217):656-8 [2539564] Cell. 1989 Jul 28;58(2):399-408 [2546681] Biochemistry. 1989 Nov 14;28(23):8972-9 [2690953] Annu Rev Biochem. 1990;59:933-69 [2197994] Biochemistry. 1990 Aug 14;29(32):7387-401 [2223770] Cell. 1992 Mar 20;68(6):1101-8 [1312394] Genes Dev. 1992 Nov;6(11):2221-32 [1330829] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Xeroderma pigmentosum knockouts. AN - 77985026; 8569358 JF - Lancet (London, England) AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/02/03/ PY - 1996 DA - 1996 Feb 03 SP - 278 EP - 279 VL - 347 IS - 8997 SN - 0140-6736, 0140-6736 KW - Neoplasm Proteins KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - DNA Repair KW - Humans KW - Cockayne Syndrome -- genetics KW - Neoplasm Proteins -- genetics KW - Mice KW - Skin Neoplasms -- genetics KW - Xeroderma Pigmentosum -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77985026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Xeroderma+pigmentosum+knockouts.&rft.au=Kraemer%2C+K+H&rft.aulast=Kraemer&rft.aufirst=K&rft.date=1996-02-03&rft.volume=347&rft.issue=8997&rft.spage=278&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect. AN - 77978646; 8569364 AB - The glutathione S-transferases (GST) mediate exposure to various cytotoxic and genotoxic agents, including those associated with increased risk of the myelodysplastic syndromes (MDS). Both GST M1 (GSTM1) and GST theta 1 (GSTT1) genes have a "null" variant allele, in which the entire gene is absent. We tested whether the homozygous null genotype of GSTM1 and GSTT1 altered the risk for MDS. In a hospital-based case-control study we analysed lymphocyte or bone-marrow DNA samples from 96 patients with MDS and 201 cancer-free controls of similar age, race, and sex. We have restricted our report to the 92 white MDS patients. We analysed GSTM1 and GSTT1 genotypes by PCR. The frequency of the GSTT1 null genotype was higher among MDS cases (46%) than among controls (16%). Inheritance of the GSTT1 null genotype conferred a 4.3-fold of MDS (odds ratio 4.3, 95% CI 2.5-7.4, p < 0.00001). The GSTM1 null genotype was not associated with increased risk of MDS (odds ratio 0.8, 0.5-1.3). Individuals with the GSTT1 null genotype may have enhanced susceptibility to MDS. The mechanism might involve decreased detoxification of environmental or endogenous carcinogens. JF - Lancet (London, England) AU - Chen, H AU - Sandler, D P AU - Taylor, J A AU - Shore, D L AU - Liu, E AU - Bloomfield, C D AU - Bell, D A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/02/03/ PY - 1996 DA - 1996 Feb 03 SP - 295 EP - 297 VL - 347 IS - 8997 SN - 0140-6736, 0140-6736 KW - DNA KW - 9007-49-2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Abridged Index Medicus KW - Index Medicus KW - Genotype KW - Risk KW - Polymerase Chain Reaction KW - Odds Ratio KW - Humans KW - DNA -- analysis KW - Case-Control Studies KW - Middle Aged KW - Male KW - Female KW - Myelodysplastic Syndromes -- enzymology KW - Glutathione Transferase -- genetics KW - Myelodysplastic Syndromes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77978646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Increased+risk+for+myelodysplastic+syndromes+in+individuals+with+glutathione+transferase+theta+1+%28GSTT1%29+gene+defect.&rft.au=Chen%2C+H%3BSandler%2C+D+P%3BTaylor%2C+J+A%3BShore%2C+D+L%3BLiu%2C+E%3BBloomfield%2C+C+D%3BBell%2C+D+A&rft.aulast=Chen&rft.aufirst=H&rft.date=1996-02-03&rft.volume=347&rft.issue=8997&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 1997 May 17;349(9063):1450-1 [9164325] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot study of low dose oral methotrexate treatment for primary biliary cirrhosis. AN - 85232966; pmid-8607496 AB - OBJECTIVE: To assess the efficacy of low doses of oral methotrexate as therapy for primary biliary cirrhosis. METHODS: Ten symptomatic patients with this disease were treated with methotrexate at a dose of 15 mg/wk in an open label trial. RESULTS: Eight patients completed 1 yr of treatment and six completed 2. Pruritus and fatigue decreased in all patients treated for at least 1 yr. Mean levels of serum alkaline phosphatase, ALT, and IgM were less at 1 and 2 yr than corresponding baseline means. Total serum bilirubin increased in three patients during treatment. Serum aminotransferases and alkaline phosphatase became normal in one patient with stage I disease. Although liver biopsies at 1 and 2 yr revealed a decrease in the intensity of the inflammatory infiltrate, they also showed an increase in fibrosis suggestive of disease progression. Methotrexate was discontinued in five patients: for disease progression in four (one at 4 months, one at 1 yr, and two at 2 yr) and for intractable pruritus in one (at 4 months). All patients experienced transient mucositis and intermittent dyspepsia. CONCLUSIONS: These findings suggest that methotrexate treatment in patients with primary biliary cirrhosis is not beneficial in patients with advanced disease; in patients with early disease, methotrexate may be associated with amelioration of symptoms, reduction in serum biochemical indices of liver disease, and reduction in hepatic inflammation. However, prospective, randomized controlled trials will be necessary for definitive evaluation of the effects of methotrexate on the quality of life and survival of patients with primary biliary cirrhosis. JF - The American Journal of Gastroenterology AU - Bergasa, N V AU - Jones, A AU - Kleiner, D E AU - Rabin, L AU - Park, Y AU - Wells, M C AU - Hoofnagle, J H AD - Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. PY - 1996 SP - 295 EP - 299 VL - 91 IS - 2 SN - 0002-9270, 0002-9270 KW - Analysis of Variance KW - Human KW - Enzyme Tests KW - Aged KW - Alkaline Phosphatase KW - Pilot Projects KW - Folic Acid Antagonists KW - Immunosuppressive Agents KW - Transaminases KW - Comparative Study KW - Evaluation Studies KW - Adult KW - Liver KW - Methotrexate KW - Middle Age KW - Bilirubin KW - Liver Cirrhosis, Biliary KW - Time Factors KW - Immunoglobulin M KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85232966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Gastroenterology&rft.atitle=Pilot+study+of+low+dose+oral+methotrexate+treatment+for+primary+biliary+cirrhosis.&rft.au=Bergasa%2C+N+V%3BJones%2C+A%3BKleiner%2C+D+E%3BRabin%2C+L%3BPark%2C+Y%3BWells%2C+M+C%3BHoofnagle%2C+J+H&rft.aulast=Bergasa&rft.aufirst=N&rft.date=1996-02-01&rft.volume=91&rft.issue=2&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Gastroenterology&rft.issn=00029270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Working Party Report by the Committee for Minimal Standards of Terminology and Documentation in Digestive Endoscopy of the European Society of Gastrointestinal Endoscopy. Minimal standard terminology for a computerized endoscopic database. Ad hoc Task Force of the Committee. AN - 85231144; pmid-8607482 JF - The American Journal of Gastroenterology AU - Crespi, M AU - Delvaux, M AU - Schaprio, M AU - Venables, C AU - Zwiebel, F AD - National Cancer Institute Regina Elena, Rome, Italy. PY - 1996 SP - 191 EP - 216 VL - 91 IS - 2 SN - 0002-9270, 0002-9270 KW - Duodenoscopy KW - Documentation KW - Colonoscopy KW - Gastroscopy KW - Medical Records KW - Comparative Study KW - Diagnosis, Differential KW - Cholangiopancreatography, Endoscopic Retrograde KW - Human KW - Europe KW - Esophagoscopy KW - Endoscopy, Gastrointestinal KW - Information Systems KW - Terminology KW - Endoscopy, Digestive System KW - Societies, Medical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85231144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Gastroenterology&rft.atitle=Working+Party+Report+by+the+Committee+for+Minimal+Standards+of+Terminology+and+Documentation+in+Digestive+Endoscopy+of+the+European+Society+of+Gastrointestinal+Endoscopy.+Minimal+standard+terminology+for+a+computerized+endoscopic+database.+Ad+hoc+Task+Force+of+the+Committee.&rft.au=Crespi%2C+M%3BDelvaux%2C+M%3BSchaprio%2C+M%3BVenables%2C+C%3BZwiebel%2C+F&rft.aulast=Crespi&rft.aufirst=M&rft.date=1996-02-01&rft.volume=91&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Gastroenterology&rft.issn=00029270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Blood and air pollution: state of knowledge and research needs. AN - 85206389; pmid-8637733 AB - The ready access to blood (plasma and formed cellular elements) makes it unusually susceptible to the deleterious effects of pollutants whose origins may be in the air. The red blood cells' hemoglobin may be rendered useless for oxygen transport by combination with carbon monoxide or conversion to methemoglobin or sulfhemoglobin. Lead and arsine can damage the erythrocytes' membranes, resulting in anemia. Metabolites of benzene and other volatile polycyclic hydrocarbons are implicated in the causation of leukemias. The extensive use of pesticides and herbicides may be associated with the development of Hodgkin's disease, non-Hodgkin's lymphoma, and aplastic anemia. The carcinogenic risks from ionizing radiation, especially for leukemia, are well known. More information is needed concerning the epidemiology of environmental factors responsible for damage to blood. Enhanced knowledge about the molecular biology of toxins' effects on the hematopoietic system and improved detection and prevention technologies are needed to answer environmentally related health questions. JF - Otolaryngology--Head and Neck Surgery AU - Badman, D G AU - Jaffé E R AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-6600, USA. PY - 1996 SP - 205 EP - 208 VL - 114 IS - 2 SN - 0194-5998, 0194-5998 KW - Air Pollution KW - Leukemia KW - Oxygen Consumption KW - Hemoglobins KW - Human KW - Erythrocytes KW - Anemia KW - Air Pollutants KW - Research KW - Carcinogens KW - Lymphoma, Non-Hodgkin KW - Hodgkin Disease KW - Blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85206389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=Blood+and+air+pollution%3A+state+of+knowledge+and+research+needs.&rft.au=Badman%2C+D+G%3BJaff%C3%A9+E+R&rft.aulast=Badman&rft.aufirst=D&rft.date=1996-02-01&rft.volume=114&rft.issue=2&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of air pollution on African-American and other minority populations. AN - 85202844; pmid-8637745 JF - Otolaryngology--Head and Neck Surgery AU - Olden, K AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 VL - 114 IS - 2 SN - 0194-5998, 0194-5998 KW - Air Pollution KW - United States KW - Urban Health KW - Human KW - Poverty KW - Minority Groups KW - Blacks UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85202844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=Effects+of+air+pollution+on+African-American+and+other+minority+populations.&rft.au=Olden%2C+K&rft.aulast=Olden&rft.aufirst=K&rft.date=1996-02-01&rft.volume=114&rft.issue=2&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Bone: target and source of environmental pollutant exposure. AN - 85202603; pmid-8637737 AB - The skeleton can play a unique role in modulating and responding to environmental air pollutants. Bone and its metabolic activities may be immediate targets for particular agents, leading to skeletal disease. However, bone is also an important storage site in the body. Chemical pollutants may be actively absorbed into bone mineral and released later during the normal process of bone remodeling. Critical periods when bone remodeling is enhanced, such as pregnancy, lactation, menopause, immobilization, and exposure to microgravity, may be important to recognize because of the potential for enhanced release of previously stored chemical agents. Lead has been identified as a "criteria air pollutant" by the 1970 Clean Air Act because of its ubiquity in the environment and its effect on a multiplicity of health outcomes. It is used in this article as an example of a substance that can have both a direct effect on bone and a latent effect on other organ systems through release from bone long after the initial exposure. JF - Otolaryngology--Head and Neck Surgery AU - McGowan, J A AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-6500, USA. PY - 1996 SP - 220 EP - 223 VL - 114 IS - 2 SN - 0194-5998, 0194-5998 KW - Bone Remodeling KW - Bone and Bones KW - Human KW - Air Pollutants, Environmental KW - Bone Diseases KW - Lead KW - Pregnancy KW - Lactation KW - Absorption KW - Environmental Exposure KW - Menopause KW - Male KW - Female KW - Immobilization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85202603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=Bone%3A+target+and+source+of+environmental+pollutant+exposure.&rft.au=McGowan%2C+J+A&rft.aulast=McGowan&rft.aufirst=J&rft.date=1996-02-01&rft.volume=114&rft.issue=2&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Dosimetry measurements using a probe tube microphone in the ear canal. AN - 85160931; pmid-8609306 AB - Federal and international standards recommended use of microphone placement either on or in the vicinity of the shoulder for dosimetry to minimize deviations from the undisturbed sound field. Probe microphone measurements from the ear canal were compared to shoulder and chest measures in order to investigate the validity of current dosimetry methodologies. Six subjects were monitored in an industrial setting. As expected, ear-canal levels exceeded other measures for all subjects. Shoulder and chest measures showed very low intersubject variability whereas ear-canal measures resulted in large intersubject variability. The ear-canal methodology has the potential to identify individuals whose external ear gain exceed the mean, putting them at increased risk of noise-induced permanent threshold shift (NIPTS). It is proposed that overall external ear pressure gain be used as an index to adjust exposure levels when predicting NIPTS using ISO 1999. A normative database of external ear pressure gain was constructed from 30 ears for this purpose. JF - The Journal of the Acoustical Society of America AU - Shotland, L I AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 979 EP - 984 VL - 99 IS - 2 SN - 0001-4966, 0001-4966 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85160931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+the+Acoustical+Society+of+America&rft.atitle=Dosimetry+measurements+using+a+probe+tube+microphone+in+the+ear+canal.&rft.au=Shotland%2C+L+I&rft.aulast=Shotland&rft.aufirst=L&rft.date=1996-02-01&rft.volume=99&rft.issue=2&rft.spage=979&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Acoustical+Society+of+America&rft.issn=00014966&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of sonication of clinical specimens on detection of cytomegalovirus in shell vial cultures. AN - 78772931; 15566863 AB - The centrifugation-enhanced shell vial (SV) method of virus culturing has decreased the time to laboratory detection of many viruses, and has become the principal method for the rapid detection of cytomegalovirus (CMV) in clinical specimens. To examine the use of sonication and centrifugation of clinical specimens as a means of optimizing the sensitivity of SV detection of CMV, decreasing the toxicity of specimens to the SV monolayer, and facilitating the examination and interpretation of SV monolayers. A total of 350 clinical specimens submitted for CMV culture were processed and then divided in half, with one-half sonicated for 1 min in a cup-horn-equipped sonicator, and the other half left unsonicated. Sonicated specimens were centrifuged to recover a cell-free supernatant. SVs containing MRC-5 fibroblast monolayers were inoculated with either the unsonicated whole specimen or the cell-free supernatant, and were stained with monoclonal antibodies directed against the immediate-early antigen of CMV after 24 and 48 h of incubation. While no significant difference was observed in the overall number of specimens in which CMV was detected following sonication, sonication did afford a 31% increase in the number of CMV-positive specimens detected at 24 h. A significant reduction in toxicity of all specimens except for blood was observed for the sonicated specimens, although sonication of blood increased the number of blood specimens toxic to the monolayer by 40%. Use of the cell-free inoculum following sonication facilitated microscopic examination and interpretation of SV monolayers without adversely affecting the sensitivity of the culture. Sonication of clinical specimens prior to shell vial culturing for CMV is beneficial and can help to reduce specimen toxicity, facilitate interpretation of monolayers, and allow the earlier detection of a positive specimen. JF - Clinical and diagnostic virology AU - Engler, H D AU - Selepak, S T AU - Callaway, J AD - Microbiology Service, Clinical Pathology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Building 10, Room 2C-385, Bethesda, MD 20892-1508, USA. hengler@nih.gov Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 67 EP - 71 VL - 5 IS - 1 SN - 0928-0197, 0928-0197 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78772931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+diagnostic+virology&rft.atitle=Effects+of+sonication+of+clinical+specimens+on+detection+of+cytomegalovirus+in+shell+vial+cultures.&rft.au=Engler%2C+H+D%3BSelepak%2C+S+T%3BCallaway%2C+J&rft.aulast=Engler&rft.aufirst=H&rft.date=1996-02-01&rft.volume=5&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Clinical+and+diagnostic+virology&rft.issn=09280197&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-24 N1 - Date created - 2004-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antibody engineering of recombinant Fv immunotoxins for improved targeting of cancer: disulfide-stabilized Fv immunotoxins. AN - 78766237; 9816166 AB - Recombinant immunotoxins are chimeric proteins in which a truncated toxin is fused to a recombinant antigen-binding domain such as a recombinant Fv or Fab. Recombinant immunotoxins target cell surface receptors and other antigens on tumor cells. The antigen-binding and -targeting domains in recombinant immunotoxins are usually single-chain Fvs (scFv), which are the antibody variable regions connected by a flexible peptide linker and fused directly to a bacterial toxin. However, Fabs have also been used. Recombinant immunotoxins have very good activity in vitro on cultured human tumor cell lines and have produced complete regressions and cures of established tumor xenografts in nude mouse models. Problems with the stability and binding of some scFv immunotoxins as well as scFvs not linked to toxin led to the development of a new type of recombinant Fv immunotoxin in which the targeting variable domains of the Fv are stabilized by an interchain disulfide bond located in structurally conserved framework positions of the VH and VL domains. These are termed disulfide-stabilized Fvs (dsFv) or dsFv immunotoxins. dsFvs and dsFv immunotoxins have several advantages over scFv immunotoxins. This review summarizes the design, construction, activities in vitro and in vivo, and biochemical characteristics of dsFv immunotoxins and compares them with scFv immunotoxins. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Reiter, Y AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 245 EP - 252 VL - 2 IS - 2 SN - 1078-0432, 1078-0432 KW - Disulfides KW - 0 KW - Immunoglobulin Fragments KW - Immunotoxins KW - Recombinant Proteins KW - immunoglobulin Fv KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Humans KW - Mice KW - Drug Design KW - Protein Engineering KW - Immunoglobulin Fragments -- pharmacology KW - Neoplasms -- therapy KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78766237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Antibody+engineering+of+recombinant+Fv+immunotoxins+for+improved+targeting+of+cancer%3A+disulfide-stabilized+Fv+immunotoxins.&rft.au=Reiter%2C+Y%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1996-02-01&rft.volume=2&rft.issue=2&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of JC virus DNA amplified from urine of chronic progressive multiple sclerosis patients. AN - 78746291; 9345433 AB - Thirty-seven chronic progressive multiple sclerosis (MS) patients, 20 of whom were taking cyclosporine, were examined for excretion of JC virus (JCV) in the urine. Polymerase chain reaction (PCR) amplification of DNA in urinary cell extracts detected JCV in 30% of the MS urines. In the cyclosporine treated group four of 20 (20%) excreted JCV, whereas in the untreated group seven of 17 (41%) excreted JCV. Thus, cyclosporine treatment did not enhance urinary excretion of the virus. A control group consisting of an unselected series of 89 patients donating urine in a general medical clinic and 16 healthy volunteers showed 41% with detectable urinary JCV. Thirty-three percent of the control females excreted JCV (18/54), as did 49% of the control males (25/51). Although the percentage of MS patients excreting detectable virus was not increased compared to the control group, the presence of JCV in the urine provides a convenient source of the virus for further characterization. Genotyping of DNA fragments amplified from the VP1 region indicates mainly the presence of JCV Type 1 in these chronic progressive MS patients. This is also the type that predominates in the control group. An apparent recombinant between Type 1 and Type 3 (African) within the VP1 region, tentatively designated Type 1/3 (or Type 4), was found in both the MS group and the controls. A larger series of MS patients that includes relapsing/remitting disease will be required to determine whether the genotype profile of JCV excreted in the urine of MS patients differs significantly from controls. JF - Multiple sclerosis (Houndmills, Basingstoke, England) AU - Stoner, G L AU - Agostini, H T AU - Ryschkewitsch, C F AU - Baumhefner, R W AU - Tourtellotte, W W AD - Laboratory of Experimental Neuropathology, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 193 EP - 199 VL - 1 IS - 4 SN - 1352-4585, 1352-4585 KW - DNA, Viral KW - 0 KW - Immunosuppressive Agents KW - Cyclosporine KW - 83HN0GTJ6D KW - Index Medicus KW - Base Sequence KW - Humans KW - Adult KW - Molecular Sequence Data KW - Disease Progression KW - Case-Control Studies KW - Middle Aged KW - Chronic Disease KW - Amino Acid Sequence KW - Male KW - Female KW - Multiple Sclerosis -- urine KW - Polymerase Chain Reaction KW - Cyclosporine -- adverse effects KW - DNA, Viral -- analysis KW - Multiple Sclerosis -- virology KW - JC Virus -- isolation & purification KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78746291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Multiple+sclerosis+%28Houndmills%2C+Basingstoke%2C+England%29&rft.atitle=Characterization+of+JC+virus+DNA+amplified+from+urine+of+chronic+progressive+multiple+sclerosis+patients.&rft.au=Stoner%2C+G+L%3BAgostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BBaumhefner%2C+R+W%3BTourtellotte%2C+W+W&rft.aulast=Stoner&rft.aufirst=G&rft.date=1996-02-01&rft.volume=1&rft.issue=4&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Multiple+sclerosis+%28Houndmills%2C+Basingstoke%2C+England%29&rft.issn=13524585&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-25 N1 - Date created - 1997-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - T1 and T2 alterations in the brains of patients with hepatic cirrhosis. AN - 78574253; 8938307 AB - To determine whether previously reported T1-weighted MR hyperintensities in the brains of patients with hepatic cirrhosis are accompanied by changes in T2. We measured T1 and T2 in the brains of 10 patients with chronic liver disease and 7 age-matched healthy volunteers, using classic spin-echo sequences with multiple saturation recovery times and multiple echoes. Both T1 and T2 were shortened in the basal ganglia, cortex, and white matter of the patients, with the greatest shortening in the globus pallidus, where 1/T1 was increased by 0.76 s-1 or 74% and 1/T2 by 1.45 s-1 or 11%. The T1 changes were accompanied by T2 changes of greater magnitude that were not as visible because T2 is normally much shorter than T1, especially in the globus pallidus. JF - AJNR. American journal of neuroradiology AU - Vymazal, J AU - Babis, M AU - Brooks, R A AU - Filip, K AU - Dezortova, M AU - Hrncarkova, H AU - Hajek, M AD - Neuroimaging Branch, NINDS, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 333 EP - 336 VL - 17 IS - 2 SN - 0195-6108, 0195-6108 KW - Index Medicus KW - Reference Values KW - Brain Mapping KW - Humans KW - Brain -- pathology KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Hepatic Encephalopathy -- diagnosis KW - Liver Cirrhosis -- diagnosis KW - Liver Cirrhosis, Alcoholic -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78574253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AJNR.+American+journal+of+neuroradiology&rft.atitle=T1+and+T2+alterations+in+the+brains+of+patients+with+hepatic+cirrhosis.&rft.au=Vymazal%2C+J%3BBabis%2C+M%3BBrooks%2C+R+A%3BFilip%2C+K%3BDezortova%2C+M%3BHrncarkova%2C+H%3BHajek%2C+M&rft.aulast=Vymazal&rft.aufirst=J&rft.date=1996-02-01&rft.volume=17&rft.issue=2&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=AJNR.+American+journal+of+neuroradiology&rft.issn=01956108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-10 N1 - Date created - 1997-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional competition and homeosis in Drosophila. AN - 78560178; 8935992 AB - Interference between different classes of RNA polymerase II alleles causes a mutant phenotype called the "Ubx effect" that resembles one seen in flies haploinsufficient for the transcription factor, Ultrabithorax (Ubx). Flies carrying the mutation in the largest subunit of Drosophila RNA polymerase II, RpII215(4), display the Ubx effect when heterozygous as in RpII215(4)/+ but not when homozygous mutant or wild type. In this report we demonstrate that the interaction between alleles in different classes of polymerase occurs even in the absence of transcription by the wild-type polymerase. We utilized the resistance to the transcriptional inhibitor alpha-amanitin conferred by RpII215(4) to show that RpII215(4)/+ flies raised on alpha-amanitin-containing food still show the Ubx effect and are indistinguishable from flies raised on normal food. We demonstrate using HPLC that the intracellular concentration of alpha-amanitin in the developing larvae is sufficient to inhibit transcription by alpha-amanitin-sensitive polymerase. Furthermore, fluorescein-labeled alpha-amanitin accumulates in imaginal discs, which are the precursor cells for the tissue showing the homeotic transformation in adults. We conclude that the interaction between different classes of RNA polymerase II alleles resulting in the Ubx effect occurs prior to the block in transcription caused by alpha-amanitin. JF - Biochemical genetics AU - Burke, L P AU - Jones, T AU - Mortin, M A AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 45 EP - 59 VL - 34 IS - 1-2 SN - 0006-2928, 0006-2928 KW - Amanitins KW - 0 KW - DNA-Binding Proteins KW - Drosophila Proteins KW - Homeodomain Proteins KW - Transcription Factors KW - Ubx protein, Drosophila KW - RNA Polymerase II KW - EC 2.7.7.- KW - Index Medicus KW - Animals KW - Blotting, Western KW - Alleles KW - Larva -- metabolism KW - Heterozygote KW - Gene Expression Regulation KW - Larva -- chemistry KW - Female KW - Chromatography, High Pressure Liquid KW - Drosophila melanogaster -- chemistry KW - RNA Polymerase II -- genetics KW - Homeodomain Proteins -- genetics KW - Drosophila melanogaster -- genetics KW - DNA-Binding Proteins -- genetics KW - Amanitins -- metabolism KW - Transcription, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78560178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+genetics&rft.atitle=Transcriptional+competition+and+homeosis+in+Drosophila.&rft.au=Burke%2C+L+P%3BJones%2C+T%3BMortin%2C+M+A&rft.aulast=Burke&rft.aufirst=L&rft.date=1996-02-01&rft.volume=34&rft.issue=1-2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Biochemical+genetics&rft.issn=00062928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-24 N1 - Date created - 1997-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Outpatient monthly oral bolus cyclophosphamide therapy in systemic lupus erythematosus. AN - 78473905; 8882031 AB - An open label study to determine the feasibility and acute toxicity of a 6 month course of outpatient intermittent bolus high dose oral cyclophosphamide in patients with active systemic lupus erythematosus (SLE). Oral cyclophosphamide in a single dose of 0.5 to 1.0 g/m2 was given monthly for 6 consecutive months. Disease activity was monitored by quantitative assessments of urine sediment, 24h urine protein excretion, and the Systemic Lupus Activity Measure (SLAM). Twelve patients (11 with glomerulonephritis and one with thrombocytopenia) were studied. Improvements in SLAM scores, proteinuria, and urinary cellular casts were observed in the majority of the 9 patients with nephritis who completed the study. Adverse effects included mild nausea in most patients and intercurrent infections in 2 patients (herpes zoster, cellulitis, urinary tract infection). Three patients failed to complete the 6 month course of therapy because of treatment failure in the patient with thrombocytopenia, pregnancy, and severe vomiting, respectively. High dose pulse oral cyclophosphamide is an acceptable alternative for the aggressive outpatient management of selected patients with lupus nephritis. JF - The Journal of rheumatology AU - Dawisha, S M AU - Yarboro, C H AU - Vaughan, E M AU - Austin, H A AU - Balow, J E AU - Klippel, J H AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 273 EP - 278 VL - 23 IS - 2 SN - 0315-162X, 0315-162X KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Administration, Oral KW - Proteinuria -- urine KW - Drug Administration Schedule KW - Humans KW - Infection -- etiology KW - Feasibility Studies KW - Immunosuppression -- adverse effects KW - Drug Eruptions KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Cyclophosphamide -- administration & dosage KW - Cyclophosphamide -- therapeutic use KW - Lupus Erythematosus, Systemic -- drug therapy KW - Lupus Erythematosus, Systemic -- urine KW - Lupus Erythematosus, Systemic -- physiopathology KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78473905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+rheumatology&rft.atitle=Outpatient+monthly+oral+bolus+cyclophosphamide+therapy+in+systemic+lupus+erythematosus.&rft.au=Dawisha%2C+S+M%3BYarboro%2C+C+H%3BVaughan%2C+E+M%3BAustin%2C+H+A%3BBalow%2C+J+E%3BKlippel%2C+J+H&rft.aulast=Dawisha&rft.aufirst=S&rft.date=1996-02-01&rft.volume=23&rft.issue=2&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+rheumatology&rft.issn=0315162X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Rheumatol. 1996 Feb;23(2):212-3 [8882020] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A prospective study of the effectiveness of low dose omeprazole as initial therapy in Zollinger-Ellison syndrome. AN - 78443569; 8871445 AB - The proton pump inhibitors (omeprazole and lansoprazole) are the drugs of choice for the medical management of gastric acid hypersecretion in Zollinger-Ellison syndrome (ZES). These drugs are safe for long-term therapy but are acid-labile and high doses are expensive. The recommended starting dose of omeprazole is 60 mg/day. However, it has been shown in recent studies that the maintenance dose of omeprazole could be safely reduced to 20 mg once or twice a day in more than two-thirds of patients with ZES. The purpose of this study is to determine if an initial starting dose of omeprazole 20 mg/day is safe and effective in patients with ZES. Forty-nine consecutive patients with ZES being treated with ranitidine for at least 2 weeks were admitted to the NIH. Omeprazole 20 mg was started on day 1 of the admission and ranitidine discontinued 4 h after the first dose. Gastric acid output was measured for 1 h prior to the next omeprazole dose on day 2, then on day 3 if the value was > 10 mmol/h on the previous day. If acid-peptic symptoms developed or the gastric acid output remained > 10 mmol/h on day 3, the patient was considered to have failed omeprazole 20 mg/day initial therapy and the dose titrated daily to achieve adequate control of acid-peptic symptoms and gastric secretion. In 33 of the 49 patients (68%) omeprazole 20 mg/day was successful as initial therapy. Sixteen patients (32%) failed this initial omeprazole dose (eight patients owing to persistent peptic symptoms and eight patients owing to inadequate acid control). The final daily omeprazole dose required in these patients was 40 mg in eight patients (16%), 60 mg in one patient (2%) and 80 mg in seven patients (14%). Basal acid output (BAO) was the only clinical or laboratory feature that was significantly different between the two groups in which low dose initial omeprazole therapy was or was not successful; all patients with basal acid output < 20 mmol/h had a successful outcome. Because of the need to rapidly control gastric acid hypersecretion owing to the high risk of complications from peptic ulcer disease, patients with ZES should continue to be started on omeprazole 60 mg/day and the dose adjusted by acute titration methods as is currently recommended. After a maintenance dose is established, attempts should be undertaken to reduce the dose to 20 mg/ day once or twice a day. Only the minority of patients with ZES in whom basal acid output is known to be < 20 mmol/h (20% of patients) should be started on a low initial omeprazole dose. JF - Alimentary pharmacology & therapeutics AU - Termanini, B AU - Gibril, F AU - Stewart, C A AU - Weber, H C AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892-1804, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 61 EP - 71 VL - 10 IS - 1 SN - 0269-2813, 0269-2813 KW - Anti-Ulcer Agents KW - 0 KW - Enzyme Inhibitors KW - Omeprazole KW - KG60484QX9 KW - Index Medicus KW - Prospective Studies KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Gastric Acid -- secretion KW - Enzyme Inhibitors -- adverse effects KW - Enzyme Inhibitors -- administration & dosage KW - Anti-Ulcer Agents -- adverse effects KW - Zollinger-Ellison Syndrome -- drug therapy KW - Omeprazole -- adverse effects KW - Omeprazole -- administration & dosage KW - Anti-Ulcer Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78443569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alimentary+pharmacology+%26+therapeutics&rft.atitle=A+prospective+study+of+the+effectiveness+of+low+dose+omeprazole+as+initial+therapy+in+Zollinger-Ellison+syndrome.&rft.au=Termanini%2C+B%3BGibril%2C+F%3BStewart%2C+C+A%3BWeber%2C+H+C%3BJensen%2C+R+T&rft.aulast=Termanini&rft.aufirst=B&rft.date=1996-02-01&rft.volume=10&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Alimentary+pharmacology+%26+therapeutics&rft.issn=02692813&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-10 N1 - Date created - 1997-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in lung cancer following radiation therapy for Hodgkin's disease. AN - 78409251; 8850268 AB - High risks of lung cancer occur after successful treatment of Hodgkin's disease. In addition to tobacco smoking, other risk factors include radiotherapy, chemotherapy, and immunosuppression, although the relative contributions of each are unknown. We conducted p53 mutational spectrum analysis in second lung cancers after radiation therapy for Hodgkin's disease in the Netherlands and in Ontario, Canada. Lung cancer tissues from 11 patients were analyzed by p53 immunohistochemistry and DNA sequence analysis. All were male cigarette smokers, all received radiation therapy, and six also received chemotherapy. The lung cancers occurred 9.8 years (mean) after treatment. Radiation doses to lung lobes that developed the tumors averaged 5.7 Gy (range, 3.7-11.7 Gy). Sequence analysis showed four missense and two silent p53 point mutations in five patients. There were four G:C-->A:T transitions; three of four mutated deoxyguanines occurred on the coding strand, and one was a CpG site. There were two transversions: one G:C-->C:G and one A:T-->C:G. Despite moderate or heavy smoking histories in all patients, the mutational spectrum appears to differ from usual smoking-related lung cancers in which G:C-->T:A transversions predominate. The absence of G:C-->T:A mutations and the prominence of G:C-->A:T transitions, which are characteristic of radiation and oxidative damage, suggest that radiotherapy might have caused some of the p53 mutations. These data illustrate the potential of mutation analysis to determine causes of human cancer. If confirmed in a larger series, these results imply that some radiation-induced cancers can be distinguished from those caused by other factors. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - De Benedetti, V M AU - Travis, L B AU - Welsh, J A AU - van Leeuwen, F E AU - Stovall, M AU - Clarke, E A AU - Boice, J D AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 93 EP - 98 VL - 5 IS - 2 SN - 1055-9965, 1055-9965 KW - Codon KW - 0 KW - DNA, Neoplasm KW - Deoxyguanine Nucleotides KW - Index Medicus KW - Point Mutation -- genetics KW - Codon -- genetics KW - Humans KW - Smoking -- adverse effects KW - Transcription, Genetic KW - Neoplasms, Radiation-Induced -- genetics KW - DNA, Neoplasm -- analysis KW - Sequence Analysis, DNA KW - DNA Damage -- genetics KW - Exons -- genetics KW - CpG Islands -- radiation effects KW - Risk Factors KW - Radiotherapy Dosage KW - Adult KW - Deoxyguanine Nucleotides -- genetics KW - CpG Islands -- genetics KW - DNA, Neoplasm -- genetics KW - Middle Aged KW - Immunohistochemistry KW - Male KW - Immunosuppression KW - Hodgkin Disease -- radiotherapy KW - Genes, p53 -- radiation effects KW - Neoplasms, Second Primary -- genetics KW - Hodgkin Disease -- drug therapy KW - Genes, p53 -- genetics KW - Mutation -- genetics KW - Lung Neoplasms -- genetics KW - Mutation -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78409251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=p53+mutations+in+lung+cancer+following+radiation+therapy+for+Hodgkin%27s+disease.&rft.au=De+Benedetti%2C+V+M%3BTravis%2C+L+B%3BWelsh%2C+J+A%3Bvan+Leeuwen%2C+F+E%3BStovall%2C+M%3BClarke%2C+E+A%3BBoice%2C+J+D%3BBennett%2C+W+P&rft.aulast=De+Benedetti&rft.aufirst=V&rft.date=1996-02-01&rft.volume=5&rft.issue=2&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-19 N1 - Date created - 1996-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Permeabilization of eggs of the malaria mosquito Anopheles gambiae. AN - 78350166; 8812094 AB - Although Anopheles gambiae embryos that have developed for 15 h at 17 degrees C are slightly permeable to water, they are impermeable to ethylene glycol, the cryoprotectant used in the cryopreservation of Drosophila melanogaster embryos. Success in cryopreservation requires that they be made permeable to protective solutes. Permeabilization of D. melanogaster was achieved by 1) dechorionation with 50% Clorox (household bleach) followed by 2) a water flush; 3) immersion in isopropyl alcohol to remove most extraembryonic water; 4) 2 min air drying to remove most isopropyl alcohol; 5) 90-s exposure to n-heptane containing 0.3% 1-butanol; and 6) 15-s exposure to pure n-heptane. The permeability of A. gambiae embryos was assessed by determining the times required for the initial dehydration of embryos in 1 M ethylene glycol in 260 mOsm Drosophila culture medium (permeability to water) and the times required for their return to normal volume (permeability to ethylene glycol). Based on these criteria, the above D. melanogaster procedure effectively permeabilizes 15 h/17 degrees C to 19 h/17 degrees C A. gambiae embryos. Nearly all collapsed in <5 min, and most returned to normal volume in approximately 40 min. Although permeable, all were killed by the permeabilization procedure. In analyzing the effect of each step on viability, 50% Clorox caused some lethality, and Clorox followed by isopropyl alcohol was 100% lethal. Decreasing the Clorox concentration to 10% still dechorionated eggs, but with reduced toxicity; substitution of a 10% solution of reagent-grade sodium hypochlorite for Clorox further decreased toxicity. The isopropyl alcohol step was also toxic. Consequently, the removal of residual surface water was achieved by substituting air drying for isopropyl alcohol. The drying took place under direct microscope observation and was continued until the embryos began to shrink. The combination of this modified method for dechorionation and controlled air drying before exposure to heptane resulted in permeabilization of all embryos in most runs and in approximately 30% survival of the permeabilized embryos. JF - Cryobiology AU - Valencia, M D AU - Miller, L H AU - Mazur, P AD - The Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 149 EP - 162 VL - 33 IS - 1 SN - 0011-2240, 0011-2240 KW - Cryoprotective Agents KW - 0 KW - Ethylene Glycols KW - Sodium Hypochlorite KW - DY38VHM5OD KW - Ethylene Glycol KW - FC72KVT52F KW - Index Medicus KW - Animals KW - Humans KW - Ovum -- drug effects KW - Ethylene Glycols -- pharmacokinetics KW - Evaluation Studies as Topic KW - Malaria -- prevention & control KW - Cell Membrane Permeability -- drug effects KW - Sodium Hypochlorite -- pharmacology KW - Drosophila melanogaster KW - Insect Vectors KW - Ovum -- metabolism KW - Female KW - Cryoprotective Agents -- pharmacokinetics KW - Anopheles -- embryology KW - Anopheles -- metabolism KW - Cryopreservation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78350166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cryobiology&rft.atitle=Permeabilization+of+eggs+of+the+malaria+mosquito+Anopheles+gambiae.&rft.au=Valencia%2C+M+D%3BMiller%2C+L+H%3BMazur%2C+P&rft.aulast=Valencia&rft.aufirst=M&rft.date=1996-02-01&rft.volume=33&rft.issue=1&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Cryobiology&rft.issn=00112240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-23 N1 - Date created - 1996-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequential trends in overall and cause-specific mortality in diabetic and nondiabetic Pima Indians. AN - 78259488; 8718428 AB - To compare sequential trends in overall and cause-specific death rates for diabetic and nondiabetic Pima Indians. Underlying causes of death in Pimas aged > or = 15 years old were determined for the years 1975-1989 from review of death certificates and medical records. Overall and cause-specific death rates were compared for consecutive intervals. The all-causes death rate, age- and sex-adjusted, did not change significantly between the first and second halves of the study for diabetic (death rate ratio [DRR] = 0.99, 95% CI 0.70-1.4) or nondiabetic Pimas (DRR = 0.92, 95% CI 0.74-1.1). Among diabetic Pimas, however, the death rate for diabetic nephropathy declined from 2.7 to 1.5/1,000 person-years (DRR = 0.55, 95% CI 0.33-0.93), with ischemic heart disease (IHD) replacing diabetic nephropathy as the leading cause in the second half (DRR = 1.5, 95% CI 0.91-2.6). For diabetic and nondiabetic Pimas combined, the death rate in three consecutive 5-year periods declined progressively for alcoholic liver disease (P = 0.024) and external causes of death (P = 0.016), the largest component of which was automobile accidents. The decrease in death rate for diabetic nephropathy may be a result of greater access to and improvements in renal replacement therapy. Because of shared risk factors, however, the IHD death rate increased and largely offset the decrease in diabetic nephropathy deaths. The decline in deaths from alcoholic liver disease and from automobile accidents parallels the national trend. JF - Diabetes care AU - Sievers, M L AU - Nelson, R G AU - Bennett, P H AD - Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Arizona, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 107 EP - 111 VL - 19 IS - 2 SN - 0149-5992, 0149-5992 KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Sex Characteristics KW - Neoplasms -- mortality KW - Cerebrovascular Disorders -- mortality KW - Humans KW - Risk Assessment KW - Ethnic Groups KW - Adult KW - Arizona KW - Liver Diseases, Alcoholic -- mortality KW - Myocardial Ischemia -- mortality KW - Adolescent KW - Communicable Diseases -- mortality KW - Indians, North American KW - Diabetic Nephropathies -- mortality KW - Diabetes Mellitus -- mortality KW - Cause of Death -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78259488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes+care&rft.atitle=Sequential+trends+in+overall+and+cause-specific+mortality+in+diabetic+and+nondiabetic+Pima+Indians.&rft.au=Sievers%2C+M+L%3BNelson%2C+R+G%3BBennett%2C+P+H&rft.aulast=Sievers&rft.aufirst=M&rft.date=1996-02-01&rft.volume=19&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Diabetes+care&rft.issn=01495992&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-11 N1 - Date created - 1996-10-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Diabetes Care. 1996 Jul;19(7):779 [8799643] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The sensitivity of the NTP bioassay for carcinogen hazard evaluation can be modulated by dietary restriction. AN - 78082210; 8672866 AB - Studies were undertaken to compare outcomes when four chemicals were evaluated under typical NTP bioassay conditions as well as by protocols employing dietary restriction. Four chemicals, using three different routes of exposure (in utero [accomplished by feeding the dam dosed feed], dosed feed, and gavage) were used to 1) evaluate the effect of diet restriction on the sensitivity of the bioassay toward chemically-induced chronic toxicity and carcinogenicity; and 2) evaluate the effect of weight-matched control groups on the sensitivity of the bioassays. Control and chemical exposed F344 rats and B6C3F1 mice (50-60/group) were fed NIH-07 diet either ad libitum or at restricted levels such that body weights were approximately 80% of ad libitum control weights. The dietary restricted groups were either sacrificed at the end of two or 3-years. Results consistently show that feed restriction decreased the incidence of neoplastic and non-neoplastic lesions at a variety of anatomic sites in both control and chemical exposed animals. Furthermore, the sensitivity of the bioassay to detect chemical carcinogenic response were altered by dietary restriction: three of the four chemicals were found to increase the incidence of neoplastic lesions at four sites when evaluated under standard ad libitum conditions for 104 weeks. When unexposed and exposed groups were both subjected to dietary restriction, none of these 4 sites were detected as a target for carcinogenesis after two or three years. Rather, two different sites of carcinogenesis were detected. When the top dosed ad libitum fed animals were compared against their weight-matched control groups, a total of 10 sites were identified as targets for carcinogenesis. These included all four sites identified under the ad libitum protocol, both sites identified under the feed restricted protocol, and an additional four sites that were not identified under the other two protocols. These studies show that dietary restriction of all animals can be expected of decrease the sensitivity of carcinogenesis bioassays. However, restricting only unexposed groups (weight matching) of control for non-specific weight loss in chemical exposed groups yielded the most sensitivity among our comparisons. JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie AU - Abdo, K M AU - Kari, F W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 129 EP - 137 VL - 48 IS - 2-3 SN - 0940-2993, 0940-2993 KW - Hydroquinones KW - 0 KW - Phthalic Acids KW - Sulfasalazine KW - 3XC8GUZ6CB KW - Scopolamine Hydrobromide KW - 451IFR0GXB KW - 2-tert-butylhydroquinone KW - C12674942B KW - butylbenzyl phthalate KW - YPC4PJX59M KW - Index Medicus KW - Sensitivity and Specificity KW - Sulfasalazine -- toxicity KW - Animals KW - Dose-Response Relationship, Drug KW - Intubation, Gastrointestinal KW - Phthalic Acids -- administration & dosage KW - Mice KW - Scopolamine Hydrobromide -- toxicity KW - Phthalic Acids -- toxicity KW - Hydroquinones -- toxicity KW - Rats KW - Eating KW - Rats, Inbred F344 KW - Scopolamine Hydrobromide -- administration & dosage KW - Body Weight -- drug effects KW - Mice, Inbred C57BL KW - Sulfasalazine -- administration & dosage KW - Hydroquinones -- administration & dosage KW - Female KW - Male KW - Carcinogenicity Tests -- methods KW - Food Deprivation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78082210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.atitle=The+sensitivity+of+the+NTP+bioassay+for+carcinogen+hazard+evaluation+can+be+modulated+by+dietary+restriction.&rft.au=Abdo%2C+K+M%3BKari%2C+F+W&rft.aulast=Abdo&rft.aufirst=K&rft.date=1996-02-01&rft.volume=48&rft.issue=2-3&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.issn=09402993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-15 N1 - Date created - 1996-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promoters for the human beta-hexosaminidase genes, HEXA and HEXB. AN - 78062441; 8634145 AB - Human lysosomal beta-hexosaminidases are encoded by two genes, HEXA and HEXB, specifying an alpha- and a beta-subunit, respectively. The subunits dimerize to form beta-hexosaminidase A (alpha beta), beta-hexosaminidase B (beta beta), and beta-hexosaminidase S (alpha alpha). This enzyme system has the capacity to degrade a variety of cellular substrates: oligosaccharides, glycosaminoglycans, and glycolipids containing beta-linked N-acetylglucosaminyl or N-galactosaminyl residues. Mutations in either the HEXA gene or HEXB gene lead to an accumulation of GM2 ganglioside in neurons, resulting in the severe neurodegenerative disorders termed the GM2 gangliosidoses. To identify the DNA elements responsible for hexosaminidase expression, we ligated the 5'-flanking sequences of both the human and mouse hexosaminidase genes to a chloramphenicol acetyltransferase (CAT) gene. The resulting plasmids were transfected into NIH-3T3 cells and CAT activity was determined as a measure of promoter strength. By 5' deletion analysis, it was found that essential sequences for HEXA expression resided within a 40-bp region between 100 bp and 60 bp upstream of the ATG initiation codon. This area contained two potential estrogen response element half-sites as well as potential binding sites for transcription factors NF-E1 and AP-2. Similarly, important HEXB promoter sequences were localized to a 60-bp region between 150 bp and 90 bp upstream of the ATG codon. By performing scanning mutagenesis on a 60-bp region within the 150-bp HEXB construct, we defined an essential promoter element of 12 bp that contained two potential AP-1 sites. The mouse Hexa and Hexb 5'-flanking sequences were found to contain regions similar in sequence, location, and activity to the essential promoter elements defined in the cognate human genes. No sequence similarity was found, however, between 5'-flanking regions of the HEXA and HEXB genes. These essential promoter elements represent potential sites for HEXA and HEXB mutations that could alter enzyme expression in Tay-Sachs and Sandhoff diseases, respectively. JF - DNA and cell biology AU - Norflus, F AU - Yamanaka, S AU - Proia, R L AD - Section on Biochemical Genetics, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 89 EP - 97 VL - 15 IS - 2 SN - 1044-5498, 1044-5498 KW - Isoenzymes KW - 0 KW - Muscle Proteins KW - Nerve Tissue Proteins KW - Recombinant Fusion Proteins KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Hexosaminidase A KW - EC 3.2.1.52 KW - Hexosaminidase B KW - beta-N-Acetylhexosaminidases KW - Index Medicus KW - Tay-Sachs Disease -- enzymology KW - Animals KW - Recombinant Fusion Proteins -- biosynthesis KW - Leydig Cells -- enzymology KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Humans KW - Nerve Tissue Proteins -- biosynthesis KW - Muscle, Skeletal -- enzymology KW - Muscle Proteins -- biosynthesis KW - Tay-Sachs Disease -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Genes, Reporter KW - Molecular Sequence Data KW - Sandhoff Disease -- genetics KW - Lysosomes -- enzymology KW - Viscera -- enzymology KW - Male KW - 3T3 Cells KW - Placenta -- enzymology KW - Sertoli Cells -- enzymology KW - Mice KW - Organ Specificity KW - Nerve Tissue Proteins -- genetics KW - Muscle Proteins -- genetics KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Brain -- enzymology KW - Base Sequence KW - Species Specificity KW - Sandhoff Disease -- enzymology KW - Female KW - Promoter Regions, Genetic KW - Isoenzymes -- genetics KW - beta-N-Acetylhexosaminidases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78062441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Promoters+for+the+human+beta-hexosaminidase+genes%2C+HEXA+and+HEXB.&rft.au=Norflus%2C+F%3BYamanaka%2C+S%3BProia%2C+R+L&rft.aulast=Norflus&rft.aufirst=F&rft.date=1996-02-01&rft.volume=15&rft.issue=2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-09 N1 - Date created - 1996-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid response elements as positive and negative regulators of the expression of the homeobox b-1 gene. AN - 78062002; 9053826 AB - Retinoic acid-dependent homeobox Hoxb-1 gene expression offers an unanticipated example of both a positive and a negative transcriptional activity of RA, as exerted at different times during embryogenesis. A paradigm for the transduction of positive and negative signaling is the discovery that retinoic acid response elements (RAREs), positioned in the 3' enhancer and 5' promoter of the Hoxb-1 gene, may function respectively as positive and negative regulators, thereby permitting a diffused (early positive) as well as segmentally specified and limited (late negative) expression of the gene. This molecular action of retinoic acid may provide a mechanism for our understanding of normal embryogenesis and of the interference with this process by ectopic retinoic acid, thereby leading to teratogenesis. JF - Nutrition reviews AU - De Luca, L M AU - Ross, S A AD - Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 61 EP - 63 VL - 54 IS - 2 Pt 1 SN - 0029-6643, 0029-6643 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Animals KW - Abnormalities, Drug-Induced KW - Humans KW - Repetitive Sequences, Nucleic Acid KW - Tretinoin -- pharmacology KW - Regulatory Sequences, Nucleic Acid KW - Gene Expression Regulation -- drug effects KW - Genes, Homeobox -- genetics KW - Tretinoin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78062002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+reviews&rft.atitle=Retinoic+acid+response+elements+as+positive+and+negative+regulators+of+the+expression+of+the+homeobox+b-1+gene.&rft.au=De+Luca%2C+L+M%3BRoss%2C+S+A&rft.aulast=De+Luca&rft.aufirst=L&rft.date=1996-02-01&rft.volume=54&rft.issue=2+Pt+1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Nutrition+reviews&rft.issn=00296643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-10 N1 - Date created - 1997-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mesothelioma, asbestos, and reported history of cancer in first-degree relatives. AN - 78052467; 8630964 AB - Although malignant mesothelioma is known to be strongly related to asbestos exposure, its relationship to familial factors is unclear. We compared reported histories of cancer in first-degree relatives, obtained from telephone interviews with the next-of-kin of 196 patients who had a pathologic diagnosis of mesothelioma, and with those from 511 decreased controls. Among men exposed to asbestos, we found a statistically significant twofold elevation in the risk of mesothelioma for patients reporting cancer in two or more first-degree relatives. We found no significant elevation in women or among the small number of men without asbestos exposure. The next-of-kin of three patients (but no controls) reported a possible mesothelioma in a first-degree relative; asbestos exposure could not be ruled out in those relatives. Associations of asbestos with pleural mesothelioma were stronger among men with a reported family history of cancer than men without, although no statistical evidence of an interaction was detected. These results provide suggestive, but limited, evidence that a family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma given asbestos exposure. JF - Cancer AU - Heineman, E F AU - Bernstein, L AU - Stark, A D AU - Spirtas, R AD - Occupational Studies Section, National Cancer Institute, Bethesda, Maryland 20892-7364, USA. Y1 - 1996/02/01/ PY - 1996 DA - 1996 Feb 01 SP - 549 EP - 554 VL - 77 IS - 3 SN - 0008-543X, 0008-543X KW - Asbestos KW - 1332-21-4 KW - Abridged Index Medicus KW - Index Medicus KW - Sex Factors KW - Humans KW - Environmental Exposure KW - Family KW - Male KW - Female KW - Mesothelioma -- genetics KW - Pleural Neoplasms -- genetics KW - Asbestos -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78052467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Mesothelioma%2C+asbestos%2C+and+reported+history+of+cancer+in+first-degree+relatives.&rft.au=Heineman%2C+E+F%3BBernstein%2C+L%3BStark%2C+A+D%3BSpirtas%2C+R&rft.aulast=Heineman&rft.aufirst=E&rft.date=1996-02-01&rft.volume=77&rft.issue=3&rft.spage=549&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-28 N1 - Date created - 1996-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Airborne pollutants and the immune system. AN - 78047215; 8637740 AB - The effects of airborne pollutants on the immune system have been most widely studied in the respiratory tract. Entry may occur as a volatile gas (ozone, benzene), as liquid droplets (sulfuric acid, nitrogen dioxide), or as particulate matter (diesel exhaust, aromatic hydrocarbons). The subsequent interaction with the immune system may result in local and systemic responses, and studies have shown examples of disease occurring from both overactive immune responses and immunosuppression. For the most part, airborne pollutants (small molecular weight chemicals) have to be coupled with other substances (proteins or conjugates) before they can be recognized by the immune system and exert their effects. Fortunately, this encounter rarely causes immunologically mediated human disorders. The following briefly reviews some of the disorders that may occur. Immunologically nonspecific inflammation of the lung can occur after inhalation of ozone in anyone given sufficient dose and time of exposure. Immunologically specific cell-mediated (T lymphocyte) reactions appear to predominate in chronic beryllium disease, which results in a granulomatous form of lung disease. Beryllium alone does not appear to be antigenic but requires chemical linkage with a larger molecule. Mercury-induced autoimmune disease (immune system attacks self-antigens) affecting kidneys and lungs has been demonstrated in animal models (changes similar to those seen in people with Goodpasture's syndrome). Immunosuppression can be demonstrated after exposure to polycyclic aromatic hydrocarbons (2,3,7,8-tetrachlorodibenzo-p-dioxin). Hypersensitivity (or allergic) reactions can occur after exposure to toluene diisocyanate (occupational asthma). In summary, airborne pollutants may cause a wide spectrum of immunologically mediated disorders. There is clearly an underlying genetic basis for the susceptibility to immunologic disease resulting from exposure to pollutants, but knowledge in this area is rudimentary at present. Studies have been impeded by lack of appropriate in vitro models, as well as difficulties in identifying the biologically active substance. JF - Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery AU - Albright, J F AU - Goldstein, R A AD - Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 232 EP - 238 VL - 114 IS - 2 SN - 0194-5998, 0194-5998 KW - Air Pollutants KW - 0 KW - Index Medicus KW - Animals KW - Respiratory Hypersensitivity -- etiology KW - Disease Susceptibility KW - Humans KW - Respiratory Tract Diseases -- etiology KW - Autoimmune Diseases -- etiology KW - Disease Models, Animal KW - Alveolitis, Extrinsic Allergic -- etiology KW - Respiratory Tract Diseases -- immunology KW - Immune Tolerance KW - T-Lymphocytes -- immunology KW - Immune System Diseases -- genetics KW - Air Pollutants -- adverse effects KW - Immune System Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78047215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--head+and+neck+surgery+%3A+official+journal+of+American+Academy+of+Otolaryngology-Head+and+Neck+Surgery&rft.atitle=Airborne+pollutants+and+the+immune+system.&rft.au=Albright%2C+J+F%3BGoldstein%2C+R+A&rft.aulast=Albright&rft.aufirst=J&rft.date=1996-02-01&rft.volume=114&rft.issue=2&rft.spage=232&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--head+and+neck+surgery+%3A+official+journal+of+American+Academy+of+Otolaryngology-Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-10 N1 - Date created - 1996-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-1 alpha-induced modulation of topoisomerase I activity and DNA damage: implications in the mechanisms of synergy with camptothecins in vitro and in vivo. AN - 78047104; 8632759 AB - Studies have shown that cytokines are directly cytotoxic to tumor cells in vitro and in vivo and that interleukin-1 alpha (IL-1 alpha) potentiates the cytotoxicity of certain clinically active drugs in a number of human tumor cells, including carcinomas of breast and ovary. We found that interleukin-1 alpha potentiated cytotoxicity of camptothecin (4-5-fold) during simultaneous drug exposure in human ovarian NIH:OVCAR-3 cancer cells in vitro. Studies indicated that IL-1 alpha significantly increased topoisomerase I-catalyzed camptothecin-induced DNA cleavable complexes in the ovarian cell line, which was not due increased intracellular camptothecin as IL-1 alpha failed to effect cellular uptake of camptothecin. Pretreatment of the ovarian cells with IL-1 alpha did not result in increased expressions of mRNA for the topoisomerase I gene, whereas a small increase (approximately 1.5-fold) in the expression of topoisomerase I protein was observed, suggesting that IL-1 modulated the activity of topoisomerase I for the observed increase in cleavable complex formation. Treatment of human ovarian tumor cells grown as xenografts in nude mice with IL-1 alpha followed by CPT-11 at minimally toxic doses significantly (5-6-fold) enhanced antitumor activity of either agent alone. Because camptothecins are active against solid tumors in vivo, combinations of IL-1 alpha with these active drugs may lead to more effective treatment of ovarian cancers in the clinic. JF - Molecular pharmacology AU - Wang, Z AU - Sinha, B K AD - Biochemical and Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 269 EP - 275 VL - 49 IS - 2 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents KW - 0 KW - Interleukin-1 KW - Nuclear Proteins KW - Recombinant Proteins KW - irinotecan KW - 0H43101T0J KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Nuclear Proteins -- isolation & purification KW - Animals KW - Drug Administration Schedule KW - Transcription, Genetic -- drug effects KW - Cell Nucleus -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Breast Neoplasms KW - Mice, Nude KW - Mice KW - Cell Nucleus -- drug effects KW - Biological Transport -- drug effects KW - Recombinant Proteins -- toxicity KW - Protein Biosynthesis -- drug effects KW - Blotting, Western KW - Cell Survival -- drug effects KW - Transplantation, Heterologous KW - Nuclear Proteins -- biosynthesis KW - Drug Synergism KW - Female KW - DNA Damage KW - Ovarian Neoplasms -- pathology KW - Camptothecin -- metabolism KW - Camptothecin -- toxicity KW - Interleukin-1 -- therapeutic use KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Agents -- toxicity KW - DNA Topoisomerases, Type I -- biosynthesis KW - Interleukin-1 -- toxicity KW - Camptothecin -- therapeutic use KW - Ovarian Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78047104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Interleukin-1+alpha-induced+modulation+of+topoisomerase+I+activity+and+DNA+damage%3A+implications+in+the+mechanisms+of+synergy+with+camptothecins+in+vitro+and+in+vivo.&rft.au=Wang%2C+Z%3BSinha%2C+B+K&rft.aulast=Wang&rft.aufirst=Z&rft.date=1996-02-01&rft.volume=49&rft.issue=2&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-03 N1 - Date created - 1996-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene-specific DNA repair and steady state transcription of the MDR1 gene in human tumor cell lines. AN - 78045483; 8637722 AB - We have explored the relationship between DNA repair and transcription in vivo. A gene-specific repair assay has been employed to study removal of ultraviolet light-induced cyclobutane pyrimidine dimers in the MDR1 gene at different levels of MDR1 mRNA expression. The parental human adenocarcinoma cell line, KB-3-1, has very low levels of MDR1 mRNA expression, but its multidrug resistant derivatives KB-8-5 and KB-C1 have 42-fold and 3800-fold increases in MDR1 mRNA expression, respectively. In the KB-3-1 cell line that has a low level of MDR1 mRNA expression, we find a low level of MDR1 gene-specific repair and inefficient repair of the transcribed strand of the gene. In the KB-8-5 cell line that has a modest increase in MDR1 mRNA expression, we find only a minor increase in dimer repair in the MDR1 gene. Here, the repair in the transcribed strand is not significantly higher than that in the KB-3-1 cell line. However, in the KB-C1 derivative, where there is a 3800-fold increase in the level of MDR1 mRNA expression, we find a substantial increase in the level of dimer repair in the MDR1 gene. In addition, the MDR1 transcribed strand repair is markedly more efficient than the repair in the nontranscribed strand. Our data suggest that the rate of transcription in the MDR1 gene must be substantially increased before there is any measurable effect on DNA repair. Repair in the housekeeping gene, dihydrofolate reductase (DHFR), was similar in all three tumor cell lines. Repair in its transcribed strand was markedly lower than previously reported in normal human fibroblasts. We suspect that these human HeLa-derived tumor cell lines have deficient gene-specific DNA repair. This may be an important aspect of their malignant phenotype. JF - Oncogene AU - Evans, M K AU - Chin, K V AU - Gottesman, M M AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1996/02/01/ PY - 1996 DA - 1996 Feb 01 SP - 651 EP - 658 VL - 12 IS - 3 SN - 0950-9232, 0950-9232 KW - Antineoplastic Agents KW - 0 KW - P-Glycoprotein KW - P-Glycoproteins KW - RNA, Messenger KW - multidrug resistance protein 3 KW - Vinblastine KW - 5V9KLZ54CY KW - Doxorubicin KW - 80168379AG KW - Globins KW - 9004-22-2 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - KB Cells KW - Humans KW - Globins -- genetics KW - Doxorubicin -- toxicity KW - Vinblastine -- toxicity KW - RNA, Messenger -- biosynthesis KW - Colchicine -- toxicity KW - Tumor Cells, Cultured KW - Kinetics KW - ATP-Binding Cassette Transporters -- biosynthesis KW - Antineoplastic Agents -- toxicity KW - Cell Line KW - Tetrahydrofolate Dehydrogenase -- genetics KW - DNA Repair KW - Transcription, Genetic KW - P-Glycoprotein -- biosynthesis KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78045483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Gene-specific+DNA+repair+and+steady+state+transcription+of+the+MDR1+gene+in+human+tumor+cell+lines.&rft.au=Evans%2C+M+K%3BChin%2C+K+V%3BGottesman%2C+M+M%3BBohr%2C+V+A&rft.aulast=Evans&rft.aufirst=M&rft.date=1996-02-01&rft.volume=12&rft.issue=3&rft.spage=651&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-05 N1 - Date created - 1996-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular effects of genistein on estrogen receptor mediated pathways. AN - 78043052; 8625449 AB - Genistein, a component of soy products, may play a role in the prevention of breast and prostate cancer. However, little is known about the molecular mechanisms involved. In the present study, we examined the effects of genistein on the estrogen receptor positive human breast cancer cell line MCF-7. We observed that genistein stimulated estrogen-responsive pS2 mRNA expression at concentrations as low as 10(-8) M and these effects can be inhibited by tamoxifen. We also showed that genistein competed with [3H]estradiol binding to the estrogen receptor with 50% inhibition at 5 x 10(-7) M. Thus, the estrogenic effect of genistein would appear to be a result of an interaction with the estrogen receptor. The effect of genistein on growth of MCF-7 cells was also examined. Genistein produced a concentration-dependent effect on the growth of MCF-7 cells. At lower concentrations (10(-8)-10(-6) M) genistein stimulated growth, but at higher concentrations (> 10(-5) M) genistein inhibited growth. The effects of genistein on growth at lower concentrations appeared to be via the estrogen receptor pathway, while the effects at higher concentrations were independent of the estrogen receptor. We also found that genistein, though estrogenic, can interfere with the effects of estradiol. In addition, prolonged exposure to genistein resulted in a decrease in estrogen receptor mRNA level as well as a decreased response to stimulation by estradiol. JF - Carcinogenesis AU - Wang, T T AU - Sathyamoorthy, N AU - Phang, J M AD - Laboratory of Nutritional and Molecular Regulation, NCI-Frederick Cancer Research and Development Center, NIH, MD 21702-1201, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 271 EP - 275 VL - 17 IS - 2 SN - 0143-3334, 0143-3334 KW - Anticarcinogenic Agents KW - 0 KW - Estrogen Antagonists KW - Isoflavones KW - Neoplasm Proteins KW - Protein Synthesis Inhibitors KW - Proteins KW - RNA, Messenger KW - Receptors, Estrogen KW - TFF1 protein, human KW - Trefoil Factor-1 KW - Tumor Suppressor Proteins KW - Dactinomycin KW - 1CC1JFE158 KW - Estradiol KW - 4TI98Z838E KW - Genistein KW - DH2M523P0H KW - Index Medicus KW - Dactinomycin -- pharmacology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Protein Synthesis Inhibitors -- pharmacology KW - Humans KW - RNA, Messenger -- drug effects KW - Estradiol -- pharmacology KW - Breast Neoplasms -- chemistry KW - Estradiol -- metabolism KW - Neoplasm Proteins -- drug effects KW - Receptors, Estrogen -- drug effects KW - Estrogen Antagonists -- pharmacology KW - Isoflavones -- pharmacology KW - Anticarcinogenic Agents -- antagonists & inhibitors KW - Anticarcinogenic Agents -- pharmacology KW - Receptors, Estrogen -- metabolism KW - Isoflavones -- antagonists & inhibitors KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78043052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Molecular+effects+of+genistein+on+estrogen+receptor+mediated+pathways.&rft.au=Wang%2C+T+T%3BSathyamoorthy%2C+N%3BPhang%2C+J+M&rft.aulast=Wang&rft.aufirst=T&rft.date=1996-02-01&rft.volume=17&rft.issue=2&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-24 N1 - Date created - 1996-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma. AN - 78042202; 8636772 AB - Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Travis, L B AU - Weeks, J AU - Curtis, R E AU - Chaffey, J T AU - Stovall, M AU - Banks, P M AU - Boice, J D AD - National Cancer Institute, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 565 EP - 571 VL - 14 IS - 2 SN - 0732-183X, 0732-183X KW - Index Medicus KW - Combined Modality Therapy KW - Radiotherapy Dosage KW - Humans KW - Salvage Therapy KW - Leukemia, Myeloid, Acute -- etiology KW - Adult KW - Aged KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Bone Marrow -- radiation effects KW - Adolescent KW - Myelodysplastic Syndromes -- etiology KW - Lymphoma, Non-Hodgkin -- therapy KW - Neoplasms, Second Primary -- etiology KW - Whole-Body Irradiation -- adverse effects KW - Leukemia, Radiation-Induced -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78042202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Leukemia+following+low-dose+total+body+irradiation+and+chemotherapy+for+non-Hodgkin%27s+lymphoma.&rft.au=Travis%2C+L+B%3BWeeks%2C+J%3BCurtis%2C+R+E%3BChaffey%2C+J+T%3BStovall%2C+M%3BBanks%2C+P+M%3BBoice%2C+J+D&rft.aulast=Travis&rft.aufirst=L&rft.date=1996-02-01&rft.volume=14&rft.issue=2&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-09 N1 - Date created - 1996-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of patients with melanoma of the extremity using hyperthermic isolated limb perfusion with melphalan, tumor necrosis factor, and interferon gamma: results of a tumor necrosis factor dose-escalation study. AN - 78042157; 8636761 AB - To evaluate response rates and systemic and regional toxicity of hyperthermic isolated limb perfusion (ILP) for treatment of in-transit metastases of extremity melanoma using escalating-dose tumor necrosis factor (TNF) in conjunction with melphalan and interferon gamma (IFN). All patients received IFN 0.2 mg2 for 2 days followed by a 90-minute ILP with TNF and IFN (0.2 mg) given at time 0 and melphalan (10 mg/L limb volume) given at 30 minutes. Twenty-six patients were treated with 4 mg of TNF and 12 patients received 6 mg of TNF. All patients had assessable disease in the perfusion field and all but two patients were assessable for response at 1 month after treatment. Mean peak perfusate TNF levels in the 4-mg group were 4.8 micrograms/mL, compared with 7.4 micrograms/mL for the 6-mg group (P = .03). The complete response rate in the 4-mg TNF group was 76%, with an overall objective response rate of 92%, compared with 36% and 100% for the 6-mg group. Subgroup analyses showed that the lower complete response rate in the 6-mg TNF group was not explained by differences in disease burden or prior regional therapy. Systemic drug toxicity was short-lived, easily managed, and related to perfusate leak more than to TNF perfusate dose. Regional toxicity, particularly painful myopathy and neuropathy, was greater with the 6-mg dose level and was considered dose-limiting. ILP with 4 mg TNF, IFN, and melphalan can lead to complete local responses in the majority of patients with extremity melanoma. Escalating the TNF dose to 6 mg did not increase the complete response rate and increased regional toxicity. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Fraker, D L AU - Alexander, H R AU - Andrich, M AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 479 EP - 489 VL - 14 IS - 2 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Alkylating KW - 0 KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Extremities KW - Aged, 80 and over KW - Melphalan -- administration & dosage KW - Humans KW - Adult KW - Treatment Outcome KW - Interferon-gamma -- administration & dosage KW - Aged KW - Middle Aged KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Recombinant Proteins -- administration & dosage KW - Male KW - Female KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion KW - Soft Tissue Neoplasms -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Melanoma -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78042157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Treatment+of+patients+with+melanoma+of+the+extremity+using+hyperthermic+isolated+limb+perfusion+with+melphalan%2C+tumor+necrosis+factor%2C+and+interferon+gamma%3A+results+of+a+tumor+necrosis+factor+dose-escalation+study.&rft.au=Fraker%2C+D+L%3BAlexander%2C+H+R%3BAndrich%2C+M%3BRosenberg%2C+S+A&rft.aulast=Fraker&rft.aufirst=D&rft.date=1996-02-01&rft.volume=14&rft.issue=2&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-09 N1 - Date created - 1996-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin. AN - 78035248; 8636745 AB - We conducted an open-label, randomized trial to determine whether ICRF-187 would reduce doxorubicin-induced cardiotoxicity in pediatric sarcoma patients. Thirty-eight patients were randomized to receive doxorubicin-containing chemotherapy (given as an intravenous bolus) with or without ICRF-187. Resting left ventricular ejection fraction (LVEF) was monitored serially with multigated radionuclide angiography (MUGA) scan. The two groups were compared for incidence and degree of cardiotoxicity, response rates to four cycles of chemotherapy, event-free and overall survival, and incidence and severity of noncardiac toxicities. Eighteen ICRF-187-treated and 15 control patients were assessable for cardiac toxicity. ICRF-187-treated patients were less likely to develop subclinical cardiotoxicity (22% v 67%, P < .01), had a smaller decline in LVEF per 100 mg/m2 of doxorubicin (1.0 v 2.7 percentage points, P = .02), and received a higher median cumulative dose of doxorubicin (410 v 310 mg/m2, P < .05) than did control patients. Objective response rates were identical in the two groups, with no significant differences seen in event-free or overall survival. ICRF-187-treated patients had a significantly higher incidence of transient grade 1 serum transaminase elevations and a trend toward increased hematologic toxicity. ICRF-187 reduces the risk of developing short-term subclinical cardiotoxicity in pediatric sarcoma patients who receive up to 410 mg/m2 of doxorubicin. Response rates to chemotherapy, event-free and overall survival, and noncardiac toxicities appear to be unaffected by the use of ICRF-187. Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incidence of late cardiac complications in long-term survivors of childhood cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wexler, L H AU - Andrich, M P AU - Venzon, D AU - Berg, S L AU - Weaver-McClure, L AU - Chen, C C AU - Dilsizian, V AU - Avila, N AU - Jarosinski, P AU - Balis, F M AU - Poplack, D G AU - Horowitz, M E AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1928, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 362 EP - 372 VL - 14 IS - 2 SN - 0732-183X, 0732-183X KW - Antibiotics, Antineoplastic KW - 0 KW - Cardiovascular Agents KW - Razoxane KW - 5AR83PR647 KW - Doxorubicin KW - 80168379AG KW - Transaminases KW - EC 2.6.1.- KW - Index Medicus KW - Transaminases -- blood KW - Survival Rate KW - Injections, Intravenous KW - Humans KW - Adult KW - Child KW - Stroke Volume -- drug effects KW - Sarcoma, Ewing -- drug therapy KW - Rhabdomyosarcoma -- drug therapy KW - Adolescent KW - Neuroectodermal Tumors, Primitive, Peripheral -- drug therapy KW - Male KW - Female KW - Razoxane -- therapeutic use KW - Doxorubicin -- adverse effects KW - Sarcoma -- mortality KW - Cardiovascular Agents -- therapeutic use KW - Razoxane -- pharmacokinetics KW - Heart -- drug effects KW - Soft Tissue Neoplasms -- drug therapy KW - Sarcoma -- drug therapy KW - Cardiovascular Agents -- pharmacokinetics KW - Antibiotics, Antineoplastic -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78035248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Randomized+trial+of+the+cardioprotective+agent+ICRF-187+in+pediatric+sarcoma+patients+treated+with+doxorubicin.&rft.au=Wexler%2C+L+H%3BAndrich%2C+M+P%3BVenzon%2C+D%3BBerg%2C+S+L%3BWeaver-McClure%2C+L%3BChen%2C+C+C%3BDilsizian%2C+V%3BAvila%2C+N%3BJarosinski%2C+P%3BBalis%2C+F+M%3BPoplack%2C+D+G%3BHorowitz%2C+M+E&rft.aulast=Wexler&rft.aufirst=L&rft.date=1996-02-01&rft.volume=14&rft.issue=2&rft.spage=362&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-09 N1 - Date created - 1996-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - bcl-2 protein downregulation is not required for differentiation of multidrug resistant HL60 leukemia cells. AN - 78010945; 8628007 AB - Parental and multidrug resistant HL60 leukemia cell lines were used to study coupling of expression of apoptotic/cytostatic (bcl-2, bax, bclxL, p21/Waf1, and c-myc) genes during differentiation. The multidrug resistant HL60 cell line, HL60/ADR, was less sensitive than parental cells to cytostatic activity of low (0.4-2 ng/ml) doses of PMA. However, during treatment with standard differentiating doses of PMA (10 ng/ml), no difference between the two cell lines in cytostasis and differentiation was found. Downregulation of c-myc and upregulation of p21/Waf1 proteins showed the same time-course in both cell lines. The bcl-2 mRNA was rapidly downregulated while bax and bclxL gene expression was not altered in both differentiating HL60 and HL60/ADR cells. Significant downregulation of bcl-2 protein occurred only in parental HL60 cells. In HL60/ADR, despite rapid cessation of bcl-2 protein synthesis, almost no change in steady-state bcl-2 protein level was found. The lack of bcl-2 protein downregulation was a result of the prolonged half-life of this protein in HL60/ADR cells. Thus, although downregulation of bcl-2 mRNA is coupled to differentiation, actual loss of bcl-2 protein is not required for accomplishment of the differentiation program. JF - Leukemia research AU - Blagosklonny, M V AU - Alvarez, M AU - Fojo, A AU - Neckers, L M AD - Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 101 EP - 107 VL - 20 IS - 2 SN - 0145-2126, 0145-2126 KW - BAX protein, human KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Proto-Oncogene Proteins c-myc KW - bcl-2-Associated X Protein KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Oncogene Protein p21(ras) -- genetics KW - Genes, myc KW - Humans KW - Leukemia, Promyelocytic, Acute -- genetics KW - Proto-Oncogene Proteins c-myc -- genetics KW - Drug Resistance, Neoplasm KW - Leukemia, Promyelocytic, Acute -- pathology KW - Drug Resistance, Multiple KW - Polymerase Chain Reaction KW - Blotting, Western KW - Half-Life KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation -- drug effects KW - HL-60 Cells -- drug effects KW - Down-Regulation KW - Proto-Oncogene Proteins -- genetics KW - HL-60 Cells -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78010945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+research&rft.atitle=bcl-2+protein+downregulation+is+not+required+for+differentiation+of+multidrug+resistant+HL60+leukemia+cells.&rft.au=Blagosklonny%2C+M+V%3BAlvarez%2C+M%3BFojo%2C+A%3BNeckers%2C+L+M&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=1996-02-01&rft.volume=20&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Leukemia+research&rft.issn=01452126&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-21 N1 - Date created - 1996-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blocking the CD40L-CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion. AN - 77997616; 8627184 AB - The recent finding that CD40L on activated T cells induces interleukin (IL) 12 secretion in human peripheral blood monocytes in vitro suggests that the CD40L-CD40 interaction may be of importance in the priming of T helper (Th) 1-type T cells. We therefore investigated the in vivo relevance of this interaction in an experimental model for a Th1-mediated disease, the hapten reagent (2,4,6-trinitrobenzene sulfonic acid [TNBS])-induced colitis. The administration of anti-gp39 (CD40L) antibodies during the induction phase of the Th1 response prevented interferon gamma production by lamina propria CD4+ T cells and also clinical and histological evidence of disease. In contrast, the secretion of IL-4, a Th2-type cytokine, was increased after anti-gp39 treatment. In further studies we showed that the prevention of disease activity was caused by an inhibition of IL-12 secretion, as demonstrated by immunohistochemistry. In addition, the injection of recombinant IL-12 p70 heterodimer into TNBS + anti-gp39-treated mice reversed the effect of anti-gp39 and resulted in severe disease activity. When anti-gp39 was given after the disease was established, no effect on the disease activity was observed. In conclusion, we demonstrated that the CD40L-CD40 interaction is crucial for the in vivo priming of Th1 T cells via the stimulation of IL-12 secretion by antigen-presenting cells (APC). JF - The Journal of experimental medicine AU - Stuber, E AU - Strober, W AU - Neurath, M AD - Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1890, USA. Y1 - 1996/02/01/ PY - 1996 DA - 1996 Feb 01 SP - 693 EP - 698 VL - 183 IS - 2 SN - 0022-1007, 0022-1007 KW - Antibodies KW - 0 KW - Membrane Glycoproteins KW - CD40 Ligand KW - 147205-72-9 KW - Interleukin-12 KW - 187348-17-0 KW - Trinitrobenzenesulfonic Acid KW - 8T3HQG2ZC4 KW - Index Medicus KW - AIDS/HIV KW - Trinitrobenzenesulfonic Acid -- pharmacology KW - Mice, Inbred Strains KW - Animals KW - Colon -- pathology KW - Antibodies -- pharmacology KW - Disease Models, Animal KW - Mice KW - Protein Binding KW - Colon -- immunology KW - Female KW - Colitis -- prevention & control KW - Th1 Cells -- immunology KW - Colitis -- etiology KW - Colitis -- immunology KW - Interleukin-12 -- secretion KW - Colitis -- chemically induced KW - Membrane Glycoproteins -- immunology KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77997616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Blocking+the+CD40L-CD40+interaction+in+vivo+specifically+prevents+the+priming+of+T+helper+1+cells+through+the+inhibition+of+interleukin+12+secretion.&rft.au=Stuber%2C+E%3BStrober%2C+W%3BNeurath%2C+M&rft.aulast=Stuber&rft.aufirst=E&rft.date=1996-02-01&rft.volume=183&rft.issue=2&rft.spage=693&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-27 N1 - Date created - 1996-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol Methods. 1987 Nov 5;103(2):161-7 [2889781] J Exp Med. 1995 Nov 1;182(5):1281-90 [7595199] Gastroenterology. 1992 May;102(5):1524-34 [1314749] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6550-4 [1378631] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5914-8 [8100998] Science. 1993 Sep 3;261(5126):1328-30 [7689748] J Exp Med. 1993 Nov 1;178(5):1567-75 [7693850] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10188-92 [7901851] Int Immunol. 1993 Sep;5(9):1119-28 [7902129] J Exp Med. 1994 Jul 1;180(1):157-63 [7516405] Annu Rev Immunol. 1994;12:635-73 [7912089] Eur J Immunol. 1994 Jan;24(1):116-23 [7517359] Immunol Rev. 1994 Apr;138:39-59 [7915248] J Clin Invest. 1994 Sep;94(3):1333-8 [7521888] Immunol Today. 1994 Sep;15(9):406-11 [7524518] Eur J Immunol. 1995 Feb;25(2):596-603 [7533092] Cell. 1995 Mar 10;80(5):707-18 [7534215] J Exp Med. 1995 Apr 1;181(4):1569-74 [7699337] Eur J Immunol. 1995 Apr;25(4):1125-8 [7537673] Immunity. 1995 May;2(5):523-32 [7538442] Annu Rev Immunol. 1995;13:251-76 [7612223] Gastroenterology. 1989 Mar;96(3):795-803 [2914642] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - von Hippel-Lindau disease gene deletion detected in microdissected sporadic human colon carcinoma specimens. AN - 77997469; 8617456 AB - The progression of human malignancies is thought to involve the inactivation or loss of tumor suppressor genes. Previous studies have suggested that inactivation of tumor suppressor genes on chromosomes 5q, 17p, 18q, and 8p play a role in the development of colorectal carcinoma. However, chromosome 3p at the von Hippel-Lindau disease (VHL) gene locus (3p25-26) has not been previously implicated in the development or progression of sporadic colorectal carcinoma. The authors have analyzed VHL gene alterations on chromosome 3p in sporadic human colon carcinomas and adenomas using modified microdissection techniques. These techniques allow for procurement and analysis of selected subpopulations of cells from both paraffin-embedded and frozen human tumor specimens. VHL disease gene deletion was detected by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis in microdissected colon carcinoma specimens. Allelic loss of VHL gene was detected in 7 of 11 (64%) informative patients who underwent colectomy for primary sporadic colon carcinoma. However, no allelic loss of VHL gene was shown in colonic adenomas of eight informative patients. These results indicate that VHL disease gene deletion frequently occurs in sporadic colon carcinoma. Because this deletion was not present in adenomas, VHL gene may play a role in colonic carcinogenesis and represent a relatively late event in colonic neoplasia progression. Additionally, microdissection of tissue sections may be especially useful in detecting allelic loss in PCR-based studies of infiltrating tumors, particularly when the tumor cells represent a relatively small percentage of the total cell population. JF - Human pathology AU - Zhuang, Z AU - Emmert-Buck, M R AU - Roth, M J AU - Gnarra, J AU - Linehan, W M AU - Liotta, L A AU - Lubensky, I A AD - Laboratory of Pathology and Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 152 EP - 156 VL - 27 IS - 2 SN - 0046-8177, 0046-8177 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Chromosomes, Human, Pair 3 KW - Base Sequence KW - Humans KW - Heterozygote KW - Molecular Sequence Data KW - DNA, Neoplasm -- analysis KW - Mutation KW - Polymorphism, Single-Stranded Conformational KW - Dissection KW - Genes, Tumor Suppressor -- genetics KW - Colorectal Neoplasms -- pathology KW - von Hippel-Lindau Disease -- genetics KW - Adenocarcinoma -- genetics KW - Colorectal Neoplasms -- genetics KW - Adenoma -- pathology KW - Adenoma -- genetics KW - Gene Deletion KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77997469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+pathology&rft.atitle=von+Hippel-Lindau+disease+gene+deletion+detected+in+microdissected+sporadic+human+colon+carcinoma+specimens.&rft.au=Zhuang%2C+Z%3BEmmert-Buck%2C+M+R%3BRoth%2C+M+J%3BGnarra%2C+J%3BLinehan%2C+W+M%3BLiotta%2C+L+A%3BLubensky%2C+I+A&rft.aulast=Zhuang&rft.aufirst=Z&rft.date=1996-02-01&rft.volume=27&rft.issue=2&rft.spage=152&rft.isbn=&rft.btitle=&rft.title=Human+pathology&rft.issn=00468177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-07 N1 - Date created - 1996-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling. AN - 77995348; 8609238 AB - Signal transduction pathways shared by different autocrine growth factors may provide an efficient approach to accomplish clinically significant control of lung cancer growth. In this study, we demonstrate that two autocrine growth factors activate 5-lipoxygenase action of the arachidonic acid metabolic pathway in lung cancer cell lines. Both growth factors increased the production of 5(S)-hydrooxyeicosa-6E,8Z,11Z,14Z-tetraeno ic acid (5-HETE), a major early 5-lipoxygenase metabolic product. Exogenously added 5-HETE stimulated lung cancer cell growth in vitro. Inhibition of 5-lipoxygenase metabolism by selective antagonists resulted in significant growth reduction for a number of lung cancer cell lines. Primary clinical specimens and lung cancer cell lines express the message for the 5-lipoxygenase enzymes responsible for the generation of active metabolites. In vivo evaluation demonstrated that interruption of 5-lipoxygenase signaling resulted in enhanced levels of programmed cell death. These findings demonstrate that 5-lipoxygenase activation is involved with growth factor-mediated growth stimulation for lung cancer cell lines. Pharmacological intervention with lipoxygenase inhibitors may be an important new clinical strategy to regulate growth factor-dependent stages of lung carcinogenesis. JF - The Journal of clinical investigation AU - Avis, I M AU - Jett, M AU - Boyle, T AU - Vos, M D AU - Moody, T AU - Treston, A M AU - Martínez, A AU - Mulshine, J L AD - National Cancer Institute, Biomarkers and Prevention Research Branch, Rockville, Maryland 20850-3300, USA. Y1 - 1996/02/01/ PY - 1996 DA - 1996 Feb 01 SP - 806 EP - 813 VL - 97 IS - 3 SN - 0021-9738, 0021-9738 KW - 5-Lipoxygenase-Activating Proteins KW - 0 KW - Alox5ap protein, mouse KW - Carrier Proteins KW - Growth Substances KW - Lipoxygenase Inhibitors KW - Membrane Proteins KW - Peptides KW - RNA, Messenger KW - Somatomedins KW - Arachidonic Acid KW - 27YG812J1I KW - Masoprocol KW - 7BO8G1BYQU KW - Gastrin-Releasing Peptide KW - 80043-53-4 KW - Arachidonate 5-Lipoxygenase KW - EC 1.13.11.34 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Somatomedins -- pharmacology KW - Carrier Proteins -- genetics KW - RNA, Messenger -- analysis KW - Cell Division -- drug effects KW - Mice, Nude KW - Mice KW - Membrane Proteins -- genetics KW - Peptides -- pharmacology KW - Arachidonic Acid -- metabolism KW - Carrier Proteins -- biosynthesis KW - Masoprocol -- therapeutic use KW - Base Sequence KW - Arachidonic Acid -- antagonists & inhibitors KW - Lipoxygenase Inhibitors -- therapeutic use KW - Membrane Proteins -- biosynthesis KW - Molecular Sequence Data KW - Carcinoma, Small Cell -- metabolism KW - Arachidonate 5-Lipoxygenase -- biosynthesis KW - Growth Substances -- pharmacology KW - Lung Neoplasms -- drug therapy KW - Carcinoma, Small Cell -- drug therapy KW - Arachidonate 5-Lipoxygenase -- genetics KW - Signal Transduction KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77995348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Growth+control+of+lung+cancer+by+interruption+of+5-lipoxygenase-mediated+growth+factor+signaling.&rft.au=Avis%2C+I+M%3BJett%2C+M%3BBoyle%2C+T%3BVos%2C+M+D%3BMoody%2C+T%3BTreston%2C+A+M%3BMart%C3%ADnez%2C+A%3BMulshine%2C+J+L&rft.aulast=Avis&rft.aufirst=I&rft.date=1996-02-01&rft.volume=97&rft.issue=3&rft.spage=806&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-29 N1 - Date created - 1996-05-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1980 Oct 9;303(15):878-80 [7412807] N Engl J Med. 1995 Sep 7;333(10):609-14 [7637720] Biochim Biophys Acta. 1984 Oct 4;795(3):458-65 [6089906] Annu Rev Physiol. 1985;47:443-67 [2986538] J Clin Invest. 1988 Jul;82(1):354-9 [2839551] Exp Cell Biol. 1988;56(1-2):74-85 [2846378] Biochem Biophys Res Commun. 1988 Nov 15;156(3):1383-9 [2847733] Cancer Res. 1989 Mar 1;49(5):1138-42 [2492901] Trends Neurosci. 1988 Mar;11(3):117-23 [2465609] Can J Physiol Pharmacol. 1989 May;67(5):456-64 [2548691] Nature. 1989 Sep 21;341(6239):197-205 [2550825] J Biol Chem. 1990 Jan 25;265(3):1436-42 [2104841] Am J Physiol. 1990 Oct;259(4 Pt 1):L255-61 [2171354] J Biol Chem. 1990 Nov 15;265(32):19973-9 [2174059] Ann N Y Acad Sci. 1990;609:146-54; discussion 154-8 [2264639] Oncology (Williston Park). 1991 May;5(5):25-32; discussion 32-3, 37 [1832003] N Engl J Med. 1991 Dec 5;325(23):1593-6 [1669840] Cancer Res. 1992 May 1;52(9 Suppl):2737s-2742s [1314136] J Natl Cancer Inst Monogr. 1992;(13):145-51 [1389687] Prog Med Chem. 1992;29:1-63 [1475368] Semin Thorac Cardiovasc Surg. 1993 Jul;5(3):201-9 [8353148] Ann Pharmacother. 1993 Jul-Aug;27(7-8):898-903 [8364276] Cancer Res. 1993 Nov 1;53(21):5181-7 [8221655] J Biol Chem. 1994 Mar 18;269(11):8596-603 [8132585] Agents Actions. 1993 Sep;40(1-2):62-71 [8147271] Anal Biochem. 1994 Feb 1;216(2):373-82 [8179192] Ann Intern Med. 1994 Aug 15;121(4):241-6 [8037405] Ann Intern Med. 1994 Nov 1;121(9):684-97 [7944079] Cell. 1994 Dec 16;79(6):927-30 [8001140] Anticancer Res. 1994 Sep-Oct;14(5A):1951-60 [7847833] Science. 1995 Mar 10;267(5203):1456-62 [7878464] Cancer Res. 1995 May 1;55(9):1811-6 [7728743] Cancer Res. 1995 Jul 15;55(14):3110-6 [7606732] J Histochem Cytochem. 1995 Aug;43(8):739-47 [7542678] J Biol Chem. 1984 Jun 10;259(11):7137-42 [6202692] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor. AN - 77989301; 8624803 AB - IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R. JF - Immunity AU - Ryan, J J AU - McReynolds, L J AU - Keegan, A AU - Wang, L H AU - Garfein, E AU - Rothman, P AU - Nelms, K AU - Paul, W E AD - National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 123 EP - 132 VL - 4 IS - 2 SN - 1074-7613, 1074-7613 KW - Antigens, CD KW - 0 KW - Insulin-Like Growth Factor Binding Protein 1 KW - Potassium Channels KW - Receptors, IgE KW - Receptors, Interleukin KW - Receptors, Interleukin-4 KW - Interleukin-4 KW - 207137-56-2 KW - Tyrosine KW - 42HK56048U KW - Index Medicus KW - Potassium Channels -- pharmacology KW - Humans KW - Cell Differentiation -- genetics KW - Amino Acid Sequence KW - Transcriptional Activation KW - Tyrosine -- analysis KW - Receptors, IgE -- biosynthesis KW - Cell Differentiation -- immunology KW - Phosphorylation -- drug effects KW - Lymphoma, B-Cell KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Tumor Cells, Cultured KW - Cell Division -- immunology KW - Molecular Sequence Data KW - Insulin-Like Growth Factor Binding Protein 1 -- pharmacology KW - Interleukin-4 -- genetics KW - Antigens, CD -- physiology KW - Gene Expression Regulation -- immunology KW - Antigens, CD -- chemistry KW - Receptors, Interleukin -- genetics KW - Receptors, Interleukin -- chemistry KW - Interleukin-4 -- pharmacology KW - Antigens, CD -- genetics KW - Receptors, Interleukin -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77989301?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunity&rft.atitle=Growth+and+gene+expression+are+predominantly+controlled+by+distinct+regions+of+the+human+IL-4+receptor.&rft.au=Ryan%2C+J+J%3BMcReynolds%2C+L+J%3BKeegan%2C+A%3BWang%2C+L+H%3BGarfein%2C+E%3BRothman%2C+P%3BNelms%2C+K%3BPaul%2C+W+E&rft.aulast=Ryan&rft.aufirst=J&rft.date=1996-02-01&rft.volume=4&rft.issue=2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Immunity&rft.issn=10747613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-27 N1 - Date created - 1996-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Women with bipolar illness: clinical and research issues. AN - 77984423; 8561195 AB - The purpose of this article is to review the literature concerning gender differences in the course of bipolar illness and discuss issues relevant to the treatment of women with the illness. The literature concerning the following topics is reviewed: gender differences in the course of bipolar illness; effects of the female reproductive cycle on the course of bipolar illness; special considerations in the treatment of bipolar women (focusing on the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes); and hypotheses to explain the greater prevalence of rapid cycling among bipolar women than among bipolar men. Data clearly indicate that rapid cycling is more common among bipolar women. Data also suggest that bipolar women may have more depressive episodes (and fewer manic episodes) and may be more likely to suffer from mixed (as opposed to pure) mania than bipolar men. While it is clear that bipolar women are at high risk for postpartum episodes, the effects of other reproductive system events (i.e., puberty, menstrual cycle, pregnancy, menopause, use of oral contraceptives or hormone replacement therapy) on the course or treatment of bipolar illness have received little systematic study. It is unclear whether women are at higher risk than men for developing lithium-induced hypothyroidism. Higher rates of hypothyroidism, greater use of antidepressants, and gonadal steroid effects are possible explanations for the greater prevalence of rapid cycling among bipolar women. Gender differences in bipolar illness and the effects of the female reproductive system on the course and treatment of the illness deserve more study. The importance of a longitudinal approach to these questions is emphasized. JF - The American journal of psychiatry AU - Leibenluft, E AD - Clinical Psychobiology Branch, NIMH, Bethesda, MD 20892-1390, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 163 EP - 173 VL - 153 IS - 2 SN - 0002-953X, 0002-953X KW - Lithium KW - 9FN79X2M3F KW - Abridged Index Medicus KW - Index Medicus KW - Estrogen Replacement Therapy KW - Sex Factors KW - Humans KW - Menstrual Cycle KW - Hypothyroidism -- chemically induced KW - Depressive Disorder -- epidemiology KW - Puerperal Disorders -- epidemiology KW - Risk Factors KW - Adult KW - Middle Aged KW - Lithium -- adverse effects KW - Female KW - Male KW - Menopause KW - Puberty KW - Prevalence KW - Bipolar Disorder -- diagnosis KW - Bipolar Disorder -- epidemiology KW - Bipolar Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77984423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Women+with+bipolar+illness%3A+clinical+and+research+issues.&rft.au=Leibenluft%2C+E&rft.aulast=Leibenluft&rft.aufirst=E&rft.date=1996-02-01&rft.volume=153&rft.issue=2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-23 N1 - Date created - 1996-02-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Psychiatry. 1997 Mar;154(3):441 [9054807] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The 1995 Walter Hubert Lecture--molecular epidemiology of human cancer: insights from the mutational analysis of the p53 tumour-suppressor gene. AN - 77983592; 8562328 JF - British journal of cancer AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 261 EP - 269 VL - 73 IS - 3 SN - 0007-0920, 0007-0920 KW - DNA, Neoplasm KW - 0 KW - Tumor Suppressor Protein p53 KW - 5-Methylcytosine KW - 6R795CQT4H KW - Cytosine KW - 8J337D1HZY KW - Index Medicus KW - Cytosine -- chemistry KW - Humans KW - DNA, Neoplasm -- genetics KW - Mutation KW - Cytosine -- analogs & derivatives KW - Genes, p53 KW - Neoplasms -- epidemiology KW - Tumor Suppressor Protein p53 -- chemistry KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77983592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=The+1995+Walter+Hubert+Lecture--molecular+epidemiology+of+human+cancer%3A+insights+from+the+mutational+analysis+of+the+p53+tumour-suppressor+gene.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1996-02-01&rft.volume=73&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-05 N1 - Date created - 1996-03-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1993 May 20;363(6426):281-3 [8387645] Mol Cell Biol. 1993 Jun;13(6):3291-300 [8497252] Nat Genet. 1993 May;4(1):42-6 [8099841] J Biol Chem. 1993 Jun 25;268(18):13062-7 [8514746] Nature. 1993 Sep 16;365(6443):207-8 [8371775] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8586-90 [8397412] N Engl J Med. 1993 Oct 28;329(18):1318-27 [8413413] Nature. 1991 Jun 6;351(6326):453-6 [2046748] Science. 1991 Jul 5;253(5015):49-53 [1905840] JAMA. 1991 Aug 7;266(5):681-7 [2072479] Cancer Res. 1991 Sep 15;51(18 Suppl):5023s-5044s [1884379] Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9248-52 [1656466] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124-8 [1946433] Cancer Res. 1993 Nov 15;53(22):5377-81 [8221675] Science. 1993 Dec 24;262(5142):1980-1 [8266092] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):413-7 [8278402] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):822-6 [8290606] Br J Cancer. 1994 Mar;69(3):409-16 [8123467] Science. 1994 Mar 11;263(5152):1436-8 [8128225] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2230-4 [8134379] Cancer Res. 1994 Apr 15;54(8):2064-8 [8174105] Mutat Res. 1994 May 1;307(1):375-86 [7513818] Science. 1994 May 27;264(5163):1317-9 [8191284] Science. 1994 Jul 15;265(5170):346-55 [8023157] Science. 1994 Jul 15;265(5170):386-91 [8023159] Cancer Res. 1994 Aug 15;54(16):4454-60 [8044795] J Virol. 1987 Nov;61(11):3448-53 [2822953] J Virol. 1988 Feb;62(2):427-34 [2826805] Cancer Genet Cytogenet. 1989 Feb;37(2):273-8 [2702627] Cell. 1989 Jun 30;57(7):1083-93 [2525423] Jpn J Cancer Res. 1989 Jul;80(7):617-21 [2507484] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8763-7 [2530586] Nature. 1990 Feb 1;343(6257):457-61 [2153938] Proc Natl Acad Sci U S A. 1990 Apr;87(8):2970-4 [2158099] Oncogene. 1990 Jul;5(7):945-52 [2142762] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6166-70 [2143581] Science. 1990 Aug 24;249(4971):912-5 [2144057] Science. 1990 Aug 31;249(4972):1046-9 [2144363] Science. 1990 Aug 31;249(4972):1049-51 [2144364] Mol Cell Biol. 1990 Nov;10(11):5772-81 [2233717] Science. 1990 Dec 14;250(4987):1576-80 [2274789] Nature. 1991 Apr 4;350(6317):427-8 [1849234] Nature. 1991 Apr 4;350(6317):429-31 [1672732] Hum Genet. 1991 Mar;86(5):425-41 [2016084] Annu Rev Genet. 1990;24:189-213 [2088167] Science. 1991 May 10;252(5007):842-4 [1827531] Science. 1991 Nov 15;254(5034):1001-3 [1948068] Nature. 1992 Jan 16;355(6357):209-10 [1309937] Cancer Res. 1992 Mar 15;52(6):1635-8 [1311638] J Natl Cancer Inst. 1992 Aug 5;84(15):1156-60 [1635084] Cell. 1992 Aug 21;70(4):523-6 [1505019] Prog Clin Biol Res. 1992;376:1-30 [1528915] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028-32 [1465435] Oncogene. 1993 Jan;8(1):209-13 [8380918] J Biol Chem. 1993 Feb 5;268(4):2284-7 [8428901] Cancer Res. 1994 Sep 15;54(18):4855-78 [8069852] Cell. 1994 Aug 26;78(4):543-6 [8069906] Am J Pathol. 1994 Sep;145(3):702-14 [8080050] Genes Dev. 1994 May 15;8(10):1235-46 [7926727] Nucleic Acids Res. 1994 Sep;22(17):3551-5 [7937055] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9700-4 [7937876] Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10350-4 [7937954] Nature. 1994 Dec 22-29;372(6508):773-6 [7997263] Science. 1995 Jan 6;267(5194):100-4 [7809597] Hepatology. 1995 Feb;21(2):313-21 [7843699] Curr Biol. 1994 Oct 1;4(10):865-75 [7850419] N Engl J Med. 1995 Mar 16;332(11):712-7 [7854378] Science. 1995 Mar 10;267(5203):1498-502 [7878469] Nat Genet. 1995 Jan;9(1):41-7 [7704023] Proc Natl Acad Sci U S A. 1995 May 23;92(11):5154-8 [7761466] Nat Struct Biol. 1994 Dec;1(12):877-90 [7773777] Oncogene. 1995 Jun 1;10(11):2103-11 [7784055] Science. 1995 Jun 23;268(5218):1749-53 [7792600] Cell. 1995 Jun 30;81(7):1021-9 [7600571] Nat Genet. 1995 Jun;10(2):188-95 [7663514] Carcinogenesis. 1993 Feb;14(2):169-73 [8382111] Oncogene. 1993 May;8(5):1109-17 [8386823] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autoimmunity in chronic active Helicobacter hepatitis of mice. Serum antibodies and expression of heat shock protein 70 in liver. AN - 77983473; 8579113 AB - Male A/JCr mice with naturally occurring Helicobacter hepaticus infection develop a progressive chronic active hepatitis and liver tumors, despite the presence of serum antibodies to Helicobacter proteins. A rabbit antiserum prepared against the bacterial proteins immunoreacted with hepatocytes present in liver sections from infected mice with progressive lesions. We found that sera from these mice contained IgG antibodies that reacted in immunoblots with recombinant heat shock protein 70 (DmaK from Escherichia coli) but not with heat shock protein 60 (GroEL) or heat shock protein 10 (GroES). A rabbit antibody to heat shock protein 70 reacted with H. hepaticus in tissue sections and to a H. hepaticus protein (70 kd) in Western blots. Immunohistochemistry and in situ hybridization for heat shock protein 70 revealed that individual hepatocytes and other cells expressed the protein in livers with hepatitis but not usually in normal livers. Liver tumors and preneoplastic lesions in infected mice did not usually express heat shock protein 70 except focally in a few tumors. In situ hybridization for H. hepaticus 16S rRNA showed that the bacteria was found throughout the liver associated with hepatitis but not within tumors. CD3+ T lymphocytes were found in close association with hepatic lesions. These data suggest a role for autoimmunity in progressive hepatitis and carcinogenesis in livers infected with H. hepaticus. JF - The American journal of pathology AU - Ward, J M AU - Benveniste, R E AU - Fox, C H AU - Battles, J K AU - Gonda, M A AU - Tully, J G AD - Veterinary and Tumor Pathology Section, National Cancer Institute, Frederick, Maryland, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 509 EP - 517 VL - 148 IS - 2 SN - 0002-9440, 0002-9440 KW - Antibodies, Bacterial KW - 0 KW - Antigens, CD3 KW - Autoantibodies KW - HSP70 Heat-Shock Proteins KW - RNA, Ribosomal, 16S KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Immunoblotting KW - Rabbits KW - Mice KW - Adenoma, Liver Cell -- microbiology KW - Liver Neoplasms -- microbiology KW - Mice, Inbred A KW - RNA, Ribosomal, 16S -- analysis KW - Antigens, CD3 -- analysis KW - In Situ Hybridization KW - Gallbladder -- microbiology KW - T-Lymphocytes -- immunology KW - Gallbladder -- pathology KW - Male KW - Liver -- pathology KW - HSP70 Heat-Shock Proteins -- biosynthesis KW - Helicobacter -- immunology KW - Liver -- immunology KW - Helicobacter -- isolation & purification KW - Helicobacter Infections -- microbiology KW - Autoantibodies -- blood KW - Hepatitis, Chronic -- microbiology KW - Liver -- metabolism KW - HSP70 Heat-Shock Proteins -- immunology KW - Hepatitis, Chronic -- immunology KW - Helicobacter Infections -- immunology KW - Hepatitis, Chronic -- pathology KW - Antibodies, Bacterial -- blood KW - Helicobacter Infections -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77983473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Autoimmunity+in+chronic+active+Helicobacter+hepatitis+of+mice.+Serum+antibodies+and+expression+of+heat+shock+protein+70+in+liver.&rft.au=Ward%2C+J+M%3BBenveniste%2C+R+E%3BFox%2C+C+H%3BBattles%2C+J+K%3BGonda%2C+M+A%3BTully%2C+J+G&rft.aulast=Ward&rft.aufirst=J&rft.date=1996-02-01&rft.volume=148&rft.issue=2&rft.spage=509&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-11 N1 - Date created - 1996-03-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Sci Am. 1993 May;268(5):56-64 [8097593] Carcinogenesis. 1992 Dec;13(12):2407-13 [1473251] Hepatology. 1993 Jun;17(6):1047-51 [8514253] J Clin Invest. 1993 Jun;91(6):2653-64 [8514873] J Exp Med. 1993 Jul 1;178(1):343-8 [8315389] Hepatology. 1993 Jul;18(1):1-9 [8325600] Microsc Res Tech. 1993 May 1;25(1):78-84 [8353310] J Exp Med. 1993 Oct 1;178(4):1391-6 [8376942] Mol Microbiol. 1993 Aug;9(3):645-52 [8105364] Hepatology. 1993 Nov;18(5):1108-14 [8225215] J Immunol. 1993 Nov 15;151(10):5516-24 [8228242] J Exp Med. 1993 Nov 1;178(5):1541-54 [8228807] J Exp Med. 1993 Dec 1;178(6):2237-42 [7504063] Zentralbl Bakteriol. 1993 Sep;280(1-2):73-85 [8280960] J Hepatol. 1993 Aug;19(1):159-66 [7905491] Eur J Biochem. 1994 Jan 15;219(1-2):11-23 [8306977] Hepatology. 1994 Apr;19(4):1029-33 [8138243] Trends Microbiol. 1993 Oct;1(7):255-60 [8162405] J Biol Chem. 1994 May 6;269(18):13670-9 [7909811] J Hepatol. 1994 Mar;20(3):359-63 [8014447] Clin Exp Immunol. 1994 Jul;97(1):126-32 [8033409] J Natl Cancer Inst. 1994 Aug 17;86(16):1222-7 [8040890] J Clin Microbiol. 1994 May;32(5):1238-45 [8051250] Gastroenterology. 1994 Nov;107(5):1436-42 [7523226] Am J Pathol. 1994 Oct;145(4):959-68 [7943185] J Cell Biol. 1994 Nov;127(4):893-902 [7962074] Science. 1994 Nov 18;266(5188):1250-3 [7973708] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12218-22 [7991609] Infect Immun. 1995 Mar;63(3):1102-6 [7868233] J Clin Microbiol. 1995 Feb;33(2):445-54 [7536217] Mol Microbiol. 1994 Dec;14(5):959-74 [7715457] J Med Microbiol. 1995 Jan;42(1):48-52 [7739025] Lab Anim Sci. 1995 Aug;45(4):373-8 [7474875] J Clin Microbiol. 1995 May;33(5):1344-7 [7542270] J Exp Med. 1987 May 1;165(5):1430-5 [3106556] J Virol. 1988 Jun;62(6):2091-101 [3285032] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4267-70 [3132709] Curr Top Microbiol Immunol. 1991;167:145-60 [1675978] Am J Gastroenterol. 1991 Aug;86(8):976-80 [1677527] J Hepatol. 1991 Jul;13(1):128-31 [1655868] Infect Immun. 1992 May;60(5):1946-51 [1563786] Infect Immun. 1992 May;60(5):2125-7 [1348725] Biochem Biophys Res Commun. 1992 Apr 15;184(1):167-74 [1567424] J Bacteriol. 1992 Jul;174(13):4193-6 [1624412] Nature. 1992 Jul 30;358(6385):377-8 [1641019] EMBO J. 1992 Oct;11(10):3513-20 [1396554] Hepatology. 1992 Oct;16(4):892-8 [1398495] J Immunol. 1993 Jun 1;150(11):4867-75 [8496591] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytoplasmic ribonucleoprotein complexes containing human LINE-1 protein and RNA. AN - 77981423; 8599946 AB - P40 is the protein encoded by the first open reading frame (ORF1) of the human LINE-1 (L1Hs) retrotransposon; it is 338 amino acids long, has a leucine zipper motif and has been found in human teratocarcinoma cell lines and some tumor cells. In this report, we describe properties of p40 in the human teratocarcinoma cell lines NTera2D1 and 2102Ep. The results indicate that: (i) most of p40 occurs in large multimeric cytoplasmic complexes, (ii) L1Hs RNA is associated with the p40 complexes, (iii) the complexes are dissociated by ribonuclease and (iv) p40 is a novel RNA-binding protein. Cross-linking experiments with full-length and truncated p40 produced in Escherichia coli also showed that: (i) p40 itself can form a multimeric complex larger than 250 kDa, (ii) the leucine zipper motif and the region conserved among the predicted ORF1 polypeptides of mammalian LINE-1s participate in complex formation and (iii) the amino terminal region is important for the stability of complex formation. Analysis of the amino acid sequence of p40 suggests that long segments of the molecule can assume an alpha-helical configuration including the leucine zipper and the conserved region. The evidence presented here suggests that the p40 complex is a ribonucleoprotein complex containing L1Hs RNA(s) and that protein-protein interactions in which alpha-helix structures participate, for example coiled-coils, may occur in the complex. JF - The EMBO journal AU - Hohjoh, H AU - Singer, M F AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/02/01/ PY - 1996 DA - 1996 Feb 01 SP - 630 EP - 639 VL - 15 IS - 3 SN - 0261-4189, 0261-4189 KW - Cross-Linking Reagents KW - 0 KW - DNA-Binding Proteins KW - RNA, Neoplasm KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Retroelements KW - Ribonucleoproteins KW - L1Hs-encoded protein p40, human KW - 148349-28-4 KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Protein Structure, Secondary KW - RNA-Binding Proteins -- genetics KW - Humans KW - Open Reading Frames KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - RNA-Binding Proteins -- chemistry KW - RNA, Neoplasm -- genetics KW - Recombinant Proteins -- genetics KW - Cytoplasm -- chemistry KW - Teratocarcinoma -- chemistry KW - RNA, Neoplasm -- chemistry KW - Retroelements -- genetics KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Teratocarcinoma -- genetics KW - DNA-Binding Proteins -- chemistry KW - Ribonucleoproteins -- chemistry KW - DNA-Binding Proteins -- genetics KW - Ribonucleoproteins -- genetics KW - RNA -- chemistry KW - RNA -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77981423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Cytoplasmic+ribonucleoprotein+complexes+containing+human+LINE-1+protein+and+RNA.&rft.au=Hohjoh%2C+H%3BSinger%2C+M+F&rft.aulast=Hohjoh&rft.aufirst=H&rft.date=1996-02-01&rft.volume=15&rft.issue=3&rft.spage=630&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-30 N1 - Date created - 1996-04-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1986 Jan 20;187(2):291-304 [3009828] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Cell. 1986 Dec 26;47(6):1007-15 [2430722] Mol Cell Biol. 1986 Jan;6(1):168-82 [3023821] Mol Cell Biol. 1986 Feb;6(2):411-24 [3023845] Cell. 1987 Apr 10;49(1):111-9 [3030564] Mol Cell Biol. 1987 Apr;7(4):1465-75 [3037321] Proc Natl Acad Sci U S A. 1987 Aug;84(16):5843-7 [2441397] EMBO J. 1987 Sep;6(9):2781-4 [3678204] Nature. 1988 Mar 10;332(6160):164-6 [2831458] Nucleic Acids Res. 1988 May 11;16(9):4161 [3287340] Cell. 1988 Oct 21;55(2):235-46 [2844414] Nature. 1988 Dec 15;336(6200):646-51 [2974122] Science. 1989 Jan 27;243(4890):538-42 [2911757] Gene. 1988 Oct 30;70(2):253-62 [2463954] Cell. 1989 Mar 10;56(5):777-83 [2493990] Science. 1989 Mar 31;243(4899):1681-8 [2494700] Science. 1989 Mar 31;243(4899):1689-94 [2494701] Science. 1989 Mar 31;243(4899):1695-9 [2494702] Q Rev Biol. 1989 Mar;64(1):1-30 [2469098] Genomics. 1989 Apr;4(3):290-6 [2497061] Nucleic Acids Res. 1980 Dec 20;8(24):6113-28 [6258162] Anal Biochem. 1980 Nov 15;109(1):76-86 [6258458] Nucleic Acids Res. 1982 May 25;10(10):3175-93 [6285290] Nucleic Acids Res. 1982 May 25;10(10):3221-39 [6285293] Nature. 1983 Mar 10;302(5904):119-24 [6186922] Nucleic Acids Res. 1983 Jan 25;11(2):321-38 [6298721] Mol Cell Biol. 1983 May;3(5):787-95 [6865942] Proc Natl Acad Sci U S A. 1983 Jul;80(13):3966-70 [6306655] Gene. 1983 Oct;24(2-3):179-90 [6315535] Proc Natl Acad Sci U S A. 1985 Apr;82(7):1896-900 [2580302] J Mol Evol. 1989 Jul;29(1):3-19 [2475641] Annu Rev Microbiol. 1989;43:403-34 [2552899] Science. 1989 Nov 17;246(4932):911-6 [2683088] J Virol. 1990 Jul;64(7):3319-30 [2191149] Cell. 1990 Aug 24;62(4):819-28 [2117501] Proc Natl Acad Sci U S A. 1990 Sep;87(18):6990-4 [1698287] EMBO J. 1990 Oct;9(10):3363-8 [1698616] J Virol. 1990 Dec;64(12):5757-63 [1700822] Mol Cell Biol. 1990 Dec;10(12):6718-29 [1701022] Mol Cell Biol. 1991 Sep;11(9):4804-7 [1715025] Trends Biochem Sci. 1991 Jun;16(6):214-20 [1716386] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9794-8 [1719539] Science. 1991 Dec 20;254(5039):1805-8 [1662412] Science. 1991 Dec 20;254(5039):1808-10 [1722352] Cancer Res. 1992 Feb 1;52(3):643-5 [1310068] EMBO J. 1992 Mar;11(3):1155-64 [1312462] Oncogene. 1992 Mar;7(3):507-10 [1312702] Gene. 1992 Oct 21;120(2):183-90 [1327974] J Biol Chem. 1992 Oct 5;267(28):19765-8 [1328181] Cell. 1993 Feb 26;72(4):595-605 [7679954] Mol Cell Biol. 1993 Sep;13(9):5383-92 [8395003] Mol Cell Biol. 1994 Apr;14(4):2584-92 [8139560] Science. 1994 Jul 29;265(5172):615-21 [8036511] Nat Genet. 1994 Jun;7(2):143-8 [7920631] J Biol Chem. 1995 Feb 10;270(6):2868-73 [7852362] Nature. 1986 Jun 5-11;321(6070):625-8 [2423883] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Severe thrombocytopenia in patients treated with suramin: evidence for an immune mechanism in one. AN - 77980955; 8579057 AB - Although suramin has long been used to treat human trypanosomiasis, recent clinical trials have tested its efficacy against the acquired immunodeficiency syndrome (AIDS) and various malignancies. Thromobocytopenia was observed in early trials with suramin in AIDS, but has been uncommon in patients treated for solid tumors. Here we describe 5 patients out of a total of 67 (7%) who developed severe thrombocytopenia while receiving suramin as part of a phase II clinical trial for metastatic prostate carcinoma refractory to hormonal therapy. IgG purified from one patient's plasma caused suramin-dependent platelet aggregation. There was also evidence of crossreactivity between suramin and heparin in this system. An immune mechanism, however, could not be documented in the other cases, suggesting that multiple mechanisms may be responsible for severe thrombocytopenia in this patient population. JF - American journal of hematology AU - Tisdale, J F AU - Figg, W D AU - Reed, E AU - McCall, N A AU - Alkins, B R AU - Horne, M K AD - Hematology Branch, National Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 152 EP - 157 VL - 51 IS - 2 SN - 0361-8609, 0361-8609 KW - Antineoplastic Agents KW - 0 KW - Immunoglobulin G KW - Suramin KW - 6032D45BEM KW - Index Medicus KW - Platelet Aggregation -- immunology KW - Humans KW - Neoplasm Metastasis KW - Middle Aged KW - Immunoglobulin G -- immunology KW - Male KW - Prostatic Neoplasms -- pathology KW - Suramin -- adverse effects KW - Prostatic Neoplasms -- immunology KW - Thrombocytopenia -- immunology KW - Thrombocytopenia -- chemically induced KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77980955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+hematology&rft.atitle=Severe+thrombocytopenia+in+patients+treated+with+suramin%3A+evidence+for+an+immune+mechanism+in+one.&rft.au=Tisdale%2C+J+F%3BFigg%2C+W+D%3BReed%2C+E%3BMcCall%2C+N+A%3BAlkins%2C+B+R%3BHorne%2C+M+K&rft.aulast=Tisdale&rft.aufirst=J&rft.date=1996-02-01&rft.volume=51&rft.issue=2&rft.spage=152&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hematology&rft.issn=03618609&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-14 N1 - Date created - 1996-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthetic analogues of conantokin-G: NMDA antagonists acting through a novel polyamine-coupled site. AN - 77980808; 8592132 AB - Conantokin-G (con-G) is a 17-amino-acid polypeptide that acts as an N-methyl-D-aspartate (NMDA) antagonist. This action has been attributed to a specific but noncompetitive inhibition of the positive modulatory effects of polyamines at NMDA receptors. Con-G possesses several unusual structural features, including five gamma-carboxyglutamate (Gla) residues and a high degree of helicity in aqueous media. Previous structure-activity studies indicated that one or more Gla residues are necessary for NMDA antagonist activity. Con-G analogues were synthesized with alanine (Ala), serine (Ser), and phosphoserine substituted for Gla to assess the contribution of individual Gla residues to biological activity and secondary structure. Replacement of Gla in positions 3 and 4 resulted in polypeptides with markedly reduced and no NMDA antagonist actions, respectively. In contrast, Gla residues in positions 7, 10, and 14 are not required for NMDA antagonist actions because the potencies of con-G analogues containing Ser7, Ser10, Ala14, and Ser14 to inhibit spermine-stimulated [3H]MK-801 binding are similar to the parent peptide. Moreover, the Ala7 derivative of con-G was about fourfold more potent than the parent peptide both as an inhibitor of spermine-stimulated increases in [3H]MK-801 binding (IC50 of approximately 45 nM) and in reducing NMDA-stimulated increases in cyclic GMP levels (IC50 of approximately 77 nM) in cerebellar granule cell cultures. Although con-G and its analogues assumed mixtures of 3(10) and alpha-helices, no clearcut relationship was evinced between the NMDA antagonist properties of these peptides and the degree of helicity they assumed in aqueous solutions. Together with the inability of con-G to affect 5,7-dichloro[3H]kynurenic acid, [3H]CGP-39653, and [3H]ifenprodil binding, these data are consistent with the hypothesis that this polypeptide acts at a unique, polyamine-associated site on NMDA receptors. JF - Journal of neurochemistry AU - Zhou, L M AU - Szendrei, G I AU - Fossom, L H AU - Maccecchini, M L AU - Skolnick, P AU - Otvos, L AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0008, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 620 EP - 628 VL - 66 IS - 2 SN - 0022-3042, 0022-3042 KW - Conotoxins KW - 0 KW - Excitatory Amino Acid Antagonists KW - Mollusk Venoms KW - Peptides, Cyclic KW - Polyamines KW - Receptors, N-Methyl-D-Aspartate KW - N-Methylaspartate KW - 6384-92-5 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - conotoxin GV KW - 93438-65-4 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Neurons -- metabolism KW - Circular Dichroism KW - Amino Acid Sequence KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Structure-Activity Relationship KW - Binding Sites KW - Cerebellum -- metabolism KW - Dizocilpine Maleate -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Cerebellum -- cytology KW - Molecular Sequence Data KW - Male KW - Excitatory Amino Acid Antagonists -- metabolism KW - Excitatory Amino Acid Antagonists -- chemistry KW - Peptides, Cyclic -- metabolism KW - N-Methylaspartate -- antagonists & inhibitors KW - Polyamines -- metabolism KW - Peptides, Cyclic -- chemistry KW - Peptides, Cyclic -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77980808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Synthetic+analogues+of+conantokin-G%3A+NMDA+antagonists+acting+through+a+novel+polyamine-coupled+site.&rft.au=Zhou%2C+L+M%3BSzendrei%2C+G+I%3BFossom%2C+L+H%3BMaccecchini%2C+M+L%3BSkolnick%2C+P%3BOtvos%2C+L&rft.aulast=Zhou&rft.aufirst=L&rft.date=1996-02-01&rft.volume=66&rft.issue=2&rft.spage=620&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-03 N1 - Date created - 1996-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of tumor promoter-induced transformation by retinoids that transrepress AP-1 without transactivating retinoic acid response element. AN - 77977283; 8564958 AB - Both retinoic acid (RA) treatment and dominant-negative c-Jun mutant expression effectively inhibit phorbol ester-induced AP-1 activity and induced neoplastic transformation in mouse epidermal JB6 cells. However, both reagents also target non-AP-1 molecules in addition. Because liganded retinoic acid receptors interact with and transactivate RA response elements (RAREs) on DNA, as well as interact with Jun protein to block AP-1 activity, the question arises as to which of these two activities of retinoids is responsible for antitumor-promoting activity. To address this question we generated JB6 promotion-sensitive (P+) cell lines that are stably transfected with a construct containing the collagenase promoter bearing one AP-1-binding site that drives a luciferase reporter gene. The stable collagenase-luciferase-transfected cell lines showed 1.5-3.5-fold enhanced AP-1 activity when treated with 12-0-tetradecanoyl-phorbol-13-acetate (TPA). Up to 90% of TPA-induced AP-1 activity was blocked by retinoids SR11238, SR11302, or trans-RA, but not by retinoid SR11235. Of these retinoids, only RA and SR11235 were able to transactivate RARE-dependent gene expression. Transrepression of TPA-induced AP-1 and transactivation of RARE by RA, SR11238, and SR11302 were concentration dependent at 10(-10) to 10(-6) M retinoid. When tested for activity in inhibiting tumor promoter-induced transformation in JB6 P+ cells, the retinoids specific for AP-1 transrepression were inhibitory, whereas SR11235, which only activated RARE, showed little effect. We thus conclude that the AP-1-blocking activity of retinoids is likely to be responsible for the antitumor-promoting activity. This result, together with the observation that dominant-negative Jun blocks transformation, argues for a requirement of induced AP-1 in the tumor promoter-induced transformation process. JF - Cancer research AU - Li, J J AU - Dong, Z AU - Dawson, M I AU - Colburn, N H AD - Cell Biology Section, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 1996/02/01/ PY - 1996 DA - 1996 Feb 01 SP - 483 EP - 489 VL - 56 IS - 3 SN - 0008-5472, 0008-5472 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Retinoids KW - Transcription Factor AP-1 KW - Tretinoin KW - 5688UTC01R KW - Luciferases KW - EC 1.13.12.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Skin -- pathology KW - Carcinogens -- toxicity KW - Gene Expression KW - Mice KW - Luciferases -- biosynthesis KW - Base Sequence KW - Promoter Regions, Genetic KW - Skin -- drug effects KW - Transfection KW - Cells, Cultured KW - Genes, Reporter KW - Molecular Sequence Data KW - Luciferases -- genetics KW - Tretinoin -- pharmacology KW - Tetradecanoylphorbol Acetate -- toxicity KW - Regulatory Sequences, Nucleic Acid KW - Anticarcinogenic Agents -- pharmacology KW - Transcriptional Activation -- drug effects KW - Transcription Factor AP-1 -- drug effects KW - Cell Transformation, Neoplastic -- drug effects KW - Retinoids -- pharmacology KW - Transcription Factor AP-1 -- physiology KW - Transcription Factor AP-1 -- genetics KW - Tetradecanoylphorbol Acetate -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77977283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Inhibition+of+tumor+promoter-induced+transformation+by+retinoids+that+transrepress+AP-1+without+transactivating+retinoic+acid+response+element.&rft.au=Li%2C+J+J%3BDong%2C+Z%3BDawson%2C+M+I%3BColburn%2C+N+H&rft.aulast=Li&rft.aufirst=J&rft.date=1996-02-01&rft.volume=56&rft.issue=3&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Self-reported allergy, infection, and autoimmune diseases among men and women exposed in utero to diethylstilbestrol. AN - 77972450; 8606329 AB - Immunotoxicology studies of prenatal or neonatal exposure to diethylstilbestrol (DES) show effects on immune function of the adult animal. Prenatally exposed humans are known to be at increased risk of vaginal adenocarcinoma, but little research has been done to assess immunologic function. A placebo-controlled clinical trial of DES was conducted in the early 1950s. The sons and daughters born to participants of this clinical trial were traced and interviewed about immune-related health problems. Symptom and disease rates for the DES exposed (253 sons and 296 daughters) were compared with rates for the unexposed (241 men and 246 women). DES-exposed men and women reported rates of allergy, infection, and autoimmune disease similar to the unexposed. However, because autoimmune diseases are rare, a larger sample is needed to evaluate further DES-associated risk of autoimmunity. JF - Journal of clinical epidemiology AU - Baird, D D AU - Wilcox, A J AU - Herbst, A L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 263 EP - 266 VL - 49 IS - 2 SN - 0895-4356, 0895-4356 KW - Estrogens, Non-Steroidal KW - 0 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Double-Blind Method KW - Humans KW - Gestational Age KW - Adult KW - Follow-Up Studies KW - Time Factors KW - Male KW - Female KW - Pregnancy KW - Diethylstilbestrol -- adverse effects KW - Hypersensitivity -- etiology KW - Autoimmune Diseases -- chemically induced KW - Estrogens, Non-Steroidal -- adverse effects KW - Prenatal Exposure Delayed Effects KW - Infection -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77972450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+epidemiology&rft.atitle=Self-reported+allergy%2C+infection%2C+and+autoimmune+diseases+among+men+and+women+exposed+in+utero+to+diethylstilbestrol.&rft.au=Baird%2C+D+D%3BWilcox%2C+A+J%3BHerbst%2C+A+L&rft.aulast=Baird&rft.aufirst=D&rft.date=1996-02-01&rft.volume=49&rft.issue=2&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+epidemiology&rft.issn=08954356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-17 N1 - Date created - 1996-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. AN - 77971629; 8564973 AB - Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation. JF - Cancer research AU - Kohn, E C AU - Reed, E AU - Sarosy, G AU - Christian, M AU - Link, C J AU - Cole, K AU - Figg, W D AU - Davis, P A AU - Jacob, J AU - Goldspiel, B AU - Liotta, L A AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/02/01/ PY - 1996 DA - 1996 Feb 01 SP - 569 EP - 573 VL - 56 IS - 3 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Calcium Channel Blockers KW - Triazoles KW - carboxyamido-triazole KW - 99519-84-3 KW - Index Medicus KW - Administration, Oral KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- pharmacokinetics KW - Calcium Channel Blockers -- adverse effects KW - Triazoles -- therapeutic use KW - Triazoles -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Triazoles -- pharmacokinetics KW - Calcium Channel Blockers -- therapeutic use KW - Calcium Channel Blockers -- pharmacokinetics KW - Neoplasms -- metabolism KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77971629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Clinical+investigation+of+a+cytostatic+calcium+influx+inhibitor+in+patients+with+refractory+cancers.&rft.au=Kohn%2C+E+C%3BReed%2C+E%3BSarosy%2C+G%3BChristian%2C+M%3BLink%2C+C+J%3BCole%2C+K%3BFigg%2C+W+D%3BDavis%2C+P+A%3BJacob%2C+J%3BGoldspiel%2C+B%3BLiotta%2C+L+A&rft.aulast=Kohn&rft.aufirst=E&rft.date=1996-02-01&rft.volume=56&rft.issue=3&rft.spage=569&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of RII beta regulatory subunit of protein kinase A in human colon carcinoma cell induces growth arrest and phenotypic changes that are abolished by site-directed mutation of RII beta. AN - 77971167; 8654392 AB - LS-174T human colon carcinoma cells that contain approximately equal amounts of cAMP-dependent protein kinase (PKA) isozymes, PKA-I and PKA-II, were infected with retroviral vectors coding for regulatory (R) and catalytic (C) subunits of human PKA. In cells overexpressing RII alpha, RII beta and RII beta-P (a RII beta mutant at the autophosphorylation site), PKA-II levels increased while PK-A levels decreased. PKA-I was almost completely eliminated in cells overexpressing RII beta or RII beta-P. In contrast, overexpression of either RI alpha or C alpha had little or no effect on PKA isozyme levels. Although all infectants expressed high levels of PKA subunit mRNAs in accordance with gene introduction, the R subunit protein expression was reflected in PKA isozyme levels rather than in subunit mRNA levels. Only RII beta infectants demonstrated marked growth inhibition in monolayer culture, reduced thymidine incorporation into DNA, and inability to grow in semisolid medium or in serum-free medium. Conversely, all other infectants displayed growth properties similar to uninfected parental cells. The growth-retardation properties of RII beta infectants were reflected in their altered phenotypic appearances. Our findings that the mutant RII beta-P could not mimic the growth-inhibitory effect of RII beta suggest the functional importance of the authophosphorylation site in RII beta. Our results suggest a role for RII beta in the suppression of neoplastic cell growth, and thus abnormal expression of R subunit isoforms of PKA may be involved in neoplastic transformation. JF - European journal of biochemistry AU - Nesterova, M AU - Yokozaki, H AU - McDuffie, E AU - Cho-Chung, Y S AD - Celluar Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/02/01/ PY - 1996 DA - 1996 Feb 01 SP - 486 EP - 494 VL - 235 IS - 3 SN - 0014-2956, 0014-2956 KW - Carrier Proteins KW - 0 KW - Culture Media, Serum-Free KW - Intracellular Signaling Peptides and Proteins KW - Isoenzymes KW - Oligonucleotides, Antisense KW - protein kinase modulator KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Thymidine -- metabolism KW - Phenotype KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Mice KW - Isoenzymes -- genetics KW - Cell Division -- genetics KW - Colonic Neoplasms -- genetics KW - Carrier Proteins -- genetics KW - Colonic Neoplasms -- pathology KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77971167?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+biochemistry&rft.atitle=Overexpression+of+RII+beta+regulatory+subunit+of+protein+kinase+A+in+human+colon+carcinoma+cell+induces+growth+arrest+and+phenotypic+changes+that+are+abolished+by+site-directed+mutation+of+RII+beta.&rft.au=Nesterova%2C+M%3BYokozaki%2C+H%3BMcDuffie%2C+E%3BCho-Chung%2C+Y+S&rft.aulast=Nesterova&rft.aufirst=M&rft.date=1996-02-01&rft.volume=235&rft.issue=3&rft.spage=486&rft.isbn=&rft.btitle=&rft.title=European+journal+of+biochemistry&rft.issn=00142956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-30 N1 - Date created - 1996-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipid metabolism as a target for brain cancer therapy: synergistic activity of lovastatin and sodium phenylacetate against human glioma cells. AN - 77969674; 8592143 AB - Malignant gliomas, the most common form of primary brain tumors, are highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical to cell replication. Human glioblastoma cells were found to be uniquely vulnerable to growth arrest by lovastatin, a competitive inhibitor of the enzyme regulating MVA synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. The sodium salt of phenylacetic acid (NaPA), an inhibitor of MVA-pyrophosphate decarboxylase, the enzyme that controls MVA use, acted synergistically with lovastatin to suppress malignant growth. When used at pharmacologically attainable concentrations, the two compounds induced profound cytostasis and loss of malignant properties such as invasiveness and expression of the transforming growth factor-beta 2 gene, coding for a potent immunosuppressive cytokine. Supplementation with exogenous ubiquinone, an end product of the MVA pathway, failed to rescue the cells, suggesting that decreased synthesis of intermediary products are responsible for the antitumor effects observed. In addition to blocking the MVA pathway, lovastatin alone and in combination with NaPA increased the expression of the peroxisome proliferator-activated receptor, a transcription factor implicated in the control of lipid metabolism, cell growth, and differentiation. Our results indicate that targeting lipid metabolism with lovastatin, used alone or in combination with the aromatic fatty acid NaPA, may offer a novel approach to the treatment of malignant gliomas. JF - Journal of neurochemistry AU - Prasanna, P AU - Thibault, A AU - Liu, L AU - Samid, D AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 710 EP - 716 VL - 66 IS - 2 SN - 0022-3042, 0022-3042 KW - Antimetabolites, Antineoplastic KW - 0 KW - Phenylacetates KW - Ubiquinone KW - 1339-63-5 KW - Lovastatin KW - 9LHU78OQFD KW - phenylacetic acid KW - ER5I1W795A KW - Mevalonic Acid KW - S5UOB36OCZ KW - Index Medicus KW - Neoplasm Invasiveness KW - Tumor Cells, Cultured KW - Humans KW - Mevalonic Acid -- metabolism KW - Cell Division -- drug effects KW - Drug Synergism KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Ubiquinone -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacology KW - Brain Neoplasms -- pathology KW - Glioma -- pathology KW - Phenylacetates -- pharmacology KW - Glioma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Lovastatin -- therapeutic use KW - Brain Neoplasms -- metabolism KW - Lovastatin -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Glioma -- metabolism KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Lipid Metabolism KW - Phenylacetates -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77969674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Lipid+metabolism+as+a+target+for+brain+cancer+therapy%3A+synergistic+activity+of+lovastatin+and+sodium+phenylacetate+against+human+glioma+cells.&rft.au=Prasanna%2C+P%3BThibault%2C+A%3BLiu%2C+L%3BSamid%2C+D&rft.aulast=Prasanna&rft.aufirst=P&rft.date=1996-02-01&rft.volume=66&rft.issue=2&rft.spage=710&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-03 N1 - Date created - 1996-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The two biological activities of human immunodeficiency virus type 1 Vpu protein involve two separable structural domains. AN - 77969199; 8551619 AB - The human immunodeficiency virus type 1 (HIV-1) Vpu protein is an integral membrane phosphoprotein that induces CD4 degradation in the endoplasmic reticulum and enhances virus release from the cell surface. CD4 degradation is specific, requires phosphorylation of Vpu, and involves the interaction between Vpu and the CD4 cytoplasmic domain. In contrast, regulation of virus release is less specific and not restricted to HIV-1 and may be mechanistically-distinct from CD4 degradation. We show here that a mutant of Vpu, Vpu35, lacking most of its cytoplasmic domain has residual biological activity for virus release but is unable to induce CD4 degradation. This finding suggests that the N terminus of Vpu encoding the transmembrane (TM) anchor represents an active domain important for the regulation of virus release but not CD4 degradation. To better define the functions of Vpu's TM anchor and cytoplasmic domain, we designed a mutant, VpuRD, containing a scrambled TM sequence with a conserved amino acid composition and alpha-helical structure. The resulting protein was integrated normally into membranes, was able to form homo-oligomers, and exhibited expression levels, protein stability, and subcellular localization similar to those of wild-type Vpu. Moreover, VpuRD was capable of binding to CD4 and to induce CD4 degradation with wild-type efficiency, confirming proper membrane topology and indicating that the alteration of the Vpu TM domain did not interfere with this function of Vpu. However, VpuRD was unable to enhance the release of virus particles from infected or transfected cells, and virus encoding VpuRD had replication characteristics in T cells indistinguishable from those of a Vpu-deficient HIV-1 isolate. Mutation of the phosphorylation sites in VpuRD resulted in a protein which was unable to perform either function of Vpu. The results of our experiments suggest that the two biological activities of Vpu operate via two distinct molecular mechanisms and involve two different structural domains of the Vpu protein. JF - Journal of virology AU - Schubert, U AU - Bour, S AU - Ferrer-Montiel, A V AU - Montal, M AU - Maldarell, F AU - Strebel, K AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-0460, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 809 EP - 819 VL - 70 IS - 2 SN - 0022-538X, 0022-538X KW - Antigens, CD4 KW - 0 KW - Human Immunodeficiency Virus Proteins KW - Membrane Proteins KW - Viral Regulatory and Accessory Proteins KW - vpu protein, Human immunodeficiency virus 1 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - HeLa Cells KW - Membrane Proteins -- chemistry KW - Humans KW - Membrane Proteins -- metabolism KW - Amino Acid Sequence KW - Virion -- metabolism KW - Membrane Proteins -- genetics KW - HIV Seropositivity -- immunology KW - Antigens, CD4 -- metabolism KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Molecular Sequence Data KW - HIV Seropositivity -- blood KW - HIV-1 -- metabolism KW - HIV-1 -- isolation & purification KW - Viral Regulatory and Accessory Proteins -- metabolism KW - Viral Regulatory and Accessory Proteins -- chemistry KW - Viral Regulatory and Accessory Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77969199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=The+two+biological+activities+of+human+immunodeficiency+virus+type+1+Vpu+protein+involve+two+separable+structural+domains.&rft.au=Schubert%2C+U%3BBour%2C+S%3BFerrer-Montiel%2C+A+V%3BMontal%2C+M%3BMaldarell%2C+F%3BStrebel%2C+K&rft.aulast=Schubert&rft.aufirst=U&rft.date=1996-02-01&rft.volume=70&rft.issue=2&rft.spage=809&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-22 N1 - Date created - 1996-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Acquir Immune Defic Syndr. 1993 Feb;6(2):135-41 [8094456] J Virol. 1993 Jul;67(7):3877-84 [8510209] J Virol. 1993 Aug;67(8):5056-61 [8331740] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7381-5 [8346259] J Virol. 1993 Sep;67(9):5538-49 [8350411] J Virol. 1993 Dec;67(12):7238-45 [8230446] J Virol. 1994 Feb;68(2):1207-12 [8289353] J Mol Biol. 1994 Feb 11;236(1):16-25 [8107101] J Virol. 1994 Apr;68(4):2260-71 [8139011] J Virol. 1994 May;68(5):3092-101 [8151774] J Virol. 1995 Mar;69(3):1510-20 [7853484] Int J Pept Protein Res. 1995 Jan;45(1):35-43 [7775007] J Virol. 1995 Dec;69(12):7699-711 [7494279] J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jan 1;8(1):10-22 [8548340] Nature. 1988 Jan 7;331(6151):82-4 [3257544] Nature. 1988 Aug 11;334(6182):532-4 [3043230] Science. 1988 Sep 2;241(4870):1221-3 [3261888] Proc Natl Acad Sci U S A. 1989 Jul;86(13):5163-7 [2472639] J Virol. 1989 Sep;63(9):3784-91 [2788224] J Virol. 1990 Feb;64(2):621-9 [2404139] Nature. 1990 May 24;345(6273):356-9 [2188136] Nature. 1990 Jun 14;345(6276):625-8 [2190096] J Virol. 1990 Nov;64(11):5585-93 [2214026] J Virol. 1990 Dec;64(12):6297-304 [2243395] J Virol. 1991 Dec;65(12):6387-96 [1942241] J Virol. 1992 Jan;66(1):226-34 [1727486] Eur J Biochem. 1992 Mar 1;204(2):875-83 [1541298] J Virol. 1992 Aug;66(8):5119-26 [1629967] J Virol. 1992 Dec;66(12):7193-200 [1433512] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Virology. 1973 Apr;52(2):456-67 [4705382] J Natl Cancer Inst. 1973 Dec;51(6):1849-60 [4358145] Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777-81 [6294651] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] J Virol. 1986 Aug;59(2):284-91 [3016298] Science. 1986 Nov 28;234(4780):1123-7 [3095925] J Virol. 1988 Jan;62(1):139-47 [3257102] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An inevitable dilemma: prenatal testing for mutations in the BRCA1 breast-ovarian cancer susceptibility gene. AN - 77968478; 8559544 AB - The BRCA1 breast-ovarian cancer susceptibility gene was identified recently. Germline mutations in BRCA1 may be responsible for as many as 5% of breast and ovarian cancers. Inherited alterations confer up to a 94% risk of developing breast and/or ovarian cancer by age 70. With the discovery of BRCA1, there will be a heavy demand for genetic testing. Because of the large size of the gene and the distribution of reported mutations, scientists face considerable technical problems in developing widely available screening tests; clinicians will face even greater ethical problems in applying them. In the context of research programs, women with BRCA1 mutations are already being identified, and their physicians are confronted with a number of complex medical, ethical, legal, and social issues. Obstetricians will be faced with counseling parents regarding prenatal testing for specific BRCA1 mutations. Although it is difficult to formulate straightforward guidelines regarding prenatal BRCA1 testing, clinicians and health care providers must be familiar with the nuances of the debate so that these issues can be discussed wisely with patients. As with many ethically challenging problems in medicine, individual clinicians and their patients will have to work together to determine the course of action with which they are most comfortable. Although elective termination of a pregnancy with a germline mutation in BRCA1 is an option, experience with other adult-onset diseases suggests that only a minority of parents will choose this option. JF - Obstetrics and gynecology AU - Lancaster, J M AU - Wiseman, R W AU - Berchuck, A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 306 EP - 309 VL - 87 IS - 2 SN - 0029-7844, 0029-7844 KW - BRCA1 Protein KW - 0 KW - Neoplasm Proteins KW - Transcription Factors KW - Abridged Index Medicus KW - Bioethics KW - Index Medicus KW - Genetics and Reproduction KW - Humans KW - Mutation KW - Female KW - Pregnancy KW - Fetal Diseases -- genetics KW - Breast Neoplasms -- genetics KW - Genetic Testing KW - Breast Neoplasms -- diagnosis KW - Ovarian Neoplasms -- genetics KW - Neoplasm Proteins -- genetics KW - Fetal Diseases -- diagnosis KW - Ethics, Medical KW - Prenatal Diagnosis KW - Transcription Factors -- genetics KW - Ovarian Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77968478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Obstetrics+and+gynecology&rft.atitle=An+inevitable+dilemma%3A+prenatal+testing+for+mutations+in+the+BRCA1+breast-ovarian+cancer+susceptibility+gene.&rft.au=Lancaster%2C+J+M%3BWiseman%2C+R+W%3BBerchuck%2C+A&rft.aulast=Lancaster&rft.aufirst=J&rft.date=1996-02-01&rft.volume=87&rft.issue=2&rft.spage=306&rft.isbn=&rft.btitle=&rft.title=Obstetrics+and+gynecology&rft.issn=00297844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-26 N1 - Date created - 1996-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suspension-induced murine keratinocyte differentiation is mediated by calcium. AN - 77966621; 8601725 AB - Modulating extracellular Ca2+ (Cao) and suspension culture are two frequently used methods to induce maturation of cultured human and mouse keratinocytes. To determine if the two methods share a common mechanism, changes in Ca2+ metabolism were studied in suspension cultures of mouse keratinocytes. Spontaneously detached and suspension- cultured keratinocytes in 0.05 microM Ca2+ medium express markers of suprabasal differentiation, while 0.05 microM Ca2+ is not permissive for marker expression by attached keratinocytes. Intracellular free Ca2+ (Cai) increased rapidly after placing keratinocytes in suspension in 0.05 microM Ca2+, reaching levels up to 3- to 4-fold higher than Cai in attached cells after 4-5 h. In suspended cells, the increase in Cai was associated with a 2- to 6- fold increase in Ca2+ transport across plasma membrane as well as depletion of intracellular Ca2+ -stores. Differentiation marker expression and terminal differentiation were inhibited in suspension-cultured keratinocytes by preventing the rise of Cai using either 1,2-bis (o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid to chelate intracellular Ca2+ or ethyleneglycol-bis (beta-aminoethyl ether)- N,N,N',N' -tetraacetic acid to reduce Cao. Together these results indicate that a rise in CAi is a common mechanism controlling differentiation in cultured mouse keratinocytes, and suspension of keratinocytes enhances Ca2+ transport and alters intracellular Ca2+ sequestration producing a rise in Cai. JF - The Journal of investigative dermatology AU - Li, L AU - Tennenbaum, T AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996/02// PY - 1996 DA - February 1996 SP - 254 EP - 260 VL - 106 IS - 2 SN - 0022-202X, 0022-202X KW - Antigens, Differentiation KW - 0 KW - Calcium Radioisotopes KW - Chelating Agents KW - Egtazic Acid KW - 526U7A2651 KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid KW - K22DDW77C0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Calcium Radioisotopes -- metabolism KW - Egtazic Acid -- analogs & derivatives KW - Antigens, Differentiation -- analysis KW - Cell Division -- drug effects KW - Mice KW - Mice, Inbred BALB C KW - Chelating Agents -- pharmacology KW - Cells, Cultured KW - Antigens, Differentiation -- drug effects KW - Cell Differentiation -- drug effects KW - Time Factors KW - Egtazic Acid -- pharmacology KW - Keratinocytes -- cytology KW - Calcium -- pharmacology KW - Keratinocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77966621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Suspension-induced+murine+keratinocyte+differentiation+is+mediated+by+calcium.&rft.au=Li%2C+L%3BTennenbaum%2C+T%3BYuspa%2C+S+H&rft.aulast=Li&rft.aufirst=L&rft.date=1996-02-01&rft.volume=106&rft.issue=2&rft.spage=254&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-03 N1 - Date created - 1996-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells. AN - 77979785; 8579579 AB - Autotaxin, a potent human tumor cell motility-stimulating exophosphodiesterase, was isolated and cloned from the human teratocarcinoma cell line NTera2D1. The deduced amino acid sequence for the teratocarcinoma autotaxin has 94% identity to the melanoma-derived protein, 90% identity to rat brain phosphodiesterase I/nucleotide pyrophosphatase (PD-I alpha), and 44% identity to the plasma cell membrane marker PC-I. Utilizing polymerase chain reaction screening of the CEPH YAC library, we localized the autotaxin gene to human chromosome 8q23-24. Northern blot analysis of relative mRNA from multiple human tissues revealed that autotaxin mRNA steady state expression is most abundant in brain, placenta, ovary, and small intestine. JF - Biochemical and biophysical research communications AU - Lee, H Y AU - Murata, J AU - Clair, T AU - Polymeropoulos, M H AU - Torres, R AU - Manrow, R E AU - Liotta, L A AU - Stracke, M L AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/01/26/ PY - 1996 DA - 1996 Jan 26 SP - 714 EP - 719 VL - 218 IS - 3 SN - 0006-291X, 0006-291X KW - DNA, Complementary KW - 0 KW - Glycoproteins KW - Multienzyme Complexes KW - RNA, Messenger KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - Phosphodiesterase I KW - EC 3.1.4.1 KW - alkylglycerophosphoethanolamine phosphodiesterase KW - EC 3.1.4.39 KW - Pyrophosphatases KW - EC 3.6.1.- KW - Glucose-6-Phosphate Isomerase KW - EC 5.3.1.9 KW - Index Medicus KW - Cell Movement KW - Animals KW - DNA, Complementary -- genetics KW - Humans KW - Gene Expression KW - Melanoma -- chemistry KW - Amino Acid Sequence KW - Chromosomes, Human, Pair 8 KW - RNA, Messenger -- genetics KW - Chromosome Mapping KW - Teratocarcinoma -- chemistry KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Genes KW - Sequence Alignment KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Chromosomes, Artificial, Yeast KW - Glycoproteins -- genetics KW - Glucose-6-Phosphate Isomerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77979785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Cloning%2C+chromosomal+localization%2C+and+tissue+expression+of+autotaxin+from+human+teratocarcinoma+cells.&rft.au=Lee%2C+H+Y%3BMurata%2C+J%3BClair%2C+T%3BPolymeropoulos%2C+M+H%3BTorres%2C+R%3BManrow%2C+R+E%3BLiotta%2C+L+A%3BStracke%2C+M+L&rft.aulast=Lee&rft.aufirst=H&rft.date=1996-01-26&rft.volume=218&rft.issue=3&rft.spage=714&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-12 N1 - Date created - 1996-03-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L46720; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The influence of single base changes on UV mutational activity at two translocated hotspots. AN - 77976871; 8568888 AB - Mutation hotspots have been a staple of mutation spectra since the introduction of fine structure mutation mapping almost 40 years ago. It has been well established that sequence context is an important determinant of mutational activity at mutagen induced hotspots and coldspots. However, our understanding of the sequence effectors of base substitution hotspots is quite limited. This is because manipulation of the sequence about a hotspot site in a marker gene is restricted by the need to maintain a functional marker. In this work, we describe a generalizable system for studying sequence context effects on mutagenesis. We have prepared a variant of the supF tRNA gene (a marker used by us in previous studies) in which an eight-base palindrome, the site of two UV hotspots in the interior of the gene, was copied into the acceptor stem and pre-tRNA region. The variant tRNA was active. The UV mutation spectrum of this variant showed that the new copy of the palindrome generated two hotspots which were as intense as the original sites in the interior of the gene. Variant genes were constructed with all possible bases at the first position in the palindrome in the pre-tRNA sequence, which does not affect tRNA function. The mutation analysis showed that activity at one of the hotspots could be reduced or enhanced by the changes, while activity at the other site was not significantly affected. The base changes did not influence the frequency of cyclobutane dimer or (6-4) photoproduct formation at the two hotspot sites. Thus, the changes in mutational activity were due to the influence of sequence context on the efficiency of mutation formation at the sites of UV lesions. JF - Journal of molecular biology AU - Levy, D D AU - Magee, A D AU - Namiki, C AU - Seidman, M M AD - Laboratory of Molecular Carcinogenesis, NCI, NIH Bethesda, MD 20892, USA. Y1 - 1996/01/26/ PY - 1996 DA - 1996 Jan 26 SP - 435 EP - 445 VL - 255 IS - 3 SN - 0022-2836, 0022-2836 KW - Genetic Markers KW - 0 KW - RNA Precursors KW - supF tRNA KW - RNA, Transfer KW - 9014-25-9 KW - Index Medicus KW - Point Mutation -- genetics KW - Xeroderma Pigmentosum KW - Ultraviolet Rays KW - Base Sequence -- genetics KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - RNA Precursors -- genetics KW - Genes, Suppressor KW - Cell Line KW - Mutagenesis -- radiation effects KW - RNA, Transfer -- genetics KW - Mutagenesis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77976871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=The+influence+of+single+base+changes+on+UV+mutational+activity+at+two+translocated+hotspots.&rft.au=Levy%2C+D+D%3BMagee%2C+A+D%3BNamiki%2C+C%3BSeidman%2C+M+M&rft.aulast=Levy&rft.aufirst=D&rft.date=1996-01-26&rft.volume=255&rft.issue=3&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequency and relationships of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats. AN - 77972594; 8597028 AB - The relative sensitivities of eight commonly used clinical chemistry end points and histopathology to detect potential toxic effects in liver and kidney were evaluated for a series of 61 13-week rat toxicity studies conducted for the National Toxicology Program. The data consisted of 1-,2- to 3-, and 13 week clinical chemistry measurements and 13-week histopathological assessments of liver and kidney. Except for serum alkaline phosphatase, treatment-related alterations of individual clinical chemistry variables occurred in 20-48% of the studies, depending on the analyte, sampling time, and sex. Liver and kidney lesions were reported for 31% and 41% of the studies respectively. There was an association between treatment-related increases in alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities and histopathological changes in the liver. SDH activity had greater positive and negative predictive values than similar changes in ALT; by week 1 in females and weeks 2-3 in both sexes. SDH predicted morphological hepatic change at study termination with 75% or better accuracy. If increases in activities of both enzymes occurred simultaneously, however, terminal histopathological changes could be predicted, in both sexes, with 75% accuracy by week 1, increasing to 100% by weeks 2-3. There also was an association between treatment-related increases in urea nitrogen (UN) and creatinine (Cre) concentrations and morphological kidney change. Cre concentration had greater positive predictive values than similar changes in UN; by weeks 2-3 in males and week 13 in both sexes. Cre predicted morphological renal change at study termination with 56% or better accuracy. UN concentration was associated and predictive of morphological kidney change only in females at week 13. Depending on time point and sex, serum alkaline phosphatase activity increased in 5-22% of the studies. Increases in total bile acid concentration occurred in 33-48% of the studies. Because both tests are used as markers of cholestasis, this marked discrepancy was unexpected. Treatment-related decreases in alkaline phosphatase activity occurred, however, in 39-56% of the studies; serum alkaline phosphatase may be more useful as an indicator of decreased food intake (decreased activity) than of cholestasis (increased activity). In summary, treatment-related alterations of clinical chemistry and histopathology occurred frequently in this series of toxicity studies in rats. Changes in the chemistry end points also occurred frequently at interim time points, indicating that clinical chemistry evaluations can be useful for detecting potential treatment effects throughout a study. This observation is important, since histopathological evaluations are limited to animal termination and not useful for detecting transient responses or the onset of treatment-related effects. JF - Toxicology AU - Travlos, G S AU - Morris, R W AU - Elwell, M R AU - Duke, A AU - Rosenblum, S AU - Thompson, M B AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/01/22/ PY - 1996 DA - 1996 Jan 22 SP - 17 EP - 29 VL - 107 IS - 1 SN - 0300-483X, 0300-483X KW - Bile Acids and Salts KW - 0 KW - Biomarkers KW - Blood Proteins KW - Serum Albumin KW - Creatinine KW - AYI8EX34EU KW - L-Iditol 2-Dehydrogenase KW - EC 1.1.1.14 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Serum Albumin -- analysis KW - Dose-Response Relationship, Drug KW - Chemical and Drug Induced Liver Injury KW - Blood Urea Nitrogen KW - Alkaline Phosphatase -- blood KW - Bile Acids and Salts -- analysis KW - Blood Proteins -- analysis KW - Rats KW - Rats, Inbred F344 KW - Alanine Transaminase -- blood KW - L-Iditol 2-Dehydrogenase -- blood KW - Biomarkers -- analysis KW - Chemistry, Clinical KW - Creatinine -- analysis KW - Male KW - Female KW - Kidney Diseases -- chemically induced KW - Liver -- pathology KW - Kidney -- pathology KW - Liver -- drug effects KW - Kidney -- drug effects KW - Toxicity Tests -- methods KW - Kidney -- chemistry KW - Liver -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77972594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Frequency+and+relationships+of+clinical+chemistry+and+liver+and+kidney+histopathology+findings+in+13-week+toxicity+studies+in+rats.&rft.au=Travlos%2C+G+S%3BMorris%2C+R+W%3BElwell%2C+M+R%3BDuke%2C+A%3BRosenblum%2C+S%3BThompson%2C+M+B&rft.aulast=Travlos&rft.aufirst=G&rft.date=1996-01-22&rft.volume=107&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-17 N1 - Date created - 1996-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral mediated transfer of the cDNA for human glucocerebrosidase into hematopoietic stem cells of patients with Gaucher disease. A phase I study. AN - 78291355; 8788174 AB - Patients with Gaucher disease suffer from a lack of functional glucocerebrosidase enzyme (Gc). Disease symptoms are a result of macrophage engorgement secondary to this enzyme deficiency. This study is designed to determine if cDNA encoding normal Gc can be introduced into macrophage precursors using a retroviral vector. CD34+ cells obtained from G-CSF mobilized peripheral blood stem cells or from bone marrow will be transduced ex vivo using one of the following three methods of transduction: 1) GlGc retroviral supernatant in the presence of autologous stroma over a period of 72 hours, 2) GlGc retroviral supernatant in the presence of interleukin-3, interleukin-6, stem cell factor and autologous stroma over a 72 hour period, 3) G1Gc retroviral supernatant in the presence of interleukin-3, interleukin-6, and stem cell factor over a 72 hour period. These transduced cells will be reinfused into the patient and the patient monitored for toxicities as well as evidence of successful gene transfer and expression. A total of twenty-four patients will be enrolled on the protocol. Patients will be assigned in equal numbers to each of six groups. The two sites participating are the National Institutes of Health and Childrens Hospital of Los Angeles. JF - Human gene therapy AU - Dunbar, C AU - Kohn, D AD - CHB, NHLBI. Y1 - 1996/01/20/ PY - 1996 DA - 1996 Jan 20 SP - 231 EP - 253 VL - 7 IS - 2 SN - 1043-0342, 1043-0342 KW - DNA, Complementary KW - 0 KW - Glucosylceramidase KW - EC 3.2.1.45 KW - Index Medicus KW - Hematopoietic Stem Cells KW - Humans KW - Genetic Vectors KW - DNA, Complementary -- administration & dosage KW - Retroviridae -- genetics KW - Clinical Protocols KW - Gene Transfer Techniques KW - Genetic Therapy -- methods KW - Glucosylceramidase -- genetics KW - Gaucher Disease -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78291355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Retroviral+mediated+transfer+of+the+cDNA+for+human+glucocerebrosidase+into+hematopoietic+stem+cells+of+patients+with+Gaucher+disease.+A+phase+I+study.&rft.au=Dunbar%2C+C%3BKohn%2C+D&rft.aulast=Dunbar&rft.aufirst=C&rft.date=1996-01-20&rft.volume=7&rft.issue=2&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Human+gene+therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-22 N1 - Date created - 1996-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of phosphorylation-defective mutants of human P-glycoprotein expressed in mammalian cells. AN - 77962831; 8576173 AB - To assess the role of phosphorylation of the human multidrug resistance MDR1 gene product P-glycoprotein for its drug transport activity, phosphorylation sites within its linker region were subjected to mutational analysis. We constructed a 5A mutant, in which serines at positions 661, 667, 671, 675, and 683 were replaced by nonphosphorylatable alanine residues, and a 5D mutant carrying aspartic acid residues at the respective positions to mimic permanently phosphorylated serine residues. Transfection studies revealed that both mutants were targeted properly to the cell surface and conferred multidrug resistance by diminishing drug accumulation. In contrast to wild-type P-glycoprotein, the overexpressed 5A and the 5D mutants exhibited no detectable levels of phosphorylation, either in vivo following metabolic labeling of cells with [32P]orthophosphate or in vitro in phosphorylation assays with protein kinase C, cAMP-dependent protein kinase, or a P-glyco-protein-specific protein kinase purified from multidrug-resistant KB-V1 cells. These results reconfirm that the major P-glycoprotein phosphorylation sites are located within the linker region. Furthermore, the first direct evidence is provided that phosphorylation/dephosphorylation mechanisms do not play an essential role in the establishment of the multidrug resistance phenotype mediated by human P-glycoprotein. JF - The Journal of biological chemistry AU - Germann, U A AU - Chambers, T C AU - Ambudkar, S V AU - Licht, T AU - Cardarelli, C O AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/01/19/ PY - 1996 DA - 1996 Jan 19 SP - 1708 EP - 1716 VL - 271 IS - 3 SN - 0021-9258, 0021-9258 KW - Oligodeoxyribonucleotides KW - 0 KW - P-Glycoprotein KW - Recombinant Proteins KW - Aspartic Acid KW - 30KYC7MIAI KW - Serine KW - 452VLY9402 KW - Vincristine KW - 5J49Q6B70F KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Mammals KW - DNA Mutational Analysis KW - Humans KW - Vincristine -- pharmacology KW - Gene Expression KW - Mice KW - Amino Acid Sequence KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Phosphorylation KW - Transfection KW - Restriction Mapping KW - Point Mutation KW - Molecular Sequence Data KW - Cell Membrane -- metabolism KW - Drug Resistance, Multiple -- genetics KW - Mutagenesis, Site-Directed KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- isolation & purification KW - P-Glycoprotein -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77962831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+phosphorylation-defective+mutants+of+human+P-glycoprotein+expressed+in+mammalian+cells.&rft.au=Germann%2C+U+A%3BChambers%2C+T+C%3BAmbudkar%2C+S+V%3BLicht%2C+T%3BCardarelli%2C+C+O%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Germann&rft.aufirst=U&rft.date=1996-01-19&rft.volume=271&rft.issue=3&rft.spage=1708&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-11 N1 - Date created - 1996-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention of mammary carcinogenesis in the rat: combined use of raloxifene and 9-cis-retinoic acid. AN - 77918456; 8537973 JF - Journal of the National Cancer Institute AU - Anzano, M A AU - Peer, C W AU - Smith, J M AU - Mullen, L T AU - Shrader, M W AU - Logsdon, D L AU - Driver, C L AU - Brown, C C AU - Roberts, A B AU - Sporn, M B AD - Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/01/17/ PY - 1996 DA - 1996 Jan 17 SP - 123 EP - 125 VL - 88 IS - 2 SN - 0027-8874, 0027-8874 KW - Estrogen Antagonists KW - 0 KW - Piperidines KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Estrogen Antagonists -- administration & dosage KW - Tretinoin -- administration & dosage KW - Piperidines -- administration & dosage KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Mammary Neoplasms, Experimental -- prevention & control KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77918456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Chemoprevention+of+mammary+carcinogenesis+in+the+rat%3A+combined+use+of+raloxifene+and+9-cis-retinoic+acid.&rft.au=Anzano%2C+M+A%3BPeer%2C+C+W%3BSmith%2C+J+M%3BMullen%2C+L+T%3BShrader%2C+M+W%3BLogsdon%2C+D+L%3BDriver%2C+C+L%3BBrown%2C+C+C%3BRoberts%2C+A+B%3BSporn%2C+M+B&rft.aulast=Anzano&rft.aufirst=M&rft.date=1996-01-17&rft.volume=88&rft.issue=2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-06 N1 - Date created - 1996-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Attention-related brain potential and cognition in alcoholism-associated organic brain disorders. AN - 78239468; 8717614 JF - Biological psychiatry AU - Eckardt, M J AU - Rohrbaugh, J W AU - Stapleton, J M AU - Davis, E Z AU - Martin, P R AU - Weingartner, H J AD - Laboratory of Clinial Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-1250, USA. Y1 - 1996/01/15/ PY - 1996 DA - 1996 Jan 15 SP - 143 EP - 146 VL - 39 IS - 2 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Intelligence KW - Memory KW - Humans KW - Aged KW - Middle Aged KW - Neuropsychological Tests KW - Male KW - Female KW - Substance-Related Disorders -- physiopathology KW - Cognition -- physiology KW - Evoked Potentials KW - Substance-Related Disorders -- etiology KW - Substance-Related Disorders -- psychology KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78239468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Attention-related+brain+potential+and+cognition+in+alcoholism-associated+organic+brain+disorders.&rft.au=Eckardt%2C+M+J%3BRohrbaugh%2C+J+W%3BStapleton%2C+J+M%3BDavis%2C+E+Z%3BMartin%2C+P+R%3BWeingartner%2C+H+J&rft.aulast=Eckardt&rft.aufirst=M&rft.date=1996-01-15&rft.volume=39&rft.issue=2&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-03 N1 - Date created - 1996-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in bladder tumors from arylamine-exposed workers. AN - 77985626; 8542583 AB - In this study we compared the frequency and pattern of p53 mutations in 34 bladder tumors from people with high-level occupational exposure to arylamines to those in 30 bladder tumors from people without such exposure. No differences were observed for p53 mutations between the two groups. The frequency of mutation was similar at 47% for arylamine-exposed individuals and 53% for unexposed individuals and showed a similar pattern of mutation, with GC to AT transitions accounting for the majority of the mutations in both groups. This finding suggests that arylamine exposure does not leave a mutational "footprint" in the p53 gene. However, compared to other tumors, bladder tumors from both exposed and unexposed individuals had a high frequency of multiple mutations and it is interesting that these mutations were highly concordant. We suggest that one explanation of this pattern of mutations could be from decreased DNA repair fidelity within tumor cells. The frequency of mutation in p53 is closely linked to tumor grade and stage and so may be a late event in the development of bladder tumors. JF - Cancer research AU - Taylor, J A AU - Li, Y AU - He, M AU - Mason, T AU - Mettlin, C AU - Vogler, W J AU - Maygarden, S AU - Liu, E AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/01/15/ PY - 1996 DA - 1996 Jan 15 SP - 294 EP - 298 VL - 56 IS - 2 SN - 0008-5472, 0008-5472 KW - Amines KW - 0 KW - Mutagens KW - Index Medicus KW - Base Sequence KW - Exons KW - Aged, 80 and over KW - Humans KW - Molecular Sequence Data KW - Aged KW - Middle Aged KW - Occupational Diseases -- genetics KW - Genes, p53 KW - Mutagens -- adverse effects KW - Urinary Bladder Neoplasms -- genetics KW - Point Mutation KW - Occupational Diseases -- chemically induced KW - Amines -- adverse effects KW - Urinary Bladder Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77985626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=p53+mutations+in+bladder+tumors+from+arylamine-exposed+workers.&rft.au=Taylor%2C+J+A%3BLi%2C+Y%3BHe%2C+M%3BMason%2C+T%3BMettlin%2C+C%3BVogler%2C+W+J%3BMaygarden%2C+S%3BLiu%2C+E&rft.aulast=Taylor&rft.aufirst=J&rft.date=1996-01-15&rft.volume=56&rft.issue=2&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-13 N1 - Date created - 1996-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-function relationships of phenylalanine hydroxylase revealed by radiation target analysis. AN - 77984204; 8561502 AB - Phenylalanine hydroxylase (PAH) purified from rat liver is an oligomeric protein (predominantly tetramers) composed of 52-kDa subunits that are identical in primary structure. We have used radiation target analysis to probe the subunit organization of the enzyme. When 6-methyltetrahydropterin was used as the cofactor, the loss of hydroxylase activity as a function of radiation dose was defined by a single exponential decay, yielding a target size of about 120 kDa. However, when the enzyme was assayed with the natural cofactor tetrahydrobiopterin (BH4), the inactivation curves were much more complex. In these cases, the activity first increased, then decreased, as a function of radiation dose. The inactivation profile at higher radiation doses implied a target size of approximately 100 kDa. Kinetic analysis of the enzyme was significantly activated relative to the nonirradiated sample. In addition, the irradiated enzyme was desensitized to substrate-level activation by phenylalanine. The initial increase in activity at low radiation doses is due to the destruction of a large inhibitor. Analysis of the irradiated samples by high-performance size-exclusion chromatography indicated that the hydroxylase tetramer was lost with a target size of 110 kDa. Our data indicate that the tetrameric form of purified PAH consists of two enzymatically active dimers and that BH4 interacts with a tetramer to inhibit or deactivate the enzymatic activity. JF - Archives of biochemistry and biophysics AU - Davis, M D AU - Parniak, M A AU - Kaufman, S AU - Kempner, E AD - National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/01/15/ PY - 1996 DA - 1996 Jan 15 SP - 235 EP - 241 VL - 325 IS - 2 SN - 0003-9861, 0003-9861 KW - Pterins KW - 0 KW - Biopterin KW - 22150-76-1 KW - 6-methyltetrahydropterin KW - 942-41-6 KW - Phenylalanine Hydroxylase KW - EC 1.14.16.1 KW - sapropterin KW - EGX657432I KW - Index Medicus KW - Rats KW - Molecular Structure KW - Biopterin -- analogs & derivatives KW - Radiation Dosage KW - Animals KW - Liver -- enzymology KW - Kinetics KW - In Vitro Techniques KW - Pterins -- metabolism KW - Biopterin -- metabolism KW - Molecular Weight KW - Protein Conformation KW - Phenylalanine Hydroxylase -- antagonists & inhibitors KW - Phenylalanine Hydroxylase -- chemistry KW - Phenylalanine Hydroxylase -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77984204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Structure-function+relationships+of+phenylalanine+hydroxylase+revealed+by+radiation+target+analysis.&rft.au=Davis%2C+M+D%3BParniak%2C+M+A%3BKaufman%2C+S%3BKempner%2C+E&rft.aulast=Davis&rft.aufirst=M&rft.date=1996-01-15&rft.volume=325&rft.issue=2&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-26 N1 - Date created - 1996-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered cJUN expression: an early event in human lung carcinogenesis. AN - 77965169; 8542585 AB - Although the c-jun oncogene is an integral part of the AP-1 transcriptional complex implicated in the process of tumor promotion, its role in the pathogenesis of human tumors is unknown. We analyzed the expression and function of cJun in 110 non-small cell lung cancer (NSCLC) primary and metastatic tumors, histologically atypical areas from the surrounding lung, and 10 NSCLC cell lines to examine the role of cJun in lung carcinogenesis. cJun was expressed in primary and metastatic lung tumors in 31% of cases, with no association with survival. Whereas normal conducting airway and alveolar epithelial in general did not express cJun by immunohistochemistry, histologically atypical areas were frequently positive for cJun, regardless of the status of the corresponding tumor. Multiple members of the jun and fos gene families were frequently expressed at the mRNA level in vitro, with detectable functional activity (as defined by AP-1-specific DNA binding and/or transactivation of an AP-1-driven reporter construct) present in all 10 NSCLC cell lines examined. Although tumor-promoting phorbol esters had little effect on c-jun expression, serum stimulation generally resulted in significant c-jun induction in NSCLC cell lines. These data show that cJun expression is altered early during human lung carcinogenesis and that cJun may function as a mediator of growth factor signals in NSCLC. JF - Cancer research AU - Szabo, E AU - Riffe, M E AU - Steinberg, S M AU - Birrer, M J AU - Linnoila, R I AD - Biomarkers and Prevention Research Branch, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1996/01/15/ PY - 1996 DA - 1996 Jan 15 SP - 305 EP - 315 VL - 56 IS - 2 SN - 0008-5472, 0008-5472 KW - Growth Substances KW - 0 KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Index Medicus KW - Signal Transduction -- physiology KW - Humans KW - Gene Expression KW - Middle Aged KW - Genes, fos KW - Proto-Oncogene Proteins c-jun -- biosynthesis KW - Transcription Factor AP-1 -- physiology KW - Proto-Oncogene Proteins c-jun -- analysis KW - Immunohistochemistry KW - Growth Substances -- physiology KW - Male KW - Female KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Lung Neoplasms -- secondary KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Lung Neoplasms -- genetics KW - Carcinoma, Non-Small-Cell Lung -- secondary KW - Lung Neoplasms -- metabolism KW - Genes, jun UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77965169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Altered+cJUN+expression%3A+an+early+event+in+human+lung+carcinogenesis.&rft.au=Szabo%2C+E%3BRiffe%2C+M+E%3BSteinberg%2C+S+M%3BBirrer%2C+M+J%3BLinnoila%2C+R+I&rft.aulast=Szabo&rft.aufirst=E&rft.date=1996-01-15&rft.volume=56&rft.issue=2&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-13 N1 - Date created - 1996-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of immunoglobulin/c-myc recombinations in mice that are resistant to plasmacytoma induction. AN - 77964022; 8542601 AB - Interchromosomal recombinations between c-myc and immunoglobulin sequences can be found in preneoplastic lesions (oil granulomata) during pristane-induced plasmacytoma development in susceptible BALB/cAn mice. In this study we used a more sensitive approach, hybridization-enriched templates with nested PCR, to detect microclones with Ig alpha/c-myc recombinations in oil granulomata of susceptible and resistant mice. Recombinations were detected in as many as 73% (32/44) of plasmacytoma-susceptible BALB/cAn mice 30 days after an injection of pristane. Mice that are resistant to plasmacytoma induction can also harbor recombination-positive cells, but these are less frequent [2/20 DBA/2N, 8/20 (BALB/cAn x DBA/2N)F1, hereafter called CD2F1]. The clones in DBA/2N mice were small (< 400 cells), whereas in BALB/cAn, the oil granuloma harbored up to several thousand of these cells. We conclude that the molecular machinery for generating characteristic interchromosomal recombinations can be found in all strains of mice. Both the frequency of generating Ig alpha/c-myc recombinations and the expansion of recombination-positive cells are greater in susceptible mice than in resistant strains. JF - Cancer research AU - Müller, J R AU - Jones, G M AU - Potter, M AU - Janz, S AD - Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/01/15/ PY - 1996 DA - 1996 Jan 15 SP - 419 EP - 423 VL - 56 IS - 2 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - DNA, Neoplasm KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Terpenes -- toxicity KW - Clone Cells KW - Sensitivity and Specificity KW - Animals KW - Disease Susceptibility KW - Carcinogens -- toxicity KW - Mice KW - Mice, Inbred BALB C KW - Mice, Inbred DBA KW - Polymerase Chain Reaction KW - Base Sequence KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Precancerous Conditions -- genetics KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Genes, myc KW - Precancerous Conditions -- chemically induced KW - Recombination, Genetic KW - Genes, Immunoglobulin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77964022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Detection+of+immunoglobulin%2Fc-myc+recombinations+in+mice+that+are+resistant+to+plasmacytoma+induction.&rft.au=M%C3%BCller%2C+J+R%3BJones%2C+G+M%3BPotter%2C+M%3BJanz%2C+S&rft.aulast=M%C3%BCller&rft.aufirst=J&rft.date=1996-01-15&rft.volume=56&rft.issue=2&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-13 N1 - Date created - 1996-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ocular manifestations of AIDS. AN - 77962526; 8531310 JF - JAMA AU - Whitcup, S M AD - Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, Md 20892-1858, USA. Y1 - 1996/01/10/ PY - 1996 DA - 1996 Jan 10 SP - 142 EP - 144 VL - 275 IS - 2 SN - 0098-7484, 0098-7484 KW - Anti-Bacterial Agents KW - 0 KW - Antiviral Agents KW - Rifabutin KW - 1W306TDA6S KW - Didanosine KW - K3GDH6OH08 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Antiviral Agents -- therapeutic use KW - Rifabutin -- adverse effects KW - Anti-Bacterial Agents -- therapeutic use KW - Ganciclovir -- therapeutic use KW - Humans KW - Anti-Bacterial Agents -- adverse effects KW - CD4 Lymphocyte Count KW - Rifabutin -- therapeutic use KW - Didanosine -- adverse effects KW - Didanosine -- therapeutic use KW - HIV Infections -- complications KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Ganciclovir -- adverse effects KW - Antiviral Agents -- adverse effects KW - Adolescent KW - Visual Acuity KW - Cytomegalovirus Retinitis -- drug therapy KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Cytomegalovirus Retinitis -- physiopathology KW - AIDS-Related Opportunistic Infections -- complications KW - Uveitis -- complications KW - Cytomegalovirus Retinitis -- diagnosis KW - AIDS-Related Opportunistic Infections -- diagnosis KW - Uveitis -- chemically induced KW - AIDS-Related Opportunistic Infections -- physiopathology KW - Cytomegalovirus Retinitis -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77962526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=JAMA&rft.atitle=Ocular+manifestations+of+AIDS.&rft.au=Whitcup%2C+S+M&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1996-01-10&rft.volume=275&rft.issue=2&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1996 Jan 10;275(2):149-50 [8531313] JAMA. 1996 May 22-29;275(20):1545 [8622240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ionization equilibria for side-chain carboxyl groups in oxidized and reduced human thioredoxin and in the complex with its target peptide from the transcription factor NF kappa B. AN - 77973566; 8555200 AB - The pH dependence of the 13C chemical shifts of the side-chain carboxyl carbons of all Asp and Glu residues in the reduced and oxidized states of human thioredoxin and in a mixed disulfide complex of human thioredoxin with a target peptide from the transcription factor NF kappa B has been investigated by multidimensional triple-resonance NMR spectroscopy. While the titration curves for most of the side-chain carboxyl resonances exhibit simple Henderson-Hasselbalch behavior with pKa values not far from those found for model compounds, several side chains give rise to two- or three-step titration curves, indicative of the influence of multiple ionizations. In particular, the triad formed by Asp58, Asp60, and Asp61 forms such a complex network of titrating groups. The ionization behavior of Asp26 shows an abnormally high pKa value for an aspartate residue in all states of human thioredoxin, with pKa values of 9.9 in the reduced state, 8.1 in the oxidized state, 8.9 in the mixed disulfide complex, and 8.6 in an active site mutant in which Cys35 was replaced by Ala. The unambiguous determination of the pKa values of Asp26 for a variety of states of human thioredoxin presented in this paper is highly significant in view of two recent reports on Escherichia coli thioredoxin which presented contradicting pKa values for Asp26 and Cys35 [Wilson et al. (1995) Biochemistry 34, 8931-8939; Jeng et al. (1995) Biochemistry 34, 10101-10105]. The stabilization of the protonated side chain of Asp26 in human thioredoxin is achieved via a hydrogen-bonding network involving the hydroxyl group of the neighboring Ser28 which is then connected to the active site region (comprising Cys32 and Cys35) via bound water molecules. The coupling of the buried Asp26 to the active site is responsible for the influence of the Asp26 ionization behavior on the titration shifts of active site residues. JF - Biochemistry AU - Qin, J AU - Clore, G M AU - Gronenborn, A M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA. Y1 - 1996/01/09/ PY - 1996 DA - 1996 Jan 09 SP - 7 EP - 13 VL - 35 IS - 1 SN - 0006-2960, 0006-2960 KW - Carbon Isotopes KW - 0 KW - NF-kappa B KW - Peptide Fragments KW - Recombinant Proteins KW - Thioredoxins KW - 52500-60-4 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Models, Molecular KW - Humans KW - Hydrogen-Ion Concentration KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - Oxidation-Reduction KW - Magnetic Resonance Spectroscopy -- methods KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Point Mutation KW - Recombinant Proteins -- chemistry KW - Peptide Fragments -- metabolism KW - NF-kappa B -- chemistry KW - Peptide Fragments -- chemistry KW - Thioredoxins -- metabolism KW - Thioredoxins -- chemistry KW - Protein Conformation KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77973566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Ionization+equilibria+for+side-chain+carboxyl+groups+in+oxidized+and+reduced+human+thioredoxin+and+in+the+complex+with+its+target+peptide+from+the+transcription+factor+NF+kappa+B.&rft.au=Qin%2C+J%3BClore%2C+G+M%3BGronenborn%2C+A+M&rft.aulast=Qin&rft.aufirst=J&rft.date=1996-01-09&rft.volume=35&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-27 N1 - Date created - 1996-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Importance of the region around glycine-338 for the activity of enzyme I of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system. AN - 77968352; 8555180 AB - The gene encoding enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system from an Escherichia coli enzyme I mutant was cloned and sequenced. The mutation was shown to be a guanine to adenine transition resulting in an altered protein in which glycine-338 was replaced by aspartic acid. The enzyme I structural gene was mutated to change glycine-338 to a variety of other amino acid residues. Fermentation tests indicated that glycine-338 could be mutated to alanine with no gross loss in phosphotransferase activity, while mutation to valine, glutamic acid, aspartic acid, arginine, histidine, or asparagine led to significant loss of activity. An expression vector for enzyme I was mutated to change glycine-338 to a variety of other amino acid residues and highly purified mutant proteins were prepared. Analysis of phosphorylation of the proteins by PEP indicated that mutation of glycine-338 to alanine had little effect on phosphorylation, mutation to valine substantially decreased phosphorylation, change to histidine or arginine drastically diminished phosphorylation, and mutation to aspartic or glutamic acids abolished phosphorylation activity. Mutation at glycine-338 influences the autophosphorylation rather than the phosphoryl transfer activity of enzyme I. JF - Biochemistry AU - Seok, Y J AU - Lee, B R AU - Gazdar, C AU - Svenson, I AU - Yadla, N AU - Peterkofsky, A AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/01/09/ PY - 1996 DA - 1996 Jan 09 SP - 236 EP - 242 VL - 35 IS - 1 SN - 0006-2960, 0006-2960 KW - Recombinant Proteins KW - 0 KW - Histidine KW - 4QD397987E KW - Phosphoenolpyruvate Sugar Phosphotransferase System KW - EC 2.7.1.- KW - Phosphotransferases (Nitrogenous Group Acceptor) KW - EC 2.7.3.- KW - phosphoenolpyruvate-protein phosphotransferase KW - EC 2.7.3.9 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Genes, Bacterial KW - Amino Acid Sequence KW - Plasmids KW - Binding Sites KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Restriction Mapping KW - Molecular Sequence Data KW - Point Mutation KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- chemistry KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- metabolism KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Phosphotransferases (Nitrogenous Group Acceptor) -- chemistry KW - Phosphotransferases (Nitrogenous Group Acceptor) -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77968352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Importance+of+the+region+around+glycine-338+for+the+activity+of+enzyme+I+of+the+Escherichia+coli+phosphoenolpyruvate%3Asugar+phosphotransferase+system.&rft.au=Seok%2C+Y+J%3BLee%2C+B+R%3BGazdar%2C+C%3BSvenson%2C+I%3BYadla%2C+N%3BPeterkofsky%2C+A&rft.aulast=Seok&rft.aufirst=Y&rft.date=1996-01-09&rft.volume=35&rft.issue=1&rft.spage=236&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-27 N1 - Date created - 1996-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. AN - 77963022; 8552665 AB - We have chosen tumors of the uterine cervix as a model system to identify chromosomal aberrations that occur during carcinogenesis. A phenotype/genotype correlation was established in defined regions of archived, formalin-fixed, and hematoxylin/eosin-stained tissue sections that were dissected from normal cervical epithelium (n = 3), from mild (n = 4), moderate (n = 6), and severe dysplasias/carcinomas in situ (CIS) (n = 13), and from invasive carcinomas (n = 10) and investigated by comparative genomic hybridization. The same tissues were analyzed for DNA ploidy, proliferative activity, and the presence of human papillomavirus (HPV) sequences. The results show that an increase in proliferative activity and tetraploidization had occurred already in mildly dysplastic lesions. No recurrent chromosomal aberrations were observed in DNA extracted from normal epithelium or from mild and moderate dysplasias, indicating that the tetraploidization precedes the loss or gain of specific chromosomes. A gain of chromosome 3q became visible in one of the severe dysplasias/CIS. Notably, chromosome 3q was overrepresented in 90% of the carcinomas and was also found to have undergone a high-level copy-number increase (amplification). We therefore conclude that the gain of chromosome 3q that occurs in HPV16-infected, aneuploid cells represents a pivotal genetic aberration at the transition from severe dysplasia/CIS to invasive cervical carcinoma. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Heselmeyer, K AU - Schröck, E AU - du Manoir, S AU - Blegen, H AU - Shah, K AU - Steinbeck, R AU - Auer, G AU - Ried, T AD - Diagnostic Development Branch, National Center for Human Genome Research/National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/01/09/ PY - 1996 DA - 1996 Jan 09 SP - 479 EP - 484 VL - 93 IS - 1 SN - 0027-8424, 0027-8424 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Cervix Uteri -- pathology KW - Aneuploidy KW - Humans KW - Carcinoma in Situ KW - In Situ Hybridization, Fluorescence KW - Chromosome Disorders KW - DNA, Neoplasm -- genetics KW - Epithelium -- pathology KW - Female KW - Chromosome Aberrations -- genetics KW - Precancerous Conditions -- genetics KW - Chromosomes, Human, Pair 3 KW - Carcinoma -- pathology KW - Uterine Cervical Neoplasms -- genetics KW - Uterine Cervical Neoplasms -- pathology KW - Precancerous Conditions -- pathology KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77963022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Gain+of+chromosome+3q+defines+the+transition+from+severe+dysplasia+to+invasive+carcinoma+of+the+uterine+cervix.&rft.au=Heselmeyer%2C+K%3BSchr%C3%B6ck%2C+E%3Bdu+Manoir%2C+S%3BBlegen%2C+H%3BShah%2C+K%3BSteinbeck%2C+R%3BAuer%2C+G%3BRied%2C+T&rft.aulast=Heselmeyer&rft.aufirst=K&rft.date=1996-01-09&rft.volume=93&rft.issue=1&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-22 N1 - Date created - 1996-02-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Hum Mol Genet. 1993 Nov;2(11):1907-14 [8281155] Cancer. 1994 Feb 1;73(3):664-71 [7905364] Cancer Res. 1994 Feb 1;54(3):637-9 [7905784] J Infect Dis. 1994 Feb;169(2):235-40 [8106758] Cancer Res. 1994 Apr 1;54(7):1801-6 [8137295] Lancet. 1994 Apr 16;343(8903):955-7 [7909014] Am J Pathol. 1994 Jun;144(6):1203-18 [8203461] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6953-7 [8041728] Am J Hum Genet. 1995 Mar;56(3):705-15 [7887426] Cytometry. 1995 Jan 1;19(1):27-41 [7705182] Acta Oncol. 1995;34(2):171-6 [7718254] J Natl Cancer Inst. 1995 Jun 7;87(11):796-802 [7791229] Cancer Res. 1995 Nov 15;55(22):5415-23 [7585611] J Chronic Dis. 1958 Jul;8(1):2-37 [13563591] Hum Genet. 1993 Feb;90(6):590-610 [8444465] Hereditas. 1971;68(2):165-218 [5173409] Science. 1976 Oct 1;194(4260):23-8 [959840] Nature. 1985 May 16-22;315(6016):190-5 [2987696] Science. 1989 Feb 17;243(4893):934-7 [2537532] Hum Pathol. 1989 Jun;20(6):518-27 [2470665] Cancer Res. 1989 Jul 1;49(13):3598-601 [2567206] Cancer Genet Cytogenet. 1990 Feb;44(2):229-41 [2297684] Cell. 1990 Jun 1;61(5):759-67 [2188735] Cell. 1990 Dec 21;63(6):1129-36 [2175676] Cell. 1991 Jan 25;64(2):235-48 [1988146] Am J Hum Genet. 1991 Oct;49(4):868-77 [1680288] Cancer Genet Cytogenet. 1992 Jun;60(2):214-5 [1318784] Science. 1992 Oct 30;258(5083):818-21 [1359641] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vanadium(IV)-mediated free radical generation and related 2'-deoxyguanosine hydroxylation and DNA damage. AN - 77967637; 8571399 AB - Free radical generation, 2'-deoxyguanosine (dG) hydroxylation and DNA damage by vanadium(IV) reactions were investigated. Vanadium(IV) caused molecular oxygen dependent dG hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15 min incubation of 1.0 mM dG and 1.0 mM VOSO4 in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31%. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Metal ion chelators, DTPA and deferoxamine, blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen-dependent DNA strand breaks in a pattern similar to that observed for dG hydroxylation. ESR spin trapping measurements demonstrated that the reaction of vanadium(IV) with H2O2 generated OH radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA double strand breaks. Sodium formate inhibited 8-OHdG formation while DTPA had no significant effect. Deferoxamine enhanced the 8-OHdG generation by 2.5-fold. ESR and UV measurements provided evidence for the complex formation between vanadium(IV) and deferoxamine. UV-visible measurements indicate that dG, vanadium(IV) and deferoxamine are able to form a complex, thereby, facilitating site-specific 8-OHdG formation. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks. DTPA and deferoxamine attenuated vanadium(IV)/t-butyl-OOH-induced DNA strand breaks. JF - Toxicology AU - Shi, X AU - Jiang, H AU - Mao, Y AU - Ye, J AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1996/01/08/ PY - 1996 DA - 1996 Jan 08 SP - 27 EP - 38 VL - 106 IS - 1-3 SN - 0300-483X, 0300-483X KW - Chelating Agents KW - 0 KW - Free Radicals KW - Peroxides KW - Vanadium KW - 00J9J9XKDE KW - Hydroxyl Radical KW - 3352-57-6 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Hydrogen Peroxide KW - BBX060AN9V KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Chelating Agents -- pharmacology KW - Peroxides -- metabolism KW - Hydroxyl Radical -- metabolism KW - Kinetics KW - Hydrogen Peroxide -- metabolism KW - Electron Spin Resonance Spectroscopy KW - Spectrophotometry, Ultraviolet KW - Lipid Peroxidation KW - Chromatography, High Pressure Liquid KW - Hydroxylation KW - Deoxyguanosine -- metabolism KW - Vanadium -- toxicity KW - Deoxyguanosine -- analogs & derivatives KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77967637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Vanadium%28IV%29-mediated+free+radical+generation+and+related+2%27-deoxyguanosine+hydroxylation+and+DNA+damage.&rft.au=Shi%2C+X%3BJiang%2C+H%3BMao%2C+Y%3BYe%2C+J%3BSaffiotti%2C+U&rft.aulast=Shi&rft.aufirst=X&rft.date=1996-01-08&rft.volume=106&rft.issue=1-3&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conformationally constrained analogues of diacylglycerol. 10. Ultrapotent protein kinase C ligands based on a racemic 5-disubstituted tetrahydro-2-furanone template. AN - 77982740; 8568806 AB - 5,5-Bis(hydroxymethyl)tetrahydro-2-furanone and its isomer 4,4-bis(hydroxymethyl)tetrahydro-2-furanone were investigated as possible templates for the construction of conformationally constrained analogues of the biologically important second messenger, diacylglycerol (DAG). The former lactone contains embedded within its structure an exact glycerol moiety, while in the latter the ring oxygen has been transposed to the other side of the carbonyl group. All target compounds were synthesized as racemates from 1,3-dihydroxy-2-propanone. The 5,5-bis(hydroxymethyl)tetrahydro-2-furanone proved to be the better template for the construction of DAG surrogates that were demonstrated to have high binding affinities for the biological target, protein kinase C (PK-C). The simplest target compounds derived from this template (3e and 3f) have one of the hydroxyl moieties functionalized either as a myristate or as an oleate ester. The simplest target compound (9c) derived from the ineffective 4,4-bis-(hydroxymethyl)tetrahydro-2-furanone template was investigated only with a myristoyl acyl chain. Reducing the long acyl chain to an acetyl moiety and attaching a compensating lipophilic chain to the lactone ring as an alpha-alkylidene moiety produced compounds 10e and 10f (Z-isomers) and 11e and 11f (E-isomers), which were constructed on the more effective 5,5-bis(hydroxymethyl)tetrahydro-2-furanone template. Targets 14c (Z-isomer) and 15c (E-isomer) were derived, in turn, from 4,4-bis(hydroxymethyl)tetrahydro-2-furanone. The affinities of these ligands for PK-C were assessed in terms of their ability to displace bound [3H-20]phorbol 12,13-dibutyrate (PDBU) from the single isozyme PK-C alpha. The biological data support the hypothesis that the increase in binding affinity for PK-C shown by some of these constrained DAG mimetics appears to be entropic in nature. Two of the designed ligands (10e and 10f) showed the highest affinities (34 and 24 nM, respectively) reported so far for a DAG analogue. Assuming that the interaction between these racemic compounds and PK-C is stereospecific, the potency of the active enantiomer is anticipated to double. JF - Journal of medicinal chemistry AU - Sharma, R AU - Lee, J AU - Wang, S AU - Milne, G W AU - Lewin, N E AU - Blumberg, P M AU - Marquez, V E AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/01/05/ PY - 1996 DA - 1996 Jan 05 SP - 19 EP - 28 VL - 39 IS - 1 SN - 0022-2623, 0022-2623 KW - 5-((acetyloxy)methyl)-5-(hydroxymethyl)-3-tetradecanylidenetetrahydro-2-furanone KW - 0 KW - 5--((acetyloxy)methyl)-5-(hydroxymethyl)-3-(9-octadecenylidene)tetrahydro-2-furanone KW - Diglycerides KW - Lactones KW - Ligands KW - Myristic Acids KW - Oleic Acids KW - Myristic Acid KW - 0I3V7S25AW KW - Oleic Acid KW - 2UMI9U37CP KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Dihydroxyacetone KW - O10DDW6JOO KW - 4-Butyrolactone KW - OL659KIY4X KW - Index Medicus KW - Molecular Structure KW - Stereoisomerism KW - Oleic Acids -- chemistry KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Models, Molecular KW - Dihydroxyacetone -- metabolism KW - Myristic Acids -- metabolism KW - Lactones -- metabolism KW - Magnetic Resonance Spectroscopy KW - Myristic Acids -- chemistry KW - Oleic Acids -- metabolism KW - Lactones -- chemistry KW - Binding, Competitive KW - Molecular Conformation KW - Lactones -- chemical synthesis KW - Protein Kinase C -- metabolism KW - Diglycerides -- chemistry KW - Diglycerides -- chemical synthesis KW - 4-Butyrolactone -- metabolism KW - 4-Butyrolactone -- chemistry KW - Diglycerides -- metabolism KW - 4-Butyrolactone -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77982740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Conformationally+constrained+analogues+of+diacylglycerol.+10.+Ultrapotent+protein+kinase+C+ligands+based+on+a+racemic+5-disubstituted+tetrahydro-2-furanone+template.&rft.au=Sharma%2C+R%3BLee%2C+J%3BWang%2C+S%3BMilne%2C+G+W%3BLewin%2C+N+E%3BBlumberg%2C+P+M%3BMarquez%2C+V+E&rft.aulast=Sharma&rft.aufirst=R&rft.date=1996-01-05&rft.volume=39&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a mutant GLUT4 lacking the N-glycosylation site: studies in transfected rat adipose cells. AN - 77970358; 8573180 AB - GLUT4, the insulin-responsive glucose transporter expressed primarily in muscle and adipose tissue, contains a single N-glycosylation site. We characterized a mutant GLUT4 lacking the N-glycosylation site (Asn57-->Gln) in primary cultures of rat adipose cells. We transiently transfected cells with expression vectors for epitope-tagged GLUT4 containing either wild-type (GLUT4-HA) or mutant (GLN57-HA) cDNA sequences. Expression of GLN57-HA in adipose cells was approximately 10-fold lower than for GLUT4-HA even though mRNA levels for both recombinant transporters were comparable. Biosynthetic labeling studies showed markedly decreased incorporation of [35S]-methionine/cysteine into GLN57-HA relative to GLUT4-HA consistent with either a decreased synthetic rate or accelerated degradation of GLN57-HA. Interestingly, transient transfection of GLUT4-HA and GLN57-HA in COS-7 cells (which do not express endogenous GLUT4) resulted in comparable levels of protein expression for both transporters. Thus, in the physiologically relevant adipose cell, glycosylation of GLUT4 appears to play an important functional role. JF - Biochemical and biophysical research communications AU - Ing, B L AU - Chen, H AU - Robinson, K A AU - Buse, M G AU - Quon, M J AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/01/05/ PY - 1996 DA - 1996 Jan 05 SP - 76 EP - 82 VL - 218 IS - 1 SN - 0006-291X, 0006-291X KW - DNA Primers KW - 0 KW - Epitopes KW - Glucose Transporter Type 4 KW - Insulin KW - Monosaccharide Transport Proteins KW - Muscle Proteins KW - RNA, Messenger KW - Recombinant Proteins KW - Slc2a4 protein, rat KW - Glutamine KW - 0RH81L854J KW - Asparagine KW - 7006-34-0 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Electroporation KW - Recombinant Proteins -- biosynthesis KW - Insulin -- pharmacology KW - Glycosylation KW - RNA, Messenger -- biosynthesis KW - Mutagenesis, Site-Directed KW - Rats KW - Recombinant Proteins -- isolation & purification KW - Molecular Sequence Data KW - Point Mutation KW - Male KW - Epididymis KW - RNA, Messenger -- analysis KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Cercopithecus aethiops KW - Cell Membrane -- metabolism KW - Cell Line KW - Monosaccharide Transport Proteins -- biosynthesis KW - Adipose Tissue -- metabolism KW - Monosaccharide Transport Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77970358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Characterization+of+a+mutant+GLUT4+lacking+the+N-glycosylation+site%3A+studies+in+transfected+rat+adipose+cells.&rft.au=Ing%2C+B+L%3BChen%2C+H%3BRobinson%2C+K+A%3BBuse%2C+M+G%3BQuon%2C+M+J&rft.aulast=Ing&rft.aufirst=B&rft.date=1996-01-05&rft.volume=218&rft.issue=1&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conformationally constrained analogues of diacylglycerol. 12. Ultrapotent protein kinase C ligands based on a chiral 4,4-disubstituted heptono-1,4-lactone template. AN - 77967195; 8568825 AB - Conformationally constrained analogues of diacylglycerol (DAG) built on a 5(-)[(acyloxy)methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template (1, Chart 1) were shown previously to bind tightly to protein kinase C alpha (PK-C alpha) in a stereospecific manner. These compounds, however, racemized readily through rapid acyl migration and lost biological potency. In order to circumvent this problem, the "reversed ester" analogues were designed as a new set of PK-C ligands. This reversal of the ester function produced some new DAG mimetics that are embedded in a C-4 doubly-branched heptono-1,4-lactone template. The reversed ester analogues were impervious to racemization, and their chemically distinct branches facilitated the enantiospecific syntheses of all targets. Compound 2, the simplest reversed ester analogue of 1 (Chart 1), exhibited a 3.5-fold reduction in binding affinity toward PK-C alpha which we attributed to the loss of a stabilizing gauche interaction that caused the ester branch in 2 to be more disordered than in the normal ester 1. However, conversion of the propanoyl branch of 2 into a propenoyl branch restored binding affinity (3 versus 5). As expected, the compounds bound to the enzyme with strict enantioselectivity (3 and 5 versus 4 and 6). Functionalization of the propenoyl-branched compounds as alpha-alkylidene lactones, in a manner which proved successful with the 5(-)[(acyloxy)methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template (9 and 10), produced stable compounds with equivalent ultrapotent binding affinities for PK-C alpha (7 and 8). The additional incorporation of the propenoyl-branched carbonyl into a gamma-lactone ring was performed (11-14) not only to derive a possible additional entropic advantage but also to confirm the spatial disposition of this carbonyl function in the ligand-enzyme complex. Although no additional entropic advantage was derived, the high binding affinities displayed by compounds 11 and 12 helped to establish the correct orientation of the equivalent carbonyl group in PK-C-bound DAG. As expected, these DAG analogues activated PK-C alpha. The most potent agonist, compound 8, stimulated phosphorylation of the alpha-pseudosubstrate peptide, and in primary mouse keratinocytes it caused inhibition of binding of epidermal growth factor with an ED50 of approximately 1 microM. In contrast to the phorbol esters, compound 8 did not induce acute edema or hyperplasia in skin of CD-1 mice, and its pattern of downregulation with several PK-C isozymes was different from that of phorbol 12-myristate 13-acetate (PMA). JF - Journal of medicinal chemistry AU - Lee, J AU - Sharma, R AU - Wang, S AU - Milne, G W AU - Lewin, N E AU - Szallasi, Z AU - Blumberg, P M AU - George, C AU - Marquez, V E AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/01/05/ PY - 1996 DA - 1996 Jan 05 SP - 36 EP - 45 VL - 39 IS - 1 SN - 0022-2623, 0022-2623 KW - 5-(hydroxymethyl)-5-(2-(methoxycarbonyl)ethenyl)-3-(9-octadecenylidene)-tetrahydro-2-furanone KW - 0 KW - Diglycerides KW - Ligands KW - Peptides KW - Phorbol Esters KW - Epidermal Growth Factor KW - 62229-50-9 KW - Protein Kinase C KW - EC 2.7.11.13 KW - 4-Butyrolactone KW - OL659KIY4X KW - Index Medicus KW - Molecular Structure KW - Animals KW - Stereoisomerism KW - Phorbol Esters -- metabolism KW - Keratinocytes -- drug effects KW - Peptides -- metabolism KW - Mice KW - Magnetic Resonance Spectroscopy KW - Phorbol Esters -- pharmacology KW - Phosphorylation KW - Binding, Competitive KW - Keratinocytes -- metabolism KW - Molecular Conformation KW - Epidermal Growth Factor -- metabolism KW - Protein Kinase C -- metabolism KW - Diglycerides -- chemistry KW - Diglycerides -- pharmacology KW - Diglycerides -- chemical synthesis KW - 4-Butyrolactone -- pharmacology KW - 4-Butyrolactone -- chemical synthesis KW - 4-Butyrolactone -- metabolism KW - 4-Butyrolactone -- chemistry KW - Diglycerides -- metabolism KW - 4-Butyrolactone -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77967195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Conformationally+constrained+analogues+of+diacylglycerol.+12.+Ultrapotent+protein+kinase+C+ligands+based+on+a+chiral+4%2C4-disubstituted+heptono-1%2C4-lactone+template.&rft.au=Lee%2C+J%3BSharma%2C+R%3BWang%2C+S%3BMilne%2C+G+W%3BLewin%2C+N+E%3BSzallasi%2C+Z%3BBlumberg%2C+P+M%3BGeorge%2C+C%3BMarquez%2C+V+E&rft.aulast=Lee&rft.aufirst=J&rft.date=1996-01-05&rft.volume=39&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conformationally constrained analogues of diacylglycerol. 11. Ultrapotent protein kinase C ligands based on a chiral 5-disubstituted tetrahydro-2-furanone template. AN - 77963783; 8568819 AB - Conformationally constrained analogues of diacylglycerol (DAG) built on a racemic 5(-)[(acyloxy)-methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template were shown previously to have excellent binding affinities for protein kinase C (PK-C). Since the interaction of PK-C with DAG is stereospecific, it was anticipated that PK-C would bind tightly to only one enantiomeric form of the compounds constructed with this new lactone template. Separation of enantiomers by chiral HPLC was discarded due to the ease with which acyl migration occurs in these class of compounds, and a total chiral synthesis was undertaken. Prior to chemical synthesis, the selection of the "correct" enantiomeric template was predicted by a molecular conformational analysis that compared the two enantiomers of DAG in their presumed "active" conformation with the two enantiomeric lactone templates. This presumed "active" conformation for DAG was derived from a previously developed pharmacophore model that uses the molecule of a potent phorbol diester as the ideal rigid template. The results from this analysis indicated that the "correct" lactone template corresponded to the inactive (R)-isomer of DAG. This analysis also predicted that the lactone template corresponding to the active (S)-DAG enantiomer would not fit adequately into the pharmacophore. The chiral syntheses of target compounds 2, 4, and 6, constructed on the selected, and presumably "correct" lactone template, were achieved from a common bicyclic intermediate (5R,8R,9R)-8,9-O-isopropylidene-2-keto-1,7-dioxaspiro[4.4]nonane (10) that was synthesized from commercially available 1,2:3,5-di-O-isopropylidene-alpha-D-threo-apiofuranose (7) by a very effective spirolactonization approach. On the basis of their ability to inhibit the binding of [3H-20]phorbol 12,13-dibutyrate (PDBU) to PK-C alpha, the enantiomeric ligands 2, 4, and 6 were twice as potent as the corresponding racemates. These results confirm that binding of these lactones is stereospecific and consistent with a binding mechanism similar to that of DAG. JF - Journal of medicinal chemistry AU - Lee, J AU - Wang, S AU - Milne, G W AU - Sharma, R AU - Lewin, N E AU - Blumberg, P M AU - Marquez, V E AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/01/05/ PY - 1996 DA - 1996 Jan 05 SP - 29 EP - 35 VL - 39 IS - 1 SN - 0022-2623, 0022-2623 KW - 5-((acetyloxy)methyl)-5-hydroxymethyl-3-(9-octadecaenylidene)tetrahydro-2-furanone KW - 0 KW - 5-hydroxymethyl-5-((tetradecanoyloxy)methyl)tetrahydro-2-furanone KW - Diglycerides KW - Lactones KW - Ligands KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - 4-Butyrolactone KW - OL659KIY4X KW - Index Medicus KW - Molecular Structure KW - Stereoisomerism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Models, Molecular KW - Lactones -- chemistry KW - Binding, Competitive KW - Molecular Conformation KW - Lactones -- chemical synthesis KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Binding Sites KW - Protein Kinase C -- metabolism KW - Diglycerides -- chemistry KW - Diglycerides -- chemical synthesis KW - 4-Butyrolactone -- pharmacology KW - 4-Butyrolactone -- metabolism KW - 4-Butyrolactone -- chemistry KW - Diglycerides -- metabolism KW - 4-Butyrolactone -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77963783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Conformationally+constrained+analogues+of+diacylglycerol.+11.+Ultrapotent+protein+kinase+C+ligands+based+on+a+chiral+5-disubstituted+tetrahydro-2-furanone+template.&rft.au=Lee%2C+J%3BWang%2C+S%3BMilne%2C+G+W%3BSharma%2C+R%3BLewin%2C+N+E%3BBlumberg%2C+P+M%3BMarquez%2C+V+E&rft.aulast=Lee&rft.aufirst=J&rft.date=1996-01-05&rft.volume=39&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Administration of interleukin 12 with pulse interleukin 2 and the rapid and complete eradication of murine renal carcinoma. AN - 77948348; 8847724 AB - Interleukin 2 (IL-2) and interleukin 12 (IL-12) are potent immunoregulatory cytokines that exhibit antitumor activity. Preliminary evidence suggests that combined administration of IL-2 and IL-12 may yield greater antitumor activity than that observed with either agent alone. We evaluated the ability of combination regimens of IL-2 and IL-12 to induce regression of established primary and metastatic murine renal carcinoma (Renca) tumors. BALB/c mice were given either subcutaneous or intrarenal injections of 10(5) Renca cells; tumor cell injections were given to 10-12 mice for each treatment group. Mice bearing subcutaneous primary tumors were treated with chronic IL-2 (300,000 IU given on a daily basis) or pulse IL-2 (300,000 IU given twice daily one day per week) alone, IL-12 alone (0.5 micrograms given on a daily basis), or IL-12 in combination with either chronic or pulse IL-2. Mice with metastatic tumors (arising from intrarenal implants; animals were nephrectomized to remove the primary tumors) were treated with IL-12 plus or minus pulse IL-2; in these experiments, IL-12 was given at doses of either 0.5 or 1.0 micrograms. In most experiments, treatment was continued for at least 3 weeks. Two-sided statistical tests were used to evaluate the data. Most mice with subcutaneous Renca tumors treated with the combination of IL-12 and chronic IL-2 died of treatment-related toxic effects within 7-14 days. In contrast, treatment with IL-12 plus pulse IL-2 was well tolerated, and six of 10 mice experienced complete tumor regression; none of the mice treated with either IL-12 alone or pulse Il-2 alone experienced a curative response. Seven of eight and nine of nine mice with metastatic tumors experienced complete tumor regression after treatment with 0.5 micrograms IL-12 plus pulse IL-2 or 1.0 microgram IL-12 plus pulse IL-2, respectively; two of 12 mice treated with pulse IL-2 alone and 10% or less of mice treated with IL-12 alone were cured of metastatic tumors (with 0.5 micrograms IL-12, none of 10 mice; with 1.0 micrograms IL-12, one of 10 mice). Five of 10 mice with metastatic tumors treated with a short-course regimen of IL-12 and pulse IL-2 (two pulses of IL-2 flanking 5 days of 0.5 micrograms IL-12) experienced complete tumor regression, while only one of the 12 mice treated with IL-2 alone and none of the mice treated with IL-12 alone experienced complete tumor regression. Virtually all curative response frequencies obtained with IL-12 and pulse IL-2 combination regimens differed significantly (P < .05) from those obtained with corresponding single-agent treatments. IL-12 administered in combination with pulse IL-2 induced rapid and complete regression of primary and metastatic Renca tumors and displayed greater antitumor activity than that observed with either IL-12 or IL-2 alone. JF - Journal of the National Cancer Institute AU - Wigginton, J M AU - Komschlies, K L AU - Back, T C AU - Franco, J L AU - Brunda, M J AU - Wiltrout, R H AD - Laboratory of Experimental Immunology, National Cancer Institute, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. Y1 - 1996/01/03/ PY - 1996 DA - 1996 Jan 03 SP - 38 EP - 43 VL - 88 IS - 1 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Interleukin-2 KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Mice KW - Mice, Inbred BALB C KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Pulsatile Flow KW - Survival Analysis KW - Kidney Neoplasms -- drug therapy KW - Interleukin-2 -- administration & dosage KW - Interleukin-12 -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Interleukin-2 -- therapeutic use KW - Carcinoma, Renal Cell -- drug therapy KW - Interleukin-12 -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77948348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Administration+of+interleukin+12+with+pulse+interleukin+2+and+the+rapid+and+complete+eradication+of+murine+renal+carcinoma.&rft.au=Wigginton%2C+J+M%3BKomschlies%2C+K+L%3BBack%2C+T+C%3BFranco%2C+J+L%3BBrunda%2C+M+J%3BWiltrout%2C+R+H&rft.aulast=Wigginton&rft.aufirst=J&rft.date=1996-01-03&rft.volume=88&rft.issue=1&rft.spage=38&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-22 N1 - Date created - 1996-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial of interleukin 1 alpha and indomethacin in treatment of metastatic melanoma. AN - 77940343; 8847725 AB - The rising incidence of malignant melanoma and the lack of curative therapies for metastatic disease represent a therapeutic challenge. New agents effective in treating this disease are needed. Because of the additive antitumor effects of interleukin 1 alpha (IL-1 alpha) and indomethacin in vivo, we conducted a phase II trial of this combination in patients with melanoma. We used the recommended dose determined from our phase I trial to ascertain the antitumor activity of the combination. From August 1, 1990, through July 28, 1992, 49 patients entered the study. They were stratified into two groups based on the presence of visceral (n = 14) and nonvisceral (n = 35) metastases. The patients received 7 days of both IL-1 alpha (O.1 micrograms/kg per day by intravenous bolus) infusion) and indomethacin (50 mg orally every 8 hours). At least two cycles of therapy, repeated at 21-day intervals, were planned. Additional treatment was given to those patients who had stable or responding lesions. A chi-squared test for homogeneity of proportions was used to compare groups on several measures. All P values resulted from two-sided tests. Fever, chills, and hypotension were among the most common side effects. None of the 14 patients with visceral metastases responded to the treatment. Of the 35 patients with non-visceral metastases, three showed a partial response for 6 months each and one showed a complete response for more than 34 months; the response rate was 11% (95% confidence interval [CI] = 5%-26%). All responding patients required phenylephrine for treatment of IL-1 alpha-induced hypotension, whereas six (19%) of 31 of the nonresponding patients with nonvisceral metastases required phenylephrine (P = .0008). The response rate in women was higher; three of 10 women (30%; 95% CI = 11%-60%) responded, whereas one of 25 men (4%; 95% CI = 0%-20%) responded (P = .029). All three women were positive for human leukocyte antigen (HLA) B7 expression (P = .011). The combination of IL-1 alpha and indomethacin has minimal antitumor activity in melanoma patients. All responses were confined to patients with nonvisceral metastases. IL-1 alpha-induced hypotension, gender, and HLA B7 expression were positively associated with response. Administration of higher doses of IL-1 alpha alone has been shown to produce hypotension in a large proportion of patients but can be given safely with phenylephrine support. Because of the association of hypotension with antitumor activity, treatment with higher IL-1 alpha doses alone may be a strategy for attaining better response rates. JF - Journal of the National Cancer Institute AU - Janik, J E AU - Miller, L L AU - Longo, D L AU - Powers, G C AU - Urba, W J AU - Kopp, W C AU - Gause, B L AU - Curti, B D AU - Fenton, R G AU - Oppenheim, J J AU - Conlon, K C AU - Holmlund, J T AU - Sznol, M AU - Sharfman, W H AU - Steis, R G AU - Creekmore, S P AU - Alvord, W G AU - Beauchamp, A E AU - Smith, J W AD - Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21701-4507, USA. Y1 - 1996/01/03/ PY - 1996 DA - 1996 Jan 03 SP - 44 EP - 49 VL - 88 IS - 1 SN - 0027-8874, 0027-8874 KW - HLA-B Antigens KW - 0 KW - Interleukin-1 KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Sex Factors KW - Interleukin-1 -- administration & dosage KW - Humans KW - Chi-Square Distribution KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Indomethacin -- administration & dosage KW - Male KW - Female KW - HLA-B Antigens -- blood KW - Skin Neoplasms -- drug therapy KW - Skin Neoplasms -- immunology KW - Melanoma -- secondary KW - Melanoma -- drug therapy KW - Skin Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Melanoma -- immunology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77940343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Phase+II+trial+of+interleukin+1+alpha+and+indomethacin+in+treatment+of+metastatic+melanoma.&rft.au=Janik%2C+J+E%3BMiller%2C+L+L%3BLongo%2C+D+L%3BPowers%2C+G+C%3BUrba%2C+W+J%3BKopp%2C+W+C%3BGause%2C+B+L%3BCurti%2C+B+D%3BFenton%2C+R+G%3BOppenheim%2C+J+J%3BConlon%2C+K+C%3BHolmlund%2C+J+T%3BSznol%2C+M%3BSharfman%2C+W+H%3BSteis%2C+R+G%3BCreekmore%2C+S+P%3BAlvord%2C+W+G%3BBeauchamp%2C+A+E%3BSmith%2C+J+W&rft.aulast=Janik&rft.aufirst=J&rft.date=1996-01-03&rft.volume=88&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-22 N1 - Date created - 1996-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased oxidative DNA damage in livers of 2,3,7,8-tetrachlorodibenzo-p-dioxin treated intact but not ovariectomized rats. AN - 77971427; 8556712 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a more potent hepatocarcinogen in female than in male or ovariectomized rats. A possible mechanism for this increased sensitivity is through enhanced metabolic activation of estrogens by TCDD-induced enzymes leading to oxidative damage in the cell. As a marker for oxidative DNA damage, 8-oxo-deoxyguanosine (8-oxo-dG) was quantitated in livers of intact and ovariectomized Sprague-Dawley rats chronically treated with TCDD (125 ng/kg per day) with and without diethylnitrosamine as initiator. Elevated levels of 8-oxo-dG were detected in a significantly greater number of the intact compared to ovariectomized TCDD-treated rats. Expression of CYP1B1 mRNA, a newly identified cytochrome P450 with proposed estrogen hydroxylase activity, was highly induced by TCDD. The results are consistent with the hypothesis that increased metabolism of endogenous estrogens to catechols by TCDD-induced enzymes may lead to increased oxidative DNA damage and hence contribute to TCDD-mediated hepatocarcinogenicity in female rats. JF - Cancer letters AU - Tritscher, A M AU - Seacat, A M AU - Yager, J D AU - Groopman, J D AU - Miller, B D AU - Bell, D AU - Sutter, T R AU - Lucier, G W AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/01/02/ PY - 1996 DA - 1996 Jan 02 SP - 219 EP - 225 VL - 98 IS - 2 SN - 0304-3835, 0304-3835 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Estradiol KW - 4TI98Z838E KW - DNA KW - 9007-49-2 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Diethylnitrosamine -- toxicity KW - Animals KW - Rats, Sprague-Dawley KW - Deoxyguanosine -- metabolism KW - Estradiol -- physiology KW - Carcinogens -- toxicity KW - Ovariectomy KW - Female KW - Cocarcinogenesis KW - Liver Neoplasms, Experimental -- metabolism KW - Liver -- drug effects KW - DNA Damage KW - DNA -- metabolism KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Liver -- metabolism KW - Ovary -- physiology KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77971427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Increased+oxidative+DNA+damage+in+livers+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+treated+intact+but+not+ovariectomized+rats.&rft.au=Tritscher%2C+A+M%3BSeacat%2C+A+M%3BYager%2C+J+D%3BGroopman%2C+J+D%3BMiller%2C+B+D%3BBell%2C+D%3BSutter%2C+T+R%3BLucier%2C+G+W&rft.aulast=Tritscher&rft.aufirst=A&rft.date=1996-01-02&rft.volume=98&rft.issue=2&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-26 N1 - Date created - 1996-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ERYTHROCYTE ALDEHYDE DEHYDROGENASE = A POTENTIAL MARKER FOR ALCOHOL DEPENDENCE AN - 876226948; 14910103 AB - The present study explored the utility of erythrocyte aldehyde dehydrogenase (ALDH) as a peripheral marker in alcoholism. The ALDH levels in aocoholics, their first degree nonalcholic relative and controls were compared. ALDH was found to be significantly lower in alcoholics (3.38+/-1.70 mU p& 0.001) and their first degree relatives (4.04+/-1.55 mU p& 0.05) compared to controls (5.06+/-1 55mU). Low ALDH levels among alcoholics persisted despite abstinence. The levels did not correlate with indices of hepatic dysfunction or with severity of alcoholism. These findings indicate that low erythrocyte ALDH may be considered as a biochemical trait marker associated with alcoholics, and the alcohol abuse would further decrease enzyme activitiy. To evaluate this proposition, logitudinal studies involving high risk progeny of alcohol dependents is being planned. JF - Indian Journal of Psychiatry AU - Murthy, Pratitma AU - Guru, S C AU - Channabasavanna, S M AU - Subbakrishna, D K AU - Shetty, Taranath AD - of Psychiatry, National Institute of Mental Health and NeuroSciences, Bangalore - 560 029, India Y1 - 1996 PY - 1996 DA - 1996 SP - 38 EP - 42 PB - Medknow Publications Pvt. Ltd., A-108/109 Kanara Business Center Mumbai 400075 India VL - 38 IS - 1 SN - 0019-5545, 0019-5545 KW - Risk Abstracts; CSA Neurosciences Abstracts KW - sexual behavior KW - Biochemistry KW - Erythrocytes KW - Drug abuse KW - Risk factors KW - Ethanol KW - Alcohol KW - Enzymes KW - Alcoholics KW - Drug dependence KW - Alcoholism KW - Liver KW - Progeny KW - Aldehydes KW - Aldehyde dehydrogenase KW - alcoholism KW - N3 11001:Behavioral and Cognitive Neuroscience KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/876226948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+Journal+of+Psychiatry&rft.atitle=ERYTHROCYTE+ALDEHYDE+DEHYDROGENASE+%3D+A+POTENTIAL+MARKER+FOR+ALCOHOL+DEPENDENCE&rft.au=Murthy%2C+Pratitma%3BGuru%2C+S+C%3BChannabasavanna%2C+S+M%3BSubbakrishna%2C+D+K%3BShetty%2C+Taranath&rft.aulast=Murthy&rft.aufirst=Pratitma&rft.date=1996-01-01&rft.volume=38&rft.issue=1&rft.spage=38&rft.isbn=&rft.btitle=&rft.title=Indian+Journal+of+Psychiatry&rft.issn=00195545&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-07-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Drug dependence; Risk factors; Alcoholism; Erythrocytes; Liver; Enzymes; Progeny; Drug abuse; Aldehyde dehydrogenase; Alcoholics; Ethanol; sexual behavior; Alcohol; Biochemistry; Aldehydes; alcoholism ER - TY - JOUR T1 - Polymerase Chain Reaction and In Situ Hybridization: Applications in Toxicological Pathology AN - 869568663; 13645681 AB - Polymerase chain reaction (PCR) and in situ hybridization (ISH) have revolutionized the study of genes and gene expression, and many of these molecular biology advances will greatly impact research in toxicological pathology. PCR is one of the most powerful tools in molecular biology and involves primer-mediated enzymatic in vitro amplification of specific target DNA sequences. Recent innovative methods utilizing PCR technology have been developed to detect mutations in neoplastic and small subpopulations of cells, to study biomarkers of genetic susceptibility and genes involved with carcinogen metabolism, to estimate mutation frequencies, to find novel genes induced by chemical exposure, and to characterize gene expression. ISH provides data on individual cells rather than an average of total cellular populations and allows analysis for heterogeneity. When combined with PCR. the sensitivity of ISH is elevated, and single-copy DNA sequences, single-base mutations, or low copies of messenger RNA (mRNA) can potentially be detected within individual cells. Herein are reviewed ISH- and PCR-based techniques such as single-strand conformation polymorphism analysis to detect point mutations, allelotypic analysis for loss of heterozygosity, differential display of mRNA to characterize gene expression, quantitative reverse transcriptase polymerase chain reaction, and in situ polymerase chain reaction with emphasis on current or potential applications in toxicological pathology. These new and evolving techniques offer tremendous potential in providing new insights into the molecular basis of toxicity and carcinogenesis. JF - Toxicologic Pathology AU - Malarkey, David E AU - Maronpot, Robert R AD - Laboratory of Experimental Pathology, Environmental Carcinogenesis Program. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 1996/01// PY - 1996 DA - Jan 1996 SP - 13 EP - 23 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 1 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Data processing KW - Single strand conformation polymorphism KW - Nucleotide sequence KW - Point mutation KW - Carcinogens KW - Toxicity KW - biomarkers KW - Loss of heterozygosity KW - mRNA KW - Reviews KW - Carcinogenesis KW - Polymerase chain reaction KW - RNA-directed DNA polymerase KW - Metabolism KW - Differential display KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/869568663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Polymerase+Chain+Reaction+and+In+Situ+Hybridization%3A+Applications+in+Toxicological+Pathology&rft.au=Malarkey%2C+David+E%3BMaronpot%2C+Robert+R&rft.aulast=Malarkey&rft.aufirst=David&rft.date=1996-01-01&rft.volume=24&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339602400104 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Data processing; Single strand conformation polymorphism; Nucleotide sequence; Point mutation; Toxicity; Carcinogens; biomarkers; mRNA; Loss of heterozygosity; Reviews; Carcinogenesis; RNA-directed DNA polymerase; Polymerase chain reaction; Differential display; Metabolism DO - http://dx.doi.org/10.1177/019262339602400104 ER - TY - JOUR T1 - Bile Acids in the Assessment of Hepatocellular Function AN - 860371494; 13645686 AB - Bile acids, which are synthesized in the liver from cholesterol, are important in the production of bile flow, excretion of cholesterol, and intestinal digestion and absorption of fats and fat-soluble vitamins. Increases and/or alterations in concentrations of bile acids in serum are specific and sensitive indicators of hepatobiliary disorders. Synthesis of bile acids in hepatocytes involves steps in endoplasmic reticulum, cytosol, mitochondria, and peroxisomes. Other important hepatocellular processes involving bile acids include active uptake by the basolateral membrane, intracellular transport, P-450-mediated conjugations and hydroxylations, and canalicular secretion. Hydrophobic bile acids produce hepatotoxicity in vivo and in vitro. In experimental and epidemiologic studies, some of these forms have been identified as causative agents in the development of colon and liver (experimental only) cancer. Conversely, several hydrophilic forms, primarily ursodeoxycholic acid, have demonstrated cytoprotective properties in a variety of clinical and experimental hepatobiliary diseases and disorders. Because bile acids can have dramatically different properties and effects, determination of mechanisms of action of these compounds has become an active area of research. Primary isolated hepatocytes provide an opportunity to investigate bile acid-related functions and effects in well-designed, carefully controlled studies. Short-term cultures have been used to study a variety of issues related to bile acids, including cytotoxicity, synthesis, and hepatocellular processing. With these systems, however, many functions of mature hepatocytes, including those pertaining to bile acids, can be lost when cultures are maintained for more than several days. Recent developments in culture techniques permit long-term maintenance of functionally stable, differentiated cells. Pertaining to bile acid research, these systems remain to be fully characterized but, in appropriate situations, they should provide important alternatives to in vivo studies and short-term in vitro assays. JF - Toxicologic Pathology AU - Thompson, M B AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 1996/01// PY - 1996 DA - Jan 1996 SP - 62 EP - 71 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 1 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Hepatocytes KW - Liver cancer KW - Secretion KW - Mitochondria KW - Hydrophobicity KW - Cell culture KW - Cholesterol KW - Peroxisomes KW - Cancer KW - hepatotoxicity KW - Hydroxylation KW - Digestion KW - Endoplasmic reticulum KW - Cytotoxicity KW - Colon KW - Vitamins KW - Bile acids KW - Liver KW - Cytosol KW - Intestine KW - Excretion KW - ursodeoxycholic acid KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/860371494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Bile+Acids+in+the+Assessment+of+Hepatocellular+Function&rft.au=Thompson%2C+M+B&rft.aulast=Thompson&rft.aufirst=M&rft.date=1996-01-01&rft.volume=24&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339602400109 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Hepatocytes; Secretion; Liver cancer; Mitochondria; Cell culture; Hydrophobicity; Cholesterol; hepatotoxicity; Cancer; Peroxisomes; Hydroxylation; Digestion; Endoplasmic reticulum; Cytotoxicity; Colon; Vitamins; Bile acids; Intestine; Cytosol; Liver; Excretion; ursodeoxycholic acid DO - http://dx.doi.org/10.1177/019262339602400109 ER - TY - JOUR T1 - Frequency-dependent changes of regional cerebral blood flow during finger movements. AN - 85274827; pmid-8530552 AB - To study the effect of the repetition rate of a simple movement on the distribution and magnitude of neuronal recruitment, we measured regional CBF (rCBF) in eight normal volunteers, using positron emission tomography and 15O-labeled water. An auditory-cued, repetitive flexion movement of the right index finger against the thumb was performed at very slow (0.25 and 0.5 Hz), slow (0.75 and 1 Hz), fast (2 and 2.5 Hz), and very fast (3 and 4 Hz) rates. The increase of rCBF during movement relative to the resting condition was calculated for each pair of movement conditions. Left primary sensorimotor cortex showed no significant activation at the very slow rates. There was a rapid rise of rCBF between the slow and the fast rates, but no further increase at the very fast rates. The right cerebellum showed similar changes. Changes in the left primary sensorimotor cortex and the cerebellum likely reflect the effect of the movement rate. The posterior supplementary motor area (SMA) showed its highest activation at the very slow rates but no significant activation at the very fast rates. Changes correlating with those in the SMA were found in the anterior cingulate gyrus, right prefrontal area, and right thalamus. The decreases in CBF may reflect a progressive change in performance from reactive to predictive. JF - Journal of Cerebral Blood Flow and Metabolism AU - Sadato, N AU - Ibañez V AU - Deiber, M P AU - Campbell, G AU - Leonardo, M AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA. PY - 1996 SP - 23 EP - 33 VL - 16 IS - 1 SN - 0271-678X, 0271-678X KW - Analysis of Variance KW - Reference Values KW - Human KW - Cerebellum KW - Cerebrovascular Circulation KW - Limbic System KW - Movement KW - Thalamus KW - Putamen KW - Cerebral Cortex KW - Fingers KW - Adult KW - Tomography, Emission-Computed KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85274827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Frequency-dependent+changes+of+regional+cerebral+blood+flow+during+finger+movements.&rft.au=Sadato%2C+N%3BIba%C3%B1ez+V%3BDeiber%2C+M+P%3BCampbell%2C+G%3BLeonardo%2C+M%3BHallett%2C+M&rft.aulast=Sadato&rft.aufirst=N&rft.date=1996-01-01&rft.volume=16&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Community panel discussions: from research to community action. AN - 85248755; pmid-8898783 AB - HYPERTENSION AND CARDIOVASCULAR DISEASE are increasing among minorities. Participants at the workshop on the Epidemiology of Hypertension in Hispanic Americans, Native Americans, and Asian/Pacific Islander Americans voiced a need to intensify a systemic approach for community-based strategies to guide prevention, treatment, and control. To answer this need, a panel addressed recommended community-based strategies from inclusion of community members in the research process to implementation and application of findings for community action. Recommended strategies include encouraging close cooperation and data sharing between investigators and community groups; including differences in culture, heritage, and local influences in hypertension research; training and working with minority researchers and health care professionals; and intensifying comprehensive and culturally appropriate education programs that focus on prevention, treatment, and control of hypertension. This article contains a summary of key areas of emphasis, as well as implementation strategies to decrease hypertension and other cardiovascular diseases in specific ethnic groups. JF - Public Health Reports (Washington, D.C. : 1974) AU - Alvarado, M AU - Smolenski, M C AD - Office of Prevention, Education, and Control, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA. PY - 1996 SP - 74 EP - 76 VL - 111 Suppl 2 SN - 0033-3549, 0033-3549 KW - Human KW - Cardiovascular Diseases KW - Hypertension KW - Community Health Planning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85248755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+Health+Reports+%28Washington%2C+D.C.+%3A+1974%29&rft.atitle=Community+panel+discussions%3A+from+research+to+community+action.&rft.au=Alvarado%2C+M%3BSmolenski%2C+M+C&rft.aulast=Alvarado&rft.aufirst=M&rft.date=1996-01-01&rft.volume=111+Suppl+2&rft.issue=&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Public+Health+Reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The swallowing side effects of botulinum toxin type A injection in spasmodic dysphonia. AN - 85195259; pmid-8544635 AB - Botulinum toxin type A (BOTOX) injection of the thyroarytenoid muscle is used to control speech symptoms in patients with adductor spasmodic dysphonia. Transient difficulty in swallowing liquids is a common treatment side effect. Laryngeal movement durations were measured during swallowing in 13 adductor spasmodic dysphonia patients undergoing treatment and in 6 normal control subjects in order to determine the following: 1. whether, prior to the injection, laryngeal movement durations were longer in the spasmodic dysphonia patients than in the control subjects; 2. whether movement durations increased following the injections; 3. whether preinjection swallowing difficulties related to postinjection swallowing measurements and postinjection patient reports of swallowing problems. A piezoelectric movement transducer was shown to be accurate for noninvasive measurement of laryngeal movement duration in relation to muscle onset and offset for hyoid elevation and relaxation. Before botulinum toxin type A injection, no significant differences in swallowing duration were found between the patient and control groups. Four patients with swallowing complaints prior to injection had longer laryngeal movement durations than the other spasmodic dysphonia patients and the control subjects. Following injection, laryngeal movement durations increased in the patients with spasmodic dysphonia, and eight patients reported dysphagia for an average of 2 weeks. Relationships were found between the patients' initial reports of swallowing problems and increased laryngeal movement durations before and after botulinum toxin type A injection. Those patients initially reporting swallowing difficulties had severe dysphagia for 2 weeks after the injection. Patient reports of dysphagia prior to injection may indicate a greater likelihood of significant dysphagia following thyroarytenoid injection with botulinum toxin type A. JF - The Laryngoscope AU - Holzer, S E AU - Ludlow, C L AD - Voice and Speech Section, National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892, USA. PY - 1996 SP - 86 EP - 92 VL - 106 IS - 1 Pt 1 SN - 0023-852X, 0023-852X KW - Spasm KW - Human KW - Injections, Intramuscular KW - Electromyography KW - Movement KW - Deglutition Disorders KW - Botulinum Toxins KW - Adult KW - Larynx KW - Middle Age KW - Voice Disorders KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85195259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Laryngoscope&rft.atitle=The+swallowing+side+effects+of+botulinum+toxin+type+A+injection+in+spasmodic+dysphonia.&rft.au=Holzer%2C+S+E%3BLudlow%2C+C+L&rft.aulast=Holzer&rft.aufirst=S&rft.date=1996-01-01&rft.volume=106&rft.issue=1+Pt+1&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Use of in vitro assays to predict the efficacy of chemopreventive agents in whole animals. AN - 78741592; 9154167 AB - Five in vitro assays have been applied to screen the efficacy of potential chemopreventive agents. These assays measure a) inhibition of morphological transformation in rat tracheal epithelial (RTE) cells, b) inhibition of anchorage independence in human lung tumor (A427) cells, c) inhibition of hyperplastic alveolar nodule formation in mouse mammary organ cultures (MMOC), d) inhibition of anchorage independence in mouse JB6 epidermal cells, and e) the inhibition of calcium tolerance in human foreskin epithelial cells. The efficacy of many of these same agents in whole animal studies of lung, colon, mammary gland, skin, and urinary bladder carcinogenesis has also been measured. The aim herein is to estimate the positive and negative predictive values of these in vitro assays against whole animal chemopreventive efficacy data using the same chemicals. For three of these assays--using RTE, A427 cells and mouse mammary organ culture (MMOC)-enough data are available to allow the estimate to be made. Such extrapolations of in vitro data to the in vivo situation are difficult at best. There are many dissimilarities between the two assay systems. The in vitro assays use respiratory and mammary epithelial cells, while the in vivo assays use respiratory, mammary, colon, bladder and skin cells. The in vitro assays use the carcinogens benzo(a)pyrene (B(a)P) and 7,12-dimethylbenz(a)anthracene (DMBA), while the in vivo assays use B(a)P, DMBA, N-methyl-N-nitrosourea (MNU), N,N'-diethylnitrosamine (DEN), azoxymethane (AOM), and N-butyl-N-(4-hydroxybutyl)nitrosoamine (OH-BBN). There are vast differences in pharmacodynamics and pharmacokinetics in vitro and in vivo, yet it is possible to rapidly screen chemicals in vitro for efficacy at one-tenth the cost and complete tests in weeks instead of months. A positive in vitro assay was defined as a 20% inhibition (compared with control) for the RTE and A427 assays and a 60% inhibition for the MMOC assay at nontoxic concentrations. For in vivo assays, the criterion for a positive result was a statistically significant inhibition of incidence, multiplicity or a significant increase in latency (mean time to first tumor). For an agent to be considered negative in animals, it required negative results in at least two different organ systems and no positive results. Using the battery of three in vitro tests, the positive predictive value for having one, two, or three positive in vitro assays and at least one positive whole animal test was 76%, 80%, and 83% respectively. The negative predictive values for one, two or all three in vitro assays was 25%, 27%, and 50%. From these data it is observed that in vitro assays give valuable positive predictive values and less valuable negative predictive values. The mechanisms of chemoprevention are not well understood. Seven categories of agents were examined for their cancer preventing both in vitro and in vivo: antiinflammatories, antioxidants, arachadonic acid metabolism inhibitors, GSH inducers, GST inducers, ODC inhibitors, and PKC inhibitors. Three or even five in vitro assays cannot be all-inclusive of the many mechanisms of cancer prevention. However, three assays help to predict whole animal efficacy with reasonable positive predictive values. Much work and development remains to be done to rapidly identify new chemopreventive drugs. JF - Journal of cellular biochemistry. Supplement AU - Steele, V E AU - Sharma, S AU - Mehta, R AU - Elmore, E AU - Redpath, L AU - Rudd, C AU - Bagheri, D AU - Sigman, C C AU - Kelloff, G J AD - Chemoprevention Branch, National Cancer Institute (NCI), Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 29 EP - 53 VL - 26 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Mammary Glands, Animal KW - Humans KW - Cell Transformation, Neoplastic -- drug effects KW - Predictive Value of Tests KW - Mice KW - Trachea -- cytology KW - Mice, Inbred BALB C KW - Rats KW - Epidermis KW - Tumor Cells, Cultured KW - Epithelial Cells KW - Cells, Cultured KW - Lung Neoplasms KW - Toxicity Tests KW - Skin -- cytology KW - Organ Culture Techniques KW - Female KW - Anticarcinogenic Agents -- toxicity KW - Anticarcinogenic Agents -- pharmacology KW - Neoplasms, Experimental -- prevention & control KW - Drug Screening Assays, Antitumor -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78741592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Use+of+in+vitro+assays+to+predict+the+efficacy+of+chemopreventive+agents+in+whole+animals.&rft.au=Steele%2C+V+E%3BSharma%2C+S%3BMehta%2C+R%3BElmore%2C+E%3BRedpath%2C+L%3BRudd%2C+C%3BBagheri%2C+D%3BSigman%2C+C+C%3BKelloff%2C+G+J&rft.aulast=Steele&rft.aufirst=V&rft.date=1996-01-01&rft.volume=26&rft.issue=&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GDNF is required for kidney development and enteric innervation. AN - 78739767; 9246473 JF - Cold Spring Harbor symposia on quantitative biology AU - Pichel, J G AU - Shen, L AU - Sheng, H Z AU - Granholm, A C AU - Drago, J AU - Grinberg, A AU - Lee, E J AU - Huang, S P AU - Saarma, M AU - Hoffer, B J AU - Sariola, H AU - Westphal, H AD - Laboratory of Mammalian Genes and Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 445 EP - 457 VL - 61 SN - 0091-7451, 0091-7451 KW - Gdnf protein, mouse KW - 0 KW - Glial Cell Line-Derived Neurotrophic Factor KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Animals KW - In Situ Hybridization KW - Digestive System -- embryology KW - Mice KW - Organ Culture Techniques KW - Mutation KW - Immunohistochemistry KW - Female KW - Pregnancy KW - Nerve Tissue Proteins -- physiology KW - Nerve Growth Factors -- genetics KW - Kidney -- embryology KW - Nerve Growth Factors -- physiology KW - Kidney -- innervation KW - Nerve Tissue Proteins -- genetics KW - Enteric Nervous System -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78739767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.atitle=GDNF+is+required+for+kidney+development+and+enteric+innervation.&rft.au=Pichel%2C+J+G%3BShen%2C+L%3BSheng%2C+H+Z%3BGranholm%2C+A+C%3BDrago%2C+J%3BGrinberg%2C+A%3BLee%2C+E+J%3BHuang%2C+S+P%3BSaarma%2C+M%3BHoffer%2C+B+J%3BSariola%2C+H%3BWestphal%2C+H&rft.aulast=Pichel&rft.aufirst=J&rft.date=1996-01-01&rft.volume=61&rft.issue=&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+symposia+on+quantitative+biology&rft.issn=00917451&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-29 N1 - Date created - 1997-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategy and planning for chemopreventive drug development: clinical development plans II. AN - 78739279; 9154168 AB - This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l-selenomethionine and 1, 4-phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs. JF - Journal of cellular biochemistry. Supplement AU - Kelloff, G J AU - Crowell, J A AU - Hawk, E T AU - Steele, V E AU - Lubet, R A AU - Boone, C W AU - Covey, J M AU - Doody, L A AU - Omenn, G S AU - Greenwald, P AU - Hong, W K AU - Parkinson, D R AU - Bagheri, D AU - Baxter, G T AU - Blunden, M AU - Doeltz, M K AU - Eisenhauer, K M AU - Johnson, K AU - Knapp, G G AU - Longfellow, D G AU - Malone, W F AU - Nayfield, S G AU - Seifried, H E AU - Swall, L M AU - Sigman, C C AD - Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI), Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 54 EP - 71 VL - 26 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Neoplasms, Experimental -- prevention & control KW - Cell Transformation, Neoplastic KW - Anticarcinogenic Agents -- therapeutic use KW - Anticarcinogenic Agents -- pharmacology KW - Clinical Trials as Topic -- standards KW - Neoplasms -- prevention & control KW - Drug Screening Assays, Antitumor -- methods KW - Clinical Trials as Topic -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78739279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Strategy+and+planning+for+chemopreventive+drug+development%3A+clinical+development+plans+II.&rft.au=Kelloff%2C+G+J%3BCrowell%2C+J+A%3BHawk%2C+E+T%3BSteele%2C+V+E%3BLubet%2C+R+A%3BBoone%2C+C+W%3BCovey%2C+J+M%3BDoody%2C+L+A%3BOmenn%2C+G+S%3BGreenwald%2C+P%3BHong%2C+W+K%3BParkinson%2C+D+R%3BBagheri%2C+D%3BBaxter%2C+G+T%3BBlunden%2C+M%3BDoeltz%2C+M+K%3BEisenhauer%2C+K+M%3BJohnson%2C+K%3BKnapp%2C+G+G%3BLongfellow%2C+D+G%3BMalone%2C+W+F%3BNayfield%2C+S+G%3BSeifried%2C+H+E%3BSwall%2C+L+M%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1996-01-01&rft.volume=26&rft.issue=&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New agents for cancer chemoprevention. AN - 78738410; 9154166 AB - Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned. The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids [e.g., retinol, retinyl palmitate, all-trans-retinoic acid, and 13-cis-retinoic acid], calcium, Beta carotene, vitamin E, tamoxifen, and finasteride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase III chemoprevention trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylornithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D3 analogs. Other agents of high interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean trypsin inhibitor). Combinations are also being considered, such as vitamin E with l-selenomethionine. Analysis of signal transduction pathways is beginning to yield classes of potentially active and selective chemopreventive drugs. Examples are ras isoprenylation and epidermal growth factor receptor inhibitors. JF - Journal of cellular biochemistry. Supplement AU - Kelloff, G J AU - Boone, C W AU - Crowell, J A AU - Steele, V E AU - Lubet, R A AU - Doody, L A AU - Malone, W F AU - Hawk, E T AU - Sigman, C C AD - Chemoprevention Branch, National Cancer Institute (NCI), Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1 EP - 28 VL - 26 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Clinical Trials as Topic KW - Neoplasms, Experimental -- prevention & control KW - Anticarcinogenic Agents -- therapeutic use KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78738410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=New+agents+for+cancer+chemoprevention.&rft.au=Kelloff%2C+G+J%3BBoone%2C+C+W%3BCrowell%2C+J+A%3BSteele%2C+V+E%3BLubet%2C+R+A%3BDoody%2C+L+A%3BMalone%2C+W+F%3BHawk%2C+E+T%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1996-01-01&rft.volume=26&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rational polypharmacy in the bipolar affective disorders. AN - 78729967; 9294735 AB - Bipolar affective illness represents a syndrome not readily treated by single agents. Approximately 50% of patients are inadequately responsive to lithium and the majority of patients require supplemental antidepressants, antimanic, antipsychotic or hypnotic medications. These traditional adjunctive medications are associated with potential problems. Antidepressants may precipitate mania (at a rate about double that of placebo) or cause cycle acceleration. Neuroleptics may be associated with either more profound or longer depressive phases, and clearly increase the risk of tardive dyskinesia, to which bipolar patients appear particularly predisposed. Moreover, there are subgroups of patients who are known to be poorly responsive to lithium. These include patients with rapid cycling, dysphoric mania, co-morbid drug or alcohol abuse, a pattern of depression-mania-well interval (D-M-I as opposed to the M-D-I pattern), and patients without a family history of bipolar illness in first-degree relatives. There is increasing recognition that the anticonvulsants carbamazepine and valproate are effective alternatives or adjuncts to lithium in the acute and long-term treatment of bipolar illness. Ideally, one would want to assess whether patients who were unresponsive to lithium were responsive to an anticonvulsant alone prior to utilizing lithium in addition to anticonvulsant combination therapy. However, from the clinical perspective, it is often more expedient to use an anticonvulsant adjunctively to lithium to assess the efficacy of this combination and establish mood stabilization. When lithium is not discontinued, the increased morbidity during lithium withdrawal also would not occur and would not confound the evaluation of the new agent. We suggest the initial use of acute adjuncts to lithium with the anticonvulsants carbamazepine or valproate (instead of neuroleptics) so that their efficacy can be assessed in the individual's acute episode, with the likelihood of a positive response in longer-term prophylaxis. Hypnotic benzodiazepines with anticonvulsant properties, such as clonazepam or lorazepam, are often used to help to induce sleep in escalating bipolar patients, and may be useful adjuncts as well. Patients who were inadequately responsive to either carbamazepine or valproate alone may be responsive to the anticonvulsant combination. In a similar fashion, one can also utilize several mood-stabilizing drugs (lithium and an anticonvulsant such as carbamazepine or valproate) in the treatment of depressive breakthroughs, and then augment this combination (if necessary) with a catecholamine-active antidepressant such as bupropion or a serotonin-selective reuptake inhibitor (SSRI) such as fluoxetine, paroxetine, sertraline or if necessary a monoamine oxidase inhibitor (MAOI). Once the patient has responded to a combination of drugs, it becomes problematic to decide whether the last agent added was the crucial ingredient in helping the patient achieve remission or that remission might have occurred with this agent alone. A conservative approach would have merit in patients who are finally stabilized on complex polypharmacy regimens only after many years of sequential trials; in this instance, the potential risk of re-exacerbating the illness with a taper of one of the drugs in the regimen. Rational polypharmacy should thus be implemented with careful delineation of the prior course of illness (typically using life chart methodology) and targeted treatment outcomes titrated against side effects, using sequential clinical trials in individual patients who have not adequately responded to monotherapy. In this fashion, it is hoped that pharmacodynamic differences among agents can be maximized and pharmacokinetic and side effects minimized. JF - Epilepsy research. Supplement AU - Post, R M AU - Ketter, T A AU - Pazzaglia, P J AU - Denicoff, K AU - George, M S AU - Callahan, A AU - Leverich, G AU - Frye, M AD - Biological Psychiatry Branch, NIMH, Bethesda, MD 20892-1272, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 153 EP - 180 VL - 11 SN - 0922-9833, 0922-9833 KW - Anticonvulsants KW - 0 KW - Antidepressive Agents KW - Antipsychotic Agents KW - Calcium Channel Blockers KW - Psychotropic Drugs KW - Lithium Carbonate KW - 2BMD2GNA4V KW - Carbamazepine KW - 33CM23913M KW - Valproic Acid KW - 614OI1Z5WI KW - Index Medicus KW - Drug Interactions KW - Humans KW - Carbamazepine -- therapeutic use KW - Antidepressive Agents -- adverse effects KW - Anticonvulsants -- therapeutic use KW - Antipsychotic Agents -- pharmacokinetics KW - Lithium Carbonate -- adverse effects KW - Calcium Channel Blockers -- adverse effects KW - Treatment Outcome KW - Valproic Acid -- therapeutic use KW - Lithium Carbonate -- therapeutic use KW - Carbamazepine -- pharmacokinetics KW - Antipsychotic Agents -- therapeutic use KW - Lithium Carbonate -- pharmacokinetics KW - Anticonvulsants -- adverse effects KW - Calcium Channel Blockers -- pharmacokinetics KW - Drug Therapy, Combination KW - Carbamazepine -- adverse effects KW - Anticonvulsants -- pharmacokinetics KW - Antidepressive Agents -- pharmacokinetics KW - Antidepressive Agents -- therapeutic use KW - Valproic Acid -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Calcium Channel Blockers -- therapeutic use KW - Valproic Acid -- pharmacokinetics KW - Bipolar Disorder -- drug therapy KW - Bipolar Disorder -- classification KW - Psychotropic Drugs -- therapeutic use KW - Psychotropic Drugs -- pharmacokinetics KW - Bipolar Disorder -- psychology KW - Psychotropic Drugs -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78729967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research.+Supplement&rft.atitle=Rational+polypharmacy+in+the+bipolar+affective+disorders.&rft.au=Post%2C+R+M%3BKetter%2C+T+A%3BPazzaglia%2C+P+J%3BDenicoff%2C+K%3BGeorge%2C+M+S%3BCallahan%2C+A%3BLeverich%2C+G%3BFrye%2C+M&rft.aulast=Post&rft.aufirst=R&rft.date=1996-01-01&rft.volume=11&rft.issue=&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research.+Supplement&rft.issn=09229833&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-24 N1 - Date created - 1997-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Myb-induced transformation. AN - 78728614; 9258605 AB - The c-myb protooncogene has been implicated in the development of avian and murine hematopoietic neoplasms of the myeloid and lymphoid lineages. The transcription factor encoded by this gene has a dual function in oncogenesis because it regulates genes that prevent apoptosis and genes involved in cellular proliferation. c-myb has repeatedly been a target of retroviral insertional mutagenesis. The most common mechanism by which retroviruses activate c-myb's oncogenic potential is by providing transcriptional control that results in constitutive expression, a feature that is consistent with the demonstration that ectopic expression of c-myb can prevent growth arrest of differentiating hematopoietic cells. In a less common mechanism of activation, carboxyl(C)-terminal truncation renders the c-Myb protein more stable and active in transcriptional transactivation. Interestingly, the ability of v-Myb, a product of the avian myeloblastosis virus (AMV), to cause rapid transformation of cells in vivo and in vitro can be explained by the combined effects of deregulated expression through the retroviral LTR, N- and C-terminal truncation, and activating mutations in its DNA binding domain. Although c-myb's involvement in human leukemia has been suggested, it has never been clearly established and should be investigated further. JF - Critical reviews in oncogenesis AU - Wolff, L AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892-4255, USA. LWOLFF@helix.nih.gov Y1 - 1996 PY - 1996 DA - 1996 SP - 245 EP - 260 VL - 7 IS - 3-4 SN - 0893-9675, 0893-9675 KW - Oncogene Proteins v-myb KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myb KW - Retroviridae Proteins, Oncogenic KW - Trans-Activators KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Retroviridae Proteins, Oncogenic -- genetics KW - Apoptosis -- genetics KW - Avian Myeloblastosis Virus -- genetics KW - Humans KW - Cell Differentiation -- genetics KW - Mutation KW - Cell Division -- genetics KW - Leukemia -- genetics KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - Proto-Oncogene Proteins -- metabolism KW - Transcription, Genetic KW - Proto-Oncogene Proteins -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78728614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+oncogenesis&rft.atitle=Myb-induced+transformation.&rft.au=Wolff%2C+L&rft.aulast=Wolff&rft.aufirst=L&rft.date=1996-01-01&rft.volume=7&rft.issue=3-4&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oncogenesis&rft.issn=08939675&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-29 N1 - Date created - 1997-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acquisition of the ts phenotype by a chemically mutagenized cold-passaged human respiratory syncytial virus vaccine candidate results from the acquisition of a single mutation in the polymerase (L) gene. AN - 78694095; 9035372 AB - A cold-passaged (cp) temperature-sensitive (ts) mutant of human respiratory syncytial virus designated RSV cpts-248 was previously derived by random chemical mutagenesis of the non-ts mutant cp-RSV that possesses one or more host range mutations. We previously demonstrated in rodents and seronegative chimpanzees that the cpts-248 virus is more attenuated than cp-RSV and is more stable genetically than previously isolated RSV ts mutants. In the present study, we determined that the acquisition of the ts phenotype and the increased attenuation of the cpts-248 virus are associated with a single nucleotide substitution at nucleotide 10,989 that results in a change in the coding region (amino acid position 831) of the polymerase gene. The identification of this attenuating ts mutation is important because cpts-248 was used as the parent virus for the generation of a number of further attenuated mutants that are currently being evaluated as candidate vaccine strains in clinical trials in infants. Furthermore, technology now exists to rationally design new vaccine candidates by incorporating multiple attenuating mutations, such as the one identified here, into infectious viruses that are genetically stable and appropriately attenuated. JF - Virus genes AU - Crowe, J E AU - Firestone, C Y AU - Whitehead, S S AU - Collins, P L AU - Murphy, B R AD - Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD 20892-0720, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 269 EP - 273 VL - 13 IS - 3 SN - 0920-8569, 0920-8569 KW - DNA, Viral KW - 0 KW - Viral Proteins KW - Viral Vaccines KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Phenotype KW - Animals KW - Base Sequence KW - Humans KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Vero Cells KW - Genes, Viral KW - Cold Temperature KW - Mutagenesis KW - Viral Proteins -- genetics KW - Respiratory Syncytial Virus, Human -- genetics KW - Respiratory Syncytial Virus, Human -- enzymology KW - Viral Vaccines -- genetics KW - DNA-Directed RNA Polymerases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78694095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virus+genes&rft.atitle=Acquisition+of+the+ts+phenotype+by+a+chemically+mutagenized+cold-passaged+human+respiratory+syncytial+virus+vaccine+candidate+results+from+the+acquisition+of+a+single+mutation+in+the+polymerase+%28L%29+gene.&rft.au=Crowe%2C+J+E%3BFirestone%2C+C+Y%3BWhitehead%2C+S+S%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Crowe&rft.aufirst=J&rft.date=1996-01-01&rft.volume=13&rft.issue=3&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Virus+genes&rft.issn=09208569&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-29 N1 - Date created - 1997-05-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U50362; GENBANK; U50363 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice. AN - 78686407; 9121607 AB - Several structurally related metabolites of progesterone (3 alpha-hydroxy pregnane-20-ones) and deoxycorticosterone (3 alpha-hydroxy pregnane-21-diol-20-ones) and their 3 beta-epimers were evaluated for protective activity against pilocarpine-, kainic acid- and N-methyl-D-aspartate (NMDA)-induced seizures in mice. Steroids with the 3-hydroxy group in the alpha-position and 5-H in the alpha- or beta-configurations were highly effective in protecting against pilocarpine (416 mg/kg, s.c.)-induced limbic motor seizures and status epilepticus (ED50 values, 7.0-18.7 mg/kg, i.p.). The corresponding epimers with the 3-hydroxy group in the beta-position were also effective but less potent (ED50 values, 33.8-63.5, i.p.). Although the neuroactive steroids were considerably less potent than the benzodiazepine clonazepam in protecting against pilocarpine seizures, steroids with the 5 alpha,3 alpha-configuration had comparable or higher protective index values (TD50 for motor impairment divided by ED50 for seizure protection) than clonazepam, indicating that some neuroactive steroids may have lower relative toxicity. Steroids with the 5 alpha,3 alpha- or 5 beta,3 alpha-configurations also produced a dose-dependent delay in the onset of limbic seizures induced by kainic acid (32 mg/kg, s.c.), but did not completely protect against the seizures. However, when a second dose of the steroid was administered 1 hr after the first dose, complete protection from the kainic acid-induced limbic seizures and status epilepticus was obtained. The steroids also caused a dose-dependent delay in NMDA (257 mg/kg, s.c.)-induced lethality, but did not completely protect against NMDA seizures or lethality. We conclude that neuroactive steroids are highly effective in protecting against pilocarpine- and kainic acid-induced seizures and status epilepticus in mice, and may be of utility in the treatment of some forms of status epilepticus in humans. JF - Neuropharmacology AU - Kokate, T G AU - Cohen, A L AU - Karp, E AU - Rogawski, M A AD - Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1049 EP - 1056 VL - 35 IS - 8 SN - 0028-3908, 0028-3908 KW - Anticonvulsants KW - 0 KW - Excitatory Amino Acid Agonists KW - Muscarinic Agonists KW - Steroids KW - Pilocarpine KW - 01MI4Q9DI3 KW - Desoxycorticosterone KW - 40GP35YQ49 KW - Progesterone KW - 4G7DS2Q64Y KW - Clonazepam KW - 5PE9FDE8GB KW - N-Methylaspartate KW - 6384-92-5 KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Anticonvulsants -- pharmacology KW - Animals KW - Dose-Response Relationship, Drug KW - Progesterone -- pharmacology KW - N-Methylaspartate -- toxicity KW - Isomerism KW - Desoxycorticosterone -- pharmacology KW - Mice KW - Male KW - Clonazepam -- pharmacology KW - Seizures -- chemically induced KW - Status Epilepticus -- prevention & control KW - Status Epilepticus -- chemically induced KW - Kainic Acid -- antagonists & inhibitors KW - Muscarinic Agonists -- toxicity KW - Pilocarpine -- antagonists & inhibitors KW - Steroids -- pharmacology KW - Seizures -- prevention & control KW - Excitatory Amino Acid Agonists -- toxicity KW - Pilocarpine -- toxicity KW - Kainic Acid -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78686407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Neuroactive+steroids+protect+against+pilocarpine-+and+kainic+acid-induced+limbic+seizures+and+status+epilepticus+in+mice.&rft.au=Kokate%2C+T+G%3BCohen%2C+A+L%3BKarp%2C+E%3BRogawski%2C+M+A&rft.aulast=Kokate&rft.aufirst=T&rft.date=1996-01-01&rft.volume=35&rft.issue=8&rft.spage=1049&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-23 N1 - Date created - 1997-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer: toxicity and response. AN - 78686094; 8995493 AB - Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 microg/ml. We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 microg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 microg/ml for 4 or more weeks. A single patient treated at 215 microg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 microg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 microg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. In summary, although plasma suramin concentrations were maintained below 300 microg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 microg/ml for 4 or more weeks. Therapy at 215 and 175 microg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin's activity in hormone-refractory prostate cancer. JF - Cancer chemotherapy and pharmacology AU - Bowden, C J AU - Figg, W D AU - Dawson, N A AU - Sartor, O AU - Bitton, R J AU - Weinberger, M S AU - Headlee, D AU - Reed, E AU - Myers, C E AU - Cooper, M R AD - Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1 EP - 8 VL - 39 IS - 1-2 SN - 0344-5704, 0344-5704 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Hormonal KW - Suramin KW - 6032D45BEM KW - Flutamide KW - 76W6J0943E KW - Index Medicus KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Aged, 80 and over KW - Humans KW - Flutamide -- therapeutic use KW - Aged KW - Middle Aged KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Male KW - Suramin -- adverse effects KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Suramin -- pharmacokinetics KW - Suramin -- administration & dosage KW - Antineoplastic Agents -- blood KW - Prostatic Neoplasms -- drug therapy KW - Suramin -- blood KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78686094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=A+phase+I%2FII+study+of+continuous+infusion+suramin+in+patients+with+hormone-refractory+prostate+cancer%3A+toxicity+and+response.&rft.au=Bowden%2C+C+J%3BFigg%2C+W+D%3BDawson%2C+N+A%3BSartor%2C+O%3BBitton%2C+R+J%3BWeinberger%2C+M+S%3BHeadlee%2C+D%3BReed%2C+E%3BMyers%2C+C+E%3BCooper%2C+M+R&rft.aulast=Bowden&rft.aufirst=C&rft.date=1996-01-01&rft.volume=39&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-04 N1 - Date created - 1997-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antitumor effects of human recombinant interleukin-1 alpha and etoposide against human tumor cells: mechanism for synergism in vitro and activity in vivo. AN - 78685455; 9012539 AB - Recombinant human interleukin 1 alpha (rh IL-1 alpha) and etoposide (VP-16) synergize for direct growth inhibition of several human tumor cell lines in vitro. Our previous studies demonstrated that VP-16 increased the number of membrane-associated IL-1 receptors (IL-1Rs) and also enhanced the internalization of receptor-bound rh IL-1 alpha. The purposes of this study were to test our hypotheses that these events were critical to the synergy between rhIL-1 alpha and VP-16, to determine whether rhIL- 1 alpha and VP-16 synergize to increase superoxide (SO) anion radical production in vitro since SO anion has been implicated in the toxic effects of IL-1, and to investigate the antitumor efficacy of the combination against tumors in vivo. A375/C6 melanoma cells and OVCAR-3 ovarian carcinoma cells were tested with IL-1 receptor antagonist (IL-1 ra) before exposure to rhIL-1 alpha, VP-16 and rhIL-1 alpha plus VP-16. The synergistic or antagonistic effects were assessed by MTT assay. SO production was measured by reduction of cytochrome C. Athymic female mice bearing the A375/C6 melanoma were treated by rhIL-1 alpha, VP-16, and rhIL- 1 alpha+VP-16. The antitumor effects were evaluated by quantitating tumor growth and survival time. Pretreatment with the IL-1ra abrogated the synergistic effects of rhIL-1 alpha and VP-16. The production of SO radical by A375/C6 cells was increased 2.5 fold by the combination of rhIL-1 alpha and VP-16, and the addition of exogenous SOD blocked the synergy between rhIL-1 alpha and VP-16. However, when A375/SOD15 cells which over-expressed manganese superoxide dismutase (MnSOD) after MnSOD cDNA transfection were exposed to rhIL-1 alpha and VP-16, in vitro antagonism was observed. In vivo studies demonstrated that the combination of rhIL-1 alpha and VP-16 delayed tumor growth better than either agent alone, although long-term survival was not improved because of substantial toxicity. Our results suggest that the synergistic antitumor effects of IL-1 alpha and VP-16 may be due to IL-1R modulation and increased internalization of IL-1-IL-1R complex by VP-16 treatment, as well as to a subsequent increase in SO anion radical production from the tumor cells exposed to both drugs. Thus, the combination of IL-1 alpha and VP-16 might prove useful for the treatment of malignant disease in vivo, if the increased toxicity can be reduced or managed. JF - Biotherapy (Dordrecht, Netherlands) AU - Usui, N AU - Matsushima, K AU - Pilaro, A M AU - Longo, D L AU - Wiltrout, R H AD - Laboratory of Experimental Immunology, National Cancer Institute, FCRDC, Maryland 21702-1201, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 199 EP - 208 VL - 9 IS - 4 SN - 0921-299X, 0921-299X KW - Antineoplastic Agents KW - 0 KW - IL1RN protein, human KW - Il1rn protein, mouse KW - Interleukin 1 Receptor Antagonist Protein KW - Interleukin-1 KW - Recombinant Proteins KW - Sialoglycoproteins KW - Superoxides KW - 11062-77-4 KW - Etoposide KW - 6PLQ3CP4P3 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Animals KW - Superoxides -- metabolism KW - Sialoglycoproteins -- pharmacology KW - Tumor Cells, Cultured KW - Humans KW - Superoxide Dismutase -- metabolism KW - Mice KW - Neoplasms, Experimental -- drug therapy KW - Mice, Inbred BALB C KW - Drug Synergism KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Recombinant Proteins -- administration & dosage KW - Female KW - Interleukin-1 -- administration & dosage KW - Etoposide -- administration & dosage KW - Antineoplastic Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78685455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotherapy+%28Dordrecht%2C+Netherlands%29&rft.atitle=Antitumor+effects+of+human+recombinant+interleukin-1+alpha+and+etoposide+against+human+tumor+cells%3A+mechanism+for+synergism+in+vitro+and+activity+in+vivo.&rft.au=Usui%2C+N%3BMatsushima%2C+K%3BPilaro%2C+A+M%3BLongo%2C+D+L%3BWiltrout%2C+R+H&rft.aulast=Usui&rft.aufirst=N&rft.date=1996-01-01&rft.volume=9&rft.issue=4&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Biotherapy+%28Dordrecht%2C+Netherlands%29&rft.issn=0921299X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-01 N1 - Date created - 1997-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of angiotensin II on immunotoxin uptake in tumor and normal tissue. AN - 78684707; 8995508 AB - To investigate the effect of the sarcosine analog of human angiotensin II ([sar]ATII) on the uptake and spatial distribution of immunotoxins (MW 210000 Da) in RD rhabdomyosarcoma xenografts in mice. This analog has a pressor activity similar to native angiotensin II (ATII) but a longer duration of action. A period of elevated blood pressure of approximately 80 min, measured by noninvasive photoplethysmography, was achieved by a 40-min continuous i.p. infusion of [sar]ATII at 0.07 microg/min. Tumor-bearing animals were injected i.v. with 125I-labeled specific and 131I-labeled nonspecific immunotoxins and made hypertensive by i.p. infusion of [sar]ATII. Radioactivity was measured in plasma, tumor, liver, kidney and muscle at 2, 6 and 24 h. Plasma radioactivity was subtracted from tissue values to calculate tissue uptake. To assess the spatial distribution of immunotoxin in the solid tumor, 125I-labeled specific immunotoxin was injected i.v. into tumor-bearing animals, and quantitative autoradiography was performed on tumor sections. The uptake of specific or nonspecific immunotoxins in tumor and normal tissues was not significantly different in [sar]ATII-hypertensive animals compared with saline-treated controls. In control animals. the spatial distribution of 125I-labeled specific immunotoxins was very heterogeneous and contained punctate accumulations throughout the tumor. Treatment with [sar]ATII did not affect this distribution qualitatively or quantitatively. To examine a possible reason for the lack of [sar]ATII effect, we measured the interstitial pressure of the RD tumor using a fluid-filled micropipette connected to a servo-null pressure transducer. The interstitial pressure in this solid tumor was unexpectedly low, only 0.6 +/- 0.9 mm Hg. The sustained period of [sar]ATII-induced hypertension had no effect on RD tumor or normal tissue uptake or tumor spatial distribution of immunotoxin. In saline-treated controls, the heterogeneity of immunotoxin distribution does not arise from an elevated interstitial pressure. Further studies are needed to determine whether a correlation exists between responsiveness to ATII-induced hypertensive chemotherapy using macromolecular drugs and tumor type and/or physiological properties. JF - Cancer chemotherapy and pharmacology AU - Elizondo, F G AU - Sung, C AD - Biomedical Engineering and Instrumentation Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 113 EP - 121 VL - 39 IS - 1-2 SN - 0344-5704, 0344-5704 KW - Immunotoxins KW - 0 KW - Vasoconstrictor Agents KW - Angiotensin II KW - 11128-99-7 KW - Index Medicus KW - Animals KW - Injections, Intravenous KW - Humans KW - Mice KW - Mice, Nude KW - Tissue Distribution KW - Autoradiography KW - Infusions, Parenteral KW - Hypertension -- chemically induced KW - Photoplethysmography KW - Blood Pressure -- drug effects KW - Female KW - Hypertension -- metabolism KW - Immunotoxins -- pharmacokinetics KW - Vasoconstrictor Agents -- pharmacology KW - Rhabdomyosarcoma -- metabolism KW - Immunotoxins -- administration & dosage KW - Immunotoxins -- blood KW - Angiotensin II -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78684707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Effect+of+angiotensin+II+on+immunotoxin+uptake+in+tumor+and+normal+tissue.&rft.au=Elizondo%2C+F+G%3BSung%2C+C&rft.aulast=Elizondo&rft.aufirst=F&rft.date=1996-01-01&rft.volume=39&rft.issue=1-2&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-04 N1 - Date created - 1997-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular characterization of the complex sex-chromosome heterochromatin in the rodent Microtus chrotorrhinus. AN - 78683541; 8995489 AB - The sex chromosomes of Microtus chrotorrhinus are unusually large compared to those of other mammals, comprising about 20% of the karyotype and containing substantial amounts of constitutive heterochromatin. Previous studies have described two highly repeated DNA families (MSAT-160 and MSAT-2570) that localize to this heterochromatin (Modi, 1992, 1993c). The present report describes a third satellite DNA family (termed MSAT-21) in M. chrotorrhinus that is also located in the sex heterochromatin. This repeat consists of diverged copies (average similarity = 75%) of a tandemly repeated 21-mer. Southern blotting of MSAT-21 revealed that although some higher order (5-20 kb) repeats do exist, none has spread throughout an appreciable portion of the genome. Pulsed field gel experiments indicated that most of the larger arrays (50-700 kb) of all three satellite families are distributed across numerous size classes, suggesting that the three repeats are interspersed with one another in this heterochromatin. Analysis of a boundary between MSAT-21 and MSAT-160 showed that the junction monomers of each satellite are intact and that a pentanucleotide has apparently been transferred from MSAT-21 to MSAT-160 via recombination. Sequence comparisons of MSAT-160 with another rodent satellite and with the U3 region of the Rous sarcoma virus (RSV) long terminal repeat identified inverted repeats and similarities with viral enhancer domains in the rodent sequences. Additionally, the MSAT-21 consensus was found to be similar to the R region of RSV, suggesting a retroviral ancestor for these rodent repeated DNA families. JF - Cytogenetics and cell genetics AU - Ivanov, S V AU - Modi, W S AD - Biological Carcinogenesis and Development Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 49 EP - 56 VL - 75 IS - 1 SN - 0301-0171, 0301-0171 KW - DNA, Satellite KW - 0 KW - Heterochromatin KW - Index Medicus KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Blotting, Southern KW - Enhancer Elements, Genetic KW - Molecular Sequence Data KW - In Situ Hybridization, Fluorescence KW - Electrophoresis, Gel, Pulsed-Field KW - Consensus Sequence KW - Repetitive Sequences, Nucleic Acid KW - Avian Sarcoma Viruses -- genetics KW - Male KW - Cloning, Molecular KW - Sex Chromosomes -- genetics KW - Heterochromatin -- genetics KW - Arvicolinae -- genetics KW - DNA, Satellite -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78683541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=Molecular+characterization+of+the+complex+sex-chromosome+heterochromatin+in+the+rodent+Microtus+chrotorrhinus.&rft.au=Ivanov%2C+S+V%3BModi%2C+W+S&rft.aulast=Ivanov&rft.aufirst=S&rft.date=1996-01-01&rft.volume=75&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-30 N1 - Date created - 1997-01-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M86667; GENBANK; M29096; X69387; L43073 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer risk factors for selecting cohorts for large-scale chemoprevention trials. AN - 78683486; 9027595 AB - Many anticipate that application of findings in molecular genetics will help to achieve greater precision in defining high-risk populations that may benefit from chemopreventive interventions. We must recognize, however, that genetic susceptibility, environmental factors, and complex gene-environment interactions are all likely to be risk determinants for most cancers. Cohort studies of twins and cancer indicate that having "identical" genes is generally not a very accurate predictor of cancer incidence. Data from twin studies support the suggestion that environmental factors such as tobacco use significantly influence cancer risk. The complexities of the genetic contribution to disease risk are exemplified by the development of Duchenne muscular dystrophy in only one of monozygotic twin girls, hypothesized to be the result of X chromosome inactivation, with the distribution patterns of the X chromosome being skewed to the female X in the manifesting twin and to the male X in the normal twin. Evidence from transgenic and genetic-environmental studies in animals support the possibility of genetic-environmental interactions. Calorie restriction modifies tumor expression in p53 knockout mice; a high-fat, low-calcium, low-vitamin D diet increases prepolyp hyperplasia formation in Apc-mutated mice; and calorie restriction early in life influences development of obesity in the genetically obese Zucker rat (fafa). Such environmental modulation of gene expression suggests that chemoprevention has the potential to reduce risk for both environmentally and genetically determined cancers. In view of the growing research efforts in chemoprevention, the NCI has developed a Prevention Trials Decision Network (PTDN) to formalize the evaluation and approval process for large-scale chemoprevention trials. The PTDN addresses large trial prioritization and the associated issues of minority recruitment and retention; identification and validation of biomarkers as intermediate endpoints for cancer; and chemopreventive agent selection and development. A comprehensive database is being established to support the PTDN's decision-making process and will help to determine which agents investigated in preclinical and early phase clinical trials should move to large-scale testing. Cohorts for large-scale chemoprevention trials include individuals who are determined to be at high risk as a result of genetic predisposition, carcinogenic exposure, or the presence of biomarkers indicative of increased risk. Current large-scale trials in well-defined, high-risk populations include the Breast Cancer Prevention Trial (tamoxifen), the Prostate Cancer Prevention Trial (finasteride), and the N-(4-hydroxyphenyl) retinamide (4-HPR) breast cancer prevention study being conducted in Milan. Biomarker studies will provide valuable information for refining the design and facilitating the implementation of future large-scale trials. For example, potential biomarkers are being assessed at biopsy in women with ductal carcinoma in situ (DCIS). The women are then randomized to either placebo, tamoxifen, 4-HPR, or tamoxifen plus 4-HPR for 2-4 weeks, at which time surgery is performed and the biomarkers reassessed to determine biomarker modulation by the interventions. For prostate cancer, modulation of prostatic intraepithelial neoplasia (PIN) by 4-HPR and difluoromethylornithine is being investigated; similar studies are being planned for oltipraz, dehydroepiandrosterone, and vitamin E plus selenomethionine. The validation of biomarkers as surrogate endpoints for cancer incidence in high-risk cohorts will allow more agents to be evaluated in shorter studies that use fewer subjects to achieve the desired statistical power. JF - Journal of cellular biochemistry. Supplement AU - Greenwald, P AD - Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. GreenwaP@DCPC31.NCI.NIH.GOV Y1 - 1996 PY - 1996 DA - 1996 SP - 29 EP - 36 VL - 25 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Biomarkers, Tumor KW - Fenretinide KW - 187EJ7QEXL KW - Index Medicus KW - United States KW - Animals KW - Fenretinide -- therapeutic use KW - Humans KW - Diseases in Twins KW - Mice KW - Research Design KW - Clinical Trials as Topic -- methods KW - Rats KW - Risk Factors KW - National Institutes of Health (U.S.) KW - Databases, Factual KW - Chemoprevention KW - Diet KW - Female KW - Male KW - Anticarcinogenic Agents -- therapeutic use KW - Biomarkers, Tumor -- analysis KW - Neoplasms -- prevention & control KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78683486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Cancer+risk+factors+for+selecting+cohorts+for+large-scale+chemoprevention+trials.&rft.au=Greenwald%2C+P&rft.aulast=Greenwald&rft.aufirst=P&rft.date=1996-01-01&rft.volume=25&rft.issue=&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence-specific DNA breaks produced by triplex-directed decay of iodine-125. AN - 78683267; 9004758 AB - Triplex forming oligonucleotides (TFO) labeled with Auger emitters could be ideal vehicles to deliver radioactive-decay energy to specific DNA sequences, causing DNA breaks and, subsequently, inactivation of these sequences. To demonstrate this approach we labeled with 125I (two 125I per molecule on average) a purine-rich 38-mer which forms a stable triplex with a polypurine x polypyrimidine stretch in the human HPRT gene. Decay of 125I in the bound TFO was shown to cause sequence-specific double strand breaks (DSB) in the target HPRT sequence cloned into plasmid DNA. No sequence-specific breaks were observed if 125I-labeled TFO were not bound to the plasmid DNA. After 60 days of decay accumulation (one 125I half-life) approximately a quarter of all plasmid molecules contained sequence-specific DSB, corresponding to 0.3 site-specific DSB per decay. Sequencing gel analysis shows that the DNA breaks are distributed within a few bases of the maxima at those bases opposite to the positions of 125I in the TFO. JF - Acta oncologica (Stockholm, Sweden) AU - Panyutin, I G AU - Neumann, R D AD - Department of Nuclear Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1180, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 817 EP - 823 VL - 35 IS - 7 SN - 0284-186X, 0284-186X KW - DNA, Single-Stranded KW - 0 KW - Iodine Radioisotopes KW - Oligonucleotide Probes KW - DNA KW - 9007-49-2 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Base Sequence -- radiation effects KW - Oligonucleotide Probes -- genetics KW - Plasmids -- genetics KW - Molecular Sequence Data KW - Oligonucleotide Probes -- metabolism KW - Plasmids -- radiation effects KW - DNA, Single-Stranded -- radiation effects KW - Mutagenesis, Site-Directed KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - DNA Damage KW - Hypoxanthine Phosphoribosyltransferase -- metabolism KW - Iodine Radioisotopes -- metabolism KW - DNA -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78683267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.atitle=Sequence-specific+DNA+breaks+produced+by+triplex-directed+decay+of+iodine-125.&rft.au=Panyutin%2C+I+G%3BNeumann%2C+R+D&rft.aulast=Panyutin&rft.aufirst=I&rft.date=1996-01-01&rft.volume=35&rft.issue=7&rft.spage=817&rft.isbn=&rft.btitle=&rft.title=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.issn=0284186X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-30 N1 - Date created - 1997-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethical and scientific considerations for chemoprevention research in cohorts at genetic risk for breast cancer. AN - 78681445; 9027608 AB - Identification of cohorts at genetic risk for cancer offers unique research opportunities to explore the steps in carcinogenesis, from the inheritance of a predisposing mutation to the development of preinvasive lesions or overt malignancy, and to evaluate interventions to modulate the carcinogenic process. However, cancer prevention strategies for most inherited cancer predisposition syndromes are of unproven benefit, and the potential for adverse psychosocial effects and employment or insurance discrimination associated with genetic testing is substantial. Thus testing for genetic cancer risk remains highly controversial, and the National Center for Human Genome Research and the American Society of Human Genetics advise DNA testing for presymptomatic identification of cancer risk only in the setting of a carefully monitored research environment. The commercial availability of predictive genetic testing, particularly for inherited susceptibility to cancer, has focused attention not only on the urgent need for research in cancer prevention for cohorts at genetic cancer risk but also on ethical considerations surrounding clinical prevention research in genetic risk groups. This paper addresses the interrelationship of ethical and scientific issues in conducting chemoprevention research in these cohorts, especially for those studies which require presymptomatic testing for specific gene mutations as a study entry criterion or as a criterion for stratification. Practical approaches to study design and implementation issues for chemoprevention research in genetic risk cohorts are discussed, emphasizing the interactions of ethical and scientific considerations at all levels of the research process. JF - Journal of cellular biochemistry. Supplement AU - Nayfield, S G AD - Chemoprevention Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 123 EP - 130 VL - 25 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - BRCA1 Protein KW - Biomarkers, Tumor KW - Bioethics KW - Index Medicus KW - American Society of Human Genetics KW - Biomedical and Behavioral Research KW - American Society of Clinical Oncology KW - Genetics and Reproduction KW - Disease Susceptibility KW - BRCA1 Protein -- genetics KW - Humans KW - Confidentiality KW - Research Subjects KW - Patient Selection KW - Research Design KW - Genetic Testing KW - BRCA1 Protein -- analysis KW - Risk Factors KW - Cohort Studies KW - Biomarkers, Tumor -- analysis KW - Informed Consent KW - Chemoprevention KW - Female KW - Breast Neoplasms -- genetics KW - Genetic Research KW - Anticarcinogenic Agents -- therapeutic use KW - Breast Neoplasms -- pathology KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology KW - Ethics, Medical KW - Breast Neoplasms -- prevention & control KW - Ovarian Neoplasms -- prevention & control KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78681445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Ethical+and+scientific+considerations+for+chemoprevention+research+in+cohorts+at+genetic+risk+for+breast+cancer.&rft.au=Nayfield%2C+S+G&rft.aulast=Nayfield&rft.aufirst=S&rft.date=1996-01-01&rft.volume=25&rft.issue=&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk biomarkers and current strategies for cancer chemoprevention. AN - 78680604; 9027592 AB - Quantifiable, well-characterized cancer risk factors demonstrate the need for chemoprevention and define cohorts for chemopreventive intervention. For chemoprevention, the important cancer risk factors are those that can be measured quantitatively in the subject at risk. These factors, called risk biomarkers, can be used to identify cohorts for chemoprevention. Those modulated by chemopreventive agents may also be used as endpoints in chemoprevention studies. Generally, the risk biomarkers fit into categories based on those previously defined by Hulka: 1) carcinogen exposure, 2) carcinogen exposure/effect, 3) genetic predisposition, 4) intermediate biomarkers of cancer, and 5) previous cancers. Besides their use in characterizing cohorts for chemoprevention trials, some risk biomarkers can be modulated by chemopreventive agents. These biomarkers may be suitable surrogate endpoints for cancer incidence in chemoprevention intervention trials. The criteria for risk biomarkers defining cohorts and serving as endpoints are the same, except that those defining cohorts are not necessarily modulated by chemopreventive agents. A primary criterion is that the biomarkers fit expected biological mechanisms of early carcinogenesis-i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, and short latency compared with cancer. They must occur in sufficient number to allow their biological and statistical evaluation. Further, the biomarkers should be assayed reliably and quantitatively, measured easily, and correlated to cancer incidence. Particularly important for cancer risk screening in normal subjects is the ability to use noninvasive techniques that are highly specific, sensitive, and quantitative. Since carcinogenesis is a multipath process, single biomarkers are difficult to correlate to cancer, as they may appear on only one or a few of the many possible causal pathways. As shown in colorectal carcinogenesis, the risks associated with the presence of biomarkers may be additive or synergistic. That is, the accumulation of genetic lesions is the more important determinant of colorectal cancer compared with the presence of any single lesion. Thus, batteries of biomarker abnormalities, particularly those representing the range of carcinogenesis pathways, may prove more useful than single biomarkers both in characterizing cohorts at risk and defining modulatable risks. Risk biomarkers are already being integrated into many chemoprevention intervention trials. One example is the phase II trial of oltipraz inhibition of carcinogen-DNA adducts in a Chinese population exposed to aflatoxin B1. Also, urine samples from subjects in this trial will be screened for the effect of oltipraz on urinary mutagens. A second example is a chemoprevention protocol developed for patients at high risk for breast cancer; the cohort is defined both by hereditary risk and the presence of biomarker abnormalities. Modulation of the biomarker abnormalities is a proposed endpoint. Also, dysplastic lesions, such as prostatic intraepithelial neoplasia, oral leukoplakia and colorectal adenomas, have been used to define high-risk cohorts and as potential modulatable surrogate endpoints in chemoprevention trials. JF - Journal of cellular biochemistry. Supplement AU - Kelloff, G J AU - Boone, C W AU - Crowell, J A AU - Nayfield, S G AU - Hawk, E AU - Malone, W F AU - Steele, V E AU - Lubet, R A AU - Sigman, C C AD - Chemoprevention Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1 EP - 14 VL - 25 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Biomarkers, Tumor KW - Index Medicus KW - Animals KW - Clinical Trials, Phase II as Topic KW - Clinical Trials, Phase III as Topic KW - Risk Factors KW - Humans KW - Cohort Studies KW - Chemoprevention KW - Research Design KW - Anticarcinogenic Agents -- therapeutic use KW - Neoplasms -- epidemiology KW - Biomarkers, Tumor -- analysis KW - Neoplasms -- prevention & control KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78680604?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Risk+biomarkers+and+current+strategies+for+cancer+chemoprevention.&rft.au=Kelloff%2C+G+J%3BBoone%2C+C+W%3BCrowell%2C+J+A%3BNayfield%2C+S+G%3BHawk%2C+E%3BMalone%2C+W+F%3BSteele%2C+V+E%3BLubet%2C+R+A%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1996-01-01&rft.volume=25&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complex association and dissociation kinetics of brevetoxin binding to voltage-sensitive rat brain sodium channels. AN - 78680524; 9029551 AB - Brevetoxins bind with high affinity to the voltage-sensitive sodium channel and cause nerve cell depolarization and increased sodium ion conductance. Using 0.6 nM tritium-labeled brevetoxin-3 and freshly prepared synaptosomes from fresh or frozen rat brain, binding results at 6 degrees C fit well to a curve for 2-phase association with 65% of the binding in the rapid phase and t1/2 values of 11 and 74 min for the rapid and slow phases, respectively. Both phases were accelerated at higher toxin concentrations, binding of 9 nM brevetoxin-3 (PbTx-3) was close to equilibrium within 1 hr. The slow phase was not apparent when binding was done at 20 degrees C or when binding was done at 6 degrees C after the membrane sample had been preincubated at 4 degrees C for 1 day or at 22 degrees C for 1 hr. The 2-phase nature of association was not affected by substitution of KCl for choline chloride in the assay medium to produce sodium channel in the inactive state. Dissociation kinetics at 6 degrees C were also complex; the results fit well to a 2-phase curve with 55% of the dissociation in the rapid phase and t1/2 values of 13 and 64 min for the rapid and slow phases, respectively. The 2-phase nature did not change significantly after preincubation at 4 degrees C for 1 day. However, dissociation at 20 degrees C was rapid and fit a curve for 1-phase dissociation with a t1/2 of 2-6 min. At higher concentrations of PbTx-3, the binding is further complicated by the presence of 2-4 low-affinity binding sites with Kd values near 700 nM. In conclusion the association and dissociation of PbTx-3 with sodium channel from rat brain are complex processes that may involve changes in sodium channel conformation or interactions with other membrane (or membrane-associated) components. JF - Natural toxins AU - Whitney, P L AU - Baden, D G AD - NIEHS Marine and Freshwater Biomedical Sciences Center, University of Miami RSMAS, Florida 33149, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 261 EP - 270 VL - 4 IS - 6 SN - 1056-9014, 1056-9014 KW - Marine Toxins KW - 0 KW - Oxocins KW - Sodium Channels KW - brevetoxin KW - 98225-48-0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Kinetics KW - Protein Binding KW - Sodium Channels -- metabolism KW - Brain -- metabolism KW - Marine Toxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78680524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Natural+toxins&rft.atitle=Complex+association+and+dissociation+kinetics+of+brevetoxin+binding+to+voltage-sensitive+rat+brain+sodium+channels.&rft.au=Whitney%2C+P+L%3BBaden%2C+D+G&rft.aulast=Whitney&rft.aufirst=P&rft.date=1996-01-01&rft.volume=4&rft.issue=6&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Natural+toxins&rft.issn=10569014&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-09 N1 - Date created - 1997-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defining and analyzing cohorts using molecular markers of cancer risk. AN - 78678339; 9027601 AB - Cancer is currently regarded to be the phenotypic expression of an accumulation of heritable alterations in the regulators of cell growth and differentiation. Though detailed knowledge of the sequence and in vivo mechanistic effects of these alterations is rudimentary for most, if not all, cancers, their identification does offer the potential for classifying groups of individuals who are heterogeneous with respect to their cancer risks, into more nearly homogeneous subgroups. In this paper, we illustrate the value of using markers, which we define as any manifestation of cellular molecular diversity, to increase subgroup homogeneity. In the context of time-to-event data, we demonstrate for both somatic mutations (acquired p53 abnormalities in gastric mucosal cells) and inherited polymorphisms (polymorphisms in the phase 1 and 2 detoxifying enzymes) how knowledge regarding the population frequency of the marker the effect of the marker on the risk of cancer development, and/or the effect of the marker on response to therapy, can be used to plan and analyze such trials. Using as paradigms demographic features of the recently begun Shandong precancerous gastric lesion intervention trial, and the recently completed alpha-tocopherol beta-carotene (ATBC) lung cancer prevention study, we review the information, assumptions, and mathematical structure required for planning cancer prevention trials. We graphically demonstrate how informative markers make available strategies for selection, stratification, and optimal weighing, which, when properly implemented, increase the power of tests of effective cancer prevention agents. JF - Journal of cellular biochemistry. Supplement AU - Mark, S D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7368, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 69 EP - 79 VL - 25 SN - 0733-1959, 0733-1959 KW - Biomarkers, Tumor KW - 0 KW - beta Carotene KW - 01YAE03M7J KW - Vitamin E KW - 1406-18-4 KW - Index Medicus KW - Stomach Neoplasms -- pathology KW - Polymorphism, Genetic KW - Humans KW - Clinical Trials as Topic KW - Vitamin E -- therapeutic use KW - Aged KW - Stomach Neoplasms -- prevention & control KW - Research Design KW - Mutagenesis KW - Japan -- epidemiology KW - Lung Neoplasms -- prevention & control KW - beta Carotene -- therapeutic use KW - Stomach Neoplasms -- genetics KW - China -- epidemiology KW - Adult KW - Cohort Studies KW - Lung Neoplasms -- genetics KW - Middle Aged KW - Lung Neoplasms -- mortality KW - Finland -- epidemiology KW - Male KW - Neoplasms -- epidemiology KW - Biomarkers, Tumor -- analysis KW - Neoplasms -- prevention & control KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78678339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Defining+and+analyzing+cohorts+using+molecular+markers+of+cancer+risk.&rft.au=Mark%2C+S+D&rft.aulast=Mark&rft.aufirst=S&rft.date=1996-01-01&rft.volume=25&rft.issue=&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 conformation and substrate interactions as probed by CO binding kinetics. AN - 78676893; 9010599 AB - The kinetics of CO binding to cytochrome P450, as measured by the flash photolysis technique, is a powerful probe of P450 structure-function relationships. The kinetics are sensitive to P450 conformation and dynamics and are modulated by P450 interactions with substrates and other components of the microsomal membrane. Application of a difference method to kinetic data analysis distinguishes the kinetic behavior of individual P450 forms in the microsomal membrane. This approach shows that substrates differentially modulate the kinetics via: 1) changes in P450 conformation/dynamics that either accelerate or reduce the binding rate; and/or 2) steric effects that reduce the rate. Both mechanisms are observed, the relative contributions of each varying in a substrate- and P450-dependent manner. In addition to microsomes, substrate interactions with individual P450s can be similarly probed using expressed P450s. Experiments with baculovirus-expressed human P450 3A4 show that this P450 consists of multiple conformers with distinct substrate specificities, an observation which provides a basis for its recognition of a wide array of structurally diverse substrates. These studies thus demonstrate the utility of CO binding kinetics in elucidating fundamental P450-substrate interactions in a biological membrane environment. JF - Biochimie AU - Koley, A P AU - Robinson, R C AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 706 EP - 713 VL - 78 IS - 8-9 SN - 0300-9084, 0300-9084 KW - Carbon Monoxide KW - 7U1EE4V452 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Index Medicus KW - Animals KW - Humans KW - Microsomes, Liver -- metabolism KW - Gene Expression KW - Structure-Activity Relationship KW - Rats KW - Baculoviridae -- genetics KW - Rats, Sprague-Dawley KW - Mixed Function Oxygenases -- metabolism KW - Kinetics KW - Substrate Specificity KW - Male KW - Mixed Function Oxygenases -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Carbon Monoxide -- metabolism KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78676893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimie&rft.atitle=Cytochrome+P450+conformation+and+substrate+interactions+as+probed+by+CO+binding+kinetics.&rft.au=Koley%2C+A+P%3BRobinson%2C+R+C%3BFriedman%2C+F+K&rft.aulast=Koley&rft.aufirst=A&rft.date=1996-01-01&rft.volume=78&rft.issue=8-9&rft.spage=706&rft.isbn=&rft.btitle=&rft.title=Biochimie&rft.issn=03009084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-08 N1 - Date created - 1997-07-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Biochimie 1997;79(1):20 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular aspects of muscarinic receptor assembly and function. AN - 78676006; 9009702 JF - Progress in brain research AU - Wess, J AU - Blin, N AU - Yun, J AU - Schöneberg, T AU - Liu, J AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 153 EP - 162 VL - 109 SN - 0079-6123, 0079-6123 KW - Receptors, Muscarinic KW - 0 KW - Recombinant Proteins KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Structural KW - Mammals KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - GTP-Binding Proteins -- physiology KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Protein Structure, Secondary KW - Receptors, Muscarinic -- biosynthesis KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78676006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+brain+research&rft.atitle=Molecular+aspects+of+muscarinic+receptor+assembly+and+function.&rft.au=Wess%2C+J%3BBlin%2C+N%3BYun%2C+J%3BSch%C3%B6neberg%2C+T%3BLiu%2C+J&rft.aulast=Wess&rft.aufirst=J&rft.date=1996-01-01&rft.volume=109&rft.issue=&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Progress+in+brain+research&rft.issn=00796123&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-07 N1 - Date created - 1997-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenic analysis of viral polymerases and related proteins. AN - 78675798; 9026658 JF - Methods in enzymology AU - Boyer, P L AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 538 EP - 555 VL - 275 SN - 0076-6879, 0076-6879 KW - DNA, Viral KW - 0 KW - Recombinant Proteins KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - AIDS/HIV KW - Cloning, Molecular -- methods KW - Escherichia coli -- genetics KW - Bacteriophage M13 -- genetics KW - HIV Reverse Transcriptase -- chemistry KW - Restriction Mapping -- methods KW - Bacteriophages -- enzymology KW - Genetic Techniques KW - Recombinant Proteins -- metabolism KW - Polymerase Chain Reaction -- methods KW - HIV Reverse Transcriptase -- metabolism KW - Templates, Genetic KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Mutagenesis, Insertional KW - DNA, Viral -- metabolism KW - Mutagenesis, Site-Directed KW - RNA-Directed DNA Polymerase -- chemistry KW - DNA-Directed RNA Polymerases -- metabolism KW - DNA-Directed RNA Polymerases -- chemistry KW - RNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78675798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Site-directed+mutagenic+analysis+of+viral+polymerases+and+related+proteins.&rft.au=Boyer%2C+P+L%3BHughes%2C+S+H&rft.aulast=Boyer&rft.aufirst=P&rft.date=1996-01-01&rft.volume=275&rft.issue=&rft.spage=538&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analyzing the fidelity of reverse transcription and transcription. AN - 78673474; 9026657 JF - Methods in enzymology AU - Boyer, J C AU - Bebenek, K AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 523 EP - 537 VL - 275 SN - 0076-6879, 0076-6879 KW - DNA Primers KW - 0 KW - DNA, Single-Stranded KW - DNA, Viral KW - Indicators and Reagents KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Index Medicus KW - AIDS/HIV KW - Viral Plaque Assay KW - Humans KW - Electrophoresis, Polyacrylamide Gel -- methods KW - Cloning, Molecular -- methods KW - HIV-1 -- enzymology KW - DNA, Single-Stranded -- biosynthesis KW - Mutagenesis KW - Frameshift Mutation KW - Base Sequence KW - Restriction Mapping KW - Point Mutation KW - Molecular Sequence Data KW - Avian Myeloblastosis Virus -- enzymology KW - DNA, Single-Stranded -- chemistry KW - Escherichia coli KW - DNA, Viral -- biosynthesis KW - DNA, Viral -- chemistry KW - HIV Reverse Transcriptase -- metabolism KW - Transcription, Genetic KW - RNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78673474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Analyzing+the+fidelity+of+reverse+transcription+and+transcription.&rft.au=Boyer%2C+J+C%3BBebenek%2C+K%3BKunkel%2C+T+A&rft.aulast=Boyer&rft.aufirst=J&rft.date=1996-01-01&rft.volume=275&rft.issue=&rft.spage=523&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms, chemical structures and drug metabolism. AN - 78653251; 8987250 AB - From the studies that have been done by many laboratories over the last 2 decades, it is now clear that the toxicities produced by many drugs are due to their reactive metabolites. It is though that, in many cases, reactive metabolites cause toxicity by binding covalently to tissue proteins. However, until recently it was difficult to identify these protein targets. Due to the development of an immunochemical approach, this problem has been overcome, as is illustrated here by studies that have been conducted on the metabolic basis of the idiosyncratic hepatitis caused by the inhalation anaesthetic halothane. The major problem to solve in the future will be to determine how protein adduct formation leads to toxicity. It is possible that protein adduct formation may alter an important cellular function or may lead to immunopathology, as is thought to occur in the case of halothane hepatitis. If an allergic reaction is suspected, purified protein targets of reactive metabolites can serve as antigens for identifying sensitized individuals. This information can be used to prevent not only an allergic reaction to the drug, but possible cross-reactions to other drugs that are structurally related. Another important application of these studies is the design of safer alternative drugs that will not produce structurally similar toxic reactive metabolites. JF - European journal of haematology. Supplementum AU - Pohl, L R AU - Pumford, N R AU - Martin, J L AD - Molecular and Cellular Toxicology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1760, USA. pohll@gwgate.nhlbi.nih.gov Y1 - 1996 PY - 1996 DA - 1996 SP - 98 EP - 104 VL - 60 SN - 0902-4506, 0902-4506 KW - Pharmaceutical Preparations KW - 0 KW - Index Medicus KW - Molecular Structure KW - Chemical and Drug Induced Liver Injury -- etiology KW - Humans KW - Chemical and Drug Induced Liver Injury -- metabolism KW - Structure-Activity Relationship KW - Pharmaceutical Preparations -- metabolism KW - Pharmacology KW - Pharmaceutical Preparations -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78653251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+haematology.+Supplementum&rft.atitle=Mechanisms%2C+chemical+structures+and+drug+metabolism.&rft.au=Pohl%2C+L+R%3BPumford%2C+N+R%3BMartin%2C+J+L&rft.aulast=Pohl&rft.aufirst=L&rft.date=1996-01-01&rft.volume=60&rft.issue=&rft.spage=98&rft.isbn=&rft.btitle=&rft.title=European+journal+of+haematology.+Supplementum&rft.issn=09024506&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-19 N1 - Date created - 1997-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-related blood dyscrasias. Introduction. AN - 78650723; 8987234 JF - European journal of haematology. Supplementum AU - Young, N S AD - Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 6 EP - 8 VL - 60 SN - 0902-4506, 0902-4506 KW - Index Medicus KW - Humans KW - Anemia, Aplastic -- chemically induced KW - Bone Marrow Diseases -- chemically induced KW - Paraproteinemias -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78650723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+haematology.+Supplementum&rft.atitle=Drug-related+blood+dyscrasias.+Introduction.&rft.au=Young%2C+N+S&rft.aulast=Young&rft.aufirst=N&rft.date=1996-01-01&rft.volume=60&rft.issue=&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=European+journal+of+haematology.+Supplementum&rft.issn=09024506&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-19 N1 - Date created - 1997-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Damage inducible mutagenesis: recent insights into the activities of the Umu family of mutagenesis proteins. AN - 78636627; 8977032 AB - Despite our advances, much remains to be elucidated about the molecular mechanisms of damage inducible mutagenesis. Although some aspects of the intricate protein interactions that lead to the formation of the mutasome have been determined, the precise nature of the interactions between pol III and the UmuD'C-RecA proteins remains entirely speculative. Further progress will depend on the development of a completely reconstituted, cell free lesion bypass system in vitro, as well as structural modelling of the mutasome in its entirety before we understand how error prone translesion DNA synthesis is achieved. Even if a structural homologue of the Escherichia coli mutasome does not exist in higher organisms, it seems quite likely that a functionally homologous mutagenic pathway will indeed be found. Such an active mutagenic process in animal cells would certainly have significant implications for our understanding of the mechanisms of genetic instability, as well as of human carcinogenesis and other pathologies associated with the formation of mutations in DNA. JF - Cancer surveys AU - Woodgate, R AU - Levine, A S AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2725, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 117 EP - 140 VL - 28 SN - 0261-2429, 0261-2429 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - UmuC protein, E coli KW - 98059-80-4 KW - DNA Polymerase III KW - EC 2.7.7.- KW - Rec A Recombinases KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Index Medicus KW - SOS Response (Genetics) -- genetics KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - DNA Polymerase III -- metabolism KW - Bacterial Proteins -- genetics KW - DNA Repair KW - DNA Damage KW - Bacterial Proteins -- metabolism KW - Mutagenesis -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78636627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+surveys&rft.atitle=Damage+inducible+mutagenesis%3A+recent+insights+into+the+activities+of+the+Umu+family+of+mutagenesis+proteins.&rft.au=Woodgate%2C+R%3BLevine%2C+A+S&rft.aulast=Woodgate&rft.aufirst=R&rft.date=1996-01-01&rft.volume=28&rft.issue=&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Cancer+surveys&rft.issn=02612429&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA synthesis errors, mutators and cancer. AN - 78635892; 8977025 AB - To quote Drake et al (1983), "The list of mutagenic mechanisms is long, and it is far more difficult to write the encyclopedia of all possible errors than the few chapters of correct procedures". We are just beginning to appreciate the "correct procedures" for replication and repair, and these require more than a "few chapters" to describe (for two excellent recent texts, see Friedberg et al, 1995 and DePamphilis, in press). Here we have considered several of the key steps and principles for high fidelity DNA synthesis and how these may be perturbed to destabilize the genome. Within this rich intellectual framework, we can anticipate the discovery of new cancer causing genes in the near future, especially given the flurry of activity resulting from recent progress on the relationships between cancer and defective mismatch and excision repair processes. JF - Cancer surveys AU - Minnick, D T AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 3 EP - 20 VL - 28 SN - 0261-2429, 0261-2429 KW - Deoxyribonucleosides KW - 0 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Phenotype KW - Animals KW - Colonic Neoplasms -- genetics KW - Humans KW - DNA-Directed DNA Polymerase -- genetics KW - DNA Repair KW - Deoxyribonucleosides -- metabolism KW - Mutagenesis -- genetics KW - Neoplasms -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78635892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+surveys&rft.atitle=DNA+synthesis+errors%2C+mutators+and+cancer.&rft.au=Minnick%2C+D+T%3BKunkel%2C+T+A&rft.aulast=Minnick&rft.aufirst=D&rft.date=1996-01-01&rft.volume=28&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Cancer+surveys&rft.issn=02612429&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TP53 tumour suppressor gene: clues to molecular carcinogenesis and cancer therapy. AN - 78635044; 8977035 AB - The tumour suppressor gene product TP53 is clearly a component in several biochemical pathways, including transcription, DNA repair, genomic stability, cell cycle control and apoptosis, that are central to human carcinogenesis. TP53 is functionally inactivated by mutational, viral and cellular mechanisms in the majority of human cancers. Analysis of the spectrum of TP53 mutations provides clues to the aetiology and molecular pathogenesis of cancer. Recent insight into the TP53 mediated biochemical pathways of cell cycle arrest and apoptosis has provided further understanding of the mechanisms related to TP53 mediated tumour suppression. This in turn may provide the potential molecular targets for the development of rational multimodality cancer therapy, including chemotherapy, immunotherapy and gene therapy strategies. The convergence of previously parallel lines of basic, clinical and epidemiological investigation may provide an opportunity for the rapid transfer of research findings from the laboratory to the clinic. JF - Cancer surveys AU - Wang, X W AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 169 EP - 196 VL - 28 SN - 0261-2429, 0261-2429 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Animals KW - Apoptosis -- genetics KW - DNA Repair KW - Phosphorylation KW - Humans KW - Mice KW - Li-Fraumeni Syndrome -- genetics KW - Cell Division -- genetics KW - Tumor Suppressor Protein p53 -- physiology KW - Genes, p53 -- physiology KW - Genes, p53 -- genetics KW - Mutation -- genetics KW - Transcription, Genetic KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms -- therapy KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78635044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+surveys&rft.atitle=TP53+tumour+suppressor+gene%3A+clues+to+molecular+carcinogenesis+and+cancer+therapy.&rft.au=Wang%2C+X+W%3BHarris%2C+C+C&rft.aulast=Wang&rft.aufirst=X&rft.date=1996-01-01&rft.volume=28&rft.issue=&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Cancer+surveys&rft.issn=02612429&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment with 5-fluorouracil of 35 patients with clinical or subclinical HPV infection of the vagina. AN - 78625990; 8971537 JF - European journal of gynaecological oncology AU - Stefanon, B AU - Pallucca, A AU - Merola, M AU - Bandieramonte, G AD - National Cancer Institute, Milan, Italy. Y1 - 1996 PY - 1996 DA - 1996 SP - 534 VL - 17 IS - 6 SN - 0392-2936, 0392-2936 KW - Antimetabolites, Antineoplastic KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Follow-Up Studies KW - Female KW - Administration, Topical KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Papillomavirus Infections -- diagnosis KW - Tumor Virus Infections -- diagnosis KW - Papillomavirus Infections -- drug therapy KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- therapeutic use KW - Papillomavirus Infections -- pathology KW - Tumor Virus Infections -- drug therapy KW - Vaginal Diseases -- drug therapy KW - Papillomaviridae -- isolation & purification KW - Tumor Virus Infections -- pathology KW - Vaginal Diseases -- etiology KW - Vaginal Diseases -- pathology KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78625990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+gynaecological+oncology&rft.atitle=Treatment+with+5-fluorouracil+of+35+patients+with+clinical+or+subclinical+HPV+infection+of+the+vagina.&rft.au=Stefanon%2C+B%3BPallucca%2C+A%3BMerola%2C+M%3BBandieramonte%2C+G&rft.aulast=Stefanon&rft.aufirst=B&rft.date=1996-01-01&rft.volume=17&rft.issue=6&rft.spage=534&rft.isbn=&rft.btitle=&rft.title=European+journal+of+gynaecological+oncology&rft.issn=03922936&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-20 N1 - Date created - 1997-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selegiline in adults with attention deficit hyperactivity disorder: clinical efficacy and safety. AN - 78617302; 8961775 AB - Clinical effects of high-dose and low-dose selegiline treatment were examined in 24 adults with attention deficit hyperactivity disorder (ADHD). The study used a double-blind randomized three-arm parallel-groups design with a 2-week placebo baseline followed by 6 weeks of treatment (placebo, 20 mg/day, or 60 mg/day selegiline) and then by 2 weeks of placebo post-treatment. A two-way repeated measures analysis of variance (ANOVA) showed no Drug x Time interaction and no main effect of Drug on severity of ADHD symptoms as self-rated by the subjects on the Conners Abbreviated Teacher Rating Scale (Conners ATRS). There was a significant effect of Time, indicating decreased ADHD symptom severity scores in all three groups. Selegiline treatment was not more effective than placebo. Side effects were more severe in the high-dose selegiline group than in either of the other groups. These preliminary results must be interpreted with caution because of methodological limitations in terms of sample size, patient population selection, and measurement tools. JF - Psychopharmacology bulletin AU - Ernst, M AU - Liebenauer, L L AU - Jons, P H AU - Tebeka, D AU - Cohen, R M AU - Zametkin, A J AD - Brain Imaging Section, Intramural Research Program, National Institute on Drug Abuse (NIDA), Baltimore, MD 21224, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 327 EP - 334 VL - 32 IS - 3 SN - 0048-5764, 0048-5764 KW - Monoamine Oxidase Inhibitors KW - 0 KW - Selegiline KW - 2K1V7GP655 KW - Index Medicus KW - Dizziness -- chemically induced KW - Humans KW - Adult KW - Male KW - Female KW - Selegiline -- adverse effects KW - Selegiline -- therapeutic use KW - Attention Deficit Disorder with Hyperactivity -- pathology KW - Monoamine Oxidase Inhibitors -- therapeutic use KW - Attention Deficit Disorder with Hyperactivity -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78617302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology+bulletin&rft.atitle=Selegiline+in+adults+with+attention+deficit+hyperactivity+disorder%3A+clinical+efficacy+and+safety.&rft.au=Ernst%2C+M%3BLiebenauer%2C+L+L%3BJons%2C+P+H%3BTebeka%2C+D%3BCohen%2C+R+M%3BZametkin%2C+A+J&rft.aulast=Ernst&rft.aufirst=M&rft.date=1996-01-01&rft.volume=32&rft.issue=3&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology+bulletin&rft.issn=00485764&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Psychopharmacology in HIV-positive patients: research perspectives. AN - 78616825; 8961771 AB - Psychotropic medications play an important role in the treatment of human immunodeficiency virus (HIV)-positive subjects suffering from neuropsychiatric disorders or other acquired immunodeficiency syndrome (AIDS)-related symptomatology. The quality of life of these patients can be significantly improved by the appropriate use of these agents. Various aspects of psychopharmacology that are relevant to HIV-positive patients include assessment of efficacy, tolerability, drug-drug interactions, and effects on cognition. These topics need further investigation and require focused research efforts. This report highlights current research needs and presents specific recommendations that emerged at a recent meeting on psychopharmacology for HIV-positive patients organized by the National Institute of Mental Health (NIMH). JF - Psychopharmacology bulletin AU - Vitiello, B AU - Stover, E S Y1 - 1996 PY - 1996 DA - 1996 SP - 293 EP - 297 VL - 32 IS - 3 KW - Anti-Anxiety Agents KW - 0 KW - Anti-HIV Agents KW - Antidepressive Agents KW - Index Medicus KW - AIDS/HIV KW - Drug Interactions KW - Anxiety Disorders -- drug therapy KW - Humans KW - Anti-Anxiety Agents -- therapeutic use KW - Depressive Disorder -- drug therapy KW - Antidepressive Agents -- therapeutic use KW - Guidelines as Topic KW - Depressive Disorder -- complications KW - Anxiety Disorders -- complications KW - Anti-HIV Agents -- therapeutic use KW - AIDS Dementia Complex -- drug therapy KW - HIV Infections -- complications KW - HIV Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78616825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Psychopharmacology+bulletin&rft.atitle=Psychopharmacology+in+HIV-positive+patients%3A+research+perspectives.&rft.au=Vitiello%2C+B%3BStover%2C+E+S&rft.aulast=Vitiello&rft.aufirst=B&rft.date=1996-01-01&rft.volume=32&rft.issue=3&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology+bulletin&rft.issn=00485764&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NIDA technical review: nitrite inhalants. AN - 78583828; 8949404 AB - Nitrite inhalants are commonly abused substances in the US and Europe. "Nitrite inhalants and AIDS" was a popular topic in the early 1980s when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use wained. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in laboratory studies, and remains a candidate "cofactor" in the pathogenesis of AIDS-related Karposi sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal. Participants recommend specific research efforts. JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie AU - Haverkos, H W AU - Drotman, D P AD - Office on AIDS, National Institute on Drug Abuse, National Institutes of Health, Rockville, MD 20857, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 228 EP - 230 VL - 50 IS - 5 SN - 0753-3322, 0753-3322 KW - Nitrites KW - 0 KW - Index Medicus KW - AIDS/HIV KW - United States KW - United States Public Health Service KW - Humans KW - Sarcoma, Kaposi -- complications KW - Administration, Inhalation KW - Male KW - Female KW - Acquired Immunodeficiency Syndrome -- complications KW - Nitrites -- administration & dosage KW - Drug and Narcotic Control KW - HIV Infections -- complications KW - Nitrites -- adverse effects KW - HIV Infections -- immunology KW - Acquired Immunodeficiency Syndrome -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78583828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biomedicine+%26+pharmacotherapy+%3D+Biomedecine+%26+pharmacotherapie&rft.atitle=NIDA+technical+review%3A+nitrite+inhalants.&rft.au=Haverkos%2C+H+W%3BDrotman%2C+D+P&rft.aulast=Haverkos&rft.aufirst=H&rft.date=1996-01-01&rft.volume=50&rft.issue=5&rft.spage=228&rft.isbn=&rft.btitle=&rft.title=Biomedicine+%26+pharmacotherapy+%3D+Biomedecine+%26+pharmacotherapie&rft.issn=07533322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine D2 receptor imaging and neuroleptic drug response. AN - 78573655; 8941175 AB - Studies with positron emission tomography and single photon emission computed tomography have yielded important findings concerning the relationship between dopamine D2 receptor occupancy and neuroleptic dose, plasma neuroleptic levels, and clinical response. For "typical" neuroleptics, therapeutic response is associated with occupancy levels as low as 60%-70%, which can be achieved at lower doses than are routinely used. For these drugs, extrapyramidal side effects increase, and therapeutic response remains unchanged with higher occupancy levels. Although the mechanisms responsible for the improved clinical efficacy and tolerability of atypical neuroleptics are still poorly understood, antipsychotic efficacy has been observed at lower D2 receptor occupancy rates than with typical neuroleptics. It is unclear whether the lower incidence of extrapyramidal side effects observed with the atypical neuroleptic clozapine can be attributed to its lower D2 occupancy, its relatively specific effects on the ventral striatum, or its nondopaminergic effects. There are a number of additional unresolved issues, including the high interindividual variation in scan outcome measurements, possible effects of concomitant medication, possible effects of endogenous dopamine, and assumptions in various strategies used to model receptor densities and occupancy rates. JF - The Journal of clinical psychiatry AU - Heinz, A AU - Knable, M B AU - Weinberger, D R AD - National Institute of Mental Health, Clinical Brain Disorders Branch, Division of Intramural Research Programs, Neuroscience Center at St. Elizabeths, Washington, D.C. 20032, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 84 EP - 8; discussion 89-93 VL - 57 Suppl 11 SN - 0160-6689, 0160-6689 KW - Antipsychotic Agents KW - 0 KW - Delayed-Action Preparations KW - Receptors, Dopamine D2 KW - Index Medicus KW - Schizophrenia -- blood KW - Corpus Striatum -- diagnostic imaging KW - Tomography, Emission-Computed, Single-Photon KW - Schizophrenia -- metabolism KW - Humans KW - Corpus Striatum -- metabolism KW - Treatment Outcome KW - Tomography, Emission-Computed KW - Schizophrenia -- drug therapy KW - Basal Ganglia Diseases -- metabolism KW - Basal Ganglia Diseases -- chemically induced KW - Antipsychotic Agents -- therapeutic use KW - Antipsychotic Agents -- pharmacology KW - Receptors, Dopamine D2 -- drug effects KW - Antipsychotic Agents -- metabolism KW - Brain -- metabolism KW - Brain -- diagnostic imaging KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78573655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+psychiatry&rft.atitle=Dopamine+D2+receptor+imaging+and+neuroleptic+drug+response.&rft.au=Heinz%2C+A%3BKnable%2C+M+B%3BWeinberger%2C+D+R&rft.aulast=Heinz&rft.aufirst=A&rft.date=1996-01-01&rft.volume=57+Suppl+11&rft.issue=&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+psychiatry&rft.issn=01606689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-02 N1 - Date created - 1997-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural model of the outer vestibule and selectivity filter of the Shaker voltage-gated K+ channel. AN - 78567817; 8938709 AB - A new generation of structural models were developed of the outer vestibule and ion-selective portion of the voltage-gated Shaker K+ channel. Some features of these models are similar to those that we have developed previously [Durrel S. R. and Guy H. R. (1992) Biophys. J. 62, 238-250; Guy H. R. (1990) In Monovalent Cations in Biological Systems (Pasternak C. A., Ed.), pp. 31-58, CRC Press, Boca Raton, FL; Guy H. R. and Durell S. R. (1994) In Molecular Evolution of Physiological processes (Fambrough D., Ed.), pp. 197-212, The Rockefeller University Press, NY; Guy H. R. and Durell S. R. (1995) In Ion Channels and Genetic Diseases (Dawson D., Ed.), pp. 1-16, The Rockefeller University Press, NY] and other features were modified to make the models more consistent with recent experimental findings. The first part of the P segment is postulated, as always, to form a short alpha helix that spans only the outer portion of the membrane. The helix is tilted so that its C-terminal is nearer the pore than its N-terminal. The latter part of the P segment, P2, is postulated to have a relatively elongated conformation that is positioned approximately parallel to the axis of the pore. Four of the P2 segments assemble to form an ion-selective region that has two narrow regions; one formed by the Y445 side-chains at the outer entrance of the pore and one formed by the backbone of the T442 residues near the innermost part of the P segments. The S6 segment is postulated to form two alpha helices. The first S6 helix packs next to the P segments in our models. The NMR structures of two scorpion toxins, charybdotoxin and agitoxin 2, have been docked into the models of the outer vestibules. The shape of the outer vestibule has been modeled so that specific toxin-channel residue-residue interactions correspond to those that have been identified experimentally. JF - Neuropharmacology AU - Durell, S R AU - Guy, H R AD - Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5567, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 761 EP - 773 VL - 35 IS - 7 SN - 0028-3908, 0028-3908 KW - Potassium Channels KW - 0 KW - Scorpion Venoms KW - Shaker Superfamily of Potassium Channels KW - Tetraethylammonium Compounds KW - Toxins, Biological KW - kaliotoxin KW - Charybdotoxin KW - 115422-61-2 KW - agitoxin 2 KW - 155646-22-3 KW - Tetraethylammonium KW - 66-40-0 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Index Medicus KW - Toxins, Biological -- metabolism KW - Ion Channel Gating KW - Scorpion Venoms -- metabolism KW - Tetraethylammonium Compounds -- metabolism KW - 4-Aminopyridine -- metabolism KW - Mutation KW - Potassium Channels -- metabolism KW - Protein Structure, Secondary KW - Potassium Channels -- chemistry KW - Models, Molecular KW - Potassium Channels -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78567817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Structural+model+of+the+outer+vestibule+and+selectivity+filter+of+the+Shaker+voltage-gated+K%2B+channel.&rft.au=Durell%2C+S+R%3BGuy%2C+H+R&rft.aulast=Durell&rft.aufirst=S&rft.date=1996-01-01&rft.volume=35&rft.issue=7&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-11 N1 - Date created - 1997-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo effect of chemically induced fibrosarcoma on copper metabolism of liver in mice. AN - 78556513; 8931753 AB - Copper and ceruloplasmin concentrations were determined in different subcellular fractions of liver of mice bearing benzo(a)pyrene induced fibrosarcoma. Though the copper content was elevated in the nuclear, mitochondrial and lysosomal fractions of tumor bearing mice, the microsomal and soluble supernatant fractions showed a downward trend in their copper concentration when compared to the controls. Similarly, ceruloplasmin concentration in the different subcellular fractions also showed variable results. This study was aimed to ascertain the distribution of copper. The incorporation of radioactive copper in different fractions was also monitored. The possible reasons for the variation in copper and ceruloplasmin concentrations observed during malignancy in the tumor bearing animals, has been discussed. JF - Neoplasma AU - Chakravarty, P K AU - Ghosh, A AD - Tumor Immunity and Gene Therapy Unit, Chittaranjan National Cancer Institute (Research Wing), Calcutta, India. Y1 - 1996 PY - 1996 DA - 1996 SP - 271 EP - 274 VL - 43 IS - 4 SN - 0028-2685, 0028-2685 KW - Carcinogens KW - 0 KW - Copper Radioisotopes KW - Benzo(a)pyrene KW - 3417WMA06D KW - Copper KW - 789U1901C5 KW - Ceruloplasmin KW - EC 1.16.3.1 KW - Index Medicus KW - Mice, Inbred A KW - Animals KW - Mice KW - Subcellular Fractions -- metabolism KW - Ceruloplasmin -- metabolism KW - Fibrosarcoma -- metabolism KW - Copper -- pharmacokinetics KW - Fibrosarcoma -- chemically induced KW - Copper -- metabolism KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78556513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=In+vivo+effect+of+chemically+induced+fibrosarcoma+on+copper+metabolism+of+liver+in+mice.&rft.au=Chakravarty%2C+P+K%3BGhosh%2C+A&rft.aulast=Chakravarty&rft.aufirst=P&rft.date=1996-01-01&rft.volume=43&rft.issue=4&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-20 N1 - Date created - 1996-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanistic considerations in the evaluation of chemopreventive data. AN - 78544559; 8923032 AB - Possible chemopreventive mechanisms include carcinogen-blocking activities, antioxidant/anti-inflammatory activities and antiproliferation/antiprogression activities. Carcinogen-blocking activities encompass inhibition of carcinogen uptake, inhibition of carcinogen formation or activation, deactivation or detoxification of carcinogens, prevention of carcinogen binding to DNA, and enhancement of the level or fidelity of DNA repair. Antioxidant/anti-inflammatory activities include scavenging of reactive electrophiles and oxygen radicals, and inhibition of arachidonic acid metabolism. Antiproliferation/antiprogression activities comprise modulation of signal transduction, modulation of hormonal and growth factor activity, inhibition of aberrant oncogene activity, inhibition of polyamine metabolism, induction of terminal differentiation, restoration of immune responses, enhancement of intercellular communication, restoration of tumour suppressor function, induction of apoptosis, telomerase inhibition, correction of DNA methylation imbalances, inhibition of angiogenesis, inhibition of basement membrane degradation, and activation of antimetastasis genes. In evaluating the potential efficacy of chemopreventive agents several mechanistic parameters are weighed: (1) the number of chemoprevention-related pharmacological activities, (2) the impact of the agent on likely carcinogenesis pathways to the targeted cancer, (3) pharmacodynamics, and (4) specificity for chemopreventive activity compared with interference with normal cellular function. Mechanistic data are important throughout the development process for chemopreventive drugs, and they are particularly important in the earlier phases of identifying promising candidate agents and characterizing efficacy. In vitro mechanistic assays are a first step in evaluating chemopreventive potential. Mechanistic considerations are also useful in defining animal efficacy models and in interpreting the results of assays in these models. Mechanistic data are also applied in designing short-term Phase II clinical chemoprevention trials that use reductions in intermediate biomarkers of cancer rather than cancer incidence as end points. The basis for identifying and evaluating these biomarkers is in understanding carcinogenesis and chemopreventive mechanisms. JF - IARC scientific publications AU - Kelloff, G J AU - Boone, C W AU - Steele, V E AU - Crowell, J A AU - Lubet, R A AU - Greenwald, P AU - Hawk, E T AU - Fay, J R AU - Sigman, C C AD - Chemoprevention Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 203 EP - 219 IS - 139 SN - 0300-5038, 0300-5038 KW - Anticarcinogenic Agents KW - 0 KW - Antioxidants KW - Carcinogens KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Carcinogens -- metabolism KW - Antioxidants -- pharmacology KW - Humans KW - DNA -- metabolism KW - Carcinogens -- pharmacokinetics KW - Antioxidants -- therapeutic use KW - Chemoprevention -- methods KW - Cell Division -- drug effects KW - Data Interpretation, Statistical KW - DNA -- drug effects KW - Anticarcinogenic Agents -- therapeutic use KW - Anticarcinogenic Agents -- pharmacology KW - Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78544559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Mechanistic+considerations+in+the+evaluation+of+chemopreventive+data.&rft.au=Kelloff%2C+G+J%3BBoone%2C+C+W%3BSteele%2C+V+E%3BCrowell%2C+J+A%3BLubet%2C+R+A%3BGreenwald%2C+P%3BHawk%2C+E+T%3BFay%2C+J+R%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1996-01-01&rft.volume=&rft.issue=139&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of chemoprevention in cancer control. AN - 78543885; 8923016 AB - Chemoprevention is a promising strategy for cancer prevention that is international in application and may be more immediate in worldwide impact than either dietary modification or prevention of exposure to carcinogens. Precedent for a chemopreventive approach is found in cardiology, where cholesterol-lowering, antihypertensive and antiplatelet agents are administered to prevent heart disease progression in high-risk individuals. The multistep nature of carcinogenesis provides many opportunities for chemopreventive interventions with agents targeted to specific mechanisms involved in cancer initiation, promotion and progression. The well-defined strategy for development of chemopreventive agents includes evaluation of leads from epidemiological and experimental research; preclinical efficacy testing of candidate agents; and assessments of the preclinical and clinical safety, toxicity, bioavailability and pharmacokinetics of those that are the most promising. Short-term clinical trials then determine optimal dosing and characterize the efficacy of the best agents against intermediate biomarkers of cancer. Large-scale randomized trials, the final stage of this strategy, evaluate whether the chemopreventive agents actually do reduce cancer risk. The systematic development of agents is coupled with basic research into mechanisms of action and subsequent application of the findings to agent design and discovery. Major objectives of chemopreventive drug development include identification and validation of intermediate biomarkers that are accurate predictors of future cancer incidence and that can serve as surrogate and points for clinical disease. Complementary international efforts to standardize chemopreventive trial designs and protocols among communities worldwide would help ensure a valid comparison of results across countries and more efficient and effective cancer-preventive regimens. JF - IARC scientific publications AU - Greenwald, P AU - Kelloff, G J AD - Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 13 EP - 22 IS - 139 SN - 0300-5038, 0300-5038 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Humans KW - Clinical Trials as Topic KW - Chemoprevention -- methods KW - Anticarcinogenic Agents -- therapeutic use KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78543885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=The+role+of+chemoprevention+in+cancer+control.&rft.au=Greenwald%2C+P%3BKelloff%2C+G+J&rft.aulast=Greenwald&rft.aufirst=P&rft.date=1996-01-01&rft.volume=&rft.issue=139&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The kynurenine pathway and neurologic disease. Therapeutic strategies. AN - 78523176; 8906254 AB - The neurotoxic effects of QUIN have been well established. Clinical conditions have been identified where substantial elevations in CNS QUIN levels occur. There is a relationship between the severity of neurologic impairments and macrophage activation, with the magnitude of the increases in QUIN. The magnitude of QUIN increases in experimental immune activation, and macrophages in vitro, are highest in non-human primates, intermediate in gerbils and guinea pigs, and lowest in mice and rats. Macrophages in vitro are a useful screening system to evaluate potential inhibitors of the kynurenine pathway. Several models of CNS inflammation are available, including brain injury in post-ischemic gerbils and spinal cord injury in guinea pigs. 4-Chloro-3-hydroxyanthranilate is a potent inhibitor of QUIN production by macrophages and reduces QUIN accumulations in spinal cord injury. Such reductions are associated with significant neurologic improvements in the early post-injury period. The results support further investigation of QUIN as a mediator of neurologic dysfunction and damage in neurologic diseases. JF - Advances in experimental medicine and biology AU - Heyes, M P AD - Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 125 EP - 129 VL - 398 SN - 0065-2598, 0065-2598 KW - Neurotoxins KW - 0 KW - 3-Hydroxyanthranilic Acid KW - 1UQB1BT4OT KW - 4-chloro-3-hydroxyanthranilic acid KW - 23219-33-2 KW - Kynurenine KW - 343-65-7 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Animals KW - Gerbillinae KW - Spinal Cord -- physiopathology KW - 3-Hydroxyanthranilic Acid -- pharmacology KW - Guinea Pigs KW - Humans KW - Macrophage Activation KW - Mice KW - Spinal Cord Injuries -- physiopathology KW - Primates KW - Rats KW - Spinal Cord -- drug effects KW - 3-Hydroxyanthranilic Acid -- analogs & derivatives KW - Quinolinic Acid -- metabolism KW - Nervous System Diseases -- immunology KW - Kynurenine -- metabolism KW - Nervous System Diseases -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78523176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=The+kynurenine+pathway+and+neurologic+disease.+Therapeutic+strategies.&rft.au=Heyes%2C+M+P&rft.aulast=Heyes&rft.aufirst=M&rft.date=1996-01-01&rft.volume=398&rft.issue=&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Aneuploidy in germ cells: etiologies and risk factors. AN - 78520276; 8908176 AB - A 2 1/2-day workshop on germ cell aneuploidy was convened September 11-13, 1995 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina to discuss current understandings of the etiology and origin of human aneuploidy, especially in regard to potential environmental causes, and to identify gaps in our research knowledge. The workshop was designed to facilitate interactions among research experts conducting studies on the fundamental biology of chromosomal movement and segregation, on aneuploidy as a human clinical problem, and on toxicological aspects of aneuploidy induction. Overview presentations provided perspectives on aneuploidy as a human clinical problem, the genetics of aneuploidy, and the issues of concern in toxicological testing and regulatory risk assessment. The four chairs introduced the topics for each of their workgroups, setting the stage for subsequent, in-depth discussions on (1) chromosome mover components, (2) altered recombination, (3) parental age effects, and (4) differential chromosome susceptibility. From these discussions, gaps in our research knowledge related to the role of the environment in the etiology of aneuploidy and associated molecular, cellular, and genetic processes involved were identified, and will be used to establish a research agenda for filling those gaps. JF - Environmental and molecular mutagenesis AU - Bishop, J B AU - Dellarco, V L AU - Hassold, T AU - Ferguson, L R AU - Wyrobek, A J AU - Friedman, J M Y1 - 1996 PY - 1996 DA - 1996 SP - 159 EP - 166 VL - 28 IS - 3 KW - Mutagens KW - 0 KW - Index Medicus KW - Animals KW - Meiosis KW - Maternal Age KW - Humans KW - Chromosomes, Human KW - Recombination, Genetic KW - Mutagens -- toxicity KW - Mice KW - Down Syndrome KW - Aneuploidy KW - Germ Cells -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78520276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Aneuploidy+in+germ+cells%3A+etiologies+and+risk+factors.&rft.au=Bishop%2C+J+B%3BDellarco%2C+V+L%3BHassold%2C+T%3BFerguson%2C+L+R%3BWyrobek%2C+A+J%3BFriedman%2C+J+M&rft.aulast=Bishop&rft.aufirst=J&rft.date=1996-01-01&rft.volume=28&rft.issue=3&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-09 N1 - Date created - 1996-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxyl radical formation in aqueous solutions of N,N-dimethylformamide, N-methylformamide, and dimethylsulfoxide by ultrasound: implications for sonosensitized cell killing. AN - 78519694; 8903689 AB - Sonodynamic therapy, which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. The sonodynamic effect was found for a number of structurally unrelated compounds, and the underlying mechanisms are still unknown. Recently, Jeffers et al. (J. Acoust. Soc. Am. 97:669-676; 1995) have shown that the sonodynamic action of nontoxic concentrations of N,N-dimethylformamide (DMF), N-methyl formamide (MMF), and dimethylsulfoxide (DMSO) combined with ultrasound, on killing of cultured HL-60 human promyelocytic leukemia cells, and attributed this toxic effect to unknown short lived reactive species produced from these solutes by ultrasonic cavitation. Using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) in nitrogen-saturated aqueous solutions of DMF, MMF, or DMSO exposed to 50 kHz ultrasound, we detected formation of .CH3 and .CH2N(CH3)CHO radical adducts for DMF, mostly .CH2NHCHO adducts for MMF, and .CH3 adducts for DMSO. These radicals were formed either by reactions of the solutes with ultrasound-generated .H and .OH radicals (such as .CH2R-type radicals in DMF and MMF, and .CH3 radicals in DMSO), or by direct pyrolysis of the weak bonds in the solute molecules (e.g., .CH3 radicals from DMF). In air-saturated sonicated solutions these carbon centered radicals were converted to the corresponding peroxyl radicals and spin trapped with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO); .OOCH2N(CH3)CHO radicals were identified in DMF, .OOCH2NHCHO radicals in MMF, and .OOCH3 radicals in DMSO solutions. We suggest that these radical species by virtue of their longer lifetimes and higher selectivity, compared to .OH radicals, which are also formed in sonicated solutions, are the species responsible for sonodynamic cell killing by the combined effect of ultrasound with DMF, MMF, or DMSO. JF - Free radical biology & medicine AU - Misik, V AU - Riesz, P AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 129 EP - 138 VL - 20 IS - 1 SN - 0891-5849, 0891-5849 KW - Benzenesulfonates KW - 0 KW - Formamides KW - Free Radicals KW - Nitroso Compounds KW - Peroxides KW - Spin Labels KW - perhydroxyl radical KW - 3170-83-0 KW - Hydroxyl Radical KW - 3352-57-6 KW - 3,5-dibromo-4-nitrosobenzenesulfonate KW - 83016-63-1 KW - Dimethylformamide KW - 8696NH0Y2X KW - methylformamide KW - XPE4G7Y986 KW - Dimethyl Sulfoxide KW - YOW8V9698H KW - Index Medicus KW - Nitroso Compounds -- metabolism KW - Dimethylformamide -- metabolism KW - Hydroxyl Radical -- metabolism KW - Benzenesulfonates -- metabolism KW - Hydroxyl Radical -- pharmacology KW - Neoplasms -- therapy KW - Free Radicals -- metabolism KW - Electron Spin Resonance Spectroscopy KW - Cell Death KW - Dimethyl Sulfoxide -- metabolism KW - Free Radicals -- chemistry KW - Free Radicals -- pharmacology KW - Formamides -- metabolism KW - Peroxides -- metabolism KW - Ultrasonics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78519694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Peroxyl+radical+formation+in+aqueous+solutions+of+N%2CN-dimethylformamide%2C+N-methylformamide%2C+and+dimethylsulfoxide+by+ultrasound%3A+implications+for+sonosensitized+cell+killing.&rft.au=Misik%2C+V%3BRiesz%2C+P&rft.aulast=Misik&rft.aufirst=V&rft.date=1996-01-01&rft.volume=20&rft.issue=1&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-14 N1 - Date created - 1997-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathogenesis of L-tryptophan eosinophilia myalgia syndrome. AN - 78516801; 8906284 AB - Taken together, these studies suggest that many different etiologic agents alone or together may initiate the common final pathways of tissue pathologic response resulting in the clinical syndrome of eosinophilia, myalgias and fasciitis. Tryptophan itself may contribute to some of the scarring features of the illness, while impure L-tryptophan, and one or more of the impurities cause the characteristic features of the illness. The altered tryptophan metabolism in EMS is secondary to inflammation. JF - Advances in experimental medicine and biology AU - Sternberg, E M AD - National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 325 EP - 330 VL - 398 SN - 0065-2598, 0065-2598 KW - Tryptophan KW - 8DUH1N11BX KW - 5-Hydroxytryptophan KW - C1LJO185Q9 KW - Index Medicus KW - Animals KW - Eosinophils -- physiology KW - 5-Hydroxytryptophan -- toxicity KW - Humans KW - Eosinophilia -- chemically induced KW - Eosinophils -- drug effects KW - Eosinophilia-Myalgia Syndrome -- epidemiology KW - Tryptophan -- adverse effects KW - Eosinophilia-Myalgia Syndrome -- etiology KW - Tryptophan -- metabolism KW - Eosinophilia-Myalgia Syndrome -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78516801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Pathogenesis+of+L-tryptophan+eosinophilia+myalgia+syndrome.&rft.au=Sternberg%2C+E+M&rft.aulast=Sternberg&rft.aufirst=E&rft.date=1996-01-01&rft.volume=398&rft.issue=&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional control of muscle plasticity: differential regulation of troponin I genes by electrical activity. AN - 78508408; 8900050 AB - Plasticity of the skeletal muscle phenotype can result from the selective repression and activation of gene expression in response to innervation patterns. Motoneurons, eliciting different patterns of depolarization, regulate the contractile properties of the myofibers they innervate by selectively activating expression of genes encoding fiber-type-specific (fast vs. slow) contractile proteins. We have analyzed the regulation of the troponin I slow (TnIs) and fast (TnIf) genes as a model to study the molecular mechanisms regulating fiber-type plasticity. We found that expression of the two TnI isoforms is downregulated by denervation. Moreover, TnI expression is upregulated by specific patterns of electrical activity [10 Hz vs. 100 Hz] used to depolarize muscle. We previously isolated the rat TnIs gene and demonstrated that regulatory sequences reside in its upstream region and second intron [Banerjee-Basu S, Buonanno A (1993), Mol Cell Biol 12:5024-5032]. Using transgenic mice, we show that the upstream region of the TnIs gene extending from -949 to +50 is sufficient to confer transcription specifically in slowtwitch muscles. Serial deletions of the TnIs upstream and intronic regions were generated in a CAT reporter vector to delineate transcriptional regulatory elements in transiently transfected Sol8 myotubes. Sequences necessary to confer the highest levels of TnIs transcription mapped to the upstream region between -0.95 and -0.72 kb, and to a 56 bp sequence located in the second intron. Comparison of the at sequence between -0.95 and -0.72 to the human TnIs gene identified a highly homologous region of 128 bp that we named the TnI SURE (slow upstream regulatory element). Alignment of these two SURE sequences with the quail TnI fast intronic regulatory element identified common motifs, namely, two A/T-rich sequences (A/T1 and A/T2) with homology to homeotic protein and MEF2 binding sites, a CACC box, an E box, and a novel motif (GCAGGCA) that we denoted the CAGG box. Mutation of either the A/T2 site, E box, or CAGG box practically abolish the SURE function in transfected myotubes; mutation of the A/T1 and CACC sites has a lesser effect. Using competitive electrophoretic mobility shift assays with nuclear extracts derived from Sol8 myotubes, we demonstrate specific binding to these motifs. The A/T1 and A/T2 sites are shown to form different complexes. The A/T2 site, which bears extensive homology to a MEF2 site, forms complexes that are super shifted by MEF2A antisera and that are competed by a consensus MEF2 site present in the MCK enhancer. Our results demonstrate that the linear arrangement of DNA sequence motifs is conserved in the regulatory elements of the TnI slow and fast genes and suggest that the interaction of multiple protein-DNA complexes are necessary for enhancer function. JF - Developmental genetics AU - Calvo, S AU - Stauffer, J AU - Nakayama, M AU - Buonanno, A AD - Unit on Molecular Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 169 EP - 181 VL - 19 IS - 2 SN - 0192-253X, 0192-253X KW - Troponin I KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Muscle Denervation KW - Mice, Transgenic KW - Rats KW - Mutagenesis, Site-Directed KW - Phenotype KW - Base Sequence KW - Sequence Alignment KW - Transfection KW - Cells, Cultured KW - Sciatic Nerve -- injuries KW - Models, Genetic KW - Rats, Wistar KW - Genes, Reporter KW - Coturnix -- genetics KW - Species Specificity KW - Troponin I -- biosynthesis KW - Enhancer Elements, Genetic KW - Muscle, Skeletal -- innervation KW - Transcription, Genetic KW - Promoter Regions, Genetic -- genetics KW - Gene Expression Regulation KW - Troponin I -- genetics KW - Electric Stimulation KW - Muscle, Skeletal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78508408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+genetics&rft.atitle=Transcriptional+control+of+muscle+plasticity%3A+differential+regulation+of+troponin+I+genes+by+electrical+activity.&rft.au=Calvo%2C+S%3BStauffer%2C+J%3BNakayama%2C+M%3BBuonanno%2C+A&rft.aulast=Calvo&rft.aufirst=S&rft.date=1996-01-01&rft.volume=19&rft.issue=2&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Developmental+genetics&rft.issn=0192253X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-03 N1 - Date created - 1997-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age- and dose-dependent transplacental carcinogenesis by N-nitrosoethylurea in Syrian golden hamsters. AN - 78491728; 8898973 AB - Syrian golden hamsters have a very short period (15 days) of gestation. The implantation of the blastocyst occurs on day 5, embryogenesis proceeds very rapidly thereafter and neural tube closure is completed by day 9. In the present study the effects of two different doses of N-nitrosoethylurea (NEU) administered at various stages of gestation were quantitatively evaluated in Syrian golden hamsters. NEU at either 0.2 or 0.5 mmol/kg was administered transplacentally as a single i.p. injection to pregnant hamsters on gestation days 7, 8, 9, 10, 11, 12, 13, or 14. The incidence, latency period and multiplicity of tumors varied with the dose of NEU and the stage of development at the time of NEU administration. Although tumors of the peripheral nervous system predominated, a variety of other tumors, including melanomas and visceral tumors of epithelial and mesenchymal origin, were also observed in hamster offspring exposed transplacentally to NEU. Sensitivity to transplacental carcinogenesis was maximal during late gestation and very low before day 9. JF - Journal of cancer research and clinical oncology AU - Diwan, B A AU - Rehm, S AU - Rice, J M AD - Biological Carcinogenesis and Development Program, SAIC Frederick, NCI-FCRDC, MD 21702-1201, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 643 EP - 652 VL - 122 IS - 11 SN - 0171-5216, 0171-5216 KW - Carcinogens KW - 0 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Maternal-Fetal Exchange KW - Animals KW - Age Factors KW - Dose-Response Relationship, Drug KW - Peripheral Nervous System KW - Mesocricetus KW - Nervous System Neoplasms -- chemically induced KW - Male KW - Female KW - Pregnancy KW - Cricetinae KW - Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78491728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cancer+research+and+clinical+oncology&rft.atitle=Age-+and+dose-dependent+transplacental+carcinogenesis+by+N-nitrosoethylurea+in+Syrian+golden+hamsters.&rft.au=Diwan%2C+B+A%3BRehm%2C+S%3BRice%2C+J+M&rft.aulast=Diwan&rft.aufirst=B&rft.date=1996-01-01&rft.volume=122&rft.issue=11&rft.spage=643&rft.isbn=&rft.btitle=&rft.title=Journal+of+cancer+research+and+clinical+oncology&rft.issn=01715216&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology. AN - 78488068; 8895987 JF - Progress in clinical and biological research AU - Shields, P G AD - Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 141 EP - 157 VL - 395 SN - 0361-7742, 0361-7742 KW - Biomarkers KW - 0 KW - Carcinogens, Environmental KW - Index Medicus KW - Risk KW - Genes KW - Cocarcinogenesis KW - Disease Susceptibility KW - Carcinogens, Environmental -- adverse effects KW - Polymorphism, Genetic KW - Humans KW - Environmental Exposure KW - Epidemiologic Methods KW - Neoplasms -- epidemiology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78488068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Molecular+epidemiology.&rft.au=Shields%2C+P+G&rft.aulast=Shields&rft.aufirst=P&rft.date=1996-01-01&rft.volume=395&rft.issue=&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-04 N1 - Date created - 1997-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in the probability of alcohol treatment. AN - 78474119; 8880661 AB - Interview data from 7,359 adults 18 years of age and over who met the DSM-IV criteria for alcohol abuse or dependence at some point during their lives revealed that 23.0% of the men and 15.1% of the women ever received treatment for alcohol problems. The median interval from onset of disorder to first treatment was between 2 and 3 years longer for men than women. This difference did not result from women being more likely than men to initiate treatment shortly after onset of an alcohol use disorder, but rather from men being more likely than women to initiate treatment in the period well after onset. Excluding treatment initiated prior to the clinical onset of the disorders or after cessation of drinking, men's and women's cumulative conditional probabilities of having initiated treatment by 30 years after onset of alcohol abuse or dependence were .424 and .356, respectively. Within the first 8 years after onset of abuse or dependence, men's and women's probabilities of initiating treatment were about the same, but men were 13% to 20% more likely to initiate treatment in the period from 8 to 25 years after onset. Use of proportional hazards models to adjust for factors including sociodemographic characteristics, prior consumption, severity of disorder, and comorbid drug use and depression revealed that men's and women's likelihoods of ever having received treatment did not differ for the most severely affected, those with 20 or more symptoms of abuse or dependence. Among those less severely affected, the male-to-female ratio in the likelihood of treatment declined with severity from 1.75 (1 symptom) to 1.24 (15 symptoms). JF - Journal of substance abuse AU - Dawson, D A AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 211 EP - 225 VL - 8 IS - 2 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Probability KW - Sex Factors KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Patient Acceptance of Health Care -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78474119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Gender+differences+in+the+probability+of+alcohol+treatment.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1996-01-01&rft.volume=8&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-29 N1 - Date created - 1997-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of clinical resistance to 5-fluorouracil chemotherapy. AN - 78470557; 8886453 JF - Cancer treatment and research AU - Chu, E AU - Allegra, C J AD - NCI-Navy Medical Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20889, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 175 EP - 195 VL - 87 SN - 0927-3042, 0927-3042 KW - Antimetabolites, Antineoplastic KW - 0 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Thymidylate Synthase -- genetics KW - Thymidylate Synthase -- antagonists & inhibitors KW - Animals KW - Humans KW - Drug Resistance KW - Fluorouracil -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78470557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+treatment+and+research&rft.atitle=Mechanisms+of+clinical+resistance+to+5-fluorouracil+chemotherapy.&rft.au=Chu%2C+E%3BAllegra%2C+C+J&rft.aulast=Chu&rft.aufirst=E&rft.date=1996-01-01&rft.volume=87&rft.issue=&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Cancer+treatment+and+research&rft.issn=09273042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence and correlates of drug use and DSM-IV drug dependence in the United States: results of the National Longitudinal Alcohol Epidemiologic Survey. AN - 78469174; 8880660 AB - This study presents updated estimates of the prevalence and examines the correlates of drug use and dependence in a representative sample of the U.S. population. The prevalence of lifetime drug use was 15.6%, with 4.9% of the respondents reporting drug use during the past 12 months. Lifetime and 12-month prevalence of drug dependence were estimated at 2.9% and 0.8%, respectively. Men were significantly more likely to use drugs than women, and drug use and dependence were much more common among cohorts born after World War II. The data indicated that rates of dependence among women were quickly approaching the rates among men in the younger cohorts. Members of the youngest cohort, between the ages of 18 and 24 years at the time of the interview, were more likely to use drugs, to become dependent, and to persist in dependence compared to the older cohorts, including Cohort 2 who experienced adolescence at the height of widespread introduction of illicit drugs among youth in the mid-1960s. The demographic correlates of first use, onset of dependence, and persistence of dependence varied as a function of the stage of progression. Implications of these findings are discussed in terms of changes over time in drugs of choice and dependence liability and vulnerability among recent drug users. JF - Journal of substance abuse AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 195 EP - 210 VL - 8 IS - 2 SN - 0899-3289, 0899-3289 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Cross-Sectional Studies KW - Humans KW - Cohort Studies KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Substance-Related Disorders -- diagnosis KW - Psychiatric Status Rating Scales KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78469174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Prevalence+and+correlates+of+drug+use+and+DSM-IV+drug+dependence+in+the+United+States%3A+results+of+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1996-01-01&rft.volume=8&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-29 N1 - Date created - 1997-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modified oral anticoagulant potency in an amitriptyline-treated patient? AN - 78453304; 8876616 AB - We report the case of a 74-year-old female patient who received the antide-pressant amitriptyline because of a major depression. Incidence of acute lower extremity venous thrombosis required an additional oral anticoagulant therapy with phenprocoumon. During the simultaneous adjustment of both substances, the Quick value displayed great fluctuations which only disappeared after discontinuation of the amitriptyline medication. This finding is discussed as an aspect of a possible drug-drug interaction between amitriptyline and phenprocoumon. JF - Acta haematologica AU - Hampel, H AU - Berger, C AU - Müller-Spahn, F AD - National Institutes of Health (NIH), National Institute on Aging (NIA), Laboratory of Neurosciences (LNS), Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 178 EP - 180 VL - 96 IS - 3 SN - 0001-5792, 0001-5792 KW - Anticoagulants KW - 0 KW - Antidepressive Agents, Tricyclic KW - Amitriptyline KW - 1806D8D52K KW - Phenprocoumon KW - Q08SIO485D KW - Index Medicus KW - Humans KW - Aged KW - Female KW - Antidepressive Agents, Tricyclic -- administration & dosage KW - Amitriptyline -- administration & dosage KW - Drug Interactions KW - Amitriptyline -- adverse effects KW - Phenprocoumon -- administration & dosage KW - Anticoagulants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78453304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+haematologica&rft.atitle=Modified+oral+anticoagulant+potency+in+an+amitriptyline-treated+patient%3F&rft.au=Hampel%2C+H%3BBerger%2C+C%3BM%C3%BCller-Spahn%2C+F&rft.aulast=Hampel&rft.aufirst=H&rft.date=1996-01-01&rft.volume=96&rft.issue=3&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Acta+haematologica&rft.issn=00015792&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-20 N1 - Date created - 1996-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutathione inhibits experimental oral carcinogenesis, p53 expression, and angiogenesis. AN - 78450738; 8875560 AB - Previous studies have shown that reduced glutathione (GSH) inhibits experimental oral carcinogenesis in the hamster buccal pouch model. To gain further understanding of molecular mechanisms in the anticancer effect of GSH, these studies examined levels of p53 protein expression. 7,12-Dimethylbenz[a]anthracene (DMBA) was applied to the buccal pouches of 20 Syrian Golden hamsters (Mesocricetus auratus) in a 0.5% solution in mineral oil thrice weekly for 14 weeks. In 10 animals, 10 mg/kg reduced glutathione (GSH) in 0.5 ml of mineral oil was administered by mouth thrice weekly on days alternate to the DMBA painting. An additional 20 animals served as DMBA-untreated and GSH controls. At the termination of the experimental period, there were fewer tumors in the DMBA-GSH than in the DMBA tumor control group, and the tumors were smaller (tumor burden 315 vs. 3,040 mm3). Histologically, the DMBA-GSH group showed a marked reduction in dysplasia, carcinoma in situ, and invasive epidermoid carcinoma sites. Immunohistochemically, by use of monoclonal antibodies for wild-type p53 (PAb 246), changes were observed in protein expression levels at dysplastic sites and within the malignant tumors. Staining for p53 protein was slightly increased in dysplasia and squamous cell carcinoma in the tumor control animals (painted with DMBA) compared with the untreated controls that were free of tumors. In the GSH and DMBA treatment group, p53 protein expression levels were strongly increased in dysplastic and tumor sites. The significant inhibition of oral carcinogenesis associated with the administration of GSH was correlated with the increased levels of the wild-type p53 tumor suppressor gene, suggesting its possible use as a biomarker for GSH chemoprevention. The inhibition of oral carcinogenesis by reduced GSH was also related to a very significant inhibition of tumor angiogenesis, defined by factor VIII staining. Thus angiogenesis inhibition may be an additional mechanism for antioxidant chemoprevention, and this suggests another possible biomarker for antioxidant chemoprevention. JF - Nutrition and cancer AU - Schwartz, J L AU - Shklar, G AD - National Institute of Dental Research (Molecular Epidemiology and Oral Disease Indicators Branch), Bethesda, MD 20892, USA. schwartz@yoda.midr.nih.gov Y1 - 1996 PY - 1996 DA - 1996 SP - 229 EP - 236 VL - 26 IS - 2 SN - 0163-5581, 0163-5581 KW - Antioxidants KW - 0 KW - Tumor Suppressor Protein p53 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Factor VIII KW - 9001-27-8 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Mesocricetus KW - Factor VIII -- analysis KW - Immunohistochemistry KW - Male KW - Cricetinae KW - Mouth Neoplasms -- chemically induced KW - Glutathione -- therapeutic use KW - Tumor Suppressor Protein p53 -- analysis KW - Mouth Neoplasms -- prevention & control KW - Antioxidants -- therapeutic use KW - Neovascularization, Pathologic -- prevention & control KW - Mouth Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78450738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Glutathione+inhibits+experimental+oral+carcinogenesis%2C+p53+expression%2C+and+angiogenesis.&rft.au=Schwartz%2C+J+L%3BShklar%2C+G&rft.aulast=Schwartz&rft.aufirst=J&rft.date=1996-01-01&rft.volume=26&rft.issue=2&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-09 N1 - Date created - 1997-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicotine dependence in women. AN - 78438127; 8868542 AB - Cigarette smoking is the most preventable cause of death in the United States, accounting for the deaths of approximately 140,000 women annually. Despite the known health risks, women continue to begin and continue smoking at high rates. Like other addictive drugs, nicotine becomes reinforcing with repeated use, induces euphoric sensations, and is self-administered. Tolerance to nicotine's effects develops rapidly and leads to increased use. Reducing or suppressing tobacco consumption produces a withdrawal syndrome characterized by irritability, difficulty concentrating, cognitive impairments, and weight gain. These withdrawal symptoms, along with other factors, lead to relapse rates comparable to those following cessation from other addictive drugs. This review article discusses the pathogenesis of nicotine addiction compared to other addictive substances such as cocaine and heroin with an effort to provide comparative data for men and women. JF - Journal of the American Medical Women's Association (1972) AU - Fant, R V AU - Everson, D AU - Dayton, G AU - Pickworth, W B AU - Henningfield, J E AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224, USA. PY - 1996 SP - 19 EP - 20, 22-4, 28 VL - 51 IS - 1-2 SN - 0098-8421, 0098-8421 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Behavior, Addictive KW - Substance Withdrawal Syndrome -- physiopathology KW - Sex Factors KW - Motivation KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Tobacco Use Disorder -- physiopathology KW - Women's Health KW - Tobacco Use Disorder -- epidemiology KW - Tobacco Use Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78438127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Medical+Women%27s+Association+%281972%29&rft.atitle=Nicotine+dependence+in+women.&rft.au=Fant%2C+R+V%3BEverson%2C+D%3BDayton%2C+G%3BPickworth%2C+W+B%3BHenningfield%2C+J+E&rft.aulast=Fant&rft.aufirst=R&rft.date=1996-01-01&rft.volume=51&rft.issue=1-2&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Women%27s+Association+%281972%29&rft.issn=00988421&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternating bolus and continuous infusion 5-fluorouracil: a strategy to overcome resistance to this fluoropyrimidine in advanced colorectal cancer patients. AN - 78430986; 8862009 AB - Focusing our effort on the importance of FUra scheduling we have tested the hypothesis that pulse and continuous infusion (CI) of the fluoropyrimidine have different mechanisms of cytotoxicity. Our initial approach was to compare the mechanism of resistance of a cell line resistant to a short term exposure to FUra (HCT-8/FU4hR) to that of a cell line resistant to a prolonged exposure to the fluoropyrimidine (HCT-8/FU7dR). Cytotoxicity studies showed that HCT-8/FU4hR cells were still sensitive to FUra given as a 7-d exposure, suggesting different mechanisms of resistance. Indeed, rapid recovery of TS activity after drug removal was evident in the HTC-8/FU7dR cell line while HCT-8/FU4hR cells were similar to the parental cell line with regard to both the degree of in situ TS inhibition by FUra and duration of inhibition after FUra removal. In contrast, labelling studies with [3H-6]FUra(4 h exposure, 100 microM) showed that the incorporation of the fluoropyrimidine into RNA is significantly decreased in HCT-8/FU4hR cells as compared to parental HCT-8 cells. Given the lack of cross resistance between the two schedules in vitro, a pilot trial was done on patients with colorectal cancer refractory to bolus FUra. On 15 patients failing after FUra+LV or FUra alone 1 PR, 3 MR, 3 SD and 8 P were observed, confirming a certain degree of activity of CI FUra in patients clinically resistant to bolus FUra. Based on this rationale, a phase II trial of schedule-oriented biochemical modulation of FUra in advanced colorectal cancer patients was conducted, employing a hybrid regimen of 2 biweekly cycles of FUra bolus (600 mg/sqm), preceeded by (24 h interval) methotrexate, 200 mg/sqm (in order to maximize the RNA effect of the drug) alternating with Fura continuous infusion, 200 mg/sqm daily for 3 weeks, modulated by leucovorin, 20 mg/sqm weekly bolus (in order to maximize the DNA effect). Thirty-three consecutive patients (median ECOG PS 1) with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study, from February 1992 to August 1993. Three complete and 13 partial responses were obtained among these 33 patients (RR = 48%, 95% confidence limits, 31-66%). After a median follow-up time of 23 months, 16 patients are still alive. The median progression free survival and overall survival were 9.6 and 20.8 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3% and vomiting 3% for the bolus part and 21%, 3% and 6% respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen. In conclusion, this experimental and clinical project has generated a novel regimen of schedule oriented biochemical modulation that is twice as active and half as toxic compared to bolus FU+LV given with either the daily x 5 or the weekly schedule. This high clinical activity is very encouraging, especially considering that 1) consecutive patients were entered, 2) the responses were independently reviewed, 3) the progression free survival and survival were much longer than those actually reported for this disease, 4) the toxicity of the program, in particular the bolus regimen, was relatively low allowing further intensification. JF - Cytotechnology AU - Guglielmi, A AU - Aschele, C AU - Grossi, F AU - Tixi, L AU - Sobrero, A AD - Dept. of Medical Oncology, National Cancer Institute, Genova, Italy. Y1 - 1996 PY - 1996 DA - 1996 SP - 215 EP - 219 VL - 19 IS - 3 SN - 0920-9069, 0920-9069 KW - Antimetabolites, Antineoplastic KW - 0 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Biotechnology KW - Disease-Free Survival KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Injections, Intravenous KW - Tumor Cells, Cultured -- drug effects KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Lung Neoplasms -- secondary KW - Humans KW - Leucovorin -- administration & dosage KW - Lung Neoplasms -- drug therapy KW - Disease Progression KW - Palliative Care KW - Leucovorin -- adverse effects KW - Pilot Projects KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Drug Resistance, Neoplasm KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Liver Neoplasms -- secondary KW - Methotrexate -- adverse effects KW - Liver Neoplasms -- drug therapy KW - Treatment Outcome KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Methotrexate -- administration & dosage KW - Remission Induction KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Colorectal Neoplasms -- mortality KW - Antimetabolites, Antineoplastic -- adverse effects KW - Adenocarcinoma -- mortality KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Colorectal Neoplasms -- drug therapy KW - Fluorouracil -- therapeutic use KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Colorectal Neoplasms -- pathology KW - Adenocarcinoma -- secondary KW - Fluorouracil -- pharmacokinetics KW - Adenocarcinoma -- drug therapy KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78430986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotechnology&rft.atitle=Alternating+bolus+and+continuous+infusion+5-fluorouracil%3A+a+strategy+to+overcome+resistance+to+this+fluoropyrimidine+in+advanced+colorectal+cancer+patients.&rft.au=Guglielmi%2C+A%3BAschele%2C+C%3BGrossi%2C+F%3BTixi%2C+L%3BSobrero%2C+A&rft.aulast=Guglielmi&rft.aufirst=A&rft.date=1996-01-01&rft.volume=19&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Cytotechnology&rft.issn=09209069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of cyclic AMP accumulation in EBV-transformed human B-lymphocytes: effects of dopamine agonists, isoproterenol, prostaglandin E1, cholera toxin, forskolin, and phorbol 12-myristate-13 acetate. AN - 78427374; 8861180 AB - 1. Phorbol 12-myristate-13-acetate (PMA), a protein kinase C activator, elevated cyclic AMP accumulation in EBV-transformed human B-lymphocytes, and potentiated isoproterenol-, prostaglandin- (PGE1), cholera toxin-, and forskolin-stimulated cyclic AMP accumulation. 2. The dopamine D1 receptor agonist, SKF38393 (10(-7) to 10(-5) MH, had no effect on cyclic AMP accumulation in transformed human B-lymphocytes. 3. The dopamine D2 receptor agonist, quinpirole (10(-7) to 10(-5) MH did not inhibit cyclic AMP accumulation even when cyclic AMP accumulation was maximized by the addition of PMA and forskolin. 4. These data suggest that dopamine D1- and D2-receptor coupling to a cyclic AMP generating system is not present at detectable levels in transformed human B-lymphocytes. JF - Progress in neuro-psychopharmacology & biological psychiatry AU - Natsukari, N AU - Kulaga, H AU - Baker, I AU - Wyatt, R J AU - Masserano, J M AD - National Institute of Mental Health, Neuroscience Center at Saint Elizabeth Hospital, Neuropsychiatry Branch, Washington, D.C., USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 99 EP - 108 VL - 20 IS - 1 SN - 0278-5846, 0278-5846 KW - Dopamine Agonists KW - 0 KW - Phorbol Esters KW - Colforsin KW - 1F7A44V6OU KW - phorbol-12,13-diacetate KW - 24928-15-2 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Alprostadil KW - F5TD010360 KW - Isoproterenol KW - L628TT009W KW - Index Medicus KW - Phorbol Esters -- pharmacology KW - Dose-Response Relationship, Drug KW - Dopamine Agonists -- pharmacology KW - Humans KW - Alprostadil -- pharmacology KW - B-Lymphocytes -- drug effects KW - Colforsin -- pharmacology KW - Cyclic AMP -- metabolism KW - Cholera Toxin -- pharmacology KW - Isoproterenol -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78427374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.atitle=Evaluation+of+cyclic+AMP+accumulation+in+EBV-transformed+human+B-lymphocytes%3A+effects+of+dopamine+agonists%2C+isoproterenol%2C+prostaglandin+E1%2C+cholera+toxin%2C+forskolin%2C+and+phorbol+12-myristate-13+acetate.&rft.au=Natsukari%2C+N%3BKulaga%2C+H%3BBaker%2C+I%3BWyatt%2C+R+J%3BMasserano%2C+J+M&rft.aulast=Natsukari&rft.aufirst=N&rft.date=1996-01-01&rft.volume=20&rft.issue=1&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.issn=02785846&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-11 N1 - Date created - 1997-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of dextromethorphan on kainic acid-induced seizures in the rat. AN - 78418083; 8856734 AB - Several studies have shown that dextromethorphan (DM) has both anticonvulsant and proconvulsant effects depending on the animal model. In this study, we examined the effects of DM on three parameters associated with kainic acid (KA)-induced seizures: cell loss in the hippocampus, increased AP-1 DNA binding activity and increased c-Jun and fos-related antigen (FRA) expression. KA administration (8 mg/kg, ip) produced robust behavioral convulsions lasting 4-6 hr. Pretreatment with DM (12.5-75 mg/kg, po) 15 min before KA injections reduced the seizures as well as mortality in a dose-dependent manner. Histological studies revealed a severe loss of cells in the CA1 and CA3 fields of the hippocampus in KA-treated rats. DM pretreatment also reduced this cell loss in a dose-dependent fashion. Biochemical studies showed that DM pretreatment also attenuated the KA-induced increase of AP-1 binding activity and c-Jun/FRA expression in the hippocampus. These results indicate that DM is an effective antagonist of KA. JF - Neurotoxicology AU - Kim, H C AU - Pennypacker, K R AU - Bing, G AU - Bronstein, D AU - McMillian, M K AU - Hong, J S AD - Section of Neuropharmacology, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 375 EP - 385 VL - 17 IS - 2 SN - 0161-813X, 0161-813X KW - Excitatory Amino Acid Agonists KW - 0 KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Dextromethorphan KW - 7355X3ROTS KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Blotting, Western KW - Transcription Factor AP-1 -- metabolism KW - Proto-Oncogene Proteins c-fos -- analysis KW - Proto-Oncogene Proteins c-jun -- analysis KW - Male KW - Seizures -- chemically induced KW - Hippocampus -- metabolism KW - Seizures -- prevention & control KW - Hippocampus -- pathology KW - Dextromethorphan -- therapeutic use KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78418083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=The+effects+of+dextromethorphan+on+kainic+acid-induced+seizures+in+the+rat.&rft.au=Kim%2C+H+C%3BPennypacker%2C+K+R%3BBing%2C+G%3BBronstein%2C+D%3BMcMillian%2C+M+K%3BHong%2C+J+S&rft.aulast=Kim&rft.aufirst=H&rft.date=1996-01-01&rft.volume=17&rft.issue=2&rft.spage=375&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-29 N1 - Date created - 1997-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Signaling events controlling the molecular response to genotoxic stress. AN - 78418081; 8856980 AB - Recently, much progress has been made in defining the signal transduction pathways mediating the cellular response to genotoxic stress. Multiple pathways involving several distinct MAP kinases (ERK, JNK/SAPK, and p38/HOG1) as well as the tumor suppressor protein p53 contribute to the response; the various pathways being differentially activated by particular genotoxic agents. Although both DNA damage and extranuclear events are important in initiating the response, recent evidence suggests the response is controlled primarily through events occurring at the plasma membrane, overlapping significantly with those important in initiating mitogenic responses. Attenuation of the responses appears to be largely controlled through feedback mechanisms involving gene products produced during the activation process. JF - EXS AU - Holbrook, N J AU - Liu, Y AU - Fornace, A J AD - Gene Expression and Aging Section, National Institute on Aging, Baltimore, MD 21244, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 273 EP - 288 VL - 77 SN - 1023-294X, 1023-294X KW - Mutagens KW - 0 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Models, Biological KW - DNA Damage -- genetics KW - Signal Transduction -- physiology KW - Mutagens -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78418081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EXS&rft.atitle=Signaling+events+controlling+the+molecular+response+to+genotoxic+stress.&rft.au=Holbrook%2C+N+J%3BLiu%2C+Y%3BFornace%2C+A+J&rft.aulast=Holbrook&rft.aufirst=N&rft.date=1996-01-01&rft.volume=77&rft.issue=&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=EXS&rft.issn=1023294X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma. AN - 78416053; 8859724 AB - The toxicity and clinical response to treatment with the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-gamma with or without IL-2. A 7-day course of subcutaneous IFN-gamma alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval. Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-gamma was established at 0.3 mg/m2 with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-gamma was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these findings, we conclude that further studies looking at this combination treatment are not warranted. JF - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy AU - Kim, C J AU - Taubenberger, J K AU - Simonis, T B AU - White, D E AU - Rosenberg, S A AU - Marincola, F M AD - Surgery Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 50 EP - 58 VL - 19 IS - 1 SN - 1067-5582, 1067-5582 KW - Interleukin-2 KW - 0 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Adult KW - Middle Aged KW - Immunohistochemistry KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Interferon-gamma -- therapeutic use KW - Melanoma -- secondary KW - Skin Neoplasms -- therapy KW - Melanoma -- chemistry KW - Skin Neoplasms -- secondary KW - Melanoma -- metabolism KW - Skin Neoplasms -- metabolism KW - Interferon-gamma -- adverse effects KW - Interleukin-2 -- therapeutic use KW - Skin Neoplasms -- chemistry KW - Interleukin-2 -- pharmacokinetics KW - Melanoma -- therapy KW - Interferon-gamma -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78416053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=Combination+therapy+with+interferon-gamma+and+interleukin-2+for+the+treatment+of+metastatic+melanoma.&rft.au=Kim%2C+C+J%3BTaubenberger%2C+J+K%3BSimonis%2C+T+B%3BWhite%2C+D+E%3BRosenberg%2C+S+A%3BMarincola%2C+F+M&rft.aulast=Kim&rft.aufirst=C&rft.date=1996-01-01&rft.volume=19&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-13 N1 - Date created - 1997-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using PCR for rapid site-specific mutagenesis in large plasmids. AN - 78415421; 8850008 JF - Methods in molecular biology (Clifton, N.J.) AU - Watkins, B A AU - Reitz, M S AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 217 EP - 227 VL - 57 SN - 1064-3745, 1064-3745 KW - DNA Primers KW - 0 KW - DNA, Recombinant KW - Index Medicus KW - Transformation, Bacterial KW - Base Sequence KW - DNA Primers -- genetics KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Templates, Genetic KW - Mutagenesis, Site-Directed KW - Genetic Vectors -- chemistry KW - Polymerase Chain Reaction -- methods KW - Genetic Vectors -- genetics KW - DNA, Recombinant -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78415421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Using+PCR+for+rapid+site-specific+mutagenesis+in+large+plasmids.&rft.au=Watkins%2C+B+A%3BReitz%2C+M+S&rft.aulast=Watkins&rft.aufirst=B&rft.date=1996-01-01&rft.volume=57&rft.issue=&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-10 N1 - Date created - 1996-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nutrition and lung cancer. AN - 78411720; 8850443 AB - Epidemiologic evidence on the relationship between nutrition and lung cancer is reviewed. Observational studies of diet and lung cancer, both prospective and retrospective, continue to suggest strongly that increased vegetable and fruit intake is associated with reduced risk in men and women; in various countries; in smokers, ex-smokers, and never-smokers; and for all histologic types of lung cancer. Prospective studies of blood beta-carotene levels, arguably the best available biomarker of vegetable and fruit intake, indicate that low levels are predictive of increased lung cancer incidence. However, in a randomized, placebo-controlled clinical trial in male smokers, lung cancer incidence and total mortality were increased significantly among the men receiving beta-carotene supplements. If beta-carotene can prevent lung carcinogenesis, which the trial cannot rule out, then the dosage, duration of use, method of administration, and/or subpopulation are critical. Ongoing clinical trials, some of which include women, will provide much-needed information. Other carotenoids, other phytochemicals, and associated dietary patterns may explain the beneficial effects of vegetables and fruits and have not been explored adequately in epidemiologic work. Several observational epidemiologic studies, both prospective and retrospective, have indicated that diets high in fat, saturated fat, and cholesterol may increase the risk of lung cancer and that the effect is not mediated through vegetable and fruit intake. The relationship, although not yet established, merits further investigation. Since beta-carotene can function as an antioxidant, other micronutrients with this potential, specifically vitamins E and C and selenium, also have been proposed to reduce lung cancer risk. However, the totality of the epidemiologic evidence is not, at present, persuasive for any one of these micronutrients. JF - Cancer causes & control : CCC AU - Ziegler, R G AU - Mayne, S T AU - Swanson, C A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 157 EP - 177 VL - 7 IS - 1 SN - 0957-5243, 0957-5243 KW - Cholesterol, Dietary KW - 0 KW - Dietary Fats KW - Fatty Acids KW - beta Carotene KW - 01YAE03M7J KW - Carotenoids KW - 36-88-4 KW - Index Medicus KW - Vegetables KW - Randomized Controlled Trials as Topic KW - Humans KW - Retrospective Studies KW - Dietary Fats -- administration & dosage KW - Feeding Behavior KW - Smoking -- epidemiology KW - Cholesterol, Dietary -- administration & dosage KW - Fatty Acids -- administration & dosage KW - Prospective Studies KW - beta Carotene -- therapeutic use KW - beta Carotene -- blood KW - Risk Factors KW - Incidence KW - Carotenoids -- administration & dosage KW - Forecasting KW - Diet KW - Fruit KW - Female KW - Male KW - Lung Neoplasms -- epidemiology KW - Nutritional Physiological Phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78411720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Nutrition+and+lung+cancer.&rft.au=Ziegler%2C+R+G%3BMayne%2C+S+T%3BSwanson%2C+C+A&rft.aulast=Ziegler&rft.aufirst=R&rft.date=1996-01-01&rft.volume=7&rft.issue=1&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-21 N1 - Date created - 1997-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxidation of brain lipids in vitro: nitric oxide versus hydroxyl radicals. AN - 78407642; 8855451 AB - The pro-oxidant effects of hydroxyl radical (.OH, ferrous ammonium sulfate/Fe2+) or nitric oxide (NO., S-nitroso-N-acetylpenicillamine/SNAP) generating compounds were studied in rat brain homogenate preparations. Submicromolar concentrations of Fe2+, but not SNAP (up to 100 microM), increased the formation of fluorescent products of malondialdehyde in cortical homogenates. In fact, iron-catalyzed brain lipid peroxidation was inhibited by SNAP (100 microM), but not by light-exposed SNAP or its degradation product penicillamine (100 microM). This study provides relevant evidence to suggest that submicromolar concentrations of Fe2+ can potentiate lipid peroxidation in disrupted brain tissue. NO. released from SNAP did not stimulate, but rather inhibited brain lipid peroxidation. These results support the hypothesis that NO., as opposed to .OH radicals, is not a pro-oxidant but rather an antioxidant. JF - Free radical biology & medicine AU - Rauhala, P AU - Sziraki, I AU - Chiueh, C C AD - Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center, Bethesda, MD 20892-1264, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 391 EP - 394 VL - 21 IS - 3 SN - 0891-5849, 0891-5849 KW - Ferrous Compounds KW - 0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydroxyl Radical KW - 3352-57-6 KW - Malondialdehyde KW - 4Y8F71G49Q KW - S-Nitroso-N-Acetylpenicillamine KW - 79032-48-7 KW - Penicillamine KW - GNN1DV99GX KW - Index Medicus KW - Rats KW - Malondialdehyde -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Penicillamine -- analogs & derivatives KW - Penicillamine -- pharmacology KW - Ferrous Compounds -- pharmacology KW - Male KW - Hydroxyl Radical -- metabolism KW - Brain -- drug effects KW - Hydroxyl Radical -- pharmacology KW - Nitric Oxide -- pharmacology KW - Nitric Oxide -- metabolism KW - Brain -- metabolism KW - Lipid Peroxidation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78407642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Peroxidation+of+brain+lipids+in+vitro%3A+nitric+oxide+versus+hydroxyl+radicals.&rft.au=Rauhala%2C+P%3BSziraki%2C+I%3BChiueh%2C+C+C&rft.aulast=Rauhala&rft.aufirst=P&rft.date=1996-01-01&rft.volume=21&rft.issue=3&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-27 N1 - Date created - 1996-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of phthalmustine, a new anticancer compound. II. Tumor inhibitory effect in murine Ehrlich ascites carcinoma and sarcoma-180. AN - 78400410; 8841510 AB - The antitumor activity of phthalmustine (Neoplasma, 41, 1994, 35) has been evaluated in murine Ehrlich ascites carcinoma (EAC) and sarcoma-180 (S-180). The hematological changes associated with the application of phthalmustine were also evaluated in tumor bearing as well as in normal male Swiss mice. The results indicate that phthalmustine induces marked inhibition of tumor growth and substantially prolongs host survival having curative effect while it does not adversely affect hematopoiesis at the optimum dose tested. No toxic symptoms were noted with respect to external appearance, body weight changes and behavioral pattern. JF - Neoplasma AU - Bhattacharya, S AU - Ghosh, M AU - Sadhu, U AU - Dutta, S AU - Sanyal, U AD - Department of Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1996 PY - 1996 DA - 1996 SP - 209 EP - 213 VL - 43 IS - 3 SN - 0028-2685, 0028-2685 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Alkylating KW - Nitrogen Mustard Compounds KW - Phthalimides KW - phthalmustine KW - 156250-83-8 KW - Index Medicus KW - Hematologic Tests KW - Animals KW - Survival Rate KW - Tumor Cells, Cultured -- drug effects KW - Lethal Dose 50 KW - Disease Progression KW - Mice KW - Spleen -- drug effects KW - Bone Marrow -- drug effects KW - Antineoplastic Agents, Alkylating -- chemistry KW - Male KW - Blood Cell Count -- drug effects KW - Sarcoma 180 -- drug therapy KW - Nitrogen Mustard Compounds -- chemical synthesis KW - Nitrogen Mustard Compounds -- chemistry KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Phthalimides -- pharmacology KW - Phthalimides -- chemistry KW - Phthalimides -- chemical synthesis KW - Antineoplastic Agents -- pharmacology KW - Nitrogen Mustard Compounds -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78400410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Evaluation+of+phthalmustine%2C+a+new+anticancer+compound.+II.+Tumor+inhibitory+effect+in+murine+Ehrlich+ascites+carcinoma+and+sarcoma-180.&rft.au=Bhattacharya%2C+S%3BGhosh%2C+M%3BSadhu%2C+U%3BDutta%2C+S%3BSanyal%2C+U&rft.aulast=Bhattacharya&rft.aufirst=S&rft.date=1996-01-01&rft.volume=43&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-05 N1 - Date created - 1996-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 5-Azacytidine-induced 6-thioguanine resistance at the gpt locus in AS52 cells: cellular response. AN - 78399799; 8844990 AB - Treatment of AS52 cells with 5-azacytidine resulted in an induction of 6-thioguanine-resistant [6TG] colonies, which reached a maximum by an expression time of 9 days. Dose responses for both cytotoxicity and mutation induction were determined following treatment with 5-azacytidine. At 20 microM treatment, 5-azacytidine exposure resulted in about 50% survival. Mutant frequency reached a maximum of 10 microM. At concentrations between 10 and 20 microM, 5-azacytidine was a potent mutagen but did not exhibit a dose response. Although many compounds both induce cell death and affect the growth rate of cells, 5-azacytidine specifically induced cell death and did not affect the doubling time of the surviving treated cell population. JF - Environmental and molecular mutagenesis AU - Spencer, D L AU - Caspary, W J AU - Hines, K C AU - Tindall, K R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 100 EP - 106 VL - 28 IS - 2 SN - 0893-6692, 0893-6692 KW - Antimetabolites, Antineoplastic KW - 0 KW - Bacterial Proteins KW - Escherichia coli Proteins KW - Mutagens KW - Proteins KW - Pentosyltransferases KW - EC 2.4.2.- KW - Gpt protein, E coli KW - EC 2.4.2.22 KW - Thioguanine KW - FTK8U1GZNX KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Mutagenesis -- drug effects KW - Animals KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Antimetabolites, Antineoplastic -- toxicity KW - Mutagens -- toxicity KW - CHO Cells KW - Time Factors KW - Mutation KW - Cricetinae KW - Bacterial Proteins -- drug effects KW - Drug Resistance -- genetics KW - Bacterial Proteins -- genetics KW - Azacitidine -- toxicity KW - Thioguanine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78399799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=5-Azacytidine-induced+6-thioguanine+resistance+at+the+gpt+locus+in+AS52+cells%3A+cellular+response.&rft.au=Spencer%2C+D+L%3BCaspary%2C+W+J%3BHines%2C+K+C%3BTindall%2C+K+R&rft.aulast=Spencer&rft.aufirst=D&rft.date=1996-01-01&rft.volume=28&rft.issue=2&rft.spage=100&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-14 N1 - Date created - 1996-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Endocrine modulation of reproduction. AN - 78393024; 8838635 AB - The ability of foreign compounds to affect the functioning of various endocrine systems is currently thought responsible for a wide variety of effects. The presentations in this Symposium reviewed the evidence for and against the involvement of endocrine systems in several different aspects of reproduction. The mechanism behind the ability of a triazine herbicide to cause enhanced appearance of mammary tumors in one strain of female rats is reviewed by Stevens. The data suggest that enhanced aging, not direct mammary modulation, is responsible. Dietary phytoestrogens, the mediators of their actions, their effects in various biological systems, and the relationships between phytoestrogen producers and consumers are all provocatively and succinctly reviewed by Hughes. Kelce presents the strategy used to dissect the mode and mechanisms of action of a fungicide that opened a new awareness in reproductive toxicology: the possibility of xenobiotics being antiandrogens. Finally, to heighten our understanding of the interplay among hormonal systems in vivo, Hess reviews the data that show that androgens are not the only hormones important in the development of the male reproductive system: the pituitary is shown to play a critical role at specific stages of development. The breadth of these presentations, and the implications of their findings, should make us pause and realize how much there is still to discover about the interaction between the reproductive system and anthropogenic compounds. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Chapin, R E AU - Stevens, J T AU - Hughes, C L AU - Kelce, W R AU - Hess, R A AU - Daston, G P Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 1 EP - 17 VL - 29 IS - 1 KW - Androgen Antagonists KW - 0 KW - Estrogens, Non-Steroidal KW - Fungicides, Industrial KW - Herbicides KW - Hormones KW - Plant Growth Regulators KW - Atrazine KW - QJA9M5H4IM KW - Index Medicus KW - Mammary Neoplasms, Animal -- physiopathology KW - Animals KW - Androgen Antagonists -- toxicity KW - Testis -- physiology KW - Pituitary Gland -- physiology KW - Humans KW - Plant Growth Regulators -- pharmacology KW - Rats KW - Mammary Neoplasms, Animal -- etiology KW - Aging -- physiology KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Testis -- drug effects KW - Aging -- drug effects KW - Herbicides -- toxicity KW - Estrogens, Non-Steroidal -- pharmacology KW - Fungicides, Industrial -- toxicity KW - Atrazine -- toxicity KW - Female KW - Male KW - Reproduction -- physiology KW - Hormones -- physiology KW - Reproduction -- drug effects KW - Endocrine Glands -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78393024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Endocrine+modulation+of+reproduction.&rft.au=Chapin%2C+R+E%3BStevens%2C+J+T%3BHughes%2C+C+L%3BKelce%2C+W+R%3BHess%2C+R+A%3BDaston%2C+G+P&rft.aulast=Chapin&rft.aufirst=R&rft.date=1996-01-01&rft.volume=29&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-11 N1 - Date created - 1996-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical effects of the mouse hepatocarcinogen oxazepam: similarities to phenobarbital. AN - 78387574; 8838650 AB - The National Toxicology Program (NTP) recently determined that the commonly prescribed sedative hypnotic agent oxazepam is a mouse liver carcinogen. Many other benzodiazepines are metabolized to oxazepam resulting in further human exposure to this drug. This has resulted in considerable interest in the mechanism of oxazepam-mediated mouse liver carcinogenesis for use in human risk assessment. Several directions for mechanistic research were examined in this study. B6C3F1 mice were treated with oxazepam-dosed feed at 125 (noncarcinogenic) and 2500 ppm (carcinogenic) for 3, 7, 10, and 21 days. Cell proliferation in liver, cytochrome P450 induction, free radical formation, GSH depletion, and levels of circulating thyroid-stimulating hormone (TSH) were analyzed at these time points. Increased levels of hepatic cell proliferation were observed by 7 days at 125 ppm and by 10 days at 2500 ppm. Microsomal enzyme induction also occurred and was associated with elevated plasma TSH levels. Hepatic GSH levels were slightly depressed but there was no evidence of increased oxidative stress. A similar pattern of biochemical events has been observed to occur during dosed feed treatment with phenobarbital. These results suggest that oxazepam and phenobarbital may induce carcinogenesis by similar mechanisms in mice. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Griffin, R J AU - Dudley, C N AU - Cunningham, M L AD - Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 147 EP - 154 VL - 29 IS - 1 SN - 0272-0590, 0272-0590 KW - Free Radicals KW - 0 KW - Hypnotics and Sedatives KW - Sulfhydryl Compounds KW - Oxazepam KW - 6GOW6DWN2A KW - Thyrotropin KW - 9002-71-5 KW - Cytochromes b5 KW - 9035-39-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Sulfhydryl Compounds -- metabolism KW - Enzyme Induction -- drug effects KW - Dose-Response Relationship, Drug KW - Cytochromes b5 -- biosynthesis KW - Microsomes, Liver -- drug effects KW - Cell Division -- drug effects KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Mice KW - Free Radicals -- metabolism KW - Male KW - Organ Size -- drug effects KW - Liver -- cytology KW - Oxazepam -- toxicity KW - Hypnotics and Sedatives -- toxicity KW - Thyrotropin -- blood KW - Phenobarbital -- metabolism KW - Liver -- drug effects KW - Thyrotropin -- drug effects KW - Oxazepam -- metabolism KW - Phenobarbital -- toxicity KW - Liver -- chemistry KW - Hypnotics and Sedatives -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78387574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Biochemical+effects+of+the+mouse+hepatocarcinogen+oxazepam%3A+similarities+to+phenobarbital.&rft.au=Griffin%2C+R+J%3BDudley%2C+C+N%3BCunningham%2C+M+L&rft.aulast=Griffin&rft.aufirst=R&rft.date=1996-01-01&rft.volume=29&rft.issue=1&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-11 N1 - Date created - 1996-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Emerging issues in mouse liver carcinogenesis. AN - 78383157; 8839290 AB - The mouse liver is the primary target site for carcinogenesis of more than 200 chemicals (including pesticides, food additives, pharmaceuticals, and industrial intermediates) tested in long-term toxicity safety assessment assays. Mouse liver tumors develop through defined morphological stages (similar to those found in other species) whether their origin is of undetermined etiology (spontaneous) or induced by chemicals. The morphologic type of hepatocytes in the various stages of hepatocarcinogenesis is sometimes associated with the specific inducing agent. Liver tumors developing in toxic livers often have more benign appearances and may progress to carcinomas at a slower rate than tumors developing in histologically normal livers. Specific tumors, dependent on the inducing chemical, may regress under defined protocols. Genotoxic and nongenotoxic mouse hepatocarcinogens each may induce tumors of either high malignant or low malignant potential. Liver tumors with specific H-ras oncogene mutations may appear morphologically and biologically similar to those without proven ras mutations. Thus, distinguishing mechanism of carcinogenesis by liver tumor morphology and mutation spectra may be difficult. Additionally, the presence of liver tumors with a morphology and a ras oncogene mutation spectrum characteristic of spontaneous tumors in histologically normal livers of mice exposed to a nongenotoxic test chemical may indicate promotion of spontaneous hepatocarcinogenesis by one of several potential mechanisms. Further research into the mechanisms responsible for the increased incidences of liver tumors in mice exposed to test chemicals could enhance human cancer risk assessments. JF - Toxicologic pathology AU - Ward, J M AU - Shibata, M A AU - Devor, D E AD - Veterinary and Tumor Pathology Section, National Cancer Institute, Frederick, Maryland 21702-1201, USA. PY - 1996 SP - 129 EP - 137 VL - 24 IS - 1 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Mice KW - Liver Neoplasms, Experimental -- pathology KW - Carcinogenicity Tests -- trends KW - Liver Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78383157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Emerging+issues+in+mouse+liver+carcinogenesis.&rft.au=Ward%2C+J+M%3BShibata%2C+M+A%3BDevor%2C+D+E&rft.aulast=Ward&rft.aufirst=J&rft.date=1996-01-01&rft.volume=24&rft.issue=1&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vanadium(IV) causes 2'-deoxyguanosine hydroxylation and deoxyribonucleic acid damage via free radical reactions. AN - 78376607; 8834359 AB - Vanadium(IV) caused molecular oxygen dependent 2'-deoxyguanosine (dG) hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15-minute incubation of 1.0 mM dG and 1.0 mM VOSO4 (vanadium(IV)) in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31 percent. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Diethylenetriaminepentaacetic acid (DTPA) and deferoxamine blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen dependent deoxyribonucleic acid (DNA) strand breaks in a pattern similar to that observed for dG hydroxylation. Reaction of vanadium(IV) with H2O2 generated OH radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA strand breaks. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks. JF - Annals of clinical and laboratory science AU - Shi, X AU - Wang, P AU - Jiang, H AU - Mao, Y AU - Ahmed, N AU - Dalal, N AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892, USA. PY - 1996 SP - 39 EP - 49 VL - 26 IS - 1 SN - 0091-7370, 0091-7370 KW - Chelating Agents KW - 0 KW - Peroxides KW - Vanadium KW - 00J9J9XKDE KW - Hydroxyl Radical KW - 3352-57-6 KW - DNA KW - 9007-49-2 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Chelating Agents -- pharmacology KW - Peroxides -- metabolism KW - Hydroxylation KW - Deoxyguanosine -- metabolism KW - Hydroxyl Radical -- metabolism KW - DNA Damage KW - Vanadium -- toxicity KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78376607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+clinical+and+laboratory+science&rft.atitle=Vanadium%28IV%29+causes+2%27-deoxyguanosine+hydroxylation+and+deoxyribonucleic+acid+damage+via+free+radical+reactions.&rft.au=Shi%2C+X%3BWang%2C+P%3BJiang%2C+H%3BMao%2C+Y%3BAhmed%2C+N%3BDalal%2C+N&rft.aulast=Shi&rft.aufirst=X&rft.date=1996-01-01&rft.volume=26&rft.issue=1&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Annals+of+clinical+and+laboratory+science&rft.issn=00917370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An isobolographic analysis of the effects of N-methyl-D-aspartate and NK1 tachykinin receptor antagonists on inflammatory hyperalgesia in the rat. AN - 78373544; 8825363 AB - 1. The interaction between N-methyl-D-aspartate (NMDA) and NK1 tachykinin receptors was analyzed isobolographically in rats with inflammatory hyperalgesia induced by intraplantar injection of complete Freund's adjuvant-saline emulsion (CFA, 100 micrograms Mycobacterium tuberculosis). 2. Thermal hyperalgesia of the inflamed paw, determined by paw withdrawal response to a heat stimulus, was dose-dependently attenuated by intrathecal administration of an NMDA receptor antagonist, dextrorphan (2.5-40 micrograms, ED50 = 7.2 micrograms), and two NK1 tachykinin receptor antagonists, WIN 51,708 (0.01-200 micrograms, ED50 = 10.4 micrograms) or CP-96,345 (5-200 micrograms, ED50 = 82.1 micrograms). There was no effect of these agents on the nociceptive threshold of the non-inflamed paw. CP-96,344, an enantiomer of CP-96,345 that is inactive as an NK1 tachykinin receptor antagonist, slightly attenuated hyperalgesia at a dose of 200 micrograms. 3. Combinations of dextrorphan and WIN 51,708 were administered at fixed ratios (10%:90%; 41%:59%; 90%:10%). Isobolographic analysis revealed that the ED50s obtained from the three combination ratios were not significantly different from those that were expected from a simple additive effect. 4. Thus, an additive interaction was demonstrated between NMDA and NK1 tachykinin receptor systems at the spinal level. These results suggest that both NMDA and NK1 tachykinin receptors are activated in response to peripheral inflammation, but that they may contribute independently to development of hyperalgesia. JF - British journal of pharmacology AU - Ren, K AU - Iadarola, M J AU - Dubner, R AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-4410, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 196 EP - 202 VL - 117 IS - 1 SN - 0007-1188, 0007-1188 KW - Androstanes KW - 0 KW - Benzimidazoles KW - Biphenyl Compounds KW - Excitatory Amino Acid Antagonists KW - Neurokinin-1 Receptor Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - WIN 51708 KW - Dextrorphan KW - 04B7QNO9WS KW - Freund's Adjuvant KW - 9007-81-2 KW - CP 96345 KW - W22ILA2I52 KW - Index Medicus KW - Rats KW - Dextrorphan -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Hindlimb KW - Dose-Response Relationship, Drug KW - Benzimidazoles -- pharmacology KW - Biphenyl Compounds -- pharmacology KW - Androstanes -- pharmacology KW - Male KW - Inflammation -- physiopathology KW - Hyperalgesia -- physiopathology KW - Inflammation -- chemically induced KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Pain Measurement -- drug effects KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78373544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=An+isobolographic+analysis+of+the+effects+of+N-methyl-D-aspartate+and+NK1+tachykinin+receptor+antagonists+on+inflammatory+hyperalgesia+in+the+rat.&rft.au=Ren%2C+K%3BIadarola%2C+M+J%3BDubner%2C+R&rft.aulast=Ren&rft.aufirst=K&rft.date=1996-01-01&rft.volume=117&rft.issue=1&rft.spage=196&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-22 N1 - Date created - 1996-11-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuroscience. 1992 Dec;51(3):641-8 [1283208] Br J Pharmacol. 1991 Oct;104(2):292-3 [1665729] J Neurochem. 1993 Mar;60(3):952-60 [7679730] Neuroscience. 1993 Feb;52(4):1039-47 [7680799] Brain Res. 1993 Mar 5;605(1):164-8 [8385540] Neurosci Lett. 1993 Mar 5;151(1):107-10 [8385757] J Pharmacol Exp Ther. 1993 Sep;266(3):1261-7 [8396630] Br J Pharmacol. 1993 Sep;110(1):385-91 [7693284] Neurosci Lett. 1993 Jul 23;157(2):149-52 [8233046] Anesthesiology. 1993 Nov;79(5):1042-50 [7694526] Neuroreport. 1993 Aug;4(8):1007-10 [8241452] Neurosci Lett. 1993 Oct 14;161(1):57-9 [8255547] J Neurosci. 1994 Feb;14(2):712-20 [8301359] Br J Pharmacol. 1993 Dec;110(4):1607-13 [8306108] Pain. 1993 Dec;55(3):313-7 [8121692] Br J Pharmacol. 1994 Jan;111(1):179-84 [8012694] Physiol Behav. 1976 Dec;17(6):1031-6 [14677603] J Neurochem. 1982 May;38(5):1383-6 [6174698] J Pharmacol Exp Ther. 1983 Aug;226(2):398-404 [6192235] Pain. 1983 Jun;16(2):109-10 [6877845] Biochem Pharmacol. 1984 Nov 15;33(22):3529-35 [6095851] Eur J Pharmacol. 1985 May 8;111(2):185-90 [2990951] Neurosci Lett. 1986 Jun 18;67(2):191-7 [2425302] Mol Pharmacol. 1992 Apr;41(4):772-8 [1373802] Pain. 1992 Apr;49(1):93-7 [1594286] Pain. 1992 May;49(2):273-8 [1376888] J Neurosci. 1992 Jul;12(7):2563-72 [1613548] Br J Pharmacol. 1992 Mar;105(3):508-10 [1320977] Br J Pharmacol. 1992 Oct;107(2):273-5 [1330170] Eur J Pharmacol. 1992 Jul 7;217(2-3):191-5 [1330589] Eur J Pharmacol. 1992 Aug 25;219(2):235-43 [1358641] Pain. 1992 Sep;50(3):331-44 [1454389] Life Sci. 1993;52(4):353-60 [7678436] Pain. 1992 Nov;51(2):195-8 [1283010] Neurosci Lett. 1994 Feb 28;168(1-2):49-52 [7518066] Ann Thorac Surg. 1994 Aug;58(2):312-9; discussion 319-20 [7915102] Pain. 1994 Nov;59(2):165-74 [7892014] Neuroscience. 1995 Feb;64(4):943-58 [7538641] J Neurophysiol. 1995 Apr;73(4):1574-83 [7643168] J Pharmacol Exp Ther. 1987 Oct;243(1):9-19 [2822907] Pain. 1988 Jan;32(1):77-88 [3340425] Proc Natl Acad Sci U S A. 1988 Oct;85(20):7820-4 [2459717] Pain. 1988 Dec;35(3):313-26 [2906426] J Comp Neurol. 1988 Nov 8;277(2):302-12 [2466061] Neurosci Lett. 1989 Mar 13;98(1):105-10 [2469044] Pain. 1989 May;37(2):229-43 [2664665] Science. 1990 Feb 23;247(4945):958-62 [2154852] Brain Res. 1990 Jun 4;518(1-2):218-26 [1975214] J Pharmacol Exp Ther. 1990 Dec;255(3):1107-16 [2262895] Science. 1991 Jan 25;251(4992):435-7 [1703323] Eur J Pharmacol. 1991 Mar 5;194(2-3):135-43 [1676373] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10208-12 [1719549] Life Sci. 1991;49(26):1955-63 [1721102] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11344-8 [1722327] J Med Chem. 1992 Jan 24;35(2):374-8 [1370695] Pain. 1991 Oct;47(1):85-93 [1722895] Neurosci Lett. 1991 Oct 28;132(1):39-43 [1724068] Neurosci Lett. 1991 Sep 30;131(1):71-4 [1686478] Neurosci Lett. 1991 Nov 25;133(1):121-4 [1724310] Neuropharmacology. 1993 Jan;32(1):37-41 [7679210] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Mechanism-based toxicology in cancer risk assessment: implications for research, regulation, and legislation. AN - 78372084; 8834866 JF - Environmental health perspectives AU - Lucier, G W Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 84 EP - 88 VL - 104 IS - 1 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Risk Assessment KW - Toxicology -- legislation & jurisprudence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78372084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Environmental+health+perspectives&rft.atitle=Mechanism-based+toxicology+in+cancer+risk+assessment%3A+implications+for+research%2C+regulation%2C+and+legislation.&rft.au=Lucier%2C+G+W&rft.aulast=Lucier&rft.aufirst=G&rft.date=1996-01-01&rft.volume=104&rft.issue=1&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-05 N1 - Date created - 1996-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemotherapy alone in the treatment of patients with early stage Hodgkin's disease. AN - 78371947; 8836416 AB - Studies employing chemotherapy in early stage Hodgkin's disease suggest that this approach is at least comparable to radiation therapy in treatment outcome. Since the long-term disease-free survival in early stages approaches 90%, it is unlikely to further improve these results substantially. Thus, the major goal is the reduction of toxicity. The future choice of therapy will be influenced by the long-term toxicity of these approaches which has to be monitored carefully. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Longo, D L AD - Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 85 EP - 89 VL - 7 Suppl 4 SN - 0923-7534, 0923-7534 KW - Index Medicus KW - Neoplasm Staging KW - Combined Modality Therapy KW - Humans KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Hodgkin Disease -- radiotherapy KW - Hodgkin Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78371947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Chemotherapy+alone+in+the+treatment+of+patients+with+early+stage+Hodgkin%27s+disease.&rft.au=Longo%2C+D+L&rft.aulast=Longo&rft.aufirst=D&rft.date=1996-01-01&rft.volume=7+Suppl+4&rft.issue=&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-06 N1 - Date created - 1996-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New concepts for the development and use of antifolates. AN - 78365800; 8820950 AB - Approximately one-third of all cases of colorectal carcinoma present in an advanced and, therefore, incurable stage. For these patients, the development of new chemotherapeutic strategies is of central importance. Biochemical modulation of 5-fluorouracil (5-FU) has resulted in approximately a two-fold increase in activity of 5-FU. Recent preclinical investigations suggest that interferon can also modulate the activity of 5-FU and may result in enhanced response rates in patients. One of the critical mechanisms of resistance to 5-FU appears to be the acute induction in thymidylate synthase (TS) levels following therapy with inhibitors of this enzyme. This mechanism is based on a novel autoregulatory feedback pathway wherein the TS protein regulates its own translational efficiency. Regulatory function of the enzyme is dependent on its state of occupancy by either the physiologic ligands or inhibitors, including fluoropyrimidines and antifolates. Ongoing efforts are directed towards utilizing knowledge of this protein/messenger RNA interaction for therapeutic benefit. Given the importance of TS, our laboratory has developed antibodies capable of quantitating the levels of this enzyme in fresh or paraffin-embedded tissues. Preliminary investigations suggest that the level of TS has prognostic importance in patients with rectal carcinoma and may be used to predict responsiveness to fluoropyrimidine agents. Novel strategies utilizing dual modulation of 5-FU with leucovorin and interferon are under investigation in both the advanced and adjuvant disease settings. Emerging mechanistic concepts regarding TS, along with the development of new, more potent inhibitors will hopefully result in future therapeutic gains. JF - Stem cells (Dayton, Ohio) AU - Chu, E AU - Grem, J L AU - Johnston, P G AU - Allegra, C J AD - NCI-Navy Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20889-5105, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 41 EP - 46 VL - 14 IS - 1 SN - 1066-5099, 1066-5099 KW - Antimetabolites, Antineoplastic KW - 0 KW - Folic Acid Antagonists KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- therapeutic use KW - Drug Therapy, Combination KW - Animals KW - Humans KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Leucovorin -- therapeutic use KW - Thymidylate Synthase -- antagonists & inhibitors KW - Folic Acid Antagonists -- therapeutic use KW - Folic Acid Antagonists -- pharmacology KW - Colorectal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78365800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=New+concepts+for+the+development+and+use+of+antifolates.&rft.au=Chu%2C+E%3BGrem%2C+J+L%3BJohnston%2C+P+G%3BAllegra%2C+C+J&rft.aulast=Chu&rft.aufirst=E&rft.date=1996-01-01&rft.volume=14&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-04 N1 - Date created - 1996-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical reversal of multidrug resistance. AN - 78365494; 8820952 AB - Reversal of drug resistance offers the hope of increasing the efficacy of conventional chemotherapy. We tested dexverapamil as a P-glycoprotein antagonist in combination with EPOCH chemotherapy in refractory non-Hodgkin's lymphoma. In a cross-over design, dexverapamil was added to EPOCH after disease stabilization or progression occurred. Objective responses were observed in 10 of 41 assessable patients. Biopsies for mdr-1 were obtained before EPOCH treatment and at the time of cross-over to dexverapamil. Levels of mdr-1 were low before EPOCH, but increased four-fold or more in 42% of patients in whom serial samples were obtained. Pharmacokinetic analysis revealed median peak concentrations of dexverapamil and its metabolite, nor-dexverapamil, of 1.66 mumol/l and 1.58 mumol/l, respectively. Since both are comparable antagonists, a median peak total reversing concentration of 3.24 mumol/l was achieved. Pharmacokinetic analysis of doxorubicin and etoposide levels confirmed a delay in the clearance of doxorubicin ranging from 5% to 24%; no change in the pharmacokinetics of etoposide was observed. This study provides sufficient rationale for testing dexverapamil in a randomized clinical trial. JF - Stem cells (Dayton, Ohio) AU - Bates, S E AU - Wilson, W H AU - Fojo, A T AU - Alvarez, M AU - Zhan, Z AU - Regis, J AU - Robey, R AU - Hose, C AU - Monks, A AU - Kang, Y K AU - Chabner, B AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 56 EP - 63 VL - 14 IS - 1 SN - 1066-5099, 1066-5099 KW - P-Glycoprotein KW - 0 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Verapamil KW - CJ0O37KU29 KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Cyclophosphamide -- therapeutic use KW - P-Glycoprotein -- analysis KW - Vincristine -- therapeutic use KW - Prednisone -- therapeutic use KW - Humans KW - Etoposide -- therapeutic use KW - Doxorubicin -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - P-Glycoprotein -- antagonists & inhibitors KW - Drug Resistance, Neoplasm KW - Verapamil -- therapeutic use KW - Drug Resistance, Multiple UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78365494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=Clinical+reversal+of+multidrug+resistance.&rft.au=Bates%2C+S+E%3BWilson%2C+W+H%3BFojo%2C+A+T%3BAlvarez%2C+M%3BZhan%2C+Z%3BRegis%2C+J%3BRobey%2C+R%3BHose%2C+C%3BMonks%2C+A%3BKang%2C+Y+K%3BChabner%2C+B&rft.aulast=Bates&rft.aufirst=S&rft.date=1996-01-01&rft.volume=14&rft.issue=1&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-04 N1 - Date created - 1996-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in endothelial cell proteinase and inhibitor polarized secretion following treatment with interleukin-1, phorbol ester, and human melanoma cell conditioned medium. AN - 78365465; 8825424 AB - Polarized secretion of matrix metalloproteinases and plasminogen activators by monkey aortic endothelial cells was studied in vitro, using transwell inserts. The endothelial cells constitutively expressed matrix metalloproteinase-2, tissue inhibitors of metalloproteinases 1 and 2, urokinase, and tissue plasminogen activator, all with basal preference. Matrix metalloproteinase-9 activity was induced by phorbol 12-myristate 13-acetate (apical), interleukin-1 alpha (basal), and by conditioned medium from DX3 human melanoma cells (basal). The DX3 melanoma conditioned medium also stimulated basal secretion of matrix metalloproteinase-2, urokinase, tissue plasminogen activator, and tissue inhibitors of metalloproteinases. The rise in proteolytic activity in the basal direction was reflected by increased capacity to degrade subendothelial basement membrane type IV collagen, shown immunohistologically, using monkey kidney tissue sections and basement membrane deposited by endothelial cells into the transwell membrane. Thus, IL-1 alpha and DX3 melanoma conditioned medium can stimulate endothelial cells in vitro to concentrate secretion of proteinases spatially onto the underlying basement membrane. We suggest that the stimulation of endothelial cell proteinase activity by tumor cells may facilitate tumor cell extravasation. JF - Journal of cellular biochemistry AU - Cottam, D W AU - Corbitt, R H AU - Gomez, D E AU - Rees, R C AU - Thorgeirsson, U P AD - Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 148 EP - 160 VL - 60 IS - 1 SN - 0730-2312, 0730-2312 KW - Culture Media, Conditioned KW - 0 KW - Interleukin-1 KW - Recombinant Proteins KW - Collagen KW - 9007-34-5 KW - Tissue Plasminogen Activator KW - EC 3.4.21.68 KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Aorta -- drug effects KW - Collagen -- metabolism KW - Cells, Cultured KW - Humans KW - Aorta -- secretion KW - Haplorhini KW - Tissue Plasminogen Activator -- secretion KW - Endothelium, Vascular -- secretion KW - Interleukin-1 -- pharmacology KW - Endothelium, Vascular -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Melanoma -- metabolism KW - Metalloendopeptidases -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78365465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry&rft.atitle=Alterations+in+endothelial+cell+proteinase+and+inhibitor+polarized+secretion+following+treatment+with+interleukin-1%2C+phorbol+ester%2C+and+human+melanoma+cell+conditioned+medium.&rft.au=Cottam%2C+D+W%3BCorbitt%2C+R+H%3BGomez%2C+D+E%3BRees%2C+R+C%3BThorgeirsson%2C+U+P&rft.aulast=Cottam&rft.aufirst=D&rft.date=1996-01-01&rft.volume=60&rft.issue=1&rft.spage=148&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry&rft.issn=07302312&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-20 N1 - Date created - 1996-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins. AN - 78364926; 8825117 AB - Pseudomonas exotoxin has been genetically modified so that it targets cancer cells. This was accomplished by deleting its cell binding domain and replacing it with Fv fragments of antibodies that react with breast, colon, and other cancers. Several recombinant immunotoxins are now in clinical trials. JF - Breast cancer research and treatment AU - Pastan, I AU - Pai, L H AU - Brinkmann, U AU - FitzGerald, D AD - Laboratory of Molecular Biology, DCBDC, National Cancer Institute, NIH, Bethesda, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 3 EP - 9 VL - 38 IS - 1 SN - 0167-6806, 0167-6806 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Humans KW - Exotoxins -- therapeutic use KW - Recombinant Proteins -- therapeutic use KW - Female KW - Antibodies, Monoclonal -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Breast Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78364926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Recombinant+immunotoxins.&rft.au=Pastan%2C+I%3BPai%2C+L+H%3BBrinkmann%2C+U%3BFitzGerald%2C+D&rft.aulast=Pastan&rft.aufirst=I&rft.date=1996-01-01&rft.volume=38&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-14 N1 - Date created - 1996-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine withdrawal reduces dopamine transporter binding in the shell of the nucleus accumbens. AN - 78356454; 8822482 AB - We have previously shown that withdrawal from repeated, intermittent infusions of cocaine in Lewis rats results in a long-lasting reduction in dopamine transporter levels in the nucleus accumbens. The reduction is dose-dependent, requires multiple injections as well as about a 10-day withdrawal period. In this investigation, we show that the decrease (34%) occurs in the shell rather than in the core of the nucleus accumbens, and that a second cycle of cocaine administration and withdrawal has no additional effect. Also, there were no changes in transporter binding in the caudate putamen, the olfactory tubercle or the ventral tegmental area. These results indicate that the limbic portions of the nucleus accumbens are involved in neurochemical adaptations during withdrawal from cocaine. JF - Synapse (New York, N.Y.) AU - Pilotte, N S AU - Sharpe, L G AU - Rountree, S D AU - Kuhar, M J AD - National Institute on Drug Abuse, Division of Intramural Research, Baltimore, Maryland 21224. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 87 EP - 92 VL - 22 IS - 1 SN - 0887-4476, 0887-4476 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Narcotics KW - Nerve Tissue Proteins KW - RTI 121 KW - 146145-21-3 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Olfactory Bulb -- pathology KW - Animals KW - Rats, Inbred Lew KW - Neostriatum -- metabolism KW - Ventral Tegmental Area -- pathology KW - Ventral Tegmental Area -- metabolism KW - Neostriatum -- pathology KW - Autoradiography KW - Olfactory Bulb -- metabolism KW - Image Processing, Computer-Assisted KW - Male KW - Substance Withdrawal Syndrome -- pathology KW - Substance Withdrawal Syndrome -- metabolism KW - Cocaine -- analogs & derivatives KW - Carrier Proteins -- metabolism KW - Nucleus Accumbens -- metabolism KW - Narcotics -- adverse effects KW - Nucleus Accumbens -- pathology KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78356454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Cocaine+withdrawal+reduces+dopamine+transporter+binding+in+the+shell+of+the+nucleus+accumbens.&rft.au=Pilotte%2C+N+S%3BSharpe%2C+L+G%3BRountree%2C+S+D%3BKuhar%2C+M+J&rft.aulast=Pilotte&rft.aufirst=N&rft.date=1996-01-01&rft.volume=22&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-08 N1 - Date created - 1996-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategies for the development of recombinant vaccines for the immunotherapy of breast cancer. AN - 78353187; 8825120 AB - The development of recombinant vaccines for specific immunotherapy of carcinoma represents a novel approach for the treatment of breast cancer and other tumor types. This article reviews the various parameters that should be considered in the development of recombinant vaccines. Several breast cancer associated antigens are also discussed which may provide potential target molecules. The human carcinoembryonic antigen (CEA), which is expressed on approximately 50% of breast cancers, represents one such target for immunotherapy. To enhance the immunogenicity of this antigen, a recombinant CEA-vaccinia vaccine, designated rV-CEA, was produced. To study the effects of this vaccine in an animal model, a murine colon carcinoma cell line was transduced with CEA and transplanted into immunocompetent mice for protection and therapy studies. Pre-clinical toxicity studies were also conducted in non-human primates. The results of these studies showed the rV-CEA vaccine to be immunogenic and safe in both rodents and primates, and to elicit good anti-tumor responses in the rodent model. In a Phase I clinical trial in metastatic breast, lung, and colorectal cancer patients involving three immunizations of rV-CEA, at three dose levels, enhancement of T-cell and antibody responses to vaccinia virus proteins were observed with no toxicity. Specific T-cell responses were studied via stimulation of peripheral blood lymphocytes with specific peptide epitopes from the CEA molecule. These studies demonstrated clear cut differences in establishment of T-cell lines pre- versus post-immunization. The T-cell lines were shown to be CD8+ and/or CD4+/CD8+, to lyse EBV transformed B-cells transduced with the CEA gene, and to lyse CEA positive carcinoma cells in a HLA restricted manner. Thus, in a Phase I clinical trial the rV-CEA vaccine has been shown to stimulate a CTL response specific for CEA defined epitopes in cancer patients. JF - Breast cancer research and treatment AU - Schlom, J AU - Kantor, J AU - Abrams, S AU - Tsang, K Y AU - Panicali, D AU - Hamilton, J M AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 27 EP - 39 VL - 38 IS - 1 SN - 0167-6806, 0167-6806 KW - Antigens, Neoplasm KW - 0 KW - Carcinoembryonic Antigen KW - Vaccines, Synthetic KW - Index Medicus KW - Animals KW - Immunity, Cellular KW - Humans KW - Clinical Trials, Phase I as Topic KW - Mice KW - Antigens, Neoplasm -- immunology KW - Female KW - Breast Neoplasms -- immunology KW - Carcinoembryonic Antigen -- immunology KW - Vaccines, Synthetic -- immunology KW - Breast Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78353187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Strategies+for+the+development+of+recombinant+vaccines+for+the+immunotherapy+of+breast+cancer.&rft.au=Schlom%2C+J%3BKantor%2C+J%3BAbrams%2C+S%3BTsang%2C+K+Y%3BPanicali%2C+D%3BHamilton%2C+J+M&rft.aulast=Schlom&rft.aufirst=J&rft.date=1996-01-01&rft.volume=38&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-14 N1 - Date created - 1996-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction to the Perinatal-20 treatment research demonstration program. AN - 78347517; 8818161 JF - NIDA research monograph AU - Rahdert, E R AD - Treatment Research Branch, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1 EP - 5 VL - 166 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Adult KW - Research Design KW - Female KW - Pregnancy KW - Pregnancy Complications -- psychology KW - Pregnancy Complications -- chemically induced KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78347517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Introduction+to+the+Perinatal-20+treatment+research+demonstration+program.&rft.au=Rahdert%2C+E+R&rft.aulast=Rahdert&rft.aufirst=E&rft.date=1996-01-01&rft.volume=166&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-11 N1 - Date created - 1996-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PET studies of cerebral glucose metabolism: acute effects of cocaine and long-term deficits in brains of drug abusers. AN - 78342921; 8809857 JF - NIDA research monograph AU - London, E D AU - Stapleton, J M AU - Phillips, R L AU - Grant, S J AU - Villemagne, V L AU - Liu, X AU - Soria, R AD - Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 146 EP - 158 VL - 163 SN - 1046-9516, 1046-9516 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Animals KW - Humans KW - Tomography, Emission-Computed KW - Opioid-Related Disorders -- metabolism KW - Opioid-Related Disorders -- psychology KW - Glucose -- metabolism KW - Brain Chemistry -- drug effects KW - Narcotics -- toxicity KW - Cocaine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78342921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=PET+studies+of+cerebral+glucose+metabolism%3A+acute+effects+of+cocaine+and+long-term+deficits+in+brains+of+drug+abusers.&rft.au=London%2C+E+D%3BStapleton%2C+J+M%3BPhillips%2C+R+L%3BGrant%2C+S+J%3BVillemagne%2C+V+L%3BLiu%2C+X%3BSoria%2C+R&rft.aulast=London&rft.aufirst=E&rft.date=1996-01-01&rft.volume=163&rft.issue=&rft.spage=146&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-10 N1 - Date created - 1996-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine addiction as a neurological disorder: implications for treatment. AN - 78342076; 8809851 AB - Clinical and preclinical studies provide convincing evidence for persistent neurological/psychiatric impairments and possible neuronal degeneration associated with chronic cocaine/stimulant abuse. These impairments include multifocal and global cerebral ischemia, cerebral hemorrhages, infarctions, optic neuropathy, cerebral atrophy, cognitive impairments, and mood and movement disorders. These findings may encourage the placement of stimulant addiction into the category of organic brain disorders. Functional and microanatomical anomalies in the frontal and temporal cortex as well as other brain regions may be responsible for certain aspects of phenomenology and neuropsychopathology that are characteristic of stimulant polydrug addictions. These may include broad spectrum of deficits in cognition, motivation, and insight; behavioral disinhibition; attention deficits; emotional instability; impulsiveness; aggressiveness; depression; anhedonia; and persistent movement disorders. Although it is still debated whether the hypofrontality and other brain anomalies observed in stimulant abusers are a consequence or an antecedent of drug abuse, this debate seems purely academic and irrelevant with respect to the importance of compensating for these deficits in the development of treatment strategies. The neuropsychiatric impairments accompanying stimulant abuse may contribute to the very high rate of relapse in addicts that can take place after long periods (years) of abstinence. It is possible that the neurological deficits present in stimulant addicts, whether they are primary or secondary to stimulant abuse, are responsible for perpetual drug abuse which may be a form of self-medication (Weiss et al. 1991, 1992). In this context, addiction to stimulants, once fully developed, may represent a true biological dependency on drugs that temporarily compensate for existing neurological deficits. The concept of self-medication by drug addicts is supported by major theories of biological psychiatry. While a majority of drug addicts are polydrug users, there seems to be a preference for a particular type of drug among different populations of addicts. Addicts who experience distress, anxious dysphoria, and turbulent anger prefer the calming actions of opiates, whereas addicts with preceding attention deficit disorder, depression, or bipolar disorder often prefer stimulants (Khantzian 1985). Figure 1 presents conceptual relationships between brain damage and cocaine/stimulant abuse. More clinical studies are needed to establish unequivocally the epidemiological relationships between preexisting neurological deficits-resulting either from genetic, developmental, traumatic, or neurotoxic factors- and vulnerability to drug addictions. Nonetheless, deducing from the results of preclinical studies, it is conceivable that individuals with neurological deficits associated with attention deficit disorder, developmental neuroanatomical abnormalities, lead poisoning, alcoholism, posttraumatic brain lesions, and PTSD may be more vulnerable to stimulant addiction. This notion has significant empirical support as preclinical studies have shown that animals with lesioned prefrontal cortex became supersensitive to cocaine (Schenk et al. 1991) and animals with lesions at the amygdala, VTA, or raphe nuclei manifest more rapid acquisition of amphetamine self-administration than control rats (Deminiere et al. 1989). The above arguments, postulating neuropathology as an intrinsic component of stimulant addiction, should be taken into consideration with the caveat that the clinical manifestations of the disease are heterogenous and addicts may express varying stages and degrees of the disease as determined by environmental and genetic factors. Therefore, it is likely that stimulant addicts who have less advanced neuropathology may recover spontaneously after detoxification with proper nutritional and psychotherapeutic support if they can sustain abstinence. (ABSTR JF - NIDA research monograph AU - Majewska, M D AD - Clinical Trial Branch, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1 EP - 26 VL - 163 SN - 1046-9516, 1046-9516 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Nervous System Diseases -- therapy KW - Opioid-Related Disorders -- pathology KW - Opioid-Related Disorders -- therapy KW - Nervous System Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78342076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Cocaine+addiction+as+a+neurological+disorder%3A+implications+for+treatment.&rft.au=Majewska%2C+M+D&rft.aulast=Majewska&rft.aufirst=M&rft.date=1996-01-01&rft.volume=163&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-10 N1 - Date created - 1996-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine withdrawal alters regulatory elements of dopamine neurons. AN - 78340689; 8809860 JF - NIDA research monograph AU - Pilotte, N S AU - Sharpe, L G AD - Neuroscience Branch, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 193 EP - 202 VL - 163 SN - 1046-9516, 1046-9516 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Narcotics KW - Nerve Tissue Proteins KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Carrier Proteins -- metabolism KW - Humans KW - Nerve Tissue Proteins -- metabolism KW - Substance Withdrawal Syndrome -- metabolism KW - Neurons -- drug effects KW - Neurons -- physiology KW - Dopamine -- physiology KW - Narcotics -- adverse effects KW - Dopamine -- metabolism KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78340689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Cocaine+withdrawal+alters+regulatory+elements+of+dopamine+neurons.&rft.au=Pilotte%2C+N+S%3BSharpe%2C+L+G&rft.aulast=Pilotte&rft.aufirst=N&rft.date=1996-01-01&rft.volume=163&rft.issue=&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-10 N1 - Date created - 1996-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hydroxypropyl cyclodextrins: potential synergism with carcinogens. AN - 78339154; 8926593 AB - The solubility of the lipophilic carcinogens benzo[a]pyrene and aflatoxin B1 in water increases linearly and substantially with the concentration of hydroxypropyl beta-cyclodextrin present. Results of a kinetic study of naphthalene, a model for more potent carcinogens, indicate that the increase in the dissolution rate and in the transport through the aqueous phase into a nonpolar phase is on the same order of magnitude as the increase in solubility. Consequently, hydroxypropyl beta-cyclodextrin, when used in pharmaceutical formulations, has the potential to increase the absorption of carcinogens which enter the gastrointestinal tract either as food components or from air pollution through saliva. Only the above mechanism's simple proportionality needs be considered for estimating the increases in carcinogen absorption in the upper gastrointestinal tract and in the colon. In the presence of bile, however, additional factors are involved and the proportionality does not apply. Bile micelles, which themselves are effective solubilizers of lipophilic carcinogens, were disrupted by hydroxypropyl beta-cyclodextrin because of the formation of complexes with bile salts. Thus, in the presence of bile, two systems for delivery of carcinogens may coexist: that of cotransport with lipids and that of delivery through solubilization by hydroxypropyl beta-cyclodextrin. JF - Journal of pharmaceutical sciences AU - Horský, J AU - Pitha, J AD - National Institutes of Health, NIA/GRC, Baltimore, MD 21224, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 96 EP - 100 VL - 85 IS - 1 SN - 0022-3549, 0022-3549 KW - Carcinogens KW - 0 KW - Cyclodextrins KW - Lipids KW - Naphthalenes KW - beta-Cyclodextrins KW - Water KW - 059QF0KO0R KW - naphthalene KW - 2166IN72UN KW - Benzo(a)pyrene KW - 3417WMA06D KW - 2-hydroxypropyl-beta-cyclodextrin KW - 94035-02-6 KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Bile -- chemistry KW - Naphthalenes -- chemistry KW - Solubility KW - Chemistry, Physical KW - Aflatoxin B1 -- chemistry KW - Water -- chemistry KW - Benzo(a)pyrene -- chemistry KW - Bile -- metabolism KW - Benzo(a)pyrene -- pharmacokinetics KW - Aflatoxin B1 -- pharmacokinetics KW - Lipids -- chemistry KW - Kinetics KW - Chemical Phenomena KW - Mathematical Computing KW - Naphthalenes -- pharmacokinetics KW - Drug Synergism KW - Lipid Metabolism KW - Cyclodextrins -- pharmacology KW - Carcinogens -- chemistry KW - Cyclodextrins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78339154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pharmaceutical+sciences&rft.atitle=Hydroxypropyl+cyclodextrins%3A+potential+synergism+with+carcinogens.&rft.au=Horsk%C3%BD%2C+J%3BPitha%2C+J&rft.aulast=Horsk%C3%BD&rft.aufirst=J&rft.date=1996-01-01&rft.volume=85&rft.issue=1&rft.spage=96&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmaceutical+sciences&rft.issn=00223549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-25 N1 - Date created - 1996-10-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Pharm Sci. 1996 Jul;85(7):789-90 [8819007] J Pharm Sci. 1997 Mar;86(3):402-4 [9050815] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EEG and evoked potentials alterations in cocaine-dependent individuals. AN - 78336494; 8809861 JF - NIDA research monograph AU - Herning, R I AU - King, D E AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 203 EP - 223 VL - 163 SN - 1046-9516, 1046-9516 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Evoked Potentials -- drug effects KW - Psychiatric Status Rating Scales KW - Beta Rhythm -- drug effects KW - Humans KW - Opioid-Related Disorders -- physiopathology KW - Opioid-Related Disorders -- psychology KW - Electroencephalography -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78336494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=EEG+and+evoked+potentials+alterations+in+cocaine-dependent+individuals.&rft.au=Herning%2C+R+I%3BKing%2C+D+E&rft.aulast=Herning&rft.aufirst=R&rft.date=1996-01-01&rft.volume=163&rft.issue=&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-10 N1 - Date created - 1996-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence that nitric oxide enhances cadmium toxicity by displacing the metal from metallothionein. AN - 78330360; 8924612 AB - Cadmium is carcinogenic in humans and rodents. Although extensive evidence indicates that the toxicity and genotoxicity of Cd is ameliorated by binding to cysteine clusters in metallothionein (MT), the factors governing Cd release at intracellular target sites remain unknown. Nitric oxide is a pollutant gas and an important intercellular messenger in the inflammatory immune response. When growing Chinese hamster ovary cells were treated for 24 h with 0.5, 0.75, or 1.0 mM CdCl2 followed by a 1-h exposure to 1.0, 1.5, or 2.0 mM 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (DEA/NO), an NO-generating sodium salt, NO enhanced Cd-induced inhibition of colony forming ability without affecting Cd-induced cytolethality. In experiments designed to determine whether NO acts by displacing Cd from cellular MT, cells treated with 2.0 mM CdCl2 followed by 1.5 or 3.0 mM DEA/NO exhibited 29 and 38% reductions, respectively, in the amount of Cd bound to MT. When purified rat liver MT was used to further characterize NO-induced release of Cd from MT, dose-related increases in Cd displacement were observed at DEA/NO concentrations between 0.1 and 0.5 mM, and a plateau was reached at 3 mol of Cd displaced/mol of MT at higher DEA/NO concentrations. Compared to cells exposed to Cd or DEA/NO alone, cells treated with Cd followed by DEA/NO also exhibited a transient 2-3-fold decrease in c-myc proto-oncogene expression. Taken together, our results support the hypothesis that NO mediates Cd release from MT in vivo and suggest that intracellular generation of free Cd may induce DNA damage and force cells into a period of growth arrest. Such findings may have particular relevance with regard to the etiology of Cd-induced carcinogenesis in human populations. JF - Chemical research in toxicology AU - Misra, R R AU - Hochadel, J F AU - Smith, G T AU - Cook, J C AU - Waalkes, M P AU - Wink, D A AD - Division of Cancer Etiology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. PY - 1996 SP - 326 EP - 332 VL - 9 IS - 1 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Nitric Oxide KW - 31C4KY9ESH KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Animals KW - CHO Cells KW - Gene Expression Regulation -- drug effects KW - Drug Synergism KW - Proto-Oncogenes -- drug effects KW - Cricetinae KW - Nitric Oxide -- toxicity KW - Cadmium -- metabolism KW - Metallothionein -- drug effects KW - Carcinogens -- toxicity KW - Cadmium -- toxicity KW - Nitric Oxide -- metabolism KW - Metallothionein -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78330360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Evidence+that+nitric+oxide+enhances+cadmium+toxicity+by+displacing+the+metal+from+metallothionein.&rft.au=Misra%2C+R+R%3BHochadel%2C+J+F%3BSmith%2C+G+T%3BCook%2C+J+C%3BWaalkes%2C+M+P%3BWink%2C+D+A&rft.aulast=Misra&rft.aufirst=R&rft.date=1996-01-01&rft.volume=9&rft.issue=1&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-05 N1 - Date created - 1996-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation biology of lung cancer. AN - 78324844; 8806097 AB - The enormous problem that is lung cancer still defies satisfactory therapeutic strategy. This article summarizes some of the more important laboratory efforts directed at understanding the biology of this complex disease. The radiation sensitivities of established lung cancer cell lines are outlined. The effect of radiation dose rate and chemotherapy is explored. The emerging biology of oncogenetic alterations is explored as it relates to radiation sensitivity in general, and lung cancer in particular. Finally, novel therapeutic approaches including photodynamic therapy are introduced. JF - Journal of cellular biochemistry. Supplement AU - Sullivan, F J AU - Carmichael, J AU - Glatstein, E AU - Mitchell, J B AD - Radiation Oncology Branch, NCI, Bethesda, Maryland 20992, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 152 EP - 159 VL - 24 SN - 0733-1959, 0733-1959 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Carcinoma, Small Cell -- pathology KW - HeLa Cells -- drug effects KW - Humans KW - Photochemotherapy KW - Radiation Tolerance KW - Drug Resistance, Neoplasm KW - Dose-Response Relationship, Radiation KW - Oncogenes -- radiation effects KW - Carcinoma, Small Cell -- drug therapy KW - Tumor Cells, Cultured -- radiation effects KW - Carcinoma, Non-Small-Cell Lung -- pathology KW - Carcinoma, Small Cell -- radiotherapy KW - Tumor Stem Cell Assay KW - Antineoplastic Agents -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Carcinoma, Non-Small-Cell Lung -- radiotherapy KW - HeLa Cells -- radiation effects KW - Lung Neoplasms -- radiotherapy KW - Lung Neoplasms -- drug therapy KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78324844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Radiation+biology+of+lung+cancer.&rft.au=Sullivan%2C+F+J%3BCarmichael%2C+J%3BGlatstein%2C+E%3BMitchell%2C+J+B&rft.aulast=Sullivan&rft.aufirst=F&rft.date=1996-01-01&rft.volume=24&rft.issue=&rft.spage=152&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spectrum of neuroendocrine differentiation in lung cancer cell lines featured by cytomorphology, markers, and their corresponding tumors. AN - 78324206; 8806093 AB - Lung cancer cell lines which show features of neuroendocrine (NE) differentiation can be divided into 4 types which have distinct clinicopathologic correlates: classic small cell lung cancer (SCLC), variant SCLC, pulmonary carcinoid, and non-small cell lung cancer with NE features (NSCLC-NE). These cell lines form a spectrum regarding their degree of NE differentiation which ranges from high levels seen in carcinoid cell lines to very low which is typical of the variant SCLC. A careful comparison of the properties of tumors and their cell lines and correlating these data with the clinical history of the patient has markedly enhanced the relevance of cell lines as models for NE biology and lung carcinogenesis. JF - Journal of cellular biochemistry. Supplement AU - Linnoila, R I AD - Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 92 EP - 106 VL - 24 SN - 0733-1959, 0733-1959 KW - Biomarkers KW - 0 KW - Biomarkers, Tumor KW - Neoplasm Proteins KW - Index Medicus KW - Carcinoid Tumor -- pathology KW - Tumor Cells, Cultured KW - Humans KW - Cell Differentiation KW - Carcinoid Tumor -- secretion KW - Neoplasm Proteins -- analysis KW - Carcinoid Tumor -- chemistry KW - Carcinoma, Small Cell -- pathology KW - Neuroendocrine Tumors -- pathology KW - Neuroendocrine Tumors -- chemistry KW - Neuroendocrine Tumors -- secretion KW - Lung Neoplasms -- secretion KW - Lung Neoplasms -- chemistry KW - Carcinoma, Non-Small-Cell Lung -- secretion KW - Carcinoma, Small Cell -- secretion KW - Carcinoma, Non-Small-Cell Lung -- chemistry KW - Carcinoma, Small Cell -- chemistry KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78324206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Spectrum+of+neuroendocrine+differentiation+in+lung+cancer+cell+lines+featured+by+cytomorphology%2C+markers%2C+and+their+corresponding+tumors.&rft.au=Linnoila%2C+R+I&rft.aulast=Linnoila&rft.aufirst=R&rft.date=1996-01-01&rft.volume=24&rft.issue=&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The promiscuous IL-2/IL-15 receptor: a target for immunotherapy of HTLV-I-associated disorders. AN - 78321554; 8797721 AB - Human T-cell lymphotrophic virus I (HTLV-I)-encoded tax plays a role in the early phases of HTLV-I-induced disease by deregulating the expression of the genes that encode interleukin-2 (IL-2) and the multisubunit (IL-2R alpha, IL-2R beta, and IL-2R gamma) IL-2 receptor (IL-2R). However, later in the course of the disease adult T-cell leukemia (ATL), cells no longer produce IL-2 yet continue to express the IL-2R. During studies to define the pathogenic mechanisms that underlie this IL-2-independent proliferation, we defined a cytokine designated IL-T/IL-15 that stimulates T-cell proliferation and requires the expression of IL-2R beta and IL-2R gamma for its action. To exploit the fact that IL-2Rs are present on abnormal T cells in patients with tropical parasitic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and ATL but not on normal resting cells, different forms of IL-2R-directed therapy have been initiated. Unmodified humanized anti-Tac is being used to treat patient with TSP/HAM. To enhance its effector function for the treatment of ATL anti-Tac was armed with alpha- and beta-emitting radionuclides. In a clinical trial with 90Y-anti-Tac at the doses used (5, 10, and 15 mCi), 9 of the 18 patients with ATL underwent a partial or sustained complete remission. Thus the clinical application of IL-2R-directed therapy using a humanized monoclonal antibody or that antibody armed with radionuclides provides a new perspective for the treatment of autoimmune disorders such as TSP/HAM and certain neoplastic diseases including ATL. JF - Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association AU - Waldmann, T A AD - Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - S179 EP - S185 VL - 13 Suppl 1 SN - 1077-9450, 1077-9450 KW - Antibodies, Neoplasm KW - 0 KW - Cytokines KW - Gene Products, tax KW - Immunotoxins KW - Neoplasm Proteins KW - Receptors, Interleukin-2 KW - adult T cell leukemia-derived factor KW - Index Medicus KW - AIDS/HIV KW - Neoplasm Proteins -- immunology KW - Humans KW - Cytokines -- immunology KW - Immunotoxins -- therapeutic use KW - Gene Products, tax -- immunology KW - Leukemia, T-Cell -- radiotherapy KW - Leukemia, T-Cell -- therapy KW - Immunotherapy KW - Human T-lymphotropic virus 1 KW - Antibodies, Neoplasm -- therapeutic use KW - Leukemia, T-Cell -- virology KW - Paraparesis, Tropical Spastic -- therapy KW - Receptors, Interleukin-2 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78321554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes+and+human+retrovirology+%3A+official+publication+of+the+International+Retrovirology+Association&rft.atitle=The+promiscuous+IL-2%2FIL-15+receptor%3A+a+target+for+immunotherapy+of+HTLV-I-associated+disorders.&rft.au=Waldmann%2C+T+A&rft.aulast=Waldmann&rft.aufirst=T&rft.date=1996-01-01&rft.volume=13+Suppl+1&rft.issue=&rft.spage=S179&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+and+human+retrovirology+%3A+official+publication+of+the+International+Retrovirology+Association&rft.issn=10779450&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-29 N1 - Date created - 1996-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of nuclear oncogenes expressed in lung cancer cell lines. AN - 78321183; 8806104 AB - Lung cancer is a major cause of mortality in the United States and accounts for the majority of all cancer deaths in both men and women. It is hoped that through broadening our understanding of the mechanisms involved in transformation of bronchial epithelial cells we will be able to improve methods of diagnosis and treatment of this disease, with the ultimate goal of reducing on lung cancer mortality. A knowledge of the molecular mechanisms involved in processes such as cell division and differentiation is paramount to this task, because it is known that aberrant responses to growth factors or cytokines found in the normal cellular milieu can lead to abnormal cell growth and/or transformation. Signals initiated at the cell membrane by tumor promoters, growth factors, or cytokines are transduced from the cell membrane to the nucleus and are, in part, mediated centrally by transcription factors encoded by nuclear protooncogenes. The transcription factors myc, jun, and fos have been characterized in both normal and transformed lung epithelial cells through detailed studies using cell lines. In this manuscript, we review what is known about the expression and regulation of these nuclear protooncogenes in normal and malignant epithelial cells of the lung, and their role in the development of lung cancer. JF - Journal of cellular biochemistry. Supplement AU - Sabichi, A L AU - Birrer, M J AD - Biomarkers and Prevention Research Branch, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 218 EP - 227 VL - 24 SN - 0733-1959, 0733-1959 KW - Carcinogens KW - 0 KW - Neoplasm Proteins KW - RNA, Messenger KW - Transcription Factors KW - Index Medicus KW - Cocarcinogenesis KW - Genes, myc KW - Humans KW - Smoking -- adverse effects KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Gene Amplification KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Genes, fos KW - Promoter Regions, Genetic -- genetics KW - Mutation KW - Female KW - Male KW - Carcinogens -- adverse effects KW - Genes, jun KW - Gene Expression Regulation, Neoplastic KW - Transcription Factors -- physiology KW - Lung Neoplasms -- etiology KW - Oncogenes KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- genetics KW - Lung Neoplasms -- genetics KW - Transcription Factors -- genetics KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78321183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Regulation+of+nuclear+oncogenes+expressed+in+lung+cancer+cell+lines.&rft.au=Sabichi%2C+A+L%3BBirrer%2C+M+J&rft.aulast=Sabichi&rft.aufirst=A&rft.date=1996-01-01&rft.volume=24&rft.issue=&rft.spage=218&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent involvement of chromosome 3p alterations in lung carcinogenesis: allelotypes of 215 established cell lines at six chromosome 3p loci. AN - 78321141; 8806102 AB - We have determined the allelotypes of 215 established lung cancer cell lines by PCR analysis at six loci on the short arm of chromosome 3 (3p): D3S3 (3p12-p13), D3S30 (3p13), D3S2 (3p14-p21.1), D3S32 (3p21), D3F15S2 (3p21), and THRB (3p24). Eighty-seven small cell lung cancer (SCLC), 93 non-small cell lung cancer (NSCLC), 6 extrapulmonary SCLC, 6 mesothelioma, and 23 normal B lymphocyte (BL) cell lines were analyzed. Low levels of heterozygosity at all six 3p loci were seen in both the SCLC and NSCLC cells. SCLC cell lines exhibited the lowest frequencies of heterozygosity at D3S3 (3%), D3S2 (3%), D3F15S2 (10%), and THRB (6%) when compared with frequencies of 8, 42, 48, and 34% at these same loci in the normal population. The lowest frequencies of heterozygosities among the NSCLC cell lines were seen at D3S3 (5%), DF15S2 (17%), and THRB (15%). Adenocarcinoma (Ad) was the only subtype of NSCLC that exhibited any heterozygosity (7%) at D3S3. In addition to D3S3, the lowest frequencies of heterozygosity were seen at D3F15S2 for Ad (9%), D3S2 for large cell carcinomas (8%), and THRB for adenosquamous (0%), bronchioloalveolar (0%), and large cell (8%) carcinomas. In summary, the 3p chromosome region near the D3S3 locus (3p12-p13) appears to be involved in all forms of lung cancer with additional involvement of regions close to the D3S2 (3p14-p21.1), D3F15S2 (3p21), and THRB (3p24) loci. JF - Journal of cellular biochemistry. Supplement AU - Buchhagen, D L AD - NCI-NMOB, National Naval Medical Center, Bethesda, Maryland, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 198 EP - 209 VL - 24 SN - 0733-1959, 0733-1959 KW - DNA, Neoplasm KW - 0 KW - Genetic Markers KW - Index Medicus KW - Carcinoma, Small Cell -- pathology KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Humans KW - Pleural Neoplasms -- pathology KW - Mesothelioma -- genetics KW - Pleural Neoplasms -- genetics KW - Herpesvirus 4, Human KW - Carcinoma, Non-Small-Cell Lung -- pathology KW - Genotype KW - Polymerase Chain Reaction KW - B-Lymphocytes -- drug effects KW - Alleles KW - Tumor Cells, Cultured KW - Mesothelioma -- pathology KW - DNA, Neoplasm -- genetics KW - Cell Line, Transformed KW - Carcinoma, Small Cell -- genetics KW - Chromosomes, Human, Pair 3 -- ultrastructure KW - Chromosomes, Human, Pair 3 -- genetics KW - Chromosome Aberrations KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78321141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Frequent+involvement+of+chromosome+3p+alterations+in+lung+carcinogenesis%3A+allelotypes+of+215+established+cell+lines+at+six+chromosome+3p+loci.&rft.au=Buchhagen%2C+D+L&rft.aulast=Buchhagen&rft.aufirst=D&rft.date=1996-01-01&rft.volume=24&rft.issue=&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dipyridamole mediated enhanced antiproliferative activity of 10-ethyl-10-deazaaminopterin (10-EDAM) against human lung cancer cell lines. AN - 78319512; 8806099 AB - 10-ethyl-10-deazaaminopterin (10-EDAM) is a rationally designed derivative of the antifolate, methotrexate (MTX). In a number of tumor models these design features have resulted in an improved spectrum of antiproliferative activity as compared with the parent compound. Using an MTT growth assay, we compared in vitro antiproliferative activity of 10-EDAM with MTX in eight lung cancer cell lines. Growth was inhibited in all lines tested by clinically achievable concentrations of 10-EDAM (0.1-1,000 nM). 10-EDAM was more cytotoxic than MTX at the same concentrations in all eight lung cancer cell lines. In an effort to enhance the antiproliferative effect, we evaluated the addition of dipyridamole (DPM), an inhibitor of nucleoside transport, to 10-EDAM (0.1-10 microns). DPM decreased the concentration of 10-EDAM required to cause 50% growth inhibition (IC50) in all eight cell lines tested. This suppression was statistically significant by 2-sided sign test (P = .0078). By contrast, the IC50 of MTX was decreased in only two of the eight cell lines when DPM was added (0.1-10 microM). In defined thymidine depleted media, cell kill by the combination of 10-EDAM and DPM was no greater than 10-EDAM alone, consistent with the possibility that DPM exerts some of its effect by inhibition of extrinsic nucleoside salvage. In consideration of the published activity of 10-EDAM in lung cancer and the modest clinical toxicity of DPM based biochemical modulation, we conclude the current in vitro data provide justification for clinical evaluation of this combination in patients with lung cancer. JF - Journal of cellular biochemistry. Supplement AU - Dearing, M P AU - Englee-Miller, M J AU - Kratzke, R A AU - Kramer, B S AU - Chu, E AU - Weinstein, J AU - Anderson, M AU - Venzon, D AU - Mulshine, J L AU - Gazdar, A F AD - NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, Bethesda, Maryland 20889, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 165 EP - 172 VL - 24 SN - 0733-1959, 0733-1959 KW - Folic Acid Antagonists KW - 0 KW - Growth Inhibitors KW - Nucleosides KW - Dipyridamole KW - 64ALC7F90C KW - edatrexate KW - JT4X6Z1HRR KW - Aminopterin KW - JYB41CTM2Q KW - Thymidine KW - VC2W18DGKR KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Methotrexate -- pharmacology KW - Nucleosides -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - Drug Synergism KW - Thymidine -- deficiency KW - Thymidine -- pharmacology KW - Depression, Chemical KW - Biological Transport -- drug effects KW - Folic Acid Antagonists -- pharmacology KW - Growth Inhibitors -- pharmacology KW - Aminopterin -- pharmacology KW - Aminopterin -- analogs & derivatives KW - Dipyridamole -- pharmacology KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78319512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Dipyridamole+mediated+enhanced+antiproliferative+activity+of+10-ethyl-10-deazaaminopterin+%2810-EDAM%29+against+human+lung+cancer+cell+lines.&rft.au=Dearing%2C+M+P%3BEnglee-Miller%2C+M+J%3BKratzke%2C+R+A%3BKramer%2C+B+S%3BChu%2C+E%3BWeinstein%2C+J%3BAnderson%2C+M%3BVenzon%2C+D%3BMulshine%2C+J+L%3BGazdar%2C+A+F&rft.aulast=Dearing&rft.aufirst=M&rft.date=1996-01-01&rft.volume=24&rft.issue=&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro and in vivo studies of mesothelioma. AN - 78318126; 8806096 AB - Pleural mesothelioma is an asbestos-related malignancy characterized by progressive local growth, late metastases, and median survivals between 8 and 18 months. It is only recently that the in vitro and in vivo characteristics of the malignancy has been investigated. These investigations have been aided by the development of cell lines from patients with the disease, as well as lines developed from asbestos-exposed animals. Nude mouse models constructed with subcutaneous, intraabdominal, or intrathoracic innoculation of cultured cell lines or fresh tumor have been used for evaluating response to innovative therapies. Karyotyping has been performed on a number of cell lines and multiple abnormalities involving many chromosomes have been identified. Aneuploidy is commonly seen, along with reported non-random patterns of chromosomal aberrations. The role of tumor suppressor genes, including p53 is controversial. Multiple growth factors including PDGF are being investigated for a possible paracrine/autocrine loop, and PDGF receptors seem to be differentially expressed in mesothelioma cells compared to normal mesothelial cells. The role of cytokines in the pathophysiology of the disease, secreted either by the tumor cells themselves or by monocyte/macrophages in the local tumor environment, remains to be defined. JF - Journal of cellular biochemistry. Supplement AU - Pass, H I AU - Mew, D J AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 142 EP - 151 VL - 24 SN - 0733-1959, 0733-1959 KW - Culture Media KW - 0 KW - Cytokines KW - DNA, Neoplasm KW - Growth Substances KW - Neoplasm Proteins KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Neoplasm Proteins -- biosynthesis KW - Animals KW - Growth Substances -- genetics KW - Cytokines -- genetics KW - Tumor Cells, Cultured -- drug effects KW - Cytokines -- biosynthesis KW - Humans KW - Tumor Cells, Cultured -- transplantation KW - Mice, Nude KW - Mice KW - Gene Amplification KW - Neoplasm Transplantation KW - Oncogenes KW - Genes, p53 KW - Neoplasm Proteins -- genetics KW - Chromosome Aberrations KW - Transplantation, Heterologous KW - Asbestos -- adverse effects KW - DNA, Neoplasm -- genetics KW - Mesothelioma -- etiology KW - Pleural Neoplasms -- pathology KW - Mesothelioma -- genetics KW - Pleural Neoplasms -- genetics KW - Mesothelioma -- pathology KW - Pleural Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78318126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=In+vitro+and+in+vivo+studies+of+mesothelioma.&rft.au=Pass%2C+H+I%3BMew%2C+D+J&rft.aulast=Pass&rft.aufirst=H&rft.date=1996-01-01&rft.volume=24&rft.issue=&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-17 N1 - Date created - 1996-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of structure-function relationship of RNA polymerase in Escherichia coli. AN - 78313654; 8791620 JF - Methods in enzymology AU - Jin, D J AU - Zhou, Y N AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 300 EP - 319 VL - 273 SN - 0076-6879, 0076-6879 KW - Aminoglycosides KW - 0 KW - Anti-Bacterial Agents KW - Bacterial Proteins KW - Nucleic Acid Synthesis Inhibitors KW - sorangicin A KW - 100415-25-6 KW - streptolydigin KW - 7229-50-7 KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Rifampin KW - VJT6J7R4TR KW - Index Medicus KW - Anti-Bacterial Agents -- metabolism KW - Genes, Bacterial KW - Transcription, Genetic -- drug effects KW - Rifampin -- metabolism KW - Anti-Bacterial Agents -- pharmacology KW - Nucleic Acid Synthesis Inhibitors -- metabolism KW - Binding Sites KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Nucleic Acid Synthesis Inhibitors -- pharmacology KW - Terminator Regions, Genetic KW - Promoter Regions, Genetic KW - Rifampin -- pharmacology KW - Catalysis KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- antagonists & inhibitors KW - Bacterial Proteins -- chemistry KW - DNA-Directed RNA Polymerases -- chemistry KW - Escherichia coli -- genetics KW - DNA-Directed RNA Polymerases -- physiology KW - DNA-Directed RNA Polymerases -- antagonists & inhibitors KW - Escherichia coli -- enzymology KW - Bacterial Proteins -- physiology KW - Protein Conformation KW - DNA-Directed RNA Polymerases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78313654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Mutational+analysis+of+structure-function+relationship+of+RNA+polymerase+in+Escherichia+coli.&rft.au=Jin%2C+D+J%3BZhou%2C+Y+N&rft.aulast=Jin&rft.aufirst=D&rft.date=1996-01-01&rft.volume=273&rft.issue=&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-11 N1 - Date created - 1996-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA damage and nitric oxide. AN - 78310518; 8794210 JF - Advances in experimental medicine and biology AU - Keefer, L K AU - Wink, D A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 177 EP - 185 VL - 387 SN - 0065-2598, 0065-2598 KW - Nitric Oxide KW - 31C4KY9ESH KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Humans KW - DNA -- chemistry KW - DNA Damage KW - Nitric Oxide -- physiology KW - Nitric Oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78310518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=DNA+damage+and+nitric+oxide.&rft.au=Keefer%2C+L+K%3BWink%2C+D+A&rft.aulast=Keefer&rft.aufirst=L&rft.date=1996-01-01&rft.volume=387&rft.issue=&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-14 N1 - Date created - 1997-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactions of reactive metabolites with hemoproteins--toxicological implications: covalent alteration of hemoproteins. AN - 78310330; 8794192 JF - Advances in experimental medicine and biology AU - Osawa, Y AU - Nakatsuka, K AU - Williams, M S AU - Kindt, J T AU - Nakatsuka, M AD - Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1760, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 37 EP - 45 VL - 387 SN - 0065-2598, 0065-2598 KW - Free Radicals KW - 0 KW - Hemeproteins KW - Hemoglobins KW - Myoglobin KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Myoglobin -- toxicity KW - Erythrocytes -- drug effects KW - Animals KW - Myoglobin -- chemistry KW - Hemoglobins -- toxicity KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Humans KW - Free Radicals -- chemistry KW - Hemoglobins -- chemistry KW - Free Radicals -- pharmacology KW - Erythrocytes -- metabolism KW - Hemeproteins -- toxicity KW - Hemeproteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78310330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Reactions+of+reactive+metabolites+with+hemoproteins--toxicological+implications%3A+covalent+alteration+of+hemoproteins.&rft.au=Osawa%2C+Y%3BNakatsuka%2C+K%3BWilliams%2C+M+S%3BKindt%2C+J+T%3BNakatsuka%2C+M&rft.aulast=Osawa&rft.aufirst=Y&rft.date=1996-01-01&rft.volume=387&rft.issue=&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-14 N1 - Date created - 1997-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for and implications of SV40-like sequences in human mesotheliomas. AN - 78306963; 8791130 JF - Important advances in oncology AU - Pass, H I AU - Kennedy, R C AU - Carbone, M AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 89 EP - 108 SN - 0883-5896, 0883-5896 KW - Antibodies, Viral KW - 0 KW - Antigens, Polyomavirus Transforming KW - DNA, Neoplasm KW - DNA, Viral KW - Poliovirus Vaccine, Inactivated KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Neoplasms, Experimental -- virology KW - Animals KW - Humans KW - Immunotherapy KW - Asbestosis -- complications KW - Antigens, Polyomavirus Transforming -- physiology KW - Child KW - Brain Neoplasms -- virology KW - Tumor Virus Infections -- transmission KW - Oncogenes KW - Adult KW - Asbestos -- adverse effects KW - Poliovirus Vaccine, Inactivated -- adverse effects KW - Antigens, Polyomavirus Transforming -- immunology KW - Virus Replication KW - Cocarcinogenesis KW - Papillomavirus Infections -- transmission KW - Drug Contamination KW - Macaca KW - Smoking -- adverse effects KW - Mice KW - Antigens, Polyomavirus Transforming -- genetics KW - Antibodies, Viral -- blood KW - DNA, Viral -- analysis KW - DNA, Neoplasm -- genetics KW - Mesocricetus KW - Follow-Up Studies KW - Genes, Viral KW - Middle Aged KW - Species Specificity KW - Cell Transformation, Viral KW - Cricetinae KW - Mesothelioma -- therapy KW - Mesothelioma -- epidemiology KW - Simian virus 40 -- genetics KW - Mesothelioma -- etiology KW - Pleural Neoplasms -- epidemiology KW - Pleural Neoplasms -- virology KW - Polyomavirus -- genetics KW - Simian virus 40 -- pathogenicity KW - Mesothelioma -- genetics KW - Pleural Neoplasms -- genetics KW - Pleural Neoplasms -- therapy KW - Simian virus 40 -- physiology KW - Polyomavirus -- pathogenicity KW - Polyomavirus -- isolation & purification KW - Mesothelioma -- virology KW - Simian virus 40 -- immunology KW - Pleural Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78306963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Important+advances+in+oncology&rft.atitle=Evidence+for+and+implications+of+SV40-like+sequences+in+human+mesotheliomas.&rft.au=Pass%2C+H+I%3BKennedy%2C+R+C%3BCarbone%2C+M&rft.aulast=Pass&rft.aufirst=H&rft.date=1996-01-01&rft.volume=&rft.issue=&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Important+advances+in+oncology&rft.issn=08835896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-09 N1 - Date created - 1996-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rebeca Gerschman: a personal remembrance. AN - 78306784; 8791086 JF - Free radical biology & medicine AU - Gilbert, D L AD - Unit on Reactive Oxygen Species, NINDS, National Institutes of Health, Bethesda, Maryland 20892-4156, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1 EP - 4 VL - 21 IS - 1 SN - 0891-5849, 0891-5849 KW - Free Radicals KW - 0 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - History of medicine KW - Gerschman KW - X-Rays KW - History, 20th Century KW - Argentina KW - Humans KW - Oxygen -- poisoning KW - Radiation Injuries KW - Physiology -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78306784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Rebeca+Gerschman%3A+a+personal+remembrance.&rft.au=Gilbert%2C+D+L&rft.aulast=Gilbert&rft.aufirst=D&rft.date=1996-01-01&rft.volume=21&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-12 N1 - Date created - 1997-02-12 N1 - Date revised - 2017-01-13 N1 - People - Gerschman N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Gerschman ER - TY - JOUR T1 - The use of data on biologically reactive intermediates in risk assessment. AN - 78304090; 8794237 JF - Advances in experimental medicine and biology AU - Buchanan, J R AU - Portier, C J AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 429 EP - 437 VL - 387 SN - 0065-2598, 0065-2598 KW - Free Radicals KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Models, Biological KW - Pharmacokinetics KW - Free Radicals -- toxicity KW - Free Radicals -- chemistry KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78304090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=The+use+of+data+on+biologically+reactive+intermediates+in+risk+assessment.&rft.au=Buchanan%2C+J+R%3BPortier%2C+C+J&rft.aulast=Buchanan&rft.aufirst=J&rft.date=1996-01-01&rft.volume=387&rft.issue=&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-14 N1 - Date created - 1997-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Covalent crosslinking of the heme prosthetic group to myoglobin by H2O2: toxicological implications. AN - 78301027; 8791091 AB - It is known that treatment of myoglobin with H2O2 leads to covalent alteration of the heme prosthetic group with concomitant formation of a protein bound heme adduct and transforms myoglobin from an oxygen storage protein to an oxidase. In the current study it was shown, with the use of 14C-labeled heme reconstituted into apomyoglobin, that up to 88% of the oxidatively altered heme can be accounted for by the protein bound product. Furthermore, a partially purified preparation of the protein bound heme adduct was introduced into human fibroblasts using the method of osmotic lysis of pinosomes and found to cause cell death (40%) within 1 h, as evidenced by trypan blue exclusion. Native myoglobin introduced into cells in the same manner or extracellular treatment by the protein bound heme adduct had no effect on cell viability. The extent of cell death could be decreased (50%) by N-acetyl-L-cysteine, indicating a potential role for reactive oxygen intermediates in this process. These results show that the covalently altered myoglobin can elicit cellular damage and suggests that similar processes may occur in vivo in pathologic conditions such as that involving cardiac ischemia and reperfusion injury, where covalently altered myoglobin may form. JF - Free radical biology & medicine AU - Osawa, Y AU - Williams, M S AD - Laboratory of Molecular Immunology, NHLBI, NIH, Bethesda, MD 20892-1760, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 35 EP - 41 VL - 21 IS - 1 SN - 0891-5849, 0891-5849 KW - Apoproteins KW - 0 KW - Carbon Radioisotopes KW - Cross-Linking Reagents KW - Myoglobin KW - apomyoglobin KW - Heme KW - 42VZT0U6YR KW - Hydrogen Peroxide KW - BBX060AN9V KW - Oxidoreductases KW - EC 1.- KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Animals KW - Humans KW - Horses KW - Radioisotope Dilution Technique KW - Acetylcysteine -- pharmacology KW - Cell Death -- drug effects KW - Protein Binding KW - Cell Line KW - Fibroblasts KW - Binding Sites KW - Apoproteins -- chemistry KW - Oxidoreductases -- metabolism KW - Myoglobin -- chemistry KW - Heme -- chemistry KW - Myoglobin -- metabolism KW - Heme -- metabolism KW - Apoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78301027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Covalent+crosslinking+of+the+heme+prosthetic+group+to+myoglobin+by+H2O2%3A+toxicological+implications.&rft.au=Osawa%2C+Y%3BWilliams%2C+M+S&rft.aulast=Osawa&rft.aufirst=Y&rft.date=1996-01-01&rft.volume=21&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-12 N1 - Date created - 1997-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of selectivity of reactive nitrogen oxide species for various substrates. AN - 78300957; 8782578 JF - Methods in enzymology AU - Wink, D A AU - Grisham, M B AU - Miles, A M AU - Nims, R W AU - Krishna, M C AU - Pacelli, R AU - Teague, D AU - Poore, C M AU - Cook, J A AU - Ford, P C AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 120 EP - 130 VL - 268 SN - 0076-6879, 0076-6879 KW - Azides KW - 0 KW - Free Radical Scavengers KW - Indicators and Reagents KW - Nitrogen Oxides KW - Reactive Oxygen Species KW - Triazoles KW - Glutathione KW - GAN16C9B8O KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Spectrometry, Fluorescence KW - Models, Chemical KW - Nitrogen Oxides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78300957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Determination+of+selectivity+of+reactive+nitrogen+oxide+species+for+various+substrates.&rft.au=Wink%2C+D+A%3BGrisham%2C+M+B%3BMiles%2C+A+M%3BNims%2C+R+W%3BKrishna%2C+M+C%3BPacelli%2C+R%3BTeague%2C+D%3BPoore%2C+C+M%3BCook%2C+J+A%3BFord%2C+P+C&rft.aulast=Wink&rft.aufirst=D&rft.date=1996-01-01&rft.volume=268&rft.issue=&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electrochemical methods for detection of nitric oxide. AN - 78300242; 8782574 JF - Methods in enzymology AU - Christodoulou, D AU - Kudo, S AU - Cook, J A AU - Krishna, M C AU - Miles, A AU - Grisham, M B AU - Murugesan, M AU - Ford, P C AU - Wink, D A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 69 EP - 83 VL - 268 SN - 0076-6879, 0076-6879 KW - Bridged Bicyclo Compounds, Heterocyclic KW - 0 KW - Indicators and Reagents KW - Phosphites KW - Porphyrins KW - trimethylolpropane phosphite KW - 1ND7080ZYD KW - Nitric Oxide KW - 31C4KY9ESH KW - linsidomine KW - 5O5U71P6VQ KW - Molsidomine KW - D46583G77X KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Sensitivity and Specificity KW - Electrochemistry -- methods KW - Molsidomine -- analysis KW - Kinetics KW - Molsidomine -- analogs & derivatives KW - Electrodes KW - Time Factors KW - Nitric Oxide -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78300242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Electrochemical+methods+for+detection+of+nitric+oxide.&rft.au=Christodoulou%2C+D%3BKudo%2C+S%3BCook%2C+J+A%3BKrishna%2C+M+C%3BMiles%2C+A%3BGrisham%2C+M+B%3BMurugesan%2C+M%3BFord%2C+P+C%3BWink%2C+D+A&rft.aulast=Christodoulou&rft.aufirst=D&rft.date=1996-01-01&rft.volume=268&rft.issue=&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - "NONOates" (1-substituted diazen-1-ium-1,2-diolates) as nitric oxide donors: convenient nitric oxide dosage forms. AN - 78298995; 8782594 JF - Methods in enzymology AU - Keefer, L K AU - Nims, R W AU - Davies, K M AU - Wink, D A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 281 EP - 293 VL - 268 SN - 0076-6879, 0076-6879 KW - Cytochrome P-450 Enzyme Inhibitors KW - 0 KW - Enzyme Inhibitors KW - Imides KW - Indicators and Reagents KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Molecular Structure KW - Drug Stability KW - Kinetics KW - Enzyme Inhibitors -- chemistry KW - Enzyme Inhibitors -- pharmacology KW - Chemistry -- methods KW - Quality Control KW - Structure-Activity Relationship KW - Nitric Oxide -- analysis KW - Imides -- chemistry KW - Nitric Oxide -- pharmacology KW - Nitric Oxide -- chemistry KW - Imides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78298995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=%22NONOates%22+%281-substituted+diazen-1-ium-1%2C2-diolates%29+as+nitric+oxide+donors%3A+convenient+nitric+oxide+dosage+forms.&rft.au=Keefer%2C+L+K%3BNims%2C+R+W%3BDavies%2C+K+M%3BWink%2C+D+A&rft.aulast=Keefer&rft.aufirst=L&rft.date=1996-01-01&rft.volume=268&rft.issue=&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium. AN - 78295787; 8788508 AB - This study sought to investigate possible interactions between antidepressant agents and lysergic acid diethylamide (LSD) in humans through the use of retrospective questionnaires. Ten subjects were identified who used LSD during chronic (3 weeks or longer) periods of antidepressant administration. These subjects were asked to describe the phenomenological effects of self-administered hallucinogens prior to and during antidepressant treatment; a structured, standardized questionnaire was used to evaluate LSD experiences. Chronic tricyclic antidepressant administration was associated with subjective increases in physical, hallucinatory and psychological responses to LSD. Similarly, subjects receiving lithium chronically also reported increases in their responses to LSD. In contrast, subjects who had been chronically taking an monoamine oxidase (MAO) inhibitor reported subjective decreases in the effects of LSD. This is similar to a previous report by our group of a decreased response to LSD in individuals who were chronically taking serotonin-selective antidepressants. These altered responses to LSD most likely involve differential changes in central serotonin and dopamine receptor systems and are consistent with other recent data suggesting that the clinical efficacy of different classes of antidepressants may not necessarily rely on a common mechanism of action in the brain. JF - Behavioural brain research AU - Bonson, K R AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892-1264, USA. kbonson@helix.nih.gov Y1 - 1996 PY - 1996 DA - 1996 SP - 229 EP - 233 VL - 73 IS - 1-2 SN - 0166-4328, 0166-4328 KW - Antidepressive Agents, Tricyclic KW - 0 KW - Hallucinogens KW - Monoamine Oxidase Inhibitors KW - Lysergic Acid Diethylamide KW - 8NA5SWF92O KW - Lithium KW - 9FN79X2M3F KW - Index Medicus KW - Drug Interactions KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Male KW - Female KW - Antidepressive Agents, Tricyclic -- pharmacology KW - Hallucinogens -- pharmacology KW - Lysergic Acid Diethylamide -- pharmacology KW - Monoamine Oxidase Inhibitors -- pharmacology KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78295787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioural+brain+research&rft.atitle=Alterations+in+responses+to+LSD+in+humans+associated+with+chronic+administration+of+tricyclic+antidepressants%2C+monoamine+oxidase+inhibitors+or+lithium.&rft.au=Bonson%2C+K+R%3BMurphy%2C+D+L&rft.aulast=Bonson&rft.aufirst=K&rft.date=1996-01-01&rft.volume=73&rft.issue=1-2&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Behavioural+brain+research&rft.issn=01664328&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of cytokines on antiviral pharmacokinetics: an alternative approach to assessment of drug interactions using bioequivalence guidelines. AN - 78295196; 8787899 AB - The effects of cytokines on the pharmacokinetics of nucleoside analogs were evaluated in two separate studies using zidovudine in combination with interleukin-2 and didanosine in combination with alpha interferon. In each study, drug interactions were evaluated by using both a standard method (Student's t test) and bioequivalence testing. Serial blood samples were collected from human immunodeficiency virus-infected patients prior to and during cytokine therapy for determination of nucleoside analog concentrations. Concentrations were fit separately to a two-compartment model by using the iterative two-stage approach to population analysis. No alterations in area under the curve or oral clearance were observed for either drug during combination therapy. In general, there was good agreement between statistical methods for determining if antiviral pharmacokinetic parameters were altered by concomitant cytokine therapy. However, large individual changes in the maximum concentration of zidovudine in serum were detected by bioequivalence testing but no difference was found by Student's t test. For didanosine, significant but clinically irrelevant decreases determined by standard hypothesis testing were seen for both the volume of the central compartment (1.91 to 1.86 liters) and the absorption rate constant (0.79 to 0.73 h-1) in the presence of alpha interferon. No interaction was noted for these parameters by using bioequivalence guidelines. Bioequivalence testing may provide an alternative approach to assessment of drug interactions. Interleukin-2 and alpha interferon do not alter the pharmacokinetics of zidovudine and didanosine, respectively. JF - Antimicrobial agents and chemotherapy AU - Piscitelli, S C AU - Amatea, M A AU - Vogel, S AU - Bechtel, C AU - Metcalf, J A AU - Kovacs, J A AD - Department of Pharmacy, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. spisc@nih.gov Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 161 EP - 165 VL - 40 IS - 1 SN - 0066-4804, 0066-4804 KW - Antiviral Agents KW - 0 KW - Cytokines KW - Interferon-alpha KW - Interleukin-2 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Interferon-alpha -- pharmacology KW - Interleukin-2 -- pharmacology KW - Reference Values KW - Drug Interactions KW - Didanosine -- standards KW - Humans KW - Reference Standards KW - Interleukin-2 -- standards KW - Didanosine -- pharmacokinetics KW - Therapeutic Equivalency KW - Drug Therapy, Combination KW - Zidovudine -- pharmacokinetics KW - Zidovudine -- standards KW - Adult KW - HIV Infections -- drug therapy KW - Interferon-alpha -- standards KW - Male KW - Female KW - Cytokines -- pharmacology KW - Antiviral Agents -- pharmacology KW - Antiviral Agents -- standards KW - Cytokines -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78295196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Effects+of+cytokines+on+antiviral+pharmacokinetics%3A+an+alternative+approach+to+assessment+of+drug+interactions+using+bioequivalence+guidelines.&rft.au=Piscitelli%2C+S+C%3BAmatea%2C+M+A%3BVogel%2C+S%3BBechtel%2C+C%3BMetcalf%2C+J+A%3BKovacs%2C+J+A&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1996-01-01&rft.volume=40&rft.issue=1&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Chromatogr. 1990 Nov 30;533:282-90 [2127936] Biotherapy. 1990;2(2):119-36 [2205261] Int J Clin Pharmacol Ther Toxicol. 1991 Aug;29(8):323-8 [1835963] J Clin Pharmacol. 1992 Mar;32(3):242-7 [1564128] Pharmacotherapy. 1993 Jul-Aug;13(4):369-77 [8361863] Ann N Y Acad Sci. 1993 Jun 23;685:687-96 [8363275] Drugs. 1993 Sep;46(3):446-514 [7693434] J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75 [671222] J Clin Invest. 1983 Jul;72(1):398-403 [6308051] Drug Metab Rev. 1984;15(1-2):265-92 [6745083] Antimicrob Agents Chemother. 1987 Feb;31(2):168-72 [3471180] N Engl J Med. 1987 Jul 23;317(4):185-91 [3299089] J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80 [3450848] J Infect Dis. 1994 Jun;169(6):1351-5 [7910838] Clin Pharmacol Ther. 1994 Jun;55(6):649-60 [8004881] N Engl J Med. 1995 Mar 2;332(9):567-75 [7646637] Ann Intern Med. 1989 Aug 15;111(4):280-7 [2757312] N Engl J Med. 1990 Apr 5;322(14):941-9 [1969115] Antimicrob Agents Chemother. 1990 Mar;34(3):394-7 [2334151] Ann Intern Med. 1990 Jun 1;112(11):805-11 [1971503] Arch Intern Med. 1991 Nov;151(11):2281-8 [1953234] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct and indirect effects of nitric oxide in chemical reactions relevant to biology. AN - 78294914; 8782570 JF - Methods in enzymology AU - Wink, D A AU - Grisham, M B AU - Mitchell, J B AU - Ford, P C AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 12 EP - 31 VL - 268 SN - 0076-6879, 0076-6879 KW - Free Radicals KW - 0 KW - Hemeproteins KW - Metals KW - Reactive Oxygen Species KW - Nitric Oxide KW - 31C4KY9ESH KW - Transferases KW - EC 2.- KW - Alkyl and Aryl Transferases KW - EC 2.5.- KW - DNA alkyltransferase KW - EC 2.5.1.- KW - Guanylate Cyclase KW - EC 4.6.1.2 KW - Index Medicus KW - Guanylate Cyclase -- metabolism KW - Animals KW - Hemeproteins -- metabolism KW - DNA Repair KW - Kinetics KW - Zinc Fingers KW - Transferases -- metabolism KW - Nitric Oxide -- physiology KW - Nitric Oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78294914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Direct+and+indirect+effects+of+nitric+oxide+in+chemical+reactions+relevant+to+biology.&rft.au=Wink%2C+D+A%3BGrisham%2C+M+B%3BMitchell%2C+J+B%3BFord%2C+P+C&rft.aulast=Wink&rft.aufirst=D&rft.date=1996-01-01&rft.volume=268&rft.issue=&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Colorimetric assays for nitric oxide and nitrogen oxide species formed from nitric oxide stock solutions and donor compounds. AN - 78292615; 8782576 JF - Methods in enzymology AU - Nims, R W AU - Cook, J C AU - Krishna, M C AU - Christodoulou, D AU - Poore, C M AU - Miles, A M AU - Grisham, M B AU - Wink, D A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 93 EP - 105 VL - 268 SN - 0076-6879, 0076-6879 KW - Ferrocyanides KW - 0 KW - Indicators and Reagents KW - Nitrogen Oxides KW - Nitroso Compounds KW - Solutions KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - hexacyanoferrate II KW - FLX0VIC39Y KW - Index Medicus KW - Oxidation-Reduction KW - Molecular Structure KW - Colorimetry -- methods KW - Spectrophotometry -- methods KW - Nitric Oxide -- analysis KW - Nitric Oxide -- chemistry KW - Nitrogen Oxides -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78292615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Colorimetric+assays+for+nitric+oxide+and+nitrogen+oxide+species+formed+from+nitric+oxide+stock+solutions+and+donor+compounds.&rft.au=Nims%2C+R+W%3BCook%2C+J+C%3BKrishna%2C+M+C%3BChristodoulou%2C+D%3BPoore%2C+C+M%3BMiles%2C+A+M%3BGrisham%2C+M+B%3BWink%2C+D+A&rft.aulast=Nims&rft.aufirst=R&rft.date=1996-01-01&rft.volume=268&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cognitive event-related potentials in populations at risk for substance abuse. AN - 78289792; 8784859 JF - NIDA research monograph AU - Herning, R I AD - Medical Affairs Branch, Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 161 EP - 85; discussion 186-92 VL - 159 SN - 1046-9516, 1046-9516 KW - Central Nervous System Stimulants KW - 0 KW - Methylphenidate KW - 207ZZ9QZ49 KW - Index Medicus KW - Attention Deficit Disorder with Hyperactivity -- psychology KW - Social Behavior Disorders KW - Evoked Potentials KW - Depressive Disorder -- psychology KW - Aggression -- psychology KW - Risk Factors KW - Humans KW - Child KW - Research Design KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - Central Nervous System Stimulants -- pharmacology KW - Methylphenidate -- pharmacology KW - Substance-Related Disorders -- psychology KW - Cognition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78289792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Cognitive+event-related+potentials+in+populations+at+risk+for+substance+abuse.&rft.au=Herning%2C+R+I&rft.aulast=Herning&rft.aufirst=R&rft.date=1996-01-01&rft.volume=159&rft.issue=&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Commentary: three approaches to drug abuse genetics. AN - 78289576; 8784857 JF - NIDA research monograph AU - Uhl, G R AD - Molecular Neurobiology Branch, Addiction Research Center, National Institute on Drug Abuse, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 123 EP - 128 VL - 159 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Psychology KW - Humans KW - Research Design KW - Comorbidity KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- genetics KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78289576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Commentary%3A+three+approaches+to+drug+abuse+genetics.&rft.au=Uhl%2C+G+R&rft.aulast=Uhl&rft.aufirst=G&rft.date=1996-01-01&rft.volume=159&rft.issue=&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: NIDA Res Monogr. 1996;159:81-112; discussion 113-22 [8784856] NIDA Res Monogr. 1996;159:16-38; discussion 39-48 [8784854] NIDA Res Monogr. 1996;159:49-72; discussion 73-80 [8784855] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction: individual differences in the biobehavioral etiology of drug abuse. AN - 78289574; 8784853 JF - NIDA research monograph AU - Gordon, H W AU - Glantz, M D AD - Biobehavioral Research Program, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1 EP - 15 VL - 159 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Public Health KW - Disease Susceptibility KW - Humans KW - Research KW - Neurochemistry KW - Neurophysiology KW - Substance-Related Disorders -- etiology KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78289574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Introduction%3A+individual+differences+in+the+biobehavioral+etiology+of+drug+abuse.&rft.au=Gordon%2C+H+W%3BGlantz%2C+M+D&rft.aulast=Gordon&rft.aufirst=H&rft.date=1996-01-01&rft.volume=159&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immune-based therapies for treatment of HIV infection. AN - 78282439; 8773168 AB - To review the in vitro, animal, and clinical data on immune-based therapies for treatment of HIV infection. An extensive MEDLINE search was performed for interleukins, interferons, immunotoxins, tumor necrosis factor (TNF)-directed agents, vaccines, and gene therapy. In vitro experiments with immune-based agents in cell lines infected with HIV were included. In addition, all human studies and case reports that used these agents in patients infected with HIV were selected. Additional literature included abstracts from international meetings on HIV and AIDS. Data regarding activity, efficacy, and toxicity were extracted from in vitro and in vivo studies. When conflicting data were observed, both viewpoints were stated to give an unbiased analysis. Because HIV research involves multiple social, ethical, and scientific issues, perspectives on these problems were addressed, where appropriate. Current antiretroviral therapy is limited to short-term responses and has minimal effect on overall survival. Because the human immune response to HIV infection is effective at keeping the virus suppressed for a number of years, a focus of HIV research has been to examine immune-based therapies for treatment of HIV infection that attempt to augment enhance, or boost the patient's immune system. Interleukins, interferons, immunotoxins, TNF-directed therapies, vaccines, and gene therapy have been studied in patients infected with HIV. Properties shared among these therapeutic modalities include adverse effect profiles, response rates dependent on baseline immunocompetence, the potential to activate viral replication, the need for supportive care, and sensitive laboratory tests required for monitoring. Immune-based agents represent a new approach to the treatment of HIV infection. Whereas antiretrovirals only inhibit viral replication, these agents are designed to enhance the immune system of the patient. Future attempts to manage HIV infection may combine standard nucleoside analogs with immune-based therapies. JF - The Annals of pharmacotherapy AU - Piscitelli, S C AU - Minor, J R AU - Saville, M W AU - Davey, R T AD - Department of Pharmacy, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 62 EP - 76 VL - 30 IS - 1 SN - 1060-0280, 1060-0280 KW - AIDS Vaccines KW - 0 KW - Adjuvants, Immunologic KW - Immunotoxins KW - Index Medicus KW - AIDS/HIV KW - Animals KW - AIDS Vaccines -- therapeutic use KW - Humans KW - Immunotoxins -- therapeutic use KW - Genetic Therapy KW - Adjuvants, Immunologic -- therapeutic use KW - Immunotherapy KW - HIV Infections -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78282439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+pharmacotherapy&rft.atitle=Immune-based+therapies+for+treatment+of+HIV+infection.&rft.au=Piscitelli%2C+S+C%3BMinor%2C+J+R%3BSaville%2C+M+W%3BDavey%2C+R+T&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1996-01-01&rft.volume=30&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+pharmacotherapy&rft.issn=10600280&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-09 N1 - Date created - 1996-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary retinoic acid inhibits mouse skin carcinogenesis irrespective of age at initiation. AN - 78276835; 8771568 AB - In the two-stage protocol of skin carcinogenesis, the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) is applied to the skin of mice at around seven weeks of age. We previously performed DMBA initiation at three weeks of age to study the effect of pharmacological (30 micrograms/g diet) dietary retinoic acid (RA) on skin carcinogenesis. In this study we asked whether dietary pharmacological RA is equally effective against skin carcinogenesis when mice are initiated with (DMBA) at 7 weeks of age and then subjected to weekly applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or mezerein (MEZ) for 20 weeks. Similar to the three-week initiation protocol, high dietary RA inhibited papilloma incidence and yield in MEZ- but not in TPA-promoted female SENCAR mice. In addition, carcinoma incidence and yield were decreased by high dietary RA in TPA- as well as MEZ-treated mice. These data demonstrate that the high dietary RA diet is as effective in inhibiting papilloma and carcinoma formation when the DMBA is applied at seven weeks of age as at three weeks. JF - Nutrition and cancer AU - De Luca, L M AU - Tarone, R AU - Huynh, M AU - Jones, C S AU - Chen, L C AD - Differentiation Control Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 249 EP - 257 VL - 25 IS - 3 SN - 0163-5581, 0163-5581 KW - Antineoplastic Agents KW - 0 KW - Carcinogens KW - Diterpenes KW - Terpenes KW - mezerein KW - 34807-41-5 KW - Tretinoin KW - 5688UTC01R KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Terpenes -- administration & dosage KW - Papilloma -- prevention & control KW - Tetradecanoylphorbol Acetate -- administration & dosage KW - Mice KW - Female KW - Skin Neoplasms -- chemically induced KW - Tretinoin -- administration & dosage KW - Aging KW - Diet KW - Skin Neoplasms -- prevention & control KW - Tretinoin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78276835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Dietary+retinoic+acid+inhibits+mouse+skin+carcinogenesis+irrespective+of+age+at+initiation.&rft.au=De+Luca%2C+L+M%3BTarone%2C+R%3BHuynh%2C+M%3BJones%2C+C+S%3BChen%2C+L+C&rft.aulast=De+Luca&rft.aufirst=L&rft.date=1996-01-01&rft.volume=25&rft.issue=3&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-01 N1 - Date created - 1996-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of kappa receptor agonists on D1 and D2 dopamine agonist and antagonist-induced behaviors. AN - 78276241; 8741947 AB - Striatal dynorphin-containing neurons receive dopaminergic inputs from the substantia nigra pars compacta and project primarily to the substantia nigra pars reticulata and entopeduncular nucleus. These neurons mainly express dopamine (DA) D1 receptors and thus dynorphin system stimulation might be expected largely to influence D1 receptor agonist or antagonist effects on motor function. It is well known the interaction existing between DA D1 and D2 drugs in the induction of behavioral effects. However, the effects of dynorphin on selective D1 and D2 DA agonist and antagonist-induced behaviors have not yet been investigated. Administration of the kappa agonists spiradoline (0.5, 1 and 5 mg/kg) or U50,488H (1, 10 and 25 mg/kg) decreased non-stereotyped grooming induced by the selective D1 agonist SKF38393. This effect was inhibited by the non-selective opioid receptor antagonist naloxone (20 mg/kg) and by the selective kappa antagonist nor-binaltorphimine (nor-BNI, 20 mg/kg). Stereotypies induced by the selective D2 agonist quinpirole were decreased by spiradoline (1 and 5 mg/kg) and by U50,488H (1, 10 and 25 mg/kg), while jerking movements of a type associated with increased D2 receptor and decreased D1 receptor stimulation emerged. Kappa agonist effects were inhibited by the prior administration of SKF38393 (10 mg/kg); these inhibitory effects were blocked by prior administration of the D1 antagonist SCH23390 (5 mg/kg). Naloxone reversed the effects of both kappa agonists on quinpirole-induced stereotypies. Kappa agonists increased D1 antagonist-induced catalepsy, but had no effect on D2 antagonist-induced catalepsy. Naloxone and nor-BNI inhibited this effect. These results suggest that the motoric effects of D1 receptor antagonists in part reflect stimulation of striatal dynorphin containing efferents. JF - Psychopharmacology AU - Marin, C AU - Engber, T M AU - Chaudhuri, P AU - Peppe, A AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 215 EP - 221 VL - 123 IS - 2 SN - 0033-3158, 0033-3158 KW - Dopamine Agonists KW - 0 KW - Dopamine Antagonists KW - Pyrrolidines KW - Receptors, Opioid, kappa KW - 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer KW - 67198-13-4 KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - spiradoline KW - N18ZH0M4NP KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Catalepsy -- chemically induced KW - Dose-Response Relationship, Drug KW - Pyrrolidines -- pharmacology KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - Male KW - Behavior, Animal -- drug effects KW - Receptors, Opioid, kappa -- agonists KW - Dopamine Agonists -- pharmacology KW - Dopamine Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78276241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Effects+of+kappa+receptor+agonists+on+D1+and+D2+dopamine+agonist+and+antagonist-induced+behaviors.&rft.au=Marin%2C+C%3BEngber%2C+T+M%3BChaudhuri%2C+P%3BPeppe%2C+A%3BChase%2C+T+N&rft.aulast=Marin&rft.aufirst=C&rft.date=1996-01-01&rft.volume=123&rft.issue=2&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improving protein secondary structure prediction with aligned homologous sequences. AN - 78275862; 8771202 AB - Most recent protein secondary structure prediction methods use sequence alignments to improve the prediction quality. We investigate the relationship between the location of secondary structural elements, gaps, and variable residue positions in multiple sequence alignments. We further investigate how these relationships compare with those found in structurally aligned protein families. We show how such associations may be used to improve the quality of prediction of the secondary structure elements, using the Quadratic-Logistic method with profiles. Furthermore, we analyze the extent to which the number of homologous sequences influences the quality of prediction. The analysis of variable residue positions shows that surprisingly, helical regions exhibit greater variability than do coil regions, which are generally thought to be the most common secondary structure elements in loops. However, the correlation between variability and the presence of helices does not significantly improve prediction quality. Gaps are a distinct signal for coil regions. Increasing the coil propensity for those residues occurring in gap regions enhances the overall prediction quality. Prediction accuracy increases initially with the number of homologues, but changes negligibly as the number of homologues exceeds about 14. The alignment quality affects the prediction more than other factors, hence a careful selection and alignment of even a small number of homologues can lead to significant improvements in prediction accuracy. JF - Protein science : a publication of the Protein Society AU - Di Francesco, V AU - Garnier, J AU - Munson, P J AD - NIH/DCRT/LSB, Bethesda, Maryland 20892-5626, USA. valedf@helix.nih.gov Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 106 EP - 113 VL - 5 IS - 1 SN - 0961-8368, 0961-8368 KW - Index Medicus KW - Animals KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutagenesis, Insertional KW - Sequence Deletion KW - Protein Structure, Secondary KW - Sequence Homology, Amino Acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78275862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Improving+protein+secondary+structure+prediction+with+aligned+homologous+sequences.&rft.au=Di+Francesco%2C+V%3BGarnier%2C+J%3BMunson%2C+P+J&rft.aulast=Di+Francesco&rft.aufirst=V&rft.date=1996-01-01&rft.volume=5&rft.issue=1&rft.spage=106&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-09 N1 - Date created - 1996-10-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Biochem. 1978;47:251-76 [354496] J Mol Biol. 1978 Mar 25;120(1):97-120 [642007] Adv Enzyme Regul. 1994;34:269-353 [7942279] J Mol Biol. 1995 Mar 17;247(1):11-5 [7897654] Proteins. 1995 Jan;21(1):1-10 [7716164] Proteins. 1995 Apr;21(4):273-81 [7567950] Biopolymers. 1983 Dec;22(12):2577-637 [6667333] EMBO J. 1986 Apr;5(4):823-6 [3709526] J Mol Biol. 1987 Jun 20;195(4):957-61 [3656439] J Mol Biol. 1987 Dec 5;198(3):425-43 [3430614] Biochim Biophys Acta. 1988 Aug 10;955(3):283-95 [3401489] Protein Eng. 1988 Sep;2(3):185-91 [3237683] Proteins. 1990;7(4):317-34 [2381905] J Mol Biol. 1990 Nov 20;216(2):441-57 [2254939] Proteins. 1991;9(1):56-68 [2017436] J Mol Biol. 1992 May 20;225(2):363-77 [1593625] J Mol Biol. 1992 Jun 20;225(4):1049-63 [1613789] J Mol Biol. 1992 Sep 20;227(2):371-4 [1404357] J Mol Biol. 1993 Jul 20;232(2):584-99 [8345525] Protein Eng. 1993 Nov;6(8):849-54 [8309932] Comput Appl Biosci. 1994 Feb;10(1):53-60 [8193956] Proteins. 1994 May;19(1):55-72 [8066087] J Mol Biol. 1981 Dec 25;153(4):1027-42 [7045378] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies on the activity of barnase toxins in vitro and in vivo. AN - 78264098; 8741987 AB - Pseudomonas exotoxin A (PE) is a protein toxin composed of three structural domains which are responsible for cell binding (domain Ia, amino acids 1-252), translocation into the cytosol (domain II, amino acids 253-364) and ADP-ribosylation activity (domain III, amino acids 405-613). We have previously described (Prior, T. I., FitzGerald, D. J., and Pastan, I. (1992) Biochem. 31, 3555-3559) a molecule composed of amino acids 1-412 of PE and the extracellular ribonuclease of Bacillus amyloliquefaciens, barnase (Bar), and shown that this protein (PE1-412-Bar) is toxic to cells due to its ribonuclease activity, which had been delivered to the cytosol. We have now used this model to evaluate the role played by the carboxyl end of domain II (amino acids 347-364), domain Ib, and the amino end of domain III (amino acids 405-412) in the translocation event. Toxins completely lacking domain III, termed PE1-380-Bar, or both domains Ib and III, termed PE1-364-Bar, were equally cytotoxic to a murine fibroblast cell line (L929) as was PE1-412-Bar. Extending the deletion to include part of the E-helix and all of the F-helix of domain II (amino acids 347-364) resulted in a toxin (PE1-346-Bar) that was 10-fold less toxic. Previously tested on only murine cell lines, we demonstrate that barnase toxins are cytotoxic also to a variety of human cell lines. Cytotoxicity was assessed by measuring inhibition of DNA synthesis. Surprisingly, PE1-380-Bar is not lethal when injected into mice, either intraperitoneally or intravenously, at 9 nmol, which is 2200-fold more than the amount required for killing by PE (4 pmol). In cell culture these barnase-containing toxins are 100-fold less toxic to murine fibroblast cells than PE. Barnase toxin has a greater survival time in the blood of mice than PE, with a half-life of 102 min. We conclude that domain II is sufficient to transport proteins into the cytosol. Further, since domain Ia can be replaced with other cell targeting moieties, we propose that barnase-toxins should be evaluated for utility in targeted cancer therapy. JF - Bioconjugate chemistry AU - Prior, T I AU - Kunwar, S AU - Pastan, I AD - Laboratory of Molecular Biology, DCBDC, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 23 EP - 29 VL - 7 IS - 1 SN - 1043-1802, 1043-1802 KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Oligodeoxyribonucleotides KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Ribonucleases KW - EC 3.1.- KW - Bacillus amyloliquefaciens ribonuclease KW - EC 3.1.4.- KW - Index Medicus KW - L Cells (Cell Line) KW - Animals KW - Humans KW - Metabolic Clearance Rate KW - Mice KW - Plasmids KW - Mice, Inbred BALB C KW - Cloning, Molecular KW - Base Sequence KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Bacterial Toxins -- pharmacokinetics KW - Kinetics KW - Molecular Sequence Data KW - Escherichia coli KW - Bacterial Toxins -- toxicity KW - Time Factors KW - Bacterial Toxins -- biosynthesis KW - Cell Line KW - Female KW - Recombinant Fusion Proteins -- biosynthesis KW - Recombinant Fusion Proteins -- pharmacokinetics KW - Ribonucleases -- toxicity KW - Exotoxins -- biosynthesis KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- toxicity KW - Exotoxins -- toxicity KW - Ribonucleases -- biosynthesis KW - Recombinant Fusion Proteins -- toxicity KW - Ribonucleases -- pharmacokinetics KW - Exotoxins -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78264098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Studies+on+the+activity+of+barnase+toxins+in+vitro+and+in+vivo.&rft.au=Prior%2C+T+I%3BKunwar%2C+S%3BPastan%2C+I&rft.aulast=Prior&rft.aufirst=T&rft.date=1996-01-01&rft.volume=7&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-11 N1 - Date created - 1996-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct structure-activity relations for stimulation of 45Ca uptake and for high affinity binding in cultured rat dorsal root ganglion neurons and dorsal root ganglion membranes. AN - 78262685; 8717353 AB - The [3H]resiniferatoxin (RTX) binding assay using membrane preparations has been used to identify and characterize the vanilloid receptors in the central and peripheral nervous system of different species. In the present study, using cultured adult rat dorsal root ganglion neurons either in suspension or attached to the tissue culture plates, we developed an assay to measure specific [3H]RTX binding by the intact cells. We were able to characterize the vanilloid binding characteristics of the neurons and compared those to the properties of vanilloid binding sites present in rat dorsal root ganglia membrane preparations. We found that [3H]RTX bound with similar affinity and positive cooperativity to attached neurons (cultured for 5 days before being assayed), neurons in suspension (using a filtration assay) and dorsal root ganglion membrane preparations. Dissociation constants obtained in the three assays were 47.6 +/- 3.5 pM, 38.4 +/- 3.1 pM and 42.6 +/- 3.1 pM, respectively. The cooperativity indexes determined by fitting the data to the Hill equation were 1.73 +/- 0.11, 1.78 +/- 0.12 and 1.78 +/- 0.09, respectively. The maximal binding capacity was 0.218 +/- 0.026 fmol/10(3) cells and 0.196 +/- 0.021 fmol/10(3) cells in the case of the attached cells and cells in suspension, respectively. Nonradioactive RTX, capsaicin, capsazepine and resiniferonol 20-homovanillylamide fully displaced specifically bound [3H]RTX from cells in suspension with Ki and Hill coefficient values of 42.5 +/- 5.3 pM, 2.06 +/- 0.16 microM, 3.16 +/- 0.21 microM and 32.4 +/- 4.1 nM and 1.79 +/- 0.17, 1.68 +/- 0.06, 1.72 +/- 0.11 and 1.81 +/- 0.12, respectively. Structure-activity analysis of different vanilloid derivatives revealed that the various compounds have distinct potencies for receptor binding and inducing 45Ca uptake in rat dorsal root ganglion neurons. Affinities for receptor binding and stimulation of 45Ca uptake of RTX, resiniferonol 20-homovanillylamide, RTX-thiourea, tinyatoxin, phorbol 12,13-dibenzoate 20-homovanillylamide and capsaicin were 38.5 +/- 2.9 pM, 25.7 +/- 3.0 nM, 68.5 +/- 3.8 nM, 173 +/- 25 pM, 7.98 +/- 0.83 microM and 4.93 +/- 0.35 microM as compared to 0.94 +/- 0.12 nM, 26.5 +/- 3.5 nM, 149 +/- 30 nM, 1.46 +/- 0.25 nM, 1.41 +/- 0.48 microM and 340 +/- 57 nM. Computer fitting of the data yielded Hill coefficient values indicating positive cooperativity of receptor binding; however, stimulation of 45Ca uptake appeared to follow a non-cooperative mechanism of action. The competitive capsaicin antagonist capsazepine inhibited specific binding of [3H]RTX by rat dorsal root ganglion membrane preparations with Ki and Hill coefficient values of 3.89 +/- 0.38 microM and 1.74 +/- 0.11. On the other hand it inhibited the induction of 45Ca uptake into the cells induced by capsaicin and RTX in a non-cooperative fashion with Ki values of 271 +/- 29 nM and 325 +/- 47 nM. Our results show that the membrane binding assay relates to the reality of receptor function in the intact, cultured neurons, both in terms of affinity and positive cooperativity. However the different vanilloid derivatives displayed markedly distinct structure-activity relations for high affinity receptor binding and stimulation of 45Ca uptake into rat dorsal root ganglion neurons. Among various explanations for this discrepancy, we favor the possibility that the two assays detect distinct classes of the vanilloid (capsaicin) receptor present in primary sensory neurons. JF - Brain research. Molecular brain research AU - Acs, G AU - Lee, J AU - Marquez, V E AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 173 EP - 182 VL - 35 IS - 1-2 SN - 0169-328X, 0169-328X KW - Diterpenes KW - 0 KW - Neurotoxins KW - Receptors, Drug KW - Tritium KW - 10028-17-8 KW - resiniferatoxin KW - A5O6P1UL4I KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Neurotoxins -- metabolism KW - Binding Sites KW - Biological Transport -- drug effects KW - Structure-Activity Relationship KW - Rats KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Kinetics KW - Binding, Competitive KW - Cell Membrane -- metabolism KW - Female KW - Diterpenes -- pharmacology KW - Calcium -- metabolism KW - Receptors, Drug -- metabolism KW - Neurons -- metabolism KW - Ganglia, Spinal -- metabolism KW - Diterpenes -- metabolism KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78262685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Distinct+structure-activity+relations+for+stimulation+of+45Ca+uptake+and+for+high+affinity+binding+in+cultured+rat+dorsal+root+ganglion+neurons+and+dorsal+root+ganglion+membranes.&rft.au=Acs%2C+G%3BLee%2C+J%3BMarquez%2C+V+E%3BBlumberg%2C+P+M&rft.aulast=Acs&rft.aufirst=G&rft.date=1996-01-01&rft.volume=35&rft.issue=1-2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-11 N1 - Date created - 1996-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intravesical suramin: a novel agent for the treatment of superficial transitional-cell carcinoma of the bladder. AN - 78235990; 8738403 AB - Patients with recurrent or high-grade superficial transitional-cell carcinoma of the bladder that has recurred after intravesical chemotherapy are at increased risk for tumor invasion and metastases. Intravesical chemotherapy is a minimally invasive technique that allows high doses of therapeutic agents to be delivered directly to the malignancy, doses that would not be tolerated systemically. In vitro studies demonstrate suramin's significant efficacy against transitional-cell carcinoma cell lines at relatively low doses. Humans treated with similar doses delivered in a systemic fashion have experienced no bladder toxicity. Suramin has been shown to block the binding of epidermal growth factor (EGF) to its receptors, which are found in large amounts in bladder cancers. Because a significant association has been found between the number of EGF receptors on a bladder-cancer cell and its sensitivity to suramin, transitional-cell carcinoma could potentially be very responsive to such therapy. On the basis of these findings, a phase I escalating-suramin-dose study is currently being conducted. JF - World journal of urology AU - Walther, M M AU - Figg, W D AU - Linehan, W M AD - Urologic Oncology Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - S8 EP - 11 VL - 14 Suppl 1 SN - 0724-4983, 0724-4983 KW - Antineoplastic Agents KW - 0 KW - Suramin KW - 6032D45BEM KW - Index Medicus KW - Animals KW - Humans KW - Treatment Outcome KW - Administration, Intravesical KW - Antineoplastic Agents -- administration & dosage KW - Urinary Bladder Neoplasms -- drug therapy KW - Suramin -- administration & dosage KW - Antineoplastic Agents -- therapeutic use KW - Carcinoma, Transitional Cell -- drug therapy KW - Suramin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78235990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=World+journal+of+urology&rft.atitle=Intravesical+suramin%3A+a+novel+agent+for+the+treatment+of+superficial+transitional-cell+carcinoma+of+the+bladder.&rft.au=Walther%2C+M+M%3BFigg%2C+W+D%3BLinehan%2C+W+M&rft.aulast=Walther&rft.aufirst=M&rft.date=1996-01-01&rft.volume=14+Suppl+1&rft.issue=&rft.spage=S8&rft.isbn=&rft.btitle=&rft.title=World+journal+of+urology&rft.issn=07244983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-02 N1 - Date created - 1996-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MMTV-induced mutations in mouse mammary tumors: their potential relevance to human breast cancer. AN - 78218153; 8738604 AB - In mouse mammary tumor virus (MMTV) infected mice, three identifiable stages of mammary tumorigenesis can be biologically defined: preneoplastic hyperplastic nodules, malignant tumor, and distant metastatic lesions (primarily in the lung). MMTV is a biological carcinogen which induces somatic mutations as consequence of its integration into the host cellular genome. Each stage of mammary tumorigenesis appears to result from the clonal outgrowth of cells containing additional integrated proviral MMTV genomes. This phenomenon has provided the basis for an approach to identify genes which, when affected, may contribute to progression through the different stages of mammary tumorigenesis. Eight different genes (Wnt1, Wnt3, Wnt10b, Fgf3, Fgf4, Fgf8, Int3, and Int6) have been shown to be genetically altered in multiple mammary tumors as a consequence of MMTV integration. Although the significance of the human homologs of these genes as targets for somatic mutation during human breast carcinogenesis is only now being explored, it is clear that this work has led to a new appreciation of the complexity of the genetic circuitry that is involved in the control of normal mammary gland growth and development. It seems likely that some of the mutations induced by MMTV, and the signaling pathways in which these target genes take part, will be relevant to the progression from preneoplastic lesions to distant metastasis in human breast cancer. JF - Breast cancer research and treatment AU - Callahan, R AD - Oncogenetics Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 33 EP - 44 VL - 39 IS - 1 SN - 0167-6806, 0167-6806 KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Animals KW - Humans KW - Mice, Inbred C3H KW - Disease Models, Animal KW - Mice KW - Research KW - Mice, Transgenic KW - Mice, Inbred BALB C KW - Female KW - Animals, Wild KW - Retroviridae Infections -- virology KW - Tumor Virus Infections -- virology KW - Tumor Virus Infections -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- virology KW - Retroviridae Infections -- genetics KW - Mutagenesis, Insertional -- genetics KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78218153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=MMTV-induced+mutations+in+mouse+mammary+tumors%3A+their+potential+relevance+to+human+breast+cancer.&rft.au=Callahan%2C+R&rft.aulast=Callahan&rft.aufirst=R&rft.date=1996-01-01&rft.volume=39&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New animals, new uses, and old issues. AN - 78209870; 8698044 JF - Environmental and molecular mutagenesis AU - Zeiger, E AU - Tennant, R W AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 3 EP - 4 VL - 28 IS - 1 SN - 0893-6692, 0893-6692 KW - Index Medicus KW - Animals KW - Mutagenicity Tests KW - Genetic Engineering KW - Carcinogenicity Tests KW - Research KW - Animals, Genetically Modified UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78209870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=New+animals%2C+new+uses%2C+and+old+issues.&rft.au=Zeiger%2C+E%3BTennant%2C+R+W&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1996-01-01&rft.volume=28&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-04 N1 - Date created - 1996-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health hazards to humans associated with domestic pets. AN - 78195613; 8724225 AB - Allergy to pets, particularly when manifested as asthma, is an important health hazard. The health impact of severe clinical disease associated with allergy to pets can be minimized by avoidance of pets. Many individuals with milder disease keep their pets and obtain medications for relief of their allergy symptoms. Bird fancier's disease can result in profound deterioration of pulmonary function, and requires avoidance of bird exposure. Animal bites are the commonest health hazard of domestic pets and result in tissue damage and infection risk. Bites are treated by cleaning the wound, and appropriate use of antibiotics and tetanus prophylaxis. Diverse infectious diseases are transmitted to humans by their pets; these diseases are particularly dangerous to immunocompromised individuals. The infectious diseases can be partly prevented by avoiding ill animals and by washing of hands following exposure to pets or pet-derived secretions. They can be treated by appropriate antibiotics and/or specific immune globulins and/or vaccines. JF - Annual review of public health AU - Plaut, M AU - Zimmerman, E M AU - Goldstein, R A AD - Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 221 EP - 245 VL - 17 SN - 0163-7525, 0163-7525 KW - Index Medicus KW - Animals KW - Humans KW - Infection Control KW - Bonding, Human-Pet KW - Communicable Diseases -- veterinary KW - Animals, Domestic KW - Bites and Stings -- prevention & control KW - Public Health KW - Bites and Stings -- etiology KW - Hypersensitivity -- etiology KW - Hypersensitivity -- prevention & control KW - Communicable Diseases -- transmission UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78195613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+public+health&rft.atitle=Health+hazards+to+humans+associated+with+domestic+pets.&rft.au=Plaut%2C+M%3BZimmerman%2C+E+M%3BGoldstein%2C+R+A&rft.aulast=Plaut&rft.aufirst=M&rft.date=1996-01-01&rft.volume=17&rft.issue=&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+public+health&rft.issn=01637525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-04 N1 - Date created - 1996-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The case against the routine use of radiation therapy in advanced-stage Hodgkin's disease. AN - 78179068; 8689431 JF - Cancer investigation AU - Longo, D L AD - National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224-2780, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 353 EP - 360 VL - 14 IS - 4 SN - 0735-7907, 0735-7907 KW - Bleomycin KW - 11056-06-7 KW - Procarbazine KW - 35S93Y190K KW - Mechlorethamine KW - 50D9XSG0VR KW - Vincristine KW - 5J49Q6B70F KW - Vinblastine KW - 5V9KLZ54CY KW - Dacarbazine KW - 7GR28W0FJI KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Mechlorethamine -- administration & dosage KW - Neoplasm Staging KW - Bleomycin -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Procarbazine -- administration & dosage KW - Vinblastine -- administration & dosage KW - Treatment Outcome KW - Dacarbazine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Prednisone -- administration & dosage KW - Hodgkin Disease -- radiotherapy KW - Hodgkin Disease -- pathology KW - Hodgkin Disease -- drug therapy KW - Radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78179068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+investigation&rft.atitle=The+case+against+the+routine+use+of+radiation+therapy+in+advanced-stage+Hodgkin%27s+disease.&rft.au=Longo%2C+D+L&rft.aulast=Longo&rft.aufirst=D&rft.date=1996-01-01&rft.volume=14&rft.issue=4&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=07357907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-23 N1 - Date created - 1996-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipid vs protein theories of alcohol action in the nervous system. AN - 78164035; 8725387 AB - There has been a long-standing debate concerning whether alcohols produce their effects in the central nervous system (CNS) by acting on lipids or proteins. Lipid theories postulate that alcohols act via some perturbation of the membrane lipids of CNS neurons, whereas protein theories propose that alcohols act by interacting with a neuronal protein site. Although the primary site of action differs in the two theories, both theories postulate that the CNS effects of alcohols ultimately result from alterations in protein function. This review discusses lipid and protein theories of alcohol action and the evidence supporting these theories. In addition, the effects of alcohols on the function of neurotransmitter-gated ion channels are discussed, as several types of these receptor-ion channels have been found to be sensitive to the actions of alcohols, and recent studies on those actions have yielded new insights into the question of whether the primary action of alcohols involves lipids or proteins. JF - Annual review of pharmacology and toxicology AU - Peoples, R W AU - Li, C AU - Weight, F F AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8205, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 185 EP - 201 VL - 36 SN - 0362-1642, 0362-1642 KW - Ion Channels KW - 0 KW - Membrane Lipids KW - Membrane Proteins KW - Receptors, Neurotransmitter KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Receptors, Neurotransmitter -- physiology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Humans KW - Ion Channels -- drug effects KW - Membrane Fluidity -- drug effects KW - Receptors, Neurotransmitter -- drug effects KW - Ethanol -- adverse effects KW - Central Nervous System -- metabolism KW - Membrane Proteins -- metabolism KW - Membrane Lipids -- metabolism KW - Central Nervous System -- drug effects KW - Alcohol Drinking -- adverse effects KW - Membrane Proteins -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78164035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Lipid+vs+protein+theories+of+alcohol+action+in+the+nervous+system.&rft.au=Peoples%2C+R+W%3BLi%2C+C%3BWeight%2C+F+F&rft.aulast=Peoples&rft.aufirst=R&rft.date=1996-01-01&rft.volume=36&rft.issue=&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=03621642&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-23 N1 - Date created - 1996-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function. AN - 78160551; 8768072 JF - Progress in nucleic acid research and molecular biology AU - Bustin, M AU - Reeves, R AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 35 EP - 100 VL - 54 SN - 0079-6603, 0079-6603 KW - Chromatin KW - 0 KW - DNA, Superhelical KW - High Mobility Group Proteins KW - Nucleosomes KW - DNA KW - 9007-49-2 KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Index Medicus KW - Animals KW - Eukaryotic Cells -- ultrastructure KW - Models, Molecular KW - CDC2 Protein Kinase -- metabolism KW - DNA -- metabolism KW - Humans KW - Nucleosomes -- metabolism KW - Cell Differentiation KW - Transcription, Genetic KW - Amino Acid Sequence KW - Protein Binding KW - Nucleic Acid Conformation KW - DNA, Superhelical -- metabolism KW - Structure-Activity Relationship KW - Magnetic Resonance Spectroscopy KW - Rats KW - Eukaryotic Cells -- metabolism KW - Sequence Alignment KW - Nucleosomes -- ultrastructure KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Gene Expression Regulation KW - Sequence Homology, Amino Acid KW - High Mobility Group Proteins -- physiology KW - High Mobility Group Proteins -- chemistry KW - Chromatin -- chemistry KW - Chromatin -- physiology KW - Protein Conformation KW - High Mobility Group Proteins -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78160551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+nucleic+acid+research+and+molecular+biology&rft.atitle=High-mobility-group+chromosomal+proteins%3A+architectural+components+that+facilitate+chromatin+function.&rft.au=Bustin%2C+M%3BReeves%2C+R&rft.aulast=Bustin&rft.aufirst=M&rft.date=1996-01-01&rft.volume=54&rft.issue=&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Progress+in+nucleic+acid+research+and+molecular+biology&rft.issn=00796603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - P18437; SWISSPROT; P05114; P12274; P18608; P02314; P80272; P02315; P09602; P05204; P02316; P12902; P02313 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination therapy with zidovudine, didanosine and saquinavir. AN - 78158220; 8721557 AB - The goal of AIDS Clinical Trials Group (ACTG) Protocol 229 was to evaluate the shorter term (24 week) and longer term (48 week) safety and activity of the HIV-1 proteinase inhibitor saquinavir in combination with zalcitabine (ddC) and zidovudine (ZDV) versus saquinavir in combination with ZDV versus ddC in combination with ZDV. This study confirms and extends the conclusions from the first 24 weeks of this study and showed that in subjects with extensive prior antiretroviral experience, the triple combination of saquinavir, ddC and ZDV was well-tolerated, safe and remained superior to the other double drug regimens as measured by CD4+ cell counts, quantitative HIV-1 microculture and plasma HIV-1 RNA levels. JF - Antiviral research AU - Collier, A C AU - Coombs, R W AU - Schoenfeld, D A AU - Bassett, R AU - Baruch, A AU - Corey, L AD - AIDS Clinical Trials Group Protocol 229 Team, NIAID, Bethesda, MD, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 99 VL - 29 IS - 1 SN - 0166-3542, 0166-3542 KW - Antiviral Agents KW - 0 KW - HIV Protease Inhibitors KW - Isoquinolines KW - Quinolines KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Saquinavir KW - L3JE09KZ2F KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Humans KW - Zidovudine -- therapeutic use KW - Antiviral Agents -- therapeutic use KW - Didanosine -- therapeutic use KW - Isoquinolines -- therapeutic use KW - Quinolines -- therapeutic use KW - HIV Infections -- drug therapy KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78158220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+research&rft.atitle=Combination+therapy+with+zidovudine%2C+didanosine+and+saquinavir.&rft.au=Collier%2C+A+C%3BCoombs%2C+R+W%3BSchoenfeld%2C+D+A%3BBassett%2C+R%3BBaruch%2C+A%3BCorey%2C+L&rft.aulast=Collier&rft.aufirst=A&rft.date=1996-01-01&rft.volume=29&rft.issue=1&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Antiviral+research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Consensus symposium on combined antiviral therapy; overview of interferon and IL-2 combinations for the treatment of HIV infection. AN - 78149047; 8721559 AB - Among the immunomodulatory cytokines that have been evaluated for the treatment of HIV disease, alpha-interferon and interleukin-2 (IL-2) have been the most extensively studied. Monotherapy with alpha-interferon is effective therapy for HIV-associated Kaposi's sarcoma (KS) in patients with CD4 counts > 150 cells/mm3. However, the doses necessary to achieve a significant anti-tumor effect are often poorly tolerated. Combination therapy with alpha-interferon and zidovudine is associated with dose-limiting toxicities and an anti-tumor effect similar to that of higher dose alpha-interferon monotherapy. The combination of alpha-interferon and zidovudine can synergistically inhibit HIV replication in vitro; however, in vivo results suggest the anti-HIV effect of this combination is no greater than that seen with zidovudine monotherapy. Whether combination of interferon-alpha and other antiviral drugs will be useful in the treatment of HIV infection remains to be seen. Recent studies employing intermittent courses of IL-2 combined with continuous antiretroviral therapy indicate that sustained rises in CD4 counts can be achieved. The ability of IL-2 therapy to result in a sustained rise in CD4 counts is critically dependent on the pre-treatment CD4 count. The immunologic and clinical significance of these IL-2-induced increases in CD4 counts is unknown. Larger, controlled trials are currently underway to evaluate the role of intermittent IL-2 therapy in HIV infection. JF - Antiviral research AU - Sneller, M C AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 105 EP - 109 VL - 29 IS - 1 SN - 0166-3542, 0166-3542 KW - Antiviral Agents KW - 0 KW - Interferon-alpha KW - Interleukin-2 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Sarcoma, Kaposi -- drug therapy KW - Acquired Immunodeficiency Syndrome -- complications KW - Humans KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - CD4 Lymphocyte Count KW - Clinical Trials as Topic -- statistics & numerical data KW - Zidovudine -- therapeutic use KW - Antiviral Agents -- therapeutic use KW - Interleukin-2 -- adverse effects KW - Interferon-alpha -- therapeutic use KW - Interferon-alpha -- adverse effects KW - Zidovudine -- adverse effects KW - Interleukin-2 -- therapeutic use KW - HIV Infections -- drug therapy KW - Antiviral Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78149047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+research&rft.atitle=Consensus+symposium+on+combined+antiviral+therapy%3B+overview+of+interferon+and+IL-2+combinations+for+the+treatment+of+HIV+infection.&rft.au=Sneller%2C+M+C&rft.aulast=Sneller&rft.aufirst=M&rft.date=1996-01-01&rft.volume=29&rft.issue=1&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Antiviral+research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of stress response genes GADD153, c-jun, and heme oxygenase-1 in H2O2- and O2-resistant fibroblasts. AN - 78141603; 8721617 AB - In the present study, the expression of the stress-inducible genes GADD153, c-jun, heme oxygenase-1 (HO-1), and HSP70 was compared among parental hamster diploid fibroblasts (HA-1), and cell lines isolated for resistance to either H2O2 (OC14) or O2 (O2R95). Both OC14 and O2R95 cell lines are known to have significantly augmented cellular antioxidant defenses, including increased glutathione content, as well as enhanced catalase, superoxide dismutase, and glutathione peroxidase activities. Northern analysis indicated that basal expression of HO-1 and c-jun is also elevated in these resistant cell lines. Relative to HA-1 values, basal GADD153 mRNA expression was approximately threefold higher in O2R95, but twofold lower in OC14 cells. HSP70 mRNA expression was comparable among parental and resistant cell lines. Both OC14 and O2R95 cells showed greatly enhanced survival following H2O2 exposure. The H2O2 doses that induced 50% toxicity in parental and resistant cells (3 vs. 30-60 x 10(-13) mol/cell, respectively) differed by more than an order of magnitude. Similarly, GADD153, c-jun, and HO-1 mRNA were elevated in control cells following exposure to doses of H2O2 an order of magnitude lower than is required for gene activation in resistant cell lines. Nonetheless, at equitoxic doses, the level of induction of GADD153 and HO-1 was greater in resistant than in parental cell lines. Taken together, our results suggest that alterations in the basal level of expression of certain stress-responsive genes, including HO-1, c-jun, and GADD153, may contribute to the H2O2-resistant phenotype in these fibroblast cell lines. Further, changes in the regulation of these genes in response to adverse stimuli may provide an additional mechanism for enhanced cell survival following oxidative stress. JF - Free radical biology & medicine AU - Guyton, K Z AU - Spitz, D R AU - Holbrook, N J AD - Section on Gene Expression and Aging, National Institute on Aging, Baltimore, MD 21224, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 735 EP - 741 VL - 20 IS - 5 SN - 0891-5849, 0891-5849 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - Transcription Factors KW - Transcription Factor CHOP KW - 147336-12-7 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Oxidoreductases KW - EC 1.- KW - Heme Oxygenase (Decyclizing) KW - EC 1.14.14.18 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Glutathione KW - GAN16C9B8O KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Cricetulus KW - Glutathione -- metabolism KW - Glutathione Transferase -- metabolism KW - DNA-Binding Proteins -- biosynthesis KW - Transcription Factors -- biosynthesis KW - Transcriptional Activation KW - Heme Oxygenase (Decyclizing) -- biosynthesis KW - Cell Survival -- drug effects KW - Oxidoreductases -- metabolism KW - Cell Line KW - Cricetinae KW - Oxygen -- pharmacology KW - Hydrogen Peroxide -- pharmacology KW - Oxidative Stress -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78141603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Expression+of+stress+response+genes+GADD153%2C+c-jun%2C+and+heme+oxygenase-1+in+H2O2-+and+O2-resistant+fibroblasts.&rft.au=Guyton%2C+K+Z%3BSpitz%2C+D+R%3BHolbrook%2C+N+J&rft.aulast=Guyton&rft.aufirst=K&rft.date=1996-01-01&rft.volume=20&rft.issue=5&rft.spage=735&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The food-derived heterocyclic amines and breast cancer: a 1995 perspective. AN - 78130862; 8787060 JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Synderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 17 EP - 25 VL - 140 SN - 0080-0015, 0080-0015 KW - Amines KW - 0 KW - Carcinogens KW - Dietary Fats KW - Heterocyclic Compounds KW - Imidazoles KW - Mutagens KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Animals KW - Dietary Fats -- adverse effects KW - Mutagens -- adverse effects KW - Humans KW - Imidazoles -- adverse effects KW - Carcinogens -- adverse effects KW - Food -- adverse effects KW - Breast Neoplasms -- metabolism KW - Heterocyclic Compounds -- adverse effects KW - Breast Neoplasms -- chemically induced KW - Amines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78130862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=The+food-derived+heterocyclic+amines+and+breast+cancer%3A+a+1995+perspective.&rft.au=Synderwine%2C+E+G&rft.aulast=Synderwine&rft.aufirst=E&rft.date=1996-01-01&rft.volume=140&rft.issue=&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-25 N1 - Date created - 1996-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential gene expression in tumor metastasis: Nm23. AN - 78124590; 9053292 JF - Current topics in microbiology and immunology AU - Freije, J M AU - MacDonald, N J AU - Steeg, P S AD - Women's Cancers Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 215 EP - 232 VL - 213 ( Pt 2) SN - 0070-217X, 0070-217X KW - NM23 Nucleoside Diphosphate Kinases KW - 0 KW - Neoplasm Proteins KW - Recombinant Proteins KW - Transcription Factors KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nme1 protein, mouse KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Melanoma, Experimental -- secondary KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Cell Division -- physiology KW - Breast Neoplasms -- chemistry KW - Transcription, Genetic KW - Mutagenesis, Site-Directed KW - Rats KW - Breast Neoplasms -- mortality KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Melanoma, Experimental -- genetics KW - Male KW - Breast Neoplasms -- genetics KW - Protein Processing, Post-Translational KW - Prognosis KW - Cell Adhesion -- genetics KW - Mice KW - Base Sequence KW - Cell Differentiation -- physiology KW - Transfection KW - Cohort Studies KW - Female KW - Gene Expression Regulation, Neoplastic KW - Transcription Factors -- physiology KW - Nucleoside-Diphosphate Kinase -- genetics KW - Neoplasm Proteins -- biosynthesis KW - Neoplasm Metastasis -- genetics KW - Nucleoside-Diphosphate Kinase -- physiology KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- genetics KW - Nucleoside-Diphosphate Kinase -- biosynthesis KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78124590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+microbiology+and+immunology&rft.atitle=Differential+gene+expression+in+tumor+metastasis%3A+Nm23.&rft.au=Freije%2C+J+M%3BMacDonald%2C+N+J%3BSteeg%2C+P+S&rft.aulast=Freije&rft.aufirst=J&rft.date=1996-01-01&rft.volume=213+%28+Pt+2%29&rft.issue=&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-13 N1 - Date created - 1997-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The epidemiology of psychiatric disorders and the de facto mental health care system. AN - 78119228; 8712797 AB - Recent national epidemiologic studies have provided data on the number of people in the United States with mental and addictive disorders. Many of these people receive their care in the general medical care sector. This has important implications for diagnosis and treatment of mental and addictive disorders. JF - Annual review of medicine AU - Norquist, G S AU - Regier, D A AD - Division of Epidemiology and Services Research, National Institute of Mental Health, Rockville, Maryland 20857, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 473 EP - 479 VL - 47 SN - 0066-4219, 0066-4219 KW - Index Medicus KW - Cross-Sectional Studies KW - Family Practice -- statistics & numerical data KW - Humans KW - Incidence KW - United States -- epidemiology KW - Mental Disorders -- rehabilitation KW - Patient Care Team -- utilization KW - Mental Disorders -- epidemiology KW - Mental Health Services -- utilization KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78119228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+medicine&rft.atitle=The+epidemiology+of+psychiatric+disorders+and+the+de+facto+mental+health+care+system.&rft.au=Norquist%2C+G+S%3BRegier%2C+D+A&rft.aulast=Norquist&rft.aufirst=G&rft.date=1996-01-01&rft.volume=47&rft.issue=&rft.spage=473&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+medicine&rft.issn=00664219&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-09 N1 - Date created - 1996-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping of 22 Notl linking clones on human chromosome 3 by polymerase chain reaction and somatic cell hybrid panels. AN - 78114900; 8653266 AB - Twenty-two human chromosome 3 derived and partially sequenced Notl linking clones were mapped using two somatic cell hybrid panels. Somatic cell hybrid mapping was performed by Southern hybridization and/or by polymerase chain reaction (PCR), using 300-500 bp CpG-rich sequences surrounding Notl sites. Thus, 22 new Notl site-tagged (sequence tagged sites) STSs were created, distributed over the entire human chromosome 3. The majority of these linking clones tag known or unknown expressed sequences (genes). Together with other physical and genetic mapping methods, localization of Notl linking clones facilitates the construction of a long-range physical map and, at the same time, a transcriptional map of human chromosome 3. JF - Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology AU - Allikmets, R AU - Kashuba, V I AU - Huebner, K AU - LaForgia, S AU - Kisselev, L L AU - Klein, G AU - Dean, M AU - Zabarovsky, E R AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21702-1201, USA. allikmet/fcrfv1.ncifcrf.gov Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 33 EP - 37 VL - 4 IS - 1 SN - 0967-3849, 0967-3849 KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - GCGGCCGC-specific type II deoxyribonucleases KW - Index Medicus KW - Genetic Linkage KW - Polymerase Chain Reaction KW - Animals KW - Humans KW - Sequence Tagged Sites KW - Mice KW - Hybrid Cells -- chemistry KW - Chromosomes, Human, Pair 3 KW - Restriction Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78114900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chromosome+research+%3A+an+international+journal+on+the+molecular%2C+supramolecular+and+evolutionary+aspects+of+chromosome+biology&rft.atitle=Mapping+of+22+Notl+linking+clones+on+human+chromosome+3+by+polymerase+chain+reaction+and+somatic+cell+hybrid+panels.&rft.au=Allikmets%2C+R%3BKashuba%2C+V+I%3BHuebner%2C+K%3BLaForgia%2C+S%3BKisselev%2C+L+L%3BKlein%2C+G%3BDean%2C+M%3BZabarovsky%2C+E+R&rft.aulast=Allikmets&rft.aufirst=R&rft.date=1996-01-01&rft.volume=4&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Chromosome+research+%3A+an+international+journal+on+the+molecular%2C+supramolecular+and+evolutionary+aspects+of+chromosome+biology&rft.issn=09673849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-01 N1 - Date created - 1996-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Granulocyte-macrophage colony-stimulating factor and interferon-gamma prevent dexamethasone-induced immunosuppression of antifungal monocyte activity against Aspergillus fumigatus hyphae. AN - 78114359; 8786473 AB - Treatment with corticosteroids is an important risk factor for development of invasive aspergillosis. We evaluated the effect of dexamethasone (DEX) on superoxide anion (O2-) release and damage caused by elutriated human monocytes (EHM) on unopsonized hyphae of Aspergillus fumigatus. In addition, we studied the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on these functions of DEX-treated EHM. Treatment of EHM with concentrations of DEX ranging from 5 to 500 nM (1.4-140 ng ml-1) for 48 h suppressed O2- release in response to phorbol myristate acetate in a dose-dependent fashion. Similarly, DEX significantly suppressed hyphal damage caused by EHM as measured by colorimetric MTT assay. Both GM-CSF (5 ng ml-1) and IFN-gamma (1.2 ng ml-1) added at day 0 to the EHM together with DEX (500 nM) significantly enhanced O2- release and percentage hyphal damage, preventing the DEX-induced suppression of EHM function. Thus, GM-CSF and IFN-gamma prevented the deleterious effects of DEX on antifungal activity of EHM against Aspergillus suggesting a potential therapeutic role in patients at risk for or suffering from invasive aspergillosis. JF - Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology AU - Roilides, E AU - Blake, C AU - Holmes, A AU - Pizzo, P A AU - Walsh, T J AD - Infectious Diseases Section, National Cancer Institute, Bethesda, MD 20892, USA. PY - 1996 SP - 63 EP - 69 VL - 34 IS - 1 SN - 0268-1218, 0268-1218 KW - Glucocorticoids KW - 0 KW - Superoxides KW - 11062-77-4 KW - Dexamethasone KW - 7S5I7G3JQL KW - Interferon-gamma KW - 82115-62-6 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Humans KW - Adult KW - Immunosuppression KW - Aspergillosis -- metabolism KW - Aspergillosis -- microbiology KW - Glucocorticoids -- antagonists & inhibitors KW - Interferon-gamma -- pharmacology KW - Monocytes -- microbiology KW - Aspergillus fumigatus -- growth & development KW - Glucocorticoids -- adverse effects KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Superoxides -- metabolism KW - Dexamethasone -- adverse effects KW - Dexamethasone -- antagonists & inhibitors KW - Monocytes -- metabolism KW - Monocytes -- drug effects KW - Aspergillus fumigatus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78114359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medical+and+veterinary+mycology+%3A+bi-monthly+publication+of+the+International+Society+for+Human+and+Animal+Mycology&rft.atitle=Granulocyte-macrophage+colony-stimulating+factor+and+interferon-gamma+prevent+dexamethasone-induced+immunosuppression+of+antifungal+monocyte+activity+against+Aspergillus+fumigatus+hyphae.&rft.au=Roilides%2C+E%3BBlake%2C+C%3BHolmes%2C+A%3BPizzo%2C+P+A%3BWalsh%2C+T+J&rft.aulast=Roilides&rft.aufirst=E&rft.date=1996-01-01&rft.volume=34&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Journal+of+medical+and+veterinary+mycology+%3A+bi-monthly+publication+of+the+International+Society+for+Human+and+Animal+Mycology&rft.issn=02681218&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-20 N1 - Date created - 1996-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modification of the sialic acid residues of choriogonadotropin affects signal transduction. AN - 78110801; 8777139 AB - Human choriogonadotropin (hCG) is a glycoprotein hormone that activates adenylyl cyclase. The carbohydrate moieties of hCG are required for biological activity, but not for binding to the gonadotropin receptors. We modified N-acetylneuraminic acid (NeuAc) on the oligosaccharide moieties of hCG, and determined the effect on its biological activity by measuring hormone-stimulated adenylyl cyclase. Treating hCG with sodium periodate to remove two carbon atoms from NeuAc or quantitatively removing NeuAc from hCG reduced its biological activity by 36% and 50%, respectively. The galactose residues of asialo-hCG were reacted with NeuAc-hydrazone or a hydrazone of the oligosaccharide from the ganglioside GM1 (Gal(beta 1-3)GalNAc(beta 1-4) [NeuAc(alpha 2-3)]Gal(beta 1-4)Glc). The gonadotropin receptor had high affinity for both derivatives, but their biological activity was less than that of hCG. These results suggest that several structural aspects of NeuAc including carbon side chain, an intact ring structure, and the position of NeuAc relative to other carbohydrate residues are important for full biological activity of hCG. JF - Cellular signalling AU - Reddy, B V AU - Bartoszewicz, Z AU - Rebois, R V AD - Membrane Biochemistry Section, NINDS, NIH, Bethesda, MD 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 35 EP - 41 VL - 8 IS - 1 SN - 0898-6568, 0898-6568 KW - Asialoglycoproteins KW - 0 KW - Carbohydrates KW - Chorionic Gonadotropin KW - Sialic Acids KW - asialo-human chorionic gonadotropin KW - Periodic Acid KW - 10450-60-9 KW - G(M1) Ganglioside KW - 37758-47-7 KW - Cholera Toxin KW - 9012-63-9 KW - metaperiodate KW - B45A1BUM4Q KW - Galactose Oxidase KW - EC 1.1.3.9 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - N-Acetylneuraminic Acid KW - GZP2782OP0 KW - Index Medicus KW - Animals KW - Galactose Oxidase -- pharmacology KW - Asialoglycoproteins -- pharmacology KW - Protein Processing, Post-Translational KW - Adenylyl Cyclases -- metabolism KW - Glycosylation KW - Oxidation-Reduction KW - Periodic Acid -- pharmacology KW - G(M1) Ganglioside -- physiology KW - Molecular Sequence Data KW - Asialoglycoproteins -- chemistry KW - Carbohydrate Sequence KW - Enzyme Activation -- drug effects KW - Carbohydrates -- analysis KW - Cell Line KW - Carbohydrate Conformation KW - Cholera Toxin -- metabolism KW - Sialic Acids -- physiology KW - Signal Transduction -- physiology KW - Chorionic Gonadotropin -- pharmacology KW - Chorionic Gonadotropin -- physiology KW - Chorionic Gonadotropin -- chemistry KW - Signal Transduction -- drug effects KW - Chorionic Gonadotropin -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78110801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+signalling&rft.atitle=Modification+of+the+sialic+acid+residues+of+choriogonadotropin+affects+signal+transduction.&rft.au=Reddy%2C+B+V%3BBartoszewicz%2C+Z%3BRebois%2C+R+V&rft.aulast=Reddy&rft.aufirst=B&rft.date=1996-01-01&rft.volume=8&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Cellular+signalling&rft.issn=08986568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-19 N1 - Date created - 1996-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered Gs alpha N-terminus affects Gs activity and interaction with the G beta gamma subunit complex in cell membranes but not in solution. AN - 78110485; 8777140 AB - The stimulatory G protein (Gs) mediates activation of adenylylcyclase by a ligand-receptor complex. Gs is heterotrimeric (alpha beta gamma) and activation can be accomplished by dissociation of the alpha-subunit (Gs alpha) from the beta gamma-subunit complex (G beta gamma). Gs alpha is also a substrate for choleragen catalyzed ADP-ribosylation when it is associated with G beta gamma but not as free Gs alpha. Using recombinant DNA techniques we modified the cDNA for the 52,000 M(r) form of Gs alpha (Gs alpha 52) to produce a protein with a 2,400 M(r) N-terminal extension (Gs alpha 54.4). This N-terminal extension could be removed with the protease Factor Xa. In vitro transcription and translation of the recombinant plasmid containing the cDNA's for Gs alpha 52 and Gs alpha 54.4 produced a 52,000 M(r) and a 54,000 M(r) protein, respectively. In solution the properties of Gs alpha 52 and Gs alpha 54.4 were indistinguishable. Both proteins: (a) formed a heterotrimer with G beta gamma and their affinities for the subunit complex were the same; (b) could be ADP-ribosylated by choleragen in the presence but not in the absence of G beta gamma; (c) bound the non-hydrolyzable GTP analogue, GTP gamma S, and were protected from chymotryptic proteolysis by the guanine nucleotide; and (d) could activate in vitro translated type IV adenylylcyclase. Gs alpha 54.4 and Gs alpha 52 were incorporated into S49 cyc-membranes, which lack Gs alpha. After incorporation, both Gs alpha 52 and Gs alpha 54.4 were protected from chymotryptic proteolysis when GTP gamma S was present, revealing that both proteins were able to bind the nucleotide and undergo a conformational change characteristic of Gs alpha activation. When Gs alpha 52 was incorporated into cyc-membranes it could mediate both hormone and GTP gamma S stimulation of adenylylcyclase and could be ADP-ribosylated by choleragen, but Gs alpha 54.4 could do neither of these things, indicating that the properties of Gs alpha 54.4 were altered by the membrane. Deletion of the N-terminal extension by treatment with Factor Xa in solution converted Gs alpha 54.4 to Gs alpha 52, and upon incorporation into cyc-membranes it behaved like Gs alpha 52 in every regard, showing that the effect of the N-terminal extension was reversible. A lack of other differences in the functional properties of Gs alpha 52 and Gs alpha 54.4 suggests a correlation between the interaction of Gs alpha with G beta gamma and its ability to activate adenylylcyclase. JF - Cellular signalling AU - Warner, D R AU - Okuya, S AU - Rebois, R V AD - Membrane Biochemistry Section, NINDS, NIH, Bethesda, MD 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 43 EP - 53 VL - 8 IS - 1 SN - 0898-6568, 0898-6568 KW - DNA, Complementary KW - 0 KW - Macromolecular Substances KW - Peptide Fragments KW - Recombinant Proteins KW - Solutions KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunits, Gs KW - EC 3.6.5.1 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Adenylyl Cyclases -- metabolism KW - Cholera Toxin -- pharmacology KW - Amino Acid Sequence KW - Adenosine Diphosphate Ribose -- metabolism KW - Protein Binding KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Molecular Weight KW - Structure-Activity Relationship KW - Rats KW - Mutagenesis, Site-Directed KW - Peptide Fragments -- chemistry KW - Recombinant Proteins -- metabolism KW - Genetic Vectors KW - Molecular Sequence Data KW - Enzyme Activation -- drug effects KW - Cell Membrane -- chemistry KW - Recombinant Proteins -- chemistry KW - Sequence Deletion KW - GTP-Binding Proteins -- chemistry KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78110485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+signalling&rft.atitle=Altered+Gs+alpha+N-terminus+affects+Gs+activity+and+interaction+with+the+G+beta+gamma+subunit+complex+in+cell+membranes+but+not+in+solution.&rft.au=Warner%2C+D+R%3BOkuya%2C+S%3BRebois%2C+R+V&rft.aulast=Warner&rft.aufirst=D&rft.date=1996-01-01&rft.volume=8&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Cellular+signalling&rft.issn=08986568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-19 N1 - Date created - 1996-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor suppressor genes: at the crossroads of molecular carcinogenesis, molecular epidemiology, and human risk assessment. AN - 78103857; 8778751 JF - Preventive medicine AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. PY - 1996 SP - 10 EP - 12 VL - 25 IS - 1 SN - 0091-7435, 0091-7435 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Animals KW - Risk Factors KW - Humans KW - DNA Mutational Analysis KW - Tumor Suppressor Protein p53 -- genetics KW - Genes, Tumor Suppressor -- genetics KW - Environmental Exposure -- adverse effects KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78103857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Preventive+medicine&rft.atitle=Tumor+suppressor+genes%3A+at+the+crossroads+of+molecular+carcinogenesis%2C+molecular+epidemiology%2C+and+human+risk+assessment.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1996-01-01&rft.volume=25&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Preventive+medicine&rft.issn=00917435&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-17 N1 - Date created - 1996-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insertional mutagenesis by Ty elements in Saccharomyces cerevisiae. AN - 78098817; 8924984 JF - Methods in molecular biology (Clifton, N.J.) AU - Garfinkel, D J AD - NCI-Frederick Cancer Research and Development Center, Laboratory of Eukaryotic Gene Expression, MD, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 227 EP - 237 VL - 53 SN - 1064-3745, 1064-3745 KW - DNA Transposable Elements KW - 0 KW - DNA, Fungal KW - Genetic Markers KW - Index Medicus KW - DNA, Fungal -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Mycology -- methods KW - DNA Transposable Elements -- genetics KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78098817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Insertional+mutagenesis+by+Ty+elements+in+Saccharomyces+cerevisiae.&rft.au=Garfinkel%2C+D+J&rft.aulast=Garfinkel&rft.aufirst=D&rft.date=1996-01-01&rft.volume=53&rft.issue=&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-25 N1 - Date created - 1996-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transplacental hormonal carcinogenesis: diethylstilbestrol as an example. AN - 78096932; 8778794 AB - Prenatal exposure to the potent synthetic estrogen DES has been associated with structural, functional, and long-term alterations, including neoplasia in both male and female offspring. The data summarized in this chapter provide the basis for studying the transplacental carcinogenic effects of other compounds, especially those with known estrogenic activity. Finally, since some of these described prenatal effects are apparently common to different species, experimental results can be predictive and informative in studying mechanisms of transplacentally induced neoplasia. JF - Progress in clinical and biological research AU - Newbold, R R AU - McLachlan, J A AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 131 EP - 147 VL - 394 SN - 0361-7742, 0361-7742 KW - Carcinogens KW - 0 KW - Estrogens, Non-Steroidal KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Humans KW - Genitalia -- abnormalities KW - Male KW - Female KW - Pregnancy KW - Maternal-Fetal Exchange KW - Diethylstilbestrol -- metabolism KW - Diethylstilbestrol -- adverse effects KW - Carcinogens -- metabolism KW - Neoplasms -- chemically induced KW - Estrogens, Non-Steroidal -- adverse effects KW - Estrogens, Non-Steroidal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78096932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Transplacental+hormonal+carcinogenesis%3A+diethylstilbestrol+as+an+example.&rft.au=Newbold%2C+R+R%3BMcLachlan%2C+J+A&rft.aulast=Newbold&rft.aufirst=R&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of estrogen-associated carcinogenesis. AN - 78082706; 8778792 JF - Progress in clinical and biological research AU - Barrett, J C AU - Tsutsui, T AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 105 EP - 111 VL - 394 SN - 0361-7742, 0361-7742 KW - Carcinogens KW - 0 KW - Estrogens KW - Index Medicus KW - Humans KW - Cell Division -- drug effects KW - Female KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Estrogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78082706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Mechanisms+of+estrogen-associated+carcinogenesis.&rft.au=Barrett%2C+J+C%3BTsutsui%2C+T&rft.aulast=Barrett&rft.aufirst=J&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulating effects of hormones on carcinogenesis. AN - 78082679; 8778811 AB - There is no doubt that hormones have a role in the development of many, perhaps most, cancers. This is because they are vital in maintaining homeostasis in multicellular organisms in which cancer appears. The stage or stages at which hormones are important in the process are not known well, but experiments in animals indicate that hormonal intervention at initiation, promotion, or progression can be important, assuming that such neat division pertains to cancer development in humans (Schmähl, 1985). Hormones may affect initiation through control of the levels of activating and detoxifying enzymes in the liver and other organs, which affect the pharmacokinetics of carcinogens to which the animal is exposed. Hormones control the levels of structural or functional components of some organs, for example, the alpha-2 micro-globulin in the kidney of male rats, which affect the disposition of foreign chemicals. Hormones have enormous influence on growth and development of animals and must play a part in the well-known heightened susceptibility of young animals (including humans) to the effects of exposure to carcinogens. Animals exposed in utero to transplacental carcinogens, or those exposed to single doses as newborns or infants, frequently develop tumors that appear in animals treated as adults not at all or after exposure to much higher doses. Examples are nervous system tumors in rodents exposed transplacentally (Ivankovic, 1979) and liver tumors in rodents treated as infants (Vesselinovitch et al., 1979). It is probable that effects of hormones on cell proliferation are an important part of these effects. From the studies of hormonal effects on carcinogenesis in animals we can conclude that alterations in the function of hormones through inheritance, or through diet, habits, accidents, disease states, or sexual maturity could affect susceptibility of an individual to carcinogens, thereby increasing or decreasing the probability of developing cancer. Compounds with antithyroid properties (e.g., thiouracil or ethylene thiourea, a contaminant and by-product of many thiocarbamates widely used in agriculture and industry) or substances affecting adrenal or pituitary secretions might be implicated as modulators of tumor development, following the leads suggested by experiments in animals described above. Castration, aging, or hypersecretion of sex hormones would also modulate the effects of carcinogens, as they do in experimental animals. There have been few studies of the effects of other hormones such as insulin, gastrin, prolactin, and so forth (Griffin et al., 1955), although these vital hormones vary in distribution even within an individual at different times. An early study (Sugiura and Benedict, 1933) failed to show an effect of treatment with a variety of hormones on the growth of several transplanted tumors. One elusive mystery is why estrogens and diethylstilbestrol induce kidney tumors in Syrian hamsters but not mammary tumors, whereas in rats they give rise to mammary tumors but not to kidney tumors. Obviously we need to know much more about biology in order to better understand the intricacies of neoplastic transformation and development of cancer. JF - Progress in clinical and biological research AU - Lijinsky, W AD - Division of Biometry and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 57 EP - 76 VL - 394 SN - 0361-7742, 0361-7742 KW - Hormones KW - 0 KW - Index Medicus KW - Animals KW - Sex Factors KW - Humans KW - Male KW - Female KW - Hormones -- physiology KW - Neoplasms, Hormone-Dependent -- etiology KW - Neoplasms, Hormone-Dependent -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78082679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Modulating+effects+of+hormones+on+carcinogenesis.&rft.au=Lijinsky%2C+W&rft.aulast=Lijinsky&rft.aufirst=W&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormonal and environmental factors affecting cell proliferation and neoplasia in the mammary gland. AN - 78078189; 8778798 AB - Although estrogens have been identified as key endocrine hormones in the control of early mitogenesis and development in the mammary gland, local control of cell proliferation during ductal morphogenesis may be regulated by polypeptides such as TGF-alpha or TGF-beta. Many breast tumors are estrogen dependent, and some breast tumor cell lines are known to produce TGF-alpha, suggesting that the mitogenic pathways controlling early normal mammary growth and the growth of some breast tumors may be similar. While progesterone does not appear to be important in the early program of ductal growth, progesterone and estrogen are necessary for the cyclic proliferation of mammary ductal cells that occurs during the menstrual cycle, and for lobuloalveolar growth during pregnancy. Since increased cell division enhances the chances for the formation of a malignant phenotype in the breast, exogenous hormones containing estrogen alone or estrogen and progesterone may increase breast cancer risk. While DES is no longer prescribed to prevent abortions, it demonstrates that high doses of an estrogen during a period of mammary proliferation can affect breast cancer risk. Whether the addition of progestogens to estrogen replacement therapy enhances breast cancer risk in postmenopausal women remains an unanswered question because of the lack of large, well-controlled prospective studies. There currently is no evidence to indicate that the progestogen-containing subdermal contraceptive Norplant increases breast cancer risk. However, it has not been determined if the elevation of serum estrogens reported in some Norplant users affects breast cancer risk. There is little evidence that combined OCAs enhance breast cancer risk in most women. More research is needed to substantiate the findings that OCA use in young women, especially before a first full-term pregnancy, may enhance breast cancer risk. Animal studies indicate that there are critical periods of susceptibility to chemical carcinogens, since the number and malignancy of tumors are increased when carcinogens are administered to young virgin animals during the proliferative period of ductal morphogenesis. Since the breast appears to be most susceptible to the carcinogenic effects of ionizing radiation during the first decade of life, exposure to other carcinogenic agents during the period of early breast development may be important in determining breast cancer risk. Therefore, more studies are needed to confirm the observation that heavy drinkers and heavy smokers are at higher risk for developing breast cancer when they start smoking or drinking at an early age. The observation that serum and urinary estrogen levels increase with alcohol consumption may provide a basis for the higher risk of developing breast cancer in heavy drinkers. While the restriction of methyxanthine intake may alleviate the symptoms associated with fibrocystic breast disease in some women, there is not enough evidence to suggest that a reduction in caffeine intake will reduce breast cancer risk. Evidence for an association between electromagnetic radiation and breast cancer is limited. Electromagnetic radiation may only pose a risk in certain occupations with exposure to very high levels for extended periods of time. It is not known whether exposure to PCBs transplacentally or though the lipid fraction of human milk can affect breast cancer rates in female offspring. The higher risk of breast cancer in women with elevated DDE levels in their blood underscores the importance of determining the extent to which environmental contaminants affect breast cancer risk. JF - Progress in clinical and biological research AU - Snedeker, S M AU - Diaugustine, R P AD - Hormone and Cancer Workgroup, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 211 EP - 253 VL - 394 SN - 0361-7742, 0361-7742 KW - Hormones KW - 0 KW - Index Medicus KW - Humans KW - Female KW - Cell Division KW - Hormones -- physiology KW - Breast Neoplasms -- pathology KW - Environmental Exposure KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- chemically induced KW - Hormones -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78078189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Hormonal+and+environmental+factors+affecting+cell+proliferation+and+neoplasia+in+the+mammary+gland.&rft.au=Snedeker%2C+S+M%3BDiaugustine%2C+R+P&rft.aulast=Snedeker&rft.aufirst=S&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular and molecular mechanisms of cancers of the uterus in animals. AN - 78076970; 8778796 JF - Progress in clinical and biological research AU - McLachlan, J A AU - Newbold, R R AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 175 EP - 182 VL - 394 SN - 0361-7742, 0361-7742 KW - Estrogens KW - 0 KW - Receptors, Estrogen KW - Epidermal Growth Factor KW - 62229-50-9 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Diethylstilbestrol -- adverse effects KW - Estrogens -- adverse effects KW - Receptors, Estrogen -- physiology KW - Female KW - Epidermal Growth Factor -- physiology KW - Uterine Neoplasms -- chemistry KW - Uterine Neoplasms -- chemically induced KW - Uterine Neoplasms -- veterinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78076970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Cellular+and+molecular+mechanisms+of+cancers+of+the+uterus+in+animals.&rft.au=McLachlan%2C+J+A%3BNewbold%2C+R+R&rft.aulast=McLachlan&rft.aufirst=J&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemically induced cancers in hormonal organs of laboratory animals and of humans. AN - 78076930; 8778812 JF - Progress in clinical and biological research AU - Huff, J AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 77 EP - 102 VL - 394 SN - 0361-7742, 0361-7742 KW - Carcinogens KW - 0 KW - Index Medicus KW - Causality KW - Animals KW - Humans KW - Carcinogenicity Tests KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Neoplasms, Hormone-Dependent -- chemically induced KW - Neoplasms, Hormone-Dependent -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78076930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Chemically+induced+cancers+in+hormonal+organs+of+laboratory+animals+and+of+humans.&rft.au=Huff%2C+J&rft.aulast=Huff&rft.aufirst=J&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extrapolation of heterocyclic amine carcinogenesis data from rodents and nonhuman primates to humans. AN - 78072842; 8678807 AB - Twenty different heterocyclic amines have been isolated and identified from cooked foods especially beef, fish, pork and fowl. Other HCAs have also been isolated but their structure remains to be elucidated and new HCAs are likely to be identified in the future. The HCAs are highly mutagenic and all ten HCAs that have been tested for carcinogenic activity, produce tumors in mice and rats. For humans the average daily intake of HCAs is in quantities of 10-20 mg/person/day. The HCAs are procarcinogens and are activated by the cytochrome P450 system especially CYP 1A2. Rodents, monkeys and humans have the capacity to activate HCAs. Studies using hepatic microsomes demonstrated that humans have a greater capacity to activate the majority of HCAs tested than rodents or cynomolgus monkeys. Three HCAs are currently under evaluation in nonhuman primates for carcinogenic activity and one, IQ, is highly carcinogenic inducing primary hepatocellular carcinomas in the majority of cynomolgus monkeys treated. Epidemiological studies, although not definitive, are supportive of an association of HCAs intake to the etiology of human cancer. Risk assessments from animal data show a risk of HCAs to humans in the range of 10(-3) to 10(-4) which is an order of magnitude greater than compounds currently regulated by the U.S. Food and Drug Administration or the Environmental Protection Agency. Taken together evidence from mutagenicity data, activation by various species including humans, carcinogenicity in animals, human consumption data, epidemiological studies and risk assessment, supports the conclusion that HCAs are probable human carcinogens. JF - Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement AU - Adamson, R H AU - Thorgeirsson, U P AU - Sugimura, T AD - National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 303 EP - 318 VL - 18 SN - 0171-9750, 0171-9750 KW - Amines KW - 0 KW - Carcinogens KW - Heterocyclic Compounds KW - Imidazoles KW - Mutagens KW - Quinoxalines KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - 2-amino-3,7,8-trimethylimidazo(4,5-f)quinoxaline KW - 92180-79-5 KW - Index Medicus KW - Animals KW - Imidazoles -- toxicity KW - Humans KW - Imidazoles -- metabolism KW - Quinoxalines -- metabolism KW - Food Handling KW - Neoplasms -- epidemiology KW - Mice KW - Primates KW - Structure-Activity Relationship KW - Risk Assessment KW - Rats KW - Quinoxalines -- adverse effects KW - Biotransformation KW - Meat -- adverse effects KW - Quinoxalines -- toxicity KW - Diet KW - Species Specificity KW - Imidazoles -- adverse effects KW - Neoplasms -- etiology KW - Heterocyclic Compounds -- metabolism KW - Carcinogens -- metabolism KW - Mutagens -- metabolism KW - Mutagens -- adverse effects KW - Amines -- toxicity KW - Carcinogens -- toxicity KW - Amines -- metabolism KW - Mutagens -- toxicity KW - Heterocyclic Compounds -- toxicity KW - Heterocyclic Compounds -- adverse effects KW - Amines -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78072842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology.+Supplement.+%3D+Archiv+fur+Toxikologie.+Supplement&rft.atitle=Extrapolation+of+heterocyclic+amine+carcinogenesis+data+from+rodents+and+nonhuman+primates+to+humans.&rft.au=Adamson%2C+R+H%3BThorgeirsson%2C+U+P%3BSugimura%2C+T&rft.aulast=Adamson&rft.aufirst=R&rft.date=1996-01-01&rft.volume=18&rft.issue=&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology.+Supplement.+%3D+Archiv+fur+Toxikologie.+Supplement&rft.issn=01719750&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-12 N1 - Date created - 1996-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormonal influence on hepatocarcinogenesis. AN - 78072017; 8778806 JF - Progress in clinical and biological research AU - Coe, J E AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 399 EP - 421 VL - 394 SN - 0361-7742, 0361-7742 KW - Gonadal Steroid Hormones KW - 0 KW - Hormones KW - Tamoxifen KW - 094ZI81Y45 KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Index Medicus KW - Animals KW - Humans KW - Tamoxifen -- adverse effects KW - Gonadal Steroid Hormones -- physiology KW - Dehydroepiandrosterone -- pharmacology KW - Cricetinae KW - Hormones -- physiology KW - Liver Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78072017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Hormonal+influence+on+hepatocarcinogenesis.&rft.au=Coe%2C+J+E&rft.aulast=Coe&rft.aufirst=J&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormonal carcinogenesis and environmental influences: background and overview. AN - 78071919; 8778803 JF - Progress in clinical and biological research AU - Huff, J AU - Boyd, J AU - Barrett, J C AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 3 EP - 23 VL - 394 SN - 0361-7742, 0361-7742 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Causality KW - Environment KW - Ovarian Neoplasms -- etiology KW - Prostatic Neoplasms -- epidemiology KW - Humans KW - Breast Neoplasms -- epidemiology KW - Prostatic Neoplasms -- etiology KW - Adult KW - Breast Neoplasms -- etiology KW - Female KW - Male KW - Ovarian Neoplasms -- epidemiology KW - Neoplasms, Hormone-Dependent -- etiology KW - Neoplasms, Hormone-Dependent -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78071919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Hormonal+carcinogenesis+and+environmental+influences%3A+background+and+overview.&rft.au=Huff%2C+J%3BBoyd%2C+J%3BBarrett%2C+J+C&rft.aulast=Huff&rft.aufirst=J&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental causes and molecular biology of breast cancer: future research directions. AN - 78067541; 8778810 JF - Progress in clinical and biological research AU - Jahnke, G D AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 455 EP - 469 VL - 394 SN - 0361-7742, 0361-7742 KW - Carcinogens, Environmental KW - 0 KW - Hormones KW - Receptors, Estrogen KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Life Style KW - Humans KW - Receptor, Epidermal Growth Factor -- physiology KW - Forecasting KW - Carcinogens, Environmental -- toxicity KW - Receptors, Estrogen -- physiology KW - Female KW - Hormones -- adverse effects KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78067541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Environmental+causes+and+molecular+biology+of+breast+cancer%3A+future+research+directions.&rft.au=Jahnke%2C+G+D%3BBarrett%2C+J+C&rft.aulast=Jahnke&rft.aufirst=G&rft.date=1996-01-01&rft.volume=394&rft.issue=&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-13 N1 - Date created - 1996-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The estrogen antagonist tamoxifen inhibits carrageenan induced inflammation in LEW/N female rats. AN - 78041034; 8614285 AB - Carrageenan induces a measurable inflammatory response in susceptible animals, and mature females are more responsive to carrageenan, than males. In the present study, we tested whether the estrogen antagonist tamoxifen influences carrageenan-induced inflammatory responses. Female LEW/N rats were treated with tamoxifen and compared to a control group of animals injected with vehicle. Tamoxifen significantly reduced estrous phase of estrous cycle during treatment, consistent with its functional anti-estrogen effects. Moreover, tamoxifen significantly decreased exudate volume but did not significantly influence relative white blood cell counts in the exudate. Interestingly, tamoxifen induced differential dose-dependent alterations in peripheral blood lymphocyte subpopulations. Low dose of tamoxifen increased CD25 cells. The high tamoxifen dose significantly increased CD8 blood lymphocytes counts. Our data indicate that tamoxifen treatment decreases carrageenan-induced inflammatory response in female LEW/N rats and suggest therefore that this inflammatory response is, at least in part, estrogen related. Moreover, our results suggest a possible role for tamoxifen in treatment of inflammatory disorders. JF - Life sciences AU - Misiewicz, B AU - Griebler, C AU - Gomez, M AU - Raybourne, R AU - Zelazowska, E AU - Gold, P W AU - Sternberg, E M AD - Clinical Neuroendocrinology Branch, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - PL281 EP - PL286 VL - 58 IS - 16 SN - 0024-3205, 0024-3205 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Estrogen Antagonists KW - Receptors, Interleukin-2 KW - Tamoxifen KW - 094ZI81Y45 KW - Carrageenan KW - 9000-07-1 KW - Index Medicus KW - AIDS/HIV KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Drug Interactions KW - CD8-Positive T-Lymphocytes -- drug effects KW - Receptors, Interleukin-2 -- analysis KW - Lymphocyte Subsets -- drug effects KW - Lymphocytes -- drug effects KW - Estrus -- drug effects KW - Female KW - Inflammation -- prevention & control KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Tamoxifen -- therapeutic use KW - Inflammation -- chemically induced KW - Inflammation -- blood KW - Carrageenan -- antagonists & inhibitors KW - Estrogen Antagonists -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78041034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=The+estrogen+antagonist+tamoxifen+inhibits+carrageenan+induced+inflammation+in+LEW%2FN+female+rats.&rft.au=Misiewicz%2C+B%3BGriebler%2C+C%3BGomez%2C+M%3BRaybourne%2C+R%3BZelazowska%2C+E%3BGold%2C+P+W%3BSternberg%2C+E+M&rft.aulast=Misiewicz&rft.aufirst=B&rft.date=1996-01-01&rft.volume=58&rft.issue=16&rft.spage=PL281&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-05 N1 - Date created - 1996-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxanes. AN - 78040491; 8639402 JF - Cancer chemotherapy and biological response modifiers AU - Fojo, A AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 57 EP - 67 VL - 16 SN - 0921-4410, 0921-4410 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Bridged-Ring Compounds KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - taxane KW - 1605-68-1 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Paclitaxel -- metabolism KW - Drug Interactions KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Paclitaxel -- pharmacokinetics KW - Humans KW - Paclitaxel -- analogs & derivatives KW - Clinical Trials as Topic KW - Paclitaxel -- pharmacology KW - Bridged-Ring Compounds -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Bridged-Ring Compounds -- metabolism KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Bridged-Ring Compounds -- pharmacology KW - Antineoplastic Agents, Phytogenic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78040491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+biological+response+modifiers&rft.atitle=Taxanes.&rft.au=Fojo%2C+A&rft.aulast=Fojo&rft.aufirst=A&rft.date=1996-01-01&rft.volume=16&rft.issue=&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical biology of nitric oxide: regulation and protective and toxic mechanisms. AN - 78035674; 8646847 JF - Current topics in cellular regulation AU - Wink, D A AU - Hanbauer, I AU - Grisham, M B AU - Laval, F AU - Nims, R W AU - Laval, J AU - Cook, J AU - Pacelli, R AU - Liebmann, J AU - Krishna, M AU - Ford, P C AU - Mitchell, J B AD - Chemistry Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 159 EP - 187 VL - 34 SN - 0070-2137, 0070-2137 KW - Enzyme Inhibitors KW - 0 KW - Free Radicals KW - Metals KW - Nitrates KW - Reactive Oxygen Species KW - peroxynitric acid KW - 26404-66-0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Chemistry, Physical KW - DNA Damage KW - Nitrates -- metabolism KW - Energy Metabolism KW - Lipid Peroxidation KW - Cytotoxicity, Immunologic KW - Oxidative Stress KW - Chemical Phenomena KW - Enzyme Inhibitors -- metabolism KW - Metals -- metabolism KW - Cells -- metabolism KW - Cells -- radiation effects KW - Nitric Oxide -- toxicity KW - Nitric Oxide -- physiology KW - Nitric Oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78035674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+cellular+regulation&rft.atitle=Chemical+biology+of+nitric+oxide%3A+regulation+and+protective+and+toxic+mechanisms.&rft.au=Wink%2C+D+A%3BHanbauer%2C+I%3BGrisham%2C+M+B%3BLaval%2C+F%3BNims%2C+R+W%3BLaval%2C+J%3BCook%2C+J%3BPacelli%2C+R%3BLiebmann%2C+J%3BKrishna%2C+M%3BFord%2C+P+C%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1996-01-01&rft.volume=34&rft.issue=&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+cellular+regulation&rft.issn=00702137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-19 N1 - Date created - 1996-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lymphomas. AN - 78035629; 8639391 JF - Cancer chemotherapy and biological response modifiers AU - Kwak, L W AU - Longo, D L AD - Clinical Research Branch, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 376 EP - 440 VL - 16 SN - 0921-4410, 0921-4410 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Hodgkin Disease -- pathology KW - Neoplasm Staging KW - HIV Seropositivity KW - Humans KW - Prognosis KW - Child KW - Radiotherapy -- adverse effects KW - Antineoplastic Agents -- adverse effects KW - Lymphoma -- therapy KW - Lymphoma -- etiology KW - Lymphoma -- epidemiology KW - Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78035629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+biological+response+modifiers&rft.atitle=Lymphomas.&rft.au=Kwak%2C+L+W%3BLongo%2C+D+L&rft.aulast=Kwak&rft.aufirst=L&rft.date=1996-01-01&rft.volume=16&rft.issue=&rft.spage=376&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer following irradiation in childhood and adolescence. AN - 78034691; 8643045 AB - The child appears more sensitive than the adult to the carcinogenic effects of radiation for certain sites such as the breast and thyroid. However, there are few studies of persons who were exposed as children and adolescents who have been followed for 40 or 50 years into the adult ages. Thus, it is extremely important that follow-up studies of children continue to evaluate the lifetime cancer risk that might be related to radiation exposures in childhood. JF - Medical and pediatric oncology. Supplement AU - Boice, J D AD - National Cancer Institute, Radiation Epidemiology Branch, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 29 EP - 34 VL - 1 SN - 0740-8226, 0740-8226 KW - Index Medicus KW - Occupational Exposure KW - Nuclear Warfare KW - Humans KW - Adult KW - Environmental Exposure KW - Follow-Up Studies KW - Child KW - Radiography -- adverse effects KW - Radiation Effects KW - Adolescent KW - Survivors KW - Radiotherapy -- adverse effects KW - Neoplasms, Radiation-Induced -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78034691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+and+pediatric+oncology.+Supplement&rft.atitle=Cancer+following+irradiation+in+childhood+and+adolescence.&rft.au=Boice%2C+J+D&rft.aulast=Boice&rft.aufirst=J&rft.date=1996-01-01&rft.volume=1&rft.issue=&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Medical+and+pediatric+oncology.+Supplement&rft.issn=07408226&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-15 N1 - Date created - 1996-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 tumor suppressor gene: implications for iatrogenic cancer and cancer therapy. AN - 78029958; 8643042 JF - Medical and pediatric oncology. Supplement AU - De Benedetti, V AU - Bennett, W P AU - Greenblatt, M S AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 2 EP - 11 VL - 1 SN - 0740-8226, 0740-8226 KW - Carcinogens KW - 0 KW - Index Medicus KW - Cocarcinogenesis KW - Iatrogenic Disease KW - Humans KW - Mutation -- genetics KW - Male KW - Female KW - Carcinogens -- adverse effects KW - Neoplasms, Second Primary -- genetics KW - Genes, p53 -- genetics KW - Neoplasms -- therapy KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78029958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+and+pediatric+oncology.+Supplement&rft.atitle=p53+tumor+suppressor+gene%3A+implications+for+iatrogenic+cancer+and+cancer+therapy.&rft.au=De+Benedetti%2C+V%3BBennett%2C+W+P%3BGreenblatt%2C+M+S%3BHarris%2C+C+C&rft.aulast=De+Benedetti&rft.aufirst=V&rft.date=1996-01-01&rft.volume=1&rft.issue=&rft.spage=2&rft.isbn=&rft.btitle=&rft.title=Medical+and+pediatric+oncology.+Supplement&rft.issn=07408226&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-15 N1 - Date created - 1996-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antimetabolites. AN - 78027156; 8639379 JF - Cancer chemotherapy and biological response modifiers AU - Johnston, P G AU - Takimoto, C H AU - Grem, J L AU - Chabner, B A AU - Allegra, C J AU - Chu, E AD - Navy Medical Oncology Branch, National Cancer Institute, Naval Hospital Bethesda, MD 20889-5105, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 1 EP - 27 VL - 16 SN - 0921-4410, 0921-4410 KW - Antimetabolites, Antineoplastic KW - 0 KW - Purines KW - Cytidine KW - 5CSZ8459RP KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Animals KW - Methotrexate -- pharmacology KW - DNA Repair KW - Cell Survival -- drug effects KW - DNA Damage KW - Humans KW - Fluorouracil -- analogs & derivatives KW - Cytidine -- pharmacology KW - Purines -- pharmacology KW - Fluorouracil -- pharmacology KW - Cytidine -- analogs & derivatives KW - Antimetabolites, Antineoplastic -- adverse effects KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78027156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+biological+response+modifiers&rft.atitle=Antimetabolites.&rft.au=Johnston%2C+P+G%3BTakimoto%2C+C+H%3BGrem%2C+J+L%3BChabner%2C+B+A%3BAllegra%2C+C+J%3BChu%2C+E&rft.aulast=Johnston&rft.aufirst=P&rft.date=1996-01-01&rft.volume=16&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-16 N1 - Date created - 1996-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of flavone acetic acid on endothelial cell proliferation: evidence for antiangiogenic properties. AN - 78010500; 8615648 AB - Flavone acetic acid (FAA) causes regression of a range of slow growing solid tumors implanted subcutaneously in mice. Although its precise mechanism of action is unknown, vascular collapse has been shown to precede tumor growth delay and regression. The aim of this study was to determine whether or not endothelial cell function was directly affected by clinically relevant concentrations of FAA. FAA at 100-250 micrograms/ml inhibited endothelial cell proliferation in vitro, but did not compromise cellular function or viability. FAA abolished tubule formation in an in vitro angiogenesis assay and reduced vascular development of the chick embryo chorioallantoic membrane. In addition to targeting established tumor vasculature, FAA may also affect proliferating endothelium which may be involved in mediating the reduced tumor growth rate or stasis often often observed after drug exposure. The chorioallantoic membrane of the chick embryo may represent an important model to elucidate more clearly the effect of FAA on a growing vascular network. JF - Anticancer research AU - Lindsay, C K AU - Gomez, D E AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1996 SP - 425 EP - 431 VL - 16 IS - 1 SN - 0250-7005, 0250-7005 KW - Antineoplastic Agents KW - 0 KW - Drug Combinations KW - Flavonoids KW - Laminin KW - Proteoglycans KW - matrigel KW - 119978-18-6 KW - flavone acetic acid KW - 87626-55-9 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Chick Embryo KW - Humans KW - Cell Division -- drug effects KW - Microtubules -- drug effects KW - Cells, Cultured KW - Allantois -- blood supply KW - Chorion -- blood supply KW - Endothelium, Vascular -- drug effects KW - Endothelium, Vascular -- cytology KW - Flavonoids -- pharmacology KW - Neovascularization, Physiologic -- drug effects KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78010500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Effect+of+flavone+acetic+acid+on+endothelial+cell+proliferation%3A+evidence+for+antiangiogenic+properties.&rft.au=Lindsay%2C+C+K%3BGomez%2C+D+E%3BThorgeirsson%2C+U+P&rft.aulast=Lindsay&rft.aufirst=C&rft.date=1996-01-01&rft.volume=16&rft.issue=1&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-05 N1 - Date created - 1996-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leishmania major: infection of human monocytes induces expression of IL-8 and MCAF. AN - 78004801; 8617327 AB - Leishmania major, the causative agent of cutaneous leishmaniasis, is an intracellular parasite of monocytic cells. Leishmania lesions are characterized by recruitment of neutrophils, eosinophils, and blood monocytes. To clarify the mechanism of this cellular influx we examined the expression of IL-8 and MCAF, cytokines chemotactic for neutrophils and monocytes, respectively, in human monocytes infected by L. major. Supernatants of monocytes infected with L. major had chemotactic activity for neutrophils and monocytes that was neutralized by anti-IL-8 and anti-MCAF antibodies. Both IL-8 and MCAF mRNAs were induced within 1 hr of infection. Furthermore we showed that infection of monocytes with L. major induces IL-8 and MCAF but not the proinflammatory cytokines IL-1 beta and TNF alpha. These data suggest that the expression of chemokines may contribute to the cellular recruitment in Leishmania lesions. JF - Experimental parasitology AU - Badolato, R AU - Sacks, D L AU - Savoia, D AU - Musso, T AD - Biological Carcinogenesis and Development Program, Program Resources, Inc/DynCorp. NCI-FCRDC, Frederick, Maryland 21702-1201, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 21 EP - 26 VL - 82 IS - 1 SN - 0014-4894, 0014-4894 KW - Chemokine CCL2 KW - 0 KW - Interleukin-8 KW - RNA, Messenger KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Neutrophils KW - Cells, Cultured KW - Humans KW - RNA, Messenger -- analysis KW - Chemotaxis, Leukocyte KW - Interleukin-8 -- biosynthesis KW - Leishmania major -- genetics KW - Chemokine CCL2 -- biosynthesis KW - Gene Expression Regulation KW - Monocytes -- parasitology KW - Leishmania major -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78004801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+parasitology&rft.atitle=Leishmania+major%3A+infection+of+human+monocytes+induces+expression+of+IL-8+and+MCAF.&rft.au=Badolato%2C+R%3BSacks%2C+D+L%3BSavoia%2C+D%3BMusso%2C+T&rft.aulast=Badolato&rft.aufirst=R&rft.date=1996-01-01&rft.volume=82&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Experimental+parasitology&rft.issn=00144894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-11 N1 - Date created - 1996-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of suppression of tumor cell phenotype by overexpression of TIMP-3 in mouse JB6 tumor cells identification of a transfectant with increased tumorigenicity and invasiveness. AN - 78003942; 8615593 AB - We have recently cloned mouse tissue inhibitor of metalloproteinases-3 (mTIMP-3) by the differential display technique and found that mTIMP-3 was expressed in preneoplastic but not in neoplastic mouse JB6 epidermal cells (Sun et at. Cancer Res. 54:11139, 1994). This down regulation of the gene is attributable at least in part to alteration in gene methylation (Sun et al., J. Biol. Chem., 270:19312, 1995). To examine the potential role of TIMP-3 in two JB6 tumor cell model, we overexpressed mouse TIMP-3 in two JB6 tumor cell lines lacking endogenous mTIMP-3 expression. Stable transfectants from each line were selected and assayed for possible changes in tumor cell phenotype. Our results showed overexpression of mTIMP-3 in these two tumor lines did not change their ability to grow in soft agar, an assay for anchorage-independent growth, nor in nude mice, an in vivo tumorigenicity assay, nor to penetrate matrigel, an assay for invasiveness We, however, isolated a clone which is highly malignant was demonstrated by a) very short latent period for tumor formation; b) very fast tumor growth; and c) highly invasive in the matrigel assay. We conclude from this study that although TIMP-3 is not expressed in mouse JB6 tumor cells, overexpression by DNA transfection did not reverse tumor cell phenotype, suggesting a complex role for TIMP-3 in tumorigenesis. The highly malignant transfectant isolated by this study can be used as a tool for the cloning of dominant oncogenes as well as tumor suppressor genes. JF - Anticancer research AU - Sun, Y AU - Kim, H AU - Parker, M AU - Stetler-Stevenson, W G AU - Colburn, N H AD - Laboratory of Viral Carcinogenesis National Cancer Institute, Frederick Cancer Research & Development Center, MD 21702, USA. PY - 1996 SP - 1 EP - 7 VL - 16 IS - 1 SN - 0250-7005, 0250-7005 KW - Proteins KW - 0 KW - Tissue Inhibitor of Metalloproteinase-3 KW - Index Medicus KW - Phenotype KW - Neoplasm Invasiveness KW - Animals KW - Tumor Cells, Cultured KW - Transfection KW - Disease Progression KW - Cell Division -- physiology KW - Mice KW - Skin Neoplasms -- genetics KW - Protein Biosynthesis KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- metabolism KW - Proteins -- genetics KW - Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78003942?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Lack+of+suppression+of+tumor+cell+phenotype+by+overexpression+of+TIMP-3+in+mouse+JB6+tumor+cells+identification+of+a+transfectant+with+increased+tumorigenicity+and+invasiveness.&rft.au=Sun%2C+Y%3BKim%2C+H%3BParker%2C+M%3BStetler-Stevenson%2C+W+G%3BColburn%2C+N+H&rft.aulast=Sun&rft.aufirst=Y&rft.date=1996-01-01&rft.volume=16&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-05 N1 - Date created - 1996-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in hepatocellular carcinoma related to oral contraceptive use. AN - 77986440; 8565124 AB - Oral contraceptives (OCs) are implicated in the development of hepatocellular carcinoma (HCC). Mitogenic stimulation may be the primary mechanism of tumorigenesis, but other factors may also contribute. Mutational spectrum analysis can provide insights into pathogenesis, therefore we analyzed the p53 tumor suppressor gene in 10 HCCs from women with a history of OC use. All were non-Asians whose average OC use was 6.7 years (range 2 months-13 years) and whose mean age at HCC diagnosis was 48.8 years (range 21-67 years). Each tumor was analyzed by immunohistochemistry, DNA sequencing and allelic deletion analysis. Three tumors were positive by p53 immunohistochemistry; allelic deletion analysis identified loss of heterozygosity in one of four informative cases. Two p53 point mutations were found in one tumor containing moderately and well-differentiated components; this patient was negative for all serological markers of hepatitis B and C infections. Both components showed p53 protein accumulation and a GTTval-->GCTala mutation at codon 274. In addition, a silent mutation (ACCthr-->ACTthr) at codon 140 of the p53 gene was detected in the moderately differentiated component of the tumor. These preliminary data indicate that p53 mutations are uncommon in OC-related HCCs. One of the two detected mutations was a G:C-->A:T transition at a non-CpG site, which is characteristic of DNA damage by free radicals. These data support a model whereby estrogens contribute to HCC development primarily through mitogen stimulation and secondarily by mutagenesis via hydroxyl radicals produced during estrogen metabolism. Confirmational analysis of a larger series is warranted. JF - Carcinogenesis AU - De Benedetti, V M AU - Welsh, J A AU - Yu, M C AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 145 EP - 149 VL - 17 IS - 1 SN - 0143-3334, 0143-3334 KW - Contraceptives, Oral KW - 0 KW - Index Medicus KW - Population KW - Laboratory Examinations And Diagnoses KW - Physiology KW - Research Report KW - Oral Contraceptives KW - Hepatic Effects KW - Contraceptive Methods KW - Cancer KW - Laboratory Procedures KW - Genetics KW - Neoplasms KW - Histology KW - Contraception KW - Examinations And Diagnoses KW - Diseases KW - Family Planning KW - Biology KW - Base Sequence KW - Humans KW - Adult KW - Molecular Sequence Data KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Female KW - Contraceptives, Oral -- adverse effects KW - Genes, p53 KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- chemically induced KW - Mutation KW - Carcinoma, Hepatocellular -- chemically induced KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77986440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=p53+mutations+in+hepatocellular+carcinoma+related+to+oral+contraceptive+use.&rft.au=De+Benedetti%2C+V+M%3BWelsh%2C+J+A%3BYu%2C+M+C%3BBennett%2C+W+P&rft.aulast=De+Benedetti&rft.aufirst=V&rft.date=1996-01-01&rft.volume=17&rft.issue=1&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of thyroid and hepatocarcinogenesis by 1,4-bis[2-(3,5- dichloropyridyloxy)]benzene in rats at doses that cause maximal induction of CYP2B. AN - 77982691; 8565134 AB - To investigate the promoting effects of 1,4-bis[2-(3,5- dichloropyridyloxy)]benzene (TCPOBOP) on liver and thyroid carcinogenesis of rats at doses that cause maximal induction of hepatic CYP2B, 5-week-old male F344 rats were given either a single i.p. dose of 75 mg N-nitrosodiethylamine (NDEA)/kg body wt in saline or saline alone. After 2 weeks the rats were fed control diet or a diet containing 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. phenobarbital (PB; a positive control group). A total of four sequential sacrifices (9, 30, 52 and 79 weeks of age) was performed. At 30 weeks the mean volume (mm3) of hepatocellular foci in NDEA-initiated rats exposed to either dose of TCPOBOP or to PB was significantly increased as compared with rats exposed to NDEA followed by control diet (P < 0.05). In addition, the volume percentage of liver occupied by foci was significantly greater in NDEA-initiated/1000 p.p.m. TCPOBOP-promoted rats as compared with rats exposed to NDEA alone (P < 0.05, n = 6). At 52 weeks of age the incidences (and multiplicities, in units of tumors per tumor-bearing rat) of hepatocellular adenomas were 0, 83 (2.6 +/- 1.3), 100 (3.4 +/- 2.1) or 67% (2.5 +/- 1.9) in rats exposed to NDEA alone or NDEA followed by 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. PB respectively (n = 12). Hepatocellular carcinomas were found only in rats given 1000 p.p.m. TCPOBOP (17% incidence) or PB (8% incidence) following NDEA initiation. The incidences of thyroid follicular cell adenomas were 0, 17, 33 or 8% in rats exposed to NDEA alone or NDEA followed by 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. PB respectively. Between 53 and 79 weeks of age 38% of rats treated with NDEA alone developed multiple (1.5 +/- 0.8) hepatocellular adenomas. This incidence was enhanced to 100% in rats exposed to NDEA followed by either 330 or 1000 p.p.m. TCPOBOP. Multiplicities of hepatocellular adenomas were also increased significantly (10.5 +/- 3.9, 10.4 +/- 7.0 and 10.1 +/- 6.7 respectively) in rats promoted with 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. PB. None of the rats exposed to NDEA alone developed hepatocellular carcinomas, while multiple hepatocellular carcinomas occurred in 38% of the rats exposed to 330 p.p.m. and 78% of the rats given 1000 p.p.m. TCPOBOP following NDEA initiation. Thyroid follicular cell tumors occurred at 79 weeks in more than 40 and 50% incidences in rats exposed to NDEA followed by 330 or 1000 p.p.m. TCPOBOP respectively. Also, a significant decrease in serum levels of triiodothyronine and thyroxine were observed in non-initiated 79-week-old rats fed 1000 p.p.m. TCPOBOP, compared with age-matched untreated controls (n = 6). Increases in hepatic CYP2B-mediated benzyloxyresorufin O-dealkylase activity detected in rats exposed to 330 and 1000 p.p.m. TCPOBOP for 2 or 23 weeks were similar in magnitude to those caused by 500 p.p.m. PB. Thus TCPOBOP at maximal CYP2B induction doses exhibits a strong promoting activity for both liver and thyroid of rats. JF - Carcinogenesis AU - Diwan, B A AU - Henneman, J R AU - Rice, J M AU - Nims, R W AD - Biological Carcinogenesis and Development Program, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 37 EP - 43 VL - 17 IS - 1 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Pyridines KW - Thyroid Hormones KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - 1,4-bis(2-(3,5-dichloropyridyloxy))benzene KW - 76150-91-9 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Weight Gain -- drug effects KW - Animals KW - Rats, Inbred F344 KW - Enzyme Induction -- drug effects KW - Precancerous Conditions -- chemically induced KW - Thyroid Hormones -- blood KW - Male KW - Thyroid Neoplasms -- chemically induced KW - Pyridines -- toxicity KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Cytochrome P-450 Enzyme System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77982691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Enhancement+of+thyroid+and+hepatocarcinogenesis+by+1%2C4-bis%5B2-%283%2C5-+dichloropyridyloxy%29%5Dbenzene+in+rats+at+doses+that+cause+maximal+induction+of+CYP2B.&rft.au=Diwan%2C+B+A%3BHenneman%2C+J+R%3BRice%2C+J+M%3BNims%2C+R+W&rft.aulast=Diwan&rft.aufirst=B&rft.date=1996-01-01&rft.volume=17&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasmacytoma development in mice injected with silicone gels. AN - 77976496; 8565584 AB - Silicone gels derived from commercially obtained implants induce plasmacytomas in 60-70% of highly susceptible BALB/cAn.DBA/2-Idh1-Pep3 congenic mice. In contrast, dimethylpolysiloxane (DMPS) silicone oils with viscosities of 5, 1000 and 12,500 cs fail to elicit these tumors. 1000 cs vinylmethylpolysiloxane is also inactive. Silicone gels, in contrast to the oils, induce a highly inflammatory silicone granuloma. Silicone gels contain chemical components not found in the oils. The chemical component responsible for inducing the permissive environment for plasmacytoma formation has not yet been identified. Silicone gels are well tolerated for long periods of time in mice without adverse effects other than plasmacytoma formation. The response to different gel preparations varies; some are associated with relatively rapid formation of plasmacytomas resembling that seen with pristane, while in others the plasmacytoma formation is extended nearly over a two year period. JF - Current topics in microbiology and immunology AU - Potter, M AU - Morrison, S AD - Laboratory of Genetics, DCBDC, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 397 EP - 407 VL - 210 SN - 0070-217X, 0070-217X KW - Silicone Oils KW - 0 KW - Silicones KW - Index Medicus KW - Injections, Intraperitoneal KW - Plasma Cells -- drug effects KW - Animals KW - Silicone Oils -- toxicity KW - Granuloma -- pathology KW - Mice KW - Mice, Inbred BALB C KW - Polyps -- etiology KW - Mice, Inbred DBA KW - Plasmacytoma -- etiology KW - Plasmacytoma -- genetics KW - Silicones -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77976496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+microbiology+and+immunology&rft.atitle=Plasmacytoma+development+in+mice+injected+with+silicone+gels.&rft.au=Potter%2C+M%3BMorrison%2C+S&rft.aulast=Potter&rft.aufirst=M&rft.date=1996-01-01&rft.volume=210&rft.issue=&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-04 N1 - Date created - 1996-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of reactive oxygen species by Co(II) from H2O2 in the presence of chelators in relation to DNA damage and 2'-deoxyguanosine hydroxylation. AN - 77976478; 8568912 AB - The generation of reactive oxygen species by Co(II) from H2O2 in the presence of chelators and related DNA damage was investigated by electron spin resonance (ESR), electrophoretic assays, and high-performance liquid chromatography (HPLC). Incubation of Co(II) with beta-alanyl-3-methyl-L-histidine (anserine) and H2O2 generated .OH radicals. Omission of any one component sharply reduced the amount of .OH radicals generated, indicating that anserine modulated the oxidation potential of Co(II) to enhance its capability to generate .OH radicals from H2O2. Formate only moderately decreased the .OH radical generation, while ethanol had no observable effect, indicating that the generation of .OH radical is site specific. The metal ion chelator 1,10-phenanthroline reduced the .OH radical generation, and deferoxamine suppressed it with the formation of deferoxamine nitroxide radical. Electrophoretic assays using both lambda Hind III linear DNA and PM2 supercoiled DNA showed that .OH radicals generated from a mixture of Co(II), H2O2, and anserine caused DNA strand breaks. A mixture of Co(II), H2O2, and 1,10-phenanthroline also caused DNA strand breaks, which were inhibited by sodium azide, indicating that 1O2 was involved in DNA damage. HPLC measurements showed that .OH radicals and 1O2 generated by Co(II) reactions caused 2'-deoxyguanosine hydroxylation to form 8-hydroxy-2'-deoxyguanosine. ESR spin trapping measurements provided evidence for 1O2 generation by Co(II) from H2O2 in the presence of 1,10-phenanthroline. The results indicate that the oxidation potential of Co(II) can be modulated by chelators to facilitate its generation of reactive oxygen species from H2O2. These species may be involved in Co(II)-induced cellular damage. JF - Journal of toxicology and environmental health AU - Mao, Y AU - Liu, K J AU - Jiang, J J AU - Shi, X AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 61 EP - 75 VL - 47 IS - 1 SN - 0098-4108, 0098-4108 KW - Azides KW - 0 KW - Chelating Agents KW - Formates KW - Mutagens KW - Phenanthrolines KW - Reactive Oxygen Species KW - formic acid KW - 0YIW783RG1 KW - Hydroxyl Radical KW - 3352-57-6 KW - Cobalt KW - 3G0H8C9362 KW - Ethanol KW - 3K9958V90M KW - Sodium Azide KW - 968JJ8C9DV KW - Hydrogen Peroxide KW - BBX060AN9V KW - Deoxyguanosine KW - G9481N71RO KW - Anserine KW - HDQ4N37UGV KW - Deferoxamine KW - J06Y7MXW4D KW - 1,10-phenanthroline KW - W4X6ZO7939 KW - Index Medicus KW - Formates -- chemistry KW - Electrophoresis KW - Anserine -- chemistry KW - Spectrophotometry, Ultraviolet KW - Mutagens -- toxicity KW - Azides -- toxicity KW - Chromatography, High Pressure Liquid KW - Phenanthrolines -- toxicity KW - Hydroxylation KW - Oxidation-Reduction KW - Deferoxamine -- toxicity KW - Electron Spin Resonance Spectroscopy KW - Ethanol -- chemistry KW - Cobalt -- toxicity KW - Reactive Oxygen Species -- metabolism KW - Chelating Agents -- pharmacology KW - Deoxyguanosine -- metabolism KW - Hydroxyl Radical -- metabolism KW - DNA Damage KW - Hydrogen Peroxide -- metabolism KW - Cobalt -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77976478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Generation+of+reactive+oxygen+species+by+Co%28II%29+from+H2O2+in+the+presence+of+chelators+in+relation+to+DNA+damage+and+2%27-deoxyguanosine+hydroxylation.&rft.au=Mao%2C+Y%3BLiu%2C+K+J%3BJiang%2C+J+J%3BShi%2C+X&rft.aulast=Mao&rft.aufirst=Y&rft.date=1996-01-01&rft.volume=47&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The National Cancer Institute Silicone Implant/Multiple Myeloma Registry. AN - 77975655; 8565581 JF - Current topics in microbiology and immunology AU - Rabkin, C S AU - Silverman, S AU - Tricot, G AU - Garland, L L AU - Ballester, O AU - Potter, M AD - Viral Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 385 EP - 387 VL - 210 SN - 0070-217X, 0070-217X KW - Silicones KW - 0 KW - Index Medicus KW - Registries KW - Age Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Female KW - Multiple Myeloma -- etiology KW - Silicones -- adverse effects KW - Breast Implants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77975655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+microbiology+and+immunology&rft.atitle=The+National+Cancer+Institute+Silicone+Implant%2FMultiple+Myeloma+Registry.&rft.au=Rabkin%2C+C+S%3BSilverman%2C+S%3BTricot%2C+G%3BGarland%2C+L+L%3BBallester%2C+O%3BPotter%2C+M&rft.aulast=Rabkin&rft.aufirst=C&rft.date=1996-01-01&rft.volume=210&rft.issue=&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-04 N1 - Date created - 1996-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral insertional mutagenesis in murine promonocytic leukemias: c-myb and Mml1. AN - 77970117; 8585950 AB - Studies have focused on two genetic loci, c-myb and Mml1, whose activation by retroviral insertional mutagenesis contribute to promonocytic leukemia in our acute monocytic leukemia (AMoL) model. Multiple mechanisms of activation of c-myb by retroviral insertional mutagenesis implicate both transcriptional deregulation and protein truncation in conversion of this proto-oncogene to an oncogene. Because transformation by c-Myb can be viewed as a block to differentiation our studies moved into two in vitro systems to evaluate effects of truncated forms of c-Myb on cytokine induced maturation of myeloid progenitors to the granulocyte and macrophage lineages. Deregulated expression of truncated and full length c-Myb did not result in maintenance of the myelomonocytic progenitor state but rather a block in differentiation at intermediate to late steps in the maturation processes of myelomonocytic cells. Our results argue that inhibition of differentiation is due to c-Myb's ability to maintain the proliferative state of cells. Interestingly, the phenotype of continuously proliferating monocytic cells resembles that of the tumor cell phenotype. Recently we identified a new target of integration, Mml1, which is rearranged in ten promonocytic leukemias that do not have c-myb rearrangements. This locus which was mapped to chromosome 10 is presently being characterized. JF - Current topics in microbiology and immunology AU - Wolff, L AU - Koller, R AU - Bies, J AU - Nazarov, V AU - Hoffman, B AU - Amanullah, A AU - Krall, M AU - Mock, B AD - Laboratory of Genetics, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 191 EP - 199 VL - 211 SN - 0070-217X, 0070-217X KW - Proto-Oncogene Proteins c-myc KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Macrophages -- physiology KW - Granulocytes -- physiology KW - Cell Differentiation KW - Leukemia Virus, Murine -- genetics KW - Leukemia, Myelomonocytic, Acute -- virology KW - Proto-Oncogene Proteins c-myc -- genetics KW - Leukemia, Myelomonocytic, Acute -- genetics KW - Virus Integration KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77970117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+microbiology+and+immunology&rft.atitle=Retroviral+insertional+mutagenesis+in+murine+promonocytic+leukemias%3A+c-myb+and+Mml1.&rft.au=Wolff%2C+L%3BKoller%2C+R%3BBies%2C+J%3BNazarov%2C+V%3BHoffman%2C+B%3BAmanullah%2C+A%3BKrall%2C+M%3BMock%2C+B&rft.aulast=Wolff&rft.aufirst=L&rft.date=1996-01-01&rft.volume=211&rft.issue=&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-22 N1 - Date created - 1996-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A mechanistic model of effects of dioxin on thyroid hormones in the rat. AN - 77968137; 8560478 AB - A physiological dosimetric model of the disposition of TCDD in the rat (Kohn et al., Toxicol. Appl. Pharmacol. 120, 138-154, 1993) was extended to include effects of dioxin on serum concentrations of thyroid hormones in the rat. The extended model included distribution of blood among major vessels and tissue capillary beds and resorption of TCDD released into the gut lumen from the liver by cell lysis consequent to cytotoxicity. TCDD metabolism was represented by Hill kinetics. Parameter values were estimated by fitting time-course data for a single oral subcutaneous injection of TCDD and dose-response data for biweekly oral dosing. The extended model included new compartments for the thyroid and thyroxine-sensitive tissues (e.g., pituitary, kidney, and brown fat), secretion and tissue uptake of thyroid hormones, binding of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (thyroxine, T4) to proteins in blood and tissues, deiodination of iodothyronines, and glucuronidation of T4 by the hepatic UDP-glucuronosyltransferase (UGT) activity induced by TCDD. Secretion of thyroid hormones was modeled as regulated by thyrotropin (TSH), whose secretion was modeled as regulated by the hypothalamic factors thyrotropin releasing hormone and somatostatin. Release of the hypothalamic factors was modeled as under feedback control by the blood T4 level. Induction of UGT was modeled as stimulated by the Ah receptor-TCDD complex. The extended model fit the observed dose-response of P450 isozymes and Ah and estrogen receptors following repeated oral doses with comparable accuracy as the earlier model. The fit to liver and fat TCDD levels following single and repeated oral and subcutaneous doses was improved over the earlier model. The revised model's predicted liver TCDD concentrations at very low doses were verified experimentally. The model reproduced the responses observed for blood T3, T4, and TSH after 31 weeks of biweekly oral dosing of rats with TCDD. The model also predicted responses of UGT mRNA and UGT enzymatic activity comparable to those observed in TCDD-treated rats in experiments whose data were not used in constructing the model. Calculated increases in blood TSH levels are consistent with prolonged stimulation of the thyroid and may represent an early stage in the induction of thyroid tumors identified in previous two-year bioassays. Thus, increases in UGT activity may be useful as a biomarker for tumorigenic changes in hormone levels subsequent to TCDD exposure. JF - Toxicology and applied pharmacology AU - Kohn, M C AU - Sewall, C H AU - Lucier, G W AU - Portier, C J AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 29 EP - 48 VL - 136 IS - 1 SN - 0041-008X, 0041-008X KW - Isoenzymes KW - 0 KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Receptors, Cholinergic KW - Receptors, Estrogen KW - Triiodothyronine KW - 06LU7C9H1V KW - Thyrotropin-Releasing Hormone KW - 5Y5F15120W KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Thyroxine KW - Q51BO43MG4 KW - Index Medicus KW - Administration, Oral KW - Animals KW - Liver -- enzymology KW - Receptors, Estrogen -- drug effects KW - Dose-Response Relationship, Drug KW - Thyrotropin-Releasing Hormone -- blood KW - Cytochrome P-450 Enzyme System -- metabolism KW - Glucuronosyltransferase -- metabolism KW - Liver -- metabolism KW - Tissue Distribution KW - Receptors, Estrogen -- metabolism KW - Receptors, Cholinergic -- metabolism KW - Models, Biological KW - Rats KW - Adipose Tissue -- metabolism KW - Receptors, Cholinergic -- drug effects KW - RNA, Messenger -- metabolism KW - Liver -- drug effects KW - Injections, Subcutaneous KW - Polychlorinated Dibenzodioxins -- pharmacokinetics KW - Thyroid Gland -- drug effects KW - Triiodothyronine -- blood KW - Triiodothyronine -- drug effects KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Polychlorinated Dibenzodioxins -- toxicity KW - Thyroid Gland -- enzymology KW - Polychlorinated Dibenzodioxins -- blood KW - Thyroxine -- blood KW - Thyroxine -- drug effects KW - Thyroid Gland -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77968137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=A+mechanistic+model+of+effects+of+dioxin+on+thyroid+hormones+in+the+rat.&rft.au=Kohn%2C+M+C%3BSewall%2C+C+H%3BLucier%2C+G+W%3BPortier%2C+C+J&rft.aulast=Kohn&rft.aufirst=M&rft.date=1996-01-01&rft.volume=136&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-23 N1 - Date created - 1996-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biological and biochemical anti-human immunodeficiency virus activity of UC 38, a new non-nucleoside reverse transcriptase inhibitor. AN - 77964851; 8558446 AB - UC 38, a simple analog of oxathiin carboxanilide, UC 84, lacking the oxathiin ring, was found to be a potent inhibitor of human immunodeficiency virus (HIV)-1-induced cell killing and HIV replication in a variety of human cell lines, as well as in human peripheral blood lymphocytes and macrophages. UC 38 was active against a wide range of biologically diverse laboratory and clinical strains of HIV-1. However, UC 38 was inactive against HIV-2 and both nevirapine- and pyridinone-resistant strains of HIV-1. UC 38 selectively inhibited HIV-1 reverse transcriptase (RT), but not HIV-2 RT. Combination of UC 38 with 3'-azido-3'-deoxythymidine synergistically inhibited HIV-induced cell killing. An HIV-1 isolate resistant to UC 38 was selected in cell culture, and the mutations in the RT nucleotide sequences were determined. Comparison with the wild-type RT sequence revealed an amino acid change at position 181 (Tyr to Cys). The UC 38-resistant virus was found to be cross-resistant to a variety of structurally diverse non-nucleoside RT inhibitors. UC 38 was susceptible to rapid degradation in vitro and in vivo; yet, nontoxic in vivo concentrations of UC 38 many-fold in excess of the in vitro effective concentrations could be achieved and maintained after s.c. or p.o. administration in hamsters. These results establish UC 38 as a new chemotype within the general class of HIV-1-specific RT inhibitors. The favorable physical characteristics, lack of toxicity, potency and bioavailability of UC 38 may make it a candidate for combination chemotherapy of acquired immune deficiency syndrome. JF - The Journal of pharmacology and experimental therapeutics AU - McMahon, J B AU - Buckheit, R W AU - Gulakowski, R J AU - Currens, M J AU - Vistica, D T AU - Shoemaker, R H AU - Stinson, S F AU - Russell, J D AU - Bader, J P AU - Narayanan, V L AU - Schultz, R J AU - Brouwer, W G AU - Felauer, E E AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 298 EP - 305 VL - 276 IS - 1 SN - 0022-3565, 0022-3565 KW - Antiviral Agents KW - 0 KW - Benzoates KW - DNA, Viral KW - NSC 615985 KW - Reverse Transcriptase Inhibitors KW - Thiocarbamates KW - NSC 629243 KW - 135812-34-9 KW - Zidovudine KW - 4B9XT59T7S KW - Carboxin KW - 5A8K850HDE KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Drug Stability KW - Drug Administration Schedule KW - Carboxin -- pharmacokinetics KW - Humans KW - DNA Mutational Analysis KW - Zidovudine -- pharmacology KW - Drug Resistance, Microbial KW - Mice KW - Carboxin -- analogs & derivatives KW - Biological Availability KW - Rats KW - Carboxin -- pharmacology KW - DNA, Viral -- analysis KW - Drug Synergism KW - Microbial Sensitivity Tests KW - DNA, Viral -- genetics KW - Male KW - Cricetinae KW - Thiocarbamates -- pharmacokinetics KW - Reverse Transcriptase Inhibitors -- pharmacokinetics KW - Antiviral Agents -- pharmacokinetics KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Benzoates -- pharmacokinetics KW - Antiviral Agents -- pharmacology KW - RNA-Directed DNA Polymerase -- drug effects KW - HIV-1 -- enzymology KW - Thiocarbamates -- pharmacology KW - HIV-1 -- drug effects KW - Benzoates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77964851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Biological+and+biochemical+anti-human+immunodeficiency+virus+activity+of+UC+38%2C+a+new+non-nucleoside+reverse+transcriptase+inhibitor.&rft.au=McMahon%2C+J+B%3BBuckheit%2C+R+W%3BGulakowski%2C+R+J%3BCurrens%2C+M+J%3BVistica%2C+D+T%3BShoemaker%2C+R+H%3BStinson%2C+S+F%3BRussell%2C+J+D%3BBader%2C+J+P%3BNarayanan%2C+V+L%3BSchultz%2C+R+J%3BBrouwer%2C+W+G%3BFelauer%2C+E+E%3BBoyd%2C+M+R&rft.aulast=McMahon&rft.aufirst=J&rft.date=1996-01-01&rft.volume=276&rft.issue=1&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-26 N1 - Date created - 1996-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. AN - 77963408; 8557195 AB - The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupted by homologous recombination in embryonic stem cells to generate mice lacking T/EBP expression. Heterozygous animals developed normally, whereas mice homozygous for the disrupted gene were born dead and lacked the lung parenchyma. Instead, they had a rudimentary bronchial tree associated with an abnormal epithelium in their pleural cavities. Furthermore, the homozygous mice had no thyroid gland but had a normal parathyroid. In addition, extensive defects were found in the brain of the homozygous mice, especially in the ventral region of the forebrain. The entire pituitary, including the anterior, intermediate, and posterior pituitary, was also missing. In situ hybridization showed that the T/ebp gene is expressed in the normal thyroid, lung bronchial epithelium, and specific areas of the forebrain during early embryogenesis. These results establish that the expression of T/EBP, a transcription factor known to control thyroid-specific gene transcription, is also essential for organogenesis of the thyroid, lung, ventral forebrain, and pituitary. JF - Genes & development AU - Kimura, S AU - Hara, Y AU - Pineau, T AU - Fernandez-Salguero, P AU - Fox, C H AU - Ward, J M AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/01/01/ PY - 1996 DA - 1996 Jan 01 SP - 60 EP - 69 VL - 10 IS - 1 SN - 0890-9369, 0890-9369 KW - Nuclear Proteins KW - 0 KW - Transcription Factors KW - thyroid nuclear factor 1 KW - Index Medicus KW - Animals, Newborn KW - Animals KW - In Situ Hybridization KW - Homozygote KW - Adrenal Cortex -- pathology KW - Adrenal Cortex -- embryology KW - Cells, Cultured KW - Genetic Vectors KW - Embryo, Mammalian -- cytology KW - Mice, Inbred C57BL KW - Mice KW - Mice, Transgenic KW - Genes, Lethal KW - Gene Expression Regulation, Developmental KW - Embryonic Induction -- genetics KW - Adrenal Cortex -- anatomy & histology KW - Pituitary Gland -- pathology KW - Pituitary Gland -- anatomy & histology KW - Lung -- anatomy & histology KW - Prosencephalon -- anatomy & histology KW - Nuclear Proteins -- genetics KW - Pituitary Gland -- embryology KW - Thyroid Gland -- embryology KW - Thyroid Gland -- anatomy & histology KW - Prosencephalon -- pathology KW - Lung -- embryology KW - Lung -- pathology KW - Transcription Factors -- genetics KW - Prosencephalon -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77963408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=The+T%2Febp+null+mouse%3A+thyroid-specific+enhancer-binding+protein+is+essential+for+the+organogenesis+of+the+thyroid%2C+lung%2C+ventral+forebrain%2C+and+pituitary.&rft.au=Kimura%2C+S%3BHara%2C+Y%3BPineau%2C+T%3BFernandez-Salguero%2C+P%3BFox%2C+C+H%3BWard%2C+J+M%3BGonzalez%2C+F+J&rft.aulast=Kimura&rft.aufirst=S&rft.date=1996-01-01&rft.volume=10&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-23 N1 - Date created - 1996-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of paclitaxel in combination with cyclophosphamide and granulocyte colony-stimulating factor in metastatic breast cancer patients. AN - 77960511; 8558227 AB - In vitro data suggest that prolonged exposure to paclitaxel enhances breast cancer cytotoxicity. Our objective in this phase I study was to determine the tolerability of paclitaxel administered by 72-hour continuous intravenous (i.v.) infusion (CIVI) in combination with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) in the ambulatory setting to metastatic breast cancer patients. Paclitaxel was administered over 72 hours by CIVI and cyclophosphamide was given daily by i.v. bolus on days 1, 2, and 3, followed by G-CSF every 21 days. The availability of ambulatory infusion pumps and paclitaxel-compatible tubing permitted outpatient administration. Fifty-five patients with metastatic breast cancer who had been previously treated with a median of two prior chemotherapy regimens were entered onto the study. Dose-limiting toxicity of grade 4 neutropenia for longer than 5 days and grade 4 thrombocytopenia occurred in three of five patients treated with paclitaxel 160 mg/m2 CIVI and cyclophosphamide 3,300 mg/m2 followed by G-CSF. The maximum-tolerated dose (MTD) was paclitaxel 160 mg/m2 CIVI and cyclophosphamide 2,700 mg/m2 in divided doses with G-CSF. Nonhematologic toxicities were moderate and included diarrhea, mucositis, and arthalgias. Although hemorrhagic cystitis developed in six patients, recurrence was prevented with i.v. and oral mesna, which permitted continued outpatient delivery. One hundred seventy-four cycles were safely administered in the ambulatory setting using infusional pumps and tubing. Objective responses occurred in 23 (one complete and 22 partial) of 42 patients with bidimensionally measurable disease (55%; 95% confidence interval, 38% to 70%), with a response rate of 73% (11 of 15) seen at the highest dose levels. Paclitaxel by 72-hour CIVI with daily cyclophosphamide followed by G-CSF can be administered safely in the ambulatory setting, has acceptable toxicity, and is an active regimen in the treatment of metastatic breast cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Tolcher, A W AU - Cowan, K H AU - Noone, M H AU - Denicoff, A M AU - Kohler, D R AU - Goldspiel, B R AU - Barnes, C S AU - McCabe, M AU - Gossard, M R AU - Zujewski, J AU - O'Shaughnessy, J A AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 95 EP - 102 VL - 14 IS - 1 SN - 0732-183X, 0732-183X KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Cyclophosphamide KW - 8N3DW7272P KW - Mesna KW - NR7O1405Q9 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Erythrocyte Transfusion KW - Drug Administration Schedule KW - Hematuria -- chemically induced KW - Hematuria -- drug therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Equipment Failure KW - Hematologic Diseases -- chemically induced KW - Diarrhea -- chemically induced KW - Drug Hypersensitivity -- etiology KW - Hematologic Diseases -- blood KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Hematologic Diseases -- therapy KW - Blood Cell Count -- drug effects KW - Female KW - Mesna -- therapeutic use KW - Home Infusion Therapy -- instrumentation KW - Drug Hypersensitivity -- drug therapy KW - Paclitaxel -- administration & dosage KW - Breast Neoplasms -- pathology KW - Breast Neoplasms -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77960511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+study+of+paclitaxel+in+combination+with+cyclophosphamide+and+granulocyte+colony-stimulating+factor+in+metastatic+breast+cancer+patients.&rft.au=Tolcher%2C+A+W%3BCowan%2C+K+H%3BNoone%2C+M+H%3BDenicoff%2C+A+M%3BKohler%2C+D+R%3BGoldspiel%2C+B+R%3BBarnes%2C+C+S%3BMcCabe%2C+M%3BGossard%2C+M+R%3BZujewski%2C+J%3BO%27Shaughnessy%2C+J+A&rft.aulast=Tolcher&rft.aufirst=A&rft.date=1996-01-01&rft.volume=14&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-23 N1 - Date created - 1996-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of ascorbic acid with the neurotoxic effects of NMDA and sodium nitroprusside. AN - 77957541; 8538373 AB - We have previously shown that ascorbic acid (AA) protects cortical neurons in culture from the toxic effects of NMDA. In the present study, we examined the interactions of AA with toxicity produced by nitric oxide (NO) that is generated from the breakdown of sodium nitroprusside (SNP), and with NMDA toxicity measured 24 h later. AA enhanced SNP toxicity, but it reduced toxicity of NMDA. We propose that these data support a model wherein AA produces neuroprotection by an action at the NMDA receptor, and indirectly with respect to NO. This effect occurs probably by antagonizing Ca2+ influx starting the cascade of biochemical events that lead to the production of NO. JF - Life sciences AU - Bell, J A AU - Beglan, C L AU - London, E D AD - Neuroimaging and Drug Action Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 367 EP - 371 VL - 58 IS - 4 SN - 0024-3205, 0024-3205 KW - Excitatory Amino Acid Agonists KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Vasodilator Agents KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - N-Methylaspartate KW - 6384-92-5 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Drug Interactions KW - Brain -- cytology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Nitric Oxide -- biosynthesis KW - Pregnancy KW - Calcium -- metabolism KW - Rats KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Cell Death KW - Brain -- embryology KW - Female KW - Nitroprusside -- toxicity KW - Neurons -- drug effects KW - N-Methylaspartate -- toxicity KW - Ascorbic Acid -- pharmacology KW - Excitatory Amino Acid Agonists -- toxicity KW - Vasodilator Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77957541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Interaction+of+ascorbic+acid+with+the+neurotoxic+effects+of+NMDA+and+sodium+nitroprusside.&rft.au=Bell%2C+J+A%3BBeglan%2C+C+L%3BLondon%2C+E+D&rft.aulast=Bell&rft.aufirst=J&rft.date=1996-01-01&rft.volume=58&rft.issue=4&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-08 N1 - Date created - 1996-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbamazepine inhibition of N-methyl-D-aspartate-evoked calcium influx in rat cerebellar granule cells. AN - 77956362; 8558424 AB - The effect of carbamazepine (CBZ) on N-methyl-D-aspartate (NMDA)-stimulated CA++ influx in rat cerebellar granule cells was studied by use of fura-2 microfluorometry. CBZ inhibited the rise in intracellular free Ca++ concentration ([Ca++]i) induced by NMDA and glycine in a rapid reversible and concentration-dependent manner. CBZ's inhibition of the [Ca++]i increase was noncompetitive with respect to NMDA, glycine and the facilitatory neurosteroid pregnenolone sulfate. The degree of inhibition of the NMDA response produced by CBZ increased with increasing concentrations of extracellular KCl. Excluding non-NMDA receptor-mediated contributions to Ca++ influx, depolarization by 50 mM KCl resulted in a 20-fold decrease (from 723 to 33 microM) in the IC50 for CBZ blockade of the NMDA response. Thus, significant blockade of NMDA receptor responses in cerebellar granule cells can occur at concentrations of CBZ within the therapeutic range under conditions believed to accompany seizures. Moreover, the common toxic side effects of CBZ, which include signs of cerebellar dysfunction, may occur as a result of CBZ blockade of the NMDA receptors of cerebellar granule cells. JF - The Journal of pharmacology and experimental therapeutics AU - Hough, C J AU - Irwin, R P AU - Gao, X M AU - Rogawski, M A AU - Chuang, D M AD - Section on Molecular Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 143 EP - 149 VL - 276 IS - 1 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - pregnenolone sulfate KW - 04Y4D91RG0 KW - Carbamazepine KW - 33CM23913M KW - N-Methylaspartate KW - 6384-92-5 KW - Potassium Chloride KW - 660YQ98I10 KW - Pregnenolone KW - 73R90F7MQ8 KW - Calcium KW - SY7Q814VUP KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Rats KW - Pregnenolone -- pharmacology KW - Animals KW - Glycine -- pharmacology KW - Potassium Chloride -- pharmacology KW - Intracellular Fluid -- metabolism KW - Drug Synergism KW - Cytoplasmic Granules -- drug effects KW - Cytoplasmic Granules -- metabolism KW - Calcium -- metabolism KW - Anticonvulsants -- pharmacology KW - N-Methylaspartate -- pharmacology KW - Cerebellum -- drug effects KW - N-Methylaspartate -- antagonists & inhibitors KW - Carbamazepine -- pharmacology KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77956362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Carbamazepine+inhibition+of+N-methyl-D-aspartate-evoked+calcium+influx+in+rat+cerebellar+granule+cells.&rft.au=Hough%2C+C+J%3BIrwin%2C+R+P%3BGao%2C+X+M%3BRogawski%2C+M+A%3BChuang%2C+D+M&rft.aulast=Hough&rft.aufirst=C&rft.date=1996-01-01&rft.volume=276&rft.issue=1&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-26 N1 - Date created - 1996-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine and cardiovascular toxicity. AN - 77939890; 12893485 AB - Over the past 10 years a great deal has been learned about the cardiovascular effects of cocaine. In particular, the acute effects of cocaine have been studied extensively. Upon acute administration cocaine increases blood pressure and heart rate, primarily through an action on the sympathetic nervous system. Cocaine also suppresses the baroreflex response and vagal tone, further contributing to its effects on heart rate. At the same time cocaine is increasing the work-load on the heart it induces coronary artery vasoconstriction, potentially leading to cardiac ischemia. At higher doses cocaine can depress ventricular function and slow electrical conduction in the heart. Both these effects appear to be mediated by cocaine's local anesthetic action. The effects of cocaine mediated by the sympathetic nervous system are greatly reduced in anesthetized animals. Further, when cocaine is administered repeatedly over a short period of time, acute tolerance can develop to the sympathomimetic effects of cocaine. In contrast, the effects of cocaine mediated by its local anesthetic action do not appear blunted by anesthesia or susceptible to acute tolerance. With chronic administration, higher doses appear to induce tolerance while lower doses may induce sensitization to cocaine's sympathomimetic effects. Cocaine also induces a variety of pathological changes in the heart, including myocardial contraction band necrosis and ventricular hypertrophy. These effects of cocaine on the heart can all contribute to potentially lethal cardiovascular events. In addition to the effects of cocaine alone, the metabolites of cocaine may also contribute to cocaine's cardiovascular toxicity, and both licit and illicit drugs used in combination with cocaine might potentially alter its cardiovascular effects. JF - Addiction biology AU - Schindler, C W AD - Preclinical Pharmacology Laboratory, National Institutes of Health/National Institute on Drug Abuse, Division of Intramural Research, Addiction Research Center, Baltimore 21224, USA. cschindl@helix.nih.gov Y1 - 1996 PY - 1996 DA - 1996 SP - 31 EP - 47 VL - 1 IS - 1 SN - 1355-6215, 1355-6215 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77939890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+biology&rft.atitle=Cocaine+and+cardiovascular+toxicity.&rft.au=Schindler%2C+C+W&rft.aulast=Schindler&rft.aufirst=C&rft.date=1996-01-01&rft.volume=1&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Addiction+biology&rft.issn=13556215&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-28 N1 - Date created - 2003-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proliferation, apoptosis, and induction of hepatic transcription factors are characteristics of the early response of biliary epithelial (oval) cells to chemical carcinogens. AN - 77921534; 8550050 AB - In this study, we used [3H]thymidine labeling of newly synthesized DNA to examine the earliest effects of 2-acetylaminofluorene (2-AAF) on the mitotic activation of cells in the adult rat liver, and in situ hybridization analysis to study the expression of three transcription factors (HNF1 beta, HNF3 gamma, and HNF4), and two of the genes (alpha-fetoprotein [AFP] and albumin) regulated by these factors. A low dose of 2-AAF (and its analogs, 2-AF [2-aminofluorene] and N-OH-2-AAF) elicited a mitogenic response in ductal cells and nondescript periductular cells within 24 hours after administration. The compounds also induced the expression of HNF1 beta, HNF3 gamma, AFP, and albumin in ductal structures but had no detectable effect of HNF4 expression. In contrast, initiation of bile duct proliferation by ligation of the common bile duct had no effect on the expression of these genes in ductal cells. In addition to inducing a mitogenic response, 2-AAF resulted in increased numbers of apoptotic cells in the portal areas, a process that contributed to overall retention of liver morphology. Our results demonstrate that 2-AAF and some of its analogs can elicit a specific mitogenic response and induce expression of the "establishment" transcription factors, HNF1 beta and HNF3 gamma, in ductal cells. Our data provide further support of a precursor-product relationship between "stem-like" cells located in ductal structures, oval cells, and hepatocytes. JF - Hepatology (Baltimore, Md.) AU - Bisgaard, H C AU - Nagy, P AU - Santoni-Rugiu, E AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 62 EP - 70 VL - 23 IS - 1 SN - 0270-9139, 0270-9139 KW - Albumins KW - 0 KW - Carcinogens KW - DNA-Binding Proteins KW - Fluorenes KW - Foxa3 protein, rat KW - Hepatocyte Nuclear Factor 4 KW - Nuclear Proteins KW - Phosphoproteins KW - Transcription Factors KW - alpha-Fetoproteins KW - Hepatocyte Nuclear Factor 3-gamma KW - 135845-91-9 KW - Hepatocyte Nuclear Factor 1-beta KW - 138674-15-4 KW - 2-aminofluorene KW - 3A69OS195N KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Animals KW - 2-Acetylaminofluorene -- toxicity KW - Albumins -- genetics KW - Rats KW - Rats, Inbred F344 KW - In Situ Hybridization KW - Fluorenes -- toxicity KW - Epithelial Cells KW - Cells, Cultured KW - Gene Expression Regulation KW - alpha-Fetoproteins -- genetics KW - Nuclear Proteins -- metabolism KW - Phosphoproteins -- metabolism KW - Cell Division KW - DNA-Binding Proteins -- metabolism KW - Liver -- pathology KW - Apoptosis KW - Transcription Factors -- metabolism KW - Liver -- drug effects KW - Bile Ducts -- pathology KW - Carcinogens -- toxicity KW - Liver -- metabolism KW - Bile Ducts -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77921534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Proliferation%2C+apoptosis%2C+and+induction+of+hepatic+transcription+factors+are+characteristics+of+the+early+response+of+biliary+epithelial+%28oval%29+cells+to+chemical+carcinogens.&rft.au=Bisgaard%2C+H+C%3BNagy%2C+P%3BSantoni-Rugiu%2C+E%3BThorgeirsson%2C+S+S&rft.aulast=Bisgaard&rft.aufirst=H&rft.date=1996-01-01&rft.volume=23&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-20 N1 - Date created - 1996-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of apoptosis by c-Fos protein. AN - 77921042; 8524298 AB - The role of c-Fos in apoptosis was examined in two Syrian hamster embryo cell lines (sup+I and sup-II) and a human colorectal carcinoma cell line (RKO), using the chimeric Fos-estrogen receptor fusion protein c-FosER. As previously reported, contrasting responses were observed when these two cell lines were placed under growth factor deprivation conditions; sup+I cells were highly susceptible to apoptosis, whereas sup-II cells were resistant. In this report, we show that the activated c-FosER protein induces apoptosis in sup-II preneoplastic cells in serum-free medium, indicating that c-Fos protein can induce apoptotic cell death in these cells. c-Fos-induced apoptosis was not blocked by the protein synthesis inhibitor cycloheximide, suggesting that the c-Fos transcriptional activation activity is not involved. This conclusion was further supported by the observation that overexpression of v-Fos, which is highly proficient in transcriptional activation but deficient in the transcriptional repression activity associated with c-Fos, did not induce apoptosis. Constitutively expressed Bcl-2 delayed the onset of low-serum-induced apoptosis in sup+I cells and enhanced survival in sup-II cells. Further, coexpression of Bcl-2 and c-FosER in sup+I or sup-II cells protected the cells from c-FosER-induced apoptosis. The possibility that c-FosER-induced apoptosis requires a p53 function was examined. Colorectal carcinoma RKOp53+/+ cells, which do not normally undergo apoptosis in serum-free medium, showed apoptotic DNA fragmentation upon expression and activation of c-FosER. Further, when the wild-type p53 protein was diminished in the RKO cells by infection with the papillomavirus E6 gene, subsequent c-FosER-induced apoptosis was blocked. The data suggest that c-Fos protein plays a causal role in the activation of apoptosis in a p53-dependent manner. This activity does not require new protein synthesis and is blocked by overexpression of Bcl-2 protein. JF - Molecular and cellular biology AU - Preston, G A AU - Lyon, T T AU - Yin, Y AU - Lang, J E AU - Solomon, G AU - Annab, L AU - Srinivasan, D G AU - Alcorta, D A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 211 EP - 218 VL - 16 IS - 1 SN - 0270-7306, 0270-7306 KW - Proto-Oncogene Proteins KW - 0 KW - Proto-Oncogene Proteins c-bcl-2 KW - Proto-Oncogene Proteins c-fos KW - Receptors, Estrogen KW - Recombinant Fusion Proteins KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Protein Biosynthesis KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Recombinant Fusion Proteins -- pharmacology KW - Receptors, Estrogen -- metabolism KW - Cell Line KW - Cricetinae KW - Proto-Oncogene Proteins c-fos -- pharmacology KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Proto-Oncogene Proteins c-fos -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77921042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Induction+of+apoptosis+by+c-Fos+protein.&rft.au=Preston%2C+G+A%3BLyon%2C+T+T%3BYin%2C+Y%3BLang%2C+J+E%3BSolomon%2C+G%3BAnnab%2C+L%3BSrinivasan%2C+D+G%3BAlcorta%2C+D+A%3BBarrett%2C+J+C&rft.aulast=Preston&rft.aufirst=G&rft.date=1996-01-01&rft.volume=16&rft.issue=1&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-19 N1 - Date created - 1996-01-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 1994 Apr;9(4):1213-23 [8134124] Int Rev Cytol. 1980;68:251-306 [7014501] Cell. 1983 Apr;32(4):1241-55 [6301687] Pathol Annu. 1982;17 Pt 2:229-59 [7182752] Proc Natl Acad Sci U S A. 1983 Oct;80(20):6361-5 [6312454] Cell. 1984 Jan;36(1):51-60 [6607118] Cell. 1984 Feb;36(2):259-68 [6319013] Nature. 1984 Oct 4-10;311(5985):438-42 [6541297] Mol Cell Biol. 1988 May;8(5):2063-9 [3133553] Mol Endocrinol. 1988 Jul;2(7):650-7 [3137456] Cell. 1988 Nov 4;55(3):395-7 [3141060] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8464-7 [3186736] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1500-3 [2493644] Cancer Res. 1989 Apr 1;49(7):1687-92 [2466559] J Cell Physiol. 1989 May;139(2):237-44 [2469685] EMBO J. 1989 Mar;8(3):805-13 [2498083] Nature. 1989 Jul 6;340(6228):64-6 [2739725] EMBO J. 1989 May;8(5):1433-9 [2504580] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8773-7 [2813423] Cell. 1989 Dec 22;59(6):999-1007 [2513130] Proc Natl Acad Sci U S A. 1990 May;87(9):3619-23 [2110368] Cell. 1990 May 4;61(3):497-504 [2159384] Mol Cell Biol. 1990 Aug;10(8):4243-55 [2115122] J Biol Chem. 1990 Aug 25;265(24):14476-80 [1696946] Science. 1990 Sep 7;249(4973):1157-61 [2118682] Nature. 1990 Nov 1;348(6296):80-2 [2122257] Brain Res. 1991 Mar 29;544(2):291-6 [1710164] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5114-8 [1711219] Nature. 1991 Jul 25;352(6333):345-7 [1852210] Hum Gene Ther. 1991 Spring;2(1):33-9 [1650586] EMBO J. 1991 Sep;10(9):2437-50 [1714376] Oncogene. 1991 Oct;6(10):1915-22 [1923514] EMBO J. 1991 Dec;10(12):3839-49 [1935903] Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129-57 [1751545] Neuron. 1992 Jan;8(1):13-23 [1730004] Environ Health Perspect. 1991 Jun;93:105-9 [1773782] Am J Pathol. 1992 Mar;140(3):545-9 [1546740] Cell. 1992 Apr 3;69(1):119-28 [1555236] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4495-9 [1584781] Science. 1992 Jul 10;257(5067):212-4 [1378649] J Biol Chem. 1992 Sep 15;267(26):18278-83 [1526968] Cancer Metastasis Rev. 1992 Sep;11(2):105-19 [1327565] J Cell Biol. 1992 Nov;119(3):493-501 [1400587] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9306-10 [1329091] Cell. 1992 Nov 13;71(4):577-86 [1423615] Nature. 1992 Dec 24-31;360(6406):741-5 [1465144] Mol Cell Biol. 1994 Apr;14(4):2556-63 [8139558] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3602-6 [8170954] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3754-8 [8170983] Nature. 1994 Jul 21;370(6486):220-3 [8028670] Cancer Res. 1994 Aug 1;54(15):4214-23 [8033154] Science. 1994 Sep 30;265(5181):2091-3 [8091232] Cell Growth Differ. 1994 Jul;5(7):735-41 [7947388] J Gerontol. 1994 Nov;49(6):B263-9 [7525690] Proc Natl Acad Sci U S A. 1985 Aug;82(15):4987-91 [2991903] EMBO J. 1985 Jul;4(7):1775-81 [3896777] Cancer Genet Cytogenet. 1986 Jul;22(3):225-37 [3708554] Cell. 1986 May 23;45(4):497-504 [3085953] EMBO J. 1986 May;5(5):913-7 [3522222] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5992-6 [3461473] Nature. 1987 Jan 29-Feb 4;325(6103):412-6 [3027573] Cell. 1987 Jun 19;49(6):835-44 [3555845] Mol Cell Biol. 1987 Jun;7(6):2201-11 [3110603] Cell. 1992 Dec 24;71(7):1103-16 [1473147] Oncogene. 1993 Feb;8(2):387-93 [8426745] Oncogene. 1993 Mar;8(3):695-701 [8437852] Mol Cell Biol. 1993 Apr;13(4):2432-40 [8455620] Genes Dev. 1993 Apr;7(4):546-54 [8384580] Methods Enzymol. 1993;217:581-99 [8386297] Nature. 1993 Apr 29;362(6423):847-9 [8479522] Nature. 1993 Apr 29;362(6423):849-52 [8479523] Nature. 1993 May 13;363(6425):166-9 [8483500] Biochem Biophys Res Commun. 1993 Apr 30;192(2):386-91 [8484751] Tohoku J Exp Med. 1992 Oct;168(2):169-74 [1306301] Oncogene. 1993 Aug;8(8):2237-44 [8336946] Cell. 1993 Aug 27;74(4):609-19 [8358790] Cancer Res. 1993 Nov 1;53(21):5071-5 [7693330] Science. 1994 Feb 25;263(5150):1143-5 [8108732] Cell Growth Differ. 1993 Dec;4(12):1013-21 [8117615] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of excitatory amino acid-induced phosphoinositide hydrolysis as a possible mechanism of nitroprusside neurotoxicity. AN - 77916404; 8522973 AB - Inclusion of sodium nitroprusside (Na2[Fe(2+)-(CN)5NO]) into the culture medium is toxic to cultured rat cerebellar granule neurons. A possible underlying mechanism may be the inhibition of phosphoinositide (PI) response to excitatory amino acids (EAAs) because activation of glutamate receptors can be neuroprotective and neurotrophic in differentiating neurons. Sodium nitroprusside selectively inhibited the PI response to EAAs (NMDA > glutamate = quisqualate > kainate) without affecting that to carbachol or KCl. In contrast, S-nitroso-N-acetyl-penicillamine (SNAP), another nitric oxide (NO) donor, potentiated NMDA-induced PI hydrolysis. Hemoglobin reversed the effects of nitroprusside and SNAP. However, NO may not be involved because NO solution was without effect and N-acetylpenicillamine, a SNAP analogue that does not contain a NO moiety, also potentiated NMDA-induced PI hydrolysis in a hemoglobin-sensitive manner. Furthermore, the metabolites of NO (nitrate and nitrite), L-arginine, reduced glutathione, 8-bromo-cyclic guanosine 3':5'-cyclic monophosphate (8-Br-cGMP), and atrial natriuretic peptide, which accelerates the production of cGMP independent of NO, were ineffective as modulators. However, potassium ferrocyanide (K4[Fe2+(CN)6]), but not potassium ferricyanide (K3[Fe3+(CN)6]), inhibited NMDA-induced PI hydrolysis as effectively as nitroprusside, but this inhibition was not reversed by hemoglobin. Cyanide, a product from the disintegration of nitroprusside, potentiated rather than inhibited NMDA-induced PI hydrolysis. Taken together, these results suggest that the parent molecule itself, nitroprusside, contributes primarily in inhibiting EAA-induced PI hydrolysis. Inhibition of EAA-induced PI hydrolysis may in part mediate the mechanisms of nitroprusside toxicity in primary cultures of differentiating cerebellar granule neurons. JF - Journal of neurochemistry AU - Yu, O AU - Chuang, D M AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892-1272, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 346 EP - 354 VL - 66 IS - 1 SN - 0022-3042, 0022-3042 KW - Cyanides KW - 0 KW - Ferricyanides KW - Ferrocyanides KW - Neurotoxins KW - Parasympathomimetics KW - Phosphatidylinositols KW - Receptors, Glutamate KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - N-acetylpenicillamine KW - 59-53-0 KW - Potassium Chloride KW - 660YQ98I10 KW - S-Nitroso-N-Acetylpenicillamine KW - 79032-48-7 KW - Carbachol KW - 8Y164V895Y KW - Penicillamine KW - GNN1DV99GX KW - potassium ferrocyanide KW - GTP1P30292 KW - Cyclic GMP KW - H2D2X058MU KW - potassium ferricyanide KW - U4MAF9C813 KW - Index Medicus KW - Animals KW - Penicillamine -- analogs & derivatives KW - Penicillamine -- pharmacology KW - Potassium Chloride -- pharmacology KW - Cyclic GMP -- physiology KW - Nitric Oxide -- physiology KW - Hydrolysis KW - Models, Biological KW - Rats KW - Ferricyanides -- pharmacology KW - Ferrocyanides -- pharmacology KW - Rats, Sprague-Dawley KW - Parasympathomimetics -- pharmacology KW - Cells, Cultured KW - Cell Differentiation -- drug effects KW - Carbachol -- pharmacology KW - Cyanides -- pharmacology KW - Phosphatidylinositols -- metabolism KW - Neurons -- metabolism KW - Receptors, Glutamate -- drug effects KW - Nitroprusside -- toxicity KW - Neurons -- drug effects KW - Cerebellum -- drug effects KW - Signal Transduction -- drug effects KW - Receptors, Glutamate -- physiology KW - Neurotoxins -- pharmacology KW - Neurotoxins -- antagonists & inhibitors KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77916404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Inhibition+of+excitatory+amino+acid-induced+phosphoinositide+hydrolysis+as+a+possible+mechanism+of+nitroprusside+neurotoxicity.&rft.au=Yu%2C+O%3BChuang%2C+D+M&rft.aulast=Yu&rft.aufirst=O&rft.date=1996-01-01&rft.volume=66&rft.issue=1&rft.spage=346&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-24 N1 - Date created - 1996-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quinolinic acid levels in a murine retrovirus-induced immunodeficiency syndrome. AN - 77910145; 8522967 AB - Mice infected with the retrovirus mixture designated LP-BM5 murine leukemia virus (MuLV) develop an immunosuppressive disease. Quinolinic acid (QUIN) is an endogenous neurotoxic N-methyl-D-aspartate agonist that may contribute to the pathogenesis of HIV-associated neurologic disease. In the present study, the levels of QUIN in brain and blood were measured in mice infected with LP-BM5 MuLV and compared with those in uninfected mice and mice infected with the nonpathogenic strain of ecotropic MuLV (helper component of LP-BM5 MuLV). Infection with LP-BM5 MuLV resulted in progressive increases in blood QUIN levels beginning 2 weeks after inoculation that peaked by 16 weeks postinfection. QUIN levels were also increased in cerebral cortex, hippocampus, and striatum. In systemic tissues, QUIN levels were increased in lung, liver, and spleen. In contrast, infection with the ecotropic viral component of the LP-BM5 MuLV mixture was not associated with any changes in brain, blood, or systemic tissue QUIN levels, even though helper virus burdens were comparable to those in mice infected with LP-BM5 MuLV. Treatment of LP-BM5 MuLV-infected mice with the antiretroviral agent zidovudine (azidothymidine) significantly reduced blood and brain QUIN levels in association with reductions in viral load in brain and spleen. These observations suggest that elevated QUIN production is not attributable to productive infection with retrovirus per se but occurs in response to an agent or agents, such as cytokines, that are produced by the host in response to virus infection. JF - Journal of neurochemistry AU - Sei, Y AU - Paul, I A AU - Saito, K AU - Layar, R AU - Hartley, J W AU - Morse, H C AU - Skolnick, P AU - Heyes, M P AD - Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 296 EP - 302 VL - 66 IS - 1 SN - 0022-3042, 0022-3042 KW - Cytokines KW - 0 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Humans KW - Mice, Inbred C57BL KW - Helper Viruses -- pathogenicity KW - Cytokines -- physiology KW - Mice KW - Defective Viruses -- pathogenicity KW - Leukemia Virus, Murine -- pathogenicity KW - Viscera -- chemistry KW - AIDS Dementia Complex KW - Quinolinic Acid -- analysis KW - Quinolinic Acid -- blood KW - Murine Acquired Immunodeficiency Syndrome -- metabolism KW - Brain Chemistry KW - Disease Models, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77910145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Quinolinic+acid+levels+in+a+murine+retrovirus-induced+immunodeficiency+syndrome.&rft.au=Sei%2C+Y%3BPaul%2C+I+A%3BSaito%2C+K%3BLayar%2C+R%3BHartley%2C+J+W%3BMorse%2C+H+C%3BSkolnick%2C+P%3BHeyes%2C+M+P&rft.aulast=Sei&rft.aufirst=Y&rft.date=1996-01-01&rft.volume=66&rft.issue=1&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-24 N1 - Date created - 1996-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo infusion of growth factors enhances the mitogenic response of rat hepatic ductal (oval) cells after administration of 2-acetylaminofluorene. AN - 77901635; 8550051 AB - Expression of several growth factors is elevated in rat liver, after induction of oval cell proliferation by chemical carcinogens. However, the exact roles played by individual factors are not defined. We infused and examined the effects of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) on the proliferation of ductal and periductal cells after their activation with 2-acetylaminofluorene (2-AAF). Furthermore, we included studies on urokinase-type plasminogen activator (uPA), because Northern blot analysis showed a strong coincidence of uPA expression with oval cell proliferation. Low doses of 2-AAF were used to activate ductal and periductal cells, whereafter growth factors were infused. Infusion of EGF, HGF, uPA, or any combination thereof for up to 7 days resulted in increased numbers of [3H]thymidine-labeled ductal and periductal cells expanding into the liver acinus. Although the growth factors all increased the number of labeled cells, they preferentially acted on different cell populations. Although exposure to 2-AAF alone or combined with infusion of HGF resulted in proliferation of almost equal numbers of ductal and Ito cells, infusion of EGF and any combination hereof resulted in 75% to 80% of labeled cells having a ductal phenotype. Also, infusion of EGF and HGF resulted in decreased numbers of cells undergoing apoptosis in response to 2-AAF. Our results demonstrate that, although 2-AAF acts as a mitogenic stimulus for ductal and periductal cells, growth factors are necessary for survival, motility, and expansion of these cells into the liver acini. JF - Hepatology (Baltimore, Md.) AU - Nagy, P AU - Bisgaard, H C AU - Santoni-Rugiu, E AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 71 EP - 79 VL - 23 IS - 1 SN - 0270-9139, 0270-9139 KW - Carcinogens KW - 0 KW - Growth Substances KW - Epidermal Growth Factor KW - 62229-50-9 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Urokinase-Type Plasminogen Activator KW - EC 3.4.21.73 KW - Index Medicus KW - Urokinase-Type Plasminogen Activator -- pharmacology KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Blotting, Northern KW - Hepatocyte Growth Factor -- pharmacology KW - Apoptosis -- drug effects KW - Mitosis -- drug effects KW - Epidermal Growth Factor -- pharmacology KW - Male KW - Liver -- pathology KW - 2-Acetylaminofluorene -- toxicity KW - Growth Substances -- administration & dosage KW - Liver -- drug effects KW - Growth Substances -- pharmacology KW - Bile Ducts -- pathology KW - Carcinogens -- toxicity KW - Bile Ducts -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77901635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=In+vivo+infusion+of+growth+factors+enhances+the+mitogenic+response+of+rat+hepatic+ductal+%28oval%29+cells+after+administration+of+2-acetylaminofluorene.&rft.au=Nagy%2C+P%3BBisgaard%2C+H+C%3BSantoni-Rugiu%2C+E%3BThorgeirsson%2C+S+S&rft.aulast=Nagy&rft.aufirst=P&rft.date=1996-01-01&rft.volume=23&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-20 N1 - Date created - 1996-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anterior paralimbic mediation of procaine-induced emotional and psychosensory experiences. AN - 77901123; 8540778 AB - Procaine activates limbic structures in animals. In humans, acute intravenous administration of procaine yields emotional and psychosensory experiences and temporal lobe fast activity. We studied procaine's acute effects on cerebral blood flow (CBF) in relationship to clinical responses. Cerebral blood flow was assessed by positron emission tomography with oxygen-15-labeled water in 32 healthy volunteers. Data were analyzed with statistical parametric mapping and magnetic resonance imaging-directed regions of interest. Procaine increased global CBF and, to a greater extent, anterior paralimbic CBF. Subjects with intense procaine-induced fear compared with those with euphoria had greater increases in left amygdalar CBF. Absolute and normalized left amygdalar CBF changes tended to correlate positively with fear and negatively with euphoria intensity. Procaine-induced visual hallucinations appeared associated with greater global and occipital CBF increases. Absolute occipital CBF increases appeared to correlate positively with visual hallucination intensity. Procaine increased anterior paralimbic CBF, and different clinical responses appeared to be associated with different patterns of CBF changes. JF - Archives of general psychiatry AU - Ketter, T A AU - Andreason, P J AU - George, M S AU - Lee, C AU - Gill, D S AU - Parekh, P I AU - Willis, M W AU - Herscovitch, P AU - Post, R M AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Md., USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 59 EP - 69 VL - 53 IS - 1 SN - 0003-990X, 0003-990X KW - Procaine KW - 4Z8Y51M438 KW - Abridged Index Medicus KW - Index Medicus KW - Hallucinations -- chemically induced KW - Humans KW - Adult KW - Middle Aged KW - Mood Disorders -- etiology KW - Adolescent KW - Visual Perception -- drug effects KW - Male KW - Female KW - Auditory Perception -- drug effects KW - Temporal Lobe -- drug effects KW - Limbic System -- drug effects KW - Temporal Lobe -- physiology KW - Emotions -- physiology KW - Limbic System -- physiology KW - Cerebrovascular Circulation -- drug effects KW - Sensation -- drug effects KW - Procaine -- pharmacology KW - Temporal Lobe -- blood supply KW - Sensation -- physiology KW - Limbic System -- blood supply KW - Emotions -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77901123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Anterior+paralimbic+mediation+of+procaine-induced+emotional+and+psychosensory+experiences.&rft.au=Ketter%2C+T+A%3BAndreason%2C+P+J%3BGeorge%2C+M+S%3BLee%2C+C%3BGill%2C+D+S%3BParekh%2C+P+I%3BWillis%2C+M+W%3BHerscovitch%2C+P%3BPost%2C+R+M&rft.aulast=Ketter&rft.aufirst=T&rft.date=1996-01-01&rft.volume=53&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-08 N1 - Date created - 1996-02-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Gen Psychiatry. 1997 Aug;54(8):763-5 [9283513] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Domains of the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic tail required for envelope incorporation into virions. AN - 77900054; 8523546 AB - We recently demonstrated that a single amino acid substitution in matrix residue 12 (12LE) or 30 (30LE) blocks the incorporation of human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into virions and that this block can be reversed by pseudotyping with heterologous retroviral envelope glycoproteins with short cytoplasmic tails or by truncating the cytoplasmic tail of HIV-1 transmembrane glycoprotein gp41 by 104 or 144 amino acids. In this study, we mapped the domain of the gp41 cytoplasmic tail responsible for the block to incorporation into virions by introducing a series of eight truncation mutations that eliminated 23 to 93 amino acids from the C terminus of gp41. We found that incorporation into virions of a HIV-1 envelope glycoprotein with a deletion of 23, 30, 51, or 56 residues from the C terminus of gp41 is specifically blocked by the 12LE matrix mutation, whereas truncations of greater than 93 amino acids reverse this defect. To elucidate the role of matrix residue 12 in this process, we introduced a number of additional single amino acid substitutions at matrix positions 12 and 13. Charged substitutions at residue 12 blocked envelope incorporation and virus infectivity, whereas more subtle amino acid substitutions resulted in a spectrum of envelope incorporation defects. To characterize further the role of matrix in envelope incorporation into virions, we obtained and analyzed second-site revertants to two different matrix residue 12 mutations. A Val-->Ile substition at matrix amino acid 34 compensated for the effects of both amino acid 12 mutations, suggesting that matrix residues 12 and 34 interact during the incorporation of HIV-1 envelope glycoproteins into nascent virions. JF - Journal of virology AU - Freed, E O AU - Martin, M A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA. Y1 - 1996/01// PY - 1996 DA - January 1996 SP - 341 EP - 351 VL - 70 IS - 1 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Gene Products, env KW - Gene Products, gag KW - HIV Antigens KW - HIV Envelope Protein gp160 KW - HIV Envelope Protein gp41 KW - Protein Precursors KW - Viral Envelope Proteins KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - p17 protein, Human Immunodeficiency Virus Type 1 KW - Index Medicus KW - AIDS/HIV KW - Protein Precursors -- metabolism KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Virion -- metabolism KW - Binding Sites KW - Mutagenesis KW - Gene Products, env -- metabolism KW - Base Sequence KW - Molecular Sequence Data KW - Mutation KW - Cell Line KW - HIV-1 -- metabolism KW - HIV Envelope Protein gp41 -- metabolism KW - HIV Antigens -- chemistry KW - Gene Products, gag -- chemistry KW - Viral Envelope Proteins -- metabolism KW - HIV Antigens -- metabolism KW - Gene Products, gag -- metabolism KW - HIV Envelope Protein gp41 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77900054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Domains+of+the+human+immunodeficiency+virus+type+1+matrix+and+gp41+cytoplasmic+tail+required+for+envelope+incorporation+into+virions.&rft.au=Freed%2C+E+O%3BMartin%2C+M+A&rft.aulast=Freed&rft.aufirst=E&rft.date=1996-01-01&rft.volume=70&rft.issue=1&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-25 N1 - Date created - 1996-01-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1993 Nov;67(11):6387-94 [8411340] Nature. 1993 Oct 14;365(6447):666-9 [8105392] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9095-9 [8415660] Virology. 1993 Nov;197(1):255-64 [8212561] AIDS Res Hum Retroviruses. 1989 Feb;5(1):7-22 [2541749] Virology. 1989 Jun;170(2):566-70 [2543131] J Virol. 1995 Jul;69(7):4060-8 [7769663] J Biol Chem. 1995 Oct 13;270(41):23883-6 [7592573] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] J Mol Biol. 1984 Apr 5;174(2):297-317 [6325711] AIDS Res Hum Retroviruses. 1989 Aug;5(4):441-9 [2788444] J Virol. 1989 Oct;63(10):4395-403 [2778881] J Virol. 1989 Nov;63(11):4670-5 [2677400] J Virol. 1989 Nov;63(11):4709-14 [2795718] Nature. 1989 Oct 19;341(6243):573-4 [2677749] Science. 1990 Feb 16;247(4944):848-52 [2305256] J Virol. 1990 May;64(5):2298-308 [1691314] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4650-4 [2191297] Cell. 1990 Oct 5;63(1):77-86 [2170021] J Virol. 1991 Jan;65(1):162-9 [1845882] J Virol. 1994 Feb;68(2):585-91 [8289362] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Mar;68(3):1773-81 [8107239] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1994 Apr;68(4):2556-69 [8139035] J Virol. 1994 May;68(5):3232-42 [8151785] J Virol. 1994 Jul;68(7):4620-7 [8207836] Virology. 1994 Aug 15;203(1):8-19 [8030287] J Virol. 1994 Aug;68(8):4857-61 [8035484] J Virol. 1994 Aug;68(8):5311-20 [8035531] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6992-6 [8041734] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311-5 [8041786] Nature. 1994 Aug 25;370(6491):666-8 [8065455] J Mol Biol. 1994 Nov 25;244(2):198-223 [7966331] J Virol. 1995 Jan;69(1):365-75 [7983731] J Virol. 1995 Mar;69(3):1984-9 [7853546] J Virol. 1995 Jun;69(6):3824-30 [7745730] J Virol. 1995 Jun;69(6):3949-54 [7745752] J Virol. 1986 Aug;59(2):284-91 [3016298] Cell. 1986 Nov 7;47(3):333-48 [3094962] J Virol. 1987 Oct;61(10):2981-8 [3041017] Science. 1987 Sep 11;237(4820):1351-5 [3629244] Methods Enzymol. 1987;154:367-82 [3323813] J Virol. 1988 Nov;62(11):3993-4002 [3262776] Nature. 1988 Nov 3;336(6194):36-42 [2460771] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] J Virol. 1989 May;63(5):2374-8 [2784836] J Virol. 1991 Jan;65(1):31-41 [1985202] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3987-91 [2023946] J Virol. 1991 Aug;65(8):4350-8 [2072454] Virology. 1991 Aug;183(2):545-54 [1853560] AIDS. 1991 Jun;5(6):617-37 [1652977] AIDS. 1991 Jun;5(6):639-54 [1883539] J Virol. 1992 Feb;66(2):790-803 [1309913] J Virol. 1992 Apr;66(4):2232-9 [1548759] J Virol. 1992 Jun;66(6):3306-15 [1583717] J Virol. 1992 Jun;66(6):3971-5 [1583738] Virology. 1992 Jul;189(1):167-77 [1604808] J Virol. 1992 Aug;66(8):4737-47 [1629953] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Sep;66(9):5667-70 [1501299] J Virol. 1992 Nov;66(11):6616-25 [1357190] J Virol. 1993 Jan;67(1):213-21 [8416370] Science. 1992 Dec 18;258(5090):1935-8 [1470916] J Virol. 1993 May;67(5):2824-31 [8474176] J Virol. 1993 Jun;67(6):3077-86 [8497044] J Virol. 1993 Jun;67(6):3489-96 [7684467] J Virol. 1993 Jul;67(7):4264-73 [7685414] N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Would You Participate in an HIV Vaccine Trial? Key Factors among Out of Treatment Injection Drug Users T2 - American Sociological Association AN - 61727929; 96S32213 AB - An assessment of the normative beliefs, personal attitudes, & structural factors contributing to the willingness of a population of out-of-treatment injection drug users (IDUs) to participate in an HIV (human immunodeficiency virus) vaccine efficacy trial, based on responses to the Vaccine Interest Questionnaire (VIQ) obtained from 982 IDUs at 10 existing HIV prevention outreach sites throughout the US. Preliminary results indicate that 81% of Ss would be willing to receive a tested HIV vaccine, & 75% to participate in an HIV vaccine study. Family members, community doctors, & study researchers were reported as the most influential, with other drug users & celebrities being the least influential, in deciding to participate in an HIV vaccine trial. To 22%, it was important to know whether they were receiving the vaccine or placebo; most reported the intention to actively unblind by one or more specific approaches if they did not know the condition to which they were assigned. Correlational & multivariate analysis of these & other factors that influence trial participation are presented, & implications for future HIV trials discussed. In conclusion, it is argued that the out-of-treatment IDU population must be included if efficiacy trials are to be able to generalize results to this important at-risk population. JF - American Sociological Association AU - Gaist, Paul A AU - Needle, Richard AU - Celentano, David Y1 - 1996///0, PY - 1996 DA - 0, 1996 KW - human immunodeficiency virus vaccine efficacy trials, out-of-treatment injection drug user participation determinants KW - questionnaire KW - Experiments KW - Drug Injection KW - Participation KW - Acquired Immune Deficiency Syndrome KW - Medical Research KW - Informed Consent KW - Research Subjects KW - Drug Use KW - Vaccination KW - proceeding KW - 2045: sociology of health and medicine; sociology of medicine & health care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61727929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=American+Sociological+Association&rft.atitle=Would+You+Participate+in+an+HIV+Vaccine+Trial%3F+Key+Factors+among+Out+of+Treatment+Injection+Drug+Users&rft.au=Gaist%2C+Paul+A%3BNeedle%2C+Richard%3BCelentano%2C+David&rft.aulast=Gaist&rft.aufirst=Paul&rft.date=1996-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=American+Sociological+Association&rft.issn=&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2009-03-10 N1 - Publication note - 1996 N1 - Last updated - 2016-09-28 ER - TY - CPAPER T1 - Self-Esteem Enhancement through Fertility? Addressing Issues of Socio-Economic Prospects, Gender, and Mutual Influence T2 - American Sociological Association AN - 61725814; 96S32401 AB - Using data from the National Longitudinal Study of Youth, examines whether or not parenthood (as measured by number of children) enhances one's self-esteem, whether the effect of parenthood on self-esteem is stronger among the less socioeconomically privileged & among women, & whether there is evidence of mutual influence in the relationship between parenthood & self-esteem. Results indicate that parenthood does not influence the self-esteem of men, & wields a modest negative effect on the self-esteem of women. The latter effect, however, appears to be a spurious consequence of the relationship between both variables & socioeconomic prospects, a variable that displays a strong positive correlation with self-esteem, & a strong negative correlation with number of children. There is no evidence that having children enhances the self-esteem of those who are less socioeconomically privileged, or any other class of individuals. Results are also more consistent with the notion that parenthood influences self-esteem, rather than the reverse. JF - American Sociological Association AU - Oates, Gary L Y1 - 1996///0, PY - 1996 DA - 0, 1996 KW - self-esteem, parenthood effects KW - socioeconomic prospects, gender KW - National Longitudinal Survey of Youth KW - Socioeconomic Factors KW - Self Esteem KW - Sex Differences KW - Parenthood KW - proceeding KW - 1941: the family and socialization; sociology of the family, marriage, & divorce UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61725814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=American+Sociological+Association&rft.atitle=Self-Esteem+Enhancement+through+Fertility%3F+Addressing+Issues+of+Socio-Economic+Prospects%2C+Gender%2C+and+Mutual+Influence&rft.au=Oates%2C+Gary+L&rft.aulast=Oates&rft.aufirst=Gary&rft.date=1996-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=American+Sociological+Association&rft.issn=&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2012-05-01 N1 - Publication note - 1996 N1 - Last updated - 2016-09-28 ER - TY - JOUR T1 - New approaches in mathematical biology; information theory and molecular machines AN - 52583652; 1998-046202 JF - Proceedings of the ... Trieste Conference on Chemical Evolution AU - Schneider, Thomas D A2 - Chela-Flores, Julian A2 - Raulin, Francois Y1 - 1996 PY - 1996 DA - 1996 SP - 313 EP - 321 PB - Kluwer Academic Publishers, Dordrecht VL - 4 KW - molecular structure KW - organic compounds KW - organic acids KW - mathematical biology KW - biochemistry KW - DNA KW - biologic evolution KW - applications KW - information theory KW - 08:General paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52583652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+...+Trieste+Conference+on+Chemical+Evolution&rft.atitle=New+approaches+in+mathematical+biology%3B+information+theory+and+molecular+machines&rft.au=Schneider%2C+Thomas+D&rft.aulast=Schneider&rft.aufirst=Thomas&rft.date=1996-01-01&rft.volume=4&rft.issue=&rft.spage=313&rft.isbn=0792341112&rft.btitle=&rft.title=Proceedings+of+the+...+Trieste+Conference+on+Chemical+Evolution&rft.issn=&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - Fourth Trieste conference on Chemical evolution N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1998-01-01 N1 - Number of references - 14 N1 - Document feature - illus. N1 - Last updated - 2012-06-07 N1 - CODEN - #04566 N1 - SubjectsTermNotLitGenreText - applications; biochemistry; biologic evolution; DNA; information theory; mathematical biology; molecular structure; organic acids; organic compounds ER - TY - JOUR T1 - CCKB/gastrin receptor antagonists: recent advances and potential uses in gastric secretory disorders. AN - 20278264; 8929226 AB - Cholecystokinin (CCK) and the structurally related peptide, gastrin, have numerous effects on tissues in the central nervous system and gastrointestinal tract. Recent studies show these effect are mediated by a CCKA and CCKB receptor. Knowledge of the physiological role and role of CCKB receptors in pathologic processes has been particularly limited by the availability of selective, potent receptor antagonists. Recently, new members of five different classes of non-peptide CCKB receptor antagonists are reported and are reviewed briefly. these include compounds isolated from Streptomyces (tetronothiodin, virginiamycin analogues), ureido-acetamide analogues (RP 69758, RP 72540, RP 73870), newer benzodiazepine analogues (L-368,935, L-740,093, YM022), pyrazolidimine analogues (LY 262,691) and glutamic acid analogues (CR2194). Many of these compounds have greater than 1000-fold selectivity for the CCKB over the CCKA receptor and some have greater than 10,000-fold selectivity. The pharmacology and effects of CCKB receptor antagonists on gastric acid secretion is briefly reviewed. Furthermore, the possible clinical usefulness of CCKB receptor antagonists in treating disorders of gastric acid secretion, in inhibiting the trophic effects of gastrin and in other clinical conditions is briefly discussed. JF - Yale Journal of Biology and Medicine AU - Jensen, R T AD - National Institutes of Health, Bethesda, Maryland 20892-1804, USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 245 EP - 259 PB - Yale Journal of Biology and Medicine, Inc., 333 Cedar St, PO Box 208000 VL - 69 IS - 3 SN - 0044-0086, 0044-0086 KW - Microbiology Abstracts B: Bacteriology KW - Central nervous system KW - Cholecystokinin KW - Pharmacology KW - Secretion KW - Virginiamycin KW - Antagonists KW - Reviews KW - Streptomyces KW - Benzodiazepine KW - Gastrin KW - Glutamic acid KW - Gastrointestinal tract KW - J 02340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20278264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Yale+Journal+of+Biology+and+Medicine&rft.atitle=CCKB%2Fgastrin+receptor+antagonists%3A+recent+advances+and+potential+uses+in+gastric+secretory+disorders.&rft.au=Jensen%2C+R+T&rft.aulast=Jensen&rft.aufirst=R&rft.date=1996-01-01&rft.volume=69&rft.issue=3&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Yale+Journal+of+Biology+and+Medicine&rft.issn=00440086&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-02-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Central nervous system; Cholecystokinin; Pharmacology; Secretion; Reviews; Benzodiazepine; Gastrin; Virginiamycin; Gastrointestinal tract; Glutamic acid; Antagonists; Streptomyces ER - TY - JOUR T1 - Dose Intensity of Chemotherapy for Childhood Cancers. AN - 1859305554; 10388007 AB - Since the formulation of the "dose-intensity" concept of anticancer therapy in the mid-1980s, the concept that "more is better" has gained general acceptance among pediatric oncologists. However, recently published clinical trials results for adults with breast cancer, germ-cell tumors, and ovarian cancer raise questions about the value of dose intensification in improving outcome. Given the differences in sensitivity between pediatric and adult tumors to cytotoxic agents, the results from these adult trials suggest a need for caution but do not suggest that evaluations of dose intensity for pediatric tumors are unwarranted (especially for a tumor such as Ewing's sarcoma, which is especially sensitive to alkylating agents). Since dose-intensive therapies have significant short- and long-term costs for the patient, it is important to obtain reliable data concerning possible benefits of this strategy. Toward this end, NCI-sponsored randomized clinical trials evaluating the role of dose intensification have been initiated for several tumors of children (including neuroblastoma, germ-cell tumors, Ewing's sarcoma, and brain tumors in infants). These trials should be completed and reported in the next two to three years, and they may make unique contributions in defining the benefits and limitations of dose intensity as a cancer treatment strategy. In the long term, however, the utility of dose intensification is limited for children with cancer because of the inherent toxicities associated with its application. Identification of agents that more specifically target tumor cells is essential. Fortunately, pediatric tumor cells do have unique biological characteristics that may be susceptible to targeting for therapeutic benefit. JF - The oncologist AU - Smith AU - Abrams AU - Trimble AU - Ungerleider AD - Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, 20892, USA. smithm@dct.nci.nih.gov Y1 - 1996 PY - 1996 DA - 1996 SP - 293 EP - 304 VL - 1 IS - 5 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859305554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+oncologist&rft.atitle=Dose+Intensity+of+Chemotherapy+for+Childhood+Cancers.&rft.au=Smith%3BAbrams%3BTrimble%3BUngerleider&rft.aulast=Smith&rft.aufirst=&rft.date=1996-01-01&rft.volume=1&rft.issue=5&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=1549-490X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 1999-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactions of nickel(II) with histones: Enhancement of 2'-deoxyguanosine oxidation by Ni(II) complexes with CH sub(3)CO-Cys-Ala-Ile-His-NH sub(2), a putative metal binding sequence of histone H3 AN - 17092196; 3900935 AB - Studies of 2'-deoxyguanosine oxidation by hydrogen peroxide in the presence of CH sub(3)CO-Cys-Ala-Ile-His-NH sub(2) (CAIH) and/or NiCl sub(2) have been carried out in 100 mM phosphate buffer (pH 7.4) at 37 degree C. The dimeric CAIH oxidation product, CAIH disulfide, and its weak, octahedral Ni(II) complex, rather than the monomeric CAIH and its strong, square-planar Ni(II) complex, were found to be major catalysts of 8-oxo-dG yield, especially at submillimolar concentrations of H sub(2)O sub(2). The reaction was found not to involve detectable amounts of free radicals or Ni(III). These results, together with those published previously [Bal, W. et al. (1995) Chem. Res. Toxicol. 8, 683-692], lay a framework for the detailed investigations of the interactions of histone octamer with Ni(II) and other metal ions. They also suggest that molecular mechanisms of nickel carcinogenesis may involve oxidative damage processes catalyzed by weak Ni(II) complexes with cellular components. JF - Chemical Research in Toxicology AU - Bal, W AU - Lukszo, J AU - Kasprzak, K S AD - NCI-FCRDC, Build. 538, Rm. 205, Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 535 EP - 540 VL - 9 IS - 2 SN - 0893-228X, 0893-228X KW - nickel KW - histones KW - histone H3 KW - 2'-deoxyguanosine KW - heavy metals KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17092196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Interactions+of+nickel%28II%29+with+histones%3A+Enhancement+of+2%27-deoxyguanosine+oxidation+by+Ni%28II%29+complexes+with+CH+sub%283%29CO-Cys-Ala-Ile-His-NH+sub%282%29%2C+a+putative+metal+binding+sequence+of+histone+H3&rft.au=Bal%2C+W%3BLukszo%2C+J%3BKasprzak%2C+K+S&rft.aulast=Bal&rft.aufirst=W&rft.date=1996-01-01&rft.volume=9&rft.issue=2&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A mutant RNA polymerase reveals a kinetic mechanism for the switch between nonproductive stuttering synthesis and productive initiation during promoter clearance AN - 17090772; 3903018 AB - During transcription initiation from galP2, one of the two promoters of the Escherichia coli galactose operon with an initially transcribed sequence of pppAUUUC, RNA polymerase (RNAP) is known to engage nonproductive stuttering synthesis, which is sensitive to the concentration of UTP. This study examines the effect of this nonproductive synthesis on promoter clearance and determines other parameters that might affect stuttering synthesis by analyzing a mutant RNAP, RpoB3449, that has altered its function at this process at galP2. RpoB3449 has dramatically diminished stuttering synthesis, and consequently, it has increased the rate of productive initiation due to its enhanced rate of promoter clearance of galP2 compared with wild-type RNAP. Thus, a direct linkage between promoter clearance and productive transcription is demonstrated. The mechanism by which the mutant RNAP has altered the switch between nonproductive stuttering synthesis and productive initiation during promoter clearance is studied. Apparently, RpoB3449 has increased its efficiency in incorporating CTP at the +5 position of the galP22 transcript leading to its reduced stuttering synthesis, indicating that the rate of an RNAP incorporating the CTP after a stretch of uridine residues is important for promoter clearance at galP2. Because RpoB3449 demonstrates "wild-type" stuttering synthesis at the mutant galP2 promoter, which contains the 6 residue at the +5 position, it indicates that the mutant RNAP has altered in binding CTP at this context. Further experiments indicate that it is the +5 position per se of the galP2 sequence rather than a particular nucleotide at that position that is critical in determining the switch between the two alternate pathways during transcription initiation. A checkpoint model for the switch between nonproductive and productive initiations during promoter clearance is discussed. JF - Journal of Biological Chemistry AU - Jin, Ding Jun AD - Lab. Mol. Biol., NCI, NIH, Bldg. 37, Rm 2E14, 9000 Rockville Pike, Bethesda, MD 20892-4255, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 11659 EP - 11667 VL - 271 IS - 20 SN - 0021-9258, 0021-9258 KW - DNA-directed RNA polymerase KW - galactose KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - gal operon KW - transcription initiation KW - gene regulation KW - J 02726:RNA and ribosomes KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17090772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=A+mutant+RNA+polymerase+reveals+a+kinetic+mechanism+for+the+switch+between+nonproductive+stuttering+synthesis+and+productive+initiation+during+promoter+clearance&rft.au=Jin%2C+Ding+Jun&rft.aulast=Jin&rft.aufirst=Ding&rft.date=1996-01-01&rft.volume=271&rft.issue=20&rft.spage=11659&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - gal operon; transcription initiation; gene regulation ER - TY - JOUR T1 - Dissociation kinetics of RepA dimers: Implications for mechanisms of activation of DNA binding by chaperones AN - 17079988; 3899374 AB - The replication initiator of plasmid P1, RepA, binds DNA as monomer. The binding is stimulated by the chaperones DnaJ, DnaK and GrpE of Escherichia coli. Two models of chaperone action have been proposed. (i) Chaperones dissociate RepA dimers, which are inactive in DNA binding, into active monomers. (ii) The dissociation occurs spontaneously but the monomeric products require the chaperones for refolding into the active form. The latter model was based on the observation that RepA diluted 1000-fold below the K sub(D) for dimer dissociation, still required the chaperones for DNA binding. We have confirmed that under the condition of DNA binding experiments, the RepA dimers dissociate reversibly into monomers with a K sub(D) value of 1.1 plus or minus 0.1 mu M. In the vicinity of this concentration, the sedimentation coefficient of RepA was concentration dependent, allowing estimation of s sub(20,w) coefficients for the RepA monomer (2.95 S) and dimer (4.01 S). Dynamic light scattering experiments indicated an increase of the monomer fraction within 5 min of RepA dilution. Circular dichroism (CD) measurements were consistent with these results. RepA monomerization is efficient without the mediation of chaperones. They are required to activate RepA most likely because they are needed to re-fold RepA monomers. JF - Genes to Cells AU - Chattoraj, D K AU - Ghirlando, R AU - Park, K AU - Dibbens, JA AU - Lewis AD - Lab. Biochem., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 189 EP - 199 VL - 1 IS - 2 SN - 1356-9597, 1356-9597 KW - chaperones KW - RepA protein KW - plasmid P1 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA KW - Escherichia coli KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17079988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+to+Cells&rft.atitle=Dissociation+kinetics+of+RepA+dimers%3A+Implications+for+mechanisms+of+activation+of+DNA+binding+by+chaperones&rft.au=Chattoraj%2C+D+K%3BGhirlando%2C+R%3BPark%2C+K%3BDibbens%2C+JA%3BLewis&rft.aulast=Chattoraj&rft.aufirst=D&rft.date=1996-01-01&rft.volume=1&rft.issue=2&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Genes+to+Cells&rft.issn=13569597&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA ER - TY - JOUR T1 - Mutagenic specificities and adduct distributions for 7-bromomethylbenz[a]anthracenes AN - 17071588; 3894312 AB - Mutation induction in the supF gene of the plasmid pS189 by 7-bromomethylbenz[a]anthracene and 7-bromomethyl-12-methylbenz[a]anthracene was examined. The former compound was substantially more mutagenic than the latter but a much greater proportion of the total mutations were located at mutation hotspots for the 12-methyl derivative. The overall correlation between sites of mutation and sites of polymerase arrest (an indicator of adduct formation) through the supF gene was poor. Although these bromocompounds should form only a single guanine adduct (unlike dihydrodiol epoxides that form both cis and trans adducts) more than one mutational change was found at a given site, although the predominant base substitution was G arrow right T for either compound. JF - Carcinogenesis AU - Page, JE AU - Ross, H L AU - Bigger, CAH AU - Dipple, A AD - Chem. Carcinog. Lab., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., PO Box B, Frederick, MD 21702, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 283 EP - 288 VL - 17 IS - 2 SN - 0143-3334, 0143-3334 KW - 7-bromomethylbenz(a)anthracene KW - 7-bromomethyl-12-methylbenz(a)anthracene KW - supF gene KW - plasmid pS189 KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - DNA adducts KW - mutagenicity KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17071588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Mutagenic+specificities+and+adduct+distributions+for+7-bromomethylbenz%5Ba%5Danthracenes&rft.au=Page%2C+JE%3BRoss%2C+H+L%3BBigger%2C+CAH%3BDipple%2C+A&rft.aulast=Page&rft.aufirst=JE&rft.date=1996-01-01&rft.volume=17&rft.issue=2&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mutagenicity; DNA adducts ER - TY - JOUR T1 - Body size and breast cancer risk among women under age 45 years AN - 17068611; 3891311 AB - In a multicenter population-based case-control study that included 1,588 cases and 1,394 controls less than age 45 years, the authors examined the relation of adult body size and breast cancer risk among young women. Breast cancer patients and healthy controls were identified in Atlanta, Georgia; Seattle/Puget Sound, Washington; and central New Jersey. Cases were newly diagnosed with in situ or invasive breast cancer during the period of May 1, 1990, through December 31, 1992. Anthropometric variables thought to reflect early environmental factors, obesity, and body fat distribution were measured directly. Height, but not sitting height or frame size, was a breast cancer risk factor. Risk of the disease was increased 46 percent among women in the fourth quartile of height compared with women in the first quartile. Body weight, but not body fat distribution, was related to breast cancer risk. Risk of the disease was 35 percent lower among women in the highest quartile of Quetelet index compared with women in the lowest quartile. Risk of the disease was increased about 2.1-fold among women who were thin and tall compared with women who were heavy and short. Thus, breast cancer risk was increased substantially among younger women with a linear body type. JF - American Journal of Epidemiology AU - Swanson, CA AU - Coates, R J AU - Schoenberg, J B AU - Malone, KE AU - Gammon, MD AU - Stanford, J L AU - Shorr, I J AU - Potischman, NA AU - Brinton, LA AD - Div. Cancer Epidemiol. and Genet., NCI/NIH, EPN Rm. 443, 6130 Executive Blvd., MSC 7374, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 698 EP - 706 VL - 143 IS - 7 SN - 0002-9262, 0002-9262 KW - body size KW - Risk Abstracts; Health & Safety Science Abstracts KW - females KW - breast cancer KW - age KW - R2 23060:Medical and environmental health KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17068611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Body+size+and+breast+cancer+risk+among+women+under+age+45+years&rft.au=Swanson%2C+CA%3BCoates%2C+R+J%3BSchoenberg%2C+J+B%3BMalone%2C+KE%3BGammon%2C+MD%3BStanford%2C+J+L%3BShorr%2C+I+J%3BPotischman%2C+NA%3BBrinton%2C+LA&rft.aulast=Swanson&rft.aufirst=CA&rft.date=1996-01-01&rft.volume=143&rft.issue=7&rft.spage=698&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - breast cancer; age; females ER - TY - JOUR T1 - Chlamydia trachomatis interrupts an exocytic pathway to acquire endogenously synthesized sphingomyelin in transit from the Golgi apparatus to the plasma membrane AN - 17064513; 3890791 AB - Chlamydia trachomatis acquires C sub(6)-NBD-sphingomyelin endogenously synthesized from C sub(6)-NBD-ceramide and transported to the vesicle (inclusion) in which they multiply. Here we explore the mechanisms of this unusual trafficking and further characterize the association of the chlamydial inclusion with the Golgi apparatus. Endocytosed chlamydiae are trafficked to the Golgi region and begin to acquire sphingolipids from the host within a few hours following infection. The transport of NBD-sphingolipid to the inclusion is energy- and temperature-dependant with the characteristics of an active, vesicle-mediated process. Photooxidation of C sub(5)-DMB-ceramide, in the presence of diaminobenzidine, identified DMB-lipids in vesicles in the process of fusing to the chlamydial inclusion membrane. C sub(6)-NBD-sphingomyelin incorporated into the plasma membrane is not trafficked to the inclusion to a significant degree, suggesting the pathway for sphingomyelin trafficking is direct from the Golgi apparatus to the chlamydial inclusion. Lectins and antibody probes for Golgi-specific glycoproteins demonstrate the close association of the chlamydial inclusion with the Golgi apparatus but do not detect these markers in the inclusion membrane. Collectively, the data are consistent with a model in which C. trachomatis inhabits a unique vesicle which interrupts an exocytic pathway to intercept host sphingolipids in transit from the Golgi apparatus to the plasma membrane. JF - EMBO Journal AU - Hackstadt, T AU - Rockey, D D AU - Heinzen, R A AU - Scidmore, MA AD - Host-Parasite Interactions Sect., Lab. Intracellular Parasites, Rocky Mountain Lab., NIAID, NIH, Hamilton, MT 59840, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 964 EP - 977 VL - 15 IS - 5 SN - 0261-4189, 0261-4189 KW - sphingomyelin KW - Microbiology Abstracts B: Bacteriology KW - Golgi apparatus KW - exocytosis KW - plasma membranes KW - Chlamydia trachomatis KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17064513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=Chlamydia+trachomatis+interrupts+an+exocytic+pathway+to+acquire+endogenously+synthesized+sphingomyelin+in+transit+from+the+Golgi+apparatus+to+the+plasma+membrane&rft.au=Hackstadt%2C+T%3BRockey%2C+D+D%3BHeinzen%2C+R+A%3BScidmore%2C+MA&rft.aulast=Hackstadt&rft.aufirst=T&rft.date=1996-01-01&rft.volume=15&rft.issue=5&rft.spage=964&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Golgi apparatus; plasma membranes; exocytosis ER - TY - JOUR T1 - Purification and characterization of a protein that permits early detection of lung cancer. Identification of heterogeneous nuclear ribonucleoprotein-A2/B1 as the antigen for monoclonal antibody 703D4 AN - 17057945; 3885670 AB - We have reported that a mouse monoclonal antibody, 703D4, detects lung cancer 2 years earlier than routine chest x-ray or cytomorphology. We purified the 703D4 antigen to elucidate its role in early lung cancer biology, using Western blot detection after SDS-polyacrylamide gel electrophoresis. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C sub(18)-like, and analytical C sub(4) reverse phase high performance liquid chromatography. After 25-50,000-fold purification, the principal immunostaining protein was >95% pure by Coomassie staining. The NH sub(2) terminus was blocked, so CNBr digestion was used to generate internal peptides. Three sequences, including one across a site of alternate exon splicing, all identified a single protein, heterogeneous nuclear ribonucleoprotein-A2 (hnRNP-A2). A minor co-purifying immunoreactive protein resolved at the final C sub(4) high performance liquid chromatography step is the splice variant hnRNP-B1. Northern analysis of RNA from primary normal bronchial epithelial cells demonstrated a low level of hnRNP-A2/B1 expression, consistent with immunohistochemical staining of clinical samples, and increased hnRNP-A2/B1 expression was found in lung cancer cells. hnRNP-A2/B1 expression is under proliferation-dependent control in normal bronchial epithelial cell primary cultures, but not in SV40-transformed bronchial epithelial cells or tumor cell lines. With our clinical data, this information suggests that hnRNP-A2/B1 is an early marker of lung epithelial transformation and carcinogenesis. JF - Journal of Biological Chemistry AU - Zhou, Jun AU - Mulshine, J L AU - Unsworth, E J AU - Scott, F M AU - Avis, I M AU - Vos, MD AU - Treston, A M AD - Biomarkers and Prevention Res. Branch, DCS, NCI, 9610 Med. Cent. Dr., Rm. 300, Rockville, MD 20850-3300, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 10760 EP - 10766 VL - 271 IS - 18 SN - 0021-9258, 0021-9258 KW - hnRNP-A2 protein KW - hnRNP-B1 protein KW - lung carcinoma KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - splicing KW - ribonucleoproteins KW - monoclonal antibodies KW - man KW - N 14910:Nucleoproteins KW - W3 33120:Receptor based (antibodies, etc.) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17057945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Purification+and+characterization+of+a+protein+that+permits+early+detection+of+lung+cancer.+Identification+of+heterogeneous+nuclear+ribonucleoprotein-A2%2FB1+as+the+antigen+for+monoclonal+antibody+703D4&rft.au=Zhou%2C+Jun%3BMulshine%2C+J+L%3BUnsworth%2C+E+J%3BScott%2C+F+M%3BAvis%2C+I+M%3BVos%2C+MD%3BTreston%2C+A+M&rft.aulast=Zhou&rft.aufirst=Jun&rft.date=1996-01-01&rft.volume=271&rft.issue=18&rft.spage=10760&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - splicing; ribonucleoproteins; monoclonal antibodies; man ER - TY - JOUR T1 - A benzoic acid glycoside from Geniostoma antherotrichum AN - 17055411; 3885861 AB - Fractionation of an HIV-inhibitory organic extract of Geniostoma antherotrichum afforded a glycoside derivative, which has been characterized as 2-hydroxy-3-O- beta -D-glucopyranosyl-benzoic acid (1) on the basis of spectral analyses. The HIV-inhibitory activity of the extract was traced to polymeric tannins, while 1 was found to be inactive in the National Cancer Institute's primary anti-HIV screen. JF - Phytochemistry AU - Rashid, MA AU - Gustafson, K R AU - Cardellina, JH II AU - Boyd, M R AD - Lab. Drug Discovery Res. and Dev., Dev. Ther. Program, Div. Cancer Treat., NCI, Bldg 1052, Rm. 121, Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1205 EP - 1207 VL - 41 IS - 4 SN - 0031-0422, 0031-0422 KW - glycosides KW - Geniostoma antherotrichum KW - 2-hydroxy-3-O- beta -D-glucopyranosylbenzoic acid KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - inhibitors KW - human immunodeficiency virus KW - spectroscopy KW - fractionation KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17055411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Phytochemistry&rft.atitle=A+benzoic+acid+glycoside+from+Geniostoma+antherotrichum&rft.au=Rashid%2C+MA%3BGustafson%2C+K+R%3BCardellina%2C+JH+II%3BBoyd%2C+M+R&rft.aulast=Rashid&rft.aufirst=MA&rft.date=1996-01-01&rft.volume=41&rft.issue=4&rft.spage=1205&rft.isbn=&rft.btitle=&rft.title=Phytochemistry&rft.issn=00310422&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus; inhibitors; spectroscopy; fractionation ER - TY - JOUR T1 - Selected new developments in computational chemistry AN - 17053665; 3882835 AB - Molecular dynamics is a general technique for simulating the time-dependent properties of molecules and their environments. Quantum mechanics, as applied to molecules or clusters of molecules, provides a prescription for predicting properties exactly (in principle). It is reasonable to expect that both will have a profound effect on our understanding of environmental chemistry in the future. In this review, we consider several recent advances and applications in computational chemistry. JF - Environmental Health Perspectives AU - Darden, T A AU - Bartolotti, L AU - Pedersen, L G AD - MD A3-06, NIEHS, P. O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996 PY - 1996 DA - 1996 VL - 104 SN - 0091-6765, 0091-6765 KW - Toxicology Abstracts KW - reviews KW - computer applications KW - quantum chemistry KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17053665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Selected+new+developments+in+computational+chemistry&rft.au=Darden%2C+T+A%3BBartolotti%2C+L%3BPedersen%2C+L+G&rft.aulast=Darden&rft.aufirst=T&rft.date=1996-01-01&rft.volume=104&rft.issue=&rft.spage=no.+1+Sul.&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - reviews; computer applications; quantum chemistry ER - TY - JOUR T1 - Hematotoxicity among Chinese workers heavily exposed benzene AN - 17052945; 3882843 AB - Benzene is a well-established hematotoxin. However, reports of its effects on specific blood cells have been somewhat inconsistent and the relative toxicity of benzene metabolites on peripheral blood cells in humans has not been evaluated. We compared hematologic outcomes in a cross-sectional study of 44 workers heavily exposed to benzene (median: 31 parts permillion [ppm] as an 8-hr time-weighted average [TWA] and 44 age and gender-matched unexposed controls from Shanghai, China. All hematologic parameters (total white blood cells [WBC], absolute lymphocyte count, platelets, red blood cells, and hematocrit) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume (MCV), which was higher among exposed subjects. In a subgroup of workers who were not exposed to more than 31 ppm benzene on any of 5 sampling days (n = 11, median 8 hr TWA = 7.6 ppm, range = 1-20 ppm), only the absolute lymphocyte count was significantly different between exposed workers (mean [sd] 1.6 [0.4] x 10 super(3) mu L) and controls (1.9 [0.4] x 10 super(3) mu L, p = 0.03). Among exposed subjects, a dose-response relationship with various measures of current benzene exposure (i.e., personal air monitoring, benzene metabolites in urine) was present only for the total WBC count, the absolute lymphocyte count, and the MCV. Correlations between benzene metabolites and hematologic parameters were generally similar, although hydroquinone was somewhat more strongly associated with a decrease in the absolute lymphocyte count, and catechol was more strongly associated with an increase in MCV. Morphologic review of peripheral blood slides demonstrated an excess of red blood cell abnormalities (i.e., stomatocytes and target cells) only in the most heavily exposed workers, with no differences in granulocyte, lymphocyte, or platelet morphology noted. Although benzene can affect all the major peripheral blood elements, our results support the use of the absolute lymphocyte count as the most sensitive indicator of benzene-induced hematotoxicity. JF - American Journal of Industrial Medicine AU - Rothman, N AU - Li, Gui-Lin AU - Dosemeci, M AU - Bechtold, W E AU - Marti, GE AU - Wang, Yao-Zu AU - Linet, M AU - Xi, Li-Qiang AU - Lu, Wei AU - Smith, M T AU - Titenko-Holland, N AU - Zhang, Luo-Ping AU - Blot, W AU - Yin, Song-Nian AU - Hayes, R B AD - NIH/NCI EPN 418, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 236 EP - 246 PB - JOHN WILEY & SONS VL - 29 IS - 3 SN - 0271-3586, 0271-3586 KW - benzene KW - Toxicology Abstracts KW - hematological diseases KW - blood KW - China, People's Rep. KW - occupational exposure KW - man KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17052945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Hematotoxicity+among+Chinese+workers+heavily+exposed+benzene&rft.au=Rothman%2C+N%3BLi%2C+Gui-Lin%3BDosemeci%2C+M%3BBechtold%2C+W+E%3BMarti%2C+GE%3BWang%2C+Yao-Zu%3BLinet%2C+M%3BXi%2C+Li-Qiang%3BLu%2C+Wei%3BSmith%2C+M+T%3BTitenko-Holland%2C+N%3BZhang%2C+Luo-Ping%3BBlot%2C+W%3BYin%2C+Song-Nian%3BHayes%2C+R+B&rft.aulast=Rothman&rft.aufirst=N&rft.date=1996-01-01&rft.volume=29&rft.issue=3&rft.spage=236&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep.; occupational exposure; blood; man; hematological diseases ER - TY - JOUR T1 - A cohort study of cancer among benzene-exposed workers in China: Overall results AN - 17052838; 3882845 AB - A large cohort study of 74,828 benzene-exposed and 35,805 unexposed workers employed between 1972 and 1987 in 12 cities in China were followed to determine mortality from all causes and the incidence of lymphohematopoietic malignancies and other hematologic disorders. Benzene-exposed study subjects were employed in a variety of occupations, including painting, printing, and the manufacture of footwear, paint, and other chemicals. All-cause mortality was similar in the benzene-exposed and unexposed comparison group. Statistically significant excess deaths were noted among benzene-exposed subjects for leukemia (RR = 2.3, 95% CI: 1.1-5.0), malignant lymphoma (RR = 4.5, 95% CI: 1.3-28.4), and non-neoplastic diseases of the blood (RR = arrow left , 95% CI: 2.5- arrow left ), and a marginally significant excess was noted for lung cancer (RR = 1.4, 95% CI: 1.0-2.0). Risk was significantly elevated for the incidence of all lymphohematopoietic malignancies (RR = 2.6, 95% CI: 1.5-5.0), malignant lymphoma (RR = 3.5, 95% CI: 1.2-14.9), and leukemia (RR = 2.6, 95% CI: 1.3-5.7). Among the leukemia subtypes, only acute myelogenous leukemia (AML) incidence was significantly elevated (RR = 3.1, 95% CI: 1.2-10.7), although nonsignificant excesses were also noted for chronic myelogenous leukemia (CML) (RR = 2.6, 95% CI: 0.7-16.9) and lymphocytic leukemias (RR = 2.8, 95% CI: 0.5-54.5). Significant excesses were found for aplastic anemia (RR = arrow left , 95% CI: 2.2- arrow left ) and myelodysplastic syndrome (RR = arrow left , 95% CI: 1.7- arrow left ). Employment in benzene-associated occupations in China is associated with a wide spectrum of myelogenous and lymphocytic malignant diseases and related disorders. Investigations continue to assess the nature of these associations. JF - American Journal of Industrial Medicine AU - Yin, Song-Nian AU - Hayes, R B AU - Linet AU - Li, Gui-Lan AU - Dosemeci, M AU - Travis, L B AU - Li, Chin-Yang AU - Zhang, Zhi-Nan AU - Li, De-Gao AU - Chow, Wong-Ho AU - Wacholder, S AU - Wang, Yao-Zu AU - Jiang, Zhong-Lian AU - Dai, Tan-Rong AD - NIH/NCI EPN, 418, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 227 EP - 235 PB - JOHN WILEY & SONS VL - 29 IS - 3 SN - 0271-3586, 0271-3586 KW - benzene KW - Toxicology Abstracts KW - epidemiology KW - China, People's Rep. KW - occupational exposure KW - man KW - cancer KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17052838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=A+cohort+study+of+cancer+among+benzene-exposed+workers+in+China%3A+Overall+results&rft.au=Yin%2C+Song-Nian%3BHayes%2C+R+B%3BLinet%3BLi%2C+Gui-Lan%3BDosemeci%2C+M%3BTravis%2C+L+B%3BLi%2C+Chin-Yang%3BZhang%2C+Zhi-Nan%3BLi%2C+De-Gao%3BChow%2C+Wong-Ho%3BWacholder%2C+S%3BWang%2C+Yao-Zu%3BJiang%2C+Zhong-Lian%3BDai%2C+Tan-Rong&rft.aulast=Yin&rft.aufirst=Song-Nian&rft.date=1996-01-01&rft.volume=29&rft.issue=3&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep.; cancer; occupational exposure; epidemiology; man ER - TY - JOUR T1 - P1 and P7 plasmid partition: ParB protein bound to its partition site makes a separate discriminator contact with the DNA that determines species specificity AN - 17051319; 3881922 AB - The cis-acting P1 and P7 parS sites are responsible for active partition of P1 and P7 plasmids to daughter cells. The two sites are similar but function only with ParB proteins from the correct species. Using hybrid ParB proteins and hybrid parS sites, we show that specificity is determined by contacts between bases that lie within two parS hexamer boxes and a region in the ParB C-terminus. We refer to these contacts as discriminator contacts. The P7 discriminator contacts were mapped to 3 and 2 bp respectively within the two parS hexamer boxes, and a 10 amino acid region of P7 ParB. Similarly placed residues of different sequence are responsible for the P1 discriminator contact. The discriminator contacts are distinct from previously identified DNA binding contacts which involve different ParB and parS regions. Deletion of the ParB C-terminus that makes the discriminator contact does not diminish in vitro binding but renders it species independent. The discriminator contact is therefore a negative function, interfering with binding of the wrong ParB, but not providing energy for the binding of the correct one. Similar discriminator contacts might be responsible for specificities seen among families of eukaryotic DNA binding proteins that share common binding motifs. JF - EMBO Journal AU - Radnedge, L AU - Davis, MA AU - Austin, S J AD - Lab. Chromosome Biol., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1155 EP - 1162 VL - 15 IS - 5 SN - 0261-4189, 0261-4189 KW - ParB protein KW - plasmid P1 KW - plasmid P7 KW - parA gene KW - parB gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02760:Plasmids KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17051319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=P1+and+P7+plasmid+partition%3A+ParB+protein+bound+to+its+partition+site+makes+a+separate+discriminator+contact+with+the+DNA+that+determines+species+specificity&rft.au=Radnedge%2C+L%3BDavis%2C+MA%3BAustin%2C+S+J&rft.aulast=Radnedge&rft.aufirst=L&rft.date=1996-01-01&rft.volume=15&rft.issue=5&rft.spage=1155&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Hypervariable DNA markers reveal high genetic variability within striped bass populations of the lower Chesapeake Bay AN - 17050062; 3880499 AB - We used a survey of hypervariable, variable number of tandem repeat (VNTR) loci to detect nuclear genetic differentiation within and among populations of striped bass Morone saxatilis in the lower Chesapeake Bay. This species has been refractory to population genetic analysis because it is depauperate in genetic variability. Previously described morphological differences and possible physiographic barriers to gene flow suggest the potential for differentiation among lower bay populations. In this study, we found considerable interindividual variation but relatively small levels of interpopulation variation among samples from the lower western shore of the Chesapeake Bay. The results suggest that stochastic genetic differentiation among these populations is unlikely and that relatively strong selection for locally adapted genotypes would be required for interpopulation differentiation to occur. JF - Transactions of the American Fisheries Society AU - Laughlin, T F AU - Turner, B J AD - Biol. Carcinogenesis and Dev. Program, Sci. Applic. Intl. Crop., NCI, Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 49 EP - 55 VL - 125 IS - 1 SN - 0002-8487, 0002-8487 KW - DNA KW - Morone saxatilis KW - USA, Chesapeake Bay KW - bass KW - fish management KW - fish populations KW - gene flow KW - genetic variance KW - genetics KW - genotypes KW - population genetics KW - Water Resources Abstracts; Ecology Abstracts; Genetics Abstracts; Oceanic Abstracts; ASFA 1: Biological Sciences & Living Resources KW - Marine KW - ANW, USA, Chesapeake Bay KW - O 1070:Ecology/Community Studies KW - Q1 08443:Population genetics KW - D 04668:Fish KW - SW 0890:Estuaries KW - G 07290:Population genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17050062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transactions+of+the+American+Fisheries+Society&rft.atitle=Hypervariable+DNA+markers+reveal+high+genetic+variability+within+striped+bass+populations+of+the+lower+Chesapeake+Bay&rft.au=Laughlin%2C+T+F%3BTurner%2C+B+J&rft.aulast=Laughlin&rft.aufirst=T&rft.date=1996-01-01&rft.volume=125&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Transactions+of+the+American+Fisheries+Society&rft.issn=00028487&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - population genetics; DNA; genotypes; gene flow; genetic variance; fish management; bass; USA, Chesapeake Bay; fish populations; Morone saxatilis; ANW, USA, Chesapeake Bay; Marine ER - TY - JOUR T1 - Mutations in the B subunit of Escherichia coli DNA gyrase that affect ATP-dependent reactions AN - 17044882; 3878933 AB - We have previously reported specific labeling of Escherichia coli DNA gyrase by the ATP affinity analog pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP), which resulted in inhibition of ATP-dependent reactions. The analog was found to be covalently bound at Lys super(103) and Lys super(110) on the gyrase B subunit. In this study, the importance of these two lysine residues is examined by site-directed mutagenesis. Substitutions of Lys super(103) result in the loss of ATP-dependent functions. These mutants are unable to super-coil DNA, to hydrolyze ATP, or to bind a nonhydrolysable ATP analog, 5'-adenylyl- beta , gamma -imidodiphosphate (ADPNP). The ATP-independent functions of gyrase, such as relaxation of negatively supercoiled DNA and oxolinic acid-induced cleavage of double-stranded DNA, are unaffected by these mutations, suggesting that the mutant B subunits are assembling correctly with the A subunits. Gyrase with substitutions of Lys super(110) retains all activities. However, the affinity of ATP is decreased. The DNA supercoiling activity of gyrase A sub(2)B sub(2) tetramers reconstituted with varying ratios of inactive mutant and wild-type gyrase B subunits is consistent with a mechanism of DNA supercoiling that requires the interdependent activity of both B subunits in ATP binding and hydrolysis. JF - Journal of Biological Chemistry AU - O'Dea, M H AU - Tamura, J K AU - Gellert, M AD - Lab. Mol. Biol., Bldg. 5, Rm. 241, NIDDK, Natl. Inst. Healt Bethesda, MD 20892-0540, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 9723 EP - 9729 VL - 271 IS - 16 SN - 0021-9258, 0021-9258 KW - DNA topoisomerase (ATP-hydrolysing) KW - ATP KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - site-directed mutagenesis KW - Escherichia coli KW - J 02728:Enzymes KW - N 14731:DNA-unwinding enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17044882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Mutations+in+the+B+subunit+of+Escherichia+coli+DNA+gyrase+that+affect+ATP-dependent+reactions&rft.au=O%27Dea%2C+M+H%3BTamura%2C+J+K%3BGellert%2C+M&rft.aulast=O%27Dea&rft.aufirst=M&rft.date=1996-01-01&rft.volume=271&rft.issue=16&rft.spage=9723&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; site-directed mutagenesis ER - TY - JOUR T1 - Treatment of lymphocutaneous and visceral sporotrichosis with fluconazole AN - 17038026; 3872491 AB - Thirty patients with documented sporotrichosis were treated with 200-800 mg of fluconazole daily. Fourteen patients had lymphocutaneous infection; only five (36%) of these patients had any underlying illnesses. Sixteen patients had osteoarticular or visceral sporotrichosis; 12 (75%) of these patients had underlying diseases, mostly alcoholism, diabetes mellitus, and chronic obstructive pulmonary disease. Eleven of the 30 patients had relapsed after prior antifungal therapy. Most patients were treated with 400 mg of fluconazole; however, four received 200 mg of fluconazole daily for the entire course, and four received 800 mg of fluconazole daily for a portion of their therapy or for the entire course of therapy. Fluconazole therapy cured 10 (71%) of 14 patients with lymphocutaneous sporotrichosis. However, only five (31%) of 16 patients with osteoarticular or visceral sporotrichosis responded to therapy; the conditions of two of these five patients improved only, and there was no documented cure of their infections. With the exception of alopecia in five patients, toxic effects were minimal. Fluconazole is only modestly effective for treatment of sporotrichosis and should be considered second-line therapy for the occasional patient who is unable to take itraconazole. JF - Clinical Infectious Diseases AU - Kauffman, CA AU - Pappas, P G AU - McKinsey, D S AU - Greenfield, R A AU - Perfect, J R AU - Cloud, G A AU - Thomas, C J AU - Dismukes, W E AD - Veterans Affairs Med. Cent., 2215 Fuller Road, Ann Arbor, MI 48105, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 46 EP - 50 VL - 22 IS - 1 SN - 1058-4838, 1058-4838 KW - fluconazole KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Sporothrix schenckii KW - sporotrichosis KW - man KW - A 01067:Antifungal & fungicidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17038026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Infectious+Diseases&rft.atitle=Treatment+of+lymphocutaneous+and+visceral+sporotrichosis+with+fluconazole&rft.au=Kauffman%2C+CA%3BPappas%2C+P+G%3BMcKinsey%2C+D+S%3BGreenfield%2C+R+A%3BPerfect%2C+J+R%3BCloud%2C+G+A%3BThomas%2C+C+J%3BDismukes%2C+W+E&rft.aulast=Kauffman&rft.aufirst=CA&rft.date=1996-01-01&rft.volume=22&rft.issue=1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sporothrix schenckii; sporotrichosis; man ER - TY - JOUR T1 - HIV reverse transcription in yeast AN - 17028258; 3859130 AB - The study of human immunodeficiency virus (HIV) reverse transcriptase/ribonuclease H (RT/RH) and other medically important reverse transcriptases would be greatly enhanced by simple, safety and inexpensive in vivo assays. We combined the reverse transcription indicator gene his3AI with hybrid Ty/HIV elements to demonstrate that HIV-1 RT/RH can substitute for the RT/RH of the Ty1 retrotransposon in Saccharomyces cerevisiae. S. cerevisiae strains harbour retrotransposons (Ty elements) which replicate like retroviruses. Ty encodes an RT/RH necessary for replicative transposition and an integrase required for insertion at novel sites. The plasmid pGTyhis3AI (a in the figure) was developed for analysis of retrotransposition. Splicing and reverse transcription of the galactose-inducible Tyhis3AI messenger RNA yields Ty complementary DNA carrying a functional HIS3 gene that can be integrated into the genome. Ty cDNA can also undergo homologous recombination with endogenous Ty elements. Both transposition and cDNA recombination result in His super(+) cells. JF - Nature AU - Nissley, D V AU - Garfinkel, D J AU - Strathern, J N AD - Gene Regulation and Chromosome Biol. Lab., NCI-Frederick Cancer Res. and Dev. Cent., ABL-Basic Res. Program, P.O. Box B, Frederick, MD 21702, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 30 VL - 380 IS - 6569 SN - 0028-0836, 0028-0836 KW - HIS3 gene KW - RNA-directed DNA polymerase KW - ribonuclease H KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - genetic engineering KW - transposons KW - human immunodeficiency virus KW - Saccharomyces cerevisiae KW - K 03079:Fungi KW - V 22002:AIDS: Molecular and in vitro aspects KW - N 14722:DNA polymerases KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17028258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=HIV+reverse+transcription+in+yeast&rft.au=Nissley%2C+D+V%3BGarfinkel%2C+D+J%3BStrathern%2C+J+N&rft.aulast=Nissley&rft.aufirst=D&rft.date=1996-01-01&rft.volume=380&rft.issue=6569&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - genetic engineering; transposons; human immunodeficiency virus; Saccharomyces cerevisiae ER - TY - JOUR T1 - Characterization of crystalline formate dehydrogenase H from Escherichia coli. Stabilization, EPR spectroscopy, and preliminary crystallographic analysis AN - 17026319; 3904723 AB - The selenocysteine-containing formate dehydrogenase H (FDH) is an 80-kDa component of the Escherichia coli formate-hydrogen lyase complex. The molybdenum-coordinated selenocysteine is essential for catalytic activity of the native enzyme. FDH in dilute solutions (30 mu g/ml) was rapidly inactivated at basic pH or in the presence of formate under anaerobic conditions, but at higher enzyme concentrations ( greater than or equal to 3 mg/ml) the enzyme was relatively stable. The formate-reduced enzyme was extremely sensitive to air inactivation under all conditions examined. Active formate-reduced FDH was crystallized under anaerobic conditions in the presence of ammonium sulfate and PEG 400. The crystals diffract to 2.6 angstrom resolution and belong to a space group of P4 sub(1)2 sub(1)2 or P4 sub(3)2 sub(1)2 with unit cell dimensions a = b = 146.1 angstrom and c = 82.7 angstrom. There is one monomer of FDH per crystallographic asymmetric unit. Similar diffraction quality crystals of oxidized FDH could be obtained by oxidation of crystals of formate-reduced enzyme with benzyl viologen. By EPR spectroscopy, a signal of a single reduced FeS cluster was found in a crystal of reduced FDH, but not in a crystal of oxidized enzyme, whereas Mo(V) signal was not detected in either form of crystalline FDH. This suggests that Mo(IV)- and the reduced FeS cluster-containing form of the enzyme was crystallized and this could be converted into Mo(VI)- and oxidized FeS cluster form upon oxidation. A procedure that combines anaerobic and cryocrystallography has been developed that is generally applicable to crystallographic studies of oxygen-sensitive enzymes. These data provide the first example of crystallization of a substrate-reduced form of a Se- and Mo-containing enzyme. JF - Journal of Biological Chemistry AU - Gladyshev, V N AU - Boyington, J C AU - Khangulov, S V AU - Grahame, DA AU - Stadtman, T C AU - Sun, P D AD - NHLBI/NIH/LB, Bldg. 3, Rm. 108, 3 Cent. Dr. MSC 0320, Bethesda, MD 20892-0320, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 8095 EP - 8100 VL - 271 IS - 14 SN - 0021-9258, 0021-9258 KW - formate dehydrogenase H KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17026319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Characterization+of+crystalline+formate+dehydrogenase+H+from+Escherichia+coli.+Stabilization%2C+EPR+spectroscopy%2C+and+preliminary+crystallographic+analysis&rft.au=Gladyshev%2C+V+N%3BBoyington%2C+J+C%3BKhangulov%2C+S+V%3BGrahame%2C+DA%3BStadtman%2C+T+C%3BSun%2C+P+D&rft.aulast=Gladyshev&rft.aufirst=V&rft.date=1996-01-01&rft.volume=271&rft.issue=14&rft.spage=8095&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli ER - TY - JOUR T1 - Baculovirus expression of chicken nonmuscle heavy meromyosin II-B: Characterization of alternatively spliced isoforms AN - 17019020; 3861006 AB - We have expressed two truncated isoforms of chicken nonmuscle myosin II-B using the baculovirus expression system. One of the expressed heavy meromyosins (HMM sub(exp)) consists of two 150-kDa myosin heavy chains (MHCs), comprising amino acids 1-1231 as well as two pairs of 20-kDa and 17-kDa myosin light chains (MLCs) in a 1:1:1 molar ratio. The second HMM sub(exp) was identical except that it contained an insert of 10 amino acids (PESPKPVKHQ) at the 25-50-kDa domain boundary in the subfragment-1 region of the MHC. These 10 amino acids include a consensus sequence (SPK) for proline-directed kinases. Expressed HMMs were soluble at low ionic strength and bound to rabbit skeletal muscle actin in an ATP-dependent manner. These properties afforded a rapid purification of milligram quantities of expressed protein. Both isoforms were capable of moving actin filaments in an in vitro motility assay and manifested a greater than 20-fold activation of actin-activated MgATPase activity following phosphorylation of the 20-kDa MLC. HMM sub(exp) with the 10-amino acid insert was phosphorylated by Cdc2, Cdk5, and mitogen-activated protein kinase in vitro to 0.3-0.4 mol of PO sub(4)/mol of MHC. The site phosphorylated in the MHC was identified as the serine residue present in the 10-amino acid insert and its presence was confirmed in bovine brain MHCs. Characterization of the baculovirus expressed noninserted and inserted MHC isoforms with respect to active-activated MgATPase activity and ability to translocate actin filaments in an in vitro motility assay produced the following average values following MLC phosphorylation: noninserted HMM sub(exp), V sub(max) = 0.28 s super(-1), K sub(m) = 12.7 mu M; translocation rate = 0.077 mu m/s; inserted HMM sub(exp), V sub(max) = 0.37 s super(-1), K sub(m) = 15.1 mu M; translocation rate = 0.092 mu m/s. JF - Journal of Biological Chemistry AU - Pato, MD AU - Sellers, J R AU - Preston, YA AU - Harvey, E V AU - Adelstein, R S AD - Lab. Molecular Cardiology, NHLBI, Bldg. 10, Rm. 8N202, 10 Cent. Dr., MSC 1762, Bethesda, MD 20892-1762, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 2689 EP - 2695 VL - 271 IS - 5 SN - 0021-9258, 0021-9258 KW - ATP KW - Cdk5 protein KW - MAP kinase KW - actin KW - adenosinetriphosphatase KW - cdc2 kinase KW - chickens KW - meromyosin KW - myosin KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - splicing KW - phosphorylation KW - W2 32070:Animals KW - N 14684:Expression of cloned genes KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17019020?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Baculovirus+expression+of+chicken+nonmuscle+heavy+meromyosin+II-B%3A+Characterization+of+alternatively+spliced+isoforms&rft.au=Pato%2C+MD%3BSellers%2C+J+R%3BPreston%2C+YA%3BHarvey%2C+E+V%3BAdelstein%2C+R+S&rft.aulast=Pato&rft.aufirst=MD&rft.date=1996-01-01&rft.volume=271&rft.issue=5&rft.spage=2689&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - splicing; phosphorylation ER - TY - JOUR T1 - Comparison of the effects of ozone on the modification of amino acid residues in glutamine synthetase and bovine serum albumin AN - 17014765; 3846064 AB - During exposure to ozone, the methionine and aromatic amino acid residues of Escherichia coli glutamine synthetase (GS) and bovine serum albumin (BSA) are oxidized rapidly in the order Met > Trp > Tyr approximately His > Phe. The loss of His is matched by a nearly equivalent formation of aspartate or of a derivative that is converted to aspartic acid upon acid hydrolysis. Conversion of His to aspartate was confirmed by showing that the oxidation of E. coli protein in which all His residues were uniformly labeled with super(14)C gave rise to super(14)C-labeled aspartic acid in 80% yield and also by the demonstration that His residues in the tripeptides Ala-His-Ala or Ala-Ala-His gave rise to nearly stoichiometric amounts of aspartic acid whereas oxidation of His-Ala-Ala yielded only 36% aspartate. The oxidation of BSA and GS led to formation, respectively, of 11 and 3.3 eq of carbonyl groups and 0.5 and 0.3 eq of quinoprotein per subunit. Although BSA and GS contain nearly identical amounts of each kind of aromatic amino acid residues, oxidation of these residues in BSA was about 1.5-2.0 times faster than in GS indicating that the susceptibility to oxidation is dependent on the primary, secondary, tertiary, and quaternary structure of the protein. JF - Journal of Biological Chemistry AU - Berlett, B S AU - Levine, R L AU - Stadtman, E R AD - Lab. Biochem., NHLBI, Natl. Inst. Health, Build. 3, Rm. 222, Bethesda, MD 20892-0342, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 4177 EP - 4182 VL - 271 IS - 8 SN - 0021-9258, 0021-9258 KW - ozone KW - glutamate-ammonia ligase KW - serum albumin KW - methionine KW - histidine KW - Toxicology Abstracts KW - amino acids KW - bovine serum albumin KW - protein structure KW - Escherichia coli KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17014765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Comparison+of+the+effects+of+ozone+on+the+modification+of+amino+acid+residues+in+glutamine+synthetase+and+bovine+serum+albumin&rft.au=Berlett%2C+B+S%3BLevine%2C+R+L%3BStadtman%2C+E+R&rft.aulast=Berlett&rft.aufirst=B&rft.date=1996-01-01&rft.volume=271&rft.issue=8&rft.spage=4177&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; bovine serum albumin; amino acids; protein structure ER - TY - JOUR T1 - Multiple actions of arylalkylamine arthropod toxins on the N-methyl-D-aspartate receptor AN - 17006727; 3853530 AB - The effects of the arylalkyamine arthropod toxins argiotoxin 636 and philanthotoxin 343 were studied on N-methyl-D-aspartate receptor currents in cultured rat hippocampal neurons using whole-cell recording techniques. Argiotoxin 636 and philanthotoxin 343 blocked 10 mu M N-methyl-D-aspartate (+ 10 mu M glycine) currents in a concentration-dependent fashion (steady-state IC sub(50) values, 0.9 and 56 mu M, respectively). The onset and recovery from argiotoxin 636 block occurred slowly (forward and reverse rate constants, 7.5 x 10 super(3) s super(-1) M super(-1) and 6.9 x 10 super(-3) s super(-1), respectively) whereas the philanthotoxin 343 block was more rapid (forward and reverse rate constants, 1.1 x 10 super(5) s super(-1) M super(-1) and 0.1 s super(-1)). A portion, but not all, of the block by the two toxins could be reversed by depolarization to positive holding potentials, indicating that there are voltage-dependent and non-voltage-dependent components of the block. The long-lasting argiotoxin 636 block at -60 mV occurred in a use-dependent fashion and could be substantially reduced by co-application with 10 mM Mg super(2+), providing evidence that the toxin has a channel blocking action. In contrast to the use dependence of the voltage-dependent argiotoxin 636 block, the non-voltage-dependent component of block (at + 60 mV) did not require agonist gating of the channel. The non-voltage-dependent block by argiotoxin 636 was unaffected by increasing the glycine concentration, but was reversed by increasing the N-methyl-D-aspartate concentration, suggesting that the toxin may act as a competitive antagonist at the N-methyl-D-aspartate recognition site. This mechanism was further supported by the near identity of the time constant for argiotoxin 636 block with the time constant for agonist dissociation, irrespective of whether the rapidly dissociating agonist N-methyl-D-aspartate or the more slowly dissociating agonist glutamate was used. With high concentrations of N-methyl-D-aspartate ( greater than or equal to 100 mu M), argiotoxin 636 produced a potentiation of the peak N-methyl-D-aspartate response (at +60 mV) that was accompanied by a slowing in the rate of current desensitization and an increase in the affinity for glycine. We conclude that the arylalkylamine toxins antagonize N-methyl-D-aspartate receptor currents by two distinct mechanisms: use-dependent and voltage-dependent open channel block and competitive antagonism at the N-methyl-D-aspartate recognition site. In addition, argiotoxin 636 exerts a polyamine-like facilitation of N-methyl-D-aspartate receptor currents. This facilitation occurs via both the glycine-dependent and glycine-independent mechanisms, whereby spermine is known to potentiate N-methyl-D-aspartate receptor responses. JF - Neuroscience AU - Donevan, S D AU - Rogawski, MA AD - Neur. Excitab. Sec., Epil. Res. Branch, NINDS/NIH, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 361 EP - 375 VL - 70 IS - 2 SN - 0306-4522, 0306-4522 KW - argiotoxin-636 KW - philanthotoxin 343 KW - N-methyl-D-aspartic acid receptors KW - rats KW - NMDA receptors KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - hippocampus KW - electrophysiological recording KW - X 24173:Animals KW - N3 11065:Central nervous system UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17006727?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Multiple+actions+of+arylalkylamine+arthropod+toxins+on+the+N-methyl-D-aspartate+receptor&rft.au=Donevan%2C+S+D%3BRogawski%2C+MA&rft.aulast=Donevan&rft.aufirst=S&rft.date=1996-01-01&rft.volume=70&rft.issue=2&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - hippocampus; electrophysiological recording ER - TY - JOUR T1 - Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers AN - 17006028; 3845442 AB - Monoclonal antibody MAb K1 recognizes a 40-kDa glycoprotein present on the surface of mesothelial cells, mesotheliomas, and ovarian cancers. We have used MAb K1 to isolate a 2138-bp cDNA that encodes this antigen. The cDNA has an 1884-bp open reading frame encoding a 69-kDa protein. When the cDNA was transfected into COS and NIH 3T3 cells, the antigen was found on the cell surface and could be released by treatment with phosphatidylinositol-specific phospholipase C. The 69-kDa precursor is processed to the 40-kDa form. The protein has been named mesothelin because it is made by mesothelial cells. Mesothelin may play a role in cellular adhesion. JF - Proceedings of the National Academy of Sciences, USA AU - Chang, Kai AU - Pastan, I AD - Lab. Mol. Biol., Div. Cancer Biol., Diagn. Cent., NCI/NIH, Bldg. 37, Rm. 4E16, 37 Convent Dr. MSC 4255, Bethesda, MA 20892-4255, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 136 EP - 140 VL - 93 IS - 1 SN - 0027-8424, 0027-8424 KW - amino acid sequence prediction KW - mesothelin KW - mesothelioma KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - nucleotide sequence KW - cDNA KW - mesothelium KW - ovaries carcinoma KW - man KW - N 14640:Structure & sequence KW - G 07471:General KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17006028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Molecular+cloning+of+mesothelin%2C+a+differentiation+antigen+present+on+mesothelium%2C+mesotheliomas%2C+and+ovarian+cancers&rft.au=Chang%2C+Kai%3BPastan%2C+I&rft.aulast=Chang&rft.aufirst=Kai&rft.date=1996-01-01&rft.volume=93&rft.issue=1&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - nucleotide sequence; cDNA; mesothelium; ovaries carcinoma; man ER - TY - JOUR T1 - PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1-associated neurologic disease AN - 17000572; 3833735 AB - PCR-in situ hybridization (PCR-ISH) was developed and utilized to determine the distribution of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes (PBL) from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). PCR-ISH of HTLV-1 tax DNA in PBL from patients with HAM/TSP revealed that 1 in 5,000 to 1 in 10,000 PBL contained virus. PCR-ISH was sensitive, because a positive signal was consistently demonstrated from the HTLV-1-infected cell lines HUT-102 (which contains four to six copies of HTLV-1 proviral DNA per cell) and MT-1 (which contains one to three copies of HTLV-1 proviral DNA per cell). Also, intracellular amplification by PCR-ISH significantly increased sensitivity compared with conventional ISH and was shown to be specific for HTLV-1 tax DNA. These results are in contrast to solution-phase PCR amplification in which greater than 1% of cells estimated to be infected. The discordance between these results is discussed and may indicate that more than one copy of HTLV-1 tax proviral DNA is present in an individual PBL. JF - Journal of Virology AU - Levin, M C AU - Fox, R J AU - Lehky, T AU - Walter, M AU - Fox, CH AU - Flerlage, N AU - Bamford, R AU - Jacobson, S AD - NINDS/NIH, Bldg. 10, Rm. 5B-16, 9000 Rockville Pike, Bethesda, MD 20852, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 924 EP - 933 VL - 70 IS - 2 SN - 0022-538X, 0022-538X KW - T cell leukemia virus I KW - myelopathy KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - nucleotide sequence KW - proviruses KW - detection KW - lymphocytes KW - DNA KW - epidemiology KW - F 06780:Genetics KW - W 30965:Miscellaneous, Reviews KW - V 22121:Diagnosis KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17000572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=PCR-in+situ+hybridization+detection+of+human+T-cell+lymphotropic+virus+type+1+%28HTLV-1%29+tax+proviral+DNA+in+peripheral+blood+lymphocytes+of+patients+with+HTLV-1-associated+neurologic+disease&rft.au=Levin%2C+M+C%3BFox%2C+R+J%3BLehky%2C+T%3BWalter%2C+M%3BFox%2C+CH%3BFlerlage%2C+N%3BBamford%2C+R%3BJacobson%2C+S&rft.aulast=Levin&rft.aufirst=M&rft.date=1996-01-01&rft.volume=70&rft.issue=2&rft.spage=924&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - nucleotide sequence; proviruses; detection; lymphocytes; DNA; epidemiology ER - TY - JOUR T1 - Differing T-cell requirements for recombinant retrovirus vaccines AN - 16988227; 3829222 AB - Friend murine leukemia virus is a retrovirus complex that induces rapid erythroleukemia and immunosuppression in susceptible strains of adult mice. Using this model, we directly examined the T-cell subsets required for a protective retrovirus vaccine. Paradoxically, recovery in mice immunized with a chimeric envelope containing only T-helper (T sub(H)) and B-cell epitopes was dependent on CD8 super(+) T cells as well as CD4 super(+) T cells despite the fact that the vaccine contained no CD8 super(+) cytolytic T-lymphocyte (CTL) epitopes. However, the requirement for CD8 super(+) T cells was overcome by inclusion of additional T sub(H) and B-cell epitopes in the immunizing protein. These additional epitopes primed for more rapid production of virus-neutralizing antibody which appeared to limit virus spread sufficiently to protect even in the absence of CD8 super(+) T cells. Inclusion of an immunodominant CTL epitope in the vaccine was not sufficient to overcome dependence on CD4 super(+) T cells. These data suggest that T sub(H) priming is more critical for retrovirus immunity than priming. JF - Journal of Virology AU - Hasenkrug, K J AU - Brooks, D M AU - Nishio, J AU - Chesebro, B AD - Lab. Persist. Viral Dis., Rocky Mount. Lab., NIAID/NIH, 903 S. 4th St., Hamilton, MT 59840, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 368 EP - 372 VL - 70 IS - 1 SN - 0022-538X, 0022-538X KW - Friend leukemia virus KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - immunization KW - antigenic determinants KW - vaccines KW - chimeras KW - lymphocytes T KW - immunity KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16988227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Differing+T-cell+requirements+for+recombinant+retrovirus+vaccines&rft.au=Hasenkrug%2C+K+J%3BBrooks%2C+D+M%3BNishio%2C+J%3BChesebro%2C+B&rft.aulast=Hasenkrug&rft.aufirst=K&rft.date=1996-01-01&rft.volume=70&rft.issue=1&rft.spage=368&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunization; antigenic determinants; vaccines; lymphocytes T; chimeras; immunity ER - TY - JOUR T1 - Recommendations for reducing the effects of exposure misclassification on relative risk estimates AN - 16262242; 4258672 AB - Misclassification of exposure can severely affect estimates of disease risks and even, in some extreme situations, result in misleading interpretations of exposure-disease associations. Although the effects of misclassification on risk estimates have been evaluated in several studies, the effect in cohort-type distributions with multiple exposure categories has not been addressed, and no recommendation has been made to exposure assessors for reducing these adverse effects of misclassification. Hypothetical distributions typically observed in occupational cohort and case-control studies were generated in order to evaluate the effects of nondifferential exposure misclassification on risk estimates. We identified four major determinants of exposure misclassification in this hypothetical exercise: (1) the size of the true risk; (2) the amount of misclassification; (3) the prevalence of the true distribution of exposure; and (4) the direction of misclassification, For cohort-type distributions, where the prevalence of exposure is high, extreme distortion was observed when misclassification was from the exposed categories to the unexposed category; little effect was observed when the misclassification was from the unexposed to the exposed categories. For the type of distribution seen in case-control studies, where the exposure prevalence is low, greater effects were observed when misclassification was from the unexposed category to the exposed categories, while little effect was observed when the misclassification was from the unexposed category to the exposed ones or between exposed categories. On the basis of these results and our experience in assessing exposure for epidemiological studies, we have developed recommendations to exposure assessors for reducing the adverse effects of exposure misclassification on relative risk estimates. JF - Occupational Hygiene AU - Dosemeci, M AU - Stewart, P A AD - Occupational Studies Section, National Cancer Institute, Building EPN Room 418 Rockville, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 169 EP - 176 VL - 3 IS - 1-3 SN - 1061-0251, 1061-0251 KW - misclassification KW - Health & Safety Science Abstracts; Risk Abstracts KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16262242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+Hygiene&rft.atitle=Recommendations+for+reducing+the+effects+of+exposure+misclassification+on+relative+risk+estimates&rft.au=Dosemeci%2C+M%3BStewart%2C+P+A&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1996-01-01&rft.volume=3&rft.issue=1-3&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Occupational+Hygiene&rft.issn=10610251&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity AN - 16059929; 4106936 AB - Acute exposure of mammals to the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a diverse set of toxicologic and pathologic effects. The mechanism of some of these effects has been studied extensively in vitro and correlative studies have indicated the involvement of a transcription factor known as the aryl hydrocarbon receptor (AHR). However, a definitive association of the AHR with TCDD-mediated toxicity has been difficult to establish due to the diversity of effects and the ubiquitous expression of this receptor. In an effort to distinguish AHR-mediated TCDD toxicities from those resulting from alternative pathways, we have made use of the recently described AHR-deficient mouse that was generated by locus-specific homologous recombination in embryonic stem cells. Present studies demonstrate that AHR-deficient mice are relatively unaffected by doses of TCDD (2000 mu g/kg) 10-fold higher than that found to induce severe toxic and pathologic effects in littermates expressing a functional AHR. Analyses of liver, thymus, heart, kidney, pancreas, spleen, lymph nodes, and uterus from AHR-deficient mice identified no significant TCDD-induced lesions. The resistance of AHR-deficient mice to TCDD-induced thymic atrophy appears restricted to processes involving AHR since the corticosteroid dexamethasone rapidly and efficiently induced cortical depletion in both AHR-deficient and normal littermate control mice. Taken together these results suggest that the pathological changes induced by TCDD in the liver and thymus are mediated entirely by the AHR. However, it is important to note that at high doses of TCDD, AHR-deficient mice displayed limited vasculitis and scattered single cell necrosis in their lungs and livers, respectively. The mechanism(s) responsible for these apparently receptor-independent processes remain unclear but may involve novel, alternative pathways for TCDD-induced toxicity. JF - Toxicology and Applied Pharmacology AU - Fernandez-Salguero, P M AU - Hilbert, D M AU - Rudikoff, S AU - Ward, J M AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 173 EP - 179 VL - 140 IS - 1 SN - 0041-008X, 0041-008X KW - 2,3,7,8-tetrachlorodibenzo(p)dioxin KW - mice KW - histopathology KW - TCDD KW - dexamethasone KW - Ah receptors KW - aryl hydrocarbon receptors KW - Toxicology Abstracts KW - stem cells KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16059929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Aryl-hydrocarbon+receptor-deficient+mice+are+resistant+to+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin-induced+toxicity&rft.au=Fernandez-Salguero%2C+P+M%3BHilbert%2C+D+M%3BRudikoff%2C+S%3BWard%2C+J+M%3BGonzalez%2C+F+J&rft.aulast=Fernandez-Salguero&rft.aufirst=P&rft.date=1996-01-01&rft.volume=140&rft.issue=1&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - stem cells ER - TY - JOUR T1 - Use of chitin and chitosan in lobster shell wastes for color removal from aqueous solutions AN - 15971609; 4067531 AB - Chitin and chitosan prepared from lobster shell wastes were used as adsorbents for the removal of various dyes from aqueous solutions. It was shown that high adsorption capacities were observed for reactive dyes. The adsorption equilibrium data could be well described by Langmuir equation under the concentration range investigated (50-500 mg/L). On the basis of Langmuir adsorption capacity, chitosan obtained in this work was found to be more effective compared to chitin and a commercial chitosan. JF - J. Environ. Sci. Health, Part A: Environ. Sci. Eng. Toxic Hazard. Subst. Control AU - Juang, Ruey-Shin AU - Tseng, Ru-Ling AU - Wu, Feng-Chin AU - Lin, Suen-Ji AD - Dep. Chem. Eng., Yuan-Ze Inst. Technol., Nei-Li, Taoyuan, 320, Taiwan Y1 - 1996 PY - 1996 DA - 1996 SP - 325 EP - 338 VL - A31 IS - 2 SN - 0360-1266, 0360-1266 KW - Homarus americanus KW - chitin KW - color removal KW - lobsters KW - ASFA 1: Biological Sciences & Living Resources; Water Resources Abstracts KW - biotechnology KW - Marine KW - dyes KW - SW 3040:Wastewater treatment processes KW - Q1 08625:Non-edible products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15971609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Awaterresources&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=J.+Environ.+Sci.+Health%2C+Part+A%3A+Environ.+Sci.+Eng.+Toxic+Hazard.+Subst.+Control&rft.atitle=Use+of+chitin+and+chitosan+in+lobster+shell+wastes+for+color+removal+from+aqueous+solutions&rft.au=Juang%2C+Ruey-Shin%3BTseng%2C+Ru-Ling%3BWu%2C+Feng-Chin%3BLin%2C+Suen-Ji&rft.aulast=Juang&rft.aufirst=Ruey-Shin&rft.date=1996-01-01&rft.volume=A31&rft.issue=2&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=J.+Environ.+Sci.+Health%2C+Part+A%3A+Environ.+Sci.+Eng.+Toxic+Hazard.+Subst.+Control&rft.issn=03601266&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - biotechnology; chitin; dyes; color removal; lobsters; Homarus americanus; Marine ER - TY - JOUR T1 - GAP-43 mRNA expression in the developing rat brain: Alterations following lead-acetate exposure AN - 15867755; 4025779 AB - The developmental neurotoxicity of environmental lead exposure manifests as alterations in neural functioning and perturbed axonal and dendritic development. To examine the hypothesis that such lead-induced alterations in the neural network are associated with an altered mRNA expression of a specific neural cell growth associated protein, mRNA levels of GAP-43 (growth associated protein 43) were measured in the cortex and hippocampus of developing Long-Evans hooded rats following various lead exposure paradigms. Postnatal developmental profiles (PND 6, 9, 12, 15, 20, and 25) of mRNA expression were generated following either prenatal (gestational day 13 to birth), postnatal (postnatal day 1 to postnatal day 20), or perinatal (gestational day 13 to postnatal day 20) exposure to lead acetate (0.2% in the drinking water of the dam). In control rats, GAP-43 mRNA levels displayed a distinct developmentally regulated profile of expression in both the cortex and hippocampus, characterized by an elevated level of expression within the first week of life. This peak level of expression was significantly depressed following either postnatal or perinatal exposure to lead acetate, while prenatal lead exposure produced an initial elevation of GAP-43 mRNA on postnatal day 6 followed by a sharp decline. These data suggest that lead exposure results in altered mRNA expression of a specific neural cell growth associated protein critical to the normal process of development. This perturbation in expression may play a role in the previously reported effects of lead acetate on axonal elongation during development of the nervous system and the subsequent alteration in nervous system functioning. JF - Neurotoxicology AU - Schmitt, T J AU - Zawia, N AU - Harry, G J AD - NIEHS, P.O. Box 12233, MD C1-04, Research Triangle Park, NC 27709, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 407 EP - 414 VL - 17 IS - 2 SN - 0161-813X, 0161-813X KW - rats KW - development KW - lead KW - GAP-43 protein KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - cortex KW - neurotoxicity KW - mRNA KW - neurogenesis KW - hippocampus KW - N3 11104:Mammals (except primates) KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15867755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=GAP-43+mRNA+expression+in+the+developing+rat+brain%3A+Alterations+following+lead-acetate+exposure&rft.au=Schmitt%2C+T+J%3BZawia%2C+N%3BHarry%2C+G+J&rft.aulast=Schmitt&rft.aufirst=T&rft.date=1996-01-01&rft.volume=17&rft.issue=2&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - neurotoxicity; mRNA; development; neurogenesis; cortex; hippocampus ER - TY - JOUR T1 - Induction of c-myc and c-jun proto-oncogene expression in rat L6 myoblasts by cadmium is inhibited by zinc preinduction of the metallothionein gene AN - 15866136; 4025514 AB - Certain proto-oncogenes transfer growth regulatory signals from the cell surface to the nucleus. These genes often show activation soon after cells are exposed to mitogenic stimulation but can also be activated as a nonmitogenic stress response. Cadmium (Cd) is a carcinogenic metal in humans and rodents and, though its mechanism of action is unknown, it could involve activation of such proto-oncogenes. Metallothionein (MT), a metal-inducible protein that binds Cd, can protect against many aspects of Cd toxicity, including genotoxicity and possibly carcinogenesis. Thus, the effects of Cd on expression of c-myc and c-jun in rat L6 myoblasts, and the effect of preactivation of the MT gene by Zn treatment on such oncogene expression, were studied. MT protein levels were determined by the Cd-heme assay, and MT, c-myc, and c-jun mRNA levels were measured using oligonucleotide hybridization and standardized to beta -actin levels. Cd (5 mu M CdCl sub(2), 0-30 h) stimulated both c-myc and c-jun mRNA expression. An initial peak of activation of c-myc expression occurred 2 h after initiation of Cd exposure, and levels remained elevated throughout the assessment period. Zn pretreatment markedly reduced the activation of c-myc expression by Cd compared to cells not receiving Zn pretreatment. Cd treatment increased c-jun mRNA levels by up to 3.5-fold. Again, Zn pretreatment markedly reduced Cd-induced activation of c-jun expression as minimal increases occurred with Cd exposures of less than or equal to 1 h, but otherwise the Zn pretreatment prevented activation of c-jun. The Zn pretreatment elevated MT protein levels >5-fold over control at the point of Cd exposure, but Cd exposure did not further elevate these Zn-induced MT levels. Similarly, Zn pretreatment did not result in increased relative MT mRNA levels above Cd exposure alone at various time points after Cd exposure. Therefore, Zn pretreatment, possibly by providing elevated MT protein levels at the point of Cd exposure, inhibited the Cd-induced c-myc and c-jun proto-oncogene expression. The extent of Cd-induced proto-oncogene activation thus may be limited by the presence of cellular MT. JF - Journal of Toxicology and Environmental Health AU - Abshire, M K AU - Buzard, G S AU - Shiraishi, N AU - Waalkes, M P AD - Inorganic Carcinogenesis Sect., NCI-FCRDC, Bldg. 538, Rm. 205E, Frederick, MD 21702, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 359 EP - 377 VL - 48 IS - 4 SN - 0098-4108, 0098-4108 KW - rats KW - c-myc gene KW - c-jun gene KW - cadmium KW - zinc KW - metallothionein KW - heavy metals KW - Toxicology Abstracts KW - myoblasts KW - oncogenes KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15866136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Toxicology+and+Environmental+Health&rft.atitle=Induction+of+c-myc+and+c-jun+proto-oncogene+expression+in+rat+L6+myoblasts+by+cadmium+is+inhibited+by+zinc+preinduction+of+the+metallothionein+gene&rft.au=Abshire%2C+M+K%3BBuzard%2C+G+S%3BShiraishi%2C+N%3BWaalkes%2C+M+P&rft.aulast=Abshire&rft.aufirst=M&rft.date=1996-01-01&rft.volume=48&rft.issue=4&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=Journal+of+Toxicology+and+Environmental+Health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - myoblasts; oncogenes ER - TY - JOUR T1 - Influence of dietary protein, fat, and fiber on growth, blood chemistry, and tumor incidences in Fischer 344 rats AN - 15854093; 4020296 AB - Composition of diets may influence growth, diseases, tumor rates, and responses to chemical treatment. For two years, Fischer 344 rats were fed the NIH-07 open-formula nonpurified diet ( similar to 23% protein, similar to 5% fat, and similar to 3.5% fiber) and nonpurified experimental diets (NTP-90, NTP-91, and NTP-92) containing lower protein and higher fat and fiber (14.6-15.3% protein, 7.2-8.5% fat, and 9.4-14% fiber) than the NIH-07 diet. Rats were evaluated for growth patterns, survival, hematology, serum chemistry, nephropathy, and tumor incidences. Growth patterns were similar in rats fed the experimental diets and in those fed the NIH-07 diet. However, in rats fed the experimental diets, the adult body weights were significantly (6-9%) lower and the survival at 110 weeks of age was significantly higher (15-20%) than in rats fed the NIH-07 diet. Lower protein content of experimental diets decreased the severity of nephropathy. Higher fat content of experimental diets appears to have decreased the incidence or delayed the development of leukemia and associated mortality in males. Higher fiber content of experimental diets appears to have delayed the development of mammary tumors and associated mortality in females. Higher fat and /or fiber of the experimental diets decreased the incidence of pheochromocytomas in males. The lower protein and higher fat and fiber contents of the experimental diets decreased the spontaneous tumor burden in two-year studies. These studies indicate that diets for rats in long-term studies could be modified to decrease the severity of nephropathy and to decrease delay the development of spontaneous tumors. JF - Nutrition and Cancer AU - Rao, G N AU - Edmondson, J AU - Hildebrandt, P K AU - Bruner, R H AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 Y1 - 1996 PY - 1996 DA - 1996 SP - 269 EP - 279 VL - 25 IS - 3 SN - 0163-5581, 0163-5581 KW - rats KW - fats KW - Toxicology Abstracts KW - nutrition KW - dietary fiber KW - diets KW - tumors KW - proteins KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15854093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+Cancer&rft.atitle=Influence+of+dietary+protein%2C+fat%2C+and+fiber+on+growth%2C+blood+chemistry%2C+and+tumor+incidences+in+Fischer+344+rats&rft.au=Rao%2C+G+N%3BEdmondson%2C+J%3BHildebrandt%2C+P+K%3BBruner%2C+R+H&rft.aulast=Rao&rft.aufirst=G&rft.date=1996-01-01&rft.volume=25&rft.issue=3&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+Cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - diets; nutrition; proteins; dietary fiber; tumors ER - TY - JOUR T1 - Effects of D&C yellow No. 11 ingestion on F344/N rats and B6C3F sub(1) mice AN - 15825663; 4007593 AB - D&C yellow no. 11 (CAS no. 8003-22-3) was administered in the feed at concentrations of 500-50,000 ppm to groups of F344/N rats and B6C3F, mice of each sex for 13 wk to determine the toxicity. In addition, a perinatal study was conducted to determine the effects of feeding diets containing D&C yellow no. 11 to female rats during reproduction and to their offspring. Although the estimated intake (g/kg) of D&C yellow no. 11 of mice was more than twice that of rats, the results were generally similar for both rats and mice. In both species, D&C yellow no. 11 caused no mortality, but it did reduce body weight gain slightly in both sexes of rats exposed to 17,000 and 50,000 ppm. Absolute and relative liver weights were significantly increased in all groups of rats and mice administered D&C yellow no. 11 in the feed. There was minimal to mild degeneration of the periportal hepatocytes in rats at doses of 1700 ppm and higher and in mice at 5000 ppm and above. A dose-related yellow-brown pigment was observed in hepatocytes, Kupffer cells, and biliary epithelium of the liver of both sexes of both species and in the renal tubule epithelium in both sexes of rats. In male rats, all treated groups had increased number and size of hyaline droplets in the renal tubule epithelium of the cortex and outer medulla. To determine if these renal and hepatic lesions were reversible, male rats were administered 5000 ppm dietary D&C yellow no. 11 for 70 d and then examined at 3, 14, and 28 d after the chemical was removed from the diet. Pigment persisted in the kidney and liver for as long as 28 d following removal of D&C yellow no. 11 from the diet, but hepatocellular degeneration and cytoplasmic alteration in the kidney completely resolved by d 3 and 14, respectively. In the perinatal toxicity study, body weight gain in rat dams given diets containing as much as 50,000 ppm D&C yellow no. 11 for 4 wk before mating to untreated males was similar to that of controls at the time of mating but was lower at parturition and weaning. However, fertility, gestation length, litter size, and pup birth weights were unaffected by treatment. At weaning, there was a significant dose-related decrease in pup body weights from the 5000, 17,000, and 50,000 ppm groups. At 8 wk of age, pups fed the same dosed-feed concentrations as the dams had depressed body weights in the 17,000 and 50,000 ppm treated groups. Microscopic lesions in the liver and kidney of the pups in all dose groups were similar to those described in the 13-wk study. The results of these studies indicate that compound-related effects occurred at all dietary concentrations of D&C yellow no. 11. Liver weights were increased in dosed rats and mice, minimal to mild hepatocellular degeneration was seen in rats receiving dietary concentrations of 1700 ppm and above and in mice at 5000 ppm and above, and there was an increase in the number and size of hyaline droplets in all dosed groups of male rats. Similar compound-related effects were also in all dosed rats in the perinatal toxicity study. With the exception of pigment accumulation, the treatment-related kidney and liver lesions in male rats were reversible by 14 d after chemical was withdrawn from the diet. JF - Journal of Toxicology and Environmental Health AU - Eastin, W C AU - Elwell, M R AU - Grumbein, S AU - Yuan, J-H AD - NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 197 EP - 213 VL - 48 IS - 2 SN - 0098-4108, 0098-4108 KW - rats KW - mice KW - dose-related effects KW - D & C yellow No.11 KW - quinoline yellow spirit soluble KW - 2-(2-quinolyl)-1,3-indanedione KW - Toxicology Abstracts KW - toxicity testing KW - cosmetics KW - additives KW - pharmaceuticals KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15825663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Toxicology+and+Environmental+Health&rft.atitle=Effects+of+D%26amp%3BC+yellow+No.+11+ingestion+on+F344%2FN+rats+and+B6C3F+sub%281%29+mice&rft.au=Eastin%2C+W+C%3BElwell%2C+M+R%3BGrumbein%2C+S%3BYuan%2C+J-H&rft.aulast=Eastin&rft.aufirst=W&rft.date=1996-01-01&rft.volume=48&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Journal+of+Toxicology+and+Environmental+Health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - additives; pharmaceuticals; cosmetics; toxicity testing ER - TY - JOUR T1 - Synthesis and characterization of composite nucleic acids containing 2',5'-oligoriboadenylate linked to antisense DNA AN - 15821771; 4007651 AB - Composite nucleic acids, known as 2-5A antisense chimeras, cause the 2-5A-dependent ribonuclease (RNase L) to catalyze the specific cleavage of RNA in cell free systems and in intact cells. Such 2-5A antisense chimeras are 5'-monophosphorylated, 2',5'-linked oligoadenylates covalently attached to antisense 3',5'-oligodeoxyribouncleotides by means of a linker containing two residues of 1,4-butanediol phosphate. Here we report a fully automated synthesis of 2-5A antisense chimeras on a solid support using phosphoramidite methodology with specific coupling time modifications and their subsequent purification by reverse-phase ion-pair and anion exchange HPLC. Purified 2-5A antisense chimeras were characterized by [ super(1)H]NMR and [ super(31)P]NMR, MALDIMS, and capillary gel electrophoresis. The synthetic 2',5'-linked oligoadenylate showed no phosphodiester isomerization to 3',5' during or after synthesis. In addition, we have developed facile methodologies to characterize the chimeras using digestion with various hydrolytic enzymes including snake venom phosphodiesterase I and nuclease P1. Finally, Maxam-Gilbert chemical sequencing protocols have been developed to confirm the entire sequence of these chimeric oligonucleotides. JF - Antisense and Nucleic Acid Drug Development AU - Xiao, Wei AU - Player, M R AU - Li, Guiying AU - Zhang, Weiteng AU - Lesiak, K AU - Torrence, P F AD - Section on Biomedical Chemistry, Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Building 8, Room B2A02, 9000 Rockville Pike, Bethesda, MD 20892-0805, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 247 EP - 258 VL - 6 IS - 4 SN - 1087-2906, 1087-2906 KW - 2',5'-oligoriboadenylate KW - chimeras KW - nucleotide sequence KW - ribonuclease L KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - antisense KW - N 14660:Biological properties KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15821771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Synthesis+and+characterization+of+composite+nucleic+acids+containing+2%27%2C5%27-oligoriboadenylate+linked+to+antisense+DNA&rft.au=Xiao%2C+Wei%3BPlayer%2C+M+R%3BLi%2C+Guiying%3BZhang%2C+Weiteng%3BLesiak%2C+K%3BTorrence%2C+P+F&rft.aulast=Xiao&rft.aufirst=Wei&rft.date=1996-01-01&rft.volume=6&rft.issue=4&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - antisense; chimeras ER - TY - JOUR T1 - Assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin induced sac fry mortality in lake trout (Salvelinus namaycush) from different regions of the Great Lakes AN - 15808552; 4000914 AB - Background levels of TCDD toxic equivalents(TEs) in lake trout (Salvelinus namaycush) eggs (calculated using fish-specific equivalency factors(TEFs) for polychlorinated dibenzo-p-dioxins(PCDDs), dibenzofurans(PCDFs) and biphenyls(PCBs)) were higher for two locations in Lake Ontario than Lake Superior and a hatchery(10.5-10.9 versus 0.3 and 0.05 pg TE/g egg). Despite the higher contamination of Lake Ontario eggs, sac fry mortality was uniformly low for all eggs. This is consistent with TCDD toxicity equivalence concentrations(TECs) of all eggs being less than the TCDD no observable adverse effect level(NOAEL) for Lake Superior lake trout sac fry mortality(34 pg TCDD/g egg). Eggs exposed in the laboratory to [ super(3)H]TCDD and maintained at either 8 or 8-3-8 degree C had similar sac fry mortalities. For all sources of eggs, [ super(3)H]TCDD-induced sac fry mortality was associated with blue sac disease, which was not affected by water temperature, and resulted in similar LD sub(50) values(42-72 pg[ super(3)H]TCDD/g egg). Lack of sac fry mortality in wild Lake Ontario lake trout eggs was not caused by lack of responsiveness to TCDD but rather was attributable to egg TECs being below the TCDD NOAEL for sac fry mortality. JF - Canadian journal of fisheries and aquatic sciences/Journal canadien des sciences halieutiques et aquatiques. Ottawa ON AU - Guiney, P D AU - Cook, P M AU - Casselman, J M AU - Fitzsimmons, J D AU - Simonin, HA AU - Zabel, E W AU - Peterson, R E AD - NIEHS Aquatic Biomedical Center, University Wisconsin-Milwaukee, Milwaukee, WI 53204, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 2080 EP - 2092 VL - 53 IS - 09 SN - 0706-652X, 0706-652X KW - ASFA 3: Aquatic Pollution & Environmental Quality KW - chlorine compounds KW - North America, Superior L. KW - mortality KW - North America, Ontario L. KW - Salvelinus namaycush KW - pollution effects KW - Freshwater KW - fry KW - fish eggs KW - Q5 08504:Effects on organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15808552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Canadian+journal+of+fisheries+and+aquatic+sciences%2FJournal+canadien+des+sciences+halieutiques+et+aquatiques.+Ottawa+ON&rft.atitle=Assessment+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+induced+sac+fry+mortality+in+lake+trout+%28Salvelinus+namaycush%29+from+different+regions+of+the+Great+Lakes&rft.au=Guiney%2C+P+D%3BCook%2C+P+M%3BCasselman%2C+J+M%3BFitzsimmons%2C+J+D%3BSimonin%2C+HA%3BZabel%2C+E+W%3BPeterson%2C+R+E&rft.aulast=Guiney&rft.aufirst=P&rft.date=1996-01-01&rft.volume=53&rft.issue=09&rft.spage=2080&rft.isbn=&rft.btitle=&rft.title=Canadian+journal+of+fisheries+and+aquatic+sciences%2FJournal+canadien+des+sciences+halieutiques+et+aquatiques.+Ottawa+ON&rft.issn=0706652X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - chlorine compounds; mortality; pollution effects; fish eggs; fry; Salvelinus namaycush; North America, Superior L.; North America, Ontario L.; Freshwater ER - TY - JOUR T1 - Mechanisms of adhesion by oral bacteria AN - 15792606; 3989564 AB - Adherence to a surface is a key element for colonization of the human oral cavity by the more than 500 bacterial taxa recorded from oral samples. Three surfaces are available: teeth, epithelial mucosa, and the nascent surface created as each new bacterial cell binds to existing dental plaque. Oral bacteria exhibit specificity for their respective colonization sites. Such specificity is directed by adhesin-receptor cognate pairs on genetically distinct cells. Colonization is successful when adherent cells grow and metabolically participate in the oral bacterial community. The potential roles of adherence-relevant molecules are discussed in the context of the dynamic nature of the oral econiche. JF - Annual Review of Microbiology AU - Whittaker, C J AU - Klier, C M AU - Kolenbrander, P E AD - Laboratory of Microbial Ecology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 513 EP - 552 VL - 50 SN - 0066-4227, 0066-4227 KW - Microbiology Abstracts B: Bacteriology KW - Prevotella KW - Streptococcus KW - Colonization KW - adherence KW - oral cavity KW - Porphyromonas KW - receptors KW - Actinomyces KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15792606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+Review+of+Microbiology&rft.atitle=Mechanisms+of+adhesion+by+oral+bacteria&rft.au=Whittaker%2C+C+J%3BKlier%2C+C+M%3BKolenbrander%2C+P+E&rft.aulast=Whittaker&rft.aufirst=C&rft.date=1996-01-01&rft.volume=50&rft.issue=&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Microbiology&rft.issn=00664227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus; Actinomyces; Prevotella; Porphyromonas; oral cavity; adherence; Colonization; receptors ER - TY - JOUR T1 - Retroviral transduction of CD34-enriched hematopoietic progenitor cells under serum-free conditions AN - 15788381; 3991198 AB - The use of defined or serum-free culture conditions during retroviral transduction of hematopoietic cells would be desirable for standardization and safety reasons, as well as potentially allowing greater expansion of progenitor cells. Retroviral vector supernatants were concentrated and purified via tangential flow filtration polyethylene glycol (PEG)-precipitation, and ultracentrifugation, allowing serum-free transductions at standard multiplicities of infection (moi). Protein content of transductions using these concentrated vectors was 5-6 logs lower than in standard transductions. Transduction efficiencies of these concentrated vector preparations added back to serum-free or serum-containing media were equivalent to standard retroviral supernatant transductions of CD34-enriched progenitors. Absolute progenitor (CFU-C) numbers at the end of transduction were higher in serum-free + concentrated virus transductions, as opposed to transductions in standard vector supernatants containing fetal calf serum. JF - Human Gene Therapy AU - Sekhar, M AU - Kotani, H AU - Doren, S AU - Agarwal, R AU - McGarrity, G AU - Dunbar, CE AD - Hematol. Branch, NHLBI, Bldg. 10, 7C103, Natl. Institutes Health, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1996/01// PY - 1996 DA - Jan 1996 SP - 33 EP - 38 VL - 7 IS - 1 SN - 1043-0342, 1043-0342 KW - CD34 antigen KW - hematopoiesis KW - man KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - cell culture KW - retrovirus KW - stem cells KW - transduction KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15788381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Retroviral+transduction+of+CD34-enriched+hematopoietic+progenitor+cells+under+serum-free+conditions&rft.au=Sekhar%2C+M%3BKotani%2C+H%3BDoren%2C+S%3BAgarwal%2C+R%3BMcGarrity%2C+G%3BDunbar%2C+CE&rft.aulast=Sekhar&rft.aufirst=M&rft.date=1996-01-01&rft.volume=7&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - cell culture; retrovirus; stem cells; transduction ER - TY - JOUR T1 - Simulation study of vertical jumping from different starting postures AN - 15771083; 246144 AB - This paper addresses the question of whether maximal vertical jump height depends on initial jumping posture. A direct dynamics computer simulation approach was used to avoid subject preference and practice effects. The human body was modeled as four rigid segments connected by ideal hinge joints, with movement constrained to the sagittal plane and driven by three single-joint torque actuators. Maximal height jumps were found for each of 125 different initial postures. For each initial posture, the optimal pattern of joint torque actuator onset times was found using a multidimensional simplex algorithm searching for maximal jump height. The model results revealed that maximal jump height is relatively insensitive to initial posture, but that the pattern of joint torque onset times necessary to effect these optimal heights varies considerably. Model kinematics indicate that the variability in onset times is necessary to allow the body to re-orient itself in different ways during the downward countermovement phase. This variable re-orientation strategy is followed by a more stereotyped upward thrust phase that is similar despite the differences in starting postures. Model center of mass, joint and segmental kinematics show many features found in experimental studies of jumping, despite the exclusive use of single joint torque actuators. However, a proximal-to-distal sequence of joint coordination was not found, possibly because of the omission of antagonist and bi-articular muscles. The results suggest that similar vertical jump heights should be obtained using a wide range of initial starting positions. JF - Journal of Biomechanics AU - Selbie, WScott AU - Caldwell, Graham E AD - NIDCD, Bethesda, MD, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1137 EP - 1146 PB - PERGAMON PRESS LTD, OXFORD, (ENGL) VL - 29 IS - 9 SN - 0021-9290, 0021-9290 KW - Actuators KW - Computer simulation KW - Joints (anatomy) KW - Jumping KW - Muscle KW - Postures KW - Single joint torque actuators KW - Torque KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Kinematics KW - Mathematical models KW - Optimization KW - W4 461.2:BIOLOGICAL MATERIALS KW - W4 921.5:OPTIMIZATION TECHNIQUES KW - W4 461.3:BIOMECHANICS KW - W4 732.2:CONTROL INSTRUMENTATION KW - W4 723.5:COMPUTER APPLICATIONS KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15771083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomechanics&rft.atitle=Simulation+study+of+vertical+jumping+from+different+starting+postures&rft.au=Selbie%2C+WScott%3BCaldwell%2C+Graham+E&rft.aulast=Selbie&rft.aufirst=WScott&rft.date=1996-01-01&rft.volume=29&rft.issue=9&rft.spage=1137&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomechanics&rft.issn=00219290&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Kinematics; Mathematical models; Optimization ER - TY - JOUR T1 - Developmentally regulated synthesis of an unusually small, basic peptide by Coxiella burnetii AN - 15770345; 3982539 AB - Coxiella burnetii undergoes a poorly defined developmental cycle within phagolysosomes of eukaryotic host cells. Two distinct developmental forms are part of this cycle: a small-cell variant (SCV) and large-cell variant (LCV). Ultrastructurally, the SCV is distinguished from the LCV by its smaller size and condensed chromatin. At a molecular level, little is known about morphogenesis in C. burnetii, and no proteins specific to the SCV have been identified. Preparative isoelectric focusing was conducted to purify basic proteins possibly involved in SCV chromatin structure. A predominant protein of low M sub(r) was present in the most basic fraction, eluting with a pH of approx. 11. Degenerate deoxyoligonucleotides corresponding to the N-terminal sequence of this protein were used to recover a cosmid clone from a C. burnetii genomic library. Nucleotide sequencing of insert DNA revealed an open reading frame designated scvA (small-cell-variant protein A) with coding potential for a 30 amino acid protein (ScvA) with a predicted M sub(r) of 3610. ScvA is 46% arginine plus 46% glutamine with a predicted pl of 12.6 SDS-PAGE and silver staining of lysates of SCV and LCV purified by caesium chloride-equilibrium density centrifugation revealed a number of proteins unique to each cell type. Immunoblot analysis with ScvA antiserum demonstrated the presence of ScvA only in the SCV. By immunoelectron microscopy, ScvA antiserum labelled only the SCV, with the label concentrated on the condensed nucleoid. In addition, ScvA bound double-stranded DNA in gel mobility-shift assays. A 66% reduction in the mean number of gold particles per Coxiella cell was observed at 12 h post-infection when compared with the starting inoculum. Collectively, these data suggest that synthesis of ScvA is developmentally regulated, and that the protein may serve a structural or functional role as an integral component of the SCV chromatin. Moreover, degradation of this protein may be a necessary prerequisite for morphogenesis from SCV to LCV. JF - Molecular Microbiology AU - Heinzen, R A AU - Howe, D AU - Mallavia, L P AU - Rockey, D D AU - Hackstadt, T AD - Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT USA. Y1 - 1996 PY - 1996 DA - 1996 SP - 9 EP - 19 VL - 22 IS - 1 SN - 0950-382X, 0950-382X KW - ScvA protein KW - scvA gene KW - Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - DNA-binding protein KW - gel electrophoresis KW - nucleotide sequence KW - Coxiella burnetii KW - chromatin KW - pH KW - N 14640:Structure & sequence KW - G 07321:GENERAL KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15770345?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Developmentally+regulated+synthesis+of+an+unusually+small%2C+basic+peptide+by+Coxiella+burnetii&rft.au=Heinzen%2C+R+A%3BHowe%2C+D%3BMallavia%2C+L+P%3BRockey%2C+D+D%3BHackstadt%2C+T&rft.aulast=Heinzen&rft.aufirst=R&rft.date=1996-01-01&rft.volume=22&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Coxiella burnetii; chromatin; pH; gel electrophoresis; DNA-binding protein; nucleotide sequence ER - TY - JOUR T1 - Construction of a chromosome map for the phage group II Staphylococcus aureus Ps55 AN - 15768212; 3985700 AB - The genome size and a partial physical and genetic map have been defined for the phage group II Staphylococcus aureus Ps55. The genome size was estimated to be 2,771 kb by pulsed-field gel electrophoresis (PFGE) using the restriction enzymes SmaI, CspI, and SgrAI. The Ps55 chromosome map was constructed by transduction of auxotrophic and cryptic transposon insertions, with known genetic and physical locations in S. aureus NCTC 8325, into the Ps55 background. PFGE and DNA hybridization analysis were used to detect the location of the transposon in Ps55. Ps55 restriction fragments were then ordered on the basis of genetic conservation between the two strains. Cloned DNA probes containing the lactose operon (lac) and genes encoding staphylococcal protein A (spa), gamma hemolysin (hlg), and coagulase (coa) were also located on the map by PFGE and hybridization analysis. This methodology enabled a direct comparison of chromosomal organization between NCTC 8325 and Ps55 strains. The chromosome size, gene order, and some of the restriction sites are conserved between the two phage group strains. JF - Journal of Bacteriology AU - Bannantine, J P AU - Pattee, P A AD - Host-Parasite Interactions Sect., Lab. Intracellular Parasites, Rocky Mountain Labs., NIAID, NIH, 903 South 4th St., Hamilton, MT 59840, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 6842 EP - 6848 VL - 178 IS - 23 SN - 0021-9193, 0021-9193 KW - phage 80a KW - phage 80^a KW - phage 80 alpha KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - transposons KW - gene mapping KW - DNA KW - transduction KW - Staphylococcus aureus KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15768212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Construction+of+a+chromosome+map+for+the+phage+group+II+Staphylococcus+aureus+Ps55&rft.au=Bannantine%2C+J+P%3BPattee%2C+P+A&rft.aulast=Bannantine&rft.aufirst=J&rft.date=1996-01-01&rft.volume=178&rft.issue=23&rft.spage=6842&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Staphylococcus aureus; transduction; DNA; transposons; gene mapping ER - TY - JOUR T1 - Emergence of protease inhibitor resistance mutations in human immunodeficiency virus type 1 isolates from patients and rapid screening procedure for their detection AN - 15760961; 3979387 AB - Patient human immunodeficiency virus type 1 (HIV-1) isolates that are resistant to protease inhibitors may contain amino acid substitutions L10I/V, M46L/I, G48V, L63P, V82A/F/T, I84V, and L90M in the protease gene. Substitutions at positions 82 and/or 90 occur in variants that display high levels of resistance to certain protease inhibitors. Nucleotide substitutions at these two sites also lead to the loss of two HindII restriction enzyme digestion sites, and these changes make possible a rapid procedure for the detection of drug-resistant variants in patients on protease inhibitor therapy. This procedure was used to detect the emergence of mutated viruses at various times after the initiation of therapy with the HIV-1 protease inhibitor indinavir. The method includes viral RNA isolation from plasma and reverse transcription PCR amplification of the protease gene with fluorescence-tagged primers. The PCR product is digested with HindII, the cleavage products are separated on a urea-acrylamide gel in a DNA sequencer, and the extent of cleavage is automatically analyzed with commercially available software. In viruses from 34 blood samples from four patients, mutations leading to an amino acid change at residue 82 appeared as early as 6 weeks after the start of therapy and persisted throughout the course of the study period (48 weeks). Mutations leading to double substitutions at residues 82 and 90 were seen at a lower frequency and appeared later than the change at position 82. The changes detected by restriction enzyme cleavage were confirmed by DNA sequencing of the cloned protease genes by reverse transcription PCR amplification of viral RNA from isolates in plasma. In addition to the changes at positions 82 and 90, we have identified M46L/I, G48V, and I54V substitutions in isolates derived from indinavir-treated patients. HindII analysis of uncloned, PCR-amplified DNA offers a rapid screening procedure for the detection of virus isolates containing mutations at amino acid residues 82 and 90 in the HIV-1 protease gene. By using other restriction enzymes, the same method can be used to detect additional protease drug-resistant variants and is generally applicable for the detection of mutations. JF - Antimicrobial Agents & Chemotherapy AU - Vasudevachari, M B AU - Zhang, Y-M AU - Imamichi, H AU - Imamichi, T AU - Falloon, J AU - Salzman, N P AD - Laboratory of Molecular Retrovirology, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 2535 EP - 2541 VL - 40 IS - 11 SN - 0066-4804, 0066-4804 KW - proteinase inhibitors KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - antiviral agents KW - human immunodeficiency virus 1 KW - mutation KW - drug resistance KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01064:Microbial resistance KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15760961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Emergence+of+protease+inhibitor+resistance+mutations+in+human+immunodeficiency+virus+type+1+isolates+from+patients+and+rapid+screening+procedure+for+their+detection&rft.au=Vasudevachari%2C+M+B%3BZhang%2C+Y-M%3BImamichi%2C+H%3BImamichi%2C+T%3BFalloon%2C+J%3BSalzman%2C+N+P&rft.aulast=Vasudevachari&rft.aufirst=M&rft.date=1996-01-01&rft.volume=40&rft.issue=11&rft.spage=2535&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1; antiviral agents; drug resistance; mutation ER - TY - JOUR T1 - Analysis of chimeric UmuC proteins: Identification of regions in Salmonella typhimurium UmuC important for mutagenic activity AN - 15755912; 3980113 AB - Unlike Escherichia coli, the closely related bacterium Salmonella typhimurium is relatively unresponsive to the mutagenic effects of DNA-damaging agents. Previous experiments have suggested that these phenotypic differences might result from reduced activity of the S. typhimurium UmuC protein. To investigate this possibility, we have taken advantage of the high degree of homology between the UmuC proteins of E. coli and S. typhimurium and have constructed a series of plasmid-encoded chimeric proteins. The possibility that the phenotypic differences might be due to differential expression of the respective UmuC proteins was eliminated by constructing chimeric proteins that retained the first 25 N-terminal amino acids of either of the UmuC proteins (and presumably the same translational signals), but substituting the remaining 397 C-terminal amino acids with the corresponding segments from the reciprocal operon. Constructs expressing mostly E. coli UmuC were moderately proficient for mutagenesis whereas those expressing mostly S. typhimurium UmuC exhibited much lower frequencies of mutation, indicating that the activity of the UmuC protein of S. typhimurium is indeed curtailed. The regions responsible for this phenotype were more precisely localized by introducing smaller segments of the S. typhimurium UmuC protein into the UmuC protein of E. coli. While some regions could be interchanged with few or no phenotypic effects, substitution of residues 212-395 and 396-422 of E. coli UmuC with those from S. typhimurium resulted in reduced mutability, while substitution of residues 26-59 caused a dramatic loss of activity. We suggest, therefore, that the primary cause for the poor mutability of S. typhimurium can be attributed to mutations located within residues 26-59 of the S. typhimurium UmuC protein. JF - Molecular and General Genetics AU - Koch, W H AU - Kopsidas, G AU - Meffle, B AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-2725, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 121 EP - 129 VL - 251 IS - 2 SN - 0026-8925, 0026-8925 KW - UmuC protein KW - SOS mutagenesis KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - DNA damage KW - Escherichia coli KW - Salmonella typhimurium KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15755912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+General+Genetics&rft.atitle=Analysis+of+chimeric+UmuC+proteins%3A+Identification+of+regions+in+Salmonella+typhimurium+UmuC+important+for+mutagenic+activity&rft.au=Koch%2C+W+H%3BKopsidas%2C+G%3BMeffle%2C+B%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Koch&rft.aufirst=W&rft.date=1996-01-01&rft.volume=251&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Molecular+and+General+Genetics&rft.issn=00268925&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella typhimurium; Escherichia coli; DNA damage ER - TY - JOUR T1 - Phylogeographic subspecies recognition in leopards (Panthera pardus): Molecular genetic variation AN - 15752195; 3972535 AB - The incorporation of precise definitions for taxonomic units into wildlife legislation has necessitated the reevaluation of the taxonomy of endangered and threatened species. We used the subspecies recognition criteria proposed by Avise and Ball (1990) and O'Brien and Mayr (1991) to examine the infraspecific taxonomy of the leopard, Panthera pardus, a geographically widespread species with 27 currently recognized trinomial designations. Samples from named subspecies revealed appreciable genetic diversity using three molecular methods: allozymes, mitochondrial DNA restriction sites, and feline-specific minisatellites. Continental populations and subspecies from Africa and Asia possessed the highest amount of molecular genetic variation, whereas relatively lower amounts of diversity were present in island populations. Molecular data were analyzed using three phylogenetic methods (distance-matrix, maximum parsimony, and maximum likelihood) to resolve genetic differentiation below the species level. The combined results revealed phylogenetic distinction of six geographically isolated groups of leopards: (1) African, (2) central Asian, (3) Indian, (4) Sri Lankan, (5) Javan, and (6) east Asian. Based on the combined molecular analyses and supporting morphological data (Miththapala 1992), we recommend that subspecific leopard taxonomy be revised to comprise eight subspecies: (1) P. p. pardus, Africa; (2) P. p. saxicolor, central Asia; (3) P. p. fusca, Indian subcontinent; (4) P. p. kotiya, Sri Lanka; (5) P. p. melas, Java; (6) P. p. orientalis, Amur; (7) P. p. japonensis, northern China; and (8) P. p. delacouri, southern China. In most cases, designated subspecies conform to historic geological barriers that would have facilitated allopatric genetic divergence. JF - Conservation Biology AU - Miththapala, S AU - Seidensticker, J AU - O'Brien, S J AD - Biological Carcinogenesis and Development Program, Program Resources Incorporated, National Cancer Institute--Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1115 EP - 1132 VL - 10 IS - 4 SN - 0888-8892, 0888-8892 KW - minisatellites KW - Genetics Abstracts; Ecology Abstracts KW - genetic diversity KW - taxonomy KW - Panthera pardus KW - geographical variations KW - mitochondrial DNA KW - G 07270:Ecological genetics KW - D 04672:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15752195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Conservation+Biology&rft.atitle=Phylogeographic+subspecies+recognition+in+leopards+%28Panthera+pardus%29%3A+Molecular+genetic+variation&rft.au=Miththapala%2C+S%3BSeidensticker%2C+J%3BO%27Brien%2C+S+J&rft.aulast=Miththapala&rft.aufirst=S&rft.date=1996-01-01&rft.volume=10&rft.issue=4&rft.spage=1115&rft.isbn=&rft.btitle=&rft.title=Conservation+Biology&rft.issn=08888892&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Panthera pardus; genetic diversity; geographical variations; taxonomy; mitochondrial DNA ER - TY - JOUR T1 - Carcinogenicity of glycidol in F344 rats and B6C3F sub(1) mice AN - 15751660; 3972778 AB - Glycidol, a simple aliphatic epoxide, was administered by gavage in water to groups of male and female F344/N rats and B6C3F sub(1) mice. Rats received 0, 37.5 or 75 mg/kg and mice received 0, 25 or 50 mg/kg daily, 5 days per week for 2 years. Exposure to glycidol was associated with dose-related increases in the incidences of neoplasms in numerous tissues in both rats and mice. Survival of rats that received glycidol was markedly reduced compared to the control because of the early induction of neoplastic disease. In male rats, mesothelioma arising in the tunica vaginalis and frequently metastasizing to the peritoneum were considered the major cause of early death. Early deaths in female rats were associated with mammary gland neoplasms. Survival of female mice that received 50 mg/kg was lower than the control after week 101 due primarily to euthanasia of moribund animals with mammary gland neoplasms. Survival of male mice and female mice that received 25 mg/kg was comparable to the control. In mice, exposure to glycidol was associated with increased incidences of neoplasms of the harderian gland in males and females, the forestomach in males and the mammary gland in females. JF - Journal of Applied Toxicology AU - Irwin, R D AU - Eustis, S L AU - Stefanski, S AU - Haseman, J K AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 201 EP - 209 PB - JOHN WILEY & SONS, LTD. VL - 16 IS - 3 SN - 0260-437X, 0260-437X KW - glycidol KW - rats KW - mice KW - Toxicology Abstracts KW - carcinogenicity KW - neoplasia KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15751660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Toxicology&rft.atitle=Carcinogenicity+of+glycidol+in+F344+rats+and+B6C3F+sub%281%29+mice&rft.au=Irwin%2C+R+D%3BEustis%2C+S+L%3BStefanski%2C+S%3BHaseman%2C+J+K&rft.aulast=Irwin&rft.aufirst=R&rft.date=1996-01-01&rft.volume=16&rft.issue=3&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Toxicology&rft.issn=0260437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - carcinogenicity; neoplasia ER - TY - JOUR T1 - Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity AN - 15751549; 3979741 AB - Dihydropyrimidine dehydrogenase (DPD) deficiency constitutes an inborn error in pyrimidine metabolism associated with thymine-uraciluria in pediatric patients and an increased risk of toxicity in cancer patients receiving 5-fluorouracil (5-FU) treatment. The molecular basis for DPD deficiency in a British family having a cancer patient that exhibited grade IV toxicity 10 d after 5-FU treatment was analyzed. A 165-bp deletion spanning a complete exon of the DPYD gene was found in some members of the pedigree having low DPD catalytic activity. Direct sequencing of lymphocyte DNA from these subjects revealed the presence of a G to A point mutation at the 5'-splicing site consensus sequence (GT to AT) that leads to skipping of the entire exon preceding the mutation during pre-RNA transcription and processing. A PCR-based diagnostic method was developed to determine that the mutation is found in Caucasian and Asian populations. This mutation was also detected in a Dutch patient with thymine-uraciluria and completely lacking DPD activity. A genotyping test for the G to A splicing point mutation could be useful in predicting cancer patients prone to toxicity upon administration of potentially toxic 5-FU and for genetic screening of heterozygous carriers and homozygous deficient subjects. JF - Journal of Clinical Investigation AU - Wei, X AU - McLeod, H L AU - McMurrough, J AU - Gonzalez, F J AU - Fernandez-Salguero, P AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Building 37, Room 3E24. National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 610 EP - 615 VL - 98 IS - 3 SN - 0021-9738, 0021-9738 KW - dihydropyrimidine dehydrogenase (NADP@u+) KW - fluorouracil KW - DPYD gene KW - dihydropyrimidine dehydrogenase (NADP super(+)) KW - Genetics Abstracts; Toxicology Abstracts KW - metabolic disorders KW - lymphocytes KW - point mutation KW - man KW - G 07490:Errors of metabolism KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15751549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Investigation&rft.atitle=Molecular+basis+of+the+human+dihydropyrimidine+dehydrogenase+deficiency+and+5-fluorouracil+toxicity&rft.au=Wei%2C+X%3BMcLeod%2C+H+L%3BMcMurrough%2C+J%3BGonzalez%2C+F+J%3BFernandez-Salguero%2C+P&rft.aulast=Wei&rft.aufirst=X&rft.date=1996-01-01&rft.volume=98&rft.issue=3&rft.spage=610&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - man; metabolic disorders; lymphocytes; point mutation ER - TY - JOUR T1 - Differential activation of ERK, JNK/SAPK and P38/CSBP/RK MAP kinase family members during the cellular response to arsenite AN - 15750520; 3979744 AB - Exposure of cells to either proliferative or stressful stimuli elicits a complex response involving one or more distinct phosphorylation cascades culminating in the activation of multiple members of the mitogen-activated protein kinase (MAPK) family, including extracellular signal regulated kinase (ERK), stress-activated c-Jun N-terminal kinase (JNK/SAPK), and p38/RK/CSBP protein kinase. While the pathways transducing mitogenic stimuli to these kinases are relatively well established, the early signalling events leading to their activation in response to stress are poorly understood. In the present study, we examined ERK, JNK/SAPK, and p38 activation in cells treated with the sulfhydryl-reactive agent sodium arsenite. Arsenite treatment potently activated both JNK/SAPK and p38, but only moderately activated ERK. Activation of all three kinases was prevented by the free radical scavenger N-Acetyl-L-cysteine, suggesting that an oxidative signal initiates the responses. Suramin, a growth factor receptor poison, significantly inhibited ERK activation by arsenite, but had little effect on either JNK/SAPK or p38 activity. In contrast, suramin inhibited the activation of all three kinases by short wavelength ultraviolet light (UVC) irradiation. In addition, comparative studies with wild-type PC12 cells and PC12 cells expressing a dominant negative Ras mutant allele indicated that arsenite activates ERK primarily through a Ras-dependent pathway(s), while activation of both JNK/SAPK and p38 occurs through a mechanism relatively independent of Ras. These results suggest that JNK/SAPK and p38 may share common upstream regulators distinct from those involved in ERK activation. JF - Free Radical Biology & Medicine AU - Liu, Y AU - Guyton, K Z AU - Gorospe, M AU - Xu, Q AU - Lee, J C AU - Holbrook, N J AD - Gerontology Research Center, Gene Expression and Aging Section, National Institute on Aging, 4940 Eastern Avenue, Baltimore, MD 21224, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 771 EP - 781 VL - 21 IS - 6 SN - 0891-5849, 0891-5849 KW - ERK protein KW - JNK protein KW - mitogen-activated protein kinase KW - arsenite KW - Ras protein KW - PCR cells KW - SAPK protein KW - MAP kinase KW - Toxicology Abstracts KW - free radicals KW - oxidative stress KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15750520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+Radical+Biology+%26+Medicine&rft.atitle=Differential+activation+of+ERK%2C+JNK%2FSAPK+and+P38%2FCSBP%2FRK+MAP+kinase+family+members+during+the+cellular+response+to+arsenite&rft.au=Liu%2C+Y%3BGuyton%2C+K+Z%3BGorospe%2C+M%3BXu%2C+Q%3BLee%2C+J+C%3BHolbrook%2C+N+J&rft.aulast=Liu&rft.aufirst=Y&rft.date=1996-01-01&rft.volume=21&rft.issue=6&rft.spage=771&rft.isbn=&rft.btitle=&rft.title=Free+Radical+Biology+%26+Medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - oxidative stress; free radicals ER - TY - JOUR T1 - Engineering antibody Fv fragments for cancer detection and therapy: Disulfide-stabilized Fv fragments AN - 15750495; 3972578 AB - Disulfide-stabilized Fv fragments of antibodies (dsFv) are molecules in which the V sub(H)-V sub(L) heterodimer is stabilized by an interchain disulfide bond engineered between structurally conserved framework positions distant from complementarity-determining regions (CDRs). This method of stabilization is applicable for the stabilization of many antibody Fvs and has also been applied to a T-cell receptor Fv. A summary of the design strategy, and the construction and production of various dsFvs and dsFv-fusion proteins is presented. Included in the discussion are the biochemical features of dsFvs in comparison with scFvs, the effect of disulfide stabilization on Fv binding and activity, and various applications of dsFvs and dsFv-immunotoxins for tumor imaging and the treatment of solid tumors in animal models. JF - Nature Biotechnology AU - Reiter, Y AU - Brinkmann, U AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1239 EP - 1243 VL - 14 IS - 10 SN - 1087-0156, 1087-0156 KW - Fv KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - reviews KW - protein engineering KW - antibodies KW - fusion protein KW - immunotherapy KW - cancer KW - immunotoxins KW - F 06818:Cancer immunotherapy KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15750495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Engineering+antibody+Fv+fragments+for+cancer+detection+and+therapy%3A+Disulfide-stabilized+Fv+fragments&rft.au=Reiter%2C+Y%3BBrinkmann%2C+U%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1996-01-01&rft.volume=14&rft.issue=10&rft.spage=1239&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; protein engineering; fusion protein; antibodies; immunotherapy; cancer; immunotoxins ER - TY - JOUR T1 - Carcinogenicity of 2',3'-dideoxycytidine in mice AN - 15749337; 3979751 AB - 2',3'-dideoxycytidine (ddC) is a synthetic pyrimidine nucleoside analogue approved for treatment of HIV-positive patients. Previous studies indicated that ddC has the potential to cause thymic lymphoma in C57BL/ 6 x C3H F sub(1) (hereafter called B6C3F sub(1)) mice. In this study, we evaluated the carcinogenic potential of ddC in two different mouse models. B6C3F sub(1) hybrid mice carry ecotropic endogenous proviral sequences that may be activated to cause lymphoma, whereas NIH Swiss mice lack proviral sequences that can be expressed. The mice were treated with ddC by gavage at 500 and 1000 mg/kg/day for up to 6 months (human dose, 2.25 mg/day) and evaluated for toxicity, plasma levels of ddC, and pathological changes. Lymphocyte cell markers from the thymic lymphomas were assessed by immunophenotyping. Expression of p53 protein was evaluated using immunohistochemical staining. Treatment-related thymic lymphomas were present in both mouse models with a higher incidence in NIH Swiss than in B6C3F sub(1) mice. The lymphomas were more prevalent in females than in males of both mouse models. Most mice with thymic lymphoma died during the course of the study. In addition to the thymus, lymphoma was often present in lymph nodes, spleen, and other organs. Lymphomas arose more frequently in mice that lack endogenous ecotropic retroviral sequences and thus were not due to activation of endogenous provirus. During the third month of the study, a few NIH Swiss mice that died had granulosa cell tumors of the ovary. Treatment-related but reversible thymic atrophy was observed in both mouse models. There was a very high correlation between the internal dose of ddC and the incidence of thymic lymphoma in both mouse models. Most of the lymphocytes from control thymuses and ddC-induced lymphomas were positive for Thy-1.2 (pan-T), heat stable antigen, and CD4 and CD8 markers, with no marked differences in the lymphocyte markers of the tumors between sexes or dose groups. p53 protein was detected in only 20% (23/115) of the ddC-induced lymphomas with mostly minimal expression in scattered cells. Because ddC induced lymphomas in two different mouse models, the potential carcinogenic risk should be considered in long-term treatment of HIV-positive patients, especially children and adolescent patients treated with ddC. JF - Cancer Research AU - Rao, G N AU - Collins, B J AU - Giles, H D AU - Heath, JE AU - Foley, J F AU - May, R D AU - Buckley, LA AD - National Institute of Environmental Health Sciences, MD B3-08, P. O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 4666 EP - 4672 VL - 56 IS - 20 SN - 0008-5472, 0008-5472 KW - zalcitabine KW - mice KW - p53 protein KW - Virology & AIDS Abstracts; Toxicology Abstracts KW - carcinogenicity KW - antiviral agents KW - human immunodeficiency virus KW - risk assessment KW - lymphoma KW - X 24117:Biochemistry KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15749337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Carcinogenicity+of+2%27%2C3%27-dideoxycytidine+in+mice&rft.au=Rao%2C+G+N%3BCollins%2C+B+J%3BGiles%2C+H+D%3BHeath%2C+JE%3BFoley%2C+J+F%3BMay%2C+R+D%3BBuckley%2C+LA&rft.aulast=Rao&rft.aufirst=G&rft.date=1996-01-01&rft.volume=56&rft.issue=20&rft.spage=4666&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus; carcinogenicity; lymphoma; risk assessment; antiviral agents ER - TY - JOUR T1 - Myopathy and spontaneous Pasteurella pneumotropica-induced abscess formation in an HIV-1 transgenic mouse model AN - 15747570; 3976692 AB - In an effort to augment human immunodeficiency virus type 1 (HIV-1) gene expression in transgenic mice, an infectious proviral DNA clone was modified by deleting the two NF Kappa B binding sites and some adjacent upstream LTR sequences and replacing them with the core enhancer of Moloney murine leukemia virus (MLV). Two independent lines of MLV/HIV transgenic mice were established that expressed HIV-1-specific RNA in lymphoid tissue, striated skeletal muscle, and the eye lens. Heterozygous animals from each transgenic line spontaneously developed an inflammatory disease of the eye associated with the production of copious amounts of purulent lacrimal secretions beginning at 2 weeks of age. Periorbital abscess formation became grossly apparent by 2 months of age and Pasteurella pneumotropica was cultured from the harderian glands and conjunctival surfaces of many of the MLV/HIV animals but not their nontransgenic, cohabiting littermates. This gram-negative commensal bacterium has been previously associated with a similar disease phenotype in immunocompromised (e.g., nude mice) rodent colonies. MLV/HIV mice developed normally until 15 weeks of age, when weight loss and wasting occurred, culminating in premature death (as earlier as 6 months of age). The cachexia was associated with an initially focal and subsequently progressive myopathy, coinciding with age-related increases of HIV gene expression in muscle. JF - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology AU - Dickie, P AU - Mounts, P AU - Purcell, D AU - Miller, G AU - Fredrickson, T AU - Chang, L-J AU - Martin, MA AD - Bldg. 4, Rm. 315, NIAID, NIH, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 101 EP - 116 VL - 13 IS - 2 SN - 1077-9450, 1077-9450 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - myopathy KW - human immunodeficiency virus 1 KW - Pasteurella pneumotropica KW - animal models KW - transgenic mice KW - abscesses KW - J 02862:Infection KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15747570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Acquired+Immune+Deficiency+Syndromes+and+Human+Retrovirology&rft.atitle=Myopathy+and+spontaneous+Pasteurella+pneumotropica-induced+abscess+formation+in+an+HIV-1+transgenic+mouse+model&rft.au=Dickie%2C+P%3BMounts%2C+P%3BPurcell%2C+D%3BMiller%2C+G%3BFredrickson%2C+T%3BChang%2C+L-J%3BMartin%2C+MA&rft.aulast=Dickie&rft.aufirst=P&rft.date=1996-01-01&rft.volume=13&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Journal+of+Acquired+Immune+Deficiency+Syndromes+and+Human+Retrovirology&rft.issn=10779450&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1; Pasteurella pneumotropica; abscesses; transgenic mice; animal models; myopathy ER - TY - JOUR T1 - Insertional inactivation of an intrageneric coaggregation-relevant adhesin locus from Streptococcus gordonii DL1 (Challis) AN - 15739556; 3972444 AB - Transposon Tn916 was used to insertionally inactivate a coaggregation-relevant locus of Streptococcus gordonii DL1 (Challis). One mutant (F11) was isolated that lost the ability to coaggregate with the streptococcal partners of DL1 but retained the ability to coaggregate with partners belonging to other genera. A probe specific for the region flanking the Tn916 insertion was used to isolate a locus-specific fragment from a chromosomal lambda library. Southern analysis of the resulting phagemids revealed that a 0.5-kb EcoRI fragment hybridized with the F11 probe. Cloning of the 0.5-kb EcoRI fragment into the E. coli-streptococcal insertion vector p Omega yielded pCW4, which was used to insertionally inactivate the putative coaggregation-relevant gene in DL1. Insertion mutants showed altered coaggregation with streptococci but retained wild-type coaggregation properties with other genera of bacteria. Comparison of immunoblots of cell surface proteins showed a 100-kDa protein in DL1 which was not detected in the Tn916 and pCW4 insertion mutants. These results indicate that the 0.5-kb EcoRI fragment is part of an adhesin-relevant locus that is involved in the production of a 100-kDa protein at the cell surface. JF - Infection and Immunity AU - Whittaker, C J AU - Clemans, D L AU - Kolenbrander, P E AD - National Institutes of Health, Building 30, Room 310, 30 Convent Dr. MSC 4350, Bethesda, MD 20892-4350, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 4137 EP - 4142 VL - 64 IS - 10 SN - 0019-9567, 0019-9567 KW - transposon Tn916 KW - adhesins KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - cell surface KW - Streptococcus gordonii KW - Escherichia coli KW - gene expression KW - N 14684:Expression of cloned genes KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15739556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Insertional+inactivation+of+an+intrageneric+coaggregation-relevant+adhesin+locus+from+Streptococcus+gordonii+DL1+%28Challis%29&rft.au=Whittaker%2C+C+J%3BClemans%2C+D+L%3BKolenbrander%2C+P+E&rft.aulast=Whittaker&rft.aufirst=C&rft.date=1996-01-01&rft.volume=64&rft.issue=10&rft.spage=4137&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus gordonii; Escherichia coli; gene expression; cell surface ER - TY - JOUR T1 - Antisense oligodeoxynucleotides selectively suppress expression of the mutant alpha 2(I) collagen allele in type IV osteogenesis imperfecta fibroblasts: A molecular approach to therapeutics of dominant negative disorders AN - 15701493; 3968843 AB - We are investigating the use of antisense oligodeoxynucleotides to selectively suppress expression of the mutant type I collagen allele in osteogenesis imperfecta (OI). In this report, we target a human collagen mutation in its natural cellular context. We used cultured fibroblasts from a case of type IV OI, in which the mutant alpha 2(I) allele produces mRNA with exon 16 deleted due to a point mutation in the splice donor site. Lipid-mediated transfection was used to deliver antisense, sense and missense phosphorothioates targeted to both the abnormal mRNA exon 15/17 junction and the nuclear level point mutation. Significant suppression of the mutant protein chain and mRNA was achieved with antisense oligonucleotide to both mRNA and nuclear levels. Mutant protein was suppressed to 44-47% and mutant alpha 2(I) mRNA to 37-43% of their levels in control cells, indicating decreased mRNA as the basis for suppression. Selectivity of mutant allele suppression was better with an mRNA target: suppression was sequence specific and normal mRNA was expressed at 79% of its level in untreated cells. With a nuclear target, significant suppression of mutant mRNA occurred not only with antisense and sense, but also with missense oligonucleotide, which suppressed mutant mRNA to 60% of its level in untreated cells. We also investigated the time course of suppression of protein and mRNA in response to a 4 h transfection of anti-sense oligonucleotide. From 24-72 h after transfection, mutant protein was suppressed to similar to 50% of its untreated level and suppression of mutant message was significantly greater than that of normal message. The suppression achieved in these studies is insufficient for clinical intervention, but our results provide support for further development of antisense therapy as an approach to the treatment of dominant negative disorders. JF - Journal of Clinical Investigation AU - Wang, Qin AU - Marini, J C AD - Heritable Disorders Branch, NICHD, Bldg. 10, Rm. 9S242, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 448 EP - 454 VL - 97 IS - 2 SN - 0021-9738, 0021-9738 KW - collagen KW - oligodeoxynucleotides KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts; Calcium & Calcified Tissue Abstracts KW - antisense KW - osteogenesis imperfecta KW - gene therapy KW - man KW - point mutation KW - T 200005:Molecular biology and genetics KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense KW - T 20051:Osteopathies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15701493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Investigation&rft.atitle=Antisense+oligodeoxynucleotides+selectively+suppress+expression+of+the+mutant+alpha+2%28I%29+collagen+allele+in+type+IV+osteogenesis+imperfecta+fibroblasts%3A+A+molecular+approach+to+therapeutics+of+dominant+negative+disorders&rft.au=Wang%2C+Qin%3BMarini%2C+J+C&rft.aulast=Wang&rft.aufirst=Qin&rft.date=1996-01-01&rft.volume=97&rft.issue=2&rft.spage=448&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; osteogenesis imperfecta; antisense; point mutation; man ER - TY - JOUR T1 - Synthesis, characterization, and immunologic properties of detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins AN - 15697618; 3970459 AB - Nontypeable Haemophilus influenzae (NTHi) is an important cause of otitis media in children and of pneumonitis in adults with depressed resistance. Lipooligosaccharide (LOS) is a major surface antigen of NTHi and elicits bactericidal and opsonic antibodies. We prepared detoxified LOS (dLOS) protein conjugates from NTHi for use as experimental vaccines. LOS from NTHi 9274 was treated with anhydrous hydrazine and had its toxicity reduced to clinically acceptable levels. dLOS was bound to tetanus toxoid (TT) or high-molecular-weight proteins (HMPs) from NTHi through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratio of the dLOS to protein carriers ranged from 26:1 to 50:1. The antigenicity of the conjugates was similar to that of the LOS alone as determined by double immunodiffusion. Subcutaneous or intramuscular injection of the conjugates elicited a 28- to 486-fold rise in the level of immunoglobulin G antibodies in mice to the homologous LOS after two or three injections and a 169- to 243-fold rise in the level of immunoglobulin G antibodies in rabbits after two injections. The immunogenicity of the conjugates in mice and rabbits was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced LOS antibodies induced complement-mediated bactericidal activity against the homologous strain 9274 and prototype strain 3189. These results indicate that a detoxified LOS-protein conjugate is a candidate vaccine for otitis media and pneumonitis caused by NTHi. JF - Infection and Immunity AU - Gu, X-X AU - Tsai, C-M AU - Ueyama, T AU - Barenkamp, S J AU - Robbins, J B AU - Lim, D J AD - NIDCD, NIH, 5 Research Ct., Rm. 2A31, Rockville, MD 20850, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 4047 EP - 4053 VL - 64 IS - 10 SN - 0019-9567, 0019-9567 KW - lipopolysaccharides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - vaccines KW - Haemophilus influenzae KW - immunogenicity KW - immunoconjugates KW - W3 33365:Vaccines (other) KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15697618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Synthesis%2C+characterization%2C+and+immunologic+properties+of+detoxified+lipooligosaccharide+from+nontypeable+Haemophilus+influenzae+conjugated+to+proteins&rft.au=Gu%2C+X-X%3BTsai%2C+C-M%3BUeyama%2C+T%3BBarenkamp%2C+S+J%3BRobbins%2C+J+B%3BLim%2C+D+J&rft.aulast=Gu&rft.aufirst=X-X&rft.date=1996-01-01&rft.volume=64&rft.issue=10&rft.spage=4047&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vaccines; immunogenicity; immunoconjugates; Haemophilus influenzae ER - TY - JOUR T1 - Recovery of reproductive function in rats treated with the aromatase inhibitor fadrozole AN - 15694993; 3966760 AB - The aromatase inhibitor, fadrozole hydrochloride (CGS 16949A), was developed for the treatment of breast cancer, and has not been available for pediatric use because of the lack of information about potential reproductive toxicology. To determine the effect of fadrozole on subsequent fertility and reproductive performance in rats, peripubertal male and female Sprague-Dawley rats (10/group) were given fadrozole by oral gavage once a day for 60 consecutive days (age 21 through 80 d) at a dose of 0, 1200, or 6000 mu g/kg/d (dose range in women with breast cancer: 60 to 240 mu g/kg/d). Following a 30-d recovery period (days 81 through 111 of age), cohabitation with untreated rats of the opposite sex was accomplished for 30 d or until positive evidence of mating was obtained (daily vaginal smears). The nonfadrozole-treated males used for cohabitation were proven fertile breeders; the females were virgin with proven 4-d estrous cycles. The duration of pregnancy, number, sex, condition, and body weight of pups were determined. Pregnant rats were weighed on gestational days 7, 14, and 20. There was a profound decrease in the number of estrous cycles at both dose levels of fadrozole compared to the control (P < 0.001). During the 30-d recovery period, estrous cycles were reestablished within a few days in the treated rats and the number and length of estrous cycles were not statistically different between fadrozole-treated and control rats. The gestational body weights of fadrozole-treated and untreated females did not differ significantly. There were no statistically significant differences in the number of matings/number of pairings, gestational length, mean live pups/litter, % pups born alive/litter, and % male pups/litter in the three groups (vehicle-, low-, and high-dose fadrozole-treated females, cohabited with untreated males and fadrozole-treated males, cohabited with untreated females). Thus, young male and female rats treated for 60 d with large doses of fadrozole had no detectable adverse effect on subsequent reproductive function. JF - Reproductive Toxicology AU - Nunez, S B AU - Blye, R P AU - Thomas, P M AU - Reel, J R AU - Barnes, K M AU - Malley, J D AU - Cutler, GB Jr AD - NIH/NICHD/DEB, Bldg. 10, Rm. 10N262, 10 Center Dr., MSC 1862, Bethesda, MD 20892-1862, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 373 EP - 377 VL - 10 IS - 5 SN - 0890-6238, 0890-6238 KW - fadrozole KW - aromatase KW - rats KW - Toxicology Abstracts KW - fertility KW - reproduction KW - X 24112:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15694993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Recovery+of+reproductive+function+in+rats+treated+with+the+aromatase+inhibitor+fadrozole&rft.au=Nunez%2C+S+B%3BBlye%2C+R+P%3BThomas%2C+P+M%3BReel%2C+J+R%3BBarnes%2C+K+M%3BMalley%2C+J+D%3BCutler%2C+GB+Jr&rft.aulast=Nunez&rft.aufirst=S&rft.date=1996-01-01&rft.volume=10&rft.issue=5&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - reproduction; fertility ER - TY - JOUR T1 - Lead-induced alterations of glial fibrillary acidic protein (GFAP) in the developing rat brain AN - 15687916; 3963127 AB - The developing nervous system is preferentially vulnerable to lead exposure with alterations in neuronal and glial cells of the brain. The present study examined early lead-induced alterations in the developing astrocyte population by examination of the developmentally regulated astrocyte specific protein, glial fibrillary acidic protein (GFAP). A developmental profile (Postnatal Day (PND) 6, 9, 12, 15, 20, and 25) for GFAP mRNA was generated for the cortex and hippocampus of developing Long-Evans hooded male rats under various lead exposure conditions: (1) prenatal (Gestational Day 13 to birth), (2) postnatal (Postnatal Day 1 to Postnatal Day 20), or (3) perinatal (Gestational Day 13 to Postnatal Day 20) exposure to lead acetate (0.2% in the drinking water of the dam). Control GFAP mRNA levels displayed a developmentally regulated profile of expression. In the cortex this was characterized by a transient elevation in peak level between PND 9 and PND 15 followed by a decline to within adult levels by PND 25. Under all lead acetate exposure conditions, the cortex showed an increase in the peak level of expression and extended the time of elevation of GFAP mRNA until PND 20. Levels of GFAP were elevated at PND 60 but not as early as PND 28. In the control hippocampus, levels of GFAP mRNA gradually increased until PND 20 followed by a sharp decline at PND 25. Postnatal and perinatal lead exposure followed a similar pattern; however, levels declined earlier at PND 20. Following prenatal lead exposure, levels of GFAP mRNA showed an earlier peak at PND 12 and a decrease as early as PND 15. By PND 60 protein level for GFAP was elevated in the postnatal lead exposure group only. As demonstrated by GFAP immunoreactivity, these lead-induced elevations were not associated with astrocyte hypertrophy. Following a physical injury in the cortex, astrocyte reactivity was similar between lead-exposed and control rats. These data suggest an alteration in the timing of astrocyte differentiation and maturation in the brain following developmental lead exposure. JF - Toxicology and Applied Pharmacology AU - Harry, G J AU - Schmitt, T J AU - Gong, Zhaolong AU - Brown, H AU - Zawia, N AU - Evans, H L AD - NIEHS, P. O. Box 12233, MD C1-04, Research Triangle Park, NC 27709, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 84 EP - 93 VL - 139 IS - 1 SN - 0041-008X, 0041-008X KW - lead KW - glial fibrillary acidic protein KW - rats KW - heavy metals KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - neurogenesis KW - neurotoxicity KW - astrocytes KW - brain KW - N3 11104:Mammals (except primates) KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15687916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Lead-induced+alterations+of+glial+fibrillary+acidic+protein+%28GFAP%29+in+the+developing+rat+brain&rft.au=Harry%2C+G+J%3BSchmitt%2C+T+J%3BGong%2C+Zhaolong%3BBrown%2C+H%3BZawia%2C+N%3BEvans%2C+H+L&rft.aulast=Harry&rft.aufirst=G&rft.date=1996-01-01&rft.volume=139&rft.issue=1&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - neurogenesis; brain; astrocytes; neurotoxicity ER - TY - JOUR T1 - Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS clinical trials group virology laboratories AN - 15686252; 3965977 AB - A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log sub(10) RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons. JF - Journal of Clinical Microbiology AU - Yen-Lieberman, B AU - Brambilla, D AU - Jackson, B AU - Bremer, J AU - Coombs, R AU - Cronin, M AU - Herman, S AU - Katzenstein, D AU - Reichelderfer, P S AD - NIH/NIAID/DAIDS, 6003 Executive Blvd., Rockville, MD 20776, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 2695 EP - 2701 VL - 34 IS - 11 SN - 0095-1137, 0095-1137 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - plasma levels KW - human immunodeficiency virus 1 KW - quantitation KW - RNA KW - quality control KW - laboratories KW - N 14510:Occurrence, isolation & assay KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01073:Quality control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15686252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Evaluation+of+a+quality+assurance+program+for+quantitation+of+human+immunodeficiency+virus+type+1+RNA+in+plasma+by+the+AIDS+clinical+trials+group+virology+laboratories&rft.au=Yen-Lieberman%2C+B%3BBrambilla%2C+D%3BJackson%2C+B%3BBremer%2C+J%3BCoombs%2C+R%3BCronin%2C+M%3BHerman%2C+S%3BKatzenstein%2C+D%3BReichelderfer%2C+P+S&rft.aulast=Yen-Lieberman&rft.aufirst=B&rft.date=1996-01-01&rft.volume=34&rft.issue=11&rft.spage=2695&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1; RNA; quantitation; plasma levels; laboratories; quality control ER - TY - JOUR T1 - Analysis of human immunodeficiency virus type 1 mRNA splicing patterns during disease progression in peripheral blood mononuclear cells from infected individuals AN - 15683971; 3965972 AB - HIV-1 produces more than 20 mRNAs encoding the viral proteins. We have used a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) approach to determine HIV-1 transcriptional patterns during the course of viral infection in unstimulated peripheral blood mononuclear cells (PBMCs) from different patients. Several sets of PCR primers, used in parallel reactions, allowed the amplification and specific detection of almost all individual HIV-1 transcripts. We investigated the transcriptional profile in two individuals during primary acute and early chronic infection. In these individuals, HIV-1 mRNA expression was elevated at the first time points examined and declined over time. In addition, we performed a detailed study of HIV-1 expression in several individuals over a minimum of 7 years following seroconversion. We found that long-term asymptomatic individuals had undetectable or low levels of the three classes of HIV-1 transcripts (unspliced, singly spliced, and multiply spliced). Individuals who demonstrated disease progression showed either a general increase in the amount of expression of all transcripts or elevated levels of unspliced transcripts in late-stage disease. The splicing pattern in each patient was conserved over the years and differed among the different individuals. No evidence of major changes in the splicing pattern was found during disease progression within the same individual. Thus, HIV-1 transcriptional patterns are viral strain specific rather than disease stage specific. These results indicate that high-level expression of any class of HIV-1 transcripts is associated with clinical progression. Our analysis also demonstrates the importance of using more than one set of primers to evaluate HIV-1 RNA expression, since virus in patient PBMCs showed sequence heterogeneity in conserved regions. JF - AIDS Research and Human Retroviruses AU - Saltarelli, MJ AU - Hadziyannis, E AU - Hart, CE AU - Harrison, J V AU - Felber, B K AU - Spira, T J AU - Pavlakis, G N AD - ABL-Basic Res. Prog., Bldg. 539, Rm. 121, NCI-FCRDC P.O. Box B, Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1443 EP - 1456 VL - 12 IS - 15 SN - 0889-2229, 0889-2229 KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - human immunodeficiency virus 1 KW - pathogenesis KW - mRNA KW - splicing KW - monocytes KW - transcription KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01114:Viruses KW - N 14554:mRNA processing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15683971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Research+and+Human+Retroviruses&rft.atitle=Analysis+of+human+immunodeficiency+virus+type+1+mRNA+splicing+patterns+during+disease+progression+in+peripheral+blood+mononuclear+cells+from+infected+individuals&rft.au=Saltarelli%2C+MJ%3BHadziyannis%2C+E%3BHart%2C+CE%3BHarrison%2C+J+V%3BFelber%2C+B+K%3BSpira%2C+T+J%3BPavlakis%2C+G+N&rft.aulast=Saltarelli&rft.aufirst=MJ&rft.date=1996-01-01&rft.volume=12&rft.issue=15&rft.spage=1443&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1; mRNA; splicing; pathogenesis; monocytes; transcription ER - TY - JOUR T1 - In utero and lactational exposure of female Holtzman rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin: Modulation of the estrogen signal AN - 15676584; 3962479 AB - The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) induces severe reproductive defects in male rats when exposure occurs in utero and during lactation. Yet there is currently a paucity of information regarding the effects of this exposure paradigm in females. In the current study, we examine the effects of TCDD during fetal and perinatal development on the estrogen-signaling system in peripubertal female rats. Pregnant Holtzman rats were given 1 mu g/kg TCDD or vehicle control by gavage on gestational Day 15. Body weights were reduced, though not significantly, on postnatal Day 21. While ovarian and uterine wet weights were not increased by TCDD exposure, the percentage of body weight attributed to the ovary was increased significantly. Through use of ribonuclease protection and gel-shift assays, exposed females were compared with nonexposed counterparts for estrogen receptor (ER) mRNA and DNA-binding activity in the following tissues: hypothalamus, pituitary (mRNA only), uterus, and ovary. ER mRNA levels increased in the hypothalamus, uterus, and ovary, and decreased in the pituitary. The results of the DNA-binding assays paralleled the mRNA results in the uterus, while DNA-binding activity was decreased in the hypothalamus and was unchanged in ovarian protein extracts. Circulating concentrations of estrogen were significantly lower in TCDD-exposed rats than in controls. These data suggest that the decrease in serum estrogen may be a cause of the alterations in ER mRNA; the changes in ER DNA-binding activity may indicate alterations in either translation or posttranslational receptor processing. Overall, this study shows that TCDD may act systemically in this model, and these effects should not necessarily be characterized as antiestrogenic. JF - Biology of Reproduction AU - Chaffin, CL AU - Peterson, R E AU - Hutz, R J AD - Dep. Biol. Sci., NIEHS Biomed. Sci. Cent., Univ. Wisconsin, 3209 N. Maryland Ave., Milwaukee, WI 53211, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 62 EP - 67 VL - 55 IS - 1 SN - 0006-3363, 0006-3363 KW - 2,3,7,8-tetrachlorodibenzo(p)dioxin KW - TCDD KW - estrogen receptors KW - rats KW - Toxicology Abstracts KW - lactation KW - intrauterine exposure KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15676584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+Reproduction&rft.atitle=In+utero+and+lactational+exposure+of+female+Holtzman+rats+to+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin%3A+Modulation+of+the+estrogen+signal&rft.au=Chaffin%2C+CL%3BPeterson%2C+R+E%3BHutz%2C+R+J&rft.aulast=Chaffin&rft.aufirst=CL&rft.date=1996-01-01&rft.volume=55&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Biology+of+Reproduction&rft.issn=00063363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - intrauterine exposure; lactation ER - TY - JOUR T1 - In vitro selection and molecular characterization of human immunodeficiency virus type 1 with reduced sensitivity to 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) AN - 15673763; 3961200 AB - 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA) is an acyclic nucleotide with potent in vitro activity against human immunodeficiency virus type 1 (HIV-1). The present study was undertaken to determine whether HIV-1 resistance to PMEA could be generated by in vitro selection and if so, to determine which mutations in reverse transcriptase (RT) were responsible. HIV-1LAI was serially passaged for 10 months in the presence of increasing concentrations of PMEA up to a maximum of 40 mu M. After 40 passages, the 50% inhibitory concentration (IC50) of PMEA had increased almost 7-fold from 4.45 to 30.5 mu M. Some cross-resistance to 2',3'-dideoxycytidine (ddC, zalcitabine), 2',3'-dideoxyinosine (ddI, didanosine), and 3'-thiacytidine (3TC, lamivudine) was also observed, but no cross-reactive resistance to 3'-azido-3'-thymidine (AZT, zidovudine). Sequencing of the RT encoding region of each of eight pol clones from resistant isolates revealed a Lys-65 arrow right Arg (K65R) substitution. HIV with the K65R mutation inserted by site-directed mutagenesis also had decreased sensitivity to PMEA in H9 cells and a similar cross-resistance profile. Thus, HIV can develop decreased sensitivity to PMEA after long-term in vitro exposure and this change is associated with a K65R substitution. Additional studies will be needed to determine whether a similar mutation in HIV RT develops in patients receiving PMEA or its orally bioavailable prodrug adefovir dipivoxil (bis-POM PMEA). JF - Antiviral Research AU - Foli, A AU - Sogocio, K M AU - Anderson, B AU - Kavlick, M AU - Saville, M W AU - Wainberg, MA AU - Gu, Zhengxian AU - Cherrington, J M AU - Mitsuya, H AU - Yarchoan, R AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892-1906 USA Y1 - 1996 PY - 1996 DA - 1996 SP - 91 EP - 98 PB - ELSEVIER SCIENCE IRELAND LTD. VL - 32 IS - 2 SN - 0166-3542, 0166-3542 KW - RNA-directed DNA polymerase KW - reverse transcriptase KW - 9-[2-(phosphonomethoxy)ethyl]adenine KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - antiviral agents KW - human immunodeficiency virus 1 KW - resistant mutant KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01064:Microbial resistance KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15673763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+Research&rft.atitle=In+vitro+selection+and+molecular+characterization+of+human+immunodeficiency+virus+type+1+with+reduced+sensitivity+to+9-%5B2-%28phosphonomethoxy%29ethyl%5Dadenine+%28PMEA%29&rft.au=Foli%2C+A%3BSogocio%2C+K+M%3BAnderson%2C+B%3BKavlick%2C+M%3BSaville%2C+M+W%3BWainberg%2C+MA%3BGu%2C+Zhengxian%3BCherrington%2C+J+M%3BMitsuya%2C+H%3BYarchoan%2C+R&rft.aulast=Foli&rft.aufirst=A&rft.date=1996-01-01&rft.volume=32&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1; resistant mutant; antiviral agents ER - TY - JOUR T1 - The P1 ParA protein and its ATPase activity play a direct role in the segregation of plasmid copies to daughter cells AN - 15671547; 3960159 AB - The P1 ParA protein is an ATPase that recognizes the parA promoter region where it acts to autoregulate the P1 parA-parB operon. The ParB protein is essential for plasmid partition and recognizes the cis-acting partition site parS. The regulatory role of ParA is also essential because a controlled level of ParB protein is critical for partition. However, we show that this regulatory activity is not the only role for ParA in partition. Efficient partition can be achieved without autoregulation as long as Par protein levels are kept within a range of low values. The properties of ParA mutants in these conditions showed that ParA is essential for some critical step in the partition process that is independent of par operon regulation. The putative nucleotide-binding site for the ParA ATPase was identified and disrupted by mutation. The resulting mutant was substantially defective for autoregulation and completely inactive for partition in a system in which the need for autoregulation is abolished. Thus, the ParA nucleotide-binding site appears to be necessary both for the repressor activity of ParA and for some essential step in the partition process itself. We propose that the nucleotide-bound form of the enzyme adopts a configuration that favours binding to the operator, but that the ATPase activity of ParA is required for some energetic step in partition of the plasmid copies to daughter cells. JF - Molecular Microbiology AU - Davis, MA AU - Radnedge, L AU - Martin, KA AU - Hayes, F AU - Youngren, B AU - Austin, S J AD - ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1029 EP - 1036 VL - 21 IS - 5 SN - 0950-382X, 0950-382X KW - ParA protein KW - adenosinetriphosphatase KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - bacteria KW - plasmids KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15671547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=The+P1+ParA+protein+and+its+ATPase+activity+play+a+direct+role+in+the+segregation+of+plasmid+copies+to+daughter+cells&rft.au=Davis%2C+MA%3BRadnedge%2C+L%3BMartin%2C+KA%3BHayes%2C+F%3BYoungren%2C+B%3BAustin%2C+S+J&rft.aulast=Davis&rft.aufirst=MA&rft.date=1996-01-01&rft.volume=21&rft.issue=5&rft.spage=1029&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - bacteria; plasmids ER - TY - JOUR T1 - Clinical benefits and immunopathological correlates of intravenous immune globulin in the treatment of inflammatory myopathies AN - 15670611; 3957568 AB - High-dose intravenous immune globulin (IVIG) is emerging as a promising therapy for patients with inflammatory myopathies who have become unresponsive to, or cannot tolerate, conventional therapies. In a double-blind, placebo-controlled study, using objective criteria for improvement, IVIG demonstrated moderate to dramatic improvement in 75% of the patients with dermatomyositis. Preliminary results from a controlled study in inclusion-body myositis show that IVIG may also exert a mild benefit, but only in a small number of patients and in certain muscle groups. In some patients with polymyositis, IVIG is reported to be of benefit but controlled studies have not yet been completed. Immunocytochemical, immunological and in vitro studies on the patients' repeated muscle biopsies and follow-up sera showed that IVIG exert its action in inflammatory myopathies by: (i) inhibiting myotoxic cytokines, such as TNF- alpha and IL-1; (ii) blockade of Fc receptors on endomysial macrophages interfering with Fc receptor-mediated phagocytosis; and (iii) inhibiting the uptake of C3 and intercepting the formation and deposition of membranolytic attack complex on the endomysial capillaries. JF - Clinical and Experimental Immunology AU - Dalakas, M C AD - NINDS, NIH, Bldg. 10, Rm. 4N248, 10 Cent. Dr., MSC 1382, Bethesda, MD 20892-1382, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 55 EP - 60 VL - 104 IS - S1 SN - 0009-9104, 0009-9104 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - polymyositis KW - inclusion bodies KW - immunoglobulins KW - reviews KW - dermatomyositis KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews KW - F 06886:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15670611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+Experimental+Immunology&rft.atitle=Clinical+benefits+and+immunopathological+correlates+of+intravenous+immune+globulin+in+the+treatment+of+inflammatory+myopathies&rft.au=Dalakas%2C+M+C&rft.aulast=Dalakas&rft.aufirst=M&rft.date=1996-01-01&rft.volume=104&rft.issue=S1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Clinical+and+Experimental+Immunology&rft.issn=00099104&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Intravenous Immune Globulin: Mechanisms of Action and Model Disease State. N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - inclusion bodies; polymyositis; reviews; immunoglobulins; dermatomyositis ER - TY - JOUR T1 - A thumb subdomain mutant of the large fragment of Escherichia coli DNA polymerase I with reduced DNA binding affinity, processivity, and frameshift fidelity AN - 15666757; 3957801 AB - In Klenow fragment DNA polymerase, a flexible 50-amino acid subdomain at the tip of the thumb which includes two alpha helices has been suggested to interact with the duplex template-primer. The present study investigates the properties of Klenow polymerase containing a 24-amino acid deletion (residues 590-613) that removes a portion of the tip of the thumb. The mutant polymerase has relatively normal dNTP binding and catalytic rate. However, its DNA binding affinity is reduced by more than 100-fold relative to the intact polymerase and its ability to conduct processive synthesis is also reduced. Although the mutant polymerase has relatively normal base substitution fidelity, it has strongly reduced frameshift fidelity, being especially error-prone for single nucleotide addition errors in homopolymeric runs. The addition error rate increases as the length of the reiterated sequence increases, indicative of errors initiated by template-primer strand slippage. These observations suggest a role for the tip of the thumb of Klenow polymerase in determining DNA binding, processivity and frameshift fidelity, perhaps by tracking the minor groove of the duplex DNA. The results are discussed in light of remarkably similar observations with T7 DNA polymerase in the presence or absence of thioredoxin, an accessory subunit that affects these same properties. JF - Journal of Biological Chemistry AU - Minnick, D T AU - Astatke, M AU - Joyce, C M AU - Kunkel, T A AD - Lab. Mol. Genet., NIEHS, P. O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 24954 EP - 24961 VL - 271 IS - 40 SN - 0021-9258, 0021-9258 KW - DNA-directed DNA polymerase I KW - thioredoxin KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA KW - Escherichia coli KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15666757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=A+thumb+subdomain+mutant+of+the+large+fragment+of+Escherichia+coli+DNA+polymerase+I+with+reduced+DNA+binding+affinity%2C+processivity%2C+and+frameshift+fidelity&rft.au=Minnick%2C+D+T%3BAstatke%2C+M%3BJoyce%2C+C+M%3BKunkel%2C+T+A&rft.aulast=Minnick&rft.aufirst=D&rft.date=1996-01-01&rft.volume=271&rft.issue=40&rft.spage=24954&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA ER - TY - JOUR T1 - Health behavior correlates of hazardous drinking by Army personnel AN - 15666238; 3951401 AB - The current investigation determined that military personnel who drink heavily differ from those who drink moderately in the practice of nine behaviors often associated with unhealthy lifestyle. In particular, excessive drinkers were found to smoke more, drive dangerously more frequently, and consume saturated fats more often. The project further found that the relationship of excessive drinking to these activities is mediated by age, marital status, and race, although not by gender or rank. Implications of the findings for prevention and treatment are suggested. JF - Military Medicine AU - Fertig, J B AU - Allen, J P AD - NIAAA, Willco Build., Suite 505, 6000 Executive Blvd. MSC 7003, Bethesda, MD 20892-7003, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 352 EP - 355 VL - 161 IS - 6 SN - 0026-4075, 0026-4075 KW - army KW - alcoholism KW - fats KW - substance abuse KW - Health & Safety Science Abstracts KW - nutrition KW - smoking KW - occupational health KW - military KW - H SM10.20:ALCOHOLISM KW - H SI12.8.4:DRUGS AND ALCOHOL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15666238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+Medicine&rft.atitle=Health+behavior+correlates+of+hazardous+drinking+by+Army+personnel&rft.au=Fertig%2C+J+B%3BAllen%2C+J+P&rft.aulast=Fertig&rft.aufirst=J&rft.date=1996-01-01&rft.volume=161&rft.issue=6&rft.spage=352&rft.isbn=&rft.btitle=&rft.title=Military+Medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - military; smoking; nutrition; occupational health ER - TY - JOUR T1 - Recovery of infectious respiratory syncytial virus expressing an additional, foreign gene AN - 15665636; 3954182 AB - A previous report described the recovery from cDNA of infectious recombinant respiratory syncytial virus (RSV) strain A2 (P. L. Collins, M. G. Hill, E. Camargo, H. Grosfeld, R. M. Chanock, and B. R. Murphy, Proc. Natl. Acad. Sci. USA, 92:11563-11567, 1995). Here, the system was used to construct recombinant RSV containing an additional gene encoding chloramphenicol acetyltransferase (CAT). The CAT coding sequence was flanked by RSV-specific gene-start and gene-end motifs, the transcription signals for the viral RNA-dependent RNA polymerase. The RSV-CAT chimeric transcription cassette was inserted into the region between the G and F genes of the complete cDNA-encoded positive-sense RSV antigenome, and infectious CAT-expressing recombinant RSV was recovered. Transcription of the inserted gene into the predicted subgenomic polyadenylated mRNA was demonstrated by Northern (RNA) blot hybridization analysis, and the encoded protein was detected by enzyme assay and by radioimmunoprecipitation. Quantitation of intracellular CAT, SH, G, and F mRNAs showed that the CAT mRNA was efficiently expressed and that the levels of the G and F mRNAs (which represent the genes on either side of the inserted CAT gene) were comparable to those expressed by a wild-type recombinant RSV. Consistent with this finding, the CAT-containing and wild-type viruses were very similar with regard to the levels of synthesis of the major viral proteins. Each of 25 RSV isolates obtained by plaque purification following eight serial passages expressed CAT, showing that the foreign gene was faithfully maintained in functional form. Analysis by reverse transcription and PCR did not reveal evidence of deletion of the foreign sequence. This finding demonstrated that the RSV genome can accept and maintain an increase in length of 762 nucleotides of foreign sequence and can be engineered to encode an additional, 11th mRNA. The presence of the additional gene resulted in a 10% decrease in plaque diameter and was associated with delay in virus growth and 20-fold decrease in virus yield in vitro. Thus, introduction of an additional gene into the RSV genome might represent a method of attenuation. The ability to express foreign genes by recombinant RSV has implications for basic studies as well as for the development of live recombinant vaccines. JF - Journal of Virology AU - Bukreyev, A AU - Camargo, E AU - Collins, P L AD - LID, NIAID, 7 Cent. Dr. MSC 0720, Bethesda, MD 20892-0720, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 6634 EP - 6641 VL - 70 IS - 10 SN - 0022-538X, 0022-538X KW - CAT gene KW - chloramphenicol O-acetyltransferase KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - respiratory syncytial virus KW - gene expression KW - V 22050:Viral genetics including virus reactivation KW - G 07313:Viruses KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15665636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Recovery+of+infectious+respiratory+syncytial+virus+expressing+an+additional%2C+foreign+gene&rft.au=Bukreyev%2C+A%3BCamargo%2C+E%3BCollins%2C+P+L&rft.aulast=Bukreyev&rft.aufirst=A&rft.date=1996-01-01&rft.volume=70&rft.issue=10&rft.spage=6634&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene expression; respiratory syncytial virus ER - TY - JOUR T1 - Identification of sigma super(s)-dependent genes associated with the stationary-phase acid-resistance phenotype of Shigella flexneri AN - 15660868; 3952100 AB - Shigella flexneri grown to stationary phase has the ability to survive for several hours at pH 2.5. This acid resistance, which may contribute to the low infective dose associated with shigellosis, is dependent upon the expression of the stationary-phase-specific sigma factor sigma super(s). Using random TnphoA and TnlacZ mutagenesis we isolated five acid-sensitive mutants of S. flexneri, which had lost their ability to survive at pH 2.5 for 2 h in vitro. Each transposon insertion with flanking S. flexneri DNA was cloned and sequenced. Database searches indicated that two TnlacZ mutants had an insertion within the hdeA gene, which is the first gene in the hdeAB operon. Acid resistance was restored in one of these mutants by a plasmid carrying the entire hdeAB operon. Further sequence analysis from the remaining TnlacZ and two TnphoA mutants demonstrated that they all had insertions within a previously unidentified open reading frame (ORF), which is directly downstream from the gadB gene. This putative ORF encodes a protein that has homology to a number of inner membrane amino acid antiporters. A 1.8 kb polymerase chain reaction (PCR) product containing this gene was cloned, which was able to restore acid resistance in each mutant. These fusions were induced during entry into late exponential phase and were positively regulated by RpoS. We confirmed that the expression of the acid-resistance phenotype in acidified minimal media was dependent upon the supplementation of glutamic acid and that this glutamate-dependent system was RpoS regulated. Southern hybridization revealed that both the gadC and hdeAB loci are absent in Salmonella. An rpoS deletion mutant of S. flexneri was also constructed to confirm the important role played by this gene in acid resistance. This rpoS super(-) derivative was extremely acid sensitive. Two-dimensional gel electrophoresis of this mutant revealed that it no longer expressed 27 proteins in late log phase that were present in its isogenic parent. These data indicate that the expression of acid resistance in S. flexneri, may be multifactorial and involve proteins located at different subcellular locations. JF - Molecular Microbiology AU - Waterman AU - Small, PLC AD - Rocky Mountain Labs., NIAID, Microscopy Branch, 903 South 4th St., Hamilton, MT 59840, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 925 EP - 940 VL - 21 IS - 5 SN - 0950-382X, 0950-382X KW - hdeAB operon KW - sigma super(s) factor KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - shigellosis KW - Shigella flexneri KW - acidity KW - mutants KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15660868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Identification+of+sigma+super%28s%29-dependent+genes+associated+with+the+stationary-phase+acid-resistance+phenotype+of+Shigella+flexneri&rft.au=Waterman%3BSmall%2C+PLC&rft.aulast=Waterman&rft.aufirst=&rft.date=1996-01-01&rft.volume=21&rft.issue=5&rft.spage=925&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Shigella flexneri; acidity; shigellosis; mutants ER - TY - JOUR T1 - Anti-HIV therapy in 1996 AN - 15648808; 3947276 AB - Single-drug and combination approaches to antiretroviral therapy offer more choices than ever. The arrival of three protease inhibitors may signal a turning point in care. JF - Patient Care AU - Davey, RT Jr AU - Goldschmidt, R H AU - Sande, MA AD - Natl. Inst. Allergy and Infect. Dis. (NIAID), HIV Res. Clin., Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 55 EP - 72 VL - 30 IS - 9 SN - 0031-305X, 0031-305X KW - proteinase KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - antiviral agents KW - inhibitors KW - treatment KW - human immunodeficiency virus KW - infection KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15648808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Patient+Care&rft.atitle=Anti-HIV+therapy+in+1996&rft.au=Davey%2C+RT+Jr%3BGoldschmidt%2C+R+H%3BSande%2C+MA&rft.aulast=Davey&rft.aufirst=RT&rft.date=1996-01-01&rft.volume=30&rft.issue=9&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Patient+Care&rft.issn=0031305X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus; infection; treatment; antiviral agents; inhibitors ER - TY - JOUR T1 - A developmental stage-specific histone H1 homolog of Coxiella burnetii AN - 15636819; 3941210 AB - Two DNA-binding proteins have been detected in Coxiella burnetii by Southwestern (DNA-protein) blotting. One of these, termed Hq1, is enriched in the small cell variant stage of the developmental cycle and displays compositional and primary amino acid sequence similarities to eukaryotic histone H1. C. burnetii appears to be another example of an intracellular parasite with morphologically distinct developmental forms whose nucleoid structure may be controlled by histone H1 homologs. JF - Journal of Bacteriology AU - Heinzen, R A AU - Hackstadt, T AD - Lab. Intracellular Parasites, Rocky Mountain Labs., NIAID, Hamilton, MT 59840, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 5049 EP - 5052 VL - 178 IS - 16 SN - 0021-9193, 0021-9193 KW - Hq1 protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - primary structure KW - Coxiella burnetii KW - DNA-binding protein KW - gene regulation KW - J 02725:DNA KW - N 14920:Chromatin & chromosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15636819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=A+developmental+stage-specific+histone+H1+homolog+of+Coxiella+burnetii&rft.au=Heinzen%2C+R+A%3BHackstadt%2C+T&rft.aulast=Heinzen&rft.aufirst=R&rft.date=1996-01-01&rft.volume=178&rft.issue=16&rft.spage=5049&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Coxiella burnetii; DNA-binding protein; primary structure; gene regulation ER - TY - JOUR T1 - Structural mechanisms of HIV drug resistance AN - 15636168; 3941231 AB - Antiviral therapy for AIDS has focused on the discovery and design of inhibitors for two main enzyme targets of the human immunodeficiency virus type 1 (HIV)-reverse transcriptase (RT) and protease (PR). Despite several classes of promising new anti-HIV agents, the clinical emergence of drug-resistant variants of HIV has severely limited the long-term effectiveness of these drugs. Genetic analysis of resistant virus has identified a number of critical mutations in the RT and PR genes. Structural analysis of inhibitor-enzyme complexes and mutational modeling studies are leading to a better understanding of how these drug-resistance mutations exert their effects at a structural level. These insights have implications for the design of new drugs and therapeutic strategies to combat drug resistance to AIDS. JF - Annual Review of Pharmacology and Toxicology AU - Erickson, J W AU - Burt, S K AD - Struct. Biochem. Program, Frederick Biomed. Supercomputing Cent., SAIC-Frederick, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 545 EP - 571 VL - 36 SN - 0362-1642, 0362-1642 KW - proteinase KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - genetic analysis KW - antiviral agents KW - human immunodeficiency virus KW - mutation KW - drug resistance KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01064:Microbial resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15636168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+Review+of+Pharmacology+and+Toxicology&rft.atitle=Structural+mechanisms+of+HIV+drug+resistance&rft.au=Erickson%2C+J+W%3BBurt%2C+S+K&rft.aulast=Erickson&rft.aufirst=J&rft.date=1996-01-01&rft.volume=36&rft.issue=&rft.spage=545&rft.isbn=0824304365&rft.btitle=&rft.title=Annual+Review+of+Pharmacology+and+Toxicology&rft.issn=03621642&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus; drug resistance; genetic analysis; mutation; antiviral agents ER - TY - JOUR T1 - Oxidative stress increases production of beta -amyloid precursor protein and beta -amyloid (A beta ) in mammalian lenses, and A beta has toxic effects on lens epithelial cells AN - 15630192; 3936120 AB - Many amyloid diseases are characterized by protein aggregations linked to oxidative stress. Such diseases including those of the brain, muscle, and blood vessels exhibit plaques containing beta -amyloid (A beta ). Here we demonstrate that Alzheimer's precursor protein ( beta APP) and A beta are present at low levels in normal lenses and increase in intact cultured monkey lenses treated with H sub(2)O sub(2) or UV radiation (known cataractogenic agents), and with phorbol 12-myristate 13-acetate. AP-1 factor binding, shown by others to up-regulate beta APP expression, increased in the monkey lenses treated with H sub(2)O sub(2), UV radiation, or phorbol 12-myristate 13-acetate and paralleled the increase in beta APP expression. Rat lenses exposed to oxidative stress showed increased beta APP in the anterior epithelium and cortex. Incubation of cultured rabbit lens N/N1003A epithelial cells with A beta induced inclusions and vacuoles and was cytotoxic. A beta cross-reacting protein was readily detected in the cortex of a cataractous human lens. Our data show that beta APP and A beta increase in mammalian lenses as part of a response to H sub(2)O sub(2) or UV radiation and suggest that they may contribute to the mechanism by which oxidative damage leads to lens opacification. JF - Journal of Biological Chemistry AU - Frederikse, PH AU - Garland, D AU - Zigler, JS Jr AU - Piatigorsky, J AD - Lab. Mol. and Dev. Biol., NEI, Natl. Inst. Health, 6 Cent. Dr., MSC 2730, Bethesda, MD 20892-2730, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 10169 EP - 10174 VL - 271 IS - 17 SN - 0021-9258, 0021-9258 KW - beta -amyloid KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - cataracts KW - Alzheimer's disease KW - eye lens KW - epithelium KW - free radicals KW - oxidative stress KW - N3 11126:Alzheimer's disease and other dementias KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15630192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Oxidative+stress+increases+production+of+beta+-amyloid+precursor+protein+and+beta+-amyloid+%28A+beta+%29+in+mammalian+lenses%2C+and+A+beta+has+toxic+effects+on+lens+epithelial+cells&rft.au=Frederikse%2C+PH%3BGarland%2C+D%3BZigler%2C+JS+Jr%3BPiatigorsky%2C+J&rft.aulast=Frederikse&rft.aufirst=PH&rft.date=1996-01-01&rft.volume=271&rft.issue=17&rft.spage=10169&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - oxidative stress; free radicals; eye lens; epithelium; cataracts; Alzheimer's disease ER - TY - JOUR T1 - Multiple immunizations with attenuated poxvirus HIV type 2 recombinants and subunit boosts required for protection of rhesus macaques AN - 15628617; 3936632 AB - Vaccine protocols involving multiple immunizations with molecularly attenuated vaccinia virus (NYVAC) or naturally attenuated canarypox virus (ALVAC) HIV-2 recombinants and subunit boosts have conferred long-lasting protection against HIV-2 infection of macaques. Similar complex protocols using HIV-1 NYVAC and ALVAC recombinants and subunit boosts have provided cross-protection against HIV-2 challenge. Here a simplified three-immunization regimen over 24 weeks was tested in 18 juvenile rhesus macaques. Twelve macaques were immunized twice with NYVAC or ALVAC recombinants carrying HIV-2 env, gag, and pol genes. Subsequently, macaques in groups of three received either an additional recombinant immunization or an HIV-2 gp160 boost. Six control macaques received three immunizations of NYVAC or ALVAC vector alone and additionally alum at the third immunization. Macaques primed with ALVAC recombinant exhibited sporadic T cell proliferative activity, and all but one failed to develop neutralizing antibodies. In contrast, macaques primed with NYVAC recombinants had no T cell proliferative activity but exhibited neutralizing antibody titers (highest in the three recombinant group) that declined by the time of challenge. None of the macaques exhibited significant cytotoxic T lymphocyte activity. Following challenge at 32 weeks with HIV-2 sub(SBL6669) all macaques became infected. Thus, the three-immunization regimen is not sufficient to confer protective immunity in the HIV-2 rhesus macaque model. However, delayed infection in macaques immunized with the NYVAC-HIV-2 recombinant may have been associated with the development of memory B cells capable of providing a neutralizing antibody response on challenge. JF - AIDS Research and Human Retroviruses AU - Myagkikh, M AU - Alipanah, S AU - Markham, P D AU - Tartaglia, J AU - Paoletti, E AU - Gallo, R C AU - Franchini, G AU - Robert-Guroff, M AD - Lab. Tumor Cell Biol. 37/6A11, NCI, 37 Convent Dr. MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 985 EP - 992 VL - 12 IS - 11 SN - 0889-2229, 0889-2229 KW - macaca rhesus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - recombinants KW - neutralization KW - antibodies KW - immunity KW - poxvirus KW - human immunodeficiency virus 2 KW - vaccination KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15628617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Research+and+Human+Retroviruses&rft.atitle=Multiple+immunizations+with+attenuated+poxvirus+HIV+type+2+recombinants+and+subunit+boosts+required+for+protection+of+rhesus+macaques&rft.au=Myagkikh%2C+M%3BAlipanah%2C+S%3BMarkham%2C+P+D%3BTartaglia%2C+J%3BPaoletti%2C+E%3BGallo%2C+R+C%3BFranchini%2C+G%3BRobert-Guroff%2C+M&rft.aulast=Myagkikh&rft.aufirst=M&rft.date=1996-01-01&rft.volume=12&rft.issue=11&rft.spage=985&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - neutralization; recombinants; antibodies; immunity; vaccination; poxvirus; human immunodeficiency virus 2 ER - TY - JOUR T1 - Adenovirus-mediated gene transfer to human breast tumor cells: An approach for cancer gene therapy and bone marrow purging AN - 15627671; 3936912 AB - To examine the potential use of adenovirus vectors in cancer gene therapy as a mechanism for purging bone marrow cells of possible breast cancer contaminants, we compared the infection efficiency of adenovirus and the transfection efficiency of plasmid DNA in the presence of adenovirus in human breast cancer and bone marrow cells. Following infection of breast cancer cells with an adenovirus expressing beta -galactosidase gene, high levels of beta -galactosidase activity were observed. No beta -galactosidase activity was observed in low-density human bone marrow cells. A replication-deficient adenovirus mutant dl312 enhanced the transfection efficiency of a plasmid DNA-expressing beta -galactosidase gene into breast cancer cells, and addition of a liposome, lipofectamine, further enhanced the transfection efficiency. In contrast, human bone marrow cells treated under the same conditions expressed very low levels of the transfected beta -galactosidase DNA. Transfection of cells with plasmid DNA expressing a truncated but fully active Pseudomonas exotoxin gene in the presence of dl312 and lipofectamine resulted in marked breast cancer cell killing, whereas colony-forming unit granulocyte-macrophage (CFU-GM) were relatively resistant to these treatments. A recombinant adenovirus expressing human wild-type p53 protein (AdWTp53) was also highly cytotoxic to breast tumor cells. Infection of breast cancer cells with AdWTp53 (100 plaque-forming units/cell) resulted in 100% loss of the clonogenicity of breast tumor cells. However, colony formation from CFU-GM was relatively resistant to the cytotoxic effects of AdWTp53 alone or in the presence of pULI100 plasmid and lipofectamine. On the basis of these results, it is proposed that human adenoviruses are potentially useful for cancer gene therapy and bone marrow purging. JF - Cancer Research AU - Seth, P AU - Brinkmann, U AU - Schwartz, G N AU - Katayose, D AU - Gress, R AU - Pastan, I AU - Cowan, K AD - Med. Branch, Bldg. 10, Rm. 12 N 226, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1346 EP - 1351 VL - 56 IS - 6 SN - 0008-5472, 0008-5472 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - gene transfer KW - gene therapy KW - adenovirus KW - breast carcinoma KW - man KW - cancer KW - bone marrow KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15627671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Adenovirus-mediated+gene+transfer+to+human+breast+tumor+cells%3A+An+approach+for+cancer+gene+therapy+and+bone+marrow+purging&rft.au=Seth%2C+P%3BBrinkmann%2C+U%3BSchwartz%2C+G+N%3BKatayose%2C+D%3BGress%2C+R%3BPastan%2C+I%3BCowan%2C+K&rft.aulast=Seth&rft.aufirst=P&rft.date=1996-01-01&rft.volume=56&rft.issue=6&rft.spage=1346&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; gene transfer; breast carcinoma; cancer; man; bone marrow; adenovirus ER - TY - JOUR T1 - Fidelity and error specificity of the alpha catalytic subunit of Escherichia coli DNA polymerase III AN - 15623235; 3934022 AB - Escherichia coli DNA polymerase III holoenzyme is the replicative enzyme primarily responsible for the duplication of the E. coli chromosome. This process occurs with high accuracy, less than 10 super(-9) to 10 super(-10) errors being committed per base pair per round of replication. As a first step in understanding the mechanisms responsible for the high fidelity of this process, we have purified the polymerase III alpha catalytic subunit, free of exonuclease activity, and analyzed its fidelity in vitro. We employed a newly developed gap-filling assay using the N-terminal 250 bases of the lacI gene as a forward mutational target. When synthesizing across this target, alpha subunit produced mutations at a frequency of 0.6%. DNA sequencing revealed that the mutants created in vitro consisted mostly of frameshift mutations, although some base substitutions were also observed. The frameshifts, occurring at more than 120-fold above the background, consisted largely of -1 deletions. Among them, about 80% were the deletion of a purine template base with a pyrimidine 5'-neighbor. These results suggest that the alpha subunit (i) has a relatively low ability to extend from misincorporated bases, accounting for the low level of observed base substitutions, and (ii) has a relatively high capability of extension after misalignment of a misincorporated base on the next (complementary) template base, accounting for the high level of frameshift mutations. This model is supported by an experiment in which alpha subunit was required to initiate DNA synthesis from a terminal mispair in a sequence context that allowed slippage on the next template base. Among the products of this reaction, frameshifts outnumbered base pair substitutions by greater than 70-fold. A comparison to in vivo mutational spectra suggests that the pol III accessory factors may play a major role in modulating the fidelity of DNA synthesis. JF - Journal of Biological Chemistry AU - Mo, Jin-Yao AU - Schaaper, R M AD - Lab. Mol. Genet., NIEHS, Natl. Inst. Health, Research Triangle Park, NC 27709, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 18947 EP - 18953 VL - 271 IS - 31 SN - 0021-9258, 0021-9258 KW - DNA-directed DNA polymerase III KW - lacI gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA biosynthesis KW - Escherichia coli KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15623235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Fidelity+and+error+specificity+of+the+alpha+catalytic+subunit+of+Escherichia+coli+DNA+polymerase+III&rft.au=Mo%2C+Jin-Yao%3BSchaaper%2C+R+M&rft.aulast=Mo&rft.aufirst=Jin-Yao&rft.date=1996-01-01&rft.volume=271&rft.issue=31&rft.spage=18947&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA biosynthesis ER - TY - JOUR T1 - Conserved region 3 of Escherichia coli sigma super(70) is implicated in the process of abortive transcription AN - 15619675; 3933957 AB - Multiple-round in vitro transcription assays were performed using purified Escherichia coli RNA polymerase reconstituted with either wild-type or mutant sigma super(70) proteins. These mutants, sigma super(70) (P504L) and sigma super(70) (S506F), bear single amino acid changes in conserved protein region 3. Behavior of the mutant enzymes on three test templates, bearing either the T7 A1, T5 N25, or T5 N25 sub(antiDSR) promoter, were characterized. Transcription of all three promoter templates produced a pattern of specific abortive RNA species, which was qualitatively different for the mutants compared to the wild-type sigma super(70) enzyme. Short abortive RNAs were produced at similar levels for mutant and wild-type enzymes. The production of longer abortive species was either reduced or increased by the mutant enzymes in a systematic manner that appears promoter-specific, and could be RNA length- or promoter distance-dependent. The process of abortive RNA transcription is thought to be tightly associated with that of promoter clearance. However, promoter clearance from these templates appears only slightly affected by the mutant enzymes. These mutants implicated region 3 of sigma super(70) in the process of abortive transcription and suggest that the sequence of enzymatic events leading to the production of abortive or full-length RNA may be separable. JF - Journal of Biological Chemistry AU - Hernandez, V J AU - Hsu, L M AU - Cashel, M AD - NIH/NICHD/LMG, 9000 Rockville Pike, Bldg. 6B, Rm. 316, Bethesda, MD 20892-2785, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 18775 EP - 18779 VL - 271 IS - 31 SN - 0021-9258, 0021-9258 KW - sigma super(70) factor KW - DNA-directed RNA polymerase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - RNA KW - Escherichia coli KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15619675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Conserved+region+3+of+Escherichia+coli+sigma+super%2870%29+is+implicated+in+the+process+of+abortive+transcription&rft.au=Hernandez%2C+V+J%3BHsu%2C+L+M%3BCashel%2C+M&rft.aulast=Hernandez&rft.aufirst=V&rft.date=1996-01-01&rft.volume=271&rft.issue=31&rft.spage=18775&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; RNA ER - TY - JOUR T1 - Concentration, phase distribution, and size distribution of atmospheric polychlorinated biphenyls measured in southern Taiwan AN - 15617593; 3933851 AB - Polychlorinated biphenyl (PCB) samples in the ambient air of rural, urban, and industrial sites were collected by two PS-1 samplers and two Micro-Orifice Uniform Deposit Impactors (MOIDIs) from July 1993 to December 1994 in southern Taiwan. The total PCB concentrations averaged 2.50, 4.51, and 5.91 ng m super(-3) for the rural, urban, and industrial sites, respectively. Mean gas phase distribution of total PCBs was 43.6%, 60.9%, and 63.1% for the rural, urban, and industrial sites, respectively. The patterns of PCB homologues were similar to the distribution of those found in the mixture of Aroclor 1242 and 1260. Particle-bound total PCBs averaged 10.3, 13.9, and 9.24 mu g g super(-1) for rural, urban, and industrial sites, respectively. For both urban and industrial sites, the particle size distribution (dC/dlogDp vs. Dp) of both total PCBs and total particle mass was found to have bimodal size distribution. The industrial aerosols were dominant in the fine particle mode (Dp2.5 mu m). JF - Environment International AU - Chen, Shui-Jen AU - Hsieh, Lien-Te AU - Hwang, Ping-Shium AD - Dep. Environ. Prot. Technol., Natl. Ping Tung Polytechnic Inst., Nei Pu 91207, Ping Tung, Taiwan Y1 - 1996 PY - 1996 DA - 1996 SP - 411 EP - 423 VL - 22 IS - 4 SN - 0160-4120, 0160-4120 KW - Taiwan, Southern KW - Pollution Abstracts KW - particle size KW - atmosphere KW - air sampling KW - PCB compounds KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15617593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environment+International&rft.atitle=Concentration%2C+phase+distribution%2C+and+size+distribution+of+atmospheric+polychlorinated+biphenyls+measured+in+southern+Taiwan&rft.au=Chen%2C+Shui-Jen%3BHsieh%2C+Lien-Te%3BHwang%2C+Ping-Shium&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=1996-01-01&rft.volume=22&rft.issue=4&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Environment+International&rft.issn=01604120&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - PCB compounds; air sampling; particle size; atmosphere ER - TY - JOUR T1 - Base sequence selectivity in the alkylation of DNA by 1,3-dialkyl-3-acyltriazenes AN - 15604471; 3925059 AB - The base sequence selectivity of DNA alkylation for a series of structurally related 1,3-dialkyl-3-acyltriazenes was examined with calf thymus DNA or polymers containing the sequences GGG, CGC, TGT, and AGA. The reaction products at the N7 and the O super(6) positions of guanine were identified, quantitated, and then correlated with the decomposition rates of the triazenes, 1-(2-chloroethyl)-3-methyl-3-carbethoxy- (CMC), 1-(2-chloroethyl)-3-methyl-3-acetyl- (CMA), 1-(2-hydroxyethyl)-3-methyl-3-carbethoxy- (HMC), 1-(2-hydroxyethyl)-3-methyl-3-acetyl- (HMA), and 1,3-dimethyl-3-acetyl-(DMA). The results of these studies revealed that DNA sequences with runs of purines were more reactive toward alkylation by all of the triazenes tested, irrespective of whether the alkylation was measured by N7, O super(6), or total guanine adducts. Within this generalization, the (hydroxyethyl)triazenes showed a preference for the AGA sequence, while the (chloroethyl)triazenes favored the GGG sequence. The structure of the 3-acyl group of the triazene also played a role in the extent of alkylation of a particular sequence of DNA. Both the (chloroethyl)- and the (hydroxyethyl)triazenes produced higher alkylation product yields for the 3-carbethoxytriazenes as compared with the 3-acetyl derivatives for most of the sequences examined. These overall patterns correlated well with the order of decomposition of the triazenes at 37 degree C: HMC > DMA > HMA > CMC > CMA. This study has demonstrated how varying the structure of 1,3-dialkyl-3-acyltriazenes can modulate DNA alkylation, a finding which may be important in the design of new triazene antitumor agents. JF - Chemical Research in Toxicology AU - Kroeger Smith, MB AU - Taneyhill, LA AU - Michejda, C J AU - Smith, RH Jr AD - Mol. Aspects Drug Design Sect., Macromolecular Structure Lab., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 341 EP - 348 VL - 9 IS - 1 SN - 0893-228X, 0893-228X KW - 1,3-dialkyl-3-acyltriazenes KW - cattle KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - nucleotide sequence KW - alkylation KW - DNA KW - antitumor agents KW - thymus KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15604471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Base+sequence+selectivity+in+the+alkylation+of+DNA+by+1%2C3-dialkyl-3-acyltriazenes&rft.au=Kroeger+Smith%2C+MB%3BTaneyhill%2C+LA%3BMichejda%2C+C+J%3BSmith%2C+RH+Jr&rft.aulast=Kroeger+Smith&rft.aufirst=MB&rft.date=1996-01-01&rft.volume=9&rft.issue=1&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - nucleotide sequence; DNA; alkylation; antitumor agents; thymus ER - TY - JOUR T1 - Benzo[c]phenanthrene-DNA adducts in mouse epidermis in relation to the tumorigenicities of four configurationally isomeric 3,4-dihydrodiol 1,2-epoxides AN - 15602346; 3929606 AB - super(32)P-Postlabeling assays were used to monitor the binding to epidermal DNA that resulted from the application of each of the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide to mouse skin in vivo. For three of these configurational isomers, there was a reasonable correlation between the relative level of binding to epidermal DNA and the known tumorigenic effects of these compounds. However, for the 4(S),3(R)-dihydrodiol 2(S),1(R)-epoxide, the tumorigenic response was considerably greater in relation to the level of DNA modification than was the case for the other isomers. This greater tumorigenic response was consistent with previous observations indicating that this isomer was more mutagenic, at equivalent levels of DNA modification, than the other two tumorigenic dihydrodiol epoxides. Additionally, the 4(S),3(R)-dihydrodiol 2(S),1(R)-epoxide reacts with DNA to generate predominantly ( similar to 80%) adducts on the amino group of adenine residues. These findings might imply a greater intrinsic biological effect of such adenine adducts with respect to the other major adduct formed on the amino group of guanine residues. JF - Chemical Research in Toxicology AU - Agarwal, R AU - Canella, KA AU - Yagi, H AU - Jerina, D M AU - Dipple, A AD - Chem. Carcinogenesis Lab., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 586 EP - 592 VL - 9 IS - 3 SN - 0893-228X, 0893-228X KW - 3,4-benzphenanthrene KW - mice KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA adducts KW - tumorigenicity KW - epidermis KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15602346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Benzo%5Bc%5Dphenanthrene-DNA+adducts+in+mouse+epidermis+in+relation+to+the+tumorigenicities+of+four+configurationally+isomeric+3%2C4-dihydrodiol+1%2C2-epoxides&rft.au=Agarwal%2C+R%3BCanella%2C+KA%3BYagi%2C+H%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Agarwal&rft.aufirst=R&rft.date=1996-01-01&rft.volume=9&rft.issue=3&rft.spage=586&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA adducts; epidermis; tumorigenicity ER - TY - JOUR T1 - Purification and characterization of human ZAP-70 protein-tyrosine kinase from a baculovirus expression system AN - 15598827; 3923587 AB - The ZAP-70 protein tyrosine kinase is essential for T cell antigen receptor (TCR)-mediated signaling. The absence of ZAP-70 results in impaired differentiation of T cells and a lack of responsiveness to antigenic stimulation. In order to study the characteristics of ZAP-70 in vitro, we overexpressed an epitopically tagged human ZAP-70 in a recombinant baculovirus expression system and purified it by column chromatography. The kinase activity of purified, recombinant ZAP-70 required cation and exhibited a strong preference for Mn super(2+) over Mg super(2+). The apparent K sub(m) of ZAP-70 for ATP was similar to 3.0 mu M. The activity of the recombinant ZAP-70, unlike that of the homologous protein tyrosine kinase, Syk, was not affected by binding of TCR-derived tyrosine phosphorylated immunoreceptor tyrosine-based activation motif peptides. Several proteins were tested as potential in vitro substrates of ZAP-70. Only alpha -tubulin and the cytoplasmic fragment of human erythrocyte band 3 (cfb3), which have a region of sequence identity at the phosphorylation site, proved to be good substrates, exhibiting K sub(m) values of similar to 3.3 and similar to 2.5 mu M, respectively ([ATP] = 50 mu M). alpha - and beta -Casein were poor substrates for ZAP-70, and no activity toward enolase, myelin basic protein, calmodulin, histone proteins, or angiotensin could be detected. In contrast to the T cell protein tyrosine kinase, Lck, ZAP-70 did not phosphorylate the cytoplasmic portion of the TCR zeta chain or short peptides corresponding to the CD3 epsilon or the TCR zeta immunoreceptor tyrosine-based activation motifs. Our studies suggest that ZAP-70 exhibits a high degree of substrate specificity. JF - Journal of Biological Chemistry AU - Isakov, N AU - Wange, R L AU - Watts, J D AU - Aebersold, R AU - Samelson, LE AD - Cell Biol. and Metabolism Branch, NICHD, Natl. Inst. Health, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 15753 EP - 15761 VL - 271 IS - 26 SN - 0021-9258, 0021-9258 KW - ATP KW - Band 3 protein KW - Syk protein KW - ZAP-70 protein KW - magnesium KW - manganese KW - protein-tyrosine kinase KW - tubulin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - baculovirus KW - T-cell receptor KW - phosphorylation KW - V 22050:Viral genetics including virus reactivation KW - W3 33310:Enzymes and cofactors KW - N 14684:Expression of cloned genes KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15598827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Purification+and+characterization+of+human+ZAP-70+protein-tyrosine+kinase+from+a+baculovirus+expression+system&rft.au=Isakov%2C+N%3BWange%2C+R+L%3BWatts%2C+J+D%3BAebersold%2C+R%3BSamelson%2C+LE&rft.aulast=Isakov&rft.aufirst=N&rft.date=1996-01-01&rft.volume=271&rft.issue=26&rft.spage=15753&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - T-cell receptor; phosphorylation; baculovirus ER - TY - JOUR T1 - Down-regulation of metallothionein expression in human and murine hepatocellular tumors: Association with the tumor-necrotizing and antineoplastic effects of cadmium in mice AN - 15593431; 3916202 AB - Previously, we found that oral cadmium (Cd) treatment either prevented or substantially reduced N-nitrosodiethylamine (NDEA)-induced tumor formation in B6C3F1 mouse liver or lung regardless of exposure interval and even when the Cd was given well after tumors were formed. Because Cd salts are powerful emetics, oral exposure would probably be impractical in humans. Thus, we studied suppression of NDEA-initiated tumors in male B6C3F1 mice by a single i.v. dose of Cd. NDEA (776 mu mol/kg i.p.) was given at time 0 followed by CdCl sub(2) (16 mu mol/kg i.v.) 40 weeks later. This dose of Cd had no effect on body weights through the conclusion of the study at 52 weeks. The NDEA-induced increase in hepatic tumor incidence (19 tumor-bearing mice/22 mice at risk, 86%) over control (5/24, 21%) was remarkably reduced by Cd treatment (13/27, 48%, P less than or equal to .05). Multiplicity and size of liver tumors induced by NDEA (2.18 tumors/liver; 31.6 mm super(3) mean volume) were also substantially reduced by the Cd exposure (0.96 tumors/liver; 17.1 mm super(3) mean volume). NDEA-induced lung tumor incidence (22/22, 100%) and multiplicity (5.09 tumors/lung) were modestly, but significantly, reduced by Cd treatment (21/27, 78%; 3.89 tumors/lung). Clear evidence of tumor-specific cytotoxicity was observed as Cd treatment induced a necrotizing effect that was localized only within the hepatic tumors. Metallothionein (MT), an inducible metal-binding protein associated with tolerance to many metals including Cd, was not detected immunohistochemically in mouse liver tumors, even those undergoing Cd-induced necrosis, whereas the surrounding normal liver cells expressed high levels of MT after Cd exposure. Likewise, in human hepatocellular carcinomas MT was only poorly or erratically expressed relative to normal tissue. These results indicate that a single, nontoxic dose of Cd dramatically reduces liver tumor burden through tumor cell-specific necrosis due to a down-regulation of MT expression in hepatic tumors of murine origin and furthermore indicate that a similar down-regulation of MT occurs in human hepatocellular carcinomas. JF - Journal of Pharmacology and Experimental Therapeutics AU - Waalkes, M P AU - Diwan, BA AU - Rehm, S AU - Ward, J M AU - Moussa, M AU - Cherian, M G AU - Goyer, R A AD - Inorganic Carcinogenesis Sect., NCI-FCRDC, Bldg. 538, Rm. 205E, Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1026 EP - 1033 VL - 277 IS - 2 SN - 0022-3565, 0022-3565 KW - metallothionein KW - cadmium KW - mice KW - heavy metals KW - N-nitrosodiethylamine KW - Toxicology Abstracts KW - gene expression KW - tumors KW - X 24200:Nitrosamines & related compounds KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15593431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Pharmacology+and+Experimental+Therapeutics&rft.atitle=Down-regulation+of+metallothionein+expression+in+human+and+murine+hepatocellular+tumors%3A+Association+with+the+tumor-necrotizing+and+antineoplastic+effects+of+cadmium+in+mice&rft.au=Waalkes%2C+M+P%3BDiwan%2C+BA%3BRehm%2C+S%3BWard%2C+J+M%3BMoussa%2C+M%3BCherian%2C+M+G%3BGoyer%2C+R+A&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1996-01-01&rft.volume=277&rft.issue=2&rft.spage=1026&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmacology+and+Experimental+Therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - tumors; gene expression ER - TY - JOUR T1 - Specificity of DNA alkylation by 1-(2-chloroethyl)-3-alkyl-3-acyltriazenes depends on the structure of the acyl group: Kinetic and product studies AN - 15592876; 3919855 AB - The reactions of calf thymus DNA with ten 1-(2-chloroethyl)-3-alkyl-3-acyltriazenes of varying acyl side chain structure were studied alone, or in the presence of porcine liver esterase in pH 7.0 phosphate buffer. In several of the key triazenes, the acyl substituent contained a free carboxylic acid group. With esterase present in the reaction mixture, the resultant levels of DNA alkylation could be correlated with the kinetic rates of decomposition of the triazenes. Under these conditions, the predominant pathway of decomposition involved deacylation of the parent triazene and eventual production of an alkanediazonium ion. This intermediate subsequently alkylated DNA-guanine to give 7-alkylguanine as the principal reaction product. In the absence of esterase, the order of DNA alkylation for all of the acyltriazenes did not correlate with their respective rates of decomposition, leading to the conclusion that the triazenes did not decompose by the expected mode of uncatalyzed N(2)-N(3) heterolyic cleavage. The major DNA alkylation product from the N(3)-methyltriazenes was 7-methylguanine, instead of the expected 7-(chloroethyl)- and 7-(hydroxyethyl)guanine products, which suggested that the acyl group was being hydrolyzed. However, acyltriazenes with an N(3)-benzyl group rather than a methyl in this position produced very little 7-benzylguanine product, contrary to prediction. An alternative mechanism involving internally assisted hydrolysis of the side chain ester is proposed to explain these results. NMR product analysis and computational studies were carried out to lend support to the postulated mechanism. JF - Chemical Research in Toxicology AU - Smith, MBK AU - Schmidt, B F AU - Czerwinski, G AU - Taneyhill, LA AU - Snyder, E J AU - Kline, A M AU - Michejda, C J AU - Smith, RH Jr AD - Molecular Aspects Drug Design Sect., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 466 EP - 475 VL - 9 IS - 2 SN - 0893-228X, 0893-228X KW - 1-(2-chloroethyl)-3-alkyl-3-acyltriazene KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - alkylation KW - DNA KW - structure-function relationships KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15592876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Specificity+of+DNA+alkylation+by+1-%282-chloroethyl%29-3-alkyl-3-acyltriazenes+depends+on+the+structure+of+the+acyl+group%3A+Kinetic+and+product+studies&rft.au=Smith%2C+MBK%3BSchmidt%2C+B+F%3BCzerwinski%2C+G%3BTaneyhill%2C+LA%3BSnyder%2C+E+J%3BKline%2C+A+M%3BMichejda%2C+C+J%3BSmith%2C+RH+Jr&rft.aulast=Smith&rft.aufirst=MBK&rft.date=1996-01-01&rft.volume=9&rft.issue=2&rft.spage=466&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA; alkylation; structure-function relationships ER - TY - JOUR T1 - Why toxins! [Chimeric toxins and cancer] AN - 15590510; 3916589 AB - Toxins are potent cytotoxic proteins which gain access to the interior of mammalian cells by receptor-mediated endocytosis. However, the trafficking pathways within mammalian cells are complex and toxins must be processed to active forms while avoiding degradation by the lysosomal system. Once delivered to an appropriate intracellular location, the active toxin fragment translocates to the cell cytosol and inhibits protein synthesis. Chimeric toxins are constructed by removing the toxins natural binding domain and placing it with an antibody or cell-binding ligand that redirects cell killing activity to cancer cells. Gaining an understanding of how toxins manoeuvre within cells is vital for improving the effectiveness of chimeric toxins. (DBO) JF - Seminars in Cancer Biology AU - Fitzgerald, D AD - Lab. Mol. Biol., DBS, NCI, Bldg. 37, 4B-03, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 87 EP - 95 VL - 7 IS - 2 SN - 1044-579X, 1044-579X KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - reviews KW - antibodies KW - endocytosis KW - translocation KW - cancer KW - immunotoxins KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15590510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+Cancer+Biology&rft.atitle=Why+toxins%21+%5BChimeric+toxins+and+cancer%5D&rft.au=Fitzgerald%2C+D&rft.aulast=Fitzgerald&rft.aufirst=D&rft.date=1996-01-01&rft.volume=7&rft.issue=2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Seminars+in+Cancer+Biology&rft.issn=1044579X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; antibodies; endocytosis; translocation; cancer; immunotoxins ER - TY - JOUR T1 - Improved antitumor activity of a recombinant anti-Lewis super(y) immunotoxin not requiring proteolytic activation AN - 15585574; 3911023 AB - B1(dsFv)-PE33 is a recombinant immunotoxin composed of a mutant form of Pseudomonas exotoxin (PE) that does not need proteolytic activation and a disulfide-stabilized Fv fragment of the anti-Lewis super(y) monoclonal antibody B1, which recognizes a carbohydrate epitope on human carcinoma cells. In this molecule, amino acids 1-279 of PE are deleted and domain Ib (amino acids 365-394) is replaced by the heavy chain variable region (V sub(H)) domain of monoclonal antibody B1. The light chain (V sub(L)) domain is connected to the V sub(H) domain by a disulfide bond. This recombinant toxin, termed B1 (dsFv)-PE33, does not require proteolytic activation and it is smaller than other immunotoxins directed at Lewis super(y), all of which require proteolytic activation. Furthermore, it is more cytotoxic to antigen-positive cell lines. B1(dsFv)-PE38 has the highest antitumor activity of anti-Lewis super(y) immunotoxins previously constructed. B1(dsFv)-PE33 caused complete regression of tumors when given at 12 mu g/kg (200 pmol/kg) every other day for three doses, whereas B1(dsFv)-PE38 did not cause regressions at 13 mu g/kg (200 pmol/kg). By bypassing the need for proteolytic activation and decreasing molecular size we have enlarged the therapeutic window for the treatment of human cancers growing in mice, so that complete remissions are observed at 2.5% of the LD sub(50). JF - Proceedings of the National Academy of Sciences, USA AU - Kuan, Chien-Tsun AU - Pastan, I AD - Lab. Molec. Biol., Div. Basic Sci., NCI/NIH, Bldg. 37, Rm. 4E16, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 974 EP - 978 VL - 93 IS - 3 SN - 0027-8424, 0027-8424 KW - Lewis Y antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - exotoxins KW - Pseudomonas KW - monoclonal antibodies KW - proteolysis KW - antitumor agents KW - immunotoxins KW - F 06818:Cancer immunotherapy KW - W3 33370:Antibiotics KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15585574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Improved+antitumor+activity+of+a+recombinant+anti-Lewis+super%28y%29+immunotoxin+not+requiring+proteolytic+activation&rft.au=Kuan%2C+Chien-Tsun%3BPastan%2C+I&rft.aulast=Kuan&rft.aufirst=Chien-Tsun&rft.date=1996-01-01&rft.volume=93&rft.issue=3&rft.spage=974&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - exotoxins; proteolysis; monoclonal antibodies; antitumor agents; immunotoxins; Pseudomonas ER - TY - JOUR T1 - Tumors in dogs exposed to experimental intraoperative radiotherapy AN - 15583180; 3910396 AB - Purpose: The frequency of radiation-induced neoplasms was determined in dogs enrolled in the National Cancer Institute canine trials of intraoperative radiotherapy (IORT). Methods and Materials: Twelve protocols assessing normal tissue response to IORT involved 238 dogs in a 15-year trial. Eighty-one dogs were followed for > 24 months postoperatively and were assessed for tumor development; 59 of these animals received IORT. Results: Twelve tumors occurred in the 59 dogs receiving IORT. Nine were in the IORT portals and were considered to be radiation induced. No tumors occurred in 13 sham animals or in 9 animals treated with external beam radiotherapy alone. The frequency of radiation-induced malignancies in dogs receiving IORT was 15%, and was 25% in animals receiving greater than or equal to 25 Gy IORT. Frequency of all tumors, including spontaneous lesions, was 20%. Conclusions: Intraoperative radiotherapy contributed to a high frequency of sarcoma induction in these dogs. Unknown to date in humans involved in clinical trials of IORT, this potential complication should be looked for as long-term survivors are followed. JF - International Journal of Radiation Oncology, Biology, & Physics AU - Johnstone, PAS AU - Laskin, W B AU - DeLuca, A M AU - Barnes, M AU - Kinsella, T J AU - Sindelar, W F AD - RBB/NCI/NIH, Bldg. 10, Rm B3B69, Bethesda, MD 20892-1002, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 853 EP - 857 VL - 34 IS - 4 SN - 0360-3016, 0360-3016 KW - dogs KW - Toxicology Abstracts KW - tumors KW - radiotherapy KW - cancer KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15583180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Tumors+in+dogs+exposed+to+experimental+intraoperative+radiotherapy&rft.au=Johnstone%2C+PAS%3BLaskin%2C+W+B%3BDeLuca%2C+A+M%3BBarnes%2C+M%3BKinsella%2C+T+J%3BSindelar%2C+W+F&rft.aulast=Johnstone&rft.aufirst=PAS&rft.date=1996-01-01&rft.volume=34&rft.issue=4&rft.spage=853&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - tumors; radiotherapy; cancer ER - TY - JOUR T1 - Angiogenin single-chain immunofusions: Influence of peptide linkers and spacers between fusion protein domains AN - 15581805; 3916574 AB - The gene for human angiogenin (Ang), a member of the ribonuclease superfamily, was fused to a gene encoding a single-chain antibody (sFv) against the human transferrin receptor. Three Ang single-chain immunofusion proteins (AngsFvs) were constructed with variations in the type of linker connecting the V sub(L) and V sub(H) chain [EGKSSGSGSESKEF, L1 or (GGGGS) sub(3), L2] as well as with or without a spacer (FB) connecting the Ang and sFv [AngFBsFvL1 or L2; AngsFv(L2)]. Although the nature of the linker did not affect the enzymatic activity of the FB-containing fusion proteins, the fusion protein containing the L2 linker was 2.3-fold more effective than the L1 linker in competing with the labeled monoclonal IgG1 antibody for binding to the transferrin receptor. The fusion protein containing the L2 linker without the FB spacer exhibited a 13-fold decrease in binding to the transferrin receptor as well as a decrease in its capacity to degrade tRNA and to inhibit translation in the rabbit reticulocyte lysate compared to its counterpart containing the FB spacer. Binding of placental ribonuclease inhibitor (PRI) to Ang also was affected by the nature of the linker and by the presence or absence of a spacer. PRI bound to Ang and AngFBsFv(L2) and inhibited their ribonuclease activity. A 3-fold greater concentration of PRI, however, did not affect the activity of AngFBsFv(L1) or AngsFv(L2). suggesting that the conformation of these fusion proteins was altered. Binding of monoclonal and polyclonal anti-Ang antibodies to AngsFvs was also used to investigate conformational alterations of the fusion proteins. AngFBsFv(L2) was the least altered while AngFBsFv(L1) exhibited the greatest change in structure. Yet maximal concentrations of all AngsFvs elicited angiogenesis in the chick chorioallantoic membrane assay, demonstrating that Ang in all three fusion proteins remained functionally active. Consistent with all the activities, the fusion protein containing the FB spacer and L2 linker was the most cytotoxic to three different human tumor cell lines. The fusion protein lacking the FB spacer exhibited the least cytotoxicity. These data demonstrate that the linker connecting the V sub(H)-V sub(L) chains can affect the binding and cellular cytotoxicity of Ang immunofusions and that placement of a spacer between the antibody binding domains and Ang is necessary for optimal activity. Thus, a new class of targeted therapeutic agents containing Ang as the toxic moiety can be designed that potentially will be less immunogenic and less toxic than immunotoxins available currently. JF - Biochemistry (Washington) AU - Newton, D L AU - Xue, Y AU - Olson, KA AU - Fett, J W AU - Rybak, S M AD - Lab. Biochem. Physiology, NCI-FCRDC, Bldg. 567, Rm. 152, Frederick, MD 21702-1201, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 545 EP - 553 VL - 35 IS - 2 SN - 0006-2960, 0006-2960 KW - AngFBsFv(L1) protein KW - AngFBsFv(L2) protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - cytotoxicity testing KW - linkage analysis KW - gene fusion KW - protein structure KW - fusion protein KW - peptides KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15581805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Angiogenin+single-chain+immunofusions%3A+Influence+of+peptide+linkers+and+spacers+between+fusion+protein+domains&rft.au=Newton%2C+D+L%3BXue%2C+Y%3BOlson%2C+KA%3BFett%2C+J+W%3BRybak%2C+S+M&rft.aulast=Newton&rft.aufirst=D&rft.date=1996-01-01&rft.volume=35&rft.issue=2&rft.spage=545&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - cytotoxicity testing; linkage analysis; gene fusion; fusion protein; protein structure; peptides ER - TY - JOUR T1 - A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31 AN - 15579073; 3908994 AB - We have identified four loci in Borrelia burgdorferi B31 that contain open reading frames capable of encoding six proteins that are related to the antigenic proteins OspE and OspF. We have designated these proteins Erp, for OspEF-related protein, and named their respective genes erp. The erpA and erpB genes are linked, as are erpC and erpD, and the pairs probably constitute two operons. The erpG and erpH genes appear to be monocistronic. The ErpA and ErpC proteins are expressed by B. burgdorferi B31 in culture and are recognized by a polyclonal antiserum raised against the OspE protein of B. burgdorferi N40. The four erp loci are each located on different 32-kb circular plasmids that contain additional DNA sequences that are homologous to each other and to an 8.3-kb circular plasmid of B. burgdorferi sensu lato Ip21. All four 32-kb plasmids can be maintained within a single bacterium, which may provide a model for the study of plasmid replication and segregation in B. burgdorferi. JF - Journal of Bacteriology AU - Stevenson, B AU - Tilly, K AU - Rosa, P A AD - Lab. Microbial Structure and Function, Rocky Mountain Lab., NIAID, NIH, 903 South Fourth St., Hamilton, MT 59840, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 3508 EP - 3516 VL - 178 IS - 12 SN - 0021-9193, 0021-9193 KW - OspE protein KW - OspF protein KW - erpA gene KW - erpB gene KW - erpC gene KW - erpD gene KW - erpG gene KW - erpH gene KW - ErpA protein KW - ErpC protein KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Borrelia burgdorferi KW - nucleotide sequence KW - plasmids KW - antigens KW - Lyme disease KW - N 14640:Structure & sequence KW - J 02760:Plasmids KW - G 07203:Plasmids KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15579073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=A+family+of+genes+located+on+four+separate+32-kilobase+circular+plasmids+in+Borrelia+burgdorferi+B31&rft.au=Stevenson%2C+B%3BTilly%2C+K%3BRosa%2C+P+A&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1996-01-01&rft.volume=178&rft.issue=12&rft.spage=3508&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; plasmids; antigens; Lyme disease; nucleotide sequence ER - TY - JOUR T1 - Properties of the selenium- and molybdenum-containing nicotinic acid hydroxylase from Clostridium barkeri AN - 15575772; 3908789 AB - NADP super(+)-coupled nicotinic acid hydroxylase (NAH) has been purified to near-homogeneity from Clostridium barkeri by an improved purification scheme that allowed the isolation of milligram amounts of enzyme of higher specific activity then previously reported. NAH is most stable at alkaline pH in the presence of glycerol. The protein which consists of four dissimilar subunits occurs in forms of different molecular masses. There are 5-7 Fe, 1 FAD, and 1 Mo per 160 kDa protein protomer. Mo in the enzyme is bound to a dinucleotide form of molybdopterin and is coordinated with selenium. Mo(V), flavin in radical, and two Fe sub(2)S sub(2) clusters could be observed with EPR spectroscopy. The Se cofactor which is essential for nicotinic acid hydroxylase activity could be released from NAH as a reactive low molecular weight compound by a number of denaturing procedures. Parallel losses of Se and catalytic activity were observed during purification and storage of the enzyme. Addition of sodium selenide or selenophosphate did not restore the catalytic activity of the enzyme. Instead, NAH is reversibly inactivated by these compounds and also by sulfide. Cyanide, a common inhibitor of Mo-containing hydroxylases, does not affect NAH catalytic activity. The "as isolated" enzyme exhibits a Mo(V) EPR signal (2.067 signal) that was detected at early stages of purification. NAH exhibits a high substrate specificity toward electron donor substrates. The ability of a nicotinate analog to reduce NAH (disappearance of 2.067 signal) correlates with the rate of oxidation of the analog in the standard assay mixture. The properties of NAH differentiate the enzyme from known Mo-containing hydroxylases. JF - Biochemistry (Washington) AU - Gladyshev, V N AU - Khangulov, S V AU - Stadtman, T C AD - NHLBI/IR/LB, Bldg. 3, Rm. 108, 3 Cent. Dr., MSC 320, Bethesda, MD 20892-0320, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 212 EP - 223 VL - 35 IS - 1 SN - 0006-2960, 0006-2960 KW - Clostridium barkeri KW - nicotinic acid hydroxylase KW - Microbiology Abstracts B: Bacteriology KW - E.S.R. KW - subunit structure KW - spectroscopy KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15575772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Properties+of+the+selenium-+and+molybdenum-containing+nicotinic+acid+hydroxylase+from+Clostridium+barkeri&rft.au=Gladyshev%2C+V+N%3BKhangulov%2C+S+V%3BStadtman%2C+T+C&rft.aulast=Gladyshev&rft.aufirst=V&rft.date=1996-01-01&rft.volume=35&rft.issue=1&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - subunit structure; E.S.R.; spectroscopy ER - TY - JOUR T1 - Gonococcal opacity protein promotes bacterial entry-associated rearrangements of the epithelial cell actin cytoskeleton AN - 15569460; 3906114 AB - Neisseria gonorrhoeae enters cultured human mucosal cells following binding of a distinct gonococcal opacity (Opa) outer membrane protein to cell surface proteoglycan receptors. We examined the route of internalization that is activated by Opa-expressing gonococci (strain VP1). Microscopy of infected Chang epithelial cells showed that gonococcal uptake was insensitive to monodansylcadaverine (150 mu M), which interferes with clathrin-mediated endocytosis. Similarly, indirect immunofluorescence staining for clathrin in infected cells showed distribution of cellular clathrin unaltered from the distribution in noninfected cells. The microtubule inhibitors colchicine (50 mu M) and nocodazole (20 mu M) but not the microtubule-stabilizing agent taxol (10 mu M) caused a moderate (30 to 50%) reduction in gonococcal entry without affecting bacterial adherence. The most dramatic effects were obtained with the microfilament-disrupting agent cytochalasin D (3 mu M), which totally blocked bacterial entry into the cells. Double immunofluorescence staining of gonococci and actin filaments in infected cells demonstrated bacterium-associated accumulations of F-actin as an early signal of bacterial entry. This recruitment of F-actin was transient and disappeared once the bacteria were inside the cells. Cytochalasin D disrupted the actin cytoskeleton architecture but did not prevent the recruitment of F-actin by the bacteria. Adherent, noninvasive gonococcal Opa variants lacked the ability to mobilize F-actin. Recombinant Escherichia coli expressing the gonococcal invasion-promoting Opa of gonococcal strain MS11 (Opa sub(50)) adhered to the epithelial cells in an Opa-dependent fashion but was not internalized and did not recruit detectable amounts of F-actin. Coinfection with the E. coli recombinant strain and gonococci resulted in specific entry of the diplococci, despite the presence of large numbers of adherent E. coli cells. Together, our results indicate that Opa-mediated gonococcal entry into Chang cells resembles phagocytosis rather than macropinocytosis reported for Salmonella spp. and sequentially involves gonococcal adherence to the cell surface, Opa-dependent and cytochalasin-insensitive recruitment of F-actin, and cytochalasin D-sensitive bacterial internalization. JF - Infection and Immunity AU - Grassme, HUC AU - Ireland, R M AU - Van Putten, JPM AD - Lab. Microbial Structure and Function, NIAID, NIH, Rocky Mountain Lab., 903 South 4th St., Hamilton, MT 59840-2999, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 1621 EP - 1630 VL - 64 IS - 5 SN - 0019-9567, 0019-9567 KW - actin KW - opacity protein KW - Microbiology Abstracts B: Bacteriology KW - membrane proteins KW - cytoskeleton KW - outer membranes KW - epithelium KW - Neisseria gonorrhoeae KW - J 02721:Cell cycle, morphology and motility KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15569460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Gonococcal+opacity+protein+promotes+bacterial+entry-associated+rearrangements+of+the+epithelial+cell+actin+cytoskeleton&rft.au=Grassme%2C+HUC%3BIreland%2C+R+M%3BVan+Putten%2C+JPM&rft.aulast=Grassme&rft.aufirst=HUC&rft.date=1996-01-01&rft.volume=64&rft.issue=5&rft.spage=1621&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria gonorrhoeae; epithelium; cytoskeleton; membrane proteins; outer membranes ER - TY - JOUR T1 - Nutrition and cervical neoplasia AN - 15568456; 3905221 AB - Epidemiologic evidence on the relation between nutrition and cervical cancer is reviewed. Cervical cancer is the leading cancer among women in many developing countries, and remains a major public health problem worldwide. This review of nutritional research on cervical neoplasia encompasses the range of epithelial abnormalities from early preneoplastic lesions to invasive cancer. Identified risk factors for cervical neoplasia suggest a multifactorial etiology with several cancer-associated human papillomaviruses (HPV) as the central cause. Studies of nutritional predictors of cervical neoplasia to date, however, have been limited by inadequate HPV measures, which compromise the interpretations of findings. Current research using accurate measures of HPV will be most revealing. Nonetheless, agreement in findings from previous studies suggest a role for nutritional factors in some or all stages of cervical neoplasia. Low vitamin C and carotenoid status are associated fairly consistently with both cervical cancer and precursors, whereas results for vitamin E status are less consistent. The effect of folate status may be restricted to early preneoplastic cervical lesions and not to more advanced disease. Current research is addressing nutritional influences on HPV infection and persistence and on progression of cervical disease. Limitations and recommendations for future research directions are discussed in light of methodologic issues related to nutritional and HPV research. JF - Cancer Causes & Control AU - Potischman, N AU - Brinton, LA AD - NCI, Executive Plaza North, Suite 443, Bethesda, MD 20892, USA Y1 - 1996 PY - 1996 DA - 1996 SP - 113 EP - 126 VL - 7 IS - 1 SN - 0957-5243, 0957-5243 KW - papilloma virus (human) KW - reproductive systems KW - cervix KW - man KW - Virology & AIDS Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - etiology KW - diets KW - females KW - reviews KW - nutrition KW - cancer KW - X 24120:Food, additives & contaminants KW - V 22114:Human oncogenic viruses KW - H SM3.8.6:DIET KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15568456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Nutrition+and+cervical+neoplasia&rft.au=Potischman%2C+N%3BBrinton%2C+LA&rft.aulast=Potischman&rft.aufirst=N&rft.date=1996-01-01&rft.volume=7&rft.issue=1&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - nutrition; cancer; diets; etiology; females; reviews; cervix; man ER - TY - JOUR T1 - Long-term cognitive impairment in MPTP-treated rhesus monkeys. AN - 77899099; 8742427 AB - Following MPTP administration, monkeys manifest cognitive deficits on tasks known to assess the fronto-striatal system; there are, however, no data regarding long-term cognitive effects. In this study, we examined the cognitive abilities of monkeys 10 years after MPTP administration. MPTP-treated monkeys and age-matched controls performed a spatial delayed response task with fixed and random delays. The MPTP-treated monkeys were impaired in both versions of the task. Both groups performed at the same level at very short delays suggesting that the nature of the impairment is related to a spatial memory deficit that is still apparent 10 years after treatment. These results suggest that, like Parkinson's patients, the MPTP-treated primates display spatial deficits. JF - Neuroreport AU - Fernandez-Ruiz, J AU - Doudet, D J AU - Aigner, T G AD - Laboratory of Neuropsychology, NIMH, Bethesda, MD 20892-4415, USA. Y1 - 1995/12/29/ PY - 1995 DA - 1995 Dec 29 SP - 102 EP - 104 VL - 7 IS - 1 SN - 0959-4965, 0959-4965 KW - Index Medicus KW - Reaction Time -- drug effects KW - Animals KW - Analysis of Variance KW - Macaca mulatta KW - Chronic Disease KW - Male KW - Spatial Behavior -- drug effects KW - MPTP Poisoning KW - Cognition Disorders -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77899099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Long-term+cognitive+impairment+in+MPTP-treated+rhesus+monkeys.&rft.au=Fernandez-Ruiz%2C+J%3BDoudet%2C+D+J%3BAigner%2C+T+G&rft.aulast=Fernandez-Ruiz&rft.aufirst=J&rft.date=1995-12-29&rft.volume=7&rft.issue=1&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-17 N1 - Date created - 1996-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of dehydroepiandrosterone on MNU-induced breast cancer in Sprague-Dawley rats. AN - 77865778; 8597482 JF - Annals of the New York Academy of Sciences AU - Lubet, R A AU - McCormick, D M AU - Gordon, G M AU - Grubbs, C AU - Lei, X D AU - Prough, R A AU - Steele, V E AU - Kelloff, G J AU - Thomas, C F AU - Moon, R D AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/12/29/ PY - 1995 DA - 1995 Dec 29 SP - 340 EP - 341 VL - 774 SN - 0077-8923, 0077-8923 KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Liver Neoplasms -- chemically induced KW - Female KW - Microbodies KW - Mammary Neoplasms, Experimental -- prevention & control KW - Dehydroepiandrosterone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77865778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Effects+of+dehydroepiandrosterone+on+MNU-induced+breast+cancer+in+Sprague-Dawley+rats.&rft.au=Lubet%2C+R+A%3BMcCormick%2C+D+M%3BGordon%2C+G+M%3BGrubbs%2C+C%3BLei%2C+X+D%3BPrough%2C+R+A%3BSteele%2C+V+E%3BKelloff%2C+G+J%3BThomas%2C+C+F%3BMoon%2C+R+D&rft.aulast=Lubet&rft.aufirst=R&rft.date=1995-12-29&rft.volume=774&rft.issue=&rft.spage=340&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-17 N1 - Date created - 1996-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Definitions of stress and sympathetic neuronal responses. AN - 77827365; 8597398 AB - 1. The precise physical definitions of stress as a force per unit area and of strain as the deformation of a solid subjected to that force are conceptually similar to the demands placed upon living organisms and the responses of organisms to those demands. 2. Cannon recognized that a "breaking strain" at a "critical stress" level can overwhelm homeostatic mechanisms and suggested that such a state is signaled by appearance of "secondary, irrelevant effects." The primary mechanisms of maintaining homeostasis are highly specific; and compensatory responses are mediated by the autonomic nervous system, and the less specific responses are mediated by the adrenal medullary hormone, epinephrine. 3. Selye extended this concept to include other hormonal responses, particularly of the hypothalamic-pituitary-adrenal axis, as components of a stereotypic response common to all stresses. He redefined stress as a state in which this stereospecific response has been evoked and popularized the notion that a variety of diseases are produced as a result of excessive or deficient adaptive processes during the stress response. 4. Both Cannon and Selye recognized that the responses to stresses differ among individuals and that such differences are due to genetic differences as modified by experience (Selye called these "conditioning factors"). Both attributed highly specific homeostatic responses to nervous control and both recognized that hormonal responses are necessarily less specific than neuronal responses. 5. Selye's concept of a single stereotypic syndrome that results from any demand upon the body, however, needs to be modified to reflect differences in the pattern of responses to various stresses. Data on responses to several stresses show that when homeostatic mechanisms do not predominate, the pattern of nonspecific, particularly hormonal, responses may differ among stresses. The essential fact, however, that most demands upon the body, when exceeding a critical level, elicit an array of complex neuroendocrine responses, and that these responses may have harmful effects, remains a landmark contribution. JF - Annals of the New York Academy of Sciences AU - Kopin, I J AD - Clinical Neuroscience Branch, NINDS, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/12/29/ PY - 1995 DA - 1995 Dec 29 SP - 19 EP - 30 VL - 771 SN - 0077-8923, 0077-8923 KW - Catecholamines KW - 0 KW - Formaldehyde KW - 1HG84L3525 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Index Medicus KW - Hypothalamo-Hypophyseal System -- physiology KW - Animals KW - Catecholamines -- blood KW - Blood Volume KW - Sympathetic Nervous System -- physiology KW - Humans KW - Homeostasis KW - Models, Biological KW - Formaldehyde -- toxicity KW - Pituitary-Adrenal System -- physiology KW - Adrenocorticotropic Hormone -- blood KW - Stress, Physiological -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77827365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Definitions+of+stress+and+sympathetic+neuronal+responses.&rft.au=Kopin%2C+I+J&rft.aulast=Kopin&rft.aufirst=I&rft.date=1995-12-29&rft.volume=771&rft.issue=&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-17 N1 - Date created - 1996-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Co-treatment with MK-801 potentiates naloxone-precipitated morphine withdrawal in the isolated spinal cord of the neonatal rat. AN - 77901510; 8788444 AB - The effects of acute and chronic administration of (MK-801: [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate) were assessed on morphine dependence in the isolated spinal cord of the neonatal rat and on behavioral measures in intact adult rats. Neonatal rats were treated chronically (3 or 4 days) with injections of either morphine, morphine + MK-801, or saline. Naloxone (10 microM) which increased baseline ventral root spontaneous firing, induced more activity in spinal cords from morphine-treated neonates than in saline controls. In spinal cords from neonates receiving MK-801 with morphine, naloxone-induced spontaneous firing was significantly greater than in saline-treated and morphine alone-treated neonates. Acute MK-801 attenuated naloxone-induced firing in the morphine-treated group. Chronic co-treatment with MK-801 increased locomotor signs of withdrawal and decreased mastication in intact adult rats which had been treated chronically with morphine. MK-801-induced enhancement of morphine withdrawal is consistent with upregulation of NMDA receptors. JF - European journal of pharmacology AU - Bell, J A AU - Beglan, C L AD - Neuroimaging and Drug Action Section, Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1995/12/27/ PY - 1995 DA - 1995 Dec 27 SP - 297 EP - 301 VL - 294 IS - 1 SN - 0014-2999, 0014-2999 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Narcotic Antagonists KW - Narcotics KW - Naloxone KW - 36B82AMQ7N KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Morphine KW - 76I7G6D29C KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Rats, Inbred F344 KW - In Vitro Techniques KW - Morphine Dependence -- prevention & control KW - Electrophysiology KW - Drug Synergism KW - Male KW - Spinal Cord -- physiopathology KW - Naloxone -- pharmacology KW - Substance Withdrawal Syndrome -- physiopathology KW - Morphine -- adverse effects KW - Spinal Cord -- drug effects KW - Narcotics -- adverse effects KW - Narcotic Antagonists -- pharmacology KW - Animals, Newborn -- physiology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77901510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Co-treatment+with+MK-801+potentiates+naloxone-precipitated+morphine+withdrawal+in+the+isolated+spinal+cord+of+the+neonatal+rat.&rft.au=Bell%2C+J+A%3BBeglan%2C+C+L&rft.aulast=Bell&rft.aufirst=J&rft.date=1995-12-27&rft.volume=294&rft.issue=1&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-12 N1 - Date created - 1997-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathway across blood-brain barrier opened by the bradykinin agonist, RMP-7. AN - 75502345; 8821743 AB - The route taken by lanthanum (MW 139) across cerebral endothelium was delineated when the blood-brain barrier was opened by RMP-7, a novel bradykinin agonist. Balb C mice were infused through a jugular vein with LaCl3 with or without RMP-7 (5 micrograms/kg). Ten minutes later, the brains were fixed with aldehydes and processed for electron microscopy. The patency of the junctions between endothelial cells was estimated by counting the number of junctions penetrated by LaCl3. Tracer penetrated the junctions in about 25% of microvessels in vehicle infused, control mice and about 58% in the RMP-7 group, where more junctions per vessel were also penetrated. The LaCl3 then penetrated the basal lamina in about 20% of all microvessels in the RMP-7 group, versus 0.50% in the control group. From the basal lamina, the tracer entered perivascular spaces in about 13% of all microvessels in the RMP-7 group and about 0.07% in the controls. Very few endocytic pits or vesicles in the RMP-7 group were labeled, so LaCl3 did not cross endothelium by transcytosis. The increased number of tight junctions penetrated by tracer and its spread into periendothelial basal lamina and interstitial clefts indicated, therefore, a paracellular route of exudation in the RMP-7 treated animals. JF - Brain research AU - Sanovich, E AU - Bartus, R T AU - Friden, P M AU - Dean, R L AU - Le, H Q AU - Brightman, M W AD - Laboratory of Neurobiology, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/12/24/ PY - 1995 DA - 1995 Dec 24 SP - 125 EP - 135 VL - 705 IS - 1-2 SN - 0006-8993, 0006-8993 KW - RMP 7 KW - 159768-75-9 KW - Sodium Chloride KW - 451W47IQ8X KW - Lanthanum KW - 6I3K30563S KW - Bradykinin KW - S8TIM42R2W KW - Index Medicus KW - Hypotension -- chemically induced KW - Animals KW - Endothelium -- metabolism KW - Injections, Intravenous KW - Cerebrovascular Circulation -- physiology KW - Mice KW - Mice, Inbred BALB C KW - Consciousness KW - Endothelium -- ultrastructure KW - Microscopy, Electron KW - Male KW - Tight Junctions -- metabolism KW - Sodium Chloride -- pharmacology KW - Blood-Brain Barrier -- drug effects KW - Bradykinin -- analogs & derivatives KW - Bradykinin -- agonists KW - Lanthanum -- pharmacokinetics KW - Bradykinin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75502345?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Pathway+across+blood-brain+barrier+opened+by+the+bradykinin+agonist%2C+RMP-7.&rft.au=Sanovich%2C+E%3BBartus%2C+R+T%3BFriden%2C+P+M%3BDean%2C+R+L%3BLe%2C+H+Q%3BBrightman%2C+M+W&rft.aulast=Sanovich&rft.aufirst=E&rft.date=1995-12-24&rft.volume=705&rft.issue=1-2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-06 N1 - Date created - 1996-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The chemopreventive agent diallyl sulfide. A structurally atypical phenobarbital-type inducer. AN - 77767770; 8849338 AB - Diallyl sulfide (DAS), a known chemopreventive agent, was administered i.g. (200 or 500 mg/kg body wt/day) to male F344/NCr rats for 4 days. Livers were removed, and hepatic levels of a variety of drug-metabolizing enzymes were determined with either catalytic assays or by quantifying levels of total cellular RNA coding for the individual genes of interest. The high dose of DAS induced the cytochrome P450 (CYP) 2B subfamily to near maximal levels [i.e. similar to those induced by phenobarbital (PB)] and induced the CYP3A subfamily, while having minimal effects on the levels of the CYP1A subfamily. In addition, DAS induced the glutathione S-transferase alpha subfamily, the glutathione S-transferase mu subfamily, and epoxide hydrolase. Unlike PB, however, DAS was also able to induce quinone oxidoreductase. In fact, the pleiotropic hepatic response to DAS appeared to be similar to that elicited by PB, with the exception that only DAS induced quinone oxidoreductase. Finally, we determined that DAS induced the levels of a specific nuclear binding protein that appears to be associated with the induction of various genes that are part of the pleiotropic response caused by PB-type inducers. JF - Biochemical pharmacology AU - Dragnev, K H AU - Nims, R W AU - Lubet, R A AD - Laboratory of Comparative Carcinogenesis, NCI-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1995/12/22/ PY - 1995 DA - 1995 Dec 22 SP - 2099 EP - 2104 VL - 50 IS - 12 SN - 0006-2952, 0006-2952 KW - Allyl Compounds KW - 0 KW - Antioxidants KW - Cytochrome P-450 Enzyme Inhibitors KW - Sulfides KW - allyl sulfide KW - 60G7CF7CWZ KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - DDT KW - CIW5S16655 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Phenobarbital -- pharmacology KW - Base Sequence KW - Glutathione Transferase -- biosynthesis KW - Molecular Sequence Data KW - Enzyme Induction KW - Transcription, Genetic KW - DDT -- pharmacology KW - Male KW - Structure-Activity Relationship KW - Liver -- enzymology KW - Antioxidants -- pharmacology KW - Liver -- drug effects KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Sulfides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77767770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=The+chemopreventive+agent+diallyl+sulfide.+A+structurally+atypical+phenobarbital-type+inducer.&rft.au=Dragnev%2C+K+H%3BNims%2C+R+W%3BLubet%2C+R+A&rft.aulast=Dragnev&rft.aufirst=K&rft.date=1995-12-22&rft.volume=50&rft.issue=12&rft.spage=2099&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenic alteration of potential active-site residues of the A subunit of Escherichia coli heat-labile enterotoxin. Evidence for a catalytic role for glutamic acid 112. AN - 77736180; 8530486 AB - Escherichia coli heat-labile enterotoxin (LT) and the related cholera toxin exert their effects on eukaryotic cells through the ADP-ribosylation of guanine nucleotide-binding proteins of the adenylate cyclase complex. The availability of the crystal structure for LT has permitted the tentative identification of residues that lie within or are vicinal to a presumptive NAD(+)-binding site and thus may play a role in substrate binding or catalysis. Using a plasmid clone encoding the A subunit of LT, we have introduced substitutions at such potential active-site residues and analyzed the enzymatic properties of the resultant mutant analogs. Enzymatic analyses, employing both transducin and agmatine as acceptor substrates, revealed that substitutions at serine 61, glutamic acid 110, and glutamic acid 112 resulted in reduction of enzyme activity to < 10% of wild-type levels. Kinetic analyses indicated that alteration of these sites affected the catalytic rate of the enzyme and had little or no effect on the binding of either NAD+ or agmatine. Of the mutant analogs analyzed, only glutamic acid 112 appeared to represent an essential catalytic residue as judged by the relative effects on kcat and kcat/Km. The results provide formal evidence that glutamic acid 112 of the A subunit of LT represents a functional homolog or analog of catalytic glutamic acid residues that have been identified in several other bacterial ADP-ribosylating toxins and that it may play an essential role in rendering NAD+ susceptible to nucleophilic attack by an incoming acceptor substrate. JF - The Journal of biological chemistry AU - Cieplak, W AU - Mead, D J AU - Messer, R J AU - Grant, C C AD - Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA. Y1 - 1995/12/22/ PY - 1995 DA - 1995 Dec 22 SP - 30545 EP - 30550 VL - 270 IS - 51 SN - 0021-9258, 0021-9258 KW - Bacterial Toxins KW - 0 KW - Enterotoxins KW - Escherichia coli Proteins KW - Macromolecular Substances KW - Peptide Fragments KW - Recombinant Proteins KW - heat-labile enterotoxin, E coli KW - Glutamic Acid KW - 3KX376GY7L KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - NAD+ Nucleosidase KW - EC 3.2.2.5 KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Peptide Fragments -- chemistry KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Peptide Fragments -- isolation & purification KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Cloning, Molecular KW - Binding Sites KW - Escherichia coli -- metabolism KW - Enterotoxins -- chemistry KW - Bacterial Toxins -- metabolism KW - Bacterial Toxins -- isolation & purification KW - Enterotoxins -- metabolism KW - NAD+ Nucleosidase -- metabolism KW - Enterotoxins -- isolation & purification KW - Escherichia coli -- genetics KW - Bacterial Toxins -- chemistry KW - Poly(ADP-ribose) Polymerases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77736180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Site-directed+mutagenic+alteration+of+potential+active-site+residues+of+the+A+subunit+of+Escherichia+coli+heat-labile+enterotoxin.+Evidence+for+a+catalytic+role+for+glutamic+acid+112.&rft.au=Cieplak%2C+W%3BMead%2C+D+J%3BMesser%2C+R+J%3BGrant%2C+C+C&rft.aulast=Cieplak&rft.aufirst=W&rft.date=1995-12-22&rft.volume=270&rft.issue=51&rft.spage=30545&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-30 N1 - Date created - 1996-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Meeting highlights: a reappraisal of research results for the local treatment of early stage breast cancer. AN - 77715657; 7494227 JF - Journal of the National Cancer Institute AU - Abrams, J S AU - Phillips, P H AU - Friedman, M A AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD, USA. Y1 - 1995/12/20/ PY - 1995 DA - 1995 Dec 20 SP - 1837 EP - 1845 VL - 87 IS - 24 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Age Factors KW - Randomized Controlled Trials as Topic KW - Combined Modality Therapy KW - Humans KW - Mastectomy, Segmental KW - Aged KW - Radiotherapy -- adverse effects KW - Risk Factors KW - Adult KW - Neoplasms, Radiation-Induced KW - Mastectomy KW - Middle Aged KW - Time Factors KW - Survival Analysis KW - Breast Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77715657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Meeting+highlights%3A+a+reappraisal+of+research+results+for+the+local+treatment+of+early+stage+breast+cancer.&rft.au=Abrams%2C+J+S%3BPhillips%2C+P+H%3BFriedman%2C+M+A&rft.aulast=Abrams&rft.aufirst=J&rft.date=1995-12-20&rft.volume=87&rft.issue=24&rft.spage=1837&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the wild-type form of 4a-carbinolamine dehydratase and two naturally occurring mutants associated with hyperphenylalaninemia. AN - 77769606; 8618906 AB - The characterization of 4a-carbinolamine dehydratase with the enzymatically synthesized natural substrate revealed non-Michaelis-Menten kinetics. A Hill coefficient of 1.8 indicates that the dehydratase exists as a multisubunit enzyme that shows cooperativity. A mild form of hyperphenylalaninemia with high 7-biopterin levels has been linked to mutations in the human 4a-carbinolamine dehydratase gene. We have now cloned and expressed two mutant forms of the protein based on a patient's DNA sequences. The kinetic parameters of the mutant C82R reveal a 60% decrease in Vmax but no change in Km (approximately 5 microM), suggesting that the cysteine residue is not involved in substrate binding. Its replacement by arginine possibly causes a conformational change in the active center. Like the wild-type enzyme, this mutant is heat stable and forms a tetramer. The susceptibility to proteolysis of C82R, however, is markedly increased in vitro compared with the wild-type protein. We have also observed a decrease in the expression levels of C82R protein in transfected mammalian cells, which could be due to proteolytic instability. The 18-amino acid-truncated mutant GLu-87--> termination could not be completely purified and characterized due to minute levels of expression and its extremely low solubility as a fusion protein. No dehydratase activity was detected in crude extracts from transformed bacteria or transfected mammalian cells. Considering the decrease in specific activity and stability of the mutants, we conclude that the patient probably has less than 10% residual dehydratase activity, which could be responsible for the mild hyperphenylalaninemia and the high 7-biopterin levels. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Johnen, G AU - Kowlessur, D AU - Citron, B A AU - Kaufman, S AD - Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1995/12/19/ PY - 1995 DA - 1995 Dec 19 SP - 12384 EP - 12388 VL - 92 IS - 26 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Macromolecular Substances KW - Recombinant Proteins KW - Phenylalanine KW - 47E5O17Y3R KW - Hydro-Lyases KW - EC 4.2.1.- KW - pterin-4a-carbinolamine dehydratase KW - EC 4.2.1.96 KW - Index Medicus KW - Animals KW - Thermodynamics KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Amino Acid Sequence KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Polymerase Chain Reaction KW - Base Sequence KW - Chromatography, Gel KW - Transfection KW - Recombinant Proteins -- metabolism KW - Enzyme Stability KW - Kinetics KW - Molecular Sequence Data KW - CHO Cells KW - Recombinant Proteins -- chemistry KW - Cricetinae KW - Phenylalanine -- metabolism KW - Hydro-Lyases -- genetics KW - Point Mutation KW - Amino Acid Metabolism, Inborn Errors -- genetics KW - Hydro-Lyases -- chemistry KW - Hydro-Lyases -- metabolism KW - Amino Acid Metabolism, Inborn Errors -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77769606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Characterization+of+the+wild-type+form+of+4a-carbinolamine+dehydratase+and+two+naturally+occurring+mutants+associated+with+hyperphenylalaninemia.&rft.au=Johnen%2C+G%3BKowlessur%2C+D%3BCitron%2C+B+A%3BKaufman%2C+S&rft.aulast=Johnen&rft.aufirst=G&rft.date=1995-12-19&rft.volume=92&rft.issue=26&rft.spage=12384&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-07 N1 - Date created - 1996-06-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1989 May 25;264(15):8585-96 [2722790] Biochem Biophys Res Commun. 1988 Jun 16;153(2):715-21 [3382399] FEBS Lett. 1991 Jul 8;285(1):17-20 [2065777] Science. 1991 Dec 20;254(5039):1762-7 [1763325] FEBS Lett. 1992 May 4;302(1):73-6 [1350256] Eur J Biochem. 1992 Aug 15;208(1):139-44 [1355046] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10109-13 [1359535] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11891-4 [1465414] PCR Methods Appl. 1992 Nov;2(2):124-30 [1477668] J Biol Chem. 1993 Mar 5;268(7):4828-31 [8444860] Curr Opin Genet Dev. 1993 Apr;3(2):246-53 [8504250] Am J Hum Genet. 1993 Sep;53(3):768-74 [8352282] Adv Exp Med Biol. 1993;338:111-4 [8304092] Adv Exp Med Biol. 1993;338:47-54 [8304161] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1366-70 [8108417] Structure. 1994 Oct 15;2(10):937-44 [7866745] Science. 1995 Apr 28;268(5210):556-9 [7725101] Biochemistry. 1995 May 2;34(17):5801-10 [7727440] Development. 1995 Apr;121(4):1217-26 [7743933] EMBO J. 1995 May 1;14(9):2034-42 [7744010] Proc Natl Acad Sci U S A. 1995 May 23;92(11):4743-7 [7761394] J Lab Clin Med. 1957 Nov;50(5):733-6 [13476030] Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):385-9 [1988938] J Biol Chem. 1970 Sep 25;245(18):4751-9 [5456148] J Biol Chem. 1973 Jun 25;248(12):4235-41 [4711606] N Engl J Med. 1975 Oct 16;293(16):785-90 [1160969] Adv Hum Genet. 1983;13:217-97 [6362361] Methods Enzymol. 1987;142:3-17 [3600372] Erratum In: Proc Natl Acad Sci U S A 1996 Apr 30;93(9):4519 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proposed active site domain in estrogen sulfotransferase as determined by mutational analysis. AN - 77763833; 8618895 AB - Point mutations were selectively introduced into a cDNA for guinea pig estrogen sulfotransferase (gpEST); each construct was then expressed in Chinese hamster ovary K1 cells. The molecular site chosen for study is a conserved GXXGXXK sequence that resembles the P-loop-type nucleotide-binding motif for ATP- and GTP-binding proteins and is located near the C terminus of all steroid and phenol(aryl) sulfotransferases for which the primary structures are known. Preliminary experiments demonstrated that the GXXGXXK motif is essential for binding the activated sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS). The present study was undertaken to ascertain the relative importance of each individual residue of the motif. While the mutation of a single motif residue had little effect on the interaction between gpEST and PAPS as determined by kinetic analysis and photoaffinity labeling, the mutation of any two residues in concert resulted in an approximate 10-fold increase in the Km for PAPS and reduced photoaffinity labeling. The mutation of all three motif residues resulted in an inactive enzyme and complete loss of photoaffinity labeling. Interestingly, several mutants also displayed a striking effect on the Km for the steroid substrate; double mutants, again, demonstrated greater perturbations (8- to 28-fold increase) than did single mutants. Unexpectedly, whereas the mutation of nonmotif residues had a negligible effect on the Km for PAPS, a marked increase in the Km for the estrogen substrate ( > 30-fold) was noted. On the basis of these findings, it is concluded that the sequence GISGDWKN within the C-terminal domain of gpEST represents a critical component of the active site. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Driscoll, W J AU - Komatsu, K AU - Strott, C A AD - Section on Steroid Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA. Y1 - 1995/12/19/ PY - 1995 DA - 1995 Dec 19 SP - 12328 EP - 12332 VL - 92 IS - 26 SN - 0027-8424, 0027-8424 KW - Affinity Labels KW - 0 KW - Recombinant Proteins KW - Sulfotransferases KW - EC 2.8.2.- KW - estrone sulfotransferase KW - EC 2.8.2.4 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Guinea Pigs KW - Cytosol -- enzymology KW - DNA Mutational Analysis KW - Amino Acid Sequence KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Polymerase Chain Reaction KW - Conserved Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Point Mutation KW - Molecular Sequence Data KW - CHO Cells KW - Recombinant Proteins -- chemistry KW - Cricetinae KW - Sulfotransferases -- metabolism KW - Sulfotransferases -- isolation & purification KW - Sulfotransferases -- chemistry KW - Sulfotransferases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77763833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Proposed+active+site+domain+in+estrogen+sulfotransferase+as+determined+by+mutational+analysis.&rft.au=Driscoll%2C+W+J%3BKomatsu%2C+K%3BStrott%2C+C+A&rft.aulast=Driscoll&rft.aufirst=W&rft.date=1995-12-19&rft.volume=92&rft.issue=26&rft.spage=12328&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-07 N1 - Date created - 1996-06-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Biol Chem. 1951 Nov;193(1):265-75 [14907713] Proc Natl Acad Sci U S A. 1986 Feb;83(4):952-6 [3513168] Science. 1988 Feb 19;239(4842):888-93 [2448879] Nature. 1989 Sep 21;341(6239):209-14 [2476675] Biotechniques. 1990 Feb;8(2):178-83 [2180450] Mol Pharmacol. 1991 Jan;39(1):34-41 [1987450] Trends Biochem Sci. 1990 Nov;15(11):430-4 [2126155] Mol Endocrinol. 1992 Aug;6(8):1216-26 [1406700] Endocrinology. 1993 Nov;133(5):2284-91 [8404682] J Biol Chem. 1993 Nov 5;268(31):23496-503 [8226877] Endocrinology. 1994 Sep;135(3):938-43 [8070389] Biochem Biophys Res Commun. 1994 Nov 15;204(3):1178-85 [7980593] J Biol Chem. 1994 Dec 2;269(48):30313-9 [7982943] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8176-9 [7667264] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determining the value of additional surrogate exposure data for improving the estimate of an odds ratio. AN - 77888515; 8746890 AB - We consider the design of both cohort and case-control studies in which an initial ('stage 1') sample of complete data on an error-free disease indicator (D), a correct ('gold standard') dichotomous exposure measurement (X) and an error-prone exposure measurement (Z) are available. We calculate the amount of additional information on the odds ratio relating D to X that one can obtain from a second ('stage 2') sample of measurements only on D and Z. If one allows for differential measurement error in Z, there is often little advantage in having more than four times as much data in stage 2 data as in stage 1. With the assumption that a non-differential measurement error model is reasonable, larger amounts of stage 2 data can be useful. Simulations indicate that stage 1 samples of modest size (50 cases in case-control studies and 50 failures in cohort studies) yield sufficiently reliable estimates of needed parameters to assist in determining an appropriate size for the stage 2 sample. These ideas apply in settings either where the amount of stage 1 data is limited and fixed by external constraints or where one has gathered stage 1 data in advance to avoid collecting superfluous stage 2 data. JF - Statistics in medicine AU - Dahm, P F AU - Gail, M H AU - Rosenberg, P S AU - Pee, D AD - Biostatistics Branch, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. Y1 - 1995/12/15/ PY - 1995 DA - 1995 Dec 15 SP - 2581 EP - 2598 VL - 14 IS - 23 SN - 0277-6715, 0277-6715 KW - Carcinogens KW - 0 KW - Index Medicus KW - Risk KW - Health Status Indicators KW - Coronary Disease -- prevention & control KW - Humans KW - Sampling Studies KW - Neoplasms -- etiology KW - Odds Ratio KW - Cohort Studies KW - Case-Control Studies KW - Data Interpretation, Statistical KW - Randomized Controlled Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77888515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=Determining+the+value+of+additional+surrogate+exposure+data+for+improving+the+estimate+of+an+odds+ratio.&rft.au=Dahm%2C+P+F%3BGail%2C+M+H%3BRosenberg%2C+P+S%3BPee%2C+D&rft.aulast=Dahm&rft.aufirst=P&rft.date=1995-12-15&rft.volume=14&rft.issue=23&rft.spage=2581&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-27 N1 - Date created - 1996-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glia-dependent neurotoxicity and neuroprotection in mesencephalic cultures. AN - 77881234; 8750970 AB - Dopaminergic neurotoxicities of 6-hydroxydopamine (6-OHDA) and the lipopolysaccharide (LPS) were compared in rat mesencephalic cultures plated on poly-L-lysine or on glial monolayers. In the neuron-enriched cultures plated on polylysine, 6-OHDA killed 89% of the tyrosine hydroxylase (TH)-immunopositive neurons, but LPS was not neurotoxic. Conversely, in mixed neuron/glial cultures, 6-OHDA killed only 27% of the TH-immunopositive neurons while LPS killed 70%. The mixed neuronal/glial mesencephalic culture offers a better in vitro model for studying possible mechanisms involved in Parkinson's disease. JF - Brain research AU - Bronstein, D M AU - Perez-Otano, I AU - Sun, V AU - Mullis Sawin, S B AU - Chan, J AU - Wu, G C AU - Hudson, P M AU - Kong, L Y AU - Hong, J S AU - McMillian, M K AD - Laboratory of Environmental Neuroscience, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1995/12/15/ PY - 1995 DA - 1995 Dec 15 SP - 112 EP - 116 VL - 704 IS - 1 SN - 0006-8993, 0006-8993 KW - Lipopolysaccharides KW - 0 KW - Neuroprotective Agents KW - Neurotoxins KW - Polylysine KW - 25104-18-1 KW - Oxidopamine KW - 8HW4YBZ748 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Index Medicus KW - Rats KW - Tyrosine 3-Monooxygenase -- analysis KW - Animals KW - Cell Count KW - Cells, Cultured KW - Neurons -- drug effects KW - Neurons -- enzymology KW - Mesencephalon -- drug effects KW - Oxidopamine -- toxicity KW - Neuroprotective Agents -- metabolism KW - Lipopolysaccharides -- toxicity KW - Neuroglia -- drug effects KW - Mesencephalon -- cytology KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77881234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Glia-dependent+neurotoxicity+and+neuroprotection+in+mesencephalic+cultures.&rft.au=Bronstein%2C+D+M%3BPerez-Otano%2C+I%3BSun%2C+V%3BMullis+Sawin%2C+S+B%3BChan%2C+J%3BWu%2C+G+C%3BHudson%2C+P+M%3BKong%2C+L+Y%3BHong%2C+J+S%3BMcMillian%2C+M+K&rft.aulast=Bronstein&rft.aufirst=D&rft.date=1995-12-15&rft.volume=704&rft.issue=1&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-17 N1 - Date created - 1996-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A prospective evaluation of ifosfamide-related nephrotoxicity in children and young adults. AN - 77868270; 8625085 AB - Ifosfamide has been associated with proximal renal tubular dysfunction resembling Fanconi-like syndrome and leading to rickets in young children. The characteristic manifestations of this nephrotoxicity include phosphaturia and hypophosphatemia, glycosuria, aminoaciduria, renal tubular acidosis, and urinary loss of low molecular weight serum proteins. However, the relationship between acute ifosfamide nephrotoxicity, which is frequently subclinical, and long term renal damage is unclear. In this prospective study, the laboratory features of ifosfamide-induced acute nephrotoxicity were characterized further and correlated with the development of chronic nephropathy. The renal function of newly diagnosed children and young adults with high risk sarcomas was followed during therapy with a high dose ifosfamide-containing regimen. Serum and urine were collected regularly immediately before and after 5-day cycles of ifosfamide throughout treatment for determination of the fractional excretion of electrolytes (sodium, potassium, phosphate, magnesium, calcium) and glucose and urinary excretion of amino acids and beta 2-microglobulin. Significant changes in the renal threshold of phosphate excretion, the fractional excretion of calcium and glucose, and the urinary excretion of beta 2-microglobulin were observed when comparing pretreatment values with those at the end of a 5-day treatment cycle. The median renal threshold of phosphate excretion decreased from 1.22 to 0.82 mmol/L (P < 0.0001). The median fractional excretions of calcium and glucose increased from 1.05% to 1.68% (P < 0.0001) and 0.05% to 0.08% (P = 0.0006), respectively. Beta 2-microglobulin excretion increased by 70-fold from 0.02 to 1.42 mg/mmol (P < 0.0001). Except for glucose and beta 2-microglobulin excretion, renal parameters returned to baseline before the next ifosfamide treatment cycle. Acute aminoaciduria was observed in 21 of 23 patients. Chronic nephrotoxicity, as defined by the development of a Fanconi-like syndrome or chronic tubular electrolyte loss requiring oral supplementation, developed in the three patients with the highest urinary excretion of beta 2-microglobulin after ifosfamide therapy. Prospectively, high dose ifosfamide was associated with a 4% incidence of Fanconi-like syndrome; however, evidence of acute reversible subclinical nephrotoxicity was observed for all patients. Severe beta 2-microglobulinuria appeared to be a prognostic laboratory indicator for the development of chronic nephrotoxicity. JF - Cancer AU - Ho, P T AU - Zimmerman, K AU - Wexler, L H AU - Blaney, S AU - Jarosinski, P AU - Weaver-McClure, L AU - Izraeli, S AU - Balis, F M AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/12/15/ PY - 1995 DA - 1995 Dec 15 SP - 2557 EP - 2564 VL - 76 IS - 12 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents, Alkylating KW - 0 KW - beta 2-Microglobulin KW - Ifosfamide KW - UM20QQM95Y KW - Abridged Index Medicus KW - Index Medicus KW - Prospective Studies KW - Humans KW - Adult KW - Prognosis KW - beta 2-Microglobulin -- urine KW - Predictive Value of Tests KW - Child KW - Sarcoma -- drug therapy KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Kidney Diseases -- physiopathology KW - Kidney Diseases -- urine KW - Ifosfamide -- adverse effects KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77868270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=A+prospective+evaluation+of+ifosfamide-related+nephrotoxicity+in+children+and+young+adults.&rft.au=Ho%2C+P+T%3BZimmerman%2C+K%3BWexler%2C+L+H%3BBlaney%2C+S%3BJarosinski%2C+P%3BWeaver-McClure%2C+L%3BIzraeli%2C+S%3BBalis%2C+F+M&rft.aulast=Ho&rft.aufirst=P&rft.date=1995-12-15&rft.volume=76&rft.issue=12&rft.spage=2557&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-26 N1 - Date created - 1996-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abrogation of p53-induced apoptosis by the hepatitis B virus X gene. AN - 77743574; 8521383 AB - The p53 tumor suppressor gene product is a transcriptional transactivator and a potent apoptotic inducer. The fact that many of the DNA tumor virus oncoproteins bind to p53 and affect these p53 functions indicates that this interaction is an important step in oncogenic transformation. We and others have recently demonstrated that the hepatitis B virus oncoprotein, HBx, can form a complex with p53 and inhibit its DNA consensus sequence binding and transcriptional transactivator activity. Using a microinjection technique, we report here that HBx efficiently blocks p53-mediated apoptosis and describe the results of studies exploring two possible mechanisms of HBx action. First, inhibition of apoptosis may be a consequence of the failure of p53, in the presence of HBx, to upregulate genes, such as p21WAF1, Bax, or Fas, that are involved in the apoptotic pathway. Data consistent with this hypothesis include HBx reduction of p53-mediated p21WAF1 expression. Alternatively, HBx could affect p53 binding to the TFIIH transcription-nucleotide excision repair complex as HBx binds to the COOH terminus of p53 and inhibits its binding to XPB or XPD. Binding of p53 to these constituents of the core TFIIH is a process that may be involved in apoptosis. Because the HBx gene is frequently integrated into the genome of hepatocellular carcinoma cells, inhibition of p53-mediated apoptosis by HBx may provide a clonal selective advantage for hepatocytes expressing this integrated viral gene during the early stages of human liver carcinogenesis. JF - Cancer research AU - Wang, X W AU - Gibson, M K AU - Vermeulen, W AU - Yeh, H AU - Forrester, K AU - Stürzbecher, H W AU - Hoeijmakers, J H AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Besthesda, Maryland 20892-4255, USA. Y1 - 1995/12/15/ PY - 1995 DA - 1995 Dec 15 SP - 6012 EP - 6016 VL - 55 IS - 24 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - Hepatitis B Antigens KW - Proteins KW - Trans-Activators KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - hepatitis B virus X protein KW - XPBC-ERCC-3 protein KW - 146045-44-5 KW - RAD51 protein, human KW - EC 2.7.7.- KW - Rad51 Recombinase KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Hepatitis B -- pathology KW - DNA Repair KW - Cells, Cultured KW - Humans KW - Hepatitis B virus -- genetics KW - Proteins -- metabolism KW - Protein Binding KW - DNA-Binding Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Trans-Activators -- physiology KW - Hepatitis B Antigens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77743574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Abrogation+of+p53-induced+apoptosis+by+the+hepatitis+B+virus+X+gene.&rft.au=Wang%2C+X+W%3BGibson%2C+M+K%3BVermeulen%2C+W%3BYeh%2C+H%3BForrester%2C+K%3BSt%C3%BCrzbecher%2C+H+W%3BHoeijmakers%2C+J+H%3BHarris%2C+C+C&rft.aulast=Wang&rft.aufirst=X&rft.date=1995-12-15&rft.volume=55&rft.issue=24&rft.spage=6012&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-22 N1 - Date created - 1996-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - O6-methylguanine DNA adduct formation and modulation by ethanol in placenta and fetal tissues after exposure of pregnant patas monkeys to N-nitrosodimethylamine. AN - 77740576; 8521384 AB - Perinatal nitrosamine exposures may contribute to childhood cancer risk. To test primate fetal susceptibility to formation of cancer initiation-related DNA adducts from nitrosamines, pregnant patas monkeys were given 1.0 or 0.1 mg/kg N-nitrosodimethylamine. Appreciable levels of the promutagenic O6-methylguanine adduct occurred in placental and fetal liver DNA after both doses and were lower but detectable in other fetal tissues after the higher dose. Coadministered ethanol (1.6 g/kg) reduced adducts in placenta and fetal liver by one-half and increased levels in other fetal tissues to the same degree. Thus, primate placenta and fetal tissues have a significant, ethanol-modulated capacity to activate N-nitrosodimethylamine, supporting implication of nitrosamines in human perinatal carcinogenesis and of alcohol as a modulating factor. JF - Cancer research AU - Chhabra, S K AU - Souliotis, V L AU - Harbaugh, J W AU - Krasnow, S W AU - Jones, A B AU - Anderson, L M AU - Kyrtopoulos, S A AD - Perinatal Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/12/15/ PY - 1995 DA - 1995 Dec 15 SP - 6017 EP - 6020 VL - 55 IS - 24 SN - 0008-5472, 0008-5472 KW - DNA Adducts KW - 0 KW - Ethanol KW - 3K9958V90M KW - Guanine KW - 5Z93L87A1R KW - O-(6)-methylguanine KW - 9B710FV2AE KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Placenta -- chemistry KW - Animals KW - Erythrocebus patas KW - Fetus -- chemistry KW - Female KW - Pregnancy KW - Maternal-Fetal Exchange KW - DNA Damage KW - Ethanol -- administration & dosage KW - Guanine -- analogs & derivatives KW - Guanine -- metabolism KW - Dimethylnitrosamine -- administration & dosage KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77740576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=O6-methylguanine+DNA+adduct+formation+and+modulation+by+ethanol+in+placenta+and+fetal+tissues+after+exposure+of+pregnant+patas+monkeys+to+N-nitrosodimethylamine.&rft.au=Chhabra%2C+S+K%3BSouliotis%2C+V+L%3BHarbaugh%2C+J+W%3BKrasnow%2C+S+W%3BJones%2C+A+B%3BAnderson%2C+L+M%3BKyrtopoulos%2C+S+A&rft.aulast=Chhabra&rft.aufirst=S&rft.date=1995-12-15&rft.volume=55&rft.issue=24&rft.spage=6017&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-22 N1 - Date created - 1996-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbamazepine induction of apoptosis in cultured cerebellar neurons: effects of N-methyl-D-aspartate, aurintricarboxylic acid and cycloheximide. AN - 77874946; 8719616 AB - We have previously demonstrated that carbamazepine (CBZ) at concentrations above the therapeutic range is toxic to cultured cerebellar granule cells. Here, we ask whether the effect of CBZ involves neuronal apoptosis or necrosis. Treatment of cultured cerebellar granule cells with CBZ for 3 days resulted in a concentration-dependent fragmentation of DNA revealed as a laddered pattern in agarose gel electrophoresis, a phenomenon characteristic of apoptosis. Pretreatment of cells with N-methyl-D-aspartate (NMDA) blocked CBZ-induced DNA fragmentation and neurotoxicity as assayed by loss of mitochondrial activity with MTT or by [3H]ouabain binding to Na+/K(+)-ATPase. Aurintricarboxylic acid (ATA), a polyanionic dye, also markedly suppressed DNA fragmentation and cell death detected by morphological examination. A considerable level of DNA ladder formation was detected in untreated cells and this basal DNA fragmentation was also blocked by NMDA and ATA. Moreover, NMDA and ATA prevented CBZ-induced chromatin condensation as revealed by DNA binding with the fluorescent dye Hoechst 33258. Pretreatment of cells with cycloheximide, a protein synthesis inhibitor, prevented CBZ-induced cell death detected morphologically and attenuated CBZ-induced neurotoxicity assessed by mitochondrial activity and [3H]ouabain binding assays. Taken together, our results suggest that CBZ-induces death of cerebellar granule cells by an apoptotic process that is sensitive to NMDA, ATA and cycloheximide. JF - Brain research AU - Gao, X M AU - Margolis, R L AU - Leeds, P AU - Hough, C AU - Post, R M AU - Chuang, D M AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, NIMH, Bethesda, MD 20892-1272, USA. Y1 - 1995/12/12/ PY - 1995 DA - 1995 Dec 12 SP - 63 EP - 71 VL - 703 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Anticonvulsants KW - 0 KW - Protein Synthesis Inhibitors KW - Carbamazepine KW - 33CM23913M KW - Aurintricarboxylic Acid KW - 4431-00-9 KW - N-Methylaspartate KW - 6384-92-5 KW - DNA KW - 9007-49-2 KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Protein Synthesis Inhibitors -- pharmacology KW - N-Methylaspartate -- pharmacology KW - Cells, Cultured KW - Cycloheximide -- pharmacology KW - Mitochondria -- drug effects KW - Aurintricarboxylic Acid -- pharmacology KW - DNA -- drug effects KW - Cerebellum -- cytology KW - Neurons -- drug effects KW - Cerebellum -- drug effects KW - Apoptosis -- drug effects KW - Carbamazepine -- toxicity KW - Anticonvulsants -- toxicity KW - Anticonvulsants -- antagonists & inhibitors KW - Carbamazepine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77874946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Carbamazepine+induction+of+apoptosis+in+cultured+cerebellar+neurons%3A+effects+of+N-methyl-D-aspartate%2C+aurintricarboxylic+acid+and+cycloheximide.&rft.au=Gao%2C+X+M%3BMargolis%2C+R+L%3BLeeds%2C+P%3BHough%2C+C%3BPost%2C+R+M%3BChuang%2C+D+M&rft.aulast=Gao&rft.aufirst=X&rft.date=1995-12-12&rft.volume=703&rft.issue=1-2&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and sequence of a processed p53 pseudogene from rat: a potential source of false 'mutations' in PCR fragments of tumor DNA. AN - 77771530; 8543183 AB - We describe here the nucleotide (nt) sequence of a p53 processed pseudogene (psi-gene) from the normal F344 rat genome. Exon-derived primers were utilized to amplify and clone a 1447-bp polymerase chain reaction (PCR) product corresponding to the coding regions of exons 2-11 of the functional gene. This psi-gene is a cDNA-like sequence possessing 87% homology with the functional rat p53. We have also partially characterized two additional and distinctly different putative rat p53 psi-genes, focussing on the sequences surrounding the reported rat p53 mutational hot spots of codons 202R and 211R within exon 6/7. Each of these three psi-gene sequences contained various single- and/or double-nt substitutions, small deletions and insertions that distinguish them from p53. One substitution, 211R CGG-->CAG, found both in the cloned psi-gene and in one of the partially characterized, putative psi-genes, corresponded precisely with the sequence that has been reported as a mutation at one of the hot spots. Co-amplification of one or more of the p53 psi-genes with portions of the functional p53 is likely, if exon-based primers are utilized for PCR amplification of rat p53. Consequently, psi-gene sequences are potential sources of sequence variations that can be misidentified as somatic cell mutations by direct sequencing of inappropriately generated PCR products. JF - Gene AU - Weghorst, C M AU - Buzard, G S AU - Calvert, R J AU - Hulla, J E AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, USA. Y1 - 1995/12/12/ PY - 1995 DA - 1995 Dec 12 SP - 317 EP - 322 VL - 166 IS - 2 SN - 0378-1119, 0378-1119 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Rats KW - Pseudogenes KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Exons KW - Multigene Family KW - Humans KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Mice KW - DNA Primers -- chemistry KW - Genes, p53 KW - Neoplasms, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77771530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Cloning+and+sequence+of+a+processed+p53+pseudogene+from+rat%3A+a+potential+source+of+false+%27mutations%27+in+PCR+fragments+of+tumor+DNA.&rft.au=Weghorst%2C+C+M%3BBuzard%2C+G+S%3BCalvert%2C+R+J%3BHulla%2C+J+E%3BRice%2C+J+M&rft.aulast=Weghorst&rft.aufirst=C&rft.date=1995-12-12&rft.volume=166&rft.issue=2&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-12 N1 - Date created - 1996-02-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U29887; GENBANK; U29886; L12046 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of human thyrotropin in cell lines with different glycosylation patterns combined with mutagenesis of specific glycosylation sites. Characterization of a novel role for the oligosaccharides in the in vitro and in vivo bioactivity. AN - 77725287; 7493973 AB - We used a novel approach to study the role of the Asn-linked oligosaccharides for human thyrotropin (hTSH) activity. Mutagenesis of Asn (N) within individual glycosylation recognition sequences to Gln (Q) was combined with expression of wild type and mutant hTSH in cell lines with different glycosylation patterns. The in vitro activity of hTSH lacking the Asn alpha 52 oligosaccharide (alpha Q52/TSH beta) expressed in CHO-K1 cells (sialylated oligosaccharides) was increased 6-fold compared with wild type, whereas the activities of alpha Q78/TSH beta and alpha/TSH beta Q23 were increased 2-3-fold. Deletion of the Asn alpha 52 oligosaccharide also increased the thyrotropic activity of human chorionic gonadotropin, in contrast to previous findings at its native receptor. The in vitro activity of wild type hTSH expressed in CHO-LEC2 cells (sialic acid-deficient oligosaccharides), CHO-LEC1 cells (Man5GlcNAc2 intermediates), and 293 cells (sulfated oligosaccharides) was 5-8-fold higher than of wild type from CHO-K1 cells. In contrast to CHO-K1 cells, there was no difference in the activity between wild type and selectively deglycosylated mutants expressed in these cell lines. Thus, in hTSH, the oligosaccharide at Asn alpha 52 and, specifically, its terminal sialic acid residues attenuate in vitro activity, in contrast to the previously reported stimulatory role of this chain for human chorionic gonadotropin and human follitropin activity. The increased thyrotropic activity of alpha Q52/CG beta suggests that receptor-related mechanisms may be responsible for these differences among the glycoprotein hormones. Despite their increased in vitro activity, alpha Q52/TSH beta, and alpha Q78/TSH beta from CHO-K1 cells had a faster serum disappearance rate and decreased effect on T4 production in mice. These findings highlight the importance of individual oligosaccharides in maintaining circulatory half-life and hence in vivo activity of hTSH. JF - The Journal of biological chemistry AU - Grossmann, M AU - Szkudlinski, M W AU - Tropea, J E AU - Bishop, L A AU - Thotakura, N R AU - Schofield, P R AU - Weintraub, B D AD - Molecular and Cellular Endocrinology Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1758, USA. Y1 - 1995/12/08/ PY - 1995 DA - 1995 Dec 08 SP - 29378 EP - 29385 VL - 270 IS - 49 SN - 0021-9258, 0021-9258 KW - Oligosaccharides KW - 0 KW - Recombinant Proteins KW - Sialic Acids KW - Thyrotropin KW - 9002-71-5 KW - Cyclic AMP KW - E0399OZS9N KW - N-Acetylneuraminic Acid KW - GZP2782OP0 KW - Index Medicus KW - Animals KW - Cyclic AMP -- biosynthesis KW - Humans KW - Mice KW - Glycosylation KW - Structure-Activity Relationship KW - Sialic Acids -- physiology KW - Mutagenesis, Site-Directed KW - Rats KW - Half-Life KW - CHO Cells KW - Male KW - Cricetinae KW - Thyrotropin -- chemistry KW - Oligosaccharides -- chemistry KW - Thyrotropin -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77725287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Expression+of+human+thyrotropin+in+cell+lines+with+different+glycosylation+patterns+combined+with+mutagenesis+of+specific+glycosylation+sites.+Characterization+of+a+novel+role+for+the+oligosaccharides+in+the+in+vitro+and+in+vivo+bioactivity.&rft.au=Grossmann%2C+M%3BSzkudlinski%2C+M+W%3BTropea%2C+J+E%3BBishop%2C+L+A%3BThotakura%2C+N+R%3BSchofield%2C+P+R%3BWeintraub%2C+B+D&rft.aulast=Grossmann&rft.aufirst=M&rft.date=1995-12-08&rft.volume=270&rft.issue=49&rft.spage=29378&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of microfilament organization and anchorage-independent growth by tropomyosin 1. AN - 77749797; 8524798 AB - Variants of chemically immortalized Syrian hamster embryo cells that had either retained (supB+) or lost (supB-) the ability to suppress tumorigenicity when hybridized with a fibrosarcoma cell line were subcloned. Both supB cell types are nontumorigenic; however, the supB- but not supB+ cells exhibit conditional anchorage-independent growth. Alterations of actin microfilament organization were observed in supB- but not supB+ cells that corresponded to a significant reduction of the actin-binding protein tropomyosin 1 (TM-1) in subB- cells. To examine the possibility of a direct relationship between TM-1 expression and the subB- phenotype, subB+ cells were transfected with an expression vector containing the TM-1 cDNA in an antisense orientation. The antisense-induced reduction of TM-1 levels in supB+ clones caused a microfilament reorganization and conferred anchorage-independent growth potential that were indistinguishable from those characteristic of supB- cells. These data provide direct evidence that TM-1 regulates both microfilament organization and anchorage-independent growth and suggest that microfilament alterations are sufficient for anchorage-independent growth. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Boyd, J AU - Risinger, J I AU - Wiseman, R W AU - Merrick, B A AU - Selkirk, J K AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 1995/12/05/ PY - 1995 DA - 1995 Dec 05 SP - 11534 EP - 11538 VL - 92 IS - 25 SN - 0027-8424, 0027-8424 KW - DNA Probes KW - 0 KW - Drosophila Proteins KW - RNA, Antisense KW - Recombinant Proteins KW - Tm2 protein, Drosophila KW - Tropomyosin KW - Index Medicus KW - Animals KW - Genetic Variation KW - Blotting, Northern KW - Recombinant Proteins -- biosynthesis KW - Genes, Tumor Suppressor KW - Cloning, Molecular KW - Microscopy, Fluorescence KW - Cells, Cultured KW - Electrophoresis, Gel, Two-Dimensional KW - Embryo, Mammalian -- cytology KW - Molecular Sequence Data KW - Mesocricetus KW - Cytoskeleton -- ultrastructure KW - Cell Division KW - Cricetinae KW - Actin Cytoskeleton -- ultrastructure KW - Cell Adhesion -- genetics KW - Tropomyosin -- genetics KW - Tropomyosin -- biosynthesis KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77749797?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Regulation+of+microfilament+organization+and+anchorage-independent+growth+by+tropomyosin+1.&rft.au=Boyd%2C+J%3BRisinger%2C+J+I%3BWiseman%2C+R+W%3BMerrick%2C+B+A%3BSelkirk%2C+J+K%3BBarrett%2C+J+C&rft.aulast=Boyd&rft.aufirst=J&rft.date=1995-12-05&rft.volume=92&rft.issue=25&rft.spage=11534&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-24 N1 - Date created - 1996-01-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U29167; GENBANK N1 - SuppNotes - Cited By: Mol Cell Biol. 1985 May;5(5):972-83 [4000123] Cell. 1993 Dec 17;75(6):1107-17 [7505203] Nature. 1985 Aug 15-21;316(6029):636-9 [2993900] J Biol Chem. 1985 Nov 25;260(27):14440-5 [3840484] Cancer Res. 1986 Apr;46(4 Pt 1):1867-73 [3948169] Cell. 1986 May 9;45(3):407-15 [3698103] Nature. 1986 Jun 19-25;321(6072):726-7 [3713859] Annu Rev Biophys Biophys Chem. 1986;15:457-75 [3013231] Nucleic Acids Res. 1986 Jul 11;14(13):5275-94 [3737401] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5992-6 [3461473] Cancer Res. 1986 Oct;46(10):5101-5 [2428471] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] J Biol Chem. 1987 Aug 5;262(22):10791-800 [3611091] Mol Cell Biol. 1987 Aug;7(8):2745-52 [3670292] Mutat Res. 1988 Jun;199(2):437-47 [3374511] Mol Cell Biol. 1988 Apr;8(4):1790-4 [3380097] J Biol Chem. 1989 Mar 25;264(9):5269-82 [2925692] Cell. 1989 Apr 21;57(2):233-42 [2649250] Cancer Res. 1989 May 15;49(10):2525-32 [2653618] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8773-7 [2813423] Cancer Res. 1990 Apr 1;50(7):2105-12 [2317800] Proc Natl Acad Sci U S A. 1990 May;87(9):3579-83 [2333303] J Cell Biol. 1976 Feb;68(2):202-19 [1107334] J Cell Physiol. 1975 Dec;87(2):213-9 [1214003] Biochim Biophys Acta. 1975 Dec 31;417(3-4):211-36 [766836] Proc Natl Acad Sci U S A. 1977 Jul;74(7):3019-22 [19740] Annu Rev Biochem. 1977;46:797-822 [143236] Biochem Biophys Res Commun. 1991 Jun 28;177(3):1068-75 [2059197] J Natl Cancer Inst. 1991 Jun 19;83(12):862-6 [2061946] Mol Carcinog. 1991;4(3):189-95 [2064724] Bioessays. 1991 Sep;13(9):429-37 [1796905] Appl Theor Electrophor. 1992;2(6):177-87 [1567919] Proc Natl Acad Sci U S A. 1978 Feb;75(2):588-99 [147464] Nature. 1978 Jun 1;273(5661):345-9 [661946] Cell. 1978 Aug;14(4):931-9 [688399] Cancer Res. 1978 Nov;38(11 Pt 2):4155-71 [359133] J Biol Chem. 1979 Aug 25;254(16):7961-77 [468801] Cell. 1981 Jan;23(1):113-20 [6260369] Nature. 1981 Nov 19;294(5838):228-32 [6272123] J Cell Sci. 1981 Dec;52:151-66 [7037799] Biochim Biophys Acta. 1982 Apr 29;720(2):154-62 [6282338] Biochemistry. 1983 Mar 1;22(5):1187-93 [6838847] J Biol Chem. 1983 May 25;258(10):6636-44 [6133866] J Biol Chem. 1983 Nov 25;258(22):13954-64 [6315714] Dev Biol. 1984 Jun;103(2):482-92 [6144605] Mol Cell Biol. 1984 Sep;4(9):1823-33 [6208481] Cancer Res. 1985 Feb;45(2):726-32 [2981612] Science. 1992 Nov 6;258(5084):955-64 [1439807] J Cell Biol. 1992 Dec;119(5):1245-60 [1360014] Cell. 1993 Mar 26;72(6):903-17 [8384533] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7039-43 [8346214] Mol Carcinog. 1993;7(4):249-56 [8394717] Biochim Biophys Acta. 1985;780(3):197-212 [3896312] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of yeast artificial chromosomes free of endogenous yeast chromosomes: construction of alternate hosts with defined karyotypic alterations. AN - 77747160; 8524833 AB - An intrinsic feature of yeast artificial chromosomes (YACs) is that the cloned DNA is generally in the same size range (i.e., approximately 200-2000 kb) as the endogenous yeast chromosomes. As a result, the isolation of YAC DNA, which typically involves separation by pulsed-field gel electrophoresis, is frequently confounded by the presence of a comigrating or closely migrating endogenous yeast chromosome(s). We have developed a strategy that reliably allows the isolation of any YAC free of endogenous yeast chromosomes. Using recombination-mediated chromosome fragmentation, a set of Saccharomyces cerevisiae host strains was systematically constructed. Each strain contains defined alterations in its electrophoretic karyotype, which provide a large-size interval devoid of endogenous chromosomes (i.e., a karyotypic "window"). All of the constructed strains contain the kar1-delta 15 mutation, thereby allowing the efficient transfer of a YAC from its original host into an appropriately selected window strain using the kar1-transfer procedure. This approach provides a robust and efficient means to obtain relatively pure YAC DNA regardless of YAC size. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hamer, L AU - Johnston, M AU - Green, E D AD - Diagnostic Development Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/12/05/ PY - 1995 DA - 1995 Dec 05 SP - 11706 EP - 11710 VL - 92 IS - 25 SN - 0027-8424, 0027-8424 KW - Index Medicus KW - Karyotyping KW - Genetic Vectors KW - Recombination, Genetic KW - Electrophoresis, Gel, Pulsed-Field KW - Mutagenesis KW - Saccharomyces cerevisiae -- genetics KW - Cloning, Molecular -- methods KW - Chromosomes, Artificial, Yeast UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77747160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Isolation+of+yeast+artificial+chromosomes+free+of+endogenous+yeast+chromosomes%3A+construction+of+alternate+hosts+with+defined+karyotypic+alterations.&rft.au=Hamer%2C+L%3BJohnston%2C+M%3BGreen%2C+E+D&rft.aulast=Hamer&rft.aufirst=L&rft.date=1995-12-05&rft.volume=92&rft.issue=25&rft.spage=11706&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-24 N1 - Date created - 1996-01-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1983 Jan;153(1):163-8 [6336730] PCR Methods Appl. 1995 Jun;4(6):322-6 [7580924] Cell. 1984 May;37(1):67-75 [6373014] Nucleic Acids Res. 1984 Jul 25;12(14):5647-64 [6379602] Mol Gen Genet. 1984;197(2):345-6 [6394957] Science. 1986 Dec 19;234(4783):1582-5 [3538420] Science. 1987 May 15;236(4803):806-12 [3033825] Mol Cell Biol. 1987 Jun;7(6):2087-96 [3037344] Genetics. 1987 Aug;116(4):541-5 [3305158] Proc Natl Acad Sci U S A. 1988 Aug;85(16):6027-31 [3045811] Science. 1989 Jun 16;244(4910):1348-51 [2544027] J Bacteriol. 1990 Feb;172(2):610-8 [2404945] Proc Natl Acad Sci U S A. 1990 Feb;87(4):1300-4 [2406718] Trends Genet. 1990 Aug;6(8):236 [2238077] Proc Natl Acad Sci U S A. 1990 Nov;87(22):8995-9 [2247475] Methods Enzymol. 1991;194:251-70 [2005791] Proc Natl Acad Sci U S A. 1991 May 1;88(9):4005-9 [1850845] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9623-7 [1946377] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9628-32 [1946378] Trends Genet. 1993 Jun;9(6):195-6 [8337760] Nucleic Acids Res. 1993 Jul 11;21(14):3329-30 [8341614] Genomics. 1994 Jul 1;22(1):108-17 [7959756] Genomics. 1994 Jul 1;22(1):118-26 [7959757] Nucleic Acids Res. 1995 Feb 25;23(4):670-4 [7899089] Genomics. 1995 Jan 1;25(1):170-83 [7774915] Methods Enzymol. 1983;101:202-11 [6310324] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a rapidly dephosphorylating 95-kDa protein as elongation factor 2 during 8-Br-cAMP treatment of N1E115 neuroblastoma cells. AN - 77744435; 8526900 AB - Treatment of 8-Br-cAMP promotes neurite outgrowth and neuronal differentiation in N1E115 mouse neuroblastoma cells. Prior or simultaneous treatment of PMA blocks 8-Br-cAMP-mediated neurite outgrowth. Phosphorylation of cellular proteins during these treatments was examined in a permeabilized cell system. While PMA promotes phosphorylation of the heat-stable protein kinase C substrates MARCKS and neuromodulin, 8-Br-cAMP hastens the dephosphorylation of a protein of M(r)95k (p95). Extensively purified, N-terminal sequenced, and judged from its phosphorylation properties, p95 was identified as the eukaryotic elongation factor-2 (eEF-2), whose dephosphorylation has been reported to be related to an increase in protein synthesis. It is likely 8-Br-cAMP stimulates dephosphorylation of eEf-2, promotes protein synthesis that eventually leads to neuronal differentiation in N1E115 cells. JF - Biochemical and biophysical research communications AU - Li, H AU - Chen, H C AU - Huang, F L AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/12/05/ PY - 1995 DA - 1995 Dec 05 SP - 131 EP - 137 VL - 217 IS - 1 SN - 0006-291X, 0006-291X KW - Nerve Tissue Proteins KW - 0 KW - Peptide Elongation Factor 2 KW - Peptide Elongation Factors KW - Phosphoproteins KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Animals KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Amino Acid Sequence KW - Mice KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Molecular Weight KW - Protein Kinase C -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - Neurons -- cytology KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation -- drug effects KW - Phosphoproteins -- genetics KW - Phosphoproteins -- chemistry KW - Peptide Elongation Factors -- metabolism KW - Peptide Elongation Factors -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry KW - Peptide Elongation Factors -- chemistry KW - Neuroblastoma -- metabolism KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77744435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Identification+of+a+rapidly+dephosphorylating+95-kDa+protein+as+elongation+factor+2+during+8-Br-cAMP+treatment+of+N1E115+neuroblastoma+cells.&rft.au=Li%2C+H%3BChen%2C+H+C%3BHuang%2C+F+L&rft.aulast=Li&rft.aufirst=H&rft.date=1995-12-05&rft.volume=217&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-19 N1 - Date created - 1996-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of mGluR1 alpha mRNA receptor in rat and guinea pig cochlear neurons. AN - 85278379; pmid-8742449 AB - Glutamate or a parent substance is thought to be the afferent neurotransmitter in the auditory system. In situ hybridization showed that mGluR1 alpha mRNA was expressed by type I and type II spiral ganglion neurons in the cochlea. The glial cells surrounding the type I spiral ganglion neurons lacked such expression. The hybridization signal was low compared to that reported for non-NMDA receptors, suggesting that mGluR1 alpha receptors, as is the case for NMDA receptors, play a minor role in auditory transmission. The uniform expression of mGluR1 alpha mRNAs along the cochlear spiral suggests their co-expression in spiral ganglion neurons with NMDA and non-NMDA receptors and thus functional cooperation. JF - Neuroreport AU - Safieddine, S AU - Eybalin, M AD - NIH/NIDCD, Bethesda, MD 20892, USA. PY - 1995 SP - 193 EP - 196 VL - 7 IS - 1 SN - 0959-4965, 0959-4965 KW - Cochlea KW - Oligonucleotide Probes KW - RNA, Messenger KW - Rats KW - In Situ Hybridization KW - Receptors, Metabotropic Glutamate KW - Guinea Pigs KW - Neurons KW - Animal KW - Rats, Wistar UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85278379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Expression+of+mGluR1+alpha+mRNA+receptor+in+rat+and+guinea+pig+cochlear+neurons.&rft.au=Safieddine%2C+S%3BEybalin%2C+M&rft.aulast=Safieddine&rft.aufirst=S&rft.date=1995-12-01&rft.volume=7&rft.issue=1&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Ultrastructural localization of G-protein Gs in the organ of Corti. AN - 85264215; pmid-8848239 AB - Immunocytochemical localization of a stimulatory GTP-binding protein Gs in the organ of Corti in the inner ear was examined with a post-embedding immunogold technique, using antibodies raised against a synthetic decapeptide (RMHLRQYELL) of the C-terminus of the alpha subunit of Gs. Immunoreactivity was strong on the membranes of supporting cells in the reticular lamina, including inner and outer pillar cells and the phalangeal process of Deiters' cells. Immunolabeling also was seen on the membranes of cell bodies of those cells which surround nerve fibers, basilar fibers, outer spiral fibers and afferent nerve endings at outer hair cells. Gold particles also labeled the membrane of inner phalangeal cells and border cells. In contrast, outer and inner hair cells were not labeled. Possible roles of Gs in the organ of Corti are discussed. JF - Neuroscience Letters AU - Mizuta, K AU - Iwasa, K H AU - Simonds, W F AU - Tachibana, M AD - Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1995 SP - 147 EP - 150 VL - 201 IS - 2 SN - 0304-3940, 0304-3940 KW - Guinea Pigs KW - Hair Cells, Outer KW - Animal KW - Molecular Sequence Data KW - Amino Acid Sequence KW - GTP-Binding Proteins KW - Organ of Corti KW - Immunohistochemistry KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85264215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+Letters&rft.atitle=Ultrastructural+localization+of+G-protein+Gs+in+the+organ+of+Corti.&rft.au=Mizuta%2C+K%3BIwasa%2C+K+H%3BSimonds%2C+W+F%3BTachibana%2C+M&rft.aulast=Mizuta&rft.aufirst=K&rft.date=1995-12-01&rft.volume=201&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Neuroscience+Letters&rft.issn=03043940&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The effects of scopolamine, lorazepam, and glycopyrrolate on classical conditioning of the human eyeblink response. AN - 85257749; pmid-8657840 AB - Human eyeblink conditioning, a relatively simple form of learning and memory, has previously been shown to be impaired by the central and peripheral anticholinergic scopolamine. The present study compared the behavioral effects of scopolamine with the benzodiazepine lorazepam and a peripherally active anticholinergic, glycopyrrolate. Thirty-six healthy normal volunteers (mean age: 23.7 years) were studied with 12 assigned double-blind to each of three drug conditions (0.5 mg scopolamine IV, 2 mg lorazepam PO, or 0.2 mg glycopyrrolate IV). Subjects underwent classical conditioning of the eyeblink response in which the conditioned stimulus was an 80 dB binaural tone, and the unconditioned stimulus was a 2 psi airpuff to the right eye. Ten trials of unpaired stimulus presentations were followed by 60 paired trials and finally by an extinction period of five tone-alone presentations. An eyeblink response that occurred during the tone but before the airpuff was scored as a conditioned response (CR). Subjects treated with lorazepam (43% mean CRs) and scopolamine (51% mean CRs) exhibited a significantly lower asymptotic level of conditioning than those treated with glycopyrrolate (85% mean CRs; P < 0.01). However, during extinction, lorazepam-treated subjects (35% CRs) showed a lower overall level of responding to the tone than either scopolamine (60% CRs) or glycopyrrolate (62% CRs) treated subjects (P < 0.05). It seems unlikely that these differences could be accounted for by drug-induced alterations in motor responses because there were no significant differences between the three drug conditions in the frequency, latency, or amplitude of unconditioned responses to the airpuff. Overall, our data indicate that scopolamine and lorazepam impair eyeblink conditioning and suggest that some of the effects of benzodiazepines and anticholinergics on learning and memory can be differentiated using this paradigm. JF - Psychopharmacology AU - Bahro, M AU - Schreurs, B G AU - Sunderland, T AU - Molchan, S E AD - Section on Geriatric Psychiatry, National Institute of Mental Health, Bethesda, Maryland 20892, USA. PY - 1995 SP - 395 EP - 400 VL - 122 IS - 4 SN - 0033-3158, 0033-3158 KW - Muscarinic Antagonists KW - Lorazepam KW - Scopolamine KW - Conditioning, Classical KW - Double-Blind Method KW - GABA Modulators KW - Glycopyrrolate KW - Human KW - Adult KW - Blinking KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85257749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=The+effects+of+scopolamine%2C+lorazepam%2C+and+glycopyrrolate+on+classical+conditioning+of+the+human+eyeblink+response.&rft.au=Bahro%2C+M%3BSchreurs%2C+B+G%3BSunderland%2C+T%3BMolchan%2C+S+E&rft.aulast=Bahro&rft.aufirst=M&rft.date=1995-12-01&rft.volume=122&rft.issue=4&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Abnormalities in long latency responses to superior laryngeal nerve stimulation in adductor spasmodic dysphonia. AN - 85172924; pmid-7492063 AB - Sensorimotor responses to repeated electrical stimulation of the superior laryngeal nerve were compared in 8 patients with adductor spasmodic dysphonia (ADSD) and 11 normal controls to determine if adductor response disinhibition occurred in ADSD. Pairs of electrical pulses were presented at interstimulus intervals varying from 100 to 5,000 milliseconds (ms). Three responses were measured in thyroarytenoid muscles: ipsilateral R1 responses at 17 ms and ipsilateral and contralateral R2 responses between 60 and 75 ms. Conditioned response characteristics, the percent occurrence and percentage amplitude of initial responses, were measures of response inhibition. As a group, the patients had reduced response inhibition: their conditioned ipsilateral R1 response amplitudes were increased, as was the frequency of their conditioned contralateral muscle responses (p < or = .002) compared to normal. However, the patients' initial responses were normal in latency and frequency characteristics, demonstrating that the brain stem mechanisms for these responses were intact. These results suggest a central disinhibition of laryngeal responses to sensory input in ADSD. JF - The Annals of Otology, Rhinology, and Laryngology AU - Ludlow, Christy L AU - Schulz, G M AU - Yamashita, T AU - Deleyiannis, F W AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke PY - 1995 SP - 928 EP - 935 VL - 104 IS - 12 SN - 0003-4894, 0003-4894 KW - Laryngeal Nerves KW - Comparative Study KW - Laryngeal Muscles KW - Humans KW - Brain Stem KW - Case-Control Studies KW - Electromyography KW - Middle Aged KW - Voice Disorders KW - Female KW - Male KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85172924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+Otology%2C+Rhinology%2C+and+Laryngology&rft.atitle=Abnormalities+in+long+latency+responses+to+superior+laryngeal+nerve+stimulation+in+adductor+spasmodic+dysphonia.&rft.au=Ludlow%2C+Christy+L%3BSchulz%2C+G+M%3BYamashita%2C+T%3BDeleyiannis%2C+F+W&rft.aulast=Ludlow&rft.aufirst=Christy&rft.date=1995-12-01&rft.volume=104&rft.issue=12&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+Otology%2C+Rhinology%2C+and+Laryngology&rft.issn=00034894&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Phase I study of intravenous Lu-labeled CC49 murine monoclonal antibody in patients with advanced adenocarcinoma. AN - 77961995; 9815943 AB - CC49, a murine monoclonal antibody that recognizes the tumor-associated glycoprotein 72, was conjugated to the chemical chelate 1,4,7,10-tetraaza-1-(1-carboxy-3-(4-aminophenyl) propyl)-tris-4,7,10- ((carboxy)methyl)cyclododecane that had been labeled with a beta emitter, Lu. Preclinical studies had shown that Lu-labeled CC49 caused regression of human colon adenocarcinoma xenografts in nude mice. Patients with advanced adenocarcinoma who had failed standard treatment and whose tumors expressed the tumor-associated glycoprotein 72 antigen were eligible for treatment to determine the maximum tolerated dose of Lu-labeled CC49. The starting dose of Lu was 10 mCi/m2 given i.v. with the dose of CC49 held constant at 20 mg. Pharmacokinetic sampling and immunoscintigraphy were performed over the ensuing 3 weeks. The dose of radioactive Lu was escalated by 15 mCi/m2 for each successive dose level. Unexpected bone marrow toxicity developed in patients treated at the second dose level with 25 mCi/m2 Lu; two patients developed grade 4 thrombocytopenia, while the third patient developed grade 3 thrombocytopenia. Pharmacokinetic studies showed that the plasma half-life of the immunoconjugate was 67 h; whole-body retention, however, was prolonged with a biological half-life of 258 h. Serial gamma camera imaging localized known tumor in all patients, and also demonstrated prolonged Lu retention in the reticuloendothelial system (RES). Bone marrow dosimetry estimates ranged from 4 to 5 REMS/mCi Lu based on imaging and biopsy data. Analysis of bone marrow biopsies demonstrated that most of the Lu was localized in the cellular compartment and not in the bone. No antitumor responses were observed. Intravenous administration of 15 mCi/m2 Lu-labeled CC49 to previously treated advanced cancer patients was associated with acceptable hematological toxicity and was the maximum tolerated dose. However, prolonged retention of Lu in the RES, including the bone marrow, was observed and limited the dose of Lu that could be given. Additional studies are indicated to reduce RES uptake and retention of this immunoconjugate. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Mulligan, T AU - Carrasquillo, J A AU - Chung, Y AU - Milenic, D E AU - Schlom, J AU - Feuerstein, I AU - Paik, C AU - Perentesis, P AU - Reynolds, J AU - Curt, G AD - Medicine Branch, Laboratory of Tumor Immunology & Biology, Division of Cancer Biology & Diagnosis, National Cancer Institute, Clinical Center, NIH, Bethesda, Maryland 20982, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1447 EP - 1454 VL - 1 IS - 12 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Neoplasm KW - Antineoplastic Agents KW - B72.3 antibody KW - Radioisotopes KW - Lutetium KW - 5H0DOZ21UJ KW - Index Medicus KW - Lung Neoplasms -- radiotherapy KW - Humans KW - Breast Neoplasms -- radiotherapy KW - Antibodies, Monoclonal -- administration & dosage KW - Colonic Neoplasms -- radiotherapy KW - Breast Neoplasms -- pathology KW - Radiotherapy Dosage KW - Adult KW - Middle Aged KW - Antibodies, Monoclonal -- adverse effects KW - Colonic Neoplasms -- pathology KW - Radioimmunotherapy -- methods KW - Female KW - Male KW - Lung Neoplasms -- pathology KW - Neoplasms -- pathology KW - Radioisotopes -- adverse effects KW - Neoplasms -- radiotherapy KW - Antineoplastic Agents -- administration & dosage KW - Antibodies, Neoplasm -- adverse effects KW - Antibodies, Neoplasm -- administration & dosage KW - Lutetium -- adverse effects KW - Adenocarcinoma -- radiotherapy KW - Radioisotopes -- administration & dosage KW - Lutetium -- administration & dosage KW - Antineoplastic Agents -- adverse effects KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77961995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+I+study+of+intravenous+Lu-labeled+CC49+murine+monoclonal+antibody+in+patients+with+advanced+adenocarcinoma.&rft.au=Mulligan%2C+T%3BCarrasquillo%2C+J+A%3BChung%2C+Y%3BMilenic%2C+D+E%3BSchlom%2C+J%3BFeuerstein%2C+I%3BPaik%2C+C%3BPerentesis%2C+P%3BReynolds%2C+J%3BCurt%2C+G&rft.aulast=Mulligan&rft.aufirst=T&rft.date=1995-12-01&rft.volume=1&rft.issue=12&rft.spage=1447&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-09 N1 - Date created - 1999-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation and characterization of a single-gene encoded single-chain immunoglobulin-interleukin-2 fusion protein. AN - 77957528; 9373351 AB - Interleukin-2 (IL-2), a potent inducer of cellular immune responses, has been used for biological therapy of human cancer; however, the high doses of IL-2 required to mediate patients' immune responses can cause considerable systemic toxicity. The murine monoclonal antibody (MAb) CC49, which reacts with tumor-associated glycoprotein (TAG)-72, expressed on a variety of human carcinomas, has shown excellent tumor localization in recent clinical trials. Development and characterization of a single-chain immunoglobulin-IL-2 (SCIg-IL-2) fusion protein which, by delivering IL-2 selectively to the tumor site, can serve as an effective reagent for CC49/IL-2 combination therapy. A single-gene encoding the SCIg-IL-2 fusion protein derived from the chimeric (c) CC49 was designed, generated and inserted in an expression vector. The monomeric single-chain protein consisted of the CC49 heavy and light chain variable domains covalently jointed through a (GGGGS)3 linker peptide. The carboxyl end of the variable domain of the light chain was linked to the amino terminus of the human gamma 1 Fc through the hinge region, and the carboxyl end of the CH3 domain was linked to the amino terminus of the human IL-2 through a GGGSGGG linker peptide. The SCIg-IL-2, expressed from the murine myeloma cells transfected with the expression construct, was characterized for its antigen-binding specificity, antibody effector functions and IL-2 biological activity. Transfection of murine myeloma cells with the single-gene expression construct SCIg-IL-2 expressed a single-chain protein of approximately 70 kD, which was secreted into tissue culture fluid as a homodimer of approximately 140 kD. SCIg-IL-2 competed completely with cCC49 for binding to the TAG-72 antigen, but approximately three- to four-fold more of the SCIg-IL-2 was required to achieve levels of competition similar to those observed with the murine or chimeric CC49. With human effector cells, the fusion protein mediated lysis of TAG-72-positive human carcinoma cells. Prior treatment of human effector cells with 100 U/ml of human IL-2 enhanced the fusion protein-mediated cytolysis from 32 to 65%. At doses of > or = 1 ng/ml, the stimulatory effect of SCIg-IL-2 on IL-2 dependent murine HT-2 cell proliferation was comparable to that of the recombinant human IL-2. The single-gene construct may also facilitate inoculation of the gene in animal tissue for in vivo expression of the fusion protein. JF - Immunotechnology : an international journal of immunological engineering AU - Shu, L AU - Qi, C F AU - Hand, P H AU - Schlom, J AU - Kashmiri, S V AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 231 EP - 241 VL - 1 IS - 3-4 SN - 1380-2933, 1380-2933 KW - Antibodies, Monoclonal KW - 0 KW - Immunoglobulin Fc Fragments KW - Interleukin-2 KW - Recombinant Fusion Proteins KW - Index Medicus KW - Immunoglobulin Fc Fragments -- administration & dosage KW - Protein Engineering KW - Immunity, Cellular KW - Tumor Cells, Cultured KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Dimerization KW - Multiple Myeloma -- metabolism KW - Immunoglobulin Fc Fragments -- genetics KW - Protein Binding KW - Immunoglobulin Fc Fragments -- immunology KW - Immunoassay KW - Interleukin-2 -- administration & dosage KW - Recombinant Fusion Proteins -- immunology KW - Recombinant Fusion Proteins -- genetics KW - Interleukin-2 -- immunology KW - Interleukin-2 -- genetics KW - Recombinant Fusion Proteins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77957528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunotechnology+%3A+an+international+journal+of+immunological+engineering&rft.atitle=Generation+and+characterization+of+a+single-gene+encoded+single-chain+immunoglobulin-interleukin-2+fusion+protein.&rft.au=Shu%2C+L%3BQi%2C+C+F%3BHand%2C+P+H%3BSchlom%2C+J%3BKashmiri%2C+S+V&rft.aulast=Shu&rft.aufirst=L&rft.date=1995-12-01&rft.volume=1&rft.issue=3-4&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Immunotechnology+%3A+an+international+journal+of+immunological+engineering&rft.issn=13802933&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-05 N1 - Date created - 1998-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins containing Pseudomonas exotoxin that target LeY damage human endothelial cells in an antibody-specific mode: relevance to vascular leak syndrome. AN - 77954283; 9815960 AB - Vascular leak syndrome (VLS) was originally found to be a major dose-limiting toxicity in humans with cancer treated with several immunotoxins (ITs) containing ricin A chain or blocked ricin. Recently, VLS has also been observed in patients treated with an IT containing the murine monoclonal antibody (MAb) B3 coupled to LysPE38, a recombinant truncated form of Pseudomonas exotoxin (PE) A. Antibody B3 (IgG1k) recognizes LewisY and related carbohydrate epitopes present on many human solid tumors, and B3-LysPE38 showed excellent antitumor activity in nude mice bearing tumors that express the B3 antigen. In the clinical trial, the development of VLS has prevented the administration of the amount of IT necessary to achieve blood levels required for good therapeutic responses. We have now investigated the effects of several PE-based ITs on different human endothelial cell lines to elucidate the mechanism of VLS induced by ITs containing PE. To assess the cytotoxic effect of IT on endothelial cells, various ITs were incubated with cells for 2 or 20 h, and the incorporation of [3H]leucine into protein was measured. The endothelial cells studied were human umbilical vein endothelial cells, human lung-derived microvascular endothelial cells (HUVECs), human adult dermal microvascular endothelial cells, human pulmonary artery endothelial cells, and human aortic endothelial cells. We found that both B3-LysPE38 (LMB-1), a chemical conjugate of MAb B3 with PE38, as well as B3(Fv)-PE38 (LMB-7), a recombinant single chain immunotoxin, inhibited protein synthesis, with 50% inhibitory concentrations between 600 and 1000 ng/ml for 20-h incubation in HUVECs, human lung-derived microvascular endothelial cells, and human adult dermal microvascular endothelial cells but not on human pulmonary artery endothelial cells. The cytotoxic effect was specific since PE38 itself or PE coupled to several other antibodies did not inhibit protein synthesis in these cells even at 10,000 ng/ml. Further evidence that the cytotoxicity of B3-containing ITs is due to specific B3 binding to endothelial cells comes from the fact that the cytotoxicity can be blocked by excess free MAb B3. HUVECs undergo overt morphological changes after treatment with B3-LysPE38 or B3(Fv)PE38. Gaps between the cells are formed after a 20-h exposure but not after 2 h. These studies suggest that VLS in patients is due to capillary damage caused by prolonged exposure to high concentrations of LMB-1. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kuan, C T AU - Pai, L H AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1589 EP - 1594 VL - 1 IS - 12 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Lewis Blood-Group System KW - Lewis Y antigen KW - Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Proteins -- drug effects KW - Antibody Specificity KW - Humans KW - Cells, Cultured -- drug effects KW - Proteins -- metabolism KW - Immunotoxins -- chemistry KW - Endothelium, Vascular -- drug effects KW - Immunotoxins -- adverse effects KW - Exotoxins -- chemistry KW - Exotoxins -- adverse effects KW - Antibodies, Monoclonal -- adverse effects KW - Capillary Leak Syndrome -- etiology KW - Lewis Blood-Group System -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77954283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Immunotoxins+containing+Pseudomonas+exotoxin+that+target+LeY+damage+human+endothelial+cells+in+an+antibody-specific+mode%3A+relevance+to+vascular+leak+syndrome.&rft.au=Kuan%2C+C+T%3BPai%2C+L+H%3BPastan%2C+I&rft.aulast=Kuan&rft.aufirst=C&rft.date=1995-12-01&rft.volume=1&rft.issue=12&rft.spage=1589&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-09 N1 - Date created - 1999-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combined intravenous ganciclovir and foscarnet for children with recurrent cytomegalovirus retinitis. AN - 77946571; 9098289 AB - Children with the acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis may not complain of symptoms despite the presence of advanced sight-threatening disease. Although little data exist regarding CMV retinitis in this population, the treatment of this disease may be difficult because of frequent, extensive recurrences after reduction of drug dose from induction to maintenance levels. The authors reported the results of the use of combined ganciclovir and foscarnet for treatment of recurrent CMV retinitis in three children with AIDS. Three children with recurrent CMV retinitis were treated with combined ganciclovir and foscarnet administered intravenously. All patients initially received induction dosages of ganciclovir followed by maintenance therapy, at which time they experienced reactivation of their disease. The dosing regimen for induction with the combined therapy was foscarnet (60 mg/kg every 8 hours) and ganciclovir (5 mg/kg daily for 3 weeks). Maintenance with combined therapy consisted of foscarnet (90 mg/ kg daily) and ganciclovir (5 mg/kg daily). All patients showed complete healing of the retinitis during the first 3 weeks of combined therapy. Median survival after initiation of combined therapy was 15 weeks (range, 12-33 weeks). None of the children experienced reactivation of CMV retinitis during combined therapy with ganciclovir and foscarnet. Combined therapy was well tolerated in all patients without major side effects. No patient required discontinuation or interruption of either drug during combined therapy. Children with recurrent CMV retinitis may not report visual symptoms, which can delay therapeutic intervention. Therefore, recurrent disease in children should be treated aggressively to avoid potentially devastating visual loss. A combination of ganciclovir and foscarnet appears to be a safe and effective therapeutic option for treatment of recurrent CMV retinitis in children with AIDS. This approach causes no additional toxic reactions and may provide improved long-term control of recurrent CMV retinitis in children. JF - Ophthalmology AU - Walton, R C AU - Whitcup, S M AU - Mueller, B U AU - Lewis, L L AU - Pizzo, P A AU - Nussenblatt, R B AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1865 EP - 1870 VL - 102 IS - 12 SN - 0161-6420, 0161-6420 KW - Antiviral Agents KW - 0 KW - Foscarnet KW - 364P9RVW4X KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Fundus Oculi KW - Infusions, Intravenous KW - Humans KW - Child KW - Retina -- pathology KW - Recurrence KW - Male KW - Female KW - Child, Preschool KW - Cytomegalovirus Retinitis -- drug therapy KW - Antiviral Agents -- therapeutic use KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Antiviral Agents -- administration & dosage KW - Ganciclovir -- therapeutic use KW - Ganciclovir -- administration & dosage KW - AIDS-Related Opportunistic Infections -- pathology KW - Ganciclovir -- adverse effects KW - Foscarnet -- administration & dosage KW - Cytomegalovirus Retinitis -- pathology KW - Antiviral Agents -- adverse effects KW - Foscarnet -- therapeutic use KW - Foscarnet -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77946571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ophthalmology&rft.atitle=Combined+intravenous+ganciclovir+and+foscarnet+for+children+with+recurrent+cytomegalovirus+retinitis.&rft.au=Walton%2C+R+C%3BWhitcup%2C+S+M%3BMueller%2C+B+U%3BLewis%2C+L+L%3BPizzo%2C+P+A%3BNussenblatt%2C+R+B&rft.aulast=Walton&rft.aufirst=R&rft.date=1995-12-01&rft.volume=102&rft.issue=12&rft.spage=1865&rft.isbn=&rft.btitle=&rft.title=Ophthalmology&rft.issn=01616420&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-08 N1 - Date created - 1997-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disulfide stabilization of antibody Fv: computer predictions and experimental evaluation. AN - 77934676; 8869646 AB - Using molecular modeling technology we have recently identified positions in conserved framework regions of Fvs which can be used to stabilize antibody Fvs by an interchain disulfide bond engineered in between the structurally conserved framework positions of the variable domains of heavy (VH) and light (VL) immunoglobulin chains (disulfide-stabilized Fv; dsFv). The computer model indicated the existence of other potential sites in the framework regions that might be suitable for disulfide bond formation between VH and VL. The possibility of obtaining dsFvs using these positions is evaluated here experimentally by constructing dsFv immunotoxins in which the Fv moiety is fused to a truncated form of Pseudomonas exotoxin. We analyzed the extent of dsFv formation and the activity of the resulting dsFv immunotoxins, and compared various dsFv molecules with the scFv immunotoxin. Our results demonstrate that position H44-L105 is the only one which gives high production yields of active dsFv. All other positions gave either low yields and activity or completely failed to produce active dsFv. With one exception, the formation and activities of the dsFvs corresponded to the C alpha-C alpha distance between the VH and VL positions, with an optimal distance of 5.7 A producing the best dsFv. Distances of 6.0-6.9 A resulted in a low yield of protein that was still capable of binding antigen, whereas distances > 7.0 A resulted in molecules in which dsFv formation was not obtained. JF - Protein engineering AU - Reiter, Y AU - Brinkmann, U AU - Jung, S H AU - Pastan, I AU - Lee, B AD - Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1323 EP - 1331 VL - 8 IS - 12 SN - 0269-2139, 0269-2139 KW - DNA Primers KW - 0 KW - Disulfides KW - Immunoglobulin Fragments KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Tryptophan KW - 8DUH1N11BX KW - Urea KW - 8W8T17847W KW - Index Medicus KW - Immunoglobulin Variable Region -- genetics KW - Computer Simulation KW - Fluorescence KW - Electrophoresis, Polyacrylamide Gel KW - Models, Molecular KW - Mutagenesis, Site-Directed -- genetics KW - Protein Denaturation KW - Escherichia coli -- genetics KW - Immunoglobulin Variable Region -- chemistry KW - Amino Acid Sequence KW - Tryptophan -- metabolism KW - Base Sequence KW - Protein Engineering KW - Cell Survival -- drug effects KW - Molecular Sequence Data KW - Urea -- pharmacology KW - DNA Primers -- chemistry KW - Immunotoxins -- chemistry KW - Immunoglobulin Fragments -- genetics KW - Recombinant Fusion Proteins -- isolation & purification KW - Immunotoxins -- isolation & purification KW - Immunotoxins -- genetics KW - Recombinant Fusion Proteins -- toxicity KW - Disulfides -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Immunoglobulin Fragments -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77934676?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=Disulfide+stabilization+of+antibody+Fv%3A+computer+predictions+and+experimental+evaluation.&rft.au=Reiter%2C+Y%3BBrinkmann%2C+U%3BJung%2C+S+H%3BPastan%2C+I%3BLee%2C+B&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1995-12-01&rft.volume=8&rft.issue=12&rft.spage=1323&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide synthase inhibitors. Preclinical studies of potential use for treatment of opioid withdrawal. AN - 77908910; 8747756 AB - Four inhibitors of nitric oxide synthase (NOS), administered as acute pretreatments, attenuated several signs of naloxone-precipitated opioid withdrawal in morphine-dependent rats. Profiles of these drugs for inhibiting the expression of withdrawal were similar to that of clonidine, a drug used clinically to treat opioid withdrawal. The nonselective NOS inhibitors, NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester, and N(5)-(1-iminoethyl)-L-ornithine, a selective inhibitor of endothelial NOS, Increased blood pressure in awake, morphine-naive and morphine-dependent rats not undergoing withdrawal. 7-Nitroindazole, a selective inhibitor of neuronal NOS, did not elevate blood pressure. Insofar as hypertension is a component of opioid withdrawal in humans, the ability of 7-nitroindazole to attenuate morphine withdrawal in rats without eliciting a vasopressor response suggests that 7-nitroindazole may have human therapeutic potential. Research directions for the continued development of 7-nitroindazole as a therapeutic modality are discussed with respect to issues of physical dependence, tolerance, and safety. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Vaupel, D B AU - Kimes, A S AU - London, E D AD - Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 315 EP - 322 VL - 13 IS - 4 SN - 0893-133X, 0893-133X KW - Adrenergic alpha-Agonists KW - 0 KW - Enzyme Inhibitors KW - Indazoles KW - Narcotics KW - Nitroarginine KW - 2149-70-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - N(G)-iminoethylornithine KW - 36889-13-1 KW - Morphine KW - 76I7G6D29C KW - Arginine KW - 94ZLA3W45F KW - Ornithine KW - E524N2IXA3 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Clonidine KW - MN3L5RMN02 KW - 7-nitroindazole KW - UX0N37CMVH KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Index Medicus KW - Animals KW - Nitric Oxide -- antagonists & inhibitors KW - Indazoles -- pharmacology KW - Ornithine -- toxicity KW - Arginine -- pharmacology KW - Depression, Chemical KW - Heart Rate -- drug effects KW - Ornithine -- pharmacology KW - Ornithine -- analogs & derivatives KW - Indazoles -- toxicity KW - Arginine -- toxicity KW - Clonidine -- pharmacology KW - Blood Pressure -- drug effects KW - Arginine -- analogs & derivatives KW - Opioid-Related Disorders -- metabolism KW - Substance Withdrawal Syndrome -- metabolism KW - Morphine -- adverse effects KW - Adrenergic alpha-Agonists -- pharmacology KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Enzyme Inhibitors -- toxicity KW - Substance Withdrawal Syndrome -- drug therapy KW - Narcotics -- adverse effects KW - Enzyme Inhibitors -- pharmacology KW - Adrenergic alpha-Agonists -- toxicity KW - Opioid-Related Disorders -- drug therapy KW - Morphine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77908910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Nitric+oxide+synthase+inhibitors.+Preclinical+studies+of+potential+use+for+treatment+of+opioid+withdrawal.&rft.au=Vaupel%2C+D+B%3BKimes%2C+A+S%3BLondon%2C+E+D&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1995-12-01&rft.volume=13&rft.issue=4&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-25 N1 - Date created - 1996-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Magnetic resonance imaging of brain iron in health and disease. AN - 77907301; 8847541 AB - Brain iron is a major contributor to magnetic resonance imaging (MRI) contrast in normal gray matter, and its role in the pathogenesis of different neurological disorders has also become apparent. Non-heme brain iron is present in the brain mainly in the form of ferritin. The unique magnetic properties of ferritin determine different signal changes on both T1- and T2-weighted images, and the T2 relaxation rates have a linear dependence on applied field strength. This finding is typical for ferric oxyhydroxide cores. The resulting T2-shortening also depends on echo-spacing used in the imaging sequence as well as on the water diffusion coefficient and the size of the ferritin cluster. Quantitation of non-heme brain iron by MRI aids in the diagnosis and monitoring of different neurological diseases. JF - Journal of the neurological sciences AU - Vymazal, J AU - Brooks, R A AU - Patronas, N AU - Hajek, M AU - Bulte, J W AU - Di Chiro, G AD - Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, NINDS, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 19 EP - 26 VL - 134 Suppl SN - 0022-510X, 0022-510X KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Humans KW - Health KW - Iron -- adverse effects KW - Brain -- pathology KW - Brain -- anatomy & histology KW - Nervous System Diseases -- pathology KW - Iron -- metabolism KW - Brain Chemistry -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77907301?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+neurological+sciences&rft.atitle=Magnetic+resonance+imaging+of+brain+iron+in+health+and+disease.&rft.au=Vymazal%2C+J%3BBrooks%2C+R+A%3BPatronas%2C+N%3BHajek%2C+M%3BBulte%2C+J+W%3BDi+Chiro%2C+G&rft.aulast=Vymazal&rft.aufirst=J&rft.date=1995-12-01&rft.volume=134+Suppl&rft.issue=&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+neurological+sciences&rft.issn=0022510X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic polymorphism of CYP2C9 and its effect on warfarin maintenance dose requirement in patients undergoing anticoagulation therapy. AN - 77904277; 8747411 JF - Pharmacogenetics AU - Furuya, H AU - Fernandez-Salguero, P AU - Gregory, W AU - Taber, H AU - Steward, A AU - Gonzalez, F J AU - Idle, J R AD - Laboratory of Molecular Carcinogenesis, NCI, NIH, Bethesda, MD 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 389 EP - 392 VL - 5 IS - 6 SN - 0960-314X, 0960-314X KW - Anticoagulants KW - 0 KW - DNA Primers KW - Warfarin KW - 5Q7ZVV76EI KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Steroid Hydroxylases KW - EC 1.14.- KW - CYP2C9 protein, human KW - EC 1.14.13.- KW - Cytochrome P-450 CYP2C9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Steroid 16-alpha-Hydroxylase KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Alleles KW - DNA Primers -- genetics KW - Humans KW - Molecular Sequence Data KW - Pharmacogenetics KW - Male KW - Female KW - Polymorphism, Genetic KW - Cytochrome P-450 Enzyme System -- genetics KW - Warfarin -- metabolism KW - Warfarin -- administration & dosage KW - Steroid Hydroxylases -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Anticoagulants -- metabolism KW - Steroid Hydroxylases -- genetics KW - Anticoagulants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77904277?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=Genetic+polymorphism+of+CYP2C9+and+its+effect+on+warfarin+maintenance+dose+requirement+in+patients+undergoing+anticoagulation+therapy.&rft.au=Furuya%2C+H%3BFernandez-Salguero%2C+P%3BGregory%2C+W%3BTaber%2C+H%3BSteward%2C+A%3BGonzalez%2C+F+J%3BIdle%2C+J+R&rft.aulast=Furuya&rft.aufirst=H&rft.date=1995-12-01&rft.volume=5&rft.issue=6&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The emerging role of cytochrome P450 3A in psychopharmacology. AN - 77902353; 8748427 AB - Recent advances in molecular pharmacology have allowed the characterization of the specific isoforms that mediate the metabolism of various medications. This information can be integrated with older clinical observations to begin to develop specific mechanistic and predictive models of psychotropic drug interactions. The polymorphic cytochrome P450 2D6 has gained much attention, because competition for this isoform is responsible for serotonin reuptake inhibitor-induced increases in tricyclic antidepressant concentrations in plasma. However, the cytochrome P450 3A subfamily and the 3A3 and 3A4 isoforms (CYP3A3/4) in particular are becoming increasingly important in psychopharmacology as a result of their central involvement in the metabolism of a wide range of steroids and medications, including antidepressants, benzodiazepines, calcium channel blockers, and carbamazepine. The inhibition of CYP3A3/4 by medications such as certain newer antidepressants, calcium channel blockers, and antibiotics can increase the concentrations of CYP3A3/4 substrates, yielding toxicity. The induction of CYP3A3/4 by medications such as carbamazepine can decrease the concentrations of CYP3A3/4 substrates, yielding inefficiency. Thus, knowledge of the substrates, inhibitors, and inducers of CYP3A3/ and other cytochrome P450 isoforms may help clinicians to anticipate and avoid pharmacokinetic drug interactions and improve rational prescribing practices. JF - Journal of clinical psychopharmacology AU - Ketter, T A AU - Flockhart, D A AU - Post, R M AU - Denicoff, K AU - Pazzaglia, P J AU - Marangell, L B AU - George, M S AU - Callahan, A M AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 387 EP - 398 VL - 15 IS - 6 SN - 0271-0749, 0271-0749 KW - Isoenzymes KW - 0 KW - Psychotropic Drugs KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Index Medicus KW - Drug Therapy, Combination KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Humans KW - Isoenzymes -- physiology KW - Cytochrome P-450 Enzyme System -- physiology KW - Psychotropic Drugs -- pharmacokinetics KW - Psychotropic Drugs -- adverse effects KW - Psychotropic Drugs -- administration & dosage KW - Oxidoreductases, N-Demethylating -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77902353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+psychopharmacology&rft.atitle=The+emerging+role+of+cytochrome+P450+3A+in+psychopharmacology.&rft.au=Ketter%2C+T+A%3BFlockhart%2C+D+A%3BPost%2C+R+M%3BDenicoff%2C+K%3BPazzaglia%2C+P+J%3BMarangell%2C+L+B%3BGeorge%2C+M+S%3BCallahan%2C+A+M&rft.aulast=Ketter&rft.aufirst=T&rft.date=1995-12-01&rft.volume=15&rft.issue=6&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+psychopharmacology&rft.issn=02710749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-26 N1 - Date created - 1996-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current topics in tardive dyskinesia in Japan. AN - 77897172; 8726107 AB - This article reviews current topics in tardive dyskinesia (TD), a movement disorder associated with the prolonged use of neuroleptic agents, especially therapeutic and preventive strategies which have been or are now being studied in Japan. Tardive dyskinesia has become a major problem in the clinical psychiatric field since the early 1970s in Japan, lagging behind Western countries by more than 10 years. The average prevalence rate of TD has been estimated as 7.7% in Japan, while it has been reported in the English literature at around 15 to 20%. Clinical trials of treatments for TD have been or are now being performed in Japan with a number of novel compounds, such as ceruletide, meclofenoxate, and rolipram; however, no effective treatment has yet been established and measures to prevent TD have therefore been emphasized. These include (i) the development of new antipsychotic drugs which are free from TD, (ii) the identification of risk factors from prospective longitudinal studies, and (iii) the investigation of genetic variations that could act as a marker to identify especially vulnerable patients within the whole population of patients who need neuroleptic therapy. JF - Psychiatry and clinical neurosciences AU - Inada, T AU - Yagi, G AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 239 EP - 244 VL - 49 IS - 5-6 SN - 1323-1316, 1323-1316 KW - Antipsychotic Agents KW - 0 KW - Central Nervous System Agents KW - Pyrrolidinones KW - Ceruletide KW - 888Y08971B KW - Meclofenoxate KW - C76QQ2I0RG KW - Rolipram KW - K676NL63N7 KW - Index Medicus KW - Ceruletide -- administration & dosage KW - Risk Factors KW - Humans KW - Cross-Cultural Comparison KW - Treatment Outcome KW - Clinical Trials as Topic KW - Meclofenoxate -- administration & dosage KW - Japan KW - Pyrrolidinones -- administration & dosage KW - Dyskinesia, Drug-Induced -- drug therapy KW - Central Nervous System Agents -- administration & dosage KW - Antipsychotic Agents -- therapeutic use KW - Dyskinesia, Drug-Induced -- prevention & control KW - Dyskinesia, Drug-Induced -- diagnosis KW - Antipsychotic Agents -- adverse effects KW - Psychotic Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77897172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+and+clinical+neurosciences&rft.atitle=Current+topics+in+tardive+dyskinesia+in+Japan.&rft.au=Inada%2C+T%3BYagi%2C+G&rft.aulast=Inada&rft.aufirst=T&rft.date=1995-12-01&rft.volume=49&rft.issue=5-6&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Psychiatry+and+clinical+neurosciences&rft.issn=13231316&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-29 N1 - Date created - 1996-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NF kappa B and interferon regulatory factor 1 physically interact and synergistically induce major histocompatibility class I gene expression. AN - 77894476; 8746784 AB - Major histocompatibility (MHC) class I gene expression is synergistically induced by the cytokines TNF-alpha and IFN-gamma. However, the mechanism that results in synergistic activation of these genes has remained unclear. We demonstrated here that TNF-alpha induced binding of NF kappa B p50 and p65 to the NF kappa B-like element of the MHC class I promoter termed region I and IFN-gamma induced binding of IRF-1 to the adjacent interferon consensus sequence (ICS). We further demonstrated that NF kappa B and IRF-1 physically interacted with each other and cooperatively induced MHC class I gene expression when cotransfected into CHP-126 neuroblastomas. These results provide a molecular mechanism by which TNF-alpha and IFN-gamma synergistically induce the expression of a variety of genes involved in immune responses, including MHC class I. JF - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research AU - Drew, P D AU - Franzoso, G AU - Becker, K G AU - Bours, V AU - Carlson, L M AU - Siebenlist, U AU - Ozato, K AD - Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1037 EP - 1045 VL - 15 IS - 12 SN - 1079-9907, 1079-9907 KW - DNA-Binding Proteins KW - 0 KW - IRF1 protein, human KW - Interferon Regulatory Factor-1 KW - NF-kappa B KW - Phosphoproteins KW - Transcription Factors KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Stimulation, Chemical KW - Promoter Regions, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Genetic Vectors KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Molecular Sequence Data KW - Interferon-gamma -- pharmacology KW - Drug Synergism KW - Transcription Factors -- metabolism KW - Gene Expression Regulation -- drug effects KW - Consensus Sequence KW - Phosphoproteins -- metabolism KW - NF-kappa B -- metabolism KW - Genes, MHC Class I KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77894476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+interferon+%26+cytokine+research+%3A+the+official+journal+of+the+International+Society+for+Interferon+and+Cytokine+Research&rft.atitle=NF+kappa+B+and+interferon+regulatory+factor+1+physically+interact+and+synergistically+induce+major+histocompatibility+class+I+gene+expression.&rft.au=Drew%2C+P+D%3BFranzoso%2C+G%3BBecker%2C+K+G%3BBours%2C+V%3BCarlson%2C+L+M%3BSiebenlist%2C+U%3BOzato%2C+K&rft.aulast=Drew&rft.aufirst=P&rft.date=1995-12-01&rft.volume=15&rft.issue=12&rft.spage=1037&rft.isbn=&rft.btitle=&rft.title=Journal+of+interferon+%26+cytokine+research+%3A+the+official+journal+of+the+International+Society+for+Interferon+and+Cytokine+Research&rft.issn=10799907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-12 N1 - Date created - 1997-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional domains of bovine beta-1,4 galactosyltransferase. AN - 77893290; 8748165 AB - A number of N- and C-terminal deletion and point mutants of bovine beta-1,4 galactosyltransferase (beta-1,4GT) were expressed in E. coli to determine the binding regions of the enzyme that interact with N-acetylglucosamine (NAG) and UDP-galactose. The N-terminal truncated forms of the enzyme between residues 1-129, do not show any significant difference in the apparent Kms towards NAG or linear oligosaccharide acceptors e.g. for chitobiose and chitotriose, or for the nucleotide donor UDP-galactose. Deletion or mutation of Cys 134 results in the loss of enzymatic activity, but does not affect the binding properties of the protein either to NAG- or UDP-agarose. From these columns the protein can be eluted with 15 mM NAG and 50 mM EDTA, like the enzymatically active protein, TL-GT129, that contains residues 130-402 of bovine beta-1,4GT. Also the N-terminus fragment, TL-GT129NAG, that contains residues 130-257 of the beta-1,4GT, binds to, and elutes with 15 mM NAG and 50 mM EDTA from the NAG-agarose column as efficiently as the enzymatically active TL-GT129. Unlike TL-GT129, the TL-GT129NAG binds to UDP-columns less efficiently and can be eluted from the column with only 15 mM NAG. The C-terminus fragment GT-257UDP, containing residues 258-402 of beta-1,4GT, binds tightly to both NAG- and UDP-agarose columns. A small fraction, 5-10% of the bound protein, can be eluted from the UDP-agarose column with 50 mM EDTA alone. The results show that the binding behaviour of N- and C-terminal fragments of beta-1,4GT towards the NAG- and UDP-agarose columns differ, the former binds preferentially to NAG-columns, while the latter binds to UDP-agarose columns via Mn2+. JF - Glycoconjugate journal AU - Boeggeman, E E AU - Balaji, P V AU - Qasba, P K AD - Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-8105, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 865 EP - 878 VL - 12 IS - 6 SN - 0282-0080, 0282-0080 KW - Recombinant Fusion Proteins KW - 0 KW - Recombinant Proteins KW - Uridine Diphosphate Galactose KW - 2956-16-3 KW - N-Acetyllactosamine Synthase KW - EC 2.4.1.90 KW - Acetylglucosamine KW - V956696549 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Cattle KW - Base Sequence KW - Solubility KW - Recombinant Proteins -- biosynthesis KW - Kinetics KW - Genetic Vectors KW - Molecular Sequence Data KW - Escherichia coli KW - Binding Sites KW - Mutagenesis, Site-Directed KW - N-Acetyllactosamine Synthase -- genetics KW - N-Acetyllactosamine Synthase -- chemistry KW - Chromosome Deletion KW - N-Acetyllactosamine Synthase -- biosynthesis KW - Uridine Diphosphate Galactose -- chemistry KW - Acetylglucosamine -- chemistry KW - Protein Structure, Tertiary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77893290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glycoconjugate+journal&rft.atitle=Functional+domains+of+bovine+beta-1%2C4+galactosyltransferase.&rft.au=Boeggeman%2C+E+E%3BBalaji%2C+P+V%3BQasba%2C+P+K&rft.aulast=Boeggeman&rft.aufirst=E&rft.date=1995-12-01&rft.volume=12&rft.issue=6&rft.spage=865&rft.isbn=&rft.btitle=&rft.title=Glycoconjugate+journal&rft.issn=02820080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-15 N1 - Date created - 1996-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fetal mouse susceptibility to transplacental carcinogenesis: differential influence of Ah receptor phenotype on effects of 3-methylcholanthrene, 12-dimethylbenz[a]anthracene, and benzo[a]pyrene. AN - 77893233; 8747408 AB - Genetic backcrosses of C57BL/6 and DBA/2 mice were used to examine the influence of maternal and fetal polymorphisms at the Ahr locus on susceptibility to transplacental carcinogenesis by 3-methylcholanthrene, 7,12-dimethylbenz[a]anthracene, and benzo[a]pyrene. (C57BL/6 x DBA/2) F1 mothers were backcrossed to DBA/2 males, and DBA/2 females to F1 males to produce both Ahr-responsive (Ah+) and nonresponsive (Ah-) fetuses carried by mothers that were themselves either Ah+ or Ah-. 3-Methylcholanthrene was given intragastrically on gestation days 13-18 and 7,12-dimethylbenz[a]anthracene or benzo[a]pyrene on day 17 as a single intraperitoneal dose. Ahr phenotype was determined by the zoxazolamine sleeping time test after beta-naphthoflavone pretreatment at 6 weeks of age. The offspring were examined for tumours at 1 year. Both 3-methylcholanthrene and 7,12-dimethylbenz[a]anthracene treatments resulted in a two- to five-fold greater incidence and multiplicity of lung and liver tumours in the Ah+ offspring compared with that in Ah- littermates. By contrast, there was no difference between Ah+ and Ah- offspring with regard to numbers of tumours caused by benzo[a]pyrene. Maternal Ahr phenotype appeared to play a role also, in that the offspring of the Ahr-responsive F1 mothers developed fewer tumours per unit dose than those of the nonresponsive DBA/2 mothers. The effect of maternal phenotype on risk was three- to five-fold. Fetal and maternal phenotype combined yielded a 10- to 20-fold risk differential for transplacental carcinogenesis by the methylated compounds, with greatest risk experienced by responsive fetuses in nonresponsive mothers, and least by nonresponsive progeny of responsive mothers. JF - Pharmacogenetics AU - Anderson, L M AU - Ruskie, S AU - Carter, J AU - Pittinger, S AU - Kovatch, R M AU - Riggs, C W AD - Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, Frederick Cancer Research and Development Center (FCRDC), MD 21702, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 364 EP - 372 VL - 5 IS - 6 SN - 0960-314X, 0960-314X KW - Carcinogens KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Benzo(a)pyrene KW - 3417WMA06D KW - Methylcholanthrene KW - 56-49-5 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Animals KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Pharmacogenetics KW - Pregnancy KW - Mice, Inbred DBA KW - Phenotype KW - Maternal-Fetal Exchange KW - Risk Factors KW - Benzo(a)pyrene -- toxicity KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Lung Neoplasms -- chemically induced KW - Female KW - Male KW - Benzo(a)pyrene -- metabolism KW - Carcinogens -- metabolism KW - Methylcholanthrene -- toxicity KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Carcinogens -- toxicity KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism KW - Methylcholanthrene -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77893233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=Fetal+mouse+susceptibility+to+transplacental+carcinogenesis%3A+differential+influence+of+Ah+receptor+phenotype+on+effects+of+3-methylcholanthrene%2C+12-dimethylbenz%5Ba%5Danthracene%2C+and+benzo%5Ba%5Dpyrene.&rft.au=Anderson%2C+L+M%3BRuskie%2C+S%3BCarter%2C+J%3BPittinger%2C+S%3BKovatch%2C+R+M%3BRiggs%2C+C+W&rft.aulast=Anderson&rft.aufirst=L&rft.date=1995-12-01&rft.volume=5&rft.issue=6&rft.spage=364&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gamma-glutamyltranspeptidase and carbohydrate deficient transferrin: alternative measures of excessive alcohol consumption. AN - 77890354; 8749824 AB - Both gamma-glutamyltranspeptidase and carbohydrate-deficient transferrin have been extensively researched as biological markers of heavy alcohol consumption. The current study briefly describes each test, identifies subject variables that influence their relative sensitivities and specificities, and examines issues surrounding use of the two markers in combination. In addition, this study suggests five design features that should characterize projects evaluating the validity of biochemical markers. JF - Alcoholism, clinical and experimental research AU - Litten, R Z AU - Allen, J P AU - Fertig, J B AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20892-7003, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1541 EP - 1546 VL - 19 IS - 6 SN - 0145-6008, 0145-6008 KW - Biomarkers KW - 0 KW - Transferrin KW - carbohydrate-deficient transferrin KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Index Medicus KW - Sensitivity and Specificity KW - Mass Screening KW - Humans KW - Biomarkers -- analysis KW - Transferrin -- analogs & derivatives KW - Alcoholism -- enzymology KW - Alcoholism -- diagnosis KW - gamma-Glutamyltransferase -- blood KW - Transferrin -- analysis KW - Liver Function Tests KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77890354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Gamma-glutamyltranspeptidase+and+carbohydrate+deficient+transferrin%3A+alternative+measures+of+excessive+alcohol+consumption.&rft.au=Litten%2C+R+Z%3BAllen%2C+J+P%3BFertig%2C+J+B&rft.aulast=Litten&rft.aufirst=R&rft.date=1995-12-01&rft.volume=19&rft.issue=6&rft.spage=1541&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-26 N1 - Date created - 1996-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal. Medication development issues for opiate addiction. AN - 77888267; 8747752 AB - This article is an exploration of the National Institute on Drug Abuse (NIDA) Technical Review on the role of glutamatergic systems in the development of opiate addiction. The effects of "glutamate antagonist" medications on opioid tolerance and withdrawal are examined. In rodents, mu opioid tolerance can be inhibited by noncompetitive N-methyl D-aspartate (NMDA) receptor antagonists [MK801, dextromethorphan (DM), ketamine, phencyclidine (PCP)], competitive NMDA receptor antagonists (LY274614, NPC17742, LY235959), partial glycine agonists (ACPC), glycine antagonists (ACEA-1328), and nitric oxide synthase (NOS) inhibitors [L-NNA, L-NMMA, methylene blue (MB)]. Similarly, some of the symptoms of opioid withdrawal observed in opioid-dependent rodents also can be inhibited by noncompetitive NMDA receptor antagonists (MK801, DM, ketamine), competitive NMDA receptor antagonists (LY274614), glycine antagonists (felbamate), and NOS inhibitors (L-NNA, L-NMMA, L-NAME, L-NIO, 7-NI, MB). There are some serious toxicological effects associated with the administration of some of the noncompetitive NMDA receptor antagonists in rodent but not in squirrel monkey brain, and some medications induce PCP-like behavioral effects. The medications with the most immediate clinical appeal are those that could be coadministered with methadone to decrease mu opioid tolerance and dependence; they include DM, MB, 7-NI, ACPC, and ACEA-1328. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Herman, B H AU - Vocci, F AU - Bridge, P AD - Medications Development Division, National Institute on Drug Abuse, National Institutes of Health, Rockville, MD 20857, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 269 EP - 293 VL - 13 IS - 4 SN - 0893-133X, 0893-133X KW - Enzyme Inhibitors KW - 0 KW - Excitatory Amino Acid Antagonists KW - Narcotics KW - Receptors, N-Methyl-D-Aspartate KW - Receptors, Opioid, delta KW - Receptors, Opioid, kappa KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Animals KW - Nitric Oxide -- antagonists & inhibitors KW - Humans KW - Receptors, Opioid, kappa -- drug effects KW - Receptors, Opioid, delta -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Excitatory Amino Acid Antagonists -- toxicity KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Substance Withdrawal Syndrome -- drug therapy KW - Narcotics -- adverse effects KW - Excitatory Amino Acid Antagonists -- adverse effects KW - Enzyme Inhibitors -- pharmacology KW - Opioid-Related Disorders -- drug therapy KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77888267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=The+effects+of+NMDA+receptor+antagonists+and+nitric+oxide+synthase+inhibitors+on+opioid+tolerance+and+withdrawal.+Medication+development+issues+for+opiate+addiction.&rft.au=Herman%2C+B+H%3BVocci%2C+F%3BBridge%2C+P&rft.aulast=Herman&rft.aufirst=B&rft.date=1995-12-01&rft.volume=13&rft.issue=4&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-25 N1 - Date created - 1996-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coadaptation and immunodeficiency virus: lessons from the Felidae. AN - 77880648; 8745072 AB - The emergence of pathogenic viruses in new species offers an unusual opportunity to monitor the coadaptation of viruses and their hosts in a dynamic ongoing process of intense biological selection. Tracking lentivirus epidemics in man, monkeys and cats reveals genomic struggles at three levels: quasispecies divergence within an individual; coadaptation of virus and host genomes subsequent to disease outbreaks; and transmission, spread and pathogenesis in related host species. Aspects of each level are revealed by examining the genetic diversity of feline immunodeficiency virus in domestic and wild cat species. This approach has been facilitated by the recent genetic characterization of a novel lentivirus in lions. JF - Current opinion in genetics & development AU - Carpenter, M A AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, NCI-FCRDC, Frederick, MD 21702-1201, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 739 EP - 745 VL - 5 IS - 6 SN - 0959-437X, 0959-437X KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Genetic Variation KW - Feline Acquired Immunodeficiency Syndrome -- immunology KW - Humans KW - Immunity, Innate KW - HIV-1 KW - Primates KW - Haplorhini KW - Cattle KW - Acquired Immunodeficiency Syndrome -- transmission KW - Lentivirus -- genetics KW - Species Specificity KW - Feline Acquired Immunodeficiency Syndrome -- transmission KW - Phylogeny KW - Cats -- virology KW - Immunodeficiency Virus, Feline -- genetics KW - Carnivora -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77880648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+genetics+%26+development&rft.atitle=Coadaptation+and+immunodeficiency+virus%3A+lessons+from+the+Felidae.&rft.au=Carpenter%2C+M+A%3BO%27Brien%2C+S+J&rft.aulast=Carpenter&rft.aufirst=M&rft.date=1995-12-01&rft.volume=5&rft.issue=6&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+genetics+%26+development&rft.issn=0959437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tat mediates transcriptional activation of HIV-1 gene in vitro. AN - 77877742; 8714203 AB - Gene expression of human immunodeficiency virus (HIV-1) is greatly enhanced by a viral transactivator, the Tat protein, which interacts with R region sequences of the HIV-1 long terminal repeat (LTR). There is no direct evidence to indicate transcriptional activation of HIV-1 by Tat. Using an in vitro transcription system, we demonstrate that an established mouse cell line, which constitutively expresses Tat protein, selectively stimulates the steady state levels of the transcripts directed from the long terminal repeat (LTR) sequences of HIV-1. The gel binding retardation assays further demonstrate a stable activated complex, formed due to direct binding of Tat to DNA elements of the HIV-1 LTR. These data implicate transcription as the site of Tat action in trans-activation and could play an essential role in human immunodeficiency virus replication, similar to the nuclear trans-activators of other viruses. JF - Indian journal of biochemistry & biophysics AU - West, M AU - Hoover, T AU - Kung, H AU - Raziuddin AD - Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 351 EP - 355 VL - 32 IS - 6 SN - 0301-1208, 0301-1208 KW - Gene Products, tat KW - 0 KW - tat Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Mice KW - Cell Line KW - Gene Products, tat -- physiology KW - HIV-1 -- genetics KW - Gene Expression Regulation, Viral -- physiology KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77877742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+journal+of+biochemistry+%26+biophysics&rft.atitle=Tat+mediates+transcriptional+activation+of+HIV-1+gene+in+vitro.&rft.au=West%2C+M%3BHoover%2C+T%3BKung%2C+H%3BRaziuddin&rft.aulast=West&rft.aufirst=M&rft.date=1995-12-01&rft.volume=32&rft.issue=6&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=Indian+journal+of+biochemistry+%26+biophysics&rft.issn=03011208&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-18 N1 - Date created - 1996-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide (NO) protects against cellular damage by reactive oxygen species. AN - 77876287; 8597056 AB - Since the discovery of nitric oxide (NO) as an endogenously formed radical, its effect on numerous physiological processes has been intensively investigated. Some studies have suggested NO to be cytotoxic while others have demonstrated it protective under various biological conditions. Though NO shows minimal cytotoxicity to a variety mammalian cell cultures, it does modulate the toxicity of some agents such as reactive oxygen species. Often, NO is generated in the presence of these reactive oxygen species in response to foreign pathogens or under various pathophysiological conditions. We will show that NO can play a protective role under oxidative stress resulting from superoxide, hydrogen peroxide and alkyl peroxides. It was found by measuring the time-concentration profiles of NO released from various NO donor compounds that only microM levels of NO were required for protection against the toxicity of these reactive species. It was found that there are several chemical reactions which may account for these protective effects such as NO preventing heme oxidation, inhibition of Fenton-type oxidation of DNA, and abatement of lipid peroxidation. Taken together, NO at low concentrations clearly protects against peroxide-mediated toxicity. JF - Toxicology letters AU - Wink, D A AU - Cook, J A AU - Pacelli, R AU - Liebmann, J AU - Krishna, M C AU - Mitchell, J B AD - Tumor Biology Section, National Institutes of Health/National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 221 EP - 226 VL - 82-83 SN - 0378-4274, 0378-4274 KW - Reactive Oxygen Species KW - 0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydrogen Peroxide KW - BBX060AN9V KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - Index Medicus KW - Hydrogen Peroxide -- toxicity KW - Xanthine Oxidase -- toxicity KW - Animals KW - Humans KW - Nitric Oxide -- physiology KW - Reactive Oxygen Species -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77876287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Nitric+oxide+%28NO%29+protects+against+cellular+damage+by+reactive+oxygen+species.&rft.au=Wink%2C+D+A%3BCook%2C+J+A%3BPacelli%2C+R%3BLiebmann%2C+J%3BKrishna%2C+M+C%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1995-12-01&rft.volume=82-83&rft.issue=&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-15 N1 - Date created - 1996-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell proliferation as a determining factor for the carcinogenicity of chemicals: studies with mutagenic carcinogens and mutagenic noncarcinogens. AN - 77876179; 8597159 AB - Recent work in our laboratory has examined mechanisms whereby chemicals produce mutagenicity in short-term in vitro assays yet fail to produce carcinogenesis in 2-year rodent bioassays. These studies have used mutagenic structural analogs of carcinogenic and noncarcinogenic chemicals for comparison. Our previous studies have determined that differences in the metabolism and disposition of these chemicals were not responsible for their observed carcinogenic differences, but that carcinogenicity correlated with the ability of the respective isomer to induce cell proliferation in the target organ. Mutagenic noncarcinogens such as 2,6-diaminotoluene (DAT), 1-nitropropane (NP), dimethoate, dioxathion, and dichlorvos failed to induce an increase in cell turnover in the target organs. An increase in cell proliferation was observed following exposure to the mutagenic carcinogen analogs 2,4-DAT (liver), 2-NP (liver), and tris(2,3-dibromopropyl)phosphate (kidney). Our recent studies have used transgenic (Big Blue) mice to detect in vivo mutagenesis induced by DAT isomers. Results of these studies demonstrate that administration of the carcinogenic isomer, 2,4-DAT, resulted in an increase in in vivo mutation frequency, whereas administration of the noncarcinogenic isomer, 2,6-DAT, failed to do so. These results indicate that cell proliferation may be requisite for expression of chemical-induced mutagenicity in vivo and thereby accommodate expression of carcinogenicity. JF - Toxicology letters AU - Cunningham, M L AU - Matthews, H B AD - Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 9 EP - 14 VL - 82-83 SN - 0378-4274, 0378-4274 KW - Carcinogens KW - 0 KW - Mutagens KW - Phenylenediamines KW - 2,6-diaminotoluene KW - H838Q10551 KW - 2,4-diaminotoluene KW - IS1AKN4HYB KW - Index Medicus KW - Animals KW - Phenylenediamines -- toxicity KW - Humans KW - Mice KW - Cell Division -- drug effects KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77876179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Cell+proliferation+as+a+determining+factor+for+the+carcinogenicity+of+chemicals%3A+studies+with+mutagenic+carcinogens+and+mutagenic+noncarcinogens.&rft.au=Cunningham%2C+M+L%3BMatthews%2C+H+B&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1995-12-01&rft.volume=82-83&rft.issue=&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-15 N1 - Date created - 1996-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A minimal, compartmental model for a dendritic origin of bistability of motoneuron firing patterns. AN - 77875774; 8746404 AB - Various nonlinear regenerative responses, including plateau potentials and bistable repetitive firing modes, have been observed in motoneurons under certain conditions. Our simulation results support the hypothesis that these responses are due to plateau-generating currents in the dendrites, consistent with a major role for a noninactivating calcium L-type current as suggested by experiments. Bistability as observed in the soma of low- and higher-frequency spiking or, under TTX, of near resting and depolarized plateau potentials, occurs because the dendrites can be in a near resting or depolarized stable steady state. We formulate and study a two-compartment minimal model of a motoneuron that segregates currents for fast spiking into a soma-like compartment and currents responsible for plateau potentials into a dendrite-like compartment. Current flows between compartments through a coupling conductance, mimicking electrotonic spread. We use bifurcation techniques to illuminate how the coupling strength affects somatic behavior. We look closely at the case of weak coupling strength to gain insight into the development of bistable patterns. Robust somatic bistability depends on the electrical separation since it occurs only for weak to moderate coupling conductance. We also illustrate that hysteresis of the two spiking states is a natural consequence of the plateau behavior in the dendrite compartment. JF - Journal of computational neuroscience AU - Booth, V AU - Rinzel, J AD - Mathematical Research Branch, NIDDK, National Institutes of Health, Bethesda, MD 20814, USA. vbooth/helix.nih.gov Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 299 EP - 312 VL - 2 IS - 4 SN - 0929-5313, 0929-5313 KW - Neurotoxins KW - 0 KW - Tetrodotoxin KW - 4368-28-9 KW - Index Medicus KW - Animals KW - Evoked Potentials KW - Neurotoxins -- pharmacology KW - Electrophysiology KW - Tetrodotoxin -- pharmacology KW - Electric Stimulation KW - Mathematics KW - Motor Neurons -- physiology KW - Dendrites -- physiology KW - Models, Neurological KW - Motor Neurons -- drug effects KW - Dendrites -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77875774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+computational+neuroscience&rft.atitle=A+minimal%2C+compartmental+model+for+a+dendritic+origin+of+bistability+of+motoneuron+firing+patterns.&rft.au=Booth%2C+V%3BRinzel%2C+J&rft.aulast=Booth&rft.aufirst=V&rft.date=1995-12-01&rft.volume=2&rft.issue=4&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Journal+of+computational+neuroscience&rft.issn=09295313&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-11 N1 - Date created - 1996-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Successful treatment of hepatosplenic candidiasis through repeated cycles of chemotherapy and neutropenia. AN - 77873213; 8635043 AB - Hepatosplenic candidiasis (HSC) or chronic disseminated candidiasis is an increasingly recognized problem in patients with cancer. Whether patients with HSC should continue to receive antineoplastic therapy, which may cause neutropenia with the risk for progressive HSC or breakthrough fungemia, can be a major dilemma. Patients with HSC at the National Cancer Institute continue antineoplastic therapy, when possible during antifungal therapy for HSC, despite repeated bouts of neutropenia. Therefore, whether this strategy resulted in breakthrough fungemia or progression of HSC was investigated. All patients consecutively treated at the National Cancer Institute at the Warren-Grant Magnuson Clinical Center from 1982-1992 for HSC were prospectively studied for therapeutic and outcome variables of antifungal and antineoplastic management. Each case was summarized on a time-event line to quantify the duration of simultaneous periods of antineoplastic therapy and antifungal therapy (AFT). Sixteen patients (median age, 22 years) with HSC were studied. Eleven patients had relapsed tumor and 5 had newly diagnosed tumor. During antifungal therapy for HSC, 12 of 16 patients were neutropenic for a median of 10 days (range, 6-91 days) and 11 were profoundly neutropenic for a median of 13 days (range, 1-55 days). Hepatosplenic candidiasis was successfully treated with complete antifungal response in 12 patients and a partial response in 2; 2 patients continued to receive AFT. No patient had breakthrough fungemia and two patients had progression of HSC, only one episode of which occurred during neutropenia. Hepatosplenic candidiasis in patients with cancer may be treated successfully under careful observation through repeated courses of chemotherapy-induced neutropenia without progression of hepatosplenic candidiasis or breakthrough fungemia. JF - Cancer AU - Walsh, T J AU - Whitcomb, P O AU - Revankar, S G AU - Pizzo, P A AD - Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/12/01/ PY - 1995 DA - 1995 Dec 01 SP - 2357 EP - 2362 VL - 76 IS - 11 SN - 0008-543X, 0008-543X KW - Antifungal Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Neoplasms -- drug therapy KW - Humans KW - Disease Progression KW - Child KW - Fungemia -- prevention & control KW - Opportunistic Infections -- drug therapy KW - Child, Preschool KW - Prospective Studies KW - Neoplasm Recurrence, Local -- drug therapy KW - Risk Factors KW - Adult KW - National Institutes of Health (U.S.) KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Female KW - Fungemia -- etiology KW - Male KW - Remission Induction KW - Splenic Diseases -- drug therapy KW - Candidiasis -- drug therapy KW - Splenic Diseases -- microbiology KW - Neutropenia -- chemically induced KW - Antifungal Agents -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Liver Diseases -- microbiology KW - Liver Diseases -- drug therapy KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77873213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Successful+treatment+of+hepatosplenic+candidiasis+through+repeated+cycles+of+chemotherapy+and+neutropenia.&rft.au=Walsh%2C+T+J%3BWhitcomb%2C+P+O%3BRevankar%2C+S+G%3BPizzo%2C+P+A&rft.aulast=Walsh&rft.aufirst=T&rft.date=1995-12-01&rft.volume=76&rft.issue=11&rft.spage=2357&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-08 N1 - Date created - 1996-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of keratinocyte-derived cytokines in chemical toxicity. AN - 77870398; 8597097 AB - Following appropriate stimulation, such as with tumor promoters, ultraviolet light or various chemical agents, keratinocytes synthesize and secrete cytokines which can mediate or participate in dermatotoxic responses such as inflammation, hyperkeratosis, hypersensitivity and skin cancer. We have determined the qualitative and quantitative cytokine response in primary human keratinocyte cultures following exposure to several non-sensitizing contact irritants, sensitizers and ulcerative agents as well as a skin carcinogen. The chemicals were also administered to mice to assess whether the dermatotoxic response correlated with the in vitro production of keratinocyte-derived cytokines. Due to the complex cellular interactions that occur in the skin, it was not possible to identify specific cytokine profiles for most of the classes of dermatotoxic agents studied. However, the non-sensitizing contact irritants produced relative increases in the synthesis and secretion of the proinflammatory cytokines, interleukin-1 and tumor necrosis factor-alpha, as well as the neutrophil chemotactic cytokine, interleukin-8 compared to the other chemical agents. While ulcerative compounds as well as irritants elicited neutrophils to the site of chemical application when applied to the mouse skin, time-dependent and chemical-specific patterns of inflammation were detected. Treatment of human keratinocyte cultures with arsenic, a human skin carcinogen, resulted in a unique cytokine profile characterized by induction of growth factors, including transforming growth factor-alpha and granulocyte-macrophage colony stimulating factor. Treatment of v-Ha-ras transgenic mice, an animal model for skin cancer, with arsenic caused an increase in the number of papillomas as well as overexpression of these growth factors suggesting that they participate in arsenic-induced skin papilloma development. These studies indicate a diverse role exists for keratinocyte-derived cytokines in dermatotoxic actions. JF - Toxicology letters AU - Luster, M I AU - Wilmer, J L AU - Germolec, D R AU - Spalding, J AU - Yoshida, T AU - Gaido, K AU - Simeonova, P P AU - Burleson, F G AU - Bruccoleri, A AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 471 EP - 476 VL - 82-83 SN - 0378-4274, 0378-4274 KW - Cytokines KW - 0 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Animals KW - Arsenic -- toxicity KW - Cells, Cultured KW - Skin Neoplasms -- chemically induced KW - Humans KW - Mice KW - Mice, Transgenic KW - Mice, Inbred BALB C KW - Female KW - Keratinocytes -- drug effects KW - Cytokines -- physiology KW - Keratinocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77870398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Role+of+keratinocyte-derived+cytokines+in+chemical+toxicity.&rft.au=Luster%2C+M+I%3BWilmer%2C+J+L%3BGermolec%2C+D+R%3BSpalding%2C+J%3BYoshida%2C+T%3BGaido%2C+K%3BSimeonova%2C+P+P%3BBurleson%2C+F+G%3BBruccoleri%2C+A&rft.aulast=Luster&rft.aufirst=M&rft.date=1995-12-01&rft.volume=82-83&rft.issue=&rft.spage=471&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-15 N1 - Date created - 1996-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term toxicity studies of ozone in F344/N rats and B6C3F1 mice. AN - 77868328; 8597069 AB - The toxicity and carcinogenicity of ozone was evaluated in Fischer 344/N rats and B6C3F1 mice exposed to 0, 0.12 (2 years only), 0.5 or 1.0 ppm ozone by inhalation for 2-year and lifetime exposures. A 2-year cocarcinogenicity study (male rats only) included the subcutaneous administration of 0, 0.1 or 1.0 mg/kg/body wt. of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for the first 20 weeks along with inhalation exposure to 0 or 0.5 ppm ozone followed by additional 84 weeks of ozone exposure alone. Ozone exposure in rats did not cause an increased incidence of lung neoplasms. In the cocarcinogenicity study, ozone exposure did not have an additive carcinogenic effect. Lifetime and 2-year ozone exposure was associated with a marginal increase in lung tumors in male B6C3F1 mice and a more pronounced increase in females. Unique mutations in the K-ras gene were found in the mouse lung neoplasms from the ozone-exposed mice. JF - Toxicology letters AU - Boorman, G A AU - Sills, R C AU - Grumbein, S AU - Hailey, R AU - Miller, R A AU - Herbert, R A AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 301 EP - 306 VL - 82-83 SN - 0378-4274, 0378-4274 KW - Ozone KW - 66H7ZZK23N KW - Index Medicus KW - Rats KW - Genes, ras KW - Animals KW - Rats, Inbred F344 KW - Mice KW - Mutation KW - Male KW - Female KW - Lung Neoplasms -- chemically induced KW - Ozone -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77868328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Long-term+toxicity+studies+of+ozone+in+F344%2FN+rats+and+B6C3F1+mice.&rft.au=Boorman%2C+G+A%3BSills%2C+R+C%3BGrumbein%2C+S%3BHailey%2C+R%3BMiller%2C+R+A%3BHerbert%2C+R+A&rft.aulast=Boorman&rft.aufirst=G&rft.date=1995-12-01&rft.volume=82-83&rft.issue=&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-15 N1 - Date created - 1996-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 1995 Deichmann Lecture--p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology and cancer risk assessment. AN - 77868236; 8597035 AB - Carcinogenesis is a multistage process involving activation of protooncogenes, e.g., ras, and inactivation of tumor suppressor genes, e.g., p53 and p16INK4.p53 is a prototype tumor suppressor gene that is well suited for analysis of mutational spectrum in human cancers; it is the most common genetic lesion in human cancers, it is a reasonable size for a molecular target, and it may indicate selection of mutations with pathobiological significance. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain and lymphoid malignancies. Mutational hotspots at CpG dinucleotides in codons 175, 245, 248, 273 and 282 may reflect endogenous mutagenic mechanisms, e.g., deamination of 5-methylcytosine to thymidine. Oxy-radicals including nitric oxide may enhance the rate of deamination. G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung, breast, esophagus and liver, and are more likely to be due to bulky carcinogen-DNA adducts. G to T transversion is more common in lung cancers from smokers when compared to never smokers. The high frequency of p53 mutations in the nontranscribed DNA strand is a reflection of strand specific repair, p53 mutation and/or accumulation of p53 protein can be preinvasive events in bronchial or esophageal carcinogenesis, p53 mutations also generally indicate a poor prognosis. In geographic areas where hepatitis B virus (HBV) and aflatoxin B1 are cancer risk factors, most mutations are at the third nucleotide pair of codon 249. In geographic areas where hepatitis B and C virus--but not aflatoxin B1--are risk factors, the p53 mutations are distributed in numerous codons. HBV X protein complexes with the p53 protein and inhibits its sequence specific DNA binding, transactivating and apoptotic capacity. The mutation load of 249ser mutant cells in nontumorous liver is positively correlated with dietary aflatoxin B1 exposure. The induction of skin carcinoma by ultraviolet light is indicated by the occurrence of p53 mutations at dipyrimidine sites including CC to TT double base changes. In summary, these differences in mutational frequency and spectrum among human cancer types suggest the etiological contributions in both exogenous and endogenous factors to human carcinogenesis and have implications for human cancer risk assessment. JF - Toxicology letters AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1 EP - 7 VL - 82-83 SN - 0378-4274, 0378-4274 KW - Index Medicus KW - Animals KW - Humans KW - Mutation KW - Risk Assessment KW - Genes, p53 KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77868236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=1995+Deichmann+Lecture--p53+tumor+suppressor+gene%3A+at+the+crossroads+of+molecular+carcinogenesis%2C+molecular+epidemiology+and+cancer+risk+assessment.&rft.au=Harris%2C+C+C&rft.aulast=Harris&rft.aufirst=C&rft.date=1995-12-01&rft.volume=82-83&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-15 N1 - Date created - 1996-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic instability in patients with Hodgkin's disease undergoing chemotherapy. AN - 77866701; 8675643 AB - We have studied the effect of chemotherapy on the level of a particular kind of genetic instability in patients with Hodgkin's disease. The particular type of genetic instability assayed is exemplified by trans-rearrangements between two (rather than within one) T cell antigen receptor. 16 patients were studied during their course of treatment. Presentation samples were available for 13 of these patients; 9 of them showed an increase in the level of trans-rearrangements during their exposure to chemotherapeutic agents (P < 0.043). All patients for whom posttherapy samples were available (10 out of 16) showed a return to baseline levels of trans-rearrangements 1-5 mo after completion of therapy (P < 0.03). Thus, this assay appears to be a marker for the "destabilizing" effects of certain chemotherapeutic agents. JF - The Journal of clinical investigation AU - Abdallah, J M AU - Lombardi, D P AU - Kirsch, I R AD - National Cancer Institute--Navy Medical Oncology Branch, Bethesda, Maryland 20889-5105, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 2744 EP - 2747 VL - 96 IS - 6 SN - 0021-9738, 0021-9738 KW - Bleomycin KW - 11056-06-7 KW - Procarbazine KW - 35S93Y190K KW - Mechlorethamine KW - 50D9XSG0VR KW - Vincristine KW - 5J49Q6B70F KW - Vinblastine KW - 5V9KLZ54CY KW - Etoposide KW - 6PLQ3CP4P3 KW - Dacarbazine KW - 7GR28W0FJI KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Mechlorethamine -- administration & dosage KW - Neoplasm Staging KW - Bleomycin -- administration & dosage KW - Humans KW - Vincristine -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Recurrence KW - Procarbazine -- administration & dosage KW - Etoposide -- administration & dosage KW - Adult KW - Vinblastine -- administration & dosage KW - Dacarbazine -- administration & dosage KW - Middle Aged KW - Time Factors KW - Prednisone -- administration & dosage KW - Female KW - Male KW - Hodgkin Disease -- pathology KW - Gene Rearrangement, T-Lymphocyte KW - Hodgkin Disease -- genetics KW - Hodgkin Disease -- drug therapy KW - Hodgkin Disease -- immunology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77866701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Genetic+instability+in+patients+with+Hodgkin%27s+disease+undergoing+chemotherapy.&rft.au=Abdallah%2C+J+M%3BLombardi%2C+D+P%3BKirsch%2C+I+R&rft.aulast=Abdallah&rft.aufirst=J&rft.date=1995-12-01&rft.volume=96&rft.issue=6&rft.spage=2744&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-13 N1 - Date created - 1996-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cold Spring Harb Symp Quant Biol. 1994;59:287-95 [7587080] Med Hypotheses. 1994 Jan;42(1):45-52 [8196560] Clin Chem. 1985 Jan;31(1):164-5 [3965205] N Engl J Med. 1988 Jan 14;318(2):76-81 [3336397] Mutat Res. 1988 Mar;204(3):509-20 [3347218] Mutat Res. 1989 Jul;221(1):39-51 [2664494] J Exp Med. 1990 Aug 1;172(2):409-18 [1695665] Environ Mol Mutagen. 1991;18(1):6-13 [1713845] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5301-5 [1608939] Cancer Res. 1992 Oct 1;52(19 Suppl):5545s-5546s [1394170] J Clin Oncol. 1994 Feb;12(2):312-25 [8113838] Lancet. 1994 Apr 2;343(8901):828-9 [7908079] Cancer Res. 1994 Jun 1;54(11):2919-22 [8187078] Ann Oncol. 1994;5 Suppl 1:19-24 [8172811] Hereditas. 1983;98(1):1-9 [6303985] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitors of glycolytic metabolism affect neurulation-staged mouse conceptuses in vitro. AN - 77858597; 8711618 AB - In order to evaluate the apparent discordance between altered glucose metabolism and embryonic energy production, the effects of inhibitors of glucose utilization on morphological development and biochemical changes in mouse embryos in culture were evaluated. Day 9 ICR mouse conceptuses having 3-6 pairs of somites were prepared for culture as previously described. 2-Deoxyglucose (2DG) produced a concentration-dependent effect on development. A 25 microM 2DG concentration did not induce neural tube closure defects (NTDs) but 100 microM, 100% of embryos exhibited this defect. A 17% reduction in the rate of lactate production by the conceptus was produced by a 24-hr exposure period to 100 microM 2DG. Iodoacetate, which inhibits glyceraldehyde-3-phosphate dehydrogenase in adult tissues, produced high rates of NTDs at concentrations > or = 2.5 microM. Following a 24 hour exposure to iodoacetate, lactate production was inhibited at 10 and 25 microM. The effects of 2DG on embryonic ATP content were assessed to test the hypothesis that effects on glucose utilization would effect embryonic ATP content. Despite using 2DG concentrations that alter development and inhibit glycolysis, there were no effects on whole embryo or visceral yolk sac (VYS) ATP content. However, when the embryo was divided into regions, there was a specific reduction in ATP content in the head following a 24-hr exposure period. No effect of 2DG on head ATP content was produced after 12 hr of exposure. To determine if there were region specific differences in 2DG uptake and distribution that could account for the differential effects of 2DG on ATP content, 14C-2DG accumulation in different regions of the embryo and VYS was determined over the 24-hr culture period. The uptake of 2DG was dependent on the medium 2DG concentration and suggested a higher accumulation in regions with decreased ATP. However, when the uptake was monitored for a 1-hr period after a 24-hr exposure, there was no region specific differences in 2DG uptake. These studies further document the adverse developmental effects of inhibitors of glucose utilization during the early stage of neurulation. The biochemical mechanism for induction of these defects is unclear, but an effect on ATP content does not appear to be solely responsible for the dysmorphogenesis. JF - Teratology AU - Hunter, E S AU - Tugman, J A AD - Systems Toxicity Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 317 EP - 323 VL - 52 IS - 6 SN - 0040-3709, 0040-3709 KW - Antimetabolites KW - 0 KW - Iodoacetates KW - Lactates KW - Lactic Acid KW - 33X04XA5AT KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Deoxyglucose KW - 9G2MP84A8W KW - Iodoacetic Acid KW - WF5188V710 KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Lactates -- biosynthesis KW - Adenosine Triphosphate -- metabolism KW - Mice KW - Tissue Distribution KW - Organ Culture Techniques KW - Male KW - Female KW - Pregnancy KW - Iodoacetates -- toxicity KW - Antimetabolites -- toxicity KW - Glycolysis -- drug effects KW - Neural Tube Defects -- chemically induced KW - Nervous System -- metabolism KW - Nervous System -- embryology KW - Deoxyglucose -- toxicity KW - Embryo, Mammalian -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77858597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Teratology&rft.atitle=Inhibitors+of+glycolytic+metabolism+affect+neurulation-staged+mouse+conceptuses+in+vitro.&rft.au=Hunter%2C+E+S%3BTugman%2C+J+A&rft.aulast=Hunter&rft.aufirst=E&rft.date=1995-12-01&rft.volume=52&rft.issue=6&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Teratology&rft.issn=00403709&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-10 N1 - Date created - 1996-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Augmentation of prefrontal cortical monoaminergic activity inhibits dopamine release in the caudate nucleus: an in vivo neurochemical assessment in the rhesus monkey. AN - 77854965; 8596654 AB - Prefrontal cortical modulation of caudate nucleus dopamine release was investigated in the rhesus monkey using the in vivo microdialysis technique. Reliable and stable basal caudate nucleus dopamine levels were quickly attained within hours following insertion of the dialysis probes. High-potassium (60 mM) or tetrodotoxin (10 microM) infusions significantly altered caudate nucleus dopamine levels in the dialysate indicating that measured dopamine levels reflected impulse-dependent release from the presynaptic pool. Pharmacological augmentation of monoaminergic transmission in the sulcus principalis region of the prefrontal cortex resulted in significant alterations in caudate nucleus dopamine levels. Increase of monoaminergic activity by infusion of either D-amphetamine (100 microM) or cocaine hydrochloride (100 microM) resulted in a gradual and prolonged decrease in caudate nucleus dopamine levels. Similar decreases were noticed in caudate nucleus dopamine metabolite levels. The present results indicate that in non-human primates modulation of dorsolateral prefrontal cortical monoaminergic transmission results in alterations in dopamine levels in subcortical structures. This observation may have clinical implications for therapeutic management of certain neuropsychiatric disorders, particularly schizophrenia. JF - Neuroscience AU - Kolachana, B S AU - Saunders, R C AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH/NIH, NIMH Neuroscience Center at St Elizabeths, Washington, DC 20032, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 859 EP - 868 VL - 69 IS - 3 SN - 0306-4522, 0306-4522 KW - Biogenic Monoamines KW - 0 KW - Tetrodotoxin KW - 4368-28-9 KW - Potassium Chloride KW - 660YQ98I10 KW - Amphetamine KW - CK833KGX7E KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Microdialysis KW - Animals KW - Potassium Chloride -- pharmacology KW - Macaca mulatta KW - Tetrodotoxin -- pharmacology KW - Injections KW - Cocaine -- pharmacology KW - Amphetamine -- pharmacology KW - Caudate Nucleus -- metabolism KW - Prefrontal Cortex -- metabolism KW - Dopamine -- metabolism KW - Biogenic Monoamines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77854965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Augmentation+of+prefrontal+cortical+monoaminergic+activity+inhibits+dopamine+release+in+the+caudate+nucleus%3A+an+in+vivo+neurochemical+assessment+in+the+rhesus+monkey.&rft.au=Kolachana%2C+B+S%3BSaunders%2C+R+C%3BWeinberger%2C+D+R&rft.aulast=Kolachana&rft.aufirst=B&rft.date=1995-12-01&rft.volume=69&rft.issue=3&rft.spage=859&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-18 N1 - Date created - 1996-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms regulating Raf-1 activity in signal transduction pathways. AN - 77839148; 8607983 AB - Raf-1 is a key protein involved in the transmission of developmental and proliferative signals generated by receptor and nonreceptor tyrosine kinases. Biochemical and genetic studies have demonstrated that Raf-1 functions downstream of activated tyrosine kinases and Ras and upstream of mitogen-activated protein kinase (MAPK) and MAPK kinase (MKK or MEK) in many signaling pathways. A major objective of our laboratory has been to determine how Raf-1 becomes activated in response to signaling events. Using mammalian, baculovirus, and Xenopus systems, we have examined the roles that phosphorylation and protein-protein interactions play in regulating the biological and biochemical activity of Raf-1. Our studies have provided evidence that the activity of Raf-1 can be modulated by both Ras-dependent and Ras-independent pathways. Recently, we reported that Arg89 of Raf-1 is a residue required for the association of Raf-1 and Ras. Mutation of this residue disrupted interaction with Ras and prevented Ras-mediated, but not protein kinase C-or tyrosine kinase-mediated, enzymatic activation of Raf-1 in the baculovirus expression system. Further analysis of this mutant demonstrated that kinase-defective Raf-1 proteins interfere with the propagation of proliferative and developmental signals by binding to Ras and blocking Ras function. Our findings have also shown that phosphorylation events play a role in regulating Raf-1. We have identified sites of in vivo phosphorylation that positively and negatively alter the biological and enzymatic activity of Raf-1. In addition, we have found that some of these phosphorylation sites are involved in mediating the interaction of Raf-1 with potential activators (Fyn and Src) and with other cellular proteins (14-3-3). Results from our work suggest that Raf-1 is regulated at multiple levels by several distinct mechanisms. JF - Molecular reproduction and development AU - Morrison, D K AD - Molecular Mechanisms of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 507 EP - 514 VL - 42 IS - 4 SN - 1040-452X, 1040-452X KW - Proto-Oncogene Proteins KW - 0 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Index Medicus KW - Animals KW - Phosphorylation KW - Humans KW - Gene Expression Regulation KW - Protein-Serine-Threonine Kinases -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77839148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+reproduction+and+development&rft.atitle=Mechanisms+regulating+Raf-1+activity+in+signal+transduction+pathways.&rft.au=Morrison%2C+D+K&rft.aulast=Morrison&rft.aufirst=D&rft.date=1995-12-01&rft.volume=42&rft.issue=4&rft.spage=507&rft.isbn=&rft.btitle=&rft.title=Molecular+reproduction+and+development&rft.issn=1040452X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-29 N1 - Date created - 1996-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cholesterol sulfate activates multiple protein kinase C isoenzymes and induces granular cell differentiation in cultured murine keratinocytes. AN - 77837495; 9019167 AB - The accumulation of cholesterol sulfate (CS) in differentiating keratinocytes coincides with the expression of protein kinase C (PKC)-regulated granular layer differentiation markers both in vitro and in vivo. In this study, we examined the ability of Cs to induce differentiation marker expression in primary mouse keratinocytes and to modulate keratinocyte PKC isozymes (alpha, delta, epsilon, eta, and sigma). Treatment of basal keratinocytes with CS induced the expression of the granular layer proteins filaggrin and loricrin and decreased the level of the spinous keratin K1. CS stimulated cornification and blocked the induction of K10 in keratinocytes induced to differentiate by calcium. The induction of filaggrin and loricrin by CS corresponds to a granular layer differentiation program, where PKC activation occurs and was blocked by the PKC inhibitor GF 109203X. Treatment of keratinocytes with CS caused PKC epsilon, eta, and sigma to be selectively lost from the cytosol fraction and increased in the cytoskeletal fraction. The loss of soluble PKC epsilon, eta, and sigma was rapid (1 h) and sustained (44 h). PKC alpha and delta were not redistributed. In vitro, CS induced kinase activity of PKC epsilon, eta, and sigma to a greater extent than did the phorbol ester 12-O-tetradecanoylphorbol-13-acetate for these isoforms. PKC alpha and delta were activated to a lesser extent by CS than by 12-O-tetradecanoylphorbol-13-acetate. The translocation of PKC epsilon, eta, and sigma in intact cells treated with CS, together with the in vitro activation of recombinant PKC epsilon, eta, and sigma preferentially by CS, suggests a role for these isoforms in the induction of keratinocyte differentiation by CS. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Denning, M F AU - Kazanietz, M G AU - Blumberg, P M AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1619 EP - 1626 VL - 6 IS - 12 SN - 1044-9523, 1044-9523 KW - Biomarkers KW - 0 KW - Cholesterol Esters KW - Intermediate Filament Proteins KW - Isoenzymes KW - Membrane Proteins KW - filaggrin KW - loricrin KW - Protein Kinase C KW - EC 2.7.11.13 KW - cholesteryl sulfate KW - KU576NT9O9 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Immunoblotting KW - Enzyme Activation KW - Cell Differentiation KW - Intermediate Filament Proteins -- analysis KW - Mice KW - Calcium -- pharmacology KW - Membrane Proteins -- analysis KW - Mice, Inbred BALB C KW - Animals, Newborn KW - Cells, Cultured KW - Intermediate Filament Proteins -- biosynthesis KW - Kinetics KW - Membrane Proteins -- biosynthesis KW - Subcellular Fractions -- enzymology KW - Protein Kinase C -- metabolism KW - Isoenzymes -- isolation & purification KW - Keratinocytes -- enzymology KW - Keratinocytes -- drug effects KW - Protein Kinase C -- isolation & purification KW - Keratinocytes -- cytology KW - Cholesterol Esters -- pharmacology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77837495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Cholesterol+sulfate+activates+multiple+protein+kinase+C+isoenzymes+and+induces+granular+cell+differentiation+in+cultured+murine+keratinocytes.&rft.au=Denning%2C+M+F%3BKazanietz%2C+M+G%3BBlumberg%2C+P+M%3BYuspa%2C+S+H&rft.aulast=Denning&rft.aufirst=M&rft.date=1995-12-01&rft.volume=6&rft.issue=12&rft.spage=1619&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-11 N1 - Date created - 1997-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of intravenous cocaine on plasma cortisol and prolactin in human cocaine abusers. AN - 77821621; 8580229 AB - The aim of the present work was to examine the cortisol and prolactin responses to acute cocaine administration in human cocaine users. Each subject served as his own control during intravenous saline placebo and cocaine (40 mg) infusion sessions. Cocaine significantly elevated plasma cortisol but did not affect prolactin. The rise in cortisol coincided with an increase in heart rate and blood pressure after cocaine. In agreement with studies in animals, our data suggest that cocaine activates the hypothalamic-pituitary-adrenal axis in humans. However, based on the well-known importance of dopamine as a prolactin-inhibiting factor, the failure of cocaine to suppress prolactin in the present study raises questions concerning the role of dopamine in the mechanism of acute cocaine action in humans. JF - Biological psychiatry AU - Baumann, M H AU - Gendron, T M AU - Becketts, K M AU - Henningfield, J E AU - Gorelick, D A AU - Rothman, R B AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1995/12/01/ PY - 1995 DA - 1995 Dec 01 SP - 751 EP - 755 VL - 38 IS - 11 SN - 0006-3223, 0006-3223 KW - Prolactin KW - 9002-62-4 KW - Cocaine KW - I5Y540LHVR KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Heart Rate -- drug effects KW - Humans KW - Adult KW - Blood Pressure -- drug effects KW - Prolactin -- blood KW - Substance Abuse, Intravenous -- blood KW - Hydrocortisone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77821621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Effects+of+intravenous+cocaine+on+plasma+cortisol+and+prolactin+in+human+cocaine+abusers.&rft.au=Baumann%2C+M+H%3BGendron%2C+T+M%3BBecketts%2C+K+M%3BHenningfield%2C+J+E%3BGorelick%2C+D+A%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=1995-12-01&rft.volume=38&rft.issue=11&rft.spage=751&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-21 N1 - Date created - 1996-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Receptor-mediated events and the evaluation of the Environmental Protection Agency (EPA) of dioxin risks. AN - 77791425; 8538618 JF - Mutation research AU - Sewall, C H AU - Lucier, G W AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 111 EP - 122 VL - 333 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - Receptors, Aryl Hydrocarbon KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - United States KW - Receptor, Epidermal Growth Factor -- drug effects KW - Rats KW - Animals KW - United States Environmental Protection Agency KW - Liver -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Cytochrome P-450 Enzyme System -- drug effects KW - Female KW - Risk Assessment KW - Receptors, Aryl Hydrocarbon -- physiology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77791425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Receptor-mediated+events+and+the+evaluation+of+the+Environmental+Protection+Agency+%28EPA%29+of+dioxin+risks.&rft.au=Sewall%2C+C+H%3BLucier%2C+G+W&rft.aulast=Sewall&rft.aufirst=C&rft.date=1995-12-01&rft.volume=333&rft.issue=1-2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-08 N1 - Date created - 1996-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repair in a UV resistant Chinese hamster ovary cell line. AN - 77784830; 8603488 AB - We have established an ultraviolet (UV) resistant Chinese hamster ovary (CHO) cell line B11UVres by repetitive UV exposure of the CHO cell line B11. We have characterized the resistant cell line with respect to growth, sensitivity to various DNA damaging agents, and the repair of UV induced DNA lesions. When examining sensitivity to UV in clonogenic survival studies, we find that the ID50 is increased 2.3-fold in the resistant cell line B11UVres compared to the parental cell line B11. Although the doubling time of the resistant cell line is greater than that of the parental cell line, there is no difference in the rate of replication after UV irradiation. When measuring repair of UV induced DNA lesions in the overall genome we find no significant difference between the two cell lines. However, at early times after UV, there is a significant increase in the rate of repair of cyclobutane pyramidine dimers (CPDs) in the transcribed strand of the dihydrofolate reductase (DHFR) gene in the B11UVres cells compared to the B11 cells. There is a small increase of steady state transcription of the DHFR gene in the UV resistant cells, but hardly enough to account for the repair increase. The UV resistant cell line B11UVres is not cross-resistant to the cross-linking agents mitomycin C or cisplatin, but shows increased sensitivity to these compounds. JF - Carcinogenesis AU - Petersen, L N AU - Stevnsner, T AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute of Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 3075 EP - 3081 VL - 16 IS - 12 SN - 0143-3334, 0143-3334 KW - Mitomycins KW - 0 KW - Pyrimidine Dimers KW - DNA KW - 9007-49-2 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Cricetulus KW - Transcription, Genetic KW - Chromosomes KW - DNA Replication -- radiation effects KW - Cell Survival -- drug effects KW - Cisplatin -- pharmacology KW - CHO Cells KW - Cell Survival -- radiation effects KW - Mitomycins -- pharmacology KW - DNA -- radiation effects KW - Tetrahydrofolate Dehydrogenase -- genetics KW - Cricetinae KW - Ultraviolet Rays KW - DNA Repair KW - Radiation Tolerance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77784830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=DNA+repair+in+a+UV+resistant+Chinese+hamster+ovary+cell+line.&rft.au=Petersen%2C+L+N%3BStevnsner%2C+T%3BBohr%2C+V+A&rft.aulast=Petersen&rft.aufirst=L&rft.date=1995-12-01&rft.volume=16&rft.issue=12&rft.spage=3075&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-16 N1 - Date created - 1996-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms for species differences in receptor-mediated carcinogenesis. AN - 77783879; 8538627 AB - Species differences resulting from a number of mechanisms are common in receptor-mediated chemical carcinogenesis. In this review, examples of possible mechanisms underlying these differences are discussed, including ligand metabolism, receptor polymorphisms, receptor isoforms, receptor levels, and crosstalk between signal transduction pathways. In addition, a number of other mechanisms also are likely to be important. The developmental state of the animal will determine the expression of receptors in different tissues. The regulatory pathways for cell proliferation and cell death and cell cycle check point controls can vary among species and tissues. Adaptation or potentiation of responses during chronic exposures to chemicals can greatly influence species differences. The mechanisms of adaptive processes are poorly understood but probably highly important for chronic toxicities such as cancer. Finally, different species may have different stem cell populations that are the targets for neoplastic transformation, and this will influence receptor-mediated carcinogenic responses. The implications of species differences in receptor-mediated responses for risk assessment are discussed. JF - Mutation research AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 189 EP - 202 VL - 333 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Estrogen KW - Transcription Factors KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tetradecanoylphorbol Acetate -- toxicity KW - Animals KW - Humans KW - Polychlorinated Dibenzodioxins -- toxicity KW - Protein Kinase C -- physiology KW - Species Specificity KW - Signal Transduction KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Receptors, Aryl Hydrocarbon -- physiology KW - Neoplasms -- chemically induced KW - Receptors, Estrogen -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77783879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Mechanisms+for+species+differences+in+receptor-mediated+carcinogenesis.&rft.au=Barrett%2C+J+C&rft.aulast=Barrett&rft.aufirst=J&rft.date=1995-12-01&rft.volume=333&rft.issue=1-2&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-08 N1 - Date created - 1996-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutathione S-transferase and S-crystallins of cephalopods: evolution from active enzyme to lens-refractive proteins. AN - 77783757; 8587103 AB - Our previous studies have shown that the S-crystallins of cephalopod (Ommastrephes sloani pacificus) eye lenses comprise a family of at least ten members which are evolutionarily related to glutathione S-transferase (GST, EC 2.5.1.18). Here we show by cDNA cloning that there are at least 24 different S-crystallins that are 46-99% identical to each other by amino acid sequence in the squid Loligo opalescens. In each species, all but one S-crystallin (SL11 in O. pacificus and Lops4 in L. opalescens) examined has an inserted central peptide of variable length and sequence. cDNA expression studies conducted in Escherichia coli showed that squid GST (which is expressed little in the lens) has very high enzymatic activity using 1-chloro-2, 4-dinitrobenzene (CDNB) as a substrate; by contrast, SL20-1 of O. pacificus and Lops12 of L. opalescens (which are encoded by abundant lens mRNAs) have no GST activity. Interestingly, SL11 and Lops4 have some enzymatic activity with the CDNB substrate. Site-specific mutations at Y7 or W38, both residues essential for activity of vertebrate GSTs, or insertion of the central peptide present in the inactive SL20-1, reduced the specific activity of squid GST by 30- to 100-fold. These data indicate that the S-crystallins consist of a family of enzymatically inactive proteins (when using CDNB as a substrate) which is considerably larger than previously believed and that GST activity was lost by gradual drift in sequence as well as by insertion of an extra peptide by exon shuffling. The results are also consistent with the idea that SL11 and Lops4 are orthologous crystallins representing the first descendants of the ancestral GST gene in the pathway which gave rise to the extensive S-crystallin family of lens proteins. JF - Journal of molecular evolution AU - Tomarev, S I AU - Chung, S AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-2730, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1048 EP - 1056 VL - 41 IS - 6 SN - 0022-2844, 0022-2844 KW - Crystallins KW - 0 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Enzyme Activation KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Evolution, Molecular KW - Cloning, Molecular KW - Glutathione Transferase -- genetics KW - Crystallins -- genetics KW - Decapodiformes -- metabolism KW - Decapodiformes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77783757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+evolution&rft.atitle=Glutathione+S-transferase+and+S-crystallins+of+cephalopods%3A+evolution+from+active+enzyme+to+lens-refractive+proteins.&rft.au=Tomarev%2C+S+I%3BChung%2C+S%3BPiatigorsky%2C+J&rft.aulast=Tomarev&rft.aufirst=S&rft.date=1995-12-01&rft.volume=41&rft.issue=6&rft.spage=1048&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-28 N1 - Date created - 1996-03-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U19388; GENBANK; U19389; U19387; U19393; U19294; U19295; U19255; U19296; U19297; U19298; U19299; U19291; U19290; U19293; U19292; U19390; U19392; U19391; U19300 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repair fine structure and its relations to genomic instability. AN - 77783104; 8603460 JF - Carcinogenesis AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 2885 EP - 2892 VL - 16 IS - 12 SN - 0143-3334, 0143-3334 KW - DNA, Mitochondrial KW - 0 KW - Index Medicus KW - Animals KW - Telomere KW - Humans KW - Xeroderma Pigmentosum -- genetics KW - Transcription, Genetic KW - Mutation KW - Aging -- genetics KW - DNA, Mitochondrial -- genetics KW - DNA Repair -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77783104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=DNA+repair+fine+structure+and+its+relations+to+genomic+instability.&rft.au=Bohr%2C+V+A&rft.aulast=Bohr&rft.aufirst=V&rft.date=1995-12-01&rft.volume=16&rft.issue=12&rft.spage=2885&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-16 N1 - Date created - 1996-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adduct formation and tumorigenesis in mice during the chronic administration of 4-aminobiphenyl at multiple dose levels. AN - 77779257; 8603464 AB - Recent studies have demonstrated the presence of DNA adducts from 4-aminobiphenyl (4-ABP) in the bladder cells of humans; however, the correlation between the concentration of these adducts and the tumorigenic response is not clear. To help elucidate this relationship, we have investigated DNA adduct formation in experimental animals continuously administered 4-ABP. Male and female BALB/c mice were treated for 28 days with 4-ABP. hydrochloride in their drinking water. DNA adducts in target tissues (liver of females and bladder of males) were identified and quantified by 32P-postlabeling analyses and radioimmunoassays. These results were compared to previously reported tumor incidences obtained from the lifetime administration of 4-ABP hydrochloride. The major adduct observed in both tissues was N-(deoxyguanosin-8-yl)-4-ABP. In the bladders of both sexes and the livers of female mice, adduct levels increased with dose at low doses, but saturation was observed at high doses. In the livers of males, the adduct levels were linearly correlated with dose throughout the entire dose range. A comparison between DNA adducts and tumorigenesis indicated a linear correlation between adduct levels and the incidence of liver tumors in female mice. In the bladders of male mice, however, the relationship was markedly nonlinear. These data suggest that adduct formation alone is insufficient for tumorigenesis in the bladder and that other factors such as cell proliferation are necessary for tumor production. JF - Carcinogenesis AU - Poirier, M C AU - Fullerton, N F AU - Smith, B A AU - Beland, F A AD - National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 2917 EP - 2921 VL - 16 IS - 12 SN - 0143-3334, 0143-3334 KW - Aminobiphenyl Compounds KW - 0 KW - DNA Adducts KW - Phosphorus Radioisotopes KW - 4-biphenylamine KW - 16054949HJ KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Mice, Inbred BALB C KW - Radioimmunoassay KW - Male KW - Female KW - Urinary Bladder Neoplasms -- chemically induced KW - DNA -- drug effects KW - Aminobiphenyl Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77779257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=DNA+adduct+formation+and+tumorigenesis+in+mice+during+the+chronic+administration+of+4-aminobiphenyl+at+multiple+dose+levels.&rft.au=Poirier%2C+M+C%3BFullerton%2C+N+F%3BSmith%2C+B+A%3BBeland%2C+F+A&rft.aulast=Poirier&rft.aufirst=M&rft.date=1995-12-01&rft.volume=16&rft.issue=12&rft.spage=2917&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-16 N1 - Date created - 1996-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of transgenic mice with an increased content of chromosomal protein HMG-14 in their chromatin. AN - 77773608; 8534374 AB - Chromosomal protein HMG-14 is a ubiquitous nuclear protein that may modulate the chromatin structure of transcriptionally active genes. To gain insights into the cellular function of the HMG-14 protein, we generated two transgenic mouse lines carrying either two or six copies of the human HMG-14 gene. The transgenic mice express human HMG-14 mRNA and protein in all tissues examined at a level reflecting the increased gene dosage, suggesting that the HMG14 transgene contains all the control regions necessary for regulated gene expression. Expression of the human HMG-14 protein does not alter the expression of the endogenous mouse HMG-14 protein or its close homolog, protein HMG-17. The intracellular distribution of the exogenous human protein is indistinguishable from that of the endogenous mouse protein, resulting in a three-fold increase in the level of the chromatin-bound HMG-14. The transgenic mice had a higher incidence of epithelial cysts in their thymus than did control animals. We conclude that the cellular levels of HMG-14/-17 are determined by gene copy number, that the DNA fragment containing the gene and about 1,000 bp flanking its 5' and 3' ends contain most of the elements necessary for gene expression, that the upper limits of HMG-14 in chromatin are not stringently regulated, and that a three-fold increase in chromatin-bound protein cause only mild phenotypic changes in the transgenic mice. JF - DNA and cell biology AU - Bustin, M AU - Alfonso, P J AU - Pash, J M AU - Ward, J M AU - Gearhart, J D AU - Reeves, R H AD - Laboratory of Molecular Carcinogenesis, NCI, NIH, Bethesda, MD 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 997 EP - 1005 VL - 14 IS - 12 SN - 1044-5498, 1044-5498 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - RNA, Messenger KW - Index Medicus KW - Animals KW - Humans KW - Heterozygote KW - Transgenes KW - Mice, Inbred C57BL KW - Gene Expression KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Transgenic KW - Male KW - Female KW - Chromatin -- metabolism KW - High Mobility Group Proteins -- genetics KW - High Mobility Group Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77773608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Characterization+of+transgenic+mice+with+an+increased+content+of+chromosomal+protein+HMG-14+in+their+chromatin.&rft.au=Bustin%2C+M%3BAlfonso%2C+P+J%3BPash%2C+J+M%3BWard%2C+J+M%3BGearhart%2C+J+D%3BReeves%2C+R+H&rft.aulast=Bustin&rft.aufirst=M&rft.date=1995-12-01&rft.volume=14&rft.issue=12&rft.spage=997&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-08 N1 - Date created - 1996-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of EGFR, TGF-alpha, neu and c-myc in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary tumors using RT-PCR. AN - 77762403; 8603490 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a mutagen found in cooked meat, has been shown to induce mammary gland tumors in rats. Our laboratory recently observed that a high fat diet enhances the incidence and severity of PhIP-induced mammary gland cancer in rats. In the current study, reverse transcription followed by polymerase chain reaction amplification was used to determine whether EGFR, TGF-alpha, neu and c-myc are differentially expressed in PhIP-induced mammary gland tumors classified histologically as benign or malignant and to evaluate whether dietary fat intake influences the expression of these genes. Of 23 total PhIP-induced mammary tumors examined, 43%, 57% and 74% had increased expression of EGFR, TGF-alpha and neu mRNA respectively. Increased expression of these genes appeared to be consistently present in tumors displaying papillomatosis. In contrast, to the other three genes, c-myc mRNA levels were infrequently elevated. The percentage of dietary fat did not appear to influence the expression of EGFR, TGF-alpha or neu in either tumors or mammary gland from control rats. However, the levels of c-myc mRNA were 1.8- and 2.9-fold higher in the control mammary gland and benign PhIP-induced tumors respectively in rats fed the high-fat diet than in rats fed the low-fat diet, suggesting a slight effect of dietary fat (P < 0.08) on c-myc expression. These results suggest that increased expression of EGFR, TGF-alpha and especially neu is associated with PhIP-induced mammary gland cancer in rats. JF - Carcinogenesis AU - Davis, C D AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 3087 EP - 3092 VL - 16 IS - 12 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA Primers KW - Dietary Fats KW - Imidazoles KW - RNA, Messenger KW - Transforming Growth Factor alpha KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Animals KW - Genes, erbB-1 KW - Genes, erbB-2 KW - Genes, myc KW - Dietary Fats -- administration & dosage KW - RNA, Messenger -- genetics KW - Rats KW - Polymerase Chain Reaction KW - Rats, Inbred F344 KW - Base Sequence KW - Transforming Growth Factor alpha -- genetics KW - Molecular Sequence Data KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Imidazoles -- toxicity KW - Carcinogens -- toxicity KW - Mammary Neoplasms, Experimental -- genetics KW - Proto-Oncogenes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77762403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Analysis+of+EGFR%2C+TGF-alpha%2C+neu+and+c-myc+in+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine-induced+mammary+tumors+using+RT-PCR.&rft.au=Davis%2C+C+D%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1995-12-01&rft.volume=16&rft.issue=12&rft.spage=3087&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-16 N1 - Date created - 1996-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diverse immunological and hematological effects of interleukin 7: implications for clinical application. AN - 77751719; 7499959 AB - Interleukin-7 (IL-7) was originally discovered to be a pre-B cell growth factor. Soon thereafter, a broader role for IL-7 in leukocyte development and function began to be identified. IL-7 now has been shown to be a critical cytokine for normal T and B lymphopoiesis and a mobilizer of pluripotent stem cells and myeloid progenitors. IL-7 has been demonstrated to enhance T cell function and induce cytokine expression in monocytes. Preclinical studies have already found that IL-7 could accelerate murine lymphocyte regeneration following chemotherapy and bone marrow transplantation, induce antitumor effects in mice, and expand anti-HIV-specific human T cells. Thus it is essential that further preclinical and clinical research be performed to evaluate IL-7 as a potential therapy for leukopenia, bone marrow/stem cell transplantation, cancer, and HIV/AIDS. JF - Journal of leukocyte biology AU - Komschlies, K L AU - Grzegorzewski, K J AU - Wiltrout, R H AD - Biological Carcinogenesis and Development Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 623 EP - 633 VL - 58 IS - 6 SN - 0741-5400, 0741-5400 KW - Antigens, CD KW - 0 KW - Interleukin-7 KW - Receptors, Interleukin KW - Receptors, Interleukin-7 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Acquired Immunodeficiency Syndrome -- therapy KW - Antigens, CD -- physiology KW - Humans KW - Cell Differentiation KW - T-Lymphocytes -- physiology KW - Receptors, Interleukin -- physiology KW - Mice KW - Neoplasms -- therapy KW - Hematopoiesis KW - Interleukin-7 -- therapeutic use KW - Interleukin-7 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77751719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Diverse+immunological+and+hematological+effects+of+interleukin+7%3A+implications+for+clinical+application.&rft.au=Komschlies%2C+K+L%3BGrzegorzewski%2C+K+J%3BWiltrout%2C+R+H&rft.aulast=Komschlies&rft.aufirst=K&rft.date=1995-12-01&rft.volume=58&rft.issue=6&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of nutrition intervention on intermediate endpoints in esophageal and gastric carcinogenesis. AN - 77748001; 7495241 AB - A nutrition intervention trial involving > 3000 participants was conducted in Linxian, China, where the esophageal and stomach cancer mortality rates are among the highest in the world and suspicion exists that chronic deficiencies of multiple nutrients are etiologically involved. The trial was randomized, double-blind, and placebo-controlled and tested the effect of multivitamin and multimineral supplements in reducing cancer incidence and mortality in adults with cytologically detected esophageal dysplasia. Endoscopic and cytologic examinations of samples of trial participants during the intervention allowed evaluation of intermediate endpoints in esophageal and gastric carcinogenesis, including asymptomatic histologic precancerous lesions and early invasive cancer, epithelial proliferation, and cytologic abnormalities. Results from these ancillary studies suggest that multivitamin and multimineral supplementation may decrease proliferation and enhance cytologic reversion to nondysplasia. JF - The American journal of clinical nutrition AU - Taylor, P R AU - Wang, G Q AU - Dawsey, S M AU - Guo, W AU - Mark, S D AU - Li, J Y AU - Blot, W J AU - Li, B AD - National Cancer Institute, Bethesda, MD 20896, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1420S EP - 1423S VL - 62 IS - 6 Suppl SN - 0002-9165, 0002-9165 KW - Minerals KW - 0 KW - Vitamins KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Precancerous Conditions -- prevention & control KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Esophageal Neoplasms -- prevention & control KW - Minerals -- administration & dosage KW - Vitamins -- administration & dosage KW - Stomach Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77748001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+clinical+nutrition&rft.atitle=Effect+of+nutrition+intervention+on+intermediate+endpoints+in+esophageal+and+gastric+carcinogenesis.&rft.au=Taylor%2C+P+R%3BWang%2C+G+Q%3BDawsey%2C+S+M%3BGuo%2C+W%3BMark%2C+S+D%3BLi%2C+J+Y%3BBlot%2C+W+J%3BLi%2C+B&rft.aulast=Taylor&rft.aufirst=P&rft.date=1995-12-01&rft.volume=62&rft.issue=6+Suppl&rft.spage=1420S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of optimal vitamin C requirements in humans. AN - 77742331; 7495230 AB - Although the recommended dietary allowance provides an estimate for vitamin C ingestion in humans, optimal vitamin C requirements are unknown. We define optimal vitamin C requirements operationally based on the following: dose-function relations, availability in the food supply, steady state concentrations in plasma and tissues achieved at each dose of vitamin C, urinary excretion, bioavailability, toxicity, and epidemiologic observations. Optimal vitamin C requirements can be estimated when information is available for at least some of these criteria. JF - The American journal of clinical nutrition AU - Levine, M AU - Dhariwal, K R AU - Welch, R W AU - Wang, Y AU - Park, J B AD - Laboratory of Cell Biology and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0850, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1347S EP - 1356S VL - 62 IS - 6 Suppl SN - 0002-9165, 0002-9165 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Abridged Index Medicus KW - Index Medicus KW - Nutritional Requirements KW - Humans KW - Diet KW - Biological Availability KW - Ascorbic Acid -- administration & dosage KW - Ascorbic Acid -- toxicity KW - Ascorbic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77742331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+clinical+nutrition&rft.atitle=Determination+of+optimal+vitamin+C+requirements+in+humans.&rft.au=Levine%2C+M%3BDhariwal%2C+K+R%3BWelch%2C+R+W%3BWang%2C+Y%3BPark%2C+J+B&rft.aulast=Levine&rft.aufirst=M&rft.date=1995-12-01&rft.volume=62&rft.issue=6+Suppl&rft.spage=1347S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discriminative stimulus effects of R-(+)-3-amino-1-hydroxypyrrolid-2-one, [(+)-HA-966], a partial agonist of the strychnine-insensitive modulatory site of the N-methyl-D-aspartate receptor. AN - 77738689; 8531091 AB - The strychnine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex is a target for development of a host of therapeutic agents including anxiolytics, antidepressants, antiepileptics, anti-ischemics and cognitive enhancers. In the present experiments, the discriminative stimulus effects of (+)-HA-966 [R-(+)-3-amino-1-hydroxypyrrolid-2-one], a low-efficacy partial agonist of the glycine site, was explored. Male, Swiss-Webster mice were trained to discriminate (+)-HA-966 (170 mg/kg i.p.) from saline in a T-maze under which behavior was controlled by food. Other glycine partial agonists, 1-amino-1-cyclopropanecarboxilic acid and D-cycloserine, fully substituted for the discriminative stimulus effects of (+)-HA-966 despite known differences in other pharmacological effects of these compounds. The glycine site antagonist, 7-chlorkynurenic acid, did not substitute for (+)-HA-966. Likewise other functional NMDA antagonists acting at nonglycine sites of the NMDA receptor also did not substitute: neither the high (dizocilpine) or low affinity (ibogaine) ion-channel blocker, the competitive antagonist, NPC 17742 [2R,4R,5S-2-amino-4,5-(1, 2-cyclohexyl)-7-phosphonoheptanoic acid], nor the polyamine antagonist, ifenprodil, substituted for (+)-HA-966. Although the full agonist, glycine, did not substitute, this compound fully blocked the discriminative stimulus effects of (+)-HA-966. In a separate group of mice trained to discriminate 0.17 mg/kg of dizocilpine from saline, (+)-HA-966 produced a maximum of only 50% dizoclipine-appropriate responses. These data suggest that the discriminative stimulus effects of (+)-HA-966 are based upon its partial agonist actions at the strychnine-insensitive glycine site.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of pharmacology and experimental therapeutics AU - Witkin, J M AU - Brave, S AU - French, D AU - Geter-Douglass, B AD - Psychobiology Section, Addiction Research Center, National Institute on Drug Abuse, National Institutes of health, Baltimore, Maryland, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1267 EP - 1273 VL - 275 IS - 3 SN - 0022-3565, 0022-3565 KW - Amino Acids KW - 0 KW - Excitatory Amino Acid Agonists KW - Excitatory Amino Acid Antagonists KW - Piperidines KW - Pyrrolidinones KW - Receptors, N-Methyl-D-Aspartate KW - NPC 12626 KW - 117571-54-7 KW - Ibogaine KW - 3S814I130U KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 1-hydroxy-3-amino-2-pyrrolidone KW - F2JLV9220T KW - Strychnine KW - H9Y79VD43J KW - ifenprodil KW - R8OE3P6O5S KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Piperidines -- pharmacology KW - Animals KW - Glycine -- metabolism KW - Mice KW - Amino Acids -- pharmacology KW - Ibogaine -- pharmacology KW - Male KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- agonists KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Strychnine -- pharmacology KW - Excitatory Amino Acid Agonists -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- chemistry KW - Pyrrolidinones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77738689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Discriminative+stimulus+effects+of+R-%28%2B%29-3-amino-1-hydroxypyrrolid-2-one%2C+%5B%28%2B%29-HA-966%5D%2C+a+partial+agonist+of+the+strychnine-insensitive+modulatory+site+of+the+N-methyl-D-aspartate+receptor.&rft.au=Witkin%2C+J+M%3BBrave%2C+S%3BFrench%2C+D%3BGeter-Douglass%2C+B&rft.aulast=Witkin&rft.aufirst=J&rft.date=1995-12-01&rft.volume=275&rft.issue=3&rft.spage=1267&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. AN - 77736126; 8613731 AB - A pathology of brain serotonergic (5-HT) systems has been found in psychiatric disturbances, normal aging and in neurodegenerative disorders including Alzheimer's and Parkinson's disease. Despite the clinical importance of 5-HT, little is known about the endogenous factors that have neurotrophic influences upon 5-HT neurons. The present study examined whether chronic pain parenchymal administration of the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or NGF could prevent the severe degenerative loss of serotonergic axons normally caused by the selective 5-HT neurotoxin p-chloroamphetamine (PCA). The neurotrophins (5-12 micrograms/d) or the control substances (cytochrome c or PBS vehicle) were continuously infused into the rat frontoparietal cortex using an osmotic minipump. One week later, rats were subcutaneously administered PCA (10 mg/kg) or vehicle, and the 5-HT innervation was evaluated after two more weeks of neurotrophin infusion. As revealed with 5-HT immunocytochemistry, BDNF infusions into the neocortex of intact (non-PCA-lesioned) rats caused a substantial increase in 5-HT axon density in a 3 mm diameter region surrounding the cannula tip. In PCA-lesioned rats, intracortical infusions of BDNF completely prevented the severe neurotoxin-induced loss of 5-HT axons near the infusion cannula. In contrast, cortical infusions of vehicle or the control protein cytochrome c did not alter the density of serotonergic axons in intact animals, nor did control infusions prevent the loss of 5-HT axons in PCA-treated rats. NT-3 caused only a modest sparing of the 5-HT innervation in PCA-treated rats, and NGF failed to prevent the loss of 5-HT axon density. The immunocytochemical data were supported by neurochemical evaluations which showed that BDNF attenuated the PCA-induced loss of 5-HT and 5-HIAA contents and 3H-5-HT uptake near the infusion cannula. Thus, BDNF can promote the sprouting of mature, uninjured serotonergic axons and dramatically enhance the survival or sprouting of 5-HT axons normally damaged by the serotonergic neurotoxin PCA. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Mamounas, L A AU - Blue, M E AU - Siuciak, J A AU - Altar, C A AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 7929 EP - 7939 VL - 15 IS - 12 SN - 0270-6474, 0270-6474 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Neurotrophin 3 KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - p-Chloroamphetamine KW - 64-12-0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - p-Chloroamphetamine -- pharmacology KW - Cell Survival -- drug effects KW - Nerve Growth Factors -- pharmacology KW - Hydroxyindoleacetic Acid -- metabolism KW - Immunohistochemistry KW - Male KW - Brain -- cytology KW - Brain -- drug effects KW - Nerve Regeneration -- drug effects KW - Serotonin -- pharmacokinetics KW - Serotonin -- metabolism KW - Brain -- physiology KW - Nerve Tissue Proteins -- pharmacology KW - Axons -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77736126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Brain-derived+neurotrophic+factor+promotes+the+survival+and+sprouting+of+serotonergic+axons+in+rat+brain.&rft.au=Mamounas%2C+L+A%3BBlue%2C+M+E%3BSiuciak%2C+J+A%3BAltar%2C+C+A&rft.aulast=Mamounas&rft.aufirst=L&rft.date=1995-12-01&rft.volume=15&rft.issue=12&rft.spage=7929&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-06 N1 - Date created - 1996-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. AN - 77732188; 7500013 AB - Picolinic acid, a catabolite of L-tryptophan, activates the transcription of the inducible nitric oxide synthase gene (iNOS) in IFN-gamma-treated murine macrophages. We performed functional studies on the 5' flanking region of the iNOS gene linked to a CAT reporter gene to identify the cis-acting element(s) responsible for the activation of iNOS transcription by picolinic acid. Transient transfection assays showed that the full-length iNOS promoter in the murine macrophage cell line ANA-1 was activated by the synergistic interaction between IFN-gamma and picolinic acid. Deletion or mutation of the iNOS promoter region from -227 to -209, containing a sequence homology to a hypoxia-responsive enhancer (iNOS-HRE), decreased picolinic acid- but not LPS-induced CAT activity by more than 70%. Functional studies using a tk promoter-CAT reporter gene plasmid demonstrated that the iNOS-HRE was sufficient to confer inducibility by picolinic acid but not by IFN-gamma or LPS. Electrophoretic mobility shift assays confirmed that picolinic acid alone induced a specific binding activity to the iNOS-HRE. Furthermore, we found that the iNOS-HRE activity was inducible by hypoxia and that hypoxia in combination with IFN-gamma activated the iNOS promoter in transient transfection assays and induced iNOS transcription and mRNA expression. These data establish that the iNOS-HRE is a novel regulatory element of the iNOS promoter activity in murine macrophages and provide the first evidence that iNOS is a hypoxia-inducible gene. JF - The Journal of experimental medicine AU - Melillo, G AU - Musso, T AU - Sica, A AU - Taylor, L S AU - Cox, G W AU - Varesio, L AD - Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/12/01/ PY - 1995 DA - 1995 Dec 01 SP - 1683 EP - 1693 VL - 182 IS - 6 SN - 0022-1007, 0022-1007 KW - DNA-Binding Proteins KW - 0 KW - Picolinic Acids KW - RNA, Messenger KW - Interferon-gamma KW - 82115-62-6 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - picolinic acid KW - QZV2W997JQ KW - Index Medicus KW - Macrophages -- enzymology KW - Animals KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Enzyme Induction KW - Transcription, Genetic KW - Mice KW - RNA, Messenger -- genetics KW - Drug Synergism KW - DNA-Binding Proteins -- metabolism KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Enzymologic KW - Nitric Oxide Synthase -- genetics KW - Interferon-gamma -- administration & dosage KW - Hypoxia -- genetics KW - Picolinic Acids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77732188?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=A+hypoxia-responsive+element+mediates+a+novel+pathway+of+activation+of+the+inducible+nitric+oxide+synthase+promoter.&rft.au=Melillo%2C+G%3BMusso%2C+T%3BSica%2C+A%3BTaylor%2C+L+S%3BCox%2C+G+W%3BVaresio%2C+L&rft.aulast=Melillo&rft.aufirst=G&rft.date=1995-12-01&rft.volume=182&rft.issue=6&rft.spage=1683&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-17 N1 - Date created - 1996-01-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6338-42 [1648737] Cell. 1994 Sep 23;78(6):915-8 [7522969] J Biol Chem. 1991 Aug 25;266(24):15563-6 [1874713] J Immunol. 1991 Dec 1;147(11):3809-14 [1940368] Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10553-7 [1961720] J Biol Chem. 1992 Mar 25;267(9):6370-4 [1372907] Science. 1992 Apr 10;256(5054):225-8 [1373522] FASEB J. 1992 Aug;6(11):2977-89 [1322853] Cell. 1992 Sep 4;70(5):705-7 [1381285] FASEB J. 1992 Sep;6(12):3051-64 [1381691] Anal Biochem. 1976 May 7;72:248-54 [942051] Proc Natl Acad Sci U S A. 1978 Aug;75(8):3998-4000 [279015] Pediatr Res. 1980 Jul;14(7):876-80 [7413302] J Natl Cancer Inst. 1982 Jan;68(1):123-6 [6948122] Am J Clin Nutr. 1982 Jan;35(1):1-5 [7064867] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] J Immunopharmacol. 1984;6(4):291-304 [6527007] Nature. 1985 Dec 19-1986 Jan 1;318(6047):667-70 [4079980] J Interferon Res. 1986 Aug;6(4):389-96 [3095441] Cancer Res. 1988 Jan 15;48(2):346-50 [3121172] Drugs Exp Clin Res. 1987;13(10):607-14 [3428125] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1242-6 [3124115] J Immunol. 1988 Sep 15;141(6):2153-7 [3139754] J Immunol. 1988 Oct 15;141(8):2819-23 [3262668] Biochim Biophys Acta. 1989 Jul 11;1012(2):140-7 [2500976] Nucleic Acids Res. 1989 Jun 26;17(12):4902 [2473446] Cancer Res. 1989 Sep 1;49(17):4941-4 [2788032] J Natl Cancer Inst. 1989 Oct 4;81(19):1492-6 [2778838] J Immunol. 1990 Aug 15;145(4):1246-50 [2116480] J Immunol. 1990 Dec 15;145(12):4265-71 [1701787] Curr Opin Immunol. 1991 Feb;3(1):65-70 [1711326] Nature. 1992 Oct 29;359(6398):843-5 [1279431] Mol Cell Biol. 1992 Dec;12(12):5447-54 [1448077] J Biol Chem. 1993 Jan 25;268(3):1908-13 [7678412] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2423-7 [8460154] J Immunol. 1993 May 1;150(9):4031-40 [8473748] Proc Natl Acad Sci U S A. 1993 May 1;90(9):4304-8 [8387214] J Clin Invest. 1993 Jun;91(6):2769-75 [8514884] J Biol Chem. 1993 Oct 15;268(29):21513-8 [8408001] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9730-4 [7692452] N Engl J Med. 1993 Dec 30;329(27):2002-12 [7504210] J Biol Chem. 1994 Feb 18;269(7):4705-8 [7508926] Science. 1994 Mar 18;263(5153):1612-5 [7510419] J Biol Chem. 1994 Mar 18;269(11):8128-33 [7510678] J Biol Chem. 1994 May 13;269(19):13725-8 [7514592] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6496-500 [8022811] J Exp Med. 1995 Jan 1;181(1):63-70 [7528779] Cancer Res. 1995 Feb 15;55(4):727-30 [7531613] J Clin Invest. 1994 Aug;94(2):714-21 [7518842] J Exp Med. 1994 Sep 1;180(3):977-84 [7520478] J Biol Chem. 1994 Sep 23;269(38):23757-63 [8089148] Transplantation. 1994 Sep 15;58(5):592-5 [7522365] FASEB J. 1991 Aug;5(11):2516-22 [1907934] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Errors in exposure assessment, statistical power and the interpretation of residential radon studies. AN - 77730322; 7494877 AB - To date, epidemiological studies of risk from residential radon have not convincingly demonstrated an association with lung cancer. These case-control studies, however, have inherent limitations due to errors in estimates of exposure to indoor radon. These errors take on special significance because the level of residential risk predicted from studies of underground miners is relatively low and possibly at the limit detectable by current epidemiological methods. To illustrate the problem caused by errors in exposure assessment, a series of case-control studies were simulated and resulting dose-response relationships evaluated. For each of four assumed error distributions for exposure to radon progeny, 10 indoor radon studies of 700 cases and 700 controls were generated randomly from a population with a risk of radon-induced lung cancer based on extrapolations from studies of underground miners. When exposures were assumed as known without error, 6 of 10 studies failed to find a significant dose response, in accord with the theoretical power of the study of 0.47. For simulations in which exposures were measured with error, the situation was worse, as the power of the study was reduced further and it was even less likely that a single study would result in a significant finding. For each error scenario, combining data from the 10 simulated studies did result in a significant dose response. However, the pooled results are somewhat misleading, because the effects of mobility, missing radon measurements, residential occupancy and potential confounding variables such as cigarette smoking were not taken into account. Empirical estimates of power were computed using 1,000 simulated case-control studies. When mobility and missing radon measurements in prior homes were incorporated into the design, the power of the study decreased, reducing the chance of detecting a significant effect of exposure. Enlarging study size to 2,000 cases and 2,000 controls increased the power of the study to 0.90 when exposure error was absent and subjects lived in one home only, but power was below 0.40 under realistic conditions for exposure error and mobility. When studies were generated under an assumption that exposure does not increase risk, up to 15% of simulated studies with 700 cases and 700 controls resulted in an estimated dose-response parameter in excess of the dose response from studies of miners. With increasing mobility and exposure error, it became virtually impossible to distinguish between the distributions of risk estimates from simulated studies based on an underlying excess relative risk of 0.015/working level month from estimates based on no risk from exposure.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Radiation research AU - Lubin, J H AU - Boice, J D AU - Samet, J M AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Maryland 20892-7368, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 329 EP - 341 VL - 144 IS - 3 SN - 0033-7587, 0033-7587 KW - Radon Daughters KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Space life sciences KW - United States KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Time Factors KW - Radon Daughters -- adverse effects KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Housing KW - Epidemiologic Methods KW - Neoplasms, Radiation-Induced -- epidemiology KW - Environmental Exposure KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77730322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Errors+in+exposure+assessment%2C+statistical+power+and+the+interpretation+of+residential+radon+studies.&rft.au=Lubin%2C+J+H%3BBoice%2C+J+D%3BSamet%2C+J+M&rft.aulast=Lubin&rft.aufirst=J&rft.date=1995-12-01&rft.volume=144&rft.issue=3&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-05 N1 - Date created - 1996-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus type 1 envelope protein does not stimulate either prostaglandin formation or the expression of prostaglandin H synthase in THP-1 human monocytes/macrophages. AN - 77701381; 7494315 AB - Prostaglandin E2 is observed at elevated levels during human immunodeficiency virus (HIV) infection and thus may contribute to the HIV-dependent immunosuppression. The mechanisms responsible for this increase are not understood. Evidence indicates that the viral envelope proteins perturb membrane signaling mediated by the CD4 receptor, suggesting that the free envelope protein and/or the intact virus may be responsible for the increase in prostaglandin E2 levels. In this study, we have used THP-1 human monocytes and THP-1 cells differentiated by 12-O-tetradecanoylphorbol-13-acetate treatment into macrophages to determine if the HIV envelope protein, gp120, or an anti-CD4 receptor antibody stimulates prostaglandin formation by interacting with the CD4 receptor. Incubation of THP-1 cells with OKT4A antibody greatly stimulated the CD4-p56lck receptor complex as estimated by enhanced p56lck autophosphorylation, while the gp120 gave small but significant responses. Monocytic THP-1 cells poorly metabolized arachidonic acid to prostaglandin E2 and thromboxane B2 as measured by high-pressure liquid chromatography analysis. Western blot (immunoblot) and Northern (RNA) blot analyses revealed that unstimulated monocytes expressed little prostaglandin H synthase 1 and 2 (PGHS-1 and -2). Incubation of the monocytes with lipopolysaccharide, OKT4A, or gp120 did not increase the formation of prostaglandins. The expression of PGHS-1 or PGHS-2 was also not increased. Differentiation of the monocytes to macrophages by 12-O-tetradecanoylphorbol-13-acetate treatment resulted in increased expression of PGHS-1 and increased formation of prostaglandins compared with that for the monocytes. Lipopolysaccharide stimulation of the macrophages increased the formation of prostaglandins and increased the expression of PGHS-2 in the macrophages. However, OKT4A or gp120 preparation, at concentrations that stimulated p56lck autophosphorylation, did not enhance the formation of prostaglandins or the expression of PGHS-1 or PGHS-2. OKT4A and gp120 also did not stimulate the release of arachidonic acid, indicating that phospholipase A2 was not activated by the CD4 receptor in either the THP-1 monocytes or macrophages. These results indicate that activation of the CD4-p56lck receptor signal transduction pathway by the HIV envelope protein does not increase prostaglandin formation. JF - Journal of virology AU - Hui, R AU - Curtis, J F AU - Sumner, M T AU - Shears, S B AU - Glasgow, W C AU - Eling, T E AD - Eicosanoid Biochemistry Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 8020 EP - 8026 VL - 69 IS - 12 SN - 0022-538X, 0022-538X KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD4 KW - Eicosanoids KW - HIV Envelope Protein gp120 KW - Isoenzymes KW - OKT4A monoclonal antibody KW - Prostaglandins KW - Thromboxane B2 KW - 54397-85-2 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Lymphocyte Specific Protein Tyrosine Kinase p56(lck) KW - EC 2.7.10.2 KW - src-Family Kinases KW - Dinoprostone KW - K7Q1JQR04M KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Thromboxane B2 -- isolation & purification KW - Enzyme Activation KW - Humans KW - Eicosanoids -- metabolism KW - Gene Expression KW - Cell Differentiation KW - Antibodies, Monoclonal -- pharmacology KW - Antigens, CD4 -- physiology KW - Kinetics KW - Isoenzymes -- biosynthesis KW - Dinoprostone -- metabolism KW - src-Family Kinases -- metabolism KW - Thromboxane B2 -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - CHO Cells KW - Dinoprostone -- isolation & purification KW - Cell Line KW - Cricetinae KW - Macrophages -- cytology KW - HIV Envelope Protein gp120 -- pharmacology KW - Monocytes -- cytology KW - Monocytes -- metabolism KW - HIV Envelope Protein gp120 -- isolation & purification KW - HIV-1 -- physiology KW - Prostaglandins -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Macrophages -- metabolism KW - HIV Envelope Protein gp120 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77701381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Human+immunodeficiency+virus+type+1+envelope+protein+does+not+stimulate+either+prostaglandin+formation+or+the+expression+of+prostaglandin+H+synthase+in+THP-1+human+monocytes%2Fmacrophages.&rft.au=Hui%2C+R%3BCurtis%2C+J+F%3BSumner%2C+M+T%3BShears%2C+S+B%3BGlasgow%2C+W+C%3BEling%2C+T+E&rft.aulast=Hui&rft.aufirst=R&rft.date=1995-12-01&rft.volume=69&rft.issue=12&rft.spage=8020&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1991 Jun 15;266(17):11176-83 [2040625] J Biol Chem. 1994 May 13;269(19):13811-6 [8188658] J Chromatogr. 1991 Sep 20;557(1-2):507-13 [1660487] Science. 1992 Feb 14;255(5046):853-5 [1311128] J Biol Chem. 1992 Mar 5;267(7):4338-44 [1339449] Cell Growth Differ. 1991 Dec;2(12):609-17 [1687313] J Biol Chem. 1992 Apr 25;267(12):7991-4 [1569057] Immunology. 1992 Mar;75(3):391-7 [1572689] Int Immunol. 1992 Feb;4(2):295-9 [1535787] Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6147-51 [1631101] J Acquir Immune Defic Syndr. 1992;5(8):760-70 [1325556] J Biol Chem. 1992 Dec 25;267(36):25934-8 [1464605] Cell. 1993 Jan 29;72(2):269-78 [8381049] Eur J Immunol. 1993 Mar;23(3):600-7 [7680610] J Biol Chem. 1993 Mar 15;268(8):5425-30 [8449903] J Biol Chem. 1993 Mar 25;268(9):6610-4 [8454631] Annu Rev Immunol. 1993;11:451-99 [8476569] Biochem Biophys Res Commun. 1993 Apr 30;192(2):787-93 [8484784] Arch Biochem Biophys. 1993 Oct;306(1):169-77 [8215400] J Immunol. 1993 Dec 15;151(12):6692-700 [8258685] Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7 [8265610] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):494-8 [8290553] J Virol. 1994 Mar;68(3):1983-6 [8107259] Ann Neurol. 1994 May;35(5):592-7 [7910004] J Clin Immunol. 1983 Oct;3(4):295-315 [6140268] Anal Biochem. 1984 Jul;140(1):87-94 [6091494] Lancet. 1985 Nov 2;2(8462):1016-7 [2865493] J Gen Virol. 1986 Nov;67 ( Pt 11):2533-8 [2431105] Virology. 1987 Jan;156(1):171-6 [3643678] Prostaglandins. 1987 Dec;34(6):783-95 [2835787] Proc Natl Acad Sci U S A. 1989 Jan;86(2):621-5 [2536171] Proc Natl Acad Sci U S A. 1990 May;87(9):3373-7 [2159148] AIDS. 1990 Apr;4(4):307-15 [2190605] Cell Signal. 1989;1(3):289-94 [2641884] J Biol Chem. 1990 Oct 5;265(28):16737-40 [2120205] J Immunol. 1991 Nov 1;147(9):2892-901 [1918997] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A bipartite operator interacts with a heat shock element to mediate early meiotic induction of Saccharomyces cerevisiae HSP82. AN - 77696246; 8524241 AB - Although key genetic regulators of early meiotic transcription in Saccharomyces cerevisiae have been well characterized, the activation of meiotic genes is still poorly understood in terms of cis-acting DNA elements and their associated factors. I report here that induction of HSP82 is regulated by the early meiotic IME1-IME2 transcriptional cascade. Vegetative repression and meiotic induction depend on interactions of the promoter-proximal heat shock element (HSE) with a nearby bipartite repression element, composed of the ubiquitous early meiotic motif, URS1 (upstream repression sequence 1), and a novel ancillary repression element. The ancillary repression element is required for efficient vegetative repression, is spatially separable from URS1, and continues to facilitate repression during sporulation. In contrast, URS1 also functions as a vegetative repression element but is converted early in meiosis into an HSE-dependent activation element. An early step in this transformation may be the antagonism of URS1-mediated repression by IME1. The HSE also nonspecifically supports a second major mode of meiotic activation that does not require URS1 but does require expression of IME2 and concurrent starvation. Interestingly, increased rather than decreased URS1-mediated vegetative transcription can be artificially achieved by introducing rare point mutations into URS1 or by deleting the UME6 gene. These lesions offer insight into mechanisms of URS-dependent repression and activation. Experiments suggest that URS1-bound factors functionally modulate heat shock factor during vegetative transcription and early meiotic induction but not during heat shock. The loss of repression and activation observed when the IME2 activation element, T4C, is substituted for the HSE suggests specific requirements for URS1-upstream activation sequence interactions. JF - Molecular and cellular biology AU - Szent-Gyorgyi, C AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 6754 EP - 6769 VL - 15 IS - 12 SN - 0270-7306, 0270-7306 KW - DNA Primers KW - 0 KW - Fungal Proteins KW - HSP82 protein, S cerevisiae KW - HSP90 Heat-Shock Proteins KW - Heat-Shock Proteins KW - Saccharomyces cerevisiae Proteins KW - Index Medicus KW - Sequence Homology, Nucleic Acid KW - Fungal Proteins -- biosynthesis KW - Transcription, Genetic KW - Plasmids KW - Gene Deletion KW - Genotype KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Meiosis KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Point Mutation KW - Spores, Fungal KW - Time Factors KW - Saccharomyces cerevisiae -- genetics KW - Gene Expression Regulation, Fungal KW - Regulatory Sequences, Nucleic Acid KW - Saccharomyces cerevisiae -- metabolism KW - Genes, Fungal KW - Heat-Shock Proteins -- biosynthesis KW - Heat-Shock Proteins -- genetics KW - Saccharomyces cerevisiae -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77696246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=A+bipartite+operator+interacts+with+a+heat+shock+element+to+mediate+early+meiotic+induction+of+Saccharomyces+cerevisiae+HSP82.&rft.au=Szent-Gyorgyi%2C+C&rft.aulast=Szent-Gyorgyi&rft.aufirst=C&rft.date=1995-12-01&rft.volume=15&rft.issue=12&rft.spage=6754&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-19 N1 - Date created - 1996-01-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1990 May;10(5):2261-8 [2183027] Cell. 1990 May 4;61(3):375-8 [2185888] Mol Cell Biol. 1990 Jun;10(6):3239-42 [2342473] EMBO J. 1990 Aug;9(8):2543-53 [1695149] Mol Cell Biol. 1990 Aug;10(8):3884-95 [2115115] Cell. 1990 Aug 24;62(4):793-805 [2201452] Cell. 1990 Aug 24;62(4):807-17 [2201453] J Biol Chem. 1990 Nov 5;265(31):18912-21 [2121731] Nature. 1990 Nov 8;348(6297):166-8 [2234079] Mol Cell Biol. 1990 Dec;10(12):6103-13 [2247050] Mol Cell Biol. 1990 Dec;10(12):6362-73 [2123293] Mol Cell Biol. 1993 Sep;13(9):5749-61 [8355713] EMBO J. 1993 Oct;12(10):3931-45 [8404861] EMBO J. 1993 Dec 15;12(13):5007-18 [8262043] Science. 1994 Feb 25;263(5150):1103-4 [8108728] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9406-10 [2123556] J Mol Biol. 1990 Dec 5;216(3):611-31 [2175361] Gene. 1990 Nov 30;96(1):125-8 [2265750] Mol Cell Biol. 1991 Feb;11(2):666-76 [1846668] EMBO J. 1991 Feb;10(2):369-75 [1899375] EMBO J. 1991 Mar;10(3):607-15 [2001676] Methods Enzymol. 1991;194:182-7 [2005786] Mol Cell Biol. 1991 May;11(5):2723-35 [2017175] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5724-8 [1648229] Nature. 1995 Mar 9;374(6518):193-6 [7877695] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4006-10 [7732022] Mol Cell Biol. 1995 Jun;15(6):2955-61 [7760793] Mol Cell Biol. 1995 Jun;15(6):3405-14 [7760837] Genetics. 1995 May;140(1):79-90 [7635311] Nature. 1980 Aug 28;286(5776):854-60 [6774262] Proc Natl Acad Sci U S A. 1981 Apr;78(4):2199-203 [6264467] J Biol Chem. 1984 May 10;259(9):5745-51 [6325446] Science. 1986 Mar 7;231(4742):1154-7 [3511530] J Mol Biol. 1987 Jan 5;193(1):71-80 [3295258] Proc Natl Acad Sci U S A. 1987 Jun;84(12):3997-4001 [3295874] Mol Cell Biol. 1987 May;7(5):1906-16 [3037338] Genetics. 1987 Aug;116(4):541-5 [3305158] Mol Cell Biol. 1988 Mar;8(3):1132-6 [2835662] Cell. 1988 Sep 9;54(6):841-53 [3044612] Genes Dev. 1991 Jul;5(7):1299-308 [2065978] Curr Genet. 1991 May;19(5):383-8 [1913877] Nature. 1991 Oct 31;353(6347):822-7 [1944557] Mol Cell Biol. 1992 Mar;12(3):1021-30 [1545786] Nucleic Acids Res. 1992 Apr 25;20(8):1909-15 [1579492] Genetics. 1992 Apr;130(4):703-16 [1582554] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7412-6 [1502152] Mol Cell Biol. 1992 Sep;12(9):3706-14 [1508177] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9166-70 [1409619] Mol Cell Biol. 1993 Jan;13(1):248-56 [8417330] Genetics. 1993 Jan;133(1):67-77 [8417990] J Bacteriol. 1993 Feb;175(4):941-51 [8432717] Genes Dev. 1993 Feb;7(2):173-9 [8436289] Mol Cell Biol. 1993 Apr;13(4):2113-25 [8455600] Mol Cell Biol. 1993 Apr;13(4):2172-81 [8455605] Genetics. 1993 Apr;133(4):775-84 [8462841] Mol Gen Genet. 1993 Mar;237(3):375-84 [8483452] Mol Cell Biol. 1993 Jun;13(6):3773-81 [7684502] J Bacteriol. 1993 Jul;175(13):4235-8 [8320238] Mol Cell Biol. 1993 Jul;13(7):4146-56 [8321219] Yeast. 1993 May;9(5):465-79 [8322510] Mol Cell Biol. 1993 Sep;13(9):5637-46 [8355706] Microbiol Rev. 1994 Mar;58(1):56-70 [8177171] Dev Genet. 1994;15(2):139-47 [8205723] EMBO J. 1994 Jun 1;13(11):2617-24 [8013461] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6559-63 [8022820] Biol Reprod. 1994 Jun;50(6):1334-43 [8080921] Genes Dev. 1994 Apr 1;8(7):796-810 [7926768] Mol Cell Biol. 1994 Dec;14(12):8155-65 [7969152] Cell. 1988 Sep 9;54(6):855-64 [3044613] Genetics. 1988 Nov;120(3):621-3 [2852134] J Bacteriol. 1989 May;171(5):2680-8 [2651414] Gene. 1988 Dec 30;74(2):491-501 [2469626] Genetics. 1989 May;122(1):19-27 [2659436] Mol Cell Biol. 1989 May;9(5):2142-52 [2664470] Mol Cell Biol. 1989 Sep;9(9):3919-30 [2674684] Cell. 1989 Dec 1;59(5):797-806 [2590940] Mol Cell Biol. 1989 Nov;9(11):4789-98 [2689867] Proc Natl Acad Sci U S A. 1989 Dec;86(24):10018-22 [2690066] Mol Cell Biol. 1990 May;10(5):2104-10 [2183020] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac. AN - 77696093; 7492762 AB - Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months; no chemotherapy regimen appears successful in inducing long-term disease-free survival. The scientific basis of the present study is that ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference, we administered anti-Tac armed with Yttrium-90 (90Y) to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of 90Y-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5- to 15-mCi doses used, 9 of 16 evaluable patients responded to 90Y anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (> or = grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with 90Y anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy. JF - Blood AU - Waldmann, T A AU - White, J D AU - Carrasquillo, J A AU - Reynolds, J C AU - Paik, C H AU - Gansow, O A AU - Brechbiel, M W AU - Jaffe, E S AU - Fleisher, T A AU - Goldman, C K AU - Top, L E AU - Bamford, R AU - Zaknoen, E AU - Roessler, E AU - Kasten-Sportes, C AU - England, R AU - Litou, H AU - Johnson, J A AU - Jackson-White, T AU - Manns, A AU - Hanchard, B AU - Junghans, R P AU - Nelson, D L AD - Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/12/01/ PY - 1995 DA - 1995 Dec 01 SP - 4063 EP - 4075 VL - 86 IS - 11 SN - 0006-4971, 0006-4971 KW - Antibodies, Anti-Idiotypic KW - 0 KW - Antibodies, Monoclonal KW - Receptors, Interleukin-2 KW - Yttrium Radioisotopes KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Humans KW - Mice KW - Antibodies, Anti-Idiotypic -- biosynthesis KW - Receptors, Interleukin-2 -- immunology KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use KW - Lymphocyte Count KW - Receptors, Interleukin-2 -- metabolism KW - Adult KW - Immunocompetence KW - Middle Aged KW - Antibodies, Monoclonal -- adverse effects KW - Female KW - Male KW - T-Lymphocytes KW - Yttrium Radioisotopes -- therapeutic use KW - Yttrium Radioisotopes -- administration & dosage KW - Radioimmunotherapy KW - Leukemia-Lymphoma, Adult T-Cell -- radiotherapy KW - Leukemia-Lymphoma, Adult T-Cell -- metabolism KW - Yttrium Radioisotopes -- adverse effects KW - Leukemia-Lymphoma, Adult T-Cell -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77696093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Radioimmunotherapy+of+interleukin-2R+alpha-expressing+adult+T-cell+leukemia+with+Yttrium-90-labeled+anti-Tac.&rft.au=Waldmann%2C+T+A%3BWhite%2C+J+D%3BCarrasquillo%2C+J+A%3BReynolds%2C+J+C%3BPaik%2C+C+H%3BGansow%2C+O+A%3BBrechbiel%2C+M+W%3BJaffe%2C+E+S%3BFleisher%2C+T+A%3BGoldman%2C+C+K%3BTop%2C+L+E%3BBamford%2C+R%3BZaknoen%2C+E%3BRoessler%2C+E%3BKasten-Sportes%2C+C%3BEngland%2C+R%3BLitou%2C+H%3BJohnson%2C+J+A%3BJackson-White%2C+T%3BManns%2C+A%3BHanchard%2C+B%3BJunghans%2C+R+P%3BNelson%2C+D+L&rft.aulast=Waldmann&rft.aufirst=T&rft.date=1995-12-01&rft.volume=86&rft.issue=11&rft.spage=4063&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Blood. 1996 Jun 15;87(12):5379-80 [8652853] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Possible role for serine/threonine phosphorylation in the regulation of the heteroprotein complex between the hsp90 stress protein and the pp60v-src tyrosine kinase. AN - 77691458; 7499384 AB - The abundant, cytoplasmic 90-kDa heat-shock protein associates transiently with the Rous sarcoma virus oncogenic protein tyrosine kinase, pp60v-src, directs its cellular trafficking and negatively regulates its kinase activity. Here we report that the serine/threonine phosphatase inhibitor, okadaic acid, destabilized the heat-shock protein 90-pp60v-src chaperone complex in v-src-transfected cells. Concomitant with complex destabilization by okadaic acid, phosphoserine was doubled and phosphothreonine was increased 20-fold in the heat-shock protein 90. Although phosphorylation of the total pool of immunoprecipitable pp60v-src was unchanged, okadaic acid slightly increased phosphoserine and phosphothreonine levels specifically in pp60v-src bound to heat-shock protein 90. The low level of tyrosine phosphorylation in the pp60v-src complexed with heat-shock protein 90 was further decreased by okadaic acid. Interestingly, okadaic acid-stabilized hyperphosphorylation of the heat-shock protein 90-pp60v-src complex lowered the level of pp60v-src in cell membranes, the functional location for pp60v-src. We suggest that serine/threonine phosphorylation of heat-shock protein 90 and/or pp60v-src functions as a regulatory molecular trigger to release pp60v-src from the chaperone complex at the inner surface of cell membranes. JF - The Journal of biological chemistry AU - Mimnaugh, E G AU - Worland, P J AU - Whitesell, L AU - Neckers, L M AD - Clinical Pharmacology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/12/01/ PY - 1995 DA - 1995 Dec 01 SP - 28654 EP - 28659 VL - 270 IS - 48 SN - 0021-9258, 0021-9258 KW - Enzyme Inhibitors KW - 0 KW - Ethers, Cyclic KW - HSP90 Heat-Shock Proteins KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Threonine KW - 2ZD004190S KW - Serine KW - 452VLY9402 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Oncogene Protein pp60(v-src) KW - EC 2.7.10.2 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Index Medicus KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Animals KW - 3T3 Cells KW - Phosphorylation KW - Cell Membrane -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Mice KW - Ethers, Cyclic -- pharmacology KW - Cell Membrane -- metabolism KW - Cell Line, Transformed KW - Threonine -- metabolism KW - Oncogene Protein pp60(v-src) -- metabolism KW - HSP90 Heat-Shock Proteins -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - Serine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77691458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Possible+role+for+serine%2Fthreonine+phosphorylation+in+the+regulation+of+the+heteroprotein+complex+between+the+hsp90+stress+protein+and+the+pp60v-src+tyrosine+kinase.&rft.au=Mimnaugh%2C+E+G%3BWorland%2C+P+J%3BWhitesell%2C+L%3BNeckers%2C+L+M&rft.aulast=Mimnaugh&rft.aufirst=E&rft.date=1995-12-01&rft.volume=270&rft.issue=48&rft.spage=28654&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modular structure of chromosomal proteins HMG-14 and HMG-17: definition of a transcriptional enhancement domain distinct from the nucleosomal binding domain. AN - 77687906; 8524231 AB - Chromosomal proteins HMG-14 and HMG-17 are the only known nuclear proteins which specifically bind to the nucleosome core particle and are implicated in the generation and/or maintenance of structural features specific to active chromatin. The two proteins facilitate polymerase II and III transcription from in vitro- and in vivo-assembled circular chromatin templates. Here we used deletion mutants and specific peptides to identify the transcriptional enhancement domain and delineate the nucleosomal binding domain of the HMG-14 and -17 proteins. Deletion of the 22 C-terminal amino acids of HMG-17 or 26 C-terminal amino acids of HMG-14 reduces significantly the ability of the proteins to enhance transcription from chromatin templates. In contrast, N-terminal truncation mutants had the same transcriptional enhancement activity as the full-length proteins. We conclude that the negatively charged C-terminal region of the proteins is required for transcriptional enhancement. Chromatin transcription enhancement assays, which involve binding competition between the full-length proteins and peptides derived from their nucleosomal binding regions, indicate that the minimal nucleosomal binding domain of human HMG-17 is 24 amino acids long and spans residues 17 to 40. The results suggest that HMG-14 and -17 proteins have a modular structure and contain distinct functional domains. JF - Molecular and cellular biology AU - Trieschmann, L AU - Postnikov, Y V AU - Rickers, A AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 6663 EP - 6669 VL - 15 IS - 12 SN - 0270-7306, 0270-7306 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - Nucleosomes KW - Peptide Fragments KW - RNA, Ribosomal, 5S KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - RNA, Ribosomal, 5S -- genetics KW - Amino Acid Sequence KW - Oocytes -- physiology KW - Binding Sites KW - Mutagenesis KW - Xenopus laevis KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Binding, Competitive KW - Peptide Fragments -- pharmacology KW - Molecular Sequence Data KW - Xenopus KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Female KW - Sequence Deletion KW - High Mobility Group Proteins -- chemistry KW - High Mobility Group Proteins -- biosynthesis KW - Chromatin -- metabolism KW - Nucleosomes -- metabolism KW - Transcription, Genetic KW - High Mobility Group Proteins -- metabolism KW - Chromatin -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77687906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Modular+structure+of+chromosomal+proteins+HMG-14+and+HMG-17%3A+definition+of+a+transcriptional+enhancement+domain+distinct+from+the+nucleosomal+binding+domain.&rft.au=Trieschmann%2C+L%3BPostnikov%2C+Y+V%3BRickers%2C+A%3BBustin%2C+M&rft.aulast=Trieschmann&rft.aufirst=L&rft.date=1995-12-01&rft.volume=15&rft.issue=12&rft.spage=6663&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-19 N1 - Date created - 1996-01-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Cell Biol. 1982 May;93(2):285-97 [7096439] J Biol Chem. 1980 Apr 25;255(8):3673-84 [7364765] Cell. 1980 May;20(1):131-41 [6248230] Proc Natl Acad Sci U S A. 1983 Nov;80(22):6735-9 [6196774] J Biol Chem. 1984 Jan 25;259(2):699-702 [6229533] J Biol Chem. 1986 Jun 5;261(16):7479-84 [3754870] Exp Cell Res. 1986 Oct;166(2):486-96 [3743668] J Biol Chem. 1986 Dec 5;261(34):16082-6 [3782107] J Biol Chem. 1986 Dec 5;261(34):16185-90 [3782113] EMBO J. 1987 Aug;6(8):2393-9 [3665881] EMBO J. 1988 Mar;7(3):665-72 [3396538] J Biol Chem. 1989 Jan 25;264(3):1799-803 [2912984] Biochim Biophys Acta. 1990 Jul 30;1049(3):231-43 [2200521] Nucleic Acids Res. 1990 Oct 11;18(19):5767-74 [2216769] J Biol Chem. 1990 Nov 25;265(33):20077-80 [2243079] Nucleic Acids Res. 1991 Feb 25;19(4):717-25 [2017359] Nucleic Acids Res. 1991 Jun 11;19(11):3115-21 [2057367] Mol Cell Biol. 1991 Sep;11(9):4483-9 [1908554] Biochemistry. 1992 Jan 21;31(2):364-70 [1731893] J Biol Chem. 1992 Sep 25;267(27):19587-95 [1527076] J Mol Biol. 1992 Nov 20;228(2):442-9 [1453455] Cell. 1993 Feb 26;72(4):481-3 [8440015] EMBO J. 1993 Oct;12(10):3855-64 [8404854] J Mol Biol. 1994 Feb 11;236(1):189-98 [8107104] Cell. 1994 Apr 8;77(1):5-8 [8156597] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7051-5 [8041744] Science. 1994 Aug 5;265(5173):796-9 [8047885] Mol Cell Biol. 1994 Nov;14(11):7226-34 [7935437] Nature. 1994 Oct 20;371(6499):717-20 [7935820] EMBO J. 1994 Oct 17;13(20):4856-62 [7957055] J Biol Chem. 1994 Nov 11;269(45):28436-42 [7961785] Nucleic Acids Res. 1994 Oct 25;22(21):4520-6 [7971283] Annu Rev Biochem. 1994;63:265-97 [7979240] EMBO J. 1995 Apr 3;14(7):1478-89 [7729423] Science. 1980 Sep 26;209(4464):1534-6 [7433974] Nucleic Acids Res. 1980 Sep 11;8(17):3757-78 [6449690] Eur J Biochem. 1980 Dec;112(3):577-80 [6257511] Eur J Biochem. 1978 Mar;84(1):173-7 [565710] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Postexposure prophylaxis for occupational exposures to hepatitis B, hepatitis C, and human immunodeficiency virus. AN - 77687874; 7482143 AB - Bloodborne pathogens are becoming increasingly prevalent in, and therefore contributing increasing levels of risk to, the health-care work-place environment. This problem is magnified in the blood-intense operating room and obstetric environments. Whereas we will never be able to eliminate such risks entirely from the health-care workplace, a multifaceted approach to the management of these risks throughout the hospital environment and particularly in risk-intense environments will likely create a safer milieu and climate. Such an improved environment will clearly be necessary as we continue to strive to provide optimal care for all patients, irrespective of their bloodborne infection status. JF - The Surgical clinics of North America AU - Henderson, D K AD - Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1175 EP - 1187 VL - 75 IS - 6 SN - 0039-6109, 0039-6109 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Occupational Exposure KW - Humans KW - Blood-Borne Pathogens KW - Health Personnel KW - Infectious Disease Transmission, Patient-to-Professional -- prevention & control KW - Hepatitis C -- prevention & control KW - Hepatitis B -- prevention & control KW - Occupational Diseases -- prevention & control KW - HIV Infections -- prevention & control KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77687874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Surgical+clinics+of+North+America&rft.atitle=Postexposure+prophylaxis+for+occupational+exposures+to+hepatitis+B%2C+hepatitis+C%2C+and+human+immunodeficiency+virus.&rft.au=Henderson%2C+D+K&rft.aulast=Henderson&rft.aufirst=D&rft.date=1995-12-01&rft.volume=75&rft.issue=6&rft.spage=1175&rft.isbn=&rft.btitle=&rft.title=The+Surgical+clinics+of+North+America&rft.issn=00396109&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of the murine alpha B-crystallin/small heat shock protein gene in cardiac muscle. AN - 77687389; 8524275 AB - The murine alpha B-crystallin/small heat shock protein gene is expressed at high levels in the lens and at lower levels in the heart, skeletal muscle, and numerous other tissues. Previously we have found a skeletal-muscle-preferred enhancer at positions -427 to -259 of the alpha B-crystallin gene containing at least four cis-acting regulatory elements (alpha BE-1, alpha BE-2, alpha BE-3, and MRF, which has an E box). Here we show that in transgenic mice, the alpha B-crystallin enhancer directs the chloramphenicol acetyltransferase reporter gene driven by the alpha B-crystallin promoter specifically to myocardiocytes of the heart. The alpha B-crystallin enhancer was active in conjugation with the herpes simplex virus thymidine kinase promoter/human growth hormone reporter gene in transfected rat myocardiocytes. DNase I footprinting and site-specific mutagenesis experiments showed that alpha BE-1, alpha BE-2, alpha BE-3, MRF, and a novel, heart-specific element called alpha BE-4 are required for alpha B-crystallin enhancer activity in transfected myocardiocytes. By contrast, alpha BE-4 is not utilized for enhancer activity in transfected lens or skeletal muscle cell lines. Alpha BE-4 contains an overlapping heat shock sequence and a reverse CArG box [5'-GG(A/T)6CC-3']. Electrophoretic mobility shift assays with an antibody to serum response factor and a CArG-box-competing sequence from the c-fos promoter indicated that a cardiac-specific protein with DNA-binding and antigenic similarities to serum response factor binds to alpha BE-4 via the reverse CArG box; electrophoretic mobility shift assays and antibody experiments with anti-USF antiserum and heart nuclear extract also raised the possibility that the MRF E box utilizes USF or an antigenically related protein. We conclude that the activity of the alpha B-crystallin enhancer in the heart utilizes a reverse CArG box and an E-box-dependent pathway. JF - Molecular and cellular biology AU - Gopal-Srivastava, R AU - Haynes, J I AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, Maryland 20892-2730, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 7081 EP - 7090 VL - 15 IS - 12 SN - 0270-7306, 0270-7306 KW - Crystallins KW - 0 KW - DNA Primers KW - Heat-Shock Proteins KW - Recombinant Fusion Proteins KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Recombinant Fusion Proteins -- analysis KW - Animals KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Rabbits KW - Organ Specificity KW - Mice KW - Lung -- metabolism KW - Mice, Transgenic KW - Chloramphenicol O-Acetyltransferase -- analysis KW - Rats KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Base Sequence KW - Transfection KW - Cells, Cultured KW - Lens, Crystalline -- metabolism KW - Enhancer Elements, Genetic KW - Molecular Sequence Data KW - Genes, fos KW - Muscle, Skeletal -- metabolism KW - Cell Line KW - Heat-Shock Proteins -- biosynthesis KW - Gene Expression Regulation KW - Crystallins -- genetics KW - Myocardium -- metabolism KW - Heat-Shock Proteins -- genetics KW - Crystallins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77687389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Regulation+of+the+murine+alpha+B-crystallin%2Fsmall+heat+shock+protein+gene+in+cardiac+muscle.&rft.au=Gopal-Srivastava%2C+R%3BHaynes%2C+J+I%3BPiatigorsky%2C+J&rft.aulast=Gopal-Srivastava&rft.aufirst=R&rft.date=1995-12-01&rft.volume=15&rft.issue=12&rft.spage=7081&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-19 N1 - Date created - 1996-01-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1991 Sep;11(9):4796-803 [1875951] Development. 1991 Apr;111(4):1097-107 [1652425] Prog Nucleic Acid Res Mol Biol. 1991;41:259-81 [1882078] J Cell Biol. 1991 Oct;115(2):423-34 [1717485] J Biol Chem. 1991 Nov 25;266(33):22678-88 [1939278] Semin Cancer Biol. 1990 Feb;1(1):47-58 [2133110] J Biochem. 1991 Nov;110(5):812-22 [1783614] J Biol Chem. 1992 Mar 5;267(7):4277-80 [1537817] Mol Cell Biol. 1992 Apr;12(4):1469-79 [1532229] Proc Natl Acad Sci U S A. 1992 May 1;89(9):4047-51 [1570331] Nature. 1985 Feb 28-Mar 6;313(6005):798-801 [3919308] Cell. 1985 Nov;43(1):165-75 [4075392] Cell. 1986 Aug 15;46(4):567-74 [3524858] Mol Cell Biol. 1985 Oct;5(10):2720-32 [3837182] Mol Cell Biol. 1986 Jun;6(6):2125-36 [3785189] Differentiation. 1986;33(2):168-74 [3569698] EMBO J. 1987 Mar;6(3):667-73 [3582369] J Biol Chem. 1987 Sep 15;262(26):12856-62 [3624281] Mol Cell Biol. 1987 Aug;7(8):2803-13 [2823106] Science. 1987 Oct 30;238(4827):684-8 [3672119] Genes Dev. 1987 Nov;1(9):973-80 [3428603] Mol Cell Biol. 1988 Apr;8(4):1800-2 [3380098] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6342-6 [3413100] J Cell Biol. 1988 Aug;107(2):573-85 [3047142] Annu Rev Biochem. 1988;57:479-504 [3052280] J Biol Chem. 1989 Jan 15;264(2):1284-92 [2910853] Biochem Biophys Res Commun. 1989 Jan 16;158(1):319-25 [2912453] Cell. 1989 Mar 10;56(5):777-83 [2493990] Cell. 1989 Apr 21;57(2):197-9 [2649248] Nucleic Acids Res. 1994 Apr 11;22(7):1281-6 [8165144] Dev Biol. 1994 May;163(1):125-32 [8174768] Mol Cell Biol. 1994 Nov;14(11):7331-9 [7935447] Mol Cell Biol. 1994 Nov;14(11):7363-76 [7935450] Gene. 1995 Apr 3;155(2):151-8 [7536694] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4681-5 [7753864] Mol Cell Biol. 1988 Jan;8(1):267-72 [3422098] Virology. 1973 Apr;52(2):456-67 [4705382] Nature. 1982 Sep 9;299(5879):165-7 [7110336] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Genomics. 1988 Nov;3(4):323-36 [2907503] Mol Cell Biol. 1989 Feb;9(2):515-22 [2710114] Mol Cell Biol. 1989 Mar;9(3):1083-91 [2725488] EMBO J. 1989 Apr;8(4):1153-61 [2743976] Nature. 1989 Sep 28;341(6240):303-7 [2552320] Trends Biochem Sci. 1989 Sep;14(9):365-8 [2688200] J Histochem Cytochem. 1990 Jan;38(1):31-9 [2294148] Mol Cell Biol. 1990 Feb;10(2):528-38 [2300053] Curr Eye Res. 1990 Jan;9(1):31-7 [2178867] Cell. 1990 Apr 6;61(1):49-59 [2156629] J Mol Biol. 1990 Jun 20;213(4):677-86 [2162966] J Biol Chem. 1990 Aug 15;265(23):13809-17 [1696258] Genes Dev. 1990 Oct;4(10):1811-22 [2123467] Science. 1990 Nov 23;250(4984):1104-10 [2174572] Genes Dev. 1990 Sep;4(9):1454-61 [2253873] J Biol Chem. 1990 Dec 25;265(36):22197-203 [2176207] Science. 1991 Feb 15;251(4995):761-6 [1846704] Mol Cell Biochem. 1990 Sep 21;97(2):121-8 [2280760] Mol Cell Biol. 1991 Apr;11(4):2273-81 [1848675] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3652-6 [2023914] Development. 1991 Nov;113(3):1017-29 [1668275] Dev Biol. 1992 Nov;154(1):1-10 [1426618] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10449-53 [1438232] J Biol Chem. 1993 Feb 5;268(4):2602-9 [8428936] Mol Biol Evol. 1993 Jan;10(1):103-26 [8450753] Mol Cell Biol. 1993 May;13(5):2753-64 [8474439] Circ Res. 1993 Sep;73(3):569-78 [8394227] J Biol Chem. 1993 Sep 5;268(25):18824-34 [8360172] Mol Cell Biol. 1993 Nov;13(11):7144-52 [8413303] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3112-6 [8159713] Cell. 1983 Apr;32(4):1171-80 [6839359] Science. 1985 Jan 11;227(4683):134-40 [3917574] J Cell Biol. 1991 Jun;113(6):1255-65 [2045411] Mol Cell Biol. 1991 Jul;11(7):3735-44 [2046675] Mol Cell Biol. 1991 Sep;11(9):4340-9 [1875925] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microsatellite instability in gynecological sarcomas and in hMSH2 mutant uterine sarcoma cell lines defective in mismatch repair activity. AN - 77686598; 7585651 AB - We have examined a panel of gynecological sarcomas for microsatellite instability. The genomic DNA from 11 of 44 sarcomas contained somatic alterations in the lengths of one or more di-, tri-, tetra-, or pentanucleotide microsatellite sequence markers, and 6 of these cases had alterations in two or more markers. In addition, di-, tri-, and tetranucleotide microsatellites were found to be highly unstable in single cell clones of two cell lines derived from a uterine mixed mesodermal tumor. Since such instability is characteristic of cells defective in postreplication mismatch repair, we examined mismatch repair activity in extracts made from these lines. Both extracts were repair deficient, while an extract of another gynecological sarcoma cell line not exhibiting microsatellite instability was repair proficient. The repair deficiency was complemented by a colon tumor cell extract that was defective in the hMLH1 protein but not by an extract defective in hMSH2 protein. This suggested that the defect in the uterine sarcoma line could be in hMSH2. Subsequent analysis of the gene revealed a 2-bp deletion in exon 14, leading to premature truncation of the hMSH2 protein at codon 796 and no detectable wild-type gene present. These data suggest that the microsatellite instability observed in these cell lines, and possibly in a significant number of gynecological sarcomas, is due to defective postreplication mismatch repair. There was no apparent correlation with microsatellite instability and clinical outcome. JF - Cancer research AU - Risinger, J I AU - Umar, A AU - Boyer, J C AU - Evans, A C AU - Berchuck, A AU - Kunkel, T A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/12/01/ PY - 1995 DA - 1995 Dec 01 SP - 5664 EP - 5669 VL - 55 IS - 23 SN - 0008-5472, 0008-5472 KW - DNA, Neoplasm KW - 0 KW - DNA, Satellite KW - DNA-Binding Proteins KW - Proto-Oncogene Proteins KW - MSH2 protein, human KW - EC 3.6.1.3 KW - MutS Homolog 2 Protein KW - Index Medicus KW - Point Mutation -- genetics KW - Tumor Cells, Cultured KW - Humans KW - Prognosis KW - Uterine Cervical Neoplasms -- genetics KW - Female KW - DNA, Satellite -- genetics KW - DNA Repair -- genetics KW - Uterine Neoplasms -- genetics KW - Ovarian Neoplasms -- genetics KW - Mixed Tumor, Mesodermal -- genetics KW - Sarcoma -- genetics KW - DNA, Neoplasm -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Leiomyosarcoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77686598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Microsatellite+instability+in+gynecological+sarcomas+and+in+hMSH2+mutant+uterine+sarcoma+cell+lines+defective+in+mismatch+repair+activity.&rft.au=Risinger%2C+J+I%3BUmar%2C+A%3BBoyer%2C+J+C%3BEvans%2C+A+C%3BBerchuck%2C+A%3BKunkel%2C+T+A%3BBarrett%2C+J+C&rft.aulast=Risinger&rft.aufirst=J&rft.date=1995-12-01&rft.volume=55&rft.issue=23&rft.spage=5664&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-14 N1 - Date created - 1995-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel non-mouse mammary tumor virus activation of the Int-3 gene in a spontaneous mouse mammary tumor. AN - 77678536; 7494323 AB - In a mouse mammary tumor model system in which carcinogenic progression can be investigated, we have found a unique mutation of Int-3 associated with progression from premalignant lobular hyperplasia to tumor. Sequence analysis of the rearranged fragment revealed an insertion of an intracisternal type A particle (IAP) within the Int-3 gene. Int-3 is mutated frequently in mouse mammary tumor virus (MMTV)-induced mammary tumors by insertion of MMTV proviral DNA into this intragenic region. In these mutations, the insertion produces a chimeric Int-3 transcript encoding the cytoplasmic portion of the Int-3 protein driven by the MMTV long terminal repeat promoter. In this case, the IAP DNA was inserted in the opposite transcriptional orientation relative to Int-3; nevertheless, a similar chimeric RNA transcript driven by a cryptic promoter in the oppositely oriented 5' IAP long terminal repeat was generated. This is the first demonstration that an insertional mutation unrelated to MMTV activates an Int gene commonly associated with mammary tumorigenesis. JF - Journal of virology AU - Kordon, E C AU - Smith, G H AU - Callahan, R AU - Gallahan, D AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 8066 EP - 8069 VL - 69 IS - 12 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Proto-Oncogene Proteins KW - Receptors, Cell Surface KW - Receptors, Notch KW - Notch4 protein, mouse KW - 146991-60-8 KW - Index Medicus KW - Animals KW - Tumor Virus Infections -- genetics KW - Gene Rearrangement KW - Mice KW - Polymerase Chain Reaction KW - Base Sequence KW - Hyperplasia KW - Promoter Regions, Genetic KW - Blotting, Southern KW - DNA, Viral -- analysis KW - Tumor Virus Infections -- pathology KW - Molecular Sequence Data KW - Genes, Viral KW - Repetitive Sequences, Nucleic Acid KW - Retroviridae Infections -- pathology KW - Retroviridae Infections -- genetics KW - Female KW - Proto-Oncogene Proteins -- biosynthesis KW - Mammary Tumor Virus, Mouse -- physiology KW - Mammary Neoplasms, Animal -- pathology KW - Gene Expression Regulation, Viral KW - Mammary Neoplasms, Animal -- genetics KW - Proto-Oncogenes KW - Mammary Neoplasms, Animal -- virology KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77678536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=A+novel+non-mouse+mammary+tumor+virus+activation+of+the+Int-3+gene+in+a+spontaneous+mouse+mammary+tumor.&rft.au=Kordon%2C+E+C%3BSmith%2C+G+H%3BCallahan%2C+R%3BGallahan%2C+D&rft.aulast=Kordon&rft.aufirst=E&rft.date=1995-12-01&rft.volume=69&rft.issue=12&rft.spage=8066&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - S80638; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1980 Jun;77(6):3571-5 [6251469] Cell. 1980 Sep;21(2):465-73 [6250723] Cell. 1984 Jun;37(2):529-36 [6327073] EMBO J. 1984 Dec 1;3(12):2937-41 [6098457] Nucleic Acids Res. 1985 Jan 11;13(1):289-302 [2987792] J Virol. 1987 Jan;61(1):66-74 [3023708] Mol Cell Biol. 1988 Mar;8(3):1093-102 [2452971] Cell. 1988 Nov 18;55(4):619-25 [3180222] Adv Cancer Res. 1988;51:183-276 [3146900] Nucleic Acids Res. 1989 Mar 11;17(5):1881-92 [2564662] EMBO J. 1988 Dec 20;7(13):4283-90 [2907477] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5678-82 [2548184] EMBO J. 1990 Mar;9(3):907-13 [1690126] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4519-23 [2162045] Cell. 1991 Jan 11;64(1):159-70 [1846087] Genes Dev. 1992 Mar;6(3):345-55 [1372276] J Biol Chem. 1992 Nov 5;267(31):22351-5 [1429588] Oncogene. 1993 May;8(5):1221-32 [8479745] Int J Cancer. 1993 Jul 9;54(5):813-9 [8392034] Genes Dev. 1994 Jun 15;8(12):1463-72 [7926745] J Virol. 1995 Mar;69(3):1932-8 [7853537] Cell Growth Differ. 1995 May;6(5):563-77 [7544153] Proc Natl Acad Sci U S A. 1968 Sep;61(1):53-60 [4301594] Int J Cancer. 1971 Jan 15;7(1):167-75 [4322935] Cell. 1982 Nov;31(1):99-109 [6297757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single hamster PrP amino acid blocks conversion to protease-resistant PrP in scrapie-infected mouse neuroblastoma cells. AN - 77677864; 7494285 AB - Neurodegeneration caused by the transmissible spongiform encephalopathies is associated with the conversion of a normal host protein, PrP-sen, into an abnormal aggregated protease-resistant form, PrP-res. In scrapie-infected mouse neuroblastoma cells, mouse PrP-sen is converted into PrP-res but recombinant hamster PrP-sen expressed in these cells is not. In the present studies, recombinant hamster/mouse PrP-sen molecules were expressed in these scrapie-infected cells to define specific PrP amino acid residues critical for the conversion to PrP-res. The results showed that homology to the region of mouse PrP-sen from amino acid residues 112 to 138 was required for conversion of recombinant PrP-sen to PrP-res in scrapie-infected mouse cells. Furthermore, a single hamster-specific PrP amino acid at residue 138 could inhibit the conversion of the recombinant PrP-sen into PrP-res. The data are consistent with studies in humans which show that specific amino acid residue changes within PrP can influence disease pathogenesis and transmission of transmissible spongiform encephalopathies across species barriers. JF - Journal of virology AU - Priola, S A AU - Chesebro, B AD - Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 7754 EP - 7758 VL - 69 IS - 12 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - Prions KW - Recombinant Proteins KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Recombinant Proteins -- drug effects KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Drug Resistance, Microbial KW - Amino Acid Sequence KW - Mice KW - Scrapie KW - Neuroblastoma KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Cell Line KW - Cricetinae KW - Prions -- genetics KW - Prions -- drug effects KW - Endopeptidases -- metabolism KW - Point Mutation KW - Endopeptidases -- pharmacology KW - Prions -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77677864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=A+single+hamster+PrP+amino+acid+blocks+conversion+to+protease-resistant+PrP+in+scrapie-infected+mouse+neuroblastoma+cells.&rft.au=Priola%2C+S+A%3BChesebro%2C+B&rft.aulast=Priola&rft.aufirst=S&rft.date=1995-12-01&rft.volume=69&rft.issue=12&rft.spage=7754&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1967 Sep 2;215(5105):1043-4 [4964084] Science. 1992 Oct 30;258(5083):806-8 [1439789] J Virol. 1993 Feb;67(2):643-50 [7678300] Biochem Biophys Res Commun. 1993 Apr 30;192(2):525-31 [8097911] Cell. 1993 Jun 4;73(5):979-88 [8098995] Protein Sci. 1992 Aug;1(8):986-97 [1338978] Cell. 1993 Jul 2;73(7):1339-47 [8100741] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5959-63 [8327467] Dev Biol Stand. 1993;80:131-40 [8270103] J Virol. 1994 Aug;68(8):4873-8 [7913509] Nature. 1994 Aug 11;370(6489):471-4 [7913989] Cell. 1994 Nov 18;79(4):695-703 [7954833] J Biol Chem. 1995 Feb 17;270(7):3299-305 [7852415] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3923-7 [7732006] Science. 1982 Apr 9;216(4542):136-44 [6801762] Cell. 1983 Nov;35(1):57-62 [6414721] Cell. 1985 Apr;40(4):735-46 [2859120] Cell. 1986 Aug 15;46(4):503-11 [3015416] Proc Natl Acad Sci U S A. 1986 Sep;83(17):6372-6 [3462700] J Gen Virol. 1987 May;68 ( Pt 5):1391-9 [3106566] J Gen Virol. 1987 Jul;68 ( Pt 7):1875-81 [3110370] J Gen Virol. 1987 Oct;68 ( Pt 10):2711-6 [2889794] J Virol. 1987 Dec;61(12):3688-93 [2446004] J Virol. 1988 Aug;62(8):2845-9 [2899175] J Gen Virol. 1989 Aug;70 ( Pt 8):2017-25 [2504883] Cell. 1989 Dec 1;59(5):847-57 [2574076] J Virol. 1990 Mar;64(3):1093-101 [1968104] J Gen Virol. 1990 Feb;71 ( Pt 2):493-7 [1968507] Microbiol Rev. 1990 Sep;54(3):242-6 [2120561] Cell. 1990 Nov 16;63(4):673-86 [1977523] Lancet. 1991 Feb 16;337(8738):425 [1671440] Neurology. 1991 May;41(5):681-4 [1674116] J Virol. 1991 Jul;65(7):3667-75 [1710287] Nature. 1991 Jul 25;352(6333):340-2 [1677164] J Virol. 1991 Dec;65(12):6597-603 [1682507] Curr Top Microbiol Immunol. 1991;172:195-232 [1687381] J Neurochem. 1992 Aug;59(2):768-71 [1352803] J Virol. 1992 Nov;66(11):6547-54 [1404602] J Gen Virol. 1978 Jun;39(3):487-96 [96212] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemopreventive activity of tamoxifen, N-(4-hydroxyphenyl)retinamide, and the vitamin D analogue Ro24-5531 for androgen-promoted carcinomas of the rat seminal vesicle and prostate. AN - 77672026; 7585644 AB - We evaluated the ability of dietary N-(4-hydroxyphenyl)retinamide; 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531); and tamoxifen to inhibit the development of androgen-promoted carcinomas of the accessory sex organs of male Lobund-Wistar rats. Invasive carcinomas of the seminal vesicle (SV) and anterior prostate (AP) were induced in Lobund-Wistar rats with three different combinations of initiator [N-nitroso-N-methylurea (NMU)] and promoter [testosterone propionate (TP)]: (a) high-dose NMU (30 mg/kg) + high-dose TP (20 mg via implant every 2 months); (b) high-dose NMU + low-dose TP (10 mg implanted every 2 months); or (c) low-dose NMU (15 mg/kg) + low-dose TP. During the period of TP administration, rats were fed a diet supplemented with either N-(4-hydroxyphenyl)retinamide (1 or 2 mmol/kg diet), Ro24-5531 (1.25 or 2.5 nmol/kg diet), tamoxifen (0.5 or 5 mg/kg diet), or vehicle alone. After sacrifice at 8.5 or 11 months, the prostate-seminal vesicle complex from each rat was processed in toto and histologically staged as to the extent of tumor involvement. In animals given low-dose TP, all three agents were significantly effective at reducing the incidence of invasive carcinomas of the SV and, to a lesser degree, the AP. Of the three agents, tamoxifen given in high dose (5 mg/kg) had the strongest activity, reducing the occurrence of invasive SV carcinomas from 72-83% in controls to 6% (P = 0.0001) and the occurrence of invasive AP carcinomas from 50-72% to 18-22% (P < 0.05). JF - Cancer research AU - Lucia, M S AU - Anzano, M A AU - Slayter, M V AU - Anver, M R AU - Green, D M AU - Shrader, M W AU - Logsdon, D L AU - Driver, C L AU - Brown, C C AU - Peer, C W AD - Laboratory of Chemoprevention, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/12/01/ PY - 1995 DA - 1995 Dec 01 SP - 5621 EP - 5627 VL - 55 IS - 23 SN - 0008-5472, 0008-5472 KW - Androgens KW - 0 KW - Anticarcinogenic Agents KW - Carcinogens KW - Ro 24-5531 KW - Tamoxifen KW - 094ZI81Y45 KW - Testosterone KW - 3XMK78S47O KW - Methylnitrosourea KW - 684-93-5 KW - Calcitriol KW - FXC9231JVH KW - Index Medicus KW - Rats KW - Prostate -- drug effects KW - Drug Screening Assays, Antitumor KW - Animals KW - Male KW - Anticarcinogenic Agents -- therapeutic use KW - Calcitriol -- therapeutic use KW - Tamoxifen -- therapeutic use KW - Prostatic Neoplasms -- chemically induced KW - Neoplasms, Hormone-Dependent -- pathology KW - Neoplasms, Hormone-Dependent -- prevention & control KW - Prostatic Neoplasms -- prevention & control KW - Neoplasms, Experimental -- prevention & control KW - Neoplasms, Hormone-Dependent -- chemically induced KW - Seminal Vesicles -- drug effects KW - Neoplasms, Experimental -- pathology KW - Seminal Vesicles -- pathology KW - Calcitriol -- analogs & derivatives KW - Prostatic Neoplasms -- pathology KW - Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77672026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Chemopreventive+activity+of+tamoxifen%2C+N-%284-hydroxyphenyl%29retinamide%2C+and+the+vitamin+D+analogue+Ro24-5531+for+androgen-promoted+carcinomas+of+the+rat+seminal+vesicle+and+prostate.&rft.au=Lucia%2C+M+S%3BAnzano%2C+M+A%3BSlayter%2C+M+V%3BAnver%2C+M+R%3BGreen%2C+D+M%3BShrader%2C+M+W%3BLogsdon%2C+D+L%3BDriver%2C+C+L%3BBrown%2C+C+C%3BPeer%2C+C+W&rft.aulast=Lucia&rft.aufirst=M&rft.date=1995-12-01&rft.volume=55&rft.issue=23&rft.spage=5621&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-14 N1 - Date created - 1995-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of cocaine administration during early organogenesis on prenatal development and postnatal growth in mice. AN - 75503189; 8835227 AB - Cocaine use has been associated with adverse developmental effects in humans. However, clinical reports both confirm and deny an association between cocaine use and malformations. Similarly, differences in species and strain, as well as route and timing of cocaine administration, have added to the difficulties in determining the teratogenicity of cocaine in animal models. This study was undertaken to compare the effects of dose, route, and timing of cocaine administration in ICR mice during early organogenesis. A single intraperitoneal (ip) administration of cocaine ( > or = 60 mg/kg) on Day 9 of gestation (plug day = 1) produced maternal lethality. The predominant developmental effect of cocaine administration was an increase in the percentage of litters exhibiting an enlarged renal pelvis. Despite a high incidence of affected pups at these doses, the enlargement was not severe. These results, in agreement with previous reports, provide further evidence that the developing urogenital system is sensitive to cocaine administration. When cocaine was administered using a subcutaneous route, pup weights were greater and the incidence of enlarged renal pelvis was lower than when an ip route was used. To better mimic human binge cocaine abuse, the toxicity of a "split dose" was determined. A 60 mg/kg dose was administered using one administration of 60 mg/kg, two treatments of 30 mg/kg, or three administrations of 20 mg/kg with 1 hr separating the treatments. The incidence of enlarged renal pelvis was similar when cocaine was administered as one or two but was decreased when cocaine was administered as three treatments. Both the route and split-dose studies suggest that high-peak serum concentrations are required to perturb development. There were no differences in the incidence or severity of enlarged renal pelvis when cocaine was administered on Day 8, 9, or 10 or on all 3 days of gestation. This suggested that the increase in enlarged renal pelvis may not be a specific teratogenic effect of cocaine administration but may be a delay of normal development induced by cocaine exposure during this early period of organogenesis. To address this hypothesis, cocaine was administered on Day 9 using an ip route and the pups were allowed to be naturally born. In pups whose mothers received cocaine there was an increase in postnatal deaths and a trend toward a reduction in pup body weight/litter at Postnatal Day 21. However, when renal morphology was assessed on Postnatal Day 21 no abnormal kidneys were seen. This supports the hypothesis that enlarged renal pelvis produced by cocaine administration during early organogenesis represents a developmental delay and not a persistent teratogenic defect. These studies suggest that high peak cocaine concentrations are required to delay normal kidney morphogenesis in mice. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Hunter, E S AU - Kotch, L E AU - Cefalo, R C AU - Sadler, T W AD - Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 177 EP - 186 VL - 28 IS - 2 SN - 0272-0590, 0272-0590 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Injections, Intraperitoneal KW - Litter Size -- drug effects KW - Animals KW - Mice, Inbred ICR KW - Fetus -- drug effects KW - Kidney -- drug effects KW - Mice KW - Fetal Viability -- drug effects KW - Kidney -- abnormalities KW - Maternal Exposure KW - Pregnancy KW - Embryonic and Fetal Development -- drug effects KW - Body Weight -- drug effects KW - Animals, Newborn -- growth & development KW - Fetus -- abnormalities KW - Fetal Death -- chemically induced KW - Embryo, Mammalian -- drug effects KW - Male KW - Female KW - Prenatal Exposure Delayed Effects KW - Narcotics -- toxicity KW - Narcotics -- administration & dosage KW - Cocaine -- toxicity KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75503189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Effects+of+cocaine+administration+during+early+organogenesis+on+prenatal+development+and+postnatal+growth+in+mice.&rft.au=Hunter%2C+E+S%3BKotch%2C+L+E%3BCefalo%2C+R+C%3BSadler%2C+T+W&rft.aulast=Hunter&rft.aufirst=E&rft.date=1995-12-01&rft.volume=28&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality among drug users in the AIDS era. AN - 75493831; 8824864 AB - Infection with human immunodeficiency virus type 1 (HIV-1) causes progressive immune deficiency, the acquired immunodeficiency syndrome (AIDS), and death. Mortality, however, particularly with causes other than AIDS, deserves further study. A retrospective cohort study among drug users in Italy was performed to estimated absolute and proportional mortality rates due to AIDS and other causes, with or without HIV-1 infection. All subjects who enrolled between January 1980 and July 1990 in the drug treatment programme in the Province of Bologna, Italy, were included in the cohort. Each subject was categorized for HIV-1 antibody status (positive, negative, untested), vital status (in 1990 by national surveillance), and causes of death (by death certificate). Data were analysed with actuarial and time-dependent covariate methods. There were 332 deaths among 4962 drug users who were followed for 21,130 person-years. This mortality rate (1.57 per 100 person-years) was increased 18-fold compared to the general population. Actuarial 10-year mortality estimates were 28.2% for the 2040 HIV-1 positive subjects, 12.1% for the 1859 HIV-1 untested subjects, and 2.5% for the 1063 HIV-1 negative subjects. AIDS contributed to 150 deaths, followed by drug overdose (64 deaths) and trauma (39 deaths). Compared to others in the cohort, mortality with AIDS and non-AIDS causes was reduced for HIV-1 negative subjects. In contrast, mortality for HIV-1 positive subjects was increased with AIDS, trauma, overdose, various bacterial infections, hepatitis, and cirrhosis. Mortality with HIV-1 infection was associated not only with opportunistic infections and malignancies but also with competing causes of death, particularly hepatic disease. Further investigation is needed to clarify whether alcohol, analgesics, hepatitis viruses, or other agents have enhanced hepatotoxicity for HIV-1 infected patients. JF - International journal of epidemiology AU - Goedert, J J AU - Pizza, G AU - Gritti, F M AU - Costigliola, P AU - Boschini, A AU - Bini, A AU - Lazzari, C AU - Palareti, A AD - AIDS and Cancer Section, Viral Epidemiology Branch, National Cancer Institute, Rockville, MD 20852, USA. Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 1204 EP - 1210 VL - 24 IS - 6 SN - 0300-5771, 0300-5771 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adult KW - Italy -- epidemiology KW - HIV Seropositivity -- epidemiology KW - Male KW - Female KW - Acquired Immunodeficiency Syndrome -- complications KW - Substance-Related Disorders -- mortality KW - Substance-Related Disorders -- complications KW - Acquired Immunodeficiency Syndrome -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75493831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+epidemiology&rft.atitle=Mortality+among+drug+users+in+the+AIDS+era.&rft.au=Goedert%2C+J+J%3BPizza%2C+G%3BGritti%2C+F+M%3BCostigliola%2C+P%3BBoschini%2C+A%3BBini%2C+A%3BLazzari%2C+C%3BPalareti%2C+A&rft.aulast=Goedert&rft.aufirst=J&rft.date=1995-12-01&rft.volume=24&rft.issue=6&rft.spage=1204&rft.isbn=&rft.btitle=&rft.title=International+journal+of+epidemiology&rft.issn=03005771&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-13 N1 - Date created - 1996-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Note bibliografiche sui conoidi alluvionali nelle Alpi italiane TT - A bibliography on alluvial fans in the Italian Alps AN - 51044054; 1998-041641 JF - GEAM. Geoingegneria Ambientale e Mineraria AU - Marchi, L AU - Tecca, P R Y1 - 1995/12// PY - 1995 DA - December 1995 SP - 225 EP - 231 PB - Associazione Mineraria Subalpina, Turin VL - 32 IS - 4 SN - 1121-9041, 1121-9041 KW - Alps KW - alluvial fans KW - fluvial features KW - Europe KW - Italy KW - bibliography KW - Southern Europe KW - 23:Geomorphology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51044054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=GEAM.+Geoingegneria+Ambientale+e+Mineraria&rft.atitle=Note+bibliografiche+sui+conoidi+alluvionali+nelle+Alpi+italiane&rft.au=Marchi%2C+L%3BTecca%2C+P+R&rft.aulast=Marchi&rft.aufirst=L&rft.date=1995-12-01&rft.volume=32&rft.issue=4&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=GEAM.+Geoingegneria+Ambientale+e+Mineraria&rft.issn=11219041&rft_id=info:doi/ LA - Italian DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1998-01-01 N1 - Number of references - 41 N1 - Document feature - illus. incl. 1 table N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - alluvial fans; Alps; bibliography; Europe; fluvial features; Italy; Southern Europe ER - TY - JOUR T1 - Genome evolution comes of age. AN - 1859120000; 8791475 JF - Current opinion in genetics & development AU - Hartl AU - Kafatos AU - O'Brien AD - Daniel L Hartl, Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA. Fotis C Kafatos, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. Stephen J O'Brien, Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 1995/12/01/ PY - 1995 DA - 1995 Dec 01 SP - 705 EP - 708 VL - 5 IS - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859120000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+genetics+%26+development&rft.atitle=Genome+evolution+comes+of+age.&rft.au=Hartl%3BKafatos%3BO%27Brien&rft.aulast=Hartl&rft.aufirst=&rft.date=1995-12-01&rft.volume=5&rft.issue=6&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+genetics+%26+development&rft.issn=1879-0380&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 1996-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Experimental studies on the long-term effects of methylphenidate hydrochloride. AN - 77783158; 8545847 AB - Toxicology and carcinogenesis studies of methylphenidate hydrochloride, a drug used in the treatment of attention-deficient disorders, were performed in F344 rats and B6C3F1 mice. In these studies, methylphenidate hydrochloride was administered for 2 years at doses of 0, 100, 500 or 1000 ppm in the feed to rats and at doses of 0, 50, 250, 500 ppm to mice in groups that consisted of 50 animals/dose/sex/species. The average amount of methylphenidate consumed per day was estimated to be 4-47 mg/kg/day for rats and 5-67 mg/kg/day for mice. Survival was similar in dosed and control groups. An increase in benign tumors of the liver and increased liver weights were observed in male and female mice at the high dose. An increase in hepatoblastomas was also seen in high dose male mice. Methylphenidate was not mutagenic in the Salmonella assay system, and it is hypothesized that this tumorigenic effect might be due to nongenotoxic effects of the chemical such as an increase in cell proliferation. Increased incidences of neoplasms were not seen in rats. However, there was a notable decrease in mammary gland fibroadenomas in female rats and a marginal decrease in benign pheochromocytomas in male rats. Epidemiology studies of methylphenidate have found no evidence of a carcinogenic effect in humans and like our findings in rats, report a less than expected rate of cancers in patients taking methylphenidate. JF - Toxicology AU - Dunnick, J K AU - Hailey, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/11/30/ PY - 1995 DA - 1995 Nov 30 SP - 77 EP - 84 VL - 103 IS - 2 SN - 0300-483X, 0300-483X KW - Dopamine Agents KW - 0 KW - Methylphenidate KW - 207ZZ9QZ49 KW - Index Medicus KW - Animals KW - Pheochromocytoma -- mortality KW - Mammary Glands, Animal KW - Pheochromocytoma -- chemically induced KW - Hepatoblastoma -- mortality KW - Hepatoblastoma -- chemically induced KW - Rats KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Male KW - Organ Size -- drug effects KW - Administration, Oral KW - Sex Factors KW - Fibroadenoma -- chemically induced KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Mice KW - Adenoma, Liver Cell -- chemically induced KW - Longitudinal Studies KW - Mutagenicity Tests KW - Fibroadenoma -- mortality KW - Adenoma, Liver Cell -- mortality KW - Body Weight -- drug effects KW - Female KW - Carcinoma, Hepatocellular -- mortality KW - Carcinoma, Hepatocellular -- chemically induced KW - Dopamine Agents -- toxicity KW - Methylphenidate -- administration & dosage KW - Liver Neoplasms -- mortality KW - Liver Neoplasms -- chemically induced KW - Adrenal Gland Neoplasms -- chemically induced KW - Methylphenidate -- toxicity KW - Mammary Neoplasms, Animal -- chemically induced KW - Mammary Neoplasms, Animal -- mortality KW - Adrenal Gland Neoplasms -- mortality KW - Dopamine Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77783158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Experimental+studies+on+the+long-term+effects+of+methylphenidate+hydrochloride.&rft.au=Dunnick%2C+J+K%3BHailey%2C+J+R&rft.aulast=Dunnick&rft.aufirst=J&rft.date=1995-11-30&rft.volume=103&rft.issue=2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-12 N1 - Date created - 1996-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory and non-inhibitory monoclonal antibodies to human cytochrome P450 3A3/4. AN - 77772152; 8615863 AB - Cytochromes P450 3A3/4 are inordinately important P450 enzymes catalyzing the metabolism of a large variety of clinically useful drugs, steroids, and carcinogens. Two monoclonal antibodies, MAb 3-29-9 and MAb 275-1-2, were prepared to human P450 3A4 from mice immunized with baculovirus-expressed human P450 3A4. MAb 3-29-9 was a powerful inhibitor of the enzymatic activity of P450 3A3/4/5. MAb 3-29-9 inhibited the P450 3A3, 3A4, and 3A5 catalyzed metabolism of substrates of divergent molecular weights, e.g., p-nitroanisole, phenanthrene, diazepam, testosterone, taxol, and cyclosporin. However, MAb 3-29-9 did not give a western blot with P450 3A3 or 3A4. MAb 275-1-2 was non-inhibitory but yielded a strong western blot with P450 3A3 and 3A4 but not with 3A5, and thus distinguished between 3A3/4 and 3A5. The two MAbs did not cross-react with human 2E1, 1A2, 2B6, 2C8, and 2C9; rat 2A1, 3A1/2, 4A1, 4A3, and 2B1; and mouse 1A1 and 1A2. MAb 3-29-9 has been used successfully to measure the quantitative contribution of P450 3A3 and 3A4 to the metabolism of the above-designated substrates in human adult liver. MAb 3-29-9 and MAb 275-1-2 are precise and sensitive reagents for P450 3A studies. JF - Biochemical pharmacology AU - Gelboin, H V AU - Krausz, K W AU - Goldfarb, I AU - Buters, J T AU - Yang, S K AU - Gonzalez, F J AU - Korzekwa, K R AU - Shou, M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/11/27/ PY - 1995 DA - 1995 Nov 27 SP - 1841 EP - 1850 VL - 50 IS - 11 SN - 0006-2952, 0006-2952 KW - Anisoles KW - 0 KW - Antibodies, Monoclonal KW - Cytochrome P-450 Enzyme Inhibitors KW - Enzyme Inhibitors KW - Indicators and Reagents KW - Recombinant Proteins KW - Testosterone KW - 3XMK78S47O KW - Cyclosporine KW - 83HN0GTJ6D KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - 4-nitroanisole KW - G989Z7WOLH KW - Paclitaxel KW - P88XT4IS4D KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Liver -- enzymology KW - Diazepam -- metabolism KW - Testosterone -- metabolism KW - Humans KW - Cyclosporine -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cross Reactions KW - Blotting, Western KW - Paclitaxel -- metabolism KW - Cytochrome P-450 Enzyme System -- immunology KW - Anisoles -- metabolism KW - Recombinant Proteins -- antagonists & inhibitors KW - Mixed Function Oxygenases -- immunology KW - Mixed Function Oxygenases -- metabolism KW - Mixed Function Oxygenases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77772152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Inhibitory+and+non-inhibitory+monoclonal+antibodies+to+human+cytochrome+P450+3A3%2F4.&rft.au=Gelboin%2C+H+V%3BKrausz%2C+K+W%3BGoldfarb%2C+I%3BButers%2C+J+T%3BYang%2C+S+K%3BGonzalez%2C+F+J%3BKorzekwa%2C+K+R%3BShou%2C+M&rft.aulast=Gelboin&rft.aufirst=H&rft.date=1995-11-27&rft.volume=50&rft.issue=11&rft.spage=1841&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-06 N1 - Date created - 1996-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An anti-CD3 single-chain immunotoxin with a truncated diphtheria toxin avoids inhibition by pre-existing antibodies in human blood. AN - 77696045; 7499288 AB - Diphtheria toxin (DT) is often used in the construction of immunotoxins. One potential problem using DT-based immunotoxins is the pre-existing anti-DT antibodies present in human blood due to vaccination. The present study examined the effect of human serum with pre-existing anti-DT antibodies on the toxicity of UCHT1-CRM9, an immunotoxin directed against CD3 molecules on T-lymphocytes. Sera with detectable anti-DT antibodies at 1:100 or greater dilutions inhibited the immunotoxin toxicity. Experiments with radio-labeled UCHT1-CRM9 indicate that anti-DT antibodies partially block its binding to the cell surface as well as inhibit the translocation from the endosome to the cytosol. The inhibitory effect could be adsorbed using a full-length DT mutant or B-subfragment. A C-terminal truncation mutant could not adsorb the inhibitory effect, suggesting that the last 150 amino acids contain the epitope(s) recognized by the inhibitory antibodies. Therefore, an anti-CD3 single-chain immunotoxin, sFv-DT390, was made with a truncated DT. The IC50 of sFv-DT390 was 4.8 x 10(-11) M, 1/16 the potency of the divalent UCHT1-CRM9. More importantly, sFv-DT390 toxicity was only slightly affected by the anti-DT antibodies in human sera. JF - The Journal of biological chemistry AU - Thompson, J AU - Hu, H AU - Scharff, J AU - Neville, D M AD - Section on Biophysical Chemistry, National Institute of Mental Health, Bethesda, Maryland 28092-4034, USA. Y1 - 1995/11/24/ PY - 1995 DA - 1995 Nov 24 SP - 28037 EP - 28041 VL - 270 IS - 47 SN - 0021-9258, 0021-9258 KW - Antibodies, Bacterial KW - 0 KW - Antigens, CD3 KW - Diphtheria Toxin KW - Epitopes KW - Immunotoxins KW - Recombinant Proteins KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Cytosol -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Endosomes -- metabolism KW - Vaccination KW - Recombinant Proteins -- toxicity KW - Mutagenesis, Site-Directed KW - Epitopes -- analysis KW - Kinetics KW - Leucine -- metabolism KW - Endocytosis -- drug effects KW - Point Mutation KW - Recombinant Proteins -- immunology KW - Cell Line KW - Antigens, CD3 -- immunology KW - Protein Biosynthesis -- drug effects KW - Immunotoxins -- toxicity KW - Diphtheria Toxin -- immunology KW - Immunotoxins -- immunology KW - Diphtheria Toxin -- toxicity KW - Antibodies, Bacterial -- immunology KW - Antibodies, Bacterial -- blood KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77696045?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=An+anti-CD3+single-chain+immunotoxin+with+a+truncated+diphtheria+toxin+avoids+inhibition+by+pre-existing+antibodies+in+human+blood.&rft.au=Thompson%2C+J%3BHu%2C+H%3BScharff%2C+J%3BNeville%2C+D+M&rft.aulast=Thompson&rft.aufirst=J&rft.date=1995-11-24&rft.volume=270&rft.issue=47&rft.spage=28037&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-17 N1 - Date created - 1996-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence-specific RNA recognition by the Xenopus Y-box proteins. An essential role for the cold shock domain. AN - 77690876; 7499328 AB - The Xenopus Y-box protein FRGY2 has a role in the translational silencing of masked maternal mRNA. Here, we determine that FRGY2 will recognize specific RNA sequences. The evolutionarily conserved nucleic acid-binding cold shock domain is required for sequence-specific interactions with RNA. However, RNA binding by FRGY2 is facilitated by N- and C-terminal regions flanking the cold shock domain. The hydrophilic C-terminal tail domain of FRGY2 interacts with RNA independent of the cold shock domain but does not determine sequence specificity. Thus, both sequence-specific and nonspecific RNA recognition domains are contained within the FRGY2 protein. JF - The Journal of biological chemistry AU - Bouvet, P AU - Matsumoto, K AU - Wolffe, A P AD - Laboratory of Molecular Embryology, NICHID, National Institutes of Health, Bethesda, Maryland 20892-2710, USA. Y1 - 1995/11/24/ PY - 1995 DA - 1995 Nov 24 SP - 28297 EP - 28303 VL - 270 IS - 47 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - FRGY2 protein, Xenopus KW - RNA-Binding Proteins KW - Recombinant Fusion Proteins KW - Transcription Factors KW - Xenopus Proteins KW - RNA KW - 63231-63-0 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Biological Evolution KW - Amino Acid Sequence KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Xenopus laevis KW - Polymerase Chain Reaction KW - Base Sequence KW - Conserved Sequence KW - RNA -- metabolism KW - Glutathione Transferase -- biosynthesis KW - Molecular Sequence Data KW - Point Mutation KW - RNA -- chemistry KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - RNA-Binding Proteins -- biosynthesis KW - RNA-Binding Proteins -- metabolism KW - Transcription Factors -- metabolism KW - Transcription Factors -- chemistry KW - RNA-Binding Proteins -- chemistry KW - Transcription Factors -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77690876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Sequence-specific+RNA+recognition+by+the+Xenopus+Y-box+proteins.+An+essential+role+for+the+cold+shock+domain.&rft.au=Bouvet%2C+P%3BMatsumoto%2C+K%3BWolffe%2C+A+P&rft.aulast=Bouvet&rft.aufirst=P&rft.date=1995-11-24&rft.volume=270&rft.issue=47&rft.spage=28297&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-17 N1 - Date created - 1996-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental changes in the inducibility of fos-like immunoreactivity in primary embryonic spinal cord cultures. AN - 77819482; 8612322 AB - The immediate early gene (IEG) transcription factor c-fos coordinates changes in the pattern of long term gene expression and, therefore, it may be involved in mediating epigenetic control during neurodevelopment. We used pharmacological treatments mimicking various environmental and intracellular signals and assessed the inducibility of fos-like immunoreactivity (LIR) at various stages of neurodifferentiation in a primary embryonic spinal cord culture system by immunohistochemistry. Constitutive fos LIR exclusively found in neurons, was driven by the onset and extent of spontaneous electrical activity, as it was blockable by tetrodotoxin (TTX) at all developmental stages. Phorbol myristate 13 acetate (PMA) increased the number of fos-LIR cells equally effectively at all stages, but the predominant cellular localization of fos-LIR changed through ontogeny. The effect of veratridine, kainate and serum-derived factors in significantly inducing fos-LIR was restricted to the earliest developmental stage (4 days in vitro; DIV) investigated; whereas forskolin, the GABAA antagonist picrotoxin and NMDA failed to induce fos-LIR at this stage, but increased the number of fos-LIR neurons at later stages. Dihydropyridine agonists of the voltage-sensitive calcium channels (VSCC) raised the number of fos-LIR neurons and also prevented TTX-mediated down-regulation; whereas antagonists markedly reduced fos-LIR at all ages. Either type of NMDA antagonists (AP5 and MK801) and the GABAA agonist muscimol significantly reduced fos-LIR at all ages. These findings demonstrate that the inducibility of fos-LIR is substantially different in embryonic neurons than in adult ones and that inducibility by various first and second messengers is dependent on the development stage. JF - Brain research. Developmental brain research AU - von Agoston, D AU - Palkovits, C G AU - Fitzgerald, S F AU - Brenneman, D E AD - National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA. vagoston@helix.nih.gov Y1 - 1995/11/21/ PY - 1995 DA - 1995 Nov 21 SP - 173 EP - 186 VL - 89 IS - 2 SN - 0165-3806, 0165-3806 KW - Proto-Oncogene Proteins c-fos KW - 0 KW - Tetrodotoxin KW - 4368-28-9 KW - Index Medicus KW - Animals KW - Second Messenger Systems KW - Neurons -- metabolism KW - Cell Differentiation -- physiology KW - Cells, Cultured KW - Neurons -- drug effects KW - Mice, Inbred C57BL KW - Embryonic and Fetal Development -- physiology KW - Mice KW - Membrane Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - Immunoenzyme Techniques KW - Ganglia, Spinal -- cytology KW - Gene Expression Regulation, Developmental -- physiology KW - Proto-Oncogene Proteins c-fos -- analysis KW - Ganglia, Spinal -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77819482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Developmental+brain+research&rft.atitle=Developmental+changes+in+the+inducibility+of+fos-like+immunoreactivity+in+primary+embryonic+spinal+cord+cultures.&rft.au=von+Agoston%2C+D%3BPalkovits%2C+C+G%3BFitzgerald%2C+S+F%3BBrenneman%2C+D+E&rft.aulast=von+Agoston&rft.aufirst=D&rft.date=1995-11-21&rft.volume=89&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-05 N1 - Date created - 1996-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA. AN - 77688336; 7478510 AB - We have previously shown (Smith et al., 1994) that antibodies raised against the growth arrest and DNA damage inducible protein Gadd45 co-precipitate proliferating cell nuclear antigen (PCNA), a protein involved in DNA replication and repair. Here we demonstrate that Gadd45 can directly bind to PCNA using a Far-western blotting approach. In this assay, a Gadd45 bacterial expression vector was modified to allow synthesis of purified 32P-labeled Gadd45 fusion protein. This protein was used to detect filter bound PCNA protein, while filter bound Gadd45 protein could also be detected by free PCNA molecules. Using recombinant proteins in conjunction with immunoprecipitation and immunoblotting, we show that Gadd45 competes with p21 for binding to PCNA and conversely, p21 blocks the ability of Gadd45 to bind PCNA. In addition, p21 appears to disrupt PCNA trimers whereas Gadd45 has a lesser effect. PCNA trimer disruption was also observed in UV-irradiated cells but not in repair-defective xeroderma pigmentosum group A (XP-A) cells. JF - Oncogene AU - Chen, I T AU - Smith, M L AU - O'Connor, P M AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/11/16/ PY - 1995 DA - 1995 Nov 16 SP - 1931 EP - 1937 VL - 11 IS - 10 SN - 0950-9232, 0950-9232 KW - CDKN1A protein, human KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Macromolecular Substances KW - Proliferating Cell Nuclear Antigen KW - Proteins KW - Recombinant Proteins KW - Index Medicus KW - Ultraviolet Rays KW - Drug Interactions KW - DNA Damage KW - Humans KW - Blotting, Western -- methods KW - Fibroblasts -- metabolism KW - Tumor Cells, Cultured -- radiation effects KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Binding, Competitive KW - Molecular Sequence Data KW - Colonic Neoplasms -- metabolism KW - Fibroblasts -- radiation effects KW - Lung Neoplasms -- metabolism KW - Proteins -- pharmacology KW - Cyclins -- pharmacology KW - Proliferating Cell Nuclear Antigen -- drug effects KW - Cyclins -- metabolism KW - Proteins -- metabolism KW - Proliferating Cell Nuclear Antigen -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77688336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Direct+interaction+of+Gadd45+with+PCNA+and+evidence+for+competitive+interaction+of+Gadd45+and+p21Waf1%2FCip1+with+PCNA.&rft.au=Chen%2C+I+T%3BSmith%2C+M+L%3BO%27Connor%2C+P+M%3BFornace%2C+A+J&rft.aulast=Chen&rft.aufirst=I&rft.date=1995-11-16&rft.volume=11&rft.issue=10&rft.spage=1931&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The epidemiology of cervical carcinogenesis. AN - 77874441; 8634980 AB - Epidemiologic and laboratory data suggest that cervical cancer typically arises from a series of causal steps. Each step can be studied separately in the hope of better etiologic understanding and improved cancer prevention. The earliest identified etiologic step is infection of young women with specific types of venereally transmissible human papillomaviruses (HPVs). Cervical HPV infections often lead to low grade squamous intraepithelial lesions (mildly abnormal Pap smears). Human papillomavirus infections and their associated lesions are extremely common among young, sexually active women. The infections typically resolve spontaneously even at the molecular level within months to a few years. Uncommonly, HPV infections and/or low grade lesions persist and progress to high grade lesions. The risk factors for progression are mainly unknown but include HPV type and intensity, cell-mediated immunity, and reproductive factors. Nutritional factors or co-infection with other pathogens may also be involved at this apparently critical etiologic step between common low grade and uncommon high grade intraepithelial lesions. Except for advancing age, no epidemiologic risk factors have been found for the next step between high grade intraepithelial lesions and invasive cancer. At the molecular level, invasion is associated with integration of viral DNA. Based on worldwide research, the steps in cervical carcinogenesis appear to be fundamentally the same everywhere, with a central role for HPV infection. The importance of etiologic cofactors like smoking, however, may vary by region. JF - Cancer AU - Schiffman, M H AU - Brinton, L A AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Maryland 20892-7374, USA. Y1 - 1995/11/15/ PY - 1995 DA - 1995 Nov 15 SP - 1888 EP - 1901 VL - 76 IS - 10 Suppl SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - Risk Factors KW - Humans KW - Smoking -- adverse effects KW - Male KW - Female KW - Cervical Intraepithelial Neoplasia -- etiology KW - Uterine Cervical Neoplasms -- etiology KW - Tumor Virus Infections -- etiology KW - Papillomavirus Infections -- etiology KW - Papillomaviridae UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77874441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=The+epidemiology+of+cervical+carcinogenesis.&rft.au=Schiffman%2C+M+H%3BBrinton%2C+L+A&rft.aulast=Schiffman&rft.aufirst=M&rft.date=1995-11-15&rft.volume=76&rft.issue=10+Suppl&rft.spage=1888&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-09 N1 - Date created - 1996-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaccines in the treatment of cancer. AN - 77817255; 8590245 AB - The development of vaccines for treating cancer is discussed. The central hypothesis behind active specific immunotherapy for cancer is that tumor cells express unique antigens that tell the immune system that something about these cells is foreign. A vaccine is a way of delivering an antigen to the immune system such that immune cells recognize the antigen as foreign and destroy any cells bearing that antigen. Early trials of vaccines for treating cancer were limited by technical problems related to poor knowledge of the immune system. Recent research has focused on expression on the surfaces of antigen-presenting cells of antigenic peptides bound to major histocompatibility complex (MHC) molecules, peptide recognition by cytotoxic T cells, and the requirement for a second signal, such as the costimulatory molecule B7, for T-cell activation. Antigenic peptides constitute the "keys" that open the "locks" of T cells; the problem is that researchers have difficulty choosing the right keys from among the myriad available. Administering an adjuvant enhances the immune response by making the antigen more recognizable as foreign. Vaccine preparation techniques include peptide pulsing (a method for bosting cell-surface expression of the antigenic peptide-MHC combinations), intramuscular injections of DNA plasmids encoding the desired antigen, and gene insertion into vaccinia virus by recombinant DNA technology. Cancer vaccines may be administered by scarification, by subcutaneous and intramuscular injection, and intranasally. Clinical trials of cancer vaccines continue to encounter problems because of the many variables in administration routes, dosages, patient populations, and methods for evaluating responses. There have been some promising results but also many treatment failures. Antigen targets in trials today include normal antigens that have a limited normal-tissue distribution or expression (e.g., carcinoembryonic antigen), viral proteins (e.g., E6 protein of human papillomavirus), and mutated oncogenes. Toxicities have been mild. Better understanding of the immune system and better technology have led to advances in the development of vaccines for treating cancer, but there is still much progress to achieve. JF - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists AU - Baltz, J K AD - National Cancer Institute, Rockville, MD 20852, USA. Y1 - 1995/11/15/ PY - 1995 DA - 1995 Nov 15 SP - 2574 EP - 85; quiz 2594-5 VL - 52 IS - 22 SN - 1079-2082, 1079-2082 KW - Antibodies, Neoplasm KW - 0 KW - Antigens, Neoplasm KW - Vaccines, Synthetic KW - Index Medicus KW - Vaccination -- methods KW - Humans KW - Clinical Trials as Topic KW - Antibodies, Neoplasm -- immunology KW - B-Lymphocytes -- immunology KW - Antigens, Neoplasm -- immunology KW - T-Lymphocytes -- immunology KW - Immunotherapy KW - Vaccines, Synthetic -- immunology KW - Neoplasms -- therapy KW - Vaccines, Synthetic -- pharmacology KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77817255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+health-system+pharmacy+%3A+AJHP+%3A+official+journal+of+the+American+Society+of+Health-System+Pharmacists&rft.atitle=Vaccines+in+the+treatment+of+cancer.&rft.au=Baltz%2C+J+K&rft.aulast=Baltz&rft.aufirst=J&rft.date=1995-11-15&rft.volume=52&rft.issue=22&rft.spage=2574&rft.isbn=&rft.btitle=&rft.title=American+journal+of+health-system+pharmacy+%3A+AJHP+%3A+official+journal+of+the+American+Society+of+Health-System+Pharmacists&rft.issn=10792082&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-27 N1 - Date created - 1996-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identifying substance abuse in primary care. AN - 77677648; 7484704 AB - Family physicians have an opportunity to identify substance abusers years before they have medical complications or present for drug treatment. Occult substance abuse can be effectively identified by simple screening questions and careful attention to clinical indicators during the history and physical examination. Early intervention may have dramatic effects on substance-abusing behavior and may prevent the many adverse medical, psychologic and social effects of substance abuse in these patients. JF - American family physician AU - Haverkos, H W AU - Stein, M D AD - National Institute on Drug Abuse, Rockville, Maryland, USA. Y1 - 1995/11/15/ PY - 1995 DA - 1995 Nov 15 SP - 2029 EP - 2035 VL - 52 IS - 7 SN - 0002-838X, 0002-838X KW - Abridged Index Medicus KW - Index Medicus KW - Family Practice KW - Humans KW - Physician's Role KW - United States -- epidemiology KW - Prevalence KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- diagnosis KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77677648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+family+physician&rft.atitle=Identifying+substance+abuse+in+primary+care.&rft.au=Haverkos%2C+H+W%3BStein%2C+M+D&rft.aulast=Haverkos&rft.aufirst=H&rft.date=1995-11-15&rft.volume=52&rft.issue=7&rft.spage=2029&rft.isbn=&rft.btitle=&rft.title=American+family+physician&rft.issn=0002838X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-21 N1 - Date created - 1995-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polymorphism in the N-acetyltransferase 1 (NAT1) polyadenylation signal: association of NAT1*10 allele with higher N-acetylation activity in bladder and colon tissue. AN - 77672482; 7585580 AB - Exposures to carcinogens present in the diet, in cigarette smoke, or in the environment have been associated with increased risk of bladder and colorectal cancer. The aromatic amines and their metabolites, a class of carcinogen implicated in these exposures, can be N- or O-acetylated by the NAT1 and NAT2 enzymes. Acetylation may result in activation to DNA-reactive metabolites or, in some cases, detoxification. Many studies have focused on genetic variation in NAT2 and its potential as a risk factor in bladder and colorectal cancer; however, NAT1 activity is higher in bladder and colonic mucosa than NAT2, and the NAT1 enzyme also exhibits phenotypic variation among human tissue samples. We hypothesized that specific genetic variants in the polyadenylation signal of the NAT1 gene would alter tissue levels of NAT1 enzyme activity and used a PCR-based method to distinguish polymorphic NAT1 alleles in samples obtained from 45 individuals. When the NAT1 genotype was compared with the NAT1 phenotype in bladder and colon tissue samples (p-aminobenzoic acid activity), we observed a approximately 2-fold higher NAT1 enzyme activity in samples from individuals who inherited a variant polyadenylation signal (NAT1*10 allele). This is the first observation relating a genetic polymorphism in NAT1 to a rapid/slow NAT1 phenotype in humans. JF - Cancer research AU - Bell, D A AU - Badawi, A F AU - Lang, N P AU - Ilett, K F AU - Kadlubar, F F AU - Hirvonen, A AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/11/15/ PY - 1995 DA - 1995 Nov 15 SP - 5226 EP - 5229 VL - 55 IS - 22 SN - 0008-5472, 0008-5472 KW - Poly A KW - 24937-83-5 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - NAT2 protein, human KW - Index Medicus KW - Acetylation KW - Base Sequence KW - Alleles KW - Humans KW - Molecular Sequence Data KW - Polymorphism, Genetic KW - Colon -- enzymology KW - Urinary Bladder -- enzymology KW - Poly A -- metabolism KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77672482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Polymorphism+in+the+N-acetyltransferase+1+%28NAT1%29+polyadenylation+signal%3A+association+of+NAT1*10+allele+with+higher+N-acetylation+activity+in+bladder+and+colon+tissue.&rft.au=Bell%2C+D+A%3BBadawi%2C+A+F%3BLang%2C+N+P%3BIlett%2C+K+F%3BKadlubar%2C+F+F%3BHirvonen%2C+A&rft.aulast=Bell&rft.aufirst=D&rft.date=1995-11-15&rft.volume=55&rft.issue=22&rft.spage=5226&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-15 N1 - Date created - 1995-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renal tubular tumors and atypical hyperplasias in B6C3F1 mice exposed to lead acetate during gestation and lactation occur with minimal chronic nephropathy. AN - 77670983; 7585586 AB - Lead is a high-priority hazardous substance in humans and a renal carcinogen in adult rodents. This study assessed the carcinogenic potential and toxicity of gestational and lactational lead exposure in (C57BL/6NCr x C3H/HeN)F1 (hereafter called B6C3F1) mice. Effects of a renal tumor promoter [barbital sodium (BB)] on lead-initiated lesions were also studied. Pregnant female C57BL/6NCr mice (10-15/group) previously bred with C3H/HeN males were given lead acetate (0, 500, 750 and 1000 ppm lead) ad libitum in their drinking water, starting on gestation day 12 and continuing to 4 weeks postpartum. Offspring were then weaned and divided into same-sex groups of 23-25 and observed for a maximum of 112 weeks. Other groups received lead and then continuous BB (500 ppm) ad libitum in their drinking water from weaning onward. In control male offspring (0 lead/0 BB), renal proliferative lesions [(RPLs); defined as atypical tubular hyperplasia or tumor] occurred rarely (1 lesion-bearing mouse/23 mice examined, 4%) and did not include tumors. RPLs increased in a dose-related fashion with lead exposure (500 lead/0 BB, 4/25, 16%; 750 lead/0 BB, 6/25, 24%; 1000 lead/0 BB, 12/25, 48%) in male offspring and were often multiple. All lead-treated groups had renal tumors, including carcinoma, but these were most common at the highest dose (1000 lead/0 BB, 5/25). Lead-induced renal tumors arose in the absence of the extensive chronic nephropathy and lead inclusion bodies typically seen with lead carcinogenesis in rodents exposed chronically as adults. Postnatal BB exposure had no effect on RPL incidence (e.g., 1000 lead/500 BB, 8/25, 32%). Lead-treated female offspring also developed RPLs, including adenoma and carcinoma, but at a much lower rate than males. Thus, short-term lead exposure during the gestational/lactational period has carcinogenic potential in the mouse kidney. JF - Cancer research AU - Waalkes, M P AU - Diwan, B A AU - Ward, J M AU - Devor, D E AU - Goyer, R A AD - Inorganic Carcinogenesis Section, Science Applications International Corporation-Frederick, National Cancer Institute, Maryland 21702-1201, USA. Y1 - 1995/11/15/ PY - 1995 DA - 1995 Nov 15 SP - 5265 EP - 5271 VL - 55 IS - 22 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Organometallic Compounds KW - Barbital KW - 5WZ53ENE2P KW - lead acetate KW - RX077P88RY KW - Index Medicus KW - Animals KW - Hyperplasia KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Mice KW - Chronic Disease KW - Barbital -- toxicity KW - Male KW - Female KW - Pregnancy KW - Lactation KW - Fetus -- drug effects KW - Kidney Tubules -- pathology KW - Kidney Tubules -- drug effects KW - Kidney Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Organometallic Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77670983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Renal+tubular+tumors+and+atypical+hyperplasias+in+B6C3F1+mice+exposed+to+lead+acetate+during+gestation+and+lactation+occur+with+minimal+chronic+nephropathy.&rft.au=Waalkes%2C+M+P%3BDiwan%2C+B+A%3BWard%2C+J+M%3BDevor%2C+D+E%3BGoyer%2C+R+A&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1995-11-15&rft.volume=55&rft.issue=22&rft.spage=5265&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-15 N1 - Date created - 1995-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative carcinogenic effects of nickel subsulfide, nickel oxide, or nickel sulfate hexahydrate chronic exposures in the lung. AN - 77654693; 7585584 AB - The relative toxicity and carcinogenicity of nickel sulfate hexahydrate (NiSO4.6H2O), nickel subsulfide (Ni3S2), and nickel oxide (NiO) were studied in F344/N rats and B6C3F1 mice after inhalation exposure for 6 h/day, 5 days/week for 2 years. Nickel subsulfide (0.15 and 1 mg/m3) and nickel oxide (1.25 and 2.5 mg/m3) caused an exposure-related increased incidence of alveolar/bronchiolar neoplasms and adrenal medulla neoplasms in male and female rats. Nickel oxide caused an equivocal exposure-related increase in alveolar/bronchiolar neoplasms in female mice. No exposure-related neoplastic responses occurred in rats or mice exposed to nickel sulfate or in mice exposed to nickel subsulfide. These findings are consistent with results from other studies, which show that nickel subsulfide and nickel oxide reach the nucleus in greater amounts than the do water-soluble nickel compounds such as nickel sulfate. It has been proposed that the more water-insoluble particles are phagocytized, whereas the vacuoles containing nickel migrate to the nuclear membrane, where they release nickel ions that effect DNA damage. The findings from these experimental studies show that chronic exposure to nickel can cause lung neoplasms in rats, and that this response is related to exposure to specific types of nickel compounds. JF - Cancer research AU - Dunnick, J K AU - Elwell, M R AU - Radovsky, A E AU - Benson, J M AU - Hahn, F F AU - Nikula, K J AU - Barr, E B AU - Hobbs, C H AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/11/15/ PY - 1995 DA - 1995 Nov 15 SP - 5251 EP - 5256 VL - 55 IS - 22 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - nickel subsulfide KW - 12035-72-2 KW - nickel sulfate KW - 4FLT4T3WUN KW - Nickel KW - 7OV03QG267 KW - nickel monoxide KW - C3574QBZ3Y KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Body Burden KW - Body Weight -- drug effects KW - Mice KW - Male KW - Female KW - Organ Size -- drug effects KW - Nickel -- pharmacokinetics KW - Carcinogens -- toxicity KW - Nickel -- toxicity KW - Lung Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77654693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Comparative+carcinogenic+effects+of+nickel+subsulfide%2C+nickel+oxide%2C+or+nickel+sulfate+hexahydrate+chronic+exposures+in+the+lung.&rft.au=Dunnick%2C+J+K%3BElwell%2C+M+R%3BRadovsky%2C+A+E%3BBenson%2C+J+M%3BHahn%2C+F+F%3BNikula%2C+K+J%3BBarr%2C+E+B%3BHobbs%2C+C+H&rft.aulast=Dunnick&rft.aufirst=J&rft.date=1995-11-15&rft.volume=55&rft.issue=22&rft.spage=5251&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-15 N1 - Date created - 1995-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human ribonuclease 4 (RNase 4): coding sequence, chromosomal localization and identification of two distinct transcripts in human somatic tissues. AN - 77728731; 7501448 AB - We have isolated a unique genomic fragment encoding human ribonuclease 4 (RNase 4) of the mammalian ribonuclease gene family, whose members include pancreatic ribonuclease, eosinophil-derived neurotoxin, eosinophil cationic protein and angiogenin. We have determined that the coding sequence of RNase 4 resides on a single exon found on human chromosome 14. The mRNA encoding RNase 4 was detected by Northern analysis in a number of human somatic tissues, including pancreas, lung, skeletal muscle, heart, kidney and placenta, but not brain; liver represents the most abundant source. Interestingly, the mRNA encoding RNase 4 is approximately 2 kb in length, which is approximately twice as large as the mRNAs encoding other members of this gene family. A larger (approximately 2.4 kb), second transcript was detected in hepatic, pancreatic and renal tissues. The approximately 2 kb RNase 4 mRNA was detected in cells of the human promyelocytic leukemia line, HL-60, that had been treated with dibutyryl-cAMP to promote neutrophilic differentiation. In contrast, no mRNA encoding RNase 4 could be detected in cells treated with phorbol myristic acid (PMA), an agent promoting differentiation toward monocyte/macrophages, suggesting the existence of elements regulating tissue specific expression of this gene. JF - Nucleic acids research AU - Rosenberg, H F AU - Dyer, K D AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/11/11/ PY - 1995 DA - 1995 Nov 11 SP - 4290 EP - 4295 VL - 23 IS - 21 SN - 0305-1048, 0305-1048 KW - RNA, Messenger KW - 0 KW - Ribonucleases KW - EC 3.1.- KW - ribonuclease 4 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Exons KW - Humans KW - Amino Acid Sequence KW - Tissue Distribution KW - Sequence Analysis, DNA KW - Chromosome Mapping KW - Polymerase Chain Reaction KW - Base Sequence KW - Gene Expression Regulation, Enzymologic KW - Tumor Cells, Cultured KW - Blotting, Southern KW - Hybrid Cells KW - Molecular Sequence Data KW - Cricetinae KW - Ribonucleases -- genetics KW - RNA, Messenger -- analysis KW - Chromosomes, Human, Pair 14 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77728731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Human+ribonuclease+4+%28RNase+4%29%3A+coding+sequence%2C+chromosomal+localization+and+identification+of+two+distinct+transcripts+in+human+somatic+tissues.&rft.au=Rosenberg%2C+H+F%3BDyer%2C+K+D&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1995-11-11&rft.volume=23&rft.issue=21&rft.spage=4290&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-17 N1 - Date created - 1996-01-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - X15161; GENBANK; U36775; M24157; X62946; M11567 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1989 Jun;86(12):4460-4 [2734298] Biochim Biophys Acta. 1995 Apr 26;1261(3):424-6 [7742370] Proc Natl Acad Sci U S A. 1989 Aug;86(16):6211-4 [2762324] Blood. 1979 Sep;54(3):713-33 [288488] Proc Natl Acad Sci U S A. 1985 Sep;82(18):6133-7 [2994062] Eur J Biochem. 1985 Oct 15;152(2):275-7 [3840434] Biochemistry. 1985 Sep 24;24(20):5494-9 [2866795] Proc Natl Acad Sci U S A. 1986 May;83(10):3146-50 [3458170] Biochemistry. 1986 Nov 18;25(23):7255-64 [3467790] Science. 1987 Jul 17;237(4812):280-2 [2440105] Biochem Biophys Res Commun. 1987 Aug 14;146(3):1240-8 [3619929] Blood. 1987 Nov;70(5):1233-44 [3311197] Biol Chem Hoppe Seyler. 1987 Oct;368(10):1305-12 [3426801] J Biochem. 1988 Aug;104(2):289-96 [3182769] Genomics. 1990 Aug;7(4):535-46 [2387583] Am J Hum Genet. 1990 Dec;47(6):973-81 [1978563] J Biol Chem. 1991 Jan 5;266(1):245-51 [1985896] Trends Biochem Sci. 1991 Mar;16(3):104-6 [2057997] Nucleic Acids Res. 1991 Dec 11;19(23):6469-74 [1754384] Nucleic Acids Res. 1992 Feb 11;20(3):612 [1741299] J Biol Chem. 1992 Oct 5;267(28):20392-9 [1400357] Biochemistry. 1993 Apr 27;32(16):4168-74 [7682842] Eur J Biochem. 1993 Oct 1;217(1):401-10 [8223579] Biosci Biotechnol Biochem. 1993 Dec;57(12):2133-8 [7764367] Eur J Biochem. 1995 May 15;230(1):242-9 [7601106] Nat Genet. 1995 Jun;10(2):219-23 [7663519] Cancer Res. 1994 Feb 15;54(4):920-7 [8313382] Protein Sci. 1994 Mar;3(3):459-66 [8019417] J Biol Chem. 1994 Oct 21;269(42):26381-9 [7929358] Biochem J. 1995 Feb 1;305 ( Pt 3):921-7 [7531438] J Biol Chem. 1995 May 5;270(18):10525-30 [7737987] J Biol Chem. 1995 May 5;270(18):10625-30 [7537735] J Exp Med. 1989 Jul 1;170(1):163-76 [2473157] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pneumocystis carinii in Africa: an emerging pathogen? AN - 77684660; 7475709 JF - Lancet (London, England) AU - Russian, D A AU - Kovacs, J A AD - Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA. Y1 - 1995/11/11/ PY - 1995 DA - 1995 Nov 11 SP - 1242 EP - 1243 VL - 346 IS - 8985 SN - 0140-6736, 0140-6736 KW - Abridged Index Medicus KW - Index Medicus KW - Population KW - AIDS/HIV KW - Viral Diseases KW - Acquired Immunodeficiency Syndrome KW - Respiratory Infections KW - Africa KW - Developing Countries KW - Diseases KW - Hiv Infections KW - Infections KW - Humans KW - Tuberculosis, Pulmonary -- diagnosis KW - Tuberculosis, Pulmonary -- drug therapy KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Pneumonia, Pneumocystis -- drug therapy KW - Pneumonia, Pneumocystis -- diagnosis KW - Pneumocystis -- isolation & purification KW - AIDS-Related Opportunistic Infections -- diagnosis KW - Pneumocystis -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77684660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Pneumocystis+carinii+in+Africa%3A+an+emerging+pathogen%3F&rft.au=Russian%2C+D+A%3BKovacs%2C+J+A&rft.aulast=Russian&rft.aufirst=D&rft.date=1995-11-11&rft.volume=346&rft.issue=8985&rft.spage=1242&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-15 N1 - Date created - 1995-12-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Lancet. 1995 Nov 11;346(8985):1258-61 [7475717] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Point mutation of the autophosphorylation site or in the nuclear location signal causes protein kinase A RII beta regulatory subunit to lose its ability to revert transformed fibroblasts. AN - 77658757; 7479855 AB - The RII beta regulatory subunit of cAMP-dependent protein kinase (PKA) contains an autophosphorylation site and a nuclear location signal, KKRK. We approached the structure-function analysis of RII beta by using site-directed mutagenesis. Ser114 (the autophosphorylation site) of human RII beta was replaced with Ala (RII beta-P) or Arg264 of KKRK was replaced with Met (RII beta-K). ras-transformed NIH 3T3 (DT) cells were transfected with expression vectors for RII beta, RII beta-P, and RII beta-K, and the effects on PKA isozyme distribution and transformation properties were analyzed. DT cells contained PKA-I and PKA-II isozymes in a 1:2 ratio. Over-expression of wild-type or mutant RII beta resulted in an increase in PKA-II and the elimination of PKA-I. Only wild-type RII beta cells demonstrated inhibition of both anchorage-dependent and -independent growth and phenotypic change. The growth inhibitory effect of RII beta overexpression was not due to suppression of ras expression but was correlated with nuclear accumulation of RII beta. DT cells demonstrated growth inhibition and phenotypic change upon treatment with 8-Cl-cAMP. RII beta-P or RII beta-K cells failed to respond to 8-Cl-cAMP. These data suggest that autophosphorylation and nuclear location signal sequences are integral parts of the growth regulatory mechanism of RII beta. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Budillon, A AU - Cereseto, A AU - Kondrashin, A AU - Nesterova, M AU - Merlo, G AU - Clair, T AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/11/07/ PY - 1995 DA - 1995 Nov 07 SP - 10634 EP - 10638 VL - 92 IS - 23 SN - 0027-8424, 0027-8424 KW - Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit KW - 0 KW - Isoenzymes KW - PRKAR2B protein, human KW - Protein Sorting Signals KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - 8-chloro-cyclic adenosine monophosphate KW - 41941-56-4 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - 8-Bromo Cyclic Adenosine Monophosphate -- analogs & derivatives KW - Cell Nucleus -- metabolism KW - Humans KW - Amino Acid Sequence KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Mutagenesis, Site-Directed KW - Genes, ras KW - Base Sequence KW - Phosphorylation KW - Cells, Cultured KW - Cell Compartmentation KW - Point Mutation KW - Molecular Sequence Data KW - Gene Expression Regulation, Neoplastic KW - Gene Expression Regulation, Enzymologic KW - Protein Sorting Signals -- genetics KW - Cyclic AMP-Dependent Protein Kinases -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77658757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Point+mutation+of+the+autophosphorylation+site+or+in+the+nuclear+location+signal+causes+protein+kinase+A+RII+beta+regulatory+subunit+to+lose+its+ability+to+revert+transformed+fibroblasts.&rft.au=Budillon%2C+A%3BCereseto%2C+A%3BKondrashin%2C+A%3BNesterova%2C+M%3BMerlo%2C+G%3BClair%2C+T%3BCho-Chung%2C+Y+S&rft.aulast=Budillon&rft.aufirst=A&rft.date=1995-11-07&rft.volume=92&rft.issue=23&rft.spage=10634&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-21 N1 - Date created - 1995-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1971 Apr 10;246(7):1986-95 [4324558] Exp Cell Res. 1956 Aug;11(2):317-21 [13375653] J Biol Chem. 1975 Jan 10;250(1):218-25 [166986] J Biol Chem. 1975 Oct 10;250(19):7788-94 [240840] J Biol Chem. 1975 Oct 10;250(19):7795-801 [170270] J Biol Chem. 1976 Jun 10;251(11):3375-80 [179996] Nature. 1976 Dec 16;264(5587):673-5 [187959] Annu Rev Biochem. 1979;48:923-59 [38740] J Cell Physiol. 1981 Aug;108(2):175-84 [6267082] J Virol. 1982 Jul;43(1):294-304 [6287003] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Proc Natl Acad Sci U S A. 1983 Sep;80(18):5602-6 [6604274] Biochemistry. 1984 Aug 28;23(18):4193-9 [6487597] Biochemistry. 1984 Aug 28;23(18):4200-6 [6386045] Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;18:63-117 [6093482] Cell. 1984 Dec;39(3 Pt 2):499-509 [6096007] J Biol Chem. 1985 May 25;260(10):6296-303 [2581952] Proc Natl Acad Sci U S A. 1985 Jul;82(14):4606-10 [2991882] Nature. 1985 Nov 7-13;318(6041):73-5 [4058592] J Biol Chem. 1986 Sep 15;261(26):12352-61 [2427518] J Biol Chem. 1986 Dec 15;261(35):16288-91 [3023347] FEBS Lett. 1987 Oct 19;223(1):97-103 [2822483] J Biol Chem. 1987 Dec 5;262(34):16566-74 [2824499] J Biol Chem. 1988 Jan 5;263(1):409-16 [2826444] J Biol Chem. 1988 Jul 5;263(19):9149-54 [3288630] FASEB J. 1988 Aug;2(11):2677-85 [3294077] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6319-22 [3413098] Nucleic Acids Res. 1988 Aug 25;16(16):8189-90 [2843813] Mol Endocrinol. 1988 Dec;2(12):1364-73 [2851102] Recent Prog Horm Res. 1988;44:307-35 [3217600] J Biol Chem. 1989 Jun 15;264(17):9807-13 [2656713] Oncogene. 1989 Nov;4(11):1375-82 [2812779] J Biol Chem. 1989 Dec 5;264(34):20255-60 [2584216] Proc Natl Acad Sci U S A. 1990 Jan;87(2):705-8 [1689049] Mol Endocrinol. 1990 Mar;4(3):465-75 [2342480] J Biol Chem. 1990 Oct 25;265(30):18067-70 [1976635] Cancer Res. 1990 Nov 15;50(22):7093-100 [2224844] Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):2011-5 [2000408] Biotechniques. 1991 Jan;10(1):62-6 [2003926] J Biol Chem. 1991 Dec 5;266(34):23074-82 [1744104] J Biol Chem. 1992 Mar 15;267(8):5374-9 [1544918] J Biol Chem. 1993 Mar 15;268(8):5774-82 [8449943] Cell Growth Differ. 1994 Jul;5(7):753-9 [7947390] Nat Med. 1995 Jun;1(6):528-33 [7585118] J Biol Chem. 1951 Nov;193(1):265-75 [14907713] Curr Top Cell Regul. 1972;5:99-133 [4358204] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel protective effect of manganese against ferrous citrate-induced lipid peroxidation and nigrostriatal neurodegeneration in vivo. AN - 77831769; 8581499 AB - Earlier studies intranigrally infusing high doses of manganese (50-250 nmol) revealed a reversible oxidative injury to nigrostriatal dopaminergic neurons. In fact, intranigral infusion of lower dose manganese (4.2 nmol) in the present study did not significantly alter dopamine levels in rat striatum. Moreover, manganese completely suppressed both acute lipid peroxidation in substantia nigra and chronic degeneration of the nigrostriatal neurons induced by intranigral infusion of ferrous citrate (4.2 nmol). These in vivo data indicate that low dose manganese is a potent antioxidant which may activate antioxidative defense mechanisms to protect brain neurons against oxidative stress induced by iron complexes. JF - Brain research AU - Sziráki, I AU - Rauhala, P AU - Chiueh, C C AD - Unit on Neurotoxicology and Neuroprotection, NIMH, Bethesda, MD 20892-1264, USA. Y1 - 1995/11/06/ PY - 1995 DA - 1995 Nov 06 SP - 285 EP - 287 VL - 698 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Ferrous Compounds KW - 0 KW - Neuroprotective Agents KW - monoferrous acid citrate KW - 33KM3X4QQW KW - Manganese KW - 42Z2K6ZL8P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Analysis of Variance KW - Ferrous Compounds -- antagonists & inhibitors KW - Male KW - Nerve Degeneration -- drug effects KW - Manganese -- pharmacology KW - Lipid Peroxidation -- drug effects KW - Substantia Nigra -- drug effects KW - Corpus Striatum -- drug effects KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77831769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Novel+protective+effect+of+manganese+against+ferrous+citrate-induced+lipid+peroxidation+and+nigrostriatal+neurodegeneration+in+vivo.&rft.au=Szir%C3%A1ki%2C+I%3BRauhala%2C+P%3BChiueh%2C+C+C&rft.aulast=Szir%C3%A1ki&rft.aufirst=I&rft.date=1995-11-06&rft.volume=698&rft.issue=1-2&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-20 N1 - Date created - 1996-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. AN - 77664262; 8521478 AB - Cyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis and the target enzymes for the widely used nonsteroidal anti-inflammatory drugs. To study the physiological roles of the individual isoforms, we have disrupted the mouse Ptgs1 gene encoding COX-1. Homozygous Ptgs1 mutant mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice, even though their gastric prostaglandin E2 levels are about 1% of wild type. The homozygous mutant mice have reduced platelet aggregation and a decreased inflammatory response to arachidonic acid, but not to tetradecanoyl phorbol acetate. Ptgs1 homozygous mutant females mated to homozygous mutant males produce few live offspring. COX-1-deficient mice provide a useful model to distinguish the physiological roles of COX-1 and COX-2. JF - Cell AU - Langenbach, R AU - Morham, S G AU - Tiano, H F AU - Loftin, C D AU - Ghanayem, B I AU - Chulada, P C AU - Mahler, J F AU - Lee, C A AU - Goulding, E H AU - Kluckman, K D AU - Kim, H S AU - Smithies, O AD - Laboratory of Experimental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/11/03/ PY - 1995 DA - 1995 Nov 03 SP - 483 EP - 492 VL - 83 IS - 3 SN - 0092-8674, 0092-8674 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Arachidonic Acid KW - 27YG812J1I KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Dinoprostone KW - K7Q1JQR04M KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Homozygote KW - Dinoprostone -- biosynthesis KW - Plasmids -- genetics KW - Mice KW - Cloning, Molecular KW - Phenotype KW - Blotting, Western KW - Platelet Aggregation -- physiology KW - Mutation -- physiology KW - Otitis Externa -- chemically induced KW - Macrophages, Peritoneal -- metabolism KW - Mice, Inbred C57BL KW - Female KW - Male KW - Stomach Ulcer -- genetics KW - Gastritis -- genetics KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Arachidonic Acid -- adverse effects KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Prostaglandin-Endoperoxide Synthases -- drug effects KW - Genetic Vectors -- genetics KW - Gastritis -- chemically induced KW - Stomach Ulcer -- chemically induced KW - Indomethacin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77664262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Prostaglandin+synthase+1+gene+disruption+in+mice+reduces+arachidonic+acid-induced+inflammation+and+indomethacin-induced+gastric+ulceration.&rft.au=Langenbach%2C+R%3BMorham%2C+S+G%3BTiano%2C+H+F%3BLoftin%2C+C+D%3BGhanayem%2C+B+I%3BChulada%2C+P+C%3BMahler%2C+J+F%3BLee%2C+C+A%3BGoulding%2C+E+H%3BKluckman%2C+K+D%3BKim%2C+H+S%3BSmithies%2C+O&rft.aulast=Langenbach&rft.aufirst=R&rft.date=1995-11-03&rft.volume=83&rft.issue=3&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-24 N1 - Date created - 1996-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicotine medications for smoking cessation. AN - 77541377; 7565976 JF - The New England journal of medicine AU - Henningfield, J E AD - Clinical Pharmacology Branch, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1995/11/02/ PY - 1995 DA - 1995 Nov 02 SP - 1196 EP - 1203 VL - 333 IS - 18 SN - 0028-4793, 0028-4793 KW - Nicotine KW - 6M3C89ZY6R KW - Abridged Index Medicus KW - Index Medicus KW - Substance-Related Disorders -- physiopathology KW - Drug Interactions KW - Humans KW - Adolescent KW - Nicotine -- therapeutic use KW - Nicotine -- pharmacokinetics KW - Nicotine -- contraindications KW - Smoking Cessation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77541377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Nicotine+medications+for+smoking+cessation.&rft.au=Henningfield%2C+J+E&rft.aulast=Henningfield&rft.aufirst=J&rft.date=1995-11-02&rft.volume=333&rft.issue=18&rft.spage=1196&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-02 N1 - Date created - 1995-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modelling the P2Y purinoceptor using rhodopsin as template. AN - 77933076; 8872457 AB - The P2Y1 purinoceptor cloned from chick brain (Webb, T. et al (1993) FEBS Lett., 324, 219-225) is a 362 amino acid, 41 kDa protein. To locate residues tentatively involved in ligand recognition a molecular model of the P2Y purinoceptor has been constructed. The model was based on the primary sequence and structural homology with the G-protein coupled photoreceptor rhodopsin, in analogy to the method proposed by Ballesteros and Weinstein ((1995) Meth. Neurosci. 25, 366-428). Transmembrane helices were constructed from the amino acid sequence, minimized individually, and positioned in a helical bundle. The helical bundle was then minimized using the Amber forcefield in Discover (BIOSYM Technologies) to obtain the final model. Several residues that have been shown to be critical in ligand binding in other GPCRs are conserved in the P2Y1 purinoceptor. According to our model the side chains of these conserved residues are facing the internal cleft in which ligand binding likely occurs. The model also suggests four basic residues (H121 in TM3, H266 and K269 in TM6 and R299 in TM7) near the extracellular surface that might be involved in ligand binding. These basic residues might be essential in coordinating the triphosphate chain of the endogenous ligand adenosine 5'-triphosphate (ATP). Potential binding sites for agonists have been explored by docking several derivatives (including newly synthesized N6-derivatives) into the model. The N6-phenylethyl substituent is tolerated pharmacologically, and in our model this substituent occupies a region predominantly defined by aromatic residues such as F51 (TM1), Y100 (TM2) and F120 (TM3). The dimethylated analogue of ATP, N6,N6-dimethyl-adenosine 5'-triphosphate, is less well tolerated pharmacologically, and our model predicts that the attenuated activity is due to interference with hydrogen bonding capacity to Q296 (TM7). JF - Drug design and discovery AU - Van Rhee, A M AU - Fischer, B AU - Van Galen, P J AU - Jacobson, K A AD - NIH, NIDDK, LBC, Molecular Recognition Section, Bethesda, Maryland 20892-0810, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 133 EP - 154 VL - 13 IS - 2 SN - 1055-9612, 1055-9612 KW - Ligands KW - 0 KW - Mutagens KW - Receptors, Purinergic P2 KW - Rhodopsin KW - 9009-81-8 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Computer Simulation KW - Chemistry, Physical KW - Chick Embryo KW - GTP-Binding Proteins -- chemistry KW - Mutagens -- toxicity KW - Amino Acid Sequence KW - Molecular Weight KW - Mutagenesis, Site-Directed KW - Conserved Sequence KW - Electron Spin Resonance Spectroscopy KW - GTP-Binding Proteins -- metabolism KW - Chemical Phenomena KW - Molecular Sequence Data KW - Models, Chemical KW - Hydrogen Bonding KW - Mutagens -- chemistry KW - Rhodopsin -- toxicity KW - Receptors, Purinergic P2 -- chemistry KW - Rhodopsin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77933076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+design+and+discovery&rft.atitle=Modelling+the+P2Y+purinoceptor+using+rhodopsin+as+template.&rft.au=Van+Rhee%2C+A+M%3BFischer%2C+B%3BVan+Galen%2C+P+J%3BJacobson%2C+K+A&rft.aulast=Van+Rhee&rft.aufirst=A&rft.date=1995-11-01&rft.volume=13&rft.issue=2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Drug+design+and+discovery&rft.issn=10559612&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Respir Cell Mol Biol. 1991 Apr;4(4):295-300 [1707633] J Mol Biol. 1991 Apr 5;218(3):499-503 [2016741] Proteins. 1991;9(1):56-68 [2017436] Mol Pharmacol. 1991 Jul;40(1):8-15 [1649965] J Biol Chem. 1991 Aug 15;266(23):15488-92 [1678390] EMBO J. 1991 Dec;10(12):3729-34 [1657592] Trends Pharmacol Sci. 1992 Mar;13(3):87-90 [1374198] Mol Pharmacol. 1992 Jul;42(1):123-33 [1635550] Nature. 1992 Sep 10;359(6391):144-7 [1381811] Int J Pept Protein Res. 1992 Apr;39(4):356-63 [1428525] Nature. 1992 Nov 12;360(6400):161-3 [1436092] Nature. 1987 Jul 16-22;328(6127):275-8 [2439921] EMBO J. 1993 Apr;12(4):1693-703 [8385611] Nature. 1993 Apr 22;362(6422):770-2 [8469290] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5113-7 [7685114] FEBS Lett. 1993 Jun 14;324(2):219-25 [8508924] J Med Chem. 1993 Nov 26;36(24):3937-46 [8254622] Nature. 1993 Dec 16;366(6456):654-63 [8259210] FEBS Lett. 1994 Jan 10;337(2):207-12 [8287978] Mol Pharmacol. 1994 Feb;45(2):165-70 [8114667] Trends Pharmacol Sci. 1994 Jan;15(1):7-9 [8140657] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3275-9 [8159738] Mol Pharmacol. 1994 Jul;46(1):8-14 [8058061] Eur J Pharmacol. 1994 Jun 15;268(1):1-7 [7925607] Eur J Pharmacol. 1994 Jun 15;268(1):95-104 [7925617] Nature. 1994 Oct 6;371(6497):516-9 [7523951] Nature. 1994 Oct 6;371(6497):519-23 [7523952] Pharmacol Rev. 1994 Jun;46(2):143-56 [7938164] Am J Respir Cell Mol Biol. 1995 Jan;12(1):27-32 [7811468] Br J Pharmacol. 1994 Nov;113(3):1015-21 [7858843] Br J Pharmacol. 1994 Nov;113(3):1057-63 [7858849] Nature. 1995 Mar 2;374(6517):74-7 [7532789] J Biol Chem. 1995 Mar 3;270(9):4185-8 [7876172] Pharmacol Ther. 1994;64(3):445-75 [7724657] J Biol Chem. 1995 Jun 9;270(23):13987-97 [7775460] Life Sci. 1995;56(11-12):823-30 [10188781] J Mol Biol. 1982 May 5;157(1):105-32 [7108955] Protein Eng. 1990 Dec;4(2):109-12 [2075184] J Biol Chem. 1990 Dec 15;265(35):21590-5 [2174879] J Mol Biol. 1990 Jun 20;213(4):899-929 [2359127] Mol Pharmacol. 1989 Dec;36(6):840-7 [2557534] Biochem J. 1988 Jun 1;252(2):583-93 [2843174] Biochem J. 1986 Jan 15;233(2):309-19 [3006665] Nature. 1986 Oct 2-8;323(6087):411-6 [3762692] Drug Des Discov. 1992;9(1):49-67 [1457698] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the pulmonary lesions induced in rats by human recombinant interleukin-2. AN - 77908981; 8772251 AB - Histologic, electron microscopic, and immunohistochemical studies were made to analyze the structural features and the cellular composition of the pulmonary lesions produced in rats by the administration of interleukin-2 (IL-2). This agent induced pulmonary edema; thickening of alveolar septa; damage to endothelial cells in capillaries and venules, marked interstitial infiltration by cytotoxic T lymphocytes, lymphokine-activated killer (LAK) cells, macrophages, and dendritic cells (as demonstrated by cell counting in preparations stained immunohistochemically with peroxidase- and fluorochrome-labeled antibodies); and injury to bronchiolar and alveolar epithelial cells. Granular and agranular lymphocytes often were closely apposed to endothelial cells in capillaries and venules. Contacts between lymphocytes and type II alveolar epithelial cells also were observed. Damaged type II alveolar epithelial cells showed nuclear and cytoplasmic features that are considered indicative of apoptosis (confirmed by nick end labeling). Phagocytosis of apoptotic bodies by macrophages was occasionally found. These results support the concept that IL-2 induces cytotoxic vascular and parenchymal cell damage that is mediated by LAK cells and cytotoxic T lymphocytes, which make contacts with endothelial cells and type II alveolar epithelial cells. This damage appears to be exacerbated by the secondary release of a variety of vasoactive agents and inflammatory mediators. JF - Toxicologic pathology AU - Zhang, J AU - Wenthold, R J AU - Yu, Z X AU - Herman, E H AU - Ferrans, V J AD - Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1518, USA. PY - 1995 SP - 653 EP - 666 VL - 23 IS - 6 SN - 0192-6233, 0192-6233 KW - Antibodies, Monoclonal KW - 0 KW - Interleukin-2 KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Humans KW - Dendritic Cells -- drug effects KW - Antibodies, Monoclonal -- chemistry KW - Recombinant Proteins -- toxicity KW - Rats KW - Rats, Sprague-Dawley KW - Endothelium, Vascular -- drug effects KW - Cell Count -- drug effects KW - Apoptosis -- drug effects KW - Killer Cells, Lymphokine-Activated -- drug effects KW - Endothelium, Vascular -- pathology KW - Endothelium, Vascular -- ultrastructure KW - Immunohistochemistry KW - Female KW - Lung -- ultrastructure KW - Lung -- drug effects KW - Lung -- pathology KW - Interleukin-2 -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77908981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Results+of+lead+research%3A+prenatal+exposure+and+neurological+consequences.&rft.au=Goyer%2C+R+A&rft.aulast=Goyer&rft.aufirst=R&rft.date=1996-10-01&rft.volume=104&rft.issue=10&rft.spage=1050&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A model for pharmacological research-treatment of cocaine dependence. AN - 77908194; 8749725 AB - Major problems for research on pharmacological treatments for cocaine dependence are lack of comparability of results from different treatment research programs and poor validity and/or reliability of results. Double-blind, placebo-controlled, random assignment, experimental designs, using standard intake and assessment procedures help to reduce these problems. Cessation or reduction of drug use and/or craving, retention in treatment, and medical and psychosocial improvement are some of the outcome variables collected in treatment research programs. A model to be followed across different outpatient clinical trials for pharmacological treatment of cocaine dependence is presented here. This model represents an effort to standardize data collection to make results more valid and comparable. JF - Journal of substance abuse treatment AU - Montoya, I D AU - Hess, J M AU - Preston, K L AU - Gorelick, D A AD - National Institutes of Health, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224, USA. PY - 1995 SP - 415 EP - 421 VL - 12 IS - 6 SN - 0740-5472, 0740-5472 KW - Psychotropic Drugs KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Double-Blind Method KW - Humans KW - Treatment Outcome KW - Psychotropic Drugs -- therapeutic use KW - Psychotropic Drugs -- adverse effects KW - Substance-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77908194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse+treatment&rft.atitle=A+model+for+pharmacological+research-treatment+of+cocaine+dependence.&rft.au=Montoya%2C+I+D%3BHess%2C+J+M%3BPreston%2C+K+L%3BGorelick%2C+D+A&rft.aulast=Montoya&rft.aufirst=I&rft.date=1995-11-01&rft.volume=12&rft.issue=6&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse+treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-27 N1 - Date created - 1996-09-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Nerv Ment Dis. 1991 Feb;179(2):89-96 [1990076] Compr Psychiatry. 1991 Jan-Feb;32(1):22-7 [2001617] Am J Drug Alcohol Abuse. 1991 Jun;17(2):137-52 [1862788] Ann Intern Med. 1991 Dec 1;115(11):901-5 [1952480] J Clin Psychopharmacol. 1991 Dec;11(6):374-8 [1837556] Stat Med. 1991 Dec;10(12):1789-817 [1805314] Am J Drug Alcohol Abuse. 1992;18(3):305-29 [1329493] Arch Gen Psychiatry. 1981 Apr;38(4):381-9 [6260053] NIDA Res Monogr. 1992;128:46-58; discussion 59-63 [1436015] NIDA Res Monogr. 1992;128:97-113; discussion 114-5 [1436019] Arch Gen Psychiatry. 1992 Nov;49(11):888-93 [1444727] Arch Gen Psychiatry. 1992 Nov;49(11):894-8 [1444728] J Nerv Ment Dis. 1993 Jun;181(6):345-50 [8501455] Arch Gen Psychiatry. 1993 Sep;50(9):739-50 [8357299] JAMA. 1994 Dec 28;272(24):1926-31 [7990245] Drug Alcohol Depend. 1995 Jun;38(3):213-9 [7555621] Arch Gen Psychiatry. 1961 Jun;4:561-71 [13688369] Stat Med. 1988 Jan-Feb;7(1-2):305-15 [3353609] Ann Intern Med. 1988 Feb;108(2):266-73 [3341656] Biometrics. 1982 Dec;38(4):963-74 [7168798] Am J Psychiatry. 1990 Aug;147(8):1043-8 [2197883] Biometrics. 1988 Dec;44(4):1049-60 [3233245] Lancet. 1989 Mar 18;1(8638):623-4 [2564153] NIDA Res Monogr. 1992;128:29-36; discussion 37-45 [1436014] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thyroid dysfunction in 281 patients with metastatic melanoma or renal carcinoma treated with interleukin-2 alone. AN - 77899139; 8680655 AB - The purpose of this prospective study was to determine the incidence of thyroid dysfunction in cancer patients receiving immunotherapy with interleukin-2 (IL-2) alone, and to assess the relationship of hypothyroidism to clinical response. A cohort of 281 consecutive patients with metastatic melanoma or renal carcinoma were treated with IL-2 alone from July 1, 1989 until June 30, 1993. The majority (n = 216) received high-dose IL-2 and the remainder (n = 65) received low-dose therapy. Thyroid function was measured before, during, and after immunotherapy. Forty-one percent of initially euthyroid patients developed thyroid dysfunction after starting high-dose IL-2-alone therapy. The most common abnormality was hypothyroidism, occurring in 35% of patients, although moderate or severe hypothyroidism requiring thyroid hormone replacement occurred in 9% of patients. Hypothyroidism was related to duration of IL-2 therapy and was not associated with clinical response. Hyperthyroidism developed in 7% of previously euthyroid patients receiving high-dose IL-2. Overall, the incidence of thyroid dysfunction was similar in the high- and low-dose IL-2 regimens. In conclusion, thyroid dysfunction is a common sequela of IL-2 therapy. Thyroid function should be measured routinely in cancer patients receiving IL-2-based treatment. It is recommended that thyroid hormone replacement be given to patients with moderate or severe hypothyroidism. JF - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy AU - Krouse, R S AU - Royal, R E AU - Heywood, G AU - Weintraub, B D AU - White, D E AU - Steinberg, S M AU - Rosenberg, S A AU - Schwartzentruber, D J AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 272 EP - 278 VL - 18 IS - 4 SN - 1067-5582, 1067-5582 KW - Interleukin-2 KW - 0 KW - Index Medicus KW - Prospective Studies KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Hypothyroidism -- chemically induced KW - Adolescent KW - Male KW - Female KW - Immunotherapy, Active -- adverse effects KW - Hyperthyroidism -- chemically induced KW - Interleukin-2 -- adverse effects KW - Carcinoma, Renal Cell -- therapy KW - Melanoma -- secondary KW - Interleukin-2 -- therapeutic use KW - Melanoma -- physiopathology KW - Melanoma -- therapy KW - Carcinoma, Renal Cell -- physiopathology KW - Thyroid Gland -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77899139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=Thyroid+dysfunction+in+281+patients+with+metastatic+melanoma+or+renal+carcinoma+treated+with+interleukin-2+alone.&rft.au=Krouse%2C+R+S%3BRoyal%2C+R+E%3BHeywood%2C+G%3BWeintraub%2C+B+D%3BWhite%2C+D+E%3BSteinberg%2C+S+M%3BRosenberg%2C+S+A%3BSchwartzentruber%2C+D+J&rft.aulast=Krouse&rft.aufirst=R&rft.date=1995-11-01&rft.volume=18&rft.issue=4&rft.spage=272&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-22 N1 - Date created - 1996-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of D-23129, a new experimental anticonvulsant drug, on neurotransmitter amino acids in the rat hippocampus in vitro. AN - 77893261; 8991783 AB - D-23129 [N-(2-amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester] and D-20443 (dihydrochloride of D-23129) are promising anticonvulsant compounds with a broad spectrum activity in animal models of epilepsy. Their effects on de novo synthesis of excitatory (glutamate and aspartate) and inhibitory (GABA) amino acids were studied in rat hippocampal slices. Like phenytoin, carbamazepine, lamotrigine, losigamone, U54494A, and flupirtine, D-23129 and D-20443 were effective in preventing the effects of a chemoconvulsant, 4-aminopyridine, on de novo synthesis of the three amino acids. However, unlike the other compounds, D-23129 and D-20443 also preferentially increased the concentrations of newly synthesized GABA. Their effect on the neosynthesis of GABA was unique, dose dependent, and not tetrodotoxin sensitive. A total of 15 compounds (including standard, new and candidate anticonvulsants) either had no effect on new GABA or decreased it. Therefore, D-23129 and D-20443 exhibited two different effects on de novo synthesis of neurotransmitter amino acids, both of which could potentially be anticonvulsant in nature. JF - Epilepsy research AU - Kapetanovic, I M AU - Yonekawa, W D AU - Kupferberg, H J AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. imkap@helix.nih.gov Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 167 EP - 173 VL - 22 IS - 3 SN - 0920-1211, 0920-1211 KW - Anticonvulsants KW - 0 KW - Carbamates KW - Nerve Tissue Proteins KW - Neurotransmitter Agents KW - Phenylenediamines KW - ezogabine KW - 12G01I6BBU KW - Tetrodotoxin KW - 4368-28-9 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Nerve Tissue Proteins -- analysis KW - Animals KW - 4-Aminopyridine -- pharmacology KW - In Vitro Techniques KW - Nerve Tissue Proteins -- biosynthesis KW - 4-Aminopyridine -- antagonists & inhibitors KW - Tetrodotoxin -- pharmacology KW - gamma-Aminobutyric Acid -- biosynthesis KW - Male KW - Carbamates -- pharmacology KW - Anticonvulsants -- pharmacology KW - Hippocampus -- metabolism KW - Phenylenediamines -- pharmacology KW - Neurotransmitter Agents -- biosynthesis KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77893261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=The+effects+of+D-23129%2C+a+new+experimental+anticonvulsant+drug%2C+on+neurotransmitter+amino+acids+in+the+rat+hippocampus+in+vitro.&rft.au=Kapetanovic%2C+I+M%3BYonekawa%2C+W+D%3BKupferberg%2C+H+J&rft.aulast=Kapetanovic&rft.aufirst=I&rft.date=1995-11-01&rft.volume=22&rft.issue=3&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-15 N1 - Date created - 1997-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Fatal occupational accidents in Lombardy]. TT - Gli infortuni sul lavoro con esito mortale in Lombardia. AN - 77887869; 8815364 AB - All fatal occupational accidents compensated in Lombardy from 1984 to 1989 were analyzed (1259 cases): significant differences between geographical distribution of fatal occupational accidents and workers were observed. Males accounted for about 95% of fatalities; an excess of cases was shown in both young and elderly workers. Death was the consequence of injuries involving most frequently the head, thorax and spinal cord. An excess of fatalities was observed in agriculture and, at a lower level, in manufacturing industries; small enterprises were involved in approximately 25% of fatalities occurring in the manufacturing industries and services. Employers were the victims of fatal accidents in 50% of cases in agriculture and in 70% of cases in craft industries. Construction, agriculture and transport accounted for about 50% of all fatalities. About 50% of fatal occupational accidents were related to vehicle use: the victim was the driver in the majority of cases, sometimes the victim was run over by a vehicle or fell from a vehicle. The results agree with some previous observations (e.g.: sex and age distribution; construction, agriculture and transport as working activities at high accident risk); but some original observations have emerged, in particular about the frequency of employers as victims and the role of vehicles in the genesis of fatal occupational accidents. If further studies confirm these latter observations, important developments could follow in preventive action design and implementation. JF - La Medicina del lavoro AU - Pianosi, G AD - Unità Operativa Tutela della Salute nei Luoghi di Lavoro, Legnano. PY - 1995 SP - 534 EP - 541 VL - 86 IS - 6 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Agriculture KW - Transportation KW - Accidents, Traffic -- mortality KW - Humans KW - Adult KW - Middle Aged KW - Textile Industry KW - Metallurgy KW - Male KW - Italy KW - Female KW - Chemical Industry KW - Accidents, Occupational -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77887869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BFatal+occupational+accidents+in+Lombardy%5D.&rft.au=Pianosi%2C+G&rft.aulast=Pianosi&rft.aufirst=G&rft.date=1995-11-01&rft.volume=86&rft.issue=6&rft.spage=534&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Racial, ethnic, and gender variations in cancer risk: considerations for future epidemiologic research. AN - 77880185; 8741799 AB - There is no question that the risk of many cancers varies substantially by race, ethnic group, and gender. Although important clues to cancer etiology may come from investigating the differences in risk across subgroups of the population, epidemiologic research has often focused on white men. More descriptive and analytic studies are needed to identify and explain variations in risk among population subgroups. Especially important are studies to clarify the role of differential exposures, susceptibility, and diagnostic factors in cancer incidence, although differences in treatment may contribute to variations in cancer mortality. Improvements in classification of ethnicity, assessment of carcinogenic exposures in various subpopulations, and measures of host susceptibility states should augment future epidemiologic research designed to better understand mechanisms underlying the racial, ethnic, and gender differences in cancer risk. JF - Environmental health perspectives AU - Zahm, S H AU - Fraumeni, J F AD - Division of Cancer Etiology, National Cancer Institute, Rockville, Maryland, USA. zahms@epndce.nci.nih.gov Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 283 EP - 286 VL - 103 Suppl 8 SN - 0091-6765, 0091-6765 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Sex Factors KW - Risk Factors KW - Humans KW - Environmental Exposure KW - Forecasting KW - Research KW - Male KW - Female KW - Neoplasms -- epidemiology KW - Neoplasms -- therapy KW - Neoplasms -- ethnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77880185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Racial%2C+ethnic%2C+and+gender+variations+in+cancer+risk%3A+considerations+for+future+epidemiologic+research.&rft.au=Zahm%2C+S+H%3BFraumeni%2C+J+F&rft.aulast=Zahm&rft.aufirst=S&rft.date=1995-11-01&rft.volume=103+Suppl+8&rft.issue=&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-30 N1 - Date created - 1996-09-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Occup Med. 1971 Feb;13(2):53-68 [5546197] J Gerontol. 1992 Nov;47 Spec No:101-10 [1430871] N Engl J Med. 1981 Mar 26;304(13):745-9 [7193288] Am J Epidemiol. 1983 Dec;118(6):818-31 [6650483] Am J Public Health. 1987 May;77(5):603-6 [3565656] Int J Cancer. 1988 May 15;41(5):670-6 [3366488] Cancer Detect Prev. 1988;11(3-6):245-9 [3390848] Cancer. 1989 Mar 1;63(5):982-7 [2914303] Epidemiol Rev. 1990;12:228-40 [2286220] J Natl Cancer Inst. 1991 Apr 17;83(8):526-7 [2005635] J Natl Cancer Inst. 1991 Apr 17;83(8):551-7 [2005640] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5237-41 [1675794] Cancer Res. 1991 Oct 1;51(19):5177-80 [1655248] Am J Public Health. 1991 Nov;81(11):1405-7 [1951795] Cancer Causes Control. 1992 Jan;3(1):17-23 [1536909] Cancer. 1992 May 1;69(9):2349-60 [1562983] J Natl Cancer Inst. 1993 Jan 6;85(1):11-2 [8416249] Environ Health Perspect. 1992 Nov;98:149-54 [1486844] J Natl Cancer Inst. 1993 Mar 17;85(6):465-73 [8445674] Int J Cancer. 1993 Apr 22;54(1):44-8 [8386708] Pharmacogenetics. 1991 Oct;1(1):20-5 [1726950] Cancer Epidemiol Biomarkers Prev. 1992 Sep-Oct;1(6):485-9 [1284589] Cancer Epidemiol Biomarkers Prev. 1992 Jan-Feb;1(2):103-7 [1306091] Pharmacogenetics. 1992 Jun;2(3):116-27 [1306111] J Natl Cancer Inst. 1993 Jul 21;85(14):1129-37 [8320742] Am J Public Health. 1993 Jul;83(7):939-41 [8328610] Am J Public Health. 1993 Jul;83(7):948-54 [8328615] Am J Epidemiol. 1993 Sep 1;138(5):281-93 [8395141] Cancer. 1993 Nov 1;72(9 Suppl):2834-8 [8402514] Cancer Epidemiol Biomarkers Prev. 1993 Sep-Oct;2(5):481-5 [8220094] J Natl Cancer Inst. 1993 Nov 17;85(22):1819-27 [8230262] Arch Intern Med. 1994 Jan 24;154(2):177-85 [8285813] Arch Intern Med. 1994 May 23;154(10):1083-8 [8185421] J Natl Cancer Inst. 1994 Sep 7;86(17):1340-5 [8064893] JAMA. 1994 Sep 28;272(12):947-54 [8084062] Cancer Epidemiol Biomarkers Prev. 1994 Jul-Aug;3(5):413-21 [7920209] J Occup Med. 1994 Aug;36(8):842-7 [7807263] J Natl Cancer Inst. 1992 Jun 17;84(12):915-6 [1629909] J Natl Cancer Inst. 1992 Jun 17;84(12):957-62 [1629916] Cancer. 1992 Sep 1;70(5):1172-6 [1515993] Am J Public Health. 1992 Oct;82(10):1383-5 [1415866] J Natl Cancer Inst. 1980 Sep;65(3):515-28 [6931932] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chelation of toxic metals: current interests. AN - 77865190; 8605861 JF - Environmental health perspectives AU - Goyer, R A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 988 EP - 989 VL - 103 IS - 11 SN - 0091-6765, 0091-6765 KW - Chelating Agents KW - 0 KW - Metals KW - Index Medicus KW - Humans KW - Child KW - Chelating Agents -- therapeutic use KW - Chelation Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77865190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Chelation+of+toxic+metals%3A+current+interests.&rft.au=Goyer%2C+R+A&rft.aulast=Goyer&rft.aufirst=R&rft.date=1995-11-01&rft.volume=103&rft.issue=11&rft.spage=988&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-17 N1 - Date created - 1996-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Pediatr. 1994 Aug;125(2):233-4 [8040769] Eur J Pediatr. 1994 Aug;153(8):607-10 [7957411] Arch Environ Health. 1994 Sep-Oct;49(5):384-94 [7944571] Environ Health Perspect. 1994 Apr;102(4):390-4 [7925179] Circulation. 1994 Sep;90(3):1194-9 [8087928] Ann Intern Med. 1994 Sep 1;121(5):384-5 [8042834] Lancet. 1990 Sep 22;336(8717):699-702 [1975890] JAMA. 1994 Jul 27;272(4):284-91 [8028141] Ann Intern Med. 1994 Mar 15;120(6):490-9 [8311372] J Toxicol Clin Toxicol. 1992;30(4):529-47 [1331492] J Intern Med. 1992 Mar;231(3):261-7 [1556523] Nature. 1991 Jan 10;349(6305):109 [1986302] Comment On: Environ Health Perspect. 1995 Nov;103(11):1048-52 [8605855] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Role of chelating agents for prevention, intervention, and treatment of exposures to toxic metals. AN - 77864755; 8605855 JF - Environmental health perspectives AU - Goyer, R A AU - Cherian, M G AU - Jones, M M AU - Reigart, J R Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1048 EP - 1052 VL - 103 IS - 11 KW - Chelating Agents KW - 0 KW - Lead KW - 2P299V784P KW - Edetic Acid KW - 9G34HU7RV0 KW - Succimer KW - DX1U2629QE KW - Mercury KW - FXS1BY2PGL KW - Penicillamine KW - GNN1DV99GX KW - Index Medicus KW - Humans KW - Chelating Agents -- therapeutic use KW - Succimer -- therapeutic use KW - Chelation Therapy KW - Edetic Acid -- therapeutic use KW - Penicillamine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77864755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Environmental+health+perspectives&rft.atitle=Role+of+chelating+agents+for+prevention%2C+intervention%2C+and+treatment+of+exposures+to+toxic+metals.&rft.au=Goyer%2C+R+A%3BCherian%2C+M+G%3BJones%2C+M+M%3BReigart%2C+J+R&rft.aulast=Goyer&rft.aufirst=R&rft.date=1995-11-01&rft.volume=103&rft.issue=11&rft.spage=1048&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-17 N1 - Date created - 1996-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Pharmacol Exp Ther. 1987 Dec;243(3):804-13 [3121845] J Pediatr. 1984 Oct;105(4):523-32 [6481529] Toxicol Appl Pharmacol. 1984 Mar 15;72(3):550-6 [6710504] Fundam Appl Toxicol. 1981 Sep-Oct;1(5):376-80 [7185586] Annu Rev Pharmacol Toxicol. 1983;23:193-215 [6307120] Environ Res. 1983 Feb;30(1):58-62 [6403349] J Pharmacol Exp Ther. 1988 May;245(2):479-84 [3367303] J Inorg Biochem. 1994 May 15;54(3):157-65 [8027739] Toxicology. 1994 Apr 18;89(2):91-100 [8197593] J Pharmacol Exp Ther. 1994 Feb;268(2):662-8 [8113976] J Pharmacol Exp Ther. 1993 Dec;267(3):1221-6 [8263783] Toxicology. 1993 Oct 25;83(1-3):149-58 [8248942] Toxicol Appl Pharmacol. 1993 Nov;123(1):89-96 [8236266] Pediatrics. 1993 Aug;92(2):265-71 [8337028] Pharmacol Toxicol. 1992 Dec;71(6):452-6 [1480554] Toxicol Appl Pharmacol. 1992 Sep;116(1):85-91 [1326794] FASEB J. 1992 Apr;6(7):2472-6 [1563599] J Pediatr. 1992 Jan;120(1):133-9 [1309865] Toxicol Appl Pharmacol. 1991 Sep 1;110(2):241-50 [1891771] Environ Res. 1989 Feb;48(1):70-5 [2492468] Toxicology. 1990 May 14;62(1):1-25 [2188397] Annu Rev Pharmacol Toxicol. 1990;30:279-306 [2160791] Toxicol Appl Pharmacol. 1990 Jun 1;104(1):67-78 [2360209] Environ Health Perspect. 1991 Feb;91:57-62 [1904023] Comment In: Environ Health Perspect. 1995 Nov;103(11):988-9 [8605861] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activity of hepatic drug metabolizing enzymes following nalidixic acid dosed feed treatment in F344 rats and B6C3F1 mice. AN - 77860058; 8778749 JF - Pharmacology & toxicology AU - Dudley, C N AU - Burka, L T AU - Griffin, R J AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 352 EP - 354 VL - 77 IS - 5 SN - 0901-9928, 0901-9928 KW - Anti-Infective Agents KW - 0 KW - Nalidixic Acid KW - 3B91HWA56M KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Oxygenases KW - EC 1.13.- KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Analysis of Variance KW - Mice KW - Oxidoreductases -- drug effects KW - Cytochrome P-450 Enzyme System -- drug effects KW - Species Specificity KW - Oxygenases -- drug effects KW - Male KW - Organ Size -- drug effects KW - Liver -- pathology KW - Liver -- enzymology KW - Anti-Infective Agents -- toxicity KW - Liver -- drug effects KW - Nalidixic Acid -- administration & dosage KW - Anti-Infective Agents -- administration & dosage KW - Nalidixic Acid -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77860058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+%26+toxicology&rft.atitle=Activity+of+hepatic+drug+metabolizing+enzymes+following+nalidixic+acid+dosed+feed+treatment+in+F344+rats+and+B6C3F1+mice.&rft.au=Dudley%2C+C+N%3BBurka%2C+L+T%3BGriffin%2C+R+J&rft.aulast=Dudley&rft.aufirst=C&rft.date=1995-11-01&rft.volume=77&rft.issue=5&rft.spage=352&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+toxicology&rft.issn=09019928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-16 N1 - Date created - 1996-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ionic mechanisms involved in the regulation of insulin secretion by muscarinic agonists. AN - 77859357; 8606366 AB - The effects of the muscarinic agonist oxotremorine-m (oxo-m) on insulin secretion, K(+)-permeability and electrical activity from isolated mouse pancreatic islets were studied. Oxo-m potentiated glucose-induced insulin secretion in a dose-dependent manner, saturating at ca. 10 microM. At 11.2 mM glucose, oxo-m (0.1 and 10 microM) had two distinct effects on beta-cell electrical activity. Both concentrations increased the steady-state burst frequency, however, at 10 microM an initial and transient polarization was measured, and the subsequent activity was accompanied by a slight depolarization. The polarizing effect of oxo-m was almost completely suppressed by charybdotoxin (ChTX), a blocker of the large conductance (maxi) [Ca2+]i-activated potassium channel (K(Ca)). In the presence of 11.2 mM glucose, oxo-m (50 microM) provoked a significant and transient increase in the 86Rb efflux from perifused islets. This effect was inhibited by ChTX. ChTX also potentiated oxo-m stimulated insulin secretion in the presence of glucose. Finally, the balance between the polarizing and depolarizing effects of oxo-m was variable in different islets and depended on glucose concentration. Insulin secretion stimulated by oxo-m in the presence of glucose was more closely correlated to the agonist induced increase in burst frequency than to an increase in plateau fraction. We conclude that muscarinic stimulation has at least two effects on beta-cell electrical activity, an initial hyperpolarization, owing to activation of K(Ca) channels, followed by depolarization and high-frequency bursts, proposed to reflect the activation of a current sensitive to the depletion of intracellular Ca2+ stores (CRAC). JF - The Journal of membrane biology AU - Bordin, S AU - Boschero, A C AU - Carneiro, E M AU - Atwater, I AD - Laboratory of Cell Biology and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0840, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 177 EP - 184 VL - 148 IS - 2 SN - 0022-2631, 0022-2631 KW - Insulin KW - 0 KW - Muscarinic Agonists KW - Potassium Channel Blockers KW - Potassium Channels KW - Charybdotoxin KW - 115422-61-2 KW - Oxotremorine KW - 5RY0UWH1JL KW - Glucose KW - IY9XDZ35W2 KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Potassium Channels -- metabolism KW - Animals KW - Glucose -- pharmacology KW - Electric Conductivity KW - Dose-Response Relationship, Drug KW - Mice KW - Membrane Potentials -- drug effects KW - Acetylcholine -- pharmacology KW - Charybdotoxin -- pharmacology KW - Female KW - Oxotremorine -- pharmacology KW - Muscarinic Agonists -- pharmacology KW - Islets of Langerhans -- drug effects KW - Islets of Langerhans -- cytology KW - Insulin -- secretion KW - Islets of Langerhans -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77859357?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+membrane+biology&rft.atitle=Ionic+mechanisms+involved+in+the+regulation+of+insulin+secretion+by+muscarinic+agonists.&rft.au=Bordin%2C+S%3BBoschero%2C+A+C%3BCarneiro%2C+E+M%3BAtwater%2C+I&rft.aulast=Bordin&rft.aufirst=S&rft.date=1995-11-01&rft.volume=148&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+membrane+biology&rft.issn=00222631&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-23 N1 - Date created - 1996-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HLA associations in the antitumor response against malignant melanoma. AN - 77858523; 8680652 AB - In this study we analyzed the human leukocyte antigen (HLA) pattern of North American Caucasian patients with metastatic melanoma as compared with the North American Caucasian (NAC) population. We also investigated whether the HLA type of melanoma patients had an effect on their tolerance and response to interleukin-2 (IL-2)-based therapy. Four hundred twelve serologic phenotypes of Caucasian melanoma patients referred to the National Cancer Institute, National Institutes of Health, from February 1989 through December 1993 were collected by typing the patient's peripheral blood lymphocytes. Furthermore, 74 melanoma patients were typed for HLA class II by high-resolution sequence specific primer-polymerase chain reaction. Response rate and treatment-related toxicity in those patients receiving IL-2-based treatment (N = 272) were compared with HLA serologic types. The frequency of four HLA-B alleles was significantly different in the melanoma compared with the NAC population: of these, HLA-B5, -B8, and -B15 had a frequency falling between the NAC and the Northern European population. No other significant differences between melanoma patients and NAC population were noted for other HLA loci. A correlation was noted between HLA-DR3 and -DR4 alleles and decreased tolerance to IL-2, whereas homozygosity for HLA-DR decreased the chance of response. There were no significant associations between HLA type and response. It is unlikely that the associations noted between some HLA-B alleles and melanoma bear significantly on the etiology of the disease. The differences seen between American melanoma patients and the NAC population are probably best explained by geographical ancestry. The association between HLA-DR and tolerance to IL-2 therapy noted in this study may offer insight toward the understanding of mechanisms regulating the cascade of events after the systemic administration of IL-2. JF - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy AU - Marincola, F M AU - Shamamian, P AU - Rivoltini, L AU - Salgaller, M AU - Cormier, J AU - Restifo, N P AU - Simonis, T B AU - Venzon, D AU - White, D E AU - Parkinson, D R AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 242 EP - 252 VL - 18 IS - 4 SN - 1067-5582, 1067-5582 KW - HLA Antigens KW - 0 KW - HLA-DR Antigens KW - Interleukin-2 KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Prospective Studies KW - Histocompatibility Testing KW - HLA-DR Antigens -- immunology KW - Gene Frequency KW - Interleukin-2 -- therapeutic use KW - Humans KW - HLA-DR Antigens -- genetics KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Immunophenotyping KW - HLA Antigens -- genetics KW - Melanoma -- genetics KW - HLA Antigens -- immunology KW - Melanoma -- therapy KW - Melanoma -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77858523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=HLA+associations+in+the+antitumor+response+against+malignant+melanoma.&rft.au=Marincola%2C+F+M%3BShamamian%2C+P%3BRivoltini%2C+L%3BSalgaller%2C+M%3BCormier%2C+J%3BRestifo%2C+N+P%3BSimonis%2C+T+B%3BVenzon%2C+D%3BWhite%2C+D+E%3BParkinson%2C+D+R&rft.aulast=Marincola&rft.aufirst=F&rft.date=1995-11-01&rft.volume=18&rft.issue=4&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-22 N1 - Date created - 1996-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1994 Aug 1;153(3):1225-37 [8027550] Tissue Antigens. 1994 Jan;43(1):7-17 [7912861] Cancer Immunol Immunother. 1994 Aug;39(2):105-16 [7519125] J Immunother Emphasis Tumor Immunol. 1994 Jul;16(1):13-23 [8081556] Melanoma Res. 1994 Jun;4(3):191-4 [7919965] Int J Cancer. 1994 Nov 15;59(4):510-3 [7960221] J Immunol. 1995 Mar 1;154(5):2257-65 [7868898] Eur J Immunol. 1995 Feb;25(2):340-7 [7875194] J Natl Cancer Inst. 1996 Jan 17;88(2):100-8 [8537970] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] Hum Hered. 1978;28(3):171-200 [649177] Hum Immunol. 1980 Dec;1(4):297-304 [7263314] Tissue Antigens. 1982 Aug;20(2):155-8 [6814009] Proc Natl Acad Sci U S A. 1986 Nov;83(22):8699-702 [3464978] Nature. 1987 Oct 8-14;329(6139):506-12 [3309677] Nature. 1987 Oct 8-14;329(6139):512-8 [2443855] Nature. 1988 Sep 15;335(6187):268-71 [3412487] N Engl J Med. 1988 Dec 22;319(25):1676-80 [3264384] J Clin Immunol. 1988 Nov;8(6):426-36 [3265420] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1233-7 [2105500] Cancer Res. 1990 Apr 15;50(8):2371-4 [2317822] Annu Rev Biochem. 1990;59:253-88 [2115762] J Clin Invest. 1991 Jan;87(1):284-92 [1898655] J Immunol. 1991 May 15;146(10):3674-81 [1902860] Nature. 1991 Aug 22;352(6337):723-5 [1876187] J Immunol. 1992 Jan 15;148(2):638-43 [1729379] Science. 1991 Dec 13;254(5038):1643-7 [1840703] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9717-21 [1946393] Nature. 1992 Mar 5;356(6364):22-3 [1538774] Nature. 1992 May 28;357(6376):329-33 [1589035] J Clin Oncol. 1992 Jul;10(7):1158-64 [1607920] Mol Immunol. 1992 Sep;29(9):1131-40 [1379681] Eur J Immunogenet. 1992 Oct;19(5):347-59 [1420120] Cancer Res. 1992 Dec 1;52(23):6561-6 [1423301] J Immunol. 1992 Dec 1;149(11):3563-8 [1385528] Eur J Immunol. 1993 Jan;23(1):224-31 [8093442] J Clin Invest. 1993 Feb;91(2):684-92 [8432869] Nature. 1993 Jul 1;364(6432):33-9 [8316295] J Immunother Emphasis Tumor Immunol. 1993 May 4;13(4):282-8 [8334112] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] Nature. 1994 Jun 2;369(6479):357 [8018207] J Exp Med. 1994 Jul 1;180(1):347-52 [7516411] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 [8022805] Tissue Antigens. 1994 Jan;43(1):18-27 [8023317] Comment In: J Immunother Emphasis Tumor Immunol. 1996 Sep;19(5):381-5 [8941878] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Paraquat-induced acute dermatitis in a child after playing with a discarded container]. TT - Dermatite acuta da paraquat in bambina che ha utilizzato per gioco un contenitore abbandonato. AN - 77853722; 8815368 AB - The improper use of pesticide waste containers is a significant risk in rural areas, especially where appropriate systems of draining off refuse are lacking. A case is reported of an eight-year-old child who had played with the abandoned Paraquat container. After contamination with the pesticide she showed several II degree caustic lesions on both thighs and knees, associated with a mild erythemato-desquamative cheilitis and a "strawberry tongue". Common laboratory findings did not reveal any kidney, liver and/or red/white cell alterations and the chest X-ray was normal even several months after the accident. No physical consequences ensued, except for hyperchromic pigmentation on the legs. Where empty pesticide containers are not properly collected, they can represent a risk of pesticide exposure for the general population. They can also be a potential source of pollution for superficial water and soil. In the district where the accident was reported it was estimated that empty containers made up 7% of the weight of the 146,330 kg of pesticides sold to local farmers in 1993, of which about 10,400 kg was burned, buried and dispersed in the soil. Within the framework of a global pesticide prevention programme launched by the Regional Government of Lombardy, local health authorities, with the contribution of farmers, are carrying out a project for the proper collection of empty pesticide containers. JF - La Medicina del lavoro AU - Villa, L AU - Pizzini, L AU - Viganò, G AU - Ferioli, A AU - Maroni, M AU - Ruggeri, R AU - Barlassina, C AU - Vannini, P AU - Salacrist, L AD - Unità Operativa Tutela della Salute nei Luoghi di Lavoro, Università di Milano. PY - 1995 SP - 563 EP - 568 VL - 86 IS - 6 SN - 0025-7818, 0025-7818 KW - Herbicides KW - 0 KW - Paraquat KW - PLG39H7695 KW - Index Medicus KW - Acute Disease KW - Humans KW - Child KW - Female KW - Herbicides -- adverse effects KW - Paraquat -- adverse effects KW - Dermatitis, Contact -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77853722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BParaquat-induced+acute+dermatitis+in+a+child+after+playing+with+a+discarded+container%5D.&rft.au=Villa%2C+L%3BPizzini%2C+L%3BVigan%C3%B2%2C+G%3BFerioli%2C+A%3BMaroni%2C+M%3BRuggeri%2C+R%3BBarlassina%2C+C%3BVannini%2C+P%3BSalacrist%2C+L&rft.aulast=Villa&rft.aufirst=L&rft.date=1995-11-01&rft.volume=86&rft.issue=6&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potential for bias in epidemiologic studies that rely on glass-based retrospective assessment of radon. AN - 77835606; 8605854 AB - Retrospective assessment of exposure to radon remains the greatest challenge in epidemiologic efforts to assess lung cancer risk associated with residential exposure. An innovative technique based on measurement of alpha-emitting, long-lived daughters embedded by recoil into household glass may one day provide improved radon dosimetry. Particulate air pollution is known, however, to retard the plate-out of radon daughters. This would be expected to result in a differential effect on dosimetry, where the calibration curve relating the actual historical radon exposure to the remaining alpha-activity in the glass would be different in historically smoky and nonsmoky environments. The resulting "measurement confounding" can distort inferences about the effect of radon and can also produce spurious evidence for synergism between radon exposure and cigarette smoking. JF - Environmental health perspectives AU - Weinberg, C R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1042 EP - 1046 VL - 103 IS - 11 SN - 0091-6765, 0091-6765 KW - Smoke KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Plants, Toxic KW - Glass -- analysis KW - Housing KW - Tobacco KW - Bias (Epidemiology) KW - Radon -- analysis KW - Environmental Monitoring -- methods KW - Air Pollution, Radioactive -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77835606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=In+vitro+binding+studies+of+drugs+to+hair%3A+Influence+of+melanin+and+lipids+on+cocaine+binding+to+Caucasoid+and+Africoid+hair&rft.au=Joseph%2C+RE+Jr%3BSu%2C+Tsung-Ping%3BCone%2C+E+J&rft.aulast=Joseph&rft.aufirst=RE&rft.date=1996-10-01&rft.volume=20&rft.issue=6&rft.spage=338&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-05-17 N1 - Date created - 1996-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Causes Control. 1994 Mar;5(2):114-28 [8167258] Radiat Res. 1994 Aug;139(2):163-9 [8052691] Am J Epidemiol. 1994 Aug 15;140(4):310-22 [8059766] N Engl J Med. 1994 Jan 20;330(3):159-64 [8264737] Health Phys. 1993 May;64(5):485-90 [8491599] Health Phys. 1993 Apr;64(4):381-91 [8449720] J Expo Anal Environ Epidemiol. 1992 Jul-Sep;2(3):309-22 [1422161] Immun Infekt. 1992 Jul;20(3):73-5 [1500075] Int J Rad Appl Instrum A. 1992 Jan-Feb;43(1-2):127-38 [1310298] Nature. 1988 Jul 28;334(6180):338-40 [3393224] Health Phys. 1988 Jan;54(1):93-8 [2826366] J Natl Cancer Inst. 1994 Dec 21;86(24):1829-37 [7990157] Science. 1986 Nov 21;234(4779):992-7 [3775373] Health Phys. 1987 Apr;52(4):411-5 [3570784] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quinolinic acid in tumors, hemorrhage and bacterial infections of the central nervous system in children. AN - 77833297; 8583213 AB - A potential mechanism that may contribute to neurological deficits following central nervous system infection in children was investigated. Quinolinic acid (QUIN) is a neurotoxic metabolite of the kynurenine pathway that accumulates within the central nervous system following immune activation. The present study determined whether the levels of QUIN are increased in the cerebrospinal fluid of children with infections of the CNS, hydrocephalus, tumors or hemorrhage. Extremely high QUIN concentrations were found in patients with bacterial infections or the CNS, despite treatment with antimicrobial agents. CSF QUIN levels were also elevated to a lesser degree in patients with hydrocephalus or tumors. CSF L-kynurenine levels increased in parallel to the accumulations in QUIN, which is consistent with increased activity of the first enzyme of the kynurenine pathway, indoleamine-2,3-dioxygenase. The CSF levels of neopterin, a marker of immune and macrophage activation, were also increase in patients with infections. The cytokines tumor necrosis factor-alpha and interleukin-6 were also detected in some patients' samples, and were highest in patients with infection. These results suggest that QUIN is a sensitive marker of the presence of immune activation within the CNS. Further studies of QUIN as a potential contributor to neurologic dysfunction and neurodegeneration in children with CNS inflammation are warranted. JF - Journal of the neurological sciences AU - Heyes, M P AU - Saito, K AU - Milstien, S AU - Schiff, S J AD - Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 112 EP - 118 VL - 133 IS - 1-2 SN - 0022-510X, 0022-510X KW - Biomarkers KW - 0 KW - Interleukin-6 KW - Tumor Necrosis Factor-alpha KW - Biopterin KW - 22150-76-1 KW - Kynurenine KW - 343-65-7 KW - Neopterin KW - 670-65-5 KW - Guanosine Triphosphate KW - 86-01-1 KW - Tryptophan Oxygenase KW - EC 1.13.11.11 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Humans KW - Infant, Newborn KW - Child KW - Tryptophan Oxygenase -- metabolism KW - Child, Preschool KW - Guanosine Triphosphate -- metabolism KW - Kynurenine -- analysis KW - Biopterin -- analogs & derivatives KW - Biopterin -- analysis KW - Infant KW - Biomarkers -- chemistry KW - Adult KW - Hydrocephalus -- metabolism KW - Tumor Necrosis Factor-alpha -- analysis KW - Adolescent KW - Interleukin-6 -- analysis KW - Male KW - Female KW - Central Nervous System Neoplasms -- chemistry KW - Bacterial Infections -- metabolism KW - Quinolinic Acid -- analysis KW - Cerebral Hemorrhage -- metabolism KW - Central Nervous System Diseases -- microbiology KW - Central Nervous System Diseases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77833297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+neurological+sciences&rft.atitle=Quinolinic+acid+in+tumors%2C+hemorrhage+and+bacterial+infections+of+the+central+nervous+system+in+children.&rft.au=Heyes%2C+M+P%3BSaito%2C+K%3BMilstien%2C+S%3BSchiff%2C+S+J&rft.aulast=Heyes&rft.aufirst=M&rft.date=1995-11-01&rft.volume=133&rft.issue=1-2&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+neurological+sciences&rft.issn=0022510X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-19 N1 - Date created - 1996-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nosocomial bacterial and fungal meningitis in cancer patients. AN - 77818667; 8564349 AB - Five cases of nosocomial meningitis are described that occurred within 5 years in a national cancer center in neutropenic cancer patients after cytotoxic chemotherapy: one caused by the yeast Aureobasidium mansoni and four caused by bacteria (two by Enterococcus faecalis and one by Salmonella enteritis and Arcanobacterium haemolyticus. Despite the severe symptoms, all cases were cured with appropriate antimicrobial therapy. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Trupl, J AU - Minarik, T AU - Spanik, S AU - Sufliarsky, J AU - Krcmery, V AD - National Cancer Institute, Bratislava, Slovak Republic. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 425 EP - 427 VL - 3 IS - 6 SN - 0941-4355, 0941-4355 KW - Index Medicus KW - Risk Factors KW - Humans KW - Neutropenia -- complications KW - Adult KW - Neutropenia -- chemically induced KW - Middle Aged KW - Infection Control KW - Cancer Care Facilities KW - Male KW - Neoplasms -- complications KW - Meningitis, Fungal -- etiology KW - Cross Infection -- etiology KW - Meningitis, Bacterial -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77818667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.atitle=Nosocomial+bacterial+and+fungal+meningitis+in+cancer+patients.&rft.au=Trupl%2C+J%3BMinarik%2C+T%3BSpanik%2C+S%3BSufliarsky%2C+J%3BKrcmery%2C+V&rft.aulast=Trupl&rft.aufirst=J&rft.date=1995-11-01&rft.volume=3&rft.issue=6&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.issn=09414355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-06 N1 - Date created - 1996-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Support Care Cancer. 1995 Nov;3(6):385-6 [8564341] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development and analysis of retroviral vectors expressing human factor VIII as a potential gene therapy for hemophilia A. AN - 77818463; 8573610 AB - To develop a potential gene therapy strategy for the treatment of hemophilia A, we constructed several retroviral vectors expressing a B-domain-deleted factor VIII (FVIII) cDNA. We confirmed previous reports that when the FVIII cDNA is inserted into a retroviral vector, the vector mRNA is decreased resulting in significantly (100- to 1,000-fold) lower vector titers. In an attempt to overcome this inhibition we pursued two independent strategies. First, site-directed mutagenesis was employed to change the structure of a putative 1.2-kb FVIII RNA inhibitory sequence (INS). Second, the FVIII gene was transcribed from a retroviral vector containing a 5' intron. Results demonstrated that the intron increased FVIII expression up to 20-fold and viral titer up to 40-fold but conservative mutagenesis of the putative FVIII INS region failed to yield a significant increase in FVIII expression or titer. Using the improved FVIII splicing vector, we transduced a variety of cell types and were able to demonstrate relatively high FVIII expression (10-60 ng of FVIII/10(6) cells/24 hr). These results underscore the usefulness of these transduced cell types for potential in vivo delivery of FVIII. JF - Human gene therapy AU - Chuah, M K AU - VandenDriessche, T AU - Morgan, R A AD - Gene Transfer Technology Section, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1363 EP - 1377 VL - 6 IS - 11 SN - 1043-0342, 1043-0342 KW - DNA, Recombinant KW - 0 KW - RNA KW - 63231-63-0 KW - Factor VIII KW - 9001-27-8 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Gene Transfer Techniques KW - Humans KW - Mice KW - Nucleic Acid Conformation KW - Cloning, Molecular KW - Mutagenesis KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - RNA -- chemistry KW - Cell Line KW - Factor VIII -- genetics KW - Hemophilia A -- therapy KW - Genetic Vectors KW - Genetic Therapy KW - Retroviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77818463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Development+and+analysis+of+retroviral+vectors+expressing+human+factor+VIII+as+a+potential+gene+therapy+for+hemophilia+A.&rft.au=Chuah%2C+M+K%3BVandenDriessche%2C+T%3BMorgan%2C+R+A&rft.aulast=Chuah&rft.aufirst=M&rft.date=1995-11-01&rft.volume=6&rft.issue=11&rft.spage=1363&rft.isbn=&rft.btitle=&rft.title=Human+gene+therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-14 N1 - Date created - 1996-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Voltage-gated potassium currents in stratum oriens-alveus inhibitory neurones of the rat CA1 hippocampus. AN - 77812842; 8576855 AB - 1. Voltage-activated K+ currents were recorded from visually identified inhibitory interneurones of the CA1 stratum oriens-alveus region in neonatal rat hippocampal slices using outside-out patch and whole-cell voltage clamp techniques. 2. Outward currents comprised both a transient and a sustained component when elicited from a holding potential of -90 mV. Tail current analysis of current reversal potentials showed that outward currents were carried by potassium ions. 3. The transient current, IA, was activated with a time to peak within 5 ms, inactivated with a time constant of approximately 15 ms at 0 mV and possessed half-activation at -14 mV. Half-inactivation of the transient current occurred at -71 mV. At -90 mV, the transient current recovered from inactivation with a time constant of 142 ms. 4. Activation of currents from a holding potential of -50 mV permitted isolation of the sustained current, IK. In Ca(2+)-free conditions the sustained current showed rapid activation, reaching about 80% of its maximum within 1.5 ms, and showed little inactivation during 1 s depolarizing steps. The majority of sustained outward currents showed no voltage-dependent inactivation. In approximately 20% of cells, a slow time-dependent inactivation of the sustained current was observed, suggesting the presence of a second type of sustained current in these cells. 5. A Ca(2+)-dependent K+ current comprised a significant portion of the total sustained current; this current was activated at voltages positive to -30 mV and showed no time-dependent inactivation over a 1 s depolarizing step. This current component was removed in Ca(2+)-free conditions or by iberiotoxin. 6. Low concentrations of 4-AP (50 microM) attenuated both the transient and sustained current components recorded in a Ca(2+)-free solution. Higher concentrations of 4-AP (< 10 mM) were without further effect on the sustained current but completely blocked the transient current with an IC50 of 1.8 mM. TEA blocked the sustained current with an IC50 of 7.9 mM without significantly reducing the transient current. Both current components were resistant to dendrotoxin (500 nM). JF - The Journal of physiology AU - Zhang, L AU - McBain, C J AD - Laboratory of Cellular and Molecular Neurophysiology, NICHD-NIH, Bethesda, MD 20892-4495, USA. Y1 - 1995/11/01/ PY - 1995 DA - 1995 Nov 01 SP - 647 EP - 660 VL - 488 ( Pt 3) SN - 0022-3751, 0022-3751 KW - Elapid Venoms KW - 0 KW - Neurotoxins KW - Potassium Channel Blockers KW - Potassium Channels KW - Tetraethylammonium Compounds KW - Tetraethylammonium KW - 66-40-0 KW - dendrotoxin KW - 74811-93-1 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Elapid Venoms -- pharmacology KW - Animals KW - Tetraethylammonium Compounds -- pharmacology KW - Membrane Potentials -- physiology KW - Neurotoxins -- pharmacology KW - Neural Inhibition -- physiology KW - Potassium -- metabolism KW - Calcium -- metabolism KW - Ion Channel Gating -- physiology KW - Rats KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Kinetics KW - Time Factors KW - Interneurons -- ultrastructure KW - Hippocampus -- physiology KW - Hippocampus -- cytology KW - Interneurons -- cytology KW - Interneurons -- chemistry KW - Potassium Channels -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77812842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+physiology&rft.atitle=Voltage-gated+potassium+currents+in+stratum+oriens-alveus+inhibitory+neurones+of+the+rat+CA1+hippocampus.&rft.au=Zhang%2C+L%3BMcBain%2C+C+J&rft.aulast=Zhang&rft.aufirst=L&rft.date=1995-11-01&rft.volume=488+%28+Pt+3%29&rft.issue=&rft.spage=647&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=00223751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-12 N1 - Date created - 1996-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biophys J. 1992 Aug;63(2):583-90 [1384740] Proc Biol Sci. 1992 Apr 22;248(1321):9-18 [1381835] J Neurosci. 1994 Mar;14(3 Pt 1):949-72 [8120636] Mol Pharmacol. 1994 Jun;45(6):1227-34 [7517498] J Neurophysiol. 1994 Oct;72(4):1516-29 [7823083] J Neurophysiol. 1994 May;71(5):1948-58 [8064358] J Neurosci. 1994 Jul;14(7):4433-45 [7517996] J Neurophysiol. 1994 Dec;72(6):2853-63 [7897494] J Neurophysiol. 1995 Jan;73(1):73-9 [7714591] J Physiol. 1995 Nov 1;488 ( Pt 3):661-72 [8576856] J Physiol. 1971 Feb;213(1):21-30 [5575340] J Physiol. 1977 Feb;265(2):465-88 [850203] Pflugers Arch. 1981 Aug;391(2):85-100 [6270629] Nature. 1982 Sep 16;299(5880):252-4 [6287290] J Neurophysiol. 1985 Apr;53(4):1038-58 [2582098] Proc Natl Acad Sci U S A. 1986 Jan;83(2):493-7 [2417246] J Neurophysiol. 1986 Aug;56(2):481-93 [2428951] J Neurosci. 1987 Jul;7(7):1979-93 [3612227] J Physiol. 1987 Dec;393:331-53 [2451740] J Gen Physiol. 1988 Aug;92(2):263-78 [2844959] Nature. 1989 Aug 24;340(6235):642-5 [2770868] Pflugers Arch. 1989 Sep;414(5):600-12 [2780225] EMBO J. 1989 Nov;8(11):3235-44 [2555158] J Neurosci Methods. 1989 Dec;30(3):203-10 [2607782] Nature. 1991 Aug 22;352(6337):711-4 [1908562] Neuron. 1992 Jun;8(6):1055-67 [1610565] EMBO J. 1992 Jul;11(7):2473-86 [1378392] J Physiol. 1992 Jan;445:431-55 [1501141] J Neurophysiol. 1992 Jul;68(1):16-27 [1355525] Physiol Rev. 1992 Oct;72(4 Suppl):S69-88 [1438587] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular phylogeny of the red panda (Ailurus fulgens). AN - 77765575; 8568209 AB - The phylogenetic placement of the red panda (Ailurus fulgens) and the giant panda (Ailuropoda melanoleuca) has been an evolutionary enigma since their original descriptions in the nineteenth century. A series of recent molecular analyses led to a consensus that the giant panda's ancestors were derived from early bears (Ursidae), but left unsettled the phylogenetic relationship of the red panda. Previous molecular and morphological phylogenies were inconclusive and varied among placement of the red panda within the raccoon family (Procyonidae), within the bear family (Ursidae), or in a separate family of carnivores equidistant between the two. To examine a relatively ancient (circa 20-30 million years before the present, MYBP) phylogenetic divergence, we used two slowly evolving genetic markers: mitochondrial 12S rRNA sequence and 592 fibroblast proteins resolved by two dimensional gel electrophoresis. Four different carnivore outgroup species, including dog (Canidae: Canis familiaris), cat (Felidae: Felis catus), fanaloka (Viverridae: Fossa fossa), and mongoose (Herpestidae: Galidia elegans), were selected to identify the root of the phylogenetic topologies. Phylogenetic reconstruction by distance-based methods, maximum parsimony, and maximum likelihood clearly indicate a distinct bifurcation forming the Ursidae and the Procyonidae. Further, our data consistently place the red panda as an early divergence within the Procyonidae radiation and confirm the inclusion of giant panda in the Ursidae lineage. JF - The Journal of heredity AU - Slattery, J P AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21702-1201, USA. PY - 1995 SP - 413 EP - 422 VL - 86 IS - 6 SN - 0022-1503, 0022-1503 KW - DNA Primers KW - 0 KW - DNA, Mitochondrial KW - RNA, Ribosomal KW - RNA, ribosomal, 12S KW - Index Medicus KW - Probability KW - Animals KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Cats -- genetics KW - Raccoons -- genetics KW - Molecular Sequence Data KW - Dogs -- genetics KW - Herpestidae -- genetics KW - Phylogeny KW - Carnivora -- genetics KW - Ursidae -- classification KW - Ursidae -- genetics KW - RNA, Ribosomal -- genetics KW - Carnivora -- classification KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77765575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=Laboratory+Validation+Study+of+Drug+Evaluation+and+Classification+Program%3A+Ethanol%2C+Cocaine%2C+and+Marijuana&rft.au=Heishman%2C+Stephen+J%3BSingleton%2C+Edward+G%3BCrouch%2C+Dennis+J&rft.aulast=Heishman&rft.aufirst=Stephen&rft.date=1996-10-01&rft.volume=20&rft.issue=6&rft.spage=468&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-06 N1 - Date created - 1996-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunocytochemical analysis of hormone mediated nuclear translocation of wild type and mutant glucocorticoid receptors. AN - 77733232; 7495692 AB - We have analyzed structural and functional features of the human glucocorticoid receptor (hGR) for their effects on receptor subcellular distribution. COS 1 cells transiently transfected with wild type and mutant hGR cDNAs were assessed immunocytochemically using well-characterized antipeptide antibodies to the hGR. The effect of administration of steroid hormones (and the antiglucocorticoid RU486) on receptor localization was evaluated. Unliganded wild type receptors expressed in COS 1 cells were predominately cytoplasmic. Addition of glucocorticoids or the glucocorticoid receptor antagonist, RU486, resulted in complete translocation of these receptors into the nucleus whereas non-glucocorticoid steroids or dibutyryl cAMP were not effective in promoting nuclear translocation. Thus, nuclear translocation was specific for steroids capable of high affinity binding to the hGR. To elucidate the potential role of receptor domains in receptor localization, COS 1 cells transiently transfected with various receptor cDNA mutants were analyzed in a similar manner. Translocation of an hGR deletion mutant lacking the majority of the amino terminus (deletion of amino acids 77-262) was identical to the wild type receptor despite the absence of a transactivation domain. Receptors in which the DNA binding domain was either partially or totally deleted showed an impaired capacity to undergo hormone-inducible nuclear translocation. Deletion of the hinge region of the hGR (which also contains part of the nuclear localization signal, NL1) resulted in receptor localization in the cytoplasm. Mutants in the ligand binding domain exhibited two localization phenotypes, exclusively nuclear or cytoplasmic. Receptor mutants truncated after amino acid 550 were found in the nucleus in the presence and absence of hormone consistent with the existence of nuclear localization inhibitory sequences in the ligand binding domain of the receptor. However, a linker insertion mutant (at amino acid 582) which results in a receptor deficient in ligand binding did not undergo nuclear translocation indicating that nuclear localization inhibitory sequences were intact in this mutant. The role of receptor phosphorylation on hormone induced nuclear translocation was also examined. Mouse glucocorticoid receptors which contained mutations of certain hormone inducible phosphorylation sites exhibited translocation properties similar to wild type mGR indicating that these phosphorylation sites on the receptor do not play a major role in hormone inducible nuclear translocation. JF - The Journal of steroid biochemistry and molecular biology AU - Jewell, C M AU - Webster, J C AU - Burnstein, K L AU - Sar, M AU - Bodwell, J E AU - Cidlowski, J A AD - Laboratory of Integrative Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 135 EP - 146 VL - 55 IS - 2 SN - 0960-0760, 0960-0760 KW - DNA, Complementary KW - 0 KW - Glucocorticoids KW - Receptors, Glucocorticoid KW - Recombinant Proteins KW - Mifepristone KW - 320T6RNW1F KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Dexamethasone -- pharmacology KW - Humans KW - Immunohistochemistry -- methods KW - Mice KW - Mifepristone -- pharmacology KW - Mutagenesis KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Cercopithecus aethiops KW - Kidney KW - Recombinant Proteins -- analysis KW - Cell Line KW - Mutagenesis, Insertional KW - Receptors, Glucocorticoid -- biosynthesis KW - Cell Nucleus -- metabolism KW - Receptors, Glucocorticoid -- analysis KW - Cell Nucleus -- drug effects KW - Receptors, Glucocorticoid -- metabolism KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77733232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+steroid+biochemistry+and+molecular+biology&rft.atitle=Immunocytochemical+analysis+of+hormone+mediated+nuclear+translocation+of+wild+type+and+mutant+glucocorticoid+receptors.&rft.au=Jewell%2C+C+M%3BWebster%2C+J+C%3BBurnstein%2C+K+L%3BSar%2C+M%3BBodwell%2C+J+E%3BCidlowski%2C+J+A&rft.aulast=Jewell&rft.aufirst=C&rft.date=1995-11-01&rft.volume=55&rft.issue=2&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+steroid+biochemistry+and+molecular+biology&rft.issn=09600760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2. AN - 77703414; 7489724 AB - Iron regulatory proteins (IRPs) regulate the expression of genes involved in iron metabolism whose transcripts contain RNA stem-loop motifs known as iron-responsive elements (IREs). When iron concentrations are low, IRPs bind to IREs in the 5' untranslated region (UTR) of transcripts where they repress translation, or the 3' UTR of transcripts where they inhibit degradation. The RNA binding activities of the homologous proteins IRP1 and IRP2 are both regulated post-translationally. The binding activity of IRP2 is regulated by the degradation of the protein when cells are iron-replete. Here, we demonstrate that a 73 amino acid sequence that corresponds to a unique exon in IRP2 contains a sequence required for rapid degradation in iron-replete cells. The deletion of this sequence eliminates the rapid turnover of IRP2, whereas the transfer of this sequence to the corresponding position in the homologous protein IRP1 confers the capacity for iron-dependent degradation upon IRP1. Site-directed mutagenesis has demonstrated that specific cysteines within the IRP2 exon are required for iron-dependent degradation. The degradation of IRP2 appears to be mediated by the proteasome in iron-replete cells. When degradation is prevented, the RNA binding activity of IRP2 is not regulated by iron concentration. Thus, degradation is required for the regulation of the RNA binding activity of IRP2. JF - The EMBO journal AU - Iwai, K AU - Klausner, R D AU - Rouault, T A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 1995/11/01/ PY - 1995 DA - 1995 Nov 01 SP - 5350 EP - 5357 VL - 14 IS - 21 SN - 0261-4189, 0261-4189 KW - Iron-Regulatory Proteins KW - 0 KW - RNA-Binding Proteins KW - Iron KW - E1UOL152H7 KW - Iron Regulatory Protein 1 KW - EC 4.2.1.3 KW - Iron Regulatory Protein 2 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Cysteine -- metabolism KW - Humans KW - Protein Processing, Post-Translational KW - Amino Acid Sequence KW - Gene Deletion KW - Exons -- genetics KW - Mutagenesis, Site-Directed KW - Cysteine -- chemistry KW - Tumor Cells, Cultured KW - Sequence Analysis KW - Molecular Sequence Data KW - RNA-Binding Proteins -- metabolism KW - RNA-Binding Proteins -- genetics KW - RNA-Binding Proteins -- chemistry KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77703414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Requirements+for+iron-regulated+degradation+of+the+RNA+binding+protein%2C+iron+regulatory+protein+2.&rft.au=Iwai%2C+K%3BKlausner%2C+R+D%3BRouault%2C+T+A&rft.aulast=Iwai&rft.aufirst=K&rft.date=1995-11-01&rft.volume=14&rft.issue=21&rft.spage=5350&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-02 N1 - Date created - 1996-01-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Baillieres Clin Haematol. 1994 Dec;7(4):763-85 [7881153] Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8797-801 [8090726] Science. 1995 May 5;268(5211):726-31 [7732382] J Biol Chem. 1995 Jun 30;270(26):15451-4 [7541043] RNA. 1995 Apr;1(2):155-63 [7585245] Science. 1989 Apr 21;244(4902):357-9 [2711187] Biofactors. 1989 Dec;2(2):77-86 [2696478] Nature. 1991 Jan 10;349(6305):132-8 [1846030] J Biol Chem. 1991 Feb 5;266(4):2005-8 [1989966] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10109-13 [1946430] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7536-40 [1502165] Science. 1992 Oct 16;258(5081):434-40 [1411536] Biometals. 1992 Autumn;5(3):131-40 [1421965] J Biol Chem. 1992 Dec 5;267(34):24466-70 [1447194] Nature. 1992 Dec 10;360(6404):597-9 [1334232] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11735-9 [1281544] Cell. 1993 Jan 15;72(1):19-28 [8380757] Cell. 1993 Jul 30;74(2):357-69 [8393731] J Biol Chem. 1993 Dec 25;268(36):27327-34 [8262972] EMBO J. 1994 Jan 15;13(2):453-61 [7508861] Blood Rev. 1993 Dec;7(4):251-8 [8130687] J Biol Chem. 1994 Sep 30;269(39):24252-60 [7523370] J Biol Chem. 1994 Dec 9;269(49):30904-10 [7983023] EMBO J. 1994 Dec 15;13(24):6021-30 [7813440] J Biol Chem. 1995 Feb 3;270(5):2344-51 [7836468] Science. 1994 Jun 3;264(5164):1427-33 [8197456] Cell. 1994 Jun 17;77(6):805-15 [7516265] J Biol Chem. 1994 Jul 1;269(26):17481-9 [8021254] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7321-5 [8041788] Cell. 1994 Sep 9;78(5):761-71 [8087844] Cell. 1994 Sep 9;78(5):773-85 [8087845] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2499-503 [7708673] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Homozygous deletions but no sequence mutations in coding regions of p15 or p16 in human primary bladder tumors. AN - 77691654; 7576106 AB - Chromosome 9p21 appears to harbor a tumor suppressor gene, as evidenced by deletions in this region in a variety of human primary tumors and cell lines. To map the deletion at 9p21 in bladder tumors, we analyzed DNA from 28 tumor and normal pairs at five microsatellite markers that flank the region occupied by the putative tumor suppressor genes p16 and p15. Loss of heterozygosity (LOH) at the markers human interferon (HIFN) alpha and D9S171, which are adjacent to the p15 and p16 loci, was detected in 41% and 33%, respectively, of informative cases of bladder tumors. No sequence mutations were detected in exons 1 or 2 of either p15 or p16 in any of the bladder tumors. Three sequence-tagged site markers in the region bordered by HIFN alpha and D9S171 were used to further map the deleted region by multiplex polymerase chain reaction with the HIFN gamma maker (on chromosome 12) as a control for amplification. Six of 11 tumors with LOH at surrounding markers had homozygous deletions of the marker c5.1, which is located within the p16 gene; and two tumors appeared to have homozygous deletions within p15 (RN1.1) but not p16 (c5.1). A recently identified microsatellite marker, p16-CA-1, located 16 kb distal to p16, proved valuable in defining the minimal deletion involved in these bladder tumors. Five tumors exhibited homozygous deletions of this marker but not HIFN alpha and two tumors showed LOH at this marker and homozygous deletion of p16. Although these data could not be used to identify p16 or p15 as the definitive tumor suppressor gene in this region that is involved in bladder carcinogenesis, they suggest that homozygous deletion is a common mechanism of loss of tumor suppressor gene function in this region. JF - Molecular carcinogenesis AU - Packenham, J P AU - Taylor, J A AU - Anna, C H AU - White, C M AU - Devereux, T R AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 147 EP - 151 VL - 14 IS - 3 SN - 0899-1987, 0899-1987 KW - CDKN2B protein, human KW - 0 KW - Carrier Proteins KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p15 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Tumor Suppressor Proteins KW - Index Medicus KW - Base Sequence KW - Homozygote KW - Humans KW - Molecular Sequence Data KW - Mutation KW - Chromosome Mapping KW - Genes, Tumor Suppressor KW - Carrier Proteins -- genetics KW - Urinary Bladder Neoplasms -- genetics KW - Chromosomes, Human, Pair 9 KW - Carcinoma, Transitional Cell -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77691654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Homozygous+deletions+but+no+sequence+mutations+in+coding+regions+of+p15+or+p16+in+human+primary+bladder+tumors.&rft.au=Packenham%2C+J+P%3BTaylor%2C+J+A%3BAnna%2C+C+H%3BWhite%2C+C+M%3BDevereux%2C+T+R&rft.aulast=Packenham&rft.aufirst=J&rft.date=1995-11-01&rft.volume=14&rft.issue=3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An in vitro flow model to study streaming during pelvic intra-arterial drug infusions. AN - 77684223; 7590489 AB - Regional delivery of suitable drugs by intra-arterial infusion may offer a therapeutic advantage. High concentrations in the tumor are sought with reduced systemic toxicity. Adequate mixing of drug solutions with perfusing blood is essential to provide uniform distribution of drug to tumor-bearing tissue distal to the infusion site. Using a glass model of the iliofemoral and pelvic arteries, we have demonstrated that a streaming phenomenon occurs. Laminar "streamers" of slowly infused drug solution originate at the catheter tip and proceed nonuniformly into distal arterial branches. The intensity of streaming and the pattern of distribution are highly sensitive to catheter tip placement and quite unpredictable. The consequence of regional therapy under streaming conditions is severe maldistribution of drug in the infused tissues with potentially high levels delivered to normal tissues and simultaneous subtherapeutic levels delivered to tumor. Our in vitro model can be used to test appropriate infusion techniques that enhance mixing such as pulsed infusions and novel catheter designs. JF - Gynecologic oncology AU - Lutz, R J AU - Epstein, A H AU - Cook, J A AU - Dedrick, R L AD - Biomedical Engineering and Instrumentation Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5766, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 288 EP - 296 VL - 59 IS - 2 SN - 0090-8258, 0090-8258 KW - Index Medicus KW - Humans KW - Femoral Artery KW - Regional Blood Flow KW - Iliac Artery KW - Models, Cardiovascular KW - Infusions, Intra-Arterial KW - Pelvis -- blood supply KW - Models, Anatomic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77684223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=An+in+vitro+flow+model+to+study+streaming+during+pelvic+intra-arterial+drug+infusions.&rft.au=Lutz%2C+R+J%3BEpstein%2C+A+H%3BCook%2C+J+A%3BDedrick%2C+R+L&rft.aulast=Lutz&rft.aufirst=R&rft.date=1995-11-01&rft.volume=59&rft.issue=2&rft.spage=288&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-19 N1 - Date created - 1995-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distribution of the DNA adducts of 2-amino-3-methylimidazo[4,5-f] quinoline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the supF gene as determined by polymerase arrest assay. AN - 77681383; 7576112 AB - The distribution of the adducts of the cooked meat-derived heterocyclic amines 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) was examined in the supF gene of PSP189 by a polymerase-arrest assay using thermal-cycle sequencing. The reactive N-acetoxy metabolites of both compounds showed an overwhelming preference for reacting with guanine residues in the supF gene of the shuttle vector pSP189. The distribution of the IQ and PhlP guanine adducts was not random; instead, patterns of adduct hot-spots and cold-spots were observed. There was a striking similarity between both compounds in their preferred sites of adduct formation. The finding that IQ and PhlP adducted to guanine concurred with previous results showing that the target sites for IQ and PhlP mutations in supF were also at guanine. However, the adduct hot-spot sites were not predictive of the known sites of mutation hot-spots. In addition, despite the similarity in adduct hot-spots for IQ and PhlP, their reported mutation spectra in the supF gene were different. Factors in addition to adduct location therefore appear to play a role in the mutation spectra induced by the heterocyclic amines in the supF gene. JF - Molecular carcinogenesis AU - Endo, H AU - Schut, H A AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 198 EP - 204 VL - 14 IS - 3 SN - 0899-1987, 0899-1987 KW - DNA Adducts KW - 0 KW - Imidazoles KW - Mutagens KW - Quinolines KW - supF tRNA KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - RNA, Transfer KW - 9014-25-9 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Base Sequence KW - Molecular Sequence Data KW - Autoradiography KW - Mutation KW - DNA-Directed DNA Polymerase -- metabolism KW - Binding Sites KW - Quinolines -- metabolism KW - RNA, Transfer -- genetics KW - DNA Adducts -- analysis KW - Mutagens -- metabolism KW - Imidazoles -- metabolism KW - Genes, Suppressor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77681383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Distribution+of+the+DNA+adducts+of+2-amino-3-methylimidazo%5B4%2C5-f%5D+quinoline+and+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+in+the+supF+gene+as+determined+by+polymerase+arrest+assay.&rft.au=Endo%2C+H%3BSchut%2C+H+A%3BSnyderwine%2C+E+G&rft.aulast=Endo&rft.aufirst=H&rft.date=1995-11-01&rft.volume=61&rft.issue=4&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurology%2C+neurosurgery%2C+and+psychiatry&rft.issn=00223050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electrocardiographic changes during desipramine and clomipramine treatment in children and adolescents. AN - 77673196; 8543513 AB - With the increased use of tricyclic antidepressants in children, and several reports of several sudden deaths associated with desipramine (DMI) treatment, systematic study of their cardiac effects is indicated. In the present study, DMI's and clomipramine's (CMI) short-term effects on the electrocardiogram (ECG) were compared, as well as the long-term effects of CMI. The ECGs of 47 children and adolescents in treatment trials were examined at baseline, after 5 weeks of CMI and of DMI treatment, and during CMI maintenance (mean duration 24.6 months). At 5 weeks of CMI and of DMI treatment, the heart rate, PR, QRS, and QT-corrected (QTc) intervals on ECG were significantly increased from baseline (p < .05); DMI increased PR and QRS intervals more than CMI (p < .05), and CMI increased QTc more (p < .05). Tachycardia was the most common change (36%). More patients experienced an incomplete intraventricular conduction delay during DMI treatment (23%, 9/39) than during CMI (2%, 1/47) (p < .05). Four patients (9%) acutely developed a prolonged QTc during either DMI or CMI. Long-term maintenance ECGs during CMI treatment (n = 25) were not significantly different from that at week 5, although some individuals developed or resolved specific ECG changes. CMI and DMI both produced ECG changes typically reported for tricyclic antidepressants, and they differed on specific ECG changes. Changes in ECG measures for individuals from short to long term suggest that continued monitoring is required. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Leonard, H L AU - Meyer, M C AU - Swedo, S E AU - Richter, D AU - Hamburger, S D AU - Allen, A J AU - Rapoport, J L AU - Tucker, E AD - Child Psychiatry Branch, NIMH, Bethesda, MD 20892-1600, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1460 EP - 1468 VL - 34 IS - 11 SN - 0890-8567, 0890-8567 KW - Antidepressive Agents, Tricyclic KW - 0 KW - Placebos KW - Clomipramine KW - NUV44L116D KW - Desipramine KW - TG537D343B KW - Index Medicus KW - Double-Blind Method KW - Death, Sudden -- etiology KW - Humans KW - Cross-Over Studies KW - Child KW - Tachycardia -- etiology KW - Adolescent KW - Male KW - Female KW - Desipramine -- pharmacology KW - Antidepressive Agents, Tricyclic -- pharmacology KW - Desipramine -- therapeutic use KW - Desipramine -- adverse effects KW - Antidepressive Agents, Tricyclic -- therapeutic use KW - Depressive Disorder -- drug therapy KW - Clomipramine -- pharmacology KW - Antidepressive Agents, Tricyclic -- adverse effects KW - Clomipramine -- adverse effects KW - Electrocardiography -- drug effects KW - Clomipramine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77673196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Electrocardiographic+changes+during+desipramine+and+clomipramine+treatment+in+children+and+adolescents.&rft.au=Leonard%2C+H+L%3BMeyer%2C+M+C%3BSwedo%2C+S+E%3BRichter%2C+D%3BHamburger%2C+S+D%3BAllen%2C+A+J%3BRapoport%2C+J+L%3BTucker%2C+E&rft.aulast=Leonard&rft.aufirst=H&rft.date=1995-11-01&rft.volume=34&rft.issue=11&rft.spage=1460&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-13 N1 - Date created - 1996-02-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Acad Child Adolesc Psychiatry. 1996 Jun;35(6):701-2 [8682748] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NMDA antagonist properties of the putative antiaddictive drug, ibogaine. AN - 77672262; 7473163 AB - Both anecdotal reports in humans and preclinical studies indicate that ibogaine interrupts addiction to a variety of abused substances including alcohol, opiates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrating that N-methyl-D-aspartate (NMDA) antagonists attenuate addiction-related phenomena, we examined the NMDA antagonist properties of ibogaine. Pharmacologically relevant concentrations of ibogaine produce a voltage-dependent block of NMDA receptors in hippocampal cultures (Ki, 2.3 microM at -60 mV). Consistent with this observation, ibogaine competitively inhibits [3H]1-[1-(2-thienyl)-cyclohexyl]piperidine binding to rat forebrain homogenates (Ki, 1.5 microM) and blocks glutamate-induced cell death in neuronal cultures (IC50, 4.5 microM). Moreover, at doses previously reported to interfere with drug-seeking behaviors, ibogaine substitutes as a discriminative stimulus (ED50, 64.9 mg/kg) in mice trained to discriminate the prototypic voltage-dependent NMDA antagonist, dizocilpine (0.17 mg/kg), from saline. Consistent with previous reports, ibogaine reduced naloxone-precipitated jumping in morphine-dependent mice (ED50, 72 mg/kg). Although pretreatment with glycine did not affect naloxone-precipitated jumping in morphine-dependent mice, it abolished the ability of ibogaine to block naloxone-precipitated jumping. Taken together, these findings link the NMDA antagonist actions of ibogaine to a putative "antiaddictive" property of this alkaloid, its ability to reduce the expression of morphine dependence. JF - The Journal of pharmacology and experimental therapeutics AU - Popik, P AU - Layer, R T AU - Fossom, L H AU - Benveniste, M AU - Geter-Douglass, B AU - Witkin, J M AU - Skolnick, P AD - Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 753 EP - 760 VL - 275 IS - 2 SN - 0022-3565, 0022-3565 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Naloxone KW - 36B82AMQ7N KW - Ibogaine KW - 3S814I130U KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Index Medicus KW - Rats KW - Naloxone -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Dizocilpine Maleate -- metabolism KW - Substance Withdrawal Syndrome KW - Electric Conductivity KW - Hippocampus KW - Cerebellum KW - Mice KW - Radioligand Assay KW - Male KW - Substance-Related Disorders -- drug therapy KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Ibogaine -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77672262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=NMDA+antagonist+properties+of+the+putative+antiaddictive+drug%2C+ibogaine.&rft.au=Popik%2C+P%3BLayer%2C+R+T%3BFossom%2C+L+H%3BBenveniste%2C+M%3BGeter-Douglass%2C+B%3BWitkin%2C+J+M%3BSkolnick%2C+P&rft.aulast=Popik&rft.aufirst=P&rft.date=1995-11-01&rft.volume=275&rft.issue=2&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-19 N1 - Date created - 1995-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Continuous intraoperative external monitoring of perfusate leak using iodine-131 human serum albumin during isolated perfusion of the liver and limbs. AN - 77654442; 8575471 AB - Regional isolated perfusion using tumor necrosis factor (TNF) shows significant promise for treatment of cancer which is limited to limbs or organs. The high toxicity of TNF requires very sensitive real time monitoring of leakage in order to avoid serious patient complications. Human serum albumin labeled with iodine-131 is used with an externally mounted and collimated NaI(Tl) detector to track the leakage of blood from the isolated perfusion blood circuit into the general systemic vascular space. Blood activity levels measured using the monitor demonstrated a very good correlation with blood serum samples taken concurrently with external monitoring. External monitoring can reduce the risks of perfusion leakage intraoperatively with the precision necessary to safely perform isolated perfusion using TNF. JF - European journal of nuclear medicine AU - Barker, W C AU - Andrich, M P AU - Alexander, H R AU - Fraker, D L AD - Nuclear Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1242 EP - 1248 VL - 22 IS - 11 SN - 0340-6997, 0340-6997 KW - Serum Albumin, Radio-Iodinated KW - 0 KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Combined Modality Therapy KW - Melphalan -- administration & dosage KW - Humans KW - Interferon-gamma -- administration & dosage KW - Extremities KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Liver Neoplasms -- therapy KW - Chemotherapy, Cancer, Regional Perfusion -- instrumentation KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Melanoma -- therapy KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Monitoring, Intraoperative -- methods KW - Liver Neoplasms -- secondary KW - Sarcoma -- therapy KW - Monitoring, Intraoperative -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77654442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+nuclear+medicine&rft.atitle=Continuous+intraoperative+external+monitoring+of+perfusate+leak+using+iodine-131+human+serum+albumin+during+isolated+perfusion+of+the+liver+and+limbs.&rft.au=Barker%2C+W+C%3BAndrich%2C+M+P%3BAlexander%2C+H+R%3BFraker%2C+D+L&rft.aulast=Barker&rft.aufirst=W&rft.date=1995-11-01&rft.volume=22&rft.issue=11&rft.spage=1242&rft.isbn=&rft.btitle=&rft.title=European+journal+of+nuclear+medicine&rft.issn=03406997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-13 N1 - Date created - 1996-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delayed effects of external radiation exposure: a brief history. AN - 77636432; 7480642 AB - Within months of Roentgen's discovery of X rays, severe adverse effects were reported, but not well publicized. As a result, over the next two decades, fluoroscope operators suffered lethal skin carcinomas. Later, case reports appeared concerning leukemia in radiation workers, and infants born with severe mental retardation after their mothers had been given pelvic radiotherapy early in pregnancy. Fluoroscopy and radiotherapy for benign disorders continued to be used with abandon until authoritative reports were published on the adverse effects of ionizing radiation by the U.S. NAS-NRC and the UK MRC in 1956. Meanwhile, exposure to the atomic bombs in Japan had occurred and epidemics of delayed effects began to be recognized among the survivors: cataracts (1949), leukemia (1952) and severe mental retardation among newborn infants after intrauterine exposure (1952). No statistically significant excess of germ-cell genetic effects was detected by six clinical measurements (1956), the F1 mortality (1981), cytogenetic studies (1987) or biochemical genetic studies (1988). Somatic cell effects were revealed by long-lasting chromosomal aberrations in peripheral lymphocytes (1968), and somatic cell mutations were found at the glycophorin A locus in erythrocytes (1992). Molecular biology is a likely focus of new studies based on the function of the gene for ataxia telangiectasia (1995), a disorder in which children have severe, even lethal acute radiation reactions when given conventional doses of radiotherapy for lymphoma, to which they are prone. Also, obligate heterozygote female relatives can be studied for increased susceptibility to radiation-induced breast cancer, as suggested by clinical studies. The tumor registries in Hiroshima and Nagasaki now provide incidence data that show the extent of increases in eight common cancers and no increase in eight others (1994). The possibility of very late effects of A-bomb exposure is suggested by recent reports of increased frequencies of hyperparathyroidism, parathyroid cancers and certain causes of death other than cancer. JF - Radiation research AU - Miller, R W AD - Genetic Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7360, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 160 EP - 169 VL - 144 IS - 2 SN - 0033-7587, 0033-7587 KW - Radioactive Fallout KW - 0 KW - Index Medicus KW - History of medicine KW - Space life sciences KW - Leukemia, Radiation-Induced -- history KW - History, 20th Century KW - Radiation Protection -- history KW - Nuclear Warfare KW - Humans KW - History, 19th Century KW - Forecasting KW - Cataract -- etiology KW - Abnormalities, Radiation-Induced KW - Time Factors KW - Female KW - Radioactive Fallout -- adverse effects KW - Pregnancy KW - Radiation Injuries -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77636432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Delayed+effects+of+external+radiation+exposure%3A+a+brief+history.&rft.au=Miller%2C+R+W&rft.aulast=Miller&rft.aufirst=R&rft.date=1995-11-01&rft.volume=144&rft.issue=2&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-30 N1 - Date created - 1995-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sorbinil prevention of diabetic-like retinopathy in the galactose-fed rat model. AN - 77619213; 7591626 AB - To determine if the retinal microangiopathies of the galactose-fed rat model of diabetic retinopathy can be prevented with the aldose reductase inhibitor sorbinil. Sprague-Dawley rats were fed 50% d-galactose with or without sorbinil (0.05% wt/wt), mixed biweekly with fresh diet. Rats in each group were examined frequently by slit lamp and were killed after 8, 16, and 24 months. Computer-assisted morphometry was performed on wholemounts of elastase retinal digest preparations. Cataracts developed in all galactose-fed untreated rats within 3 weeks but not in the sorbinil-treated rats even after 24 months. At 8 months, the galactose-fed untreated rats exhibited statistically significant increases in the mean capillary width, the percent of retinal area occupied by capillaries (capillary density), and the percent of microvascular area with capillaries > 20 microns wide (dilated channels), compared to controls. At 16 months, the galactose-fed untreated rats showed statistically significant increases over controls in both total mean capillary length and density, and two of the four rats examined had microaneurysms. At 24 months, all the galactose-fed untreated rats had microaneurysms and extensive areas with hypercellular meshworks composed of dilated channels characteristic of intraretinal microvascular abnormalities (IRMA). By contrast, galactose-fed, sorbinil-treated rats, at 24 months, had no IRMA and showed no statistically significant differences from control rats in any of the parameters measured morphometrically. All the galactose-induced retinal microangiopathies were prevented with sorbinil. Aldose reductase inhibitors may be beneficial in ameliorating the similar vascular lesions characteristic of human diabetic retinopathy, though the mechanism remains obscure. JF - Investigative ophthalmology & visual science AU - Robison, W G AU - Laver, N M AU - Jacot, J L AU - Glover, J P AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 2368 EP - 2380 VL - 36 IS - 12 SN - 0146-0404, 0146-0404 KW - Enzyme Inhibitors KW - 0 KW - Imidazoles KW - Imidazolidines KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - sorbinil KW - G4186B906P KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Capillaries -- pathology KW - Cataract -- prevention & control KW - Cataract -- chemically induced KW - Retinal Vessels -- drug effects KW - Disease Models, Animal KW - Image Processing, Computer-Assisted KW - Male KW - Retinal Vessels -- pathology KW - Diabetic Retinopathy -- pathology KW - Imidazoles -- pharmacology KW - Enzyme Inhibitors -- therapeutic use KW - Diabetic Retinopathy -- chemically induced KW - Imidazoles -- therapeutic use KW - Enzyme Inhibitors -- pharmacology KW - Aldehyde Reductase -- antagonists & inhibitors KW - Diabetic Retinopathy -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77619213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=Sorbinil+prevention+of+diabetic-like+retinopathy+in+the+galactose-fed+rat+model.&rft.au=Robison%2C+W+G%3BLaver%2C+N+M%3BJacot%2C+J+L%3BGlover%2C+J+P&rft.aulast=Robison&rft.aufirst=W&rft.date=1995-11-01&rft.volume=36&rft.issue=12&rft.spage=2368&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide potentiates hydrogen peroxide-induced killing of Escherichia coli. AN - 77616643; 7595217 AB - Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells from the cytotoxic effects of hydrogen peroxide (H2O2). Murine neutrophils and activated macrophages, however, produce NO, H2O2, and other reactive oxygen species to kill microorganisms, which suggests a paradox. In this study, we treated bacteria (Escherichia coli) with NO and H2O2 for 30 min and found that exposure to NO resulted in minimal toxicity, but greatly potentiated (up to 1,000-fold) H2O2-mediated killing, as evaluated by a clonogenic assay. The combination of NO/H2O2 induced DNA double strand breaks in the bacterial genome, as shown by field-inverted gel electrophoresis, and this increased DNA damage may correlate with cell killing. NO was also shown to alter cellular respiration and decrease the concentration of the antioxidant glutathione to a residual level of 15-20% in bacterial cells. The iron chelator desferrioxamine did not stop the action of NO on respiration and glutathione decrease, yet it prevented the NO/H2O2 synergistic cytotoxicity, implicating metal ions as critical participants in the NO/H2O2 cytocidal mechanism. Our results suggest a possible mechanism of modulation of H2O2-mediated toxicity, and we propose a new key role in the antimicrobial macrophagic response for NO. JF - The Journal of experimental medicine AU - Pacelli, R AU - Wink, D A AU - Cook, J A AU - Krishna, M C AU - DeGraff, W AU - Friedman, N AU - Tsokos, M AU - Samuni, A AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland 20892-1002, USA. Y1 - 1995/11/01/ PY - 1995 DA - 1995 Nov 01 SP - 1469 EP - 1479 VL - 182 IS - 5 SN - 0022-1007, 0022-1007 KW - DNA, Bacterial KW - 0 KW - Diethylamines KW - Isoenzymes KW - Siderophores KW - Nitric Oxide KW - 31C4KY9ESH KW - diethylamine KW - B035PIS86W KW - Hydrogen Peroxide KW - BBX060AN9V KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Glutathione KW - GAN16C9B8O KW - Deferoxamine KW - J06Y7MXW4D KW - Index Medicus KW - Superoxide Dismutase -- pharmacology KW - Deferoxamine -- pharmacology KW - Diethylamines -- pharmacology KW - DNA Damage KW - Drug Synergism KW - Cell Hypoxia KW - Glutathione -- pharmacology KW - Catalase -- pharmacology KW - Isoenzymes -- pharmacology KW - DNA, Bacterial -- drug effects KW - Siderophores -- pharmacology KW - Neutrophils -- drug effects KW - Escherichia coli -- metabolism KW - Hydrogen Peroxide -- pharmacology KW - Escherichia coli -- drug effects KW - Nitric Oxide -- pharmacology KW - Neutrophils -- physiology KW - Escherichia coli -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77616643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Nitric+oxide+potentiates+hydrogen+peroxide-induced+killing+of+Escherichia+coli.&rft.au=Pacelli%2C+R%3BWink%2C+D+A%3BCook%2C+J+A%3BKrishna%2C+M+C%3BDeGraff%2C+W%3BFriedman%2C+N%3BTsokos%2C+M%3BSamuni%2C+A%3BMitchell%2C+J+B&rft.aulast=Pacelli&rft.aufirst=R&rft.date=1995-11-01&rft.volume=182&rft.issue=5&rft.spage=1469&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-04 N1 - Date created - 1995-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1969 Nov 25;244(22):6049-55 [5389100] J Biol Chem. 1994 Nov 25;269(47):29409-15 [7961920] Anal Biochem. 1976 May 7;72:248-54 [942051] J Biol Chem. 1977 Nov 10;252(21):7667-72 [334765] Nucleic Acids Res. 1981 Jan 24;9(2):309-21 [6259625] Mol Cell Biochem. 1982 Dec 10;49(3):143-9 [6298593] Annu Rev Biochem. 1983;52:711-60 [6137189] Cell. 1984 May;37(1):67-75 [6373014] J Clin Invest. 1987 Feb;79(2):319-26 [3543052] Science. 1988 Apr 29;240(4852):640-2 [2834821] J Immunol. 1988 Oct 1;141(7):2407-12 [3139757] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1223-7 [2153975] Radiat Res. 1990 Feb;121(2):196-205 [2305038] Radiat Res. 1990 May;122(2):181-7 [2336464] Annu Rev Pharmacol Toxicol. 1990;30:535-60 [2188578] Biofactors. 1990 Oct;2(4):219-25 [2282138] Prog Nucleic Acid Res Mol Biol. 1991;40:221-53 [1851570] Pharmacol Rev. 1991 Jun;43(2):109-42 [1852778] Arch Biochem Biophys. 1991 Aug 1;288(2):481-7 [1654835] Science. 1991 Nov 15;254(5034):1001-3 [1948068] J Med Chem. 1991 Nov;34(11):3242-7 [1956043] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):444-8 [1346070] Eur J Immunol. 1992 Feb;22(2):441-6 [1537380] J Biol Chem. 1992 Mar 25;267(9):6370-4 [1372907] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030-4 [1557408] Science. 1992 Apr 10;256(5054):225-8 [1373522] J Immunol. 1992 Jun 15;148(12):3999-4005 [1318338] Biochim Biophys Acta. 1992 Jul 29;1127(2):131-40 [1643097] Lipids. 1992 Apr;27(4):261-5 [1518382] FASEB J. 1992 Sep;6(12):3051-64 [1381691] Arch Biochem Biophys. 1992 Nov 1;298(2):452-7 [1416976] Arch Biochem Biophys. 1993 Jan;300(1):115-23 [8424643] Chem Res Toxicol. 1992 Nov-Dec;5(6):834-42 [1336991] Free Radic Res Commun. 1993;18(4):195-9 [8396550] Free Radic Biol Med. 1993 Oct;15(4):447-51 [8225026] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9813-7 [8234317] EMBO J. 1993 Sep;12(9):3643-9 [7504626] Carcinogenesis. 1994 Mar;15(3):443-7 [8118926] Methods Enzymol. 1994;233:229-40 [8015460] Exp Cell Res. 1994 Sep;214(1):418-28 [7521848] J Biol Chem. 1994 Oct 14;269(41):25310-4 [7929223] Anal Biochem. 1969 Mar;27(3):502-22 [4388022] Carcinogenesis. 1994 Oct;15(10):2125-9 [7955043] J Biol Chem. 1994 Nov 25;269(47):29405-8 [7961919] Bacteriol Rev. 1974 Mar;38(1):87-110 [4601163] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Felbamate monotherapy: implications for antiepileptic drug development. AN - 77608428; 7588454 AB - We studied the effect of felbamate (FBM) monotherapy on seizure rate in patients with partial and secondarily generalized seizures undergoing presurgical monitoring at a single site. The study design was a double-blind placebo-controlled parallel monotherapy trial. Forty patients whose seizures had not been controlled by standard antiepileptic drugs (AEDs) were randomized. Seizure type was confirmed by video-EEG monitoring. All baseline AEDs were discontinued, and patients were drug-free for 5.3 +/- 2.4 days before randomization to FBM or placebo. After a 4-day titration, seizures were counted for 14 days. Patients receiving FBM had significantly lower seizure rates, whether all randomized patients, patients who survived titration, or study completers were compared. Eight of 19 placebo patients randomized to placebo, as compared with 13 of 21 receiving FBM, completed the 18-day study. Two FBM patients dropped out due to seizures, and 6 dropped out due to side effects, including anxiety, difficulty sleeping, abdominal discomfort, acute psychosis, and orobuccal dyskinesias. Ten placebo patients met the criteria for premature discontinuation owing to seizures, and 1 hd an episode of panic. There was no evidence of hepatic or hematologic toxicity. FBM reduces seizure frequency in patients with localization-related epilepsy. JF - Epilepsia AU - Theodore, W H AU - Albert, P AU - Stertz, B AU - Malow, B AU - Ko, D AU - White, S AU - Flamini, R AU - Ketter, T AD - National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1105 EP - 1110 VL - 36 IS - 11 SN - 0013-9580, 0013-9580 KW - Anticonvulsants KW - 0 KW - Drugs, Investigational KW - Phenylcarbamates KW - Placebos KW - Propylene Glycols KW - felbamate KW - X72RBB02N8 KW - Index Medicus KW - Drug Administration Schedule KW - Double-Blind Method KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - Propylene Glycols -- therapeutic use KW - Epilepsy -- drug therapy KW - Anticonvulsants -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77608428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=Felbamate+monotherapy%3A+implications+for+antiepileptic+drug+development.&rft.au=Theodore%2C+W+H%3BAlbert%2C+P%3BStertz%2C+B%3BMalow%2C+B%3BKo%2C+D%3BWhite%2C+S%3BFlamini%2C+R%3BKetter%2C+T&rft.aulast=Theodore&rft.aufirst=W&rft.date=1995-11-01&rft.volume=36&rft.issue=11&rft.spage=1105&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=00139580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-30 N1 - Date created - 1995-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single tyrosine substitution in the insulin-like growth factor I receptor inhibits ligand-induced receptor autophosphorylation and internalization, but not mitogenesis. AN - 77606834; 7588225 AB - The tyrosine kinase domains of the insulin and insulin-like growth factor I (IGF-I) receptors play an essential role in signal transduction. After ligand binding, these receptors undergo autophosphorylation, with a cluster of three tyrosines (residues 1131, 1135, and 1136 in the IGF-I receptor) being the first to be phosphorylated. Mutation of the ATP-binding site or substitution of this triple tyrosine cluster in the catalytic domain blocks essentially all of the functions of these receptors. Using stably transfected NIH-3T3 cell lines, we studied the effect of a mutation of tyrosine 1131 of the triple tyrosine cluster of the IGF-I receptor to phenylalanine. This mutation significantly reduced IGF-I-induced beta-subunit autophosphorylation, whereas phosphorylation of the endogenous substrate IRS-1 was unaffected. Despite the reduction in autophosphorylation and receptor internalization, IGF-I-induced thymidine incorporation and cellular proliferation were unaffected. Thus, the extent of receptor autophosphorylation and internalization does not appear to be a limiting factor for IGF-I-stimulated mitogenesis. JF - Endocrinology AU - Stannard, B AU - Blakesley, V AU - Kato, H AU - Roberts, C T AU - LeRoith, D AD - Section on Molecular and Cellular Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 4918 EP - 4924 VL - 136 IS - 11 SN - 0013-7227, 0013-7227 KW - Tyrosine KW - 42HK56048U KW - Phenylalanine KW - 47E5O17Y3R KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - DNA KW - 9007-49-2 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Base Sequence KW - Phosphorylation KW - Transfection KW - Adenosine Triphosphate -- metabolism KW - Molecular Sequence Data KW - Mice KW - DNA -- biosynthesis KW - Structure-Activity Relationship KW - Mutagenesis KW - Binding Sites KW - Tyrosine -- chemistry KW - Receptor, IGF Type 1 -- physiology KW - Receptor, IGF Type 1 -- chemistry KW - Cell Division -- physiology KW - Tyrosine -- genetics KW - Receptor, IGF Type 1 -- genetics KW - Tyrosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77606834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Single+tyrosine+substitution+in+the+insulin-like+growth+factor+I+receptor+inhibits+ligand-induced+receptor+autophosphorylation+and+internalization%2C+but+not+mitogenesis.&rft.au=Stannard%2C+B%3BBlakesley%2C+V%3BKato%2C+H%3BRoberts%2C+C+T%3BLeRoith%2C+D&rft.aulast=Stannard&rft.aufirst=B&rft.date=1995-11-01&rft.volume=136&rft.issue=11&rft.spage=4918&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-27 N1 - Date created - 1995-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucagon-like peptide-1 affects gene transcription and messenger ribonucleic acid stability of components of the insulin secretory system in RIN 1046-38 cells. AN - 77600866; 7588224 AB - It has been previously demonstrated that the enteric hormone glucagon-like peptide-1 (7-36 amide) (GLP-1) has acute effects on glucose-induced insulin secretion by RIN 1046-38 cells. In this study, we investigated the effects of extended exposure of RIN 1046-38 cells to GLP-1 and examine the mechanism by which GLP-1 synergizes with glucose in stimulating insulin secretion. Compared with cells cultured with glucose alone, incubation of cells with glucose plus 1 or 10 nM GLP-1 for 12 or 24 h significantly increased insulin release by about 3-fold, intracellular insulin content by 1.5-fold, and insulin messenger RNA (mRNA) by almost 2.5-fold. The insulinotropic effects of GLP-1 on RIN 1046-38 cells were accompanied by an up-regulation of both glucose transporter-1 (GLUT-1) and hexokinase I mRNA by about 2-fold. mRNA levels of GLUT-2 and glucokinase, which were low in controls, were unchanged by GLP-1 treatment. Treatment of cells with a transcription inhibitor, actinomycin D, demonstrated that elevated insulin mRNA levels after a GLP-1 exposure are mainly due to stabilization of the mRNA. In contrast, the elevated mRNA levels of GLUT-1 and hexokinase I are the result of increased transcription stimulated by GLP-1 exposure. Actinomycin D blunted the GLP-1 effect on insulin release but did not affect GLP-1 mediated elevation of insulin mRNA. This suggests that actinomycin D inhibits the transcription of the proteins necessary for insulin biosynthesis and insulin release, such as GLUT-1 and hexokinase I. Our study suggests that the mechanisms by which extended exposure of RIN 1046-38 cells to GLP-1 increases glucose-stimulated insulin secretion include significant up-regulation of glucose-sensing elements. JF - Endocrinology AU - Wang, Y AU - Egan, J M AU - Raygada, M AU - Nadiv, O AU - Roth, J AU - Montrose-Rafizadeh, C AD - Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 4910 EP - 4917 VL - 136 IS - 11 SN - 0013-7227, 0013-7227 KW - Culture Media, Conditioned KW - 0 KW - Glucose Transporter Type 1 KW - Insulin KW - Monosaccharide Transport Proteins KW - Peptide Fragments KW - Protein Precursors KW - RNA, Messenger KW - Slc2a1 protein, rat KW - Dactinomycin KW - 1CC1JFE158 KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - Cycloheximide KW - 98600C0908 KW - Hexokinase KW - EC 2.7.1.1 KW - Glucose KW - IY9XDZ35W2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Drug Stability KW - Pancreatic Neoplasms KW - Insulinoma KW - Rats KW - Dactinomycin -- pharmacology KW - Tumor Cells, Cultured KW - Glucose -- pharmacology KW - Cycloheximide -- pharmacology KW - Hexokinase -- genetics KW - Drug Synergism KW - Monosaccharide Transport Proteins -- genetics KW - Protein Precursors -- pharmacology KW - Transcription, Genetic -- drug effects KW - RNA, Messenger -- metabolism KW - Peptide Fragments -- pharmacology KW - Glucagon -- pharmacology KW - Insulin -- genetics KW - Insulin -- secretion KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77600866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Glucagon-like+peptide-1+affects+gene+transcription+and+messenger+ribonucleic+acid+stability+of+components+of+the+insulin+secretory+system+in+RIN+1046-38+cells.&rft.au=Wang%2C+Y%3BEgan%2C+J+M%3BRaygada%2C+M%3BNadiv%2C+O%3BRoth%2C+J%3BMontrose-Rafizadeh%2C+C&rft.aulast=Wang&rft.aufirst=Y&rft.date=1995-11-01&rft.volume=136&rft.issue=11&rft.spage=4910&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-27 N1 - Date created - 1995-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antibodies to interleukin 12 abrogate established experimental colitis in mice. AN - 77600030; 7595199 AB - In this study, we describe a novel murine model of chronic intestinal inflammation induced by the hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB/c and SJL/J mice resulted in a chronic transmural colitis with severe diarrhea, weight loss, and rectal prolapse, an illness that mimics some characteristics of Crohn's disease in humans. The colon of TNBS-treated mice on day 7 was marked by infiltration of CD4+ T cells; furthermore, in situ polymerase chain reaction studies revealed high levels of interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria (LP) CD4+ T cells from TNBS-treated mice stimulated with anti-CD3 and anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a 20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease in IL-4 levels as compared with those of stimulated LP CD4+ T cells from control BALB/c mice. Administration of monoclonal anti-IL-12 antibodies to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after induction of colitis led to a striking improvement in both the clinical and histopathological aspects of the disease and frequently abrogated the established colitis completely. Furthermore, LP CD4+ T cells isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon in vitro stimulation. In summary, the data demonstrate the pivotal role of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic intestinal inflammation. Furthermore, they suggest the potential utility of anti-IL-12 antibodies in patients with Crohn's disease. JF - The Journal of experimental medicine AU - Neurath, M F AU - Fuss, I AU - Kelsall, B L AU - Stüber, E AU - Strober, W AD - Mucosal Immunity Section, National Institutes of Health/National Institute of Allergy and Infectious Diseases/LCI, Bethesda, Maryland 20892-1890, USA. Y1 - 1995/11/01/ PY - 1995 DA - 1995 Nov 01 SP - 1281 EP - 1290 VL - 182 IS - 5 SN - 0022-1007, 0022-1007 KW - Antibodies, Monoclonal KW - 0 KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Trinitrobenzenesulfonic Acid KW - 8T3HQG2ZC4 KW - Index Medicus KW - AIDS/HIV KW - Trinitrobenzenesulfonic Acid -- toxicity KW - Animals KW - Colon -- pathology KW - Spleen -- pathology KW - Mice KW - CD4 Lymphocyte Count KW - Mice, Inbred BALB C KW - Colon -- immunology KW - Lymphocyte Activation KW - Mice, Inbred Strains KW - Base Sequence KW - Molecular Sequence Data KW - Spleen -- immunology KW - Interferon-gamma -- physiology KW - Interleukin-12 -- immunology KW - Colitis -- immunology KW - Interleukin-12 -- physiology KW - Crohn Disease KW - Disease Models, Animal KW - Colitis -- chemically induced KW - Interleukin-12 -- antagonists & inhibitors KW - Antibodies, Monoclonal -- therapeutic use KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77600030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Antibodies+to+interleukin+12+abrogate+established+experimental+colitis+in+mice.&rft.au=Neurath%2C+M+F%3BFuss%2C+I%3BKelsall%2C+B+L%3BSt%C3%BCber%2C+E%3BStrober%2C+W&rft.aulast=Neurath&rft.aufirst=M&rft.date=1995-11-01&rft.volume=182&rft.issue=5&rft.spage=1281&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-04 N1 - Date created - 1995-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunology. 1993 Jan;78(1):127-31 [8436398] Arch Biochem Biophys. 1992 Apr;294(1):230-7 [1347984] Cell. 1993 Oct 22;75(2):203-5 [8402907] Cell. 1993 Oct 22;75(2):253-61 [8402910] Cell. 1993 Oct 22;75(2):263-74 [8402911] Cell. 1993 Oct 22;75(2):274-82 [8104709] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10188-92 [7901851] J Exp Med. 1994 May 1;179(5):1551-61 [7909326] J Exp Med. 1994 Jul 1;180(1):211-22 [7516408] J Immunol. 1994 Nov 1;153(9):3967-78 [7930605] Infect Immun. 1994 Dec;62(12):5353-60 [7960114] Blood. 1994 Dec 15;84(12):4008-27 [7994020] J Immunol. 1995 Jan 1;154(1):116-27 [7527811] J Exp Med. 1995 Jan 1;181(1):381-6 [7528773] J Exp Med. 1995 Jan 1;181(1):387-91 [7807019] J Immunol. 1995 Feb 1;154(3):1232-8 [7529797] Eur J Immunol. 1995 Mar;25(3):672-6 [7705395] Immunity. 1994 Oct;1(7):553-62 [7600284] Gastroenterology. 1992 May;102(5):1524-34 [1314749] Proc Natl Acad Sci U S A. 1983 Oct;80(19):5842-6 [6310596] J Immunol Methods. 1987 Nov 5;103(2):161-7 [2889781] Gastroenterology. 1989 Mar;96(3):795-803 [2914642] J Exp Med. 1989 Sep 1;170(3):827-45 [2504877] Cell. 1990 Nov 30;63(5):1099-112 [2257626] N Engl J Med. 1991 Sep 26;325(13):928-37 [1881418] Nucleic Acids Res. 1993 Jul 11;21(14):3159-66 [7688113] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The varicella-zoster virus (VZV) open reading frame 47 (ORF47) protein kinase is dispensable for viral replication and is not required for phosphorylation of ORF63 protein, the VZV homolog of herpes simplex virus ICP22. AN - 77558817; 7474171 AB - To investigate the role of varicella-zoster virus (VZV) open reading frame 47 (ORF47) protein kinase during infection, a VZV mutant was generated in which two contiguous stop codons were introduced into ORF47, thus eliminating expression of the ORF47 kinase. ORF47 kinase was not essential for the growth of VZV in cultured cells, and the growth rate of the VZV mutant lacking ORF47 protein was indistinguishable from that of parental VZV. Nuclear extracts from cells infected with parental VZV contained several phosphorylated proteins which were not detected in extracts from cells infected with the ORF47 mutant. The herpes simplex virus type 1 (HSV-1) UL13 protein (the homolog of VZV ORF47 protein) is responsible for the posttranslational processing associated with phosphorylation of HSV-1 ICP22 (the homolog of VZV ORF63 protein). Immunoprecipitation of 32P-labeled proteins from cells infected with parental virus and those infected with ORF47 mutant virus yielded similar amounts of the VZV phosphoproteins encoded by ORF4, ORF62, ORF63, and ORF68 (VZV gE), and the electrophoretic migration of these proteins was not affected by the lack of ORF47 kinase. Therefore, while the VZV ORF47 protein is capable of phosphorylating several cellular or viral proteins, it is not required for phosphorylation of the ORF63 protein in virus-infected cells. JF - Journal of virology AU - Heineman, T C AU - Cohen, J I AD - Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 7367 EP - 7370 VL - 69 IS - 11 SN - 0022-538X, 0022-538X KW - ICP22 protein, human herpesvirus 1 KW - 0 KW - Immediate-Early Proteins KW - Nucleoproteins KW - Phosphoproteins KW - Recombinant Proteins KW - Viral Envelope Proteins KW - Viral Proteins KW - Viral Regulatory and Accessory Proteins KW - immediate early protein 63, Human herpesvirus 3 KW - EUS1 protein, Equine herpesvirus 1 KW - 149058-98-0 KW - Protein Kinases KW - EC 2.7.- KW - Varicella-Zoster ORF47-associated protein kinase KW - EC 2.7.1.- KW - Index Medicus KW - Humans KW - Nucleoproteins -- metabolism KW - Simplexvirus -- physiology KW - Cell Nucleus KW - Melanoma KW - Mutagenesis KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Nucleoproteins -- isolation & purification KW - Phosphoproteins -- isolation & purification KW - Cell Line KW - Phosphoproteins -- metabolism KW - Virus Replication KW - Protein Kinases -- metabolism KW - Herpesvirus 3, Human -- genetics KW - Immediate-Early Proteins -- metabolism KW - Open Reading Frames KW - Herpesvirus 3, Human -- enzymology KW - Herpesvirus 3, Human -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77558817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=The+varicella-zoster+virus+%28VZV%29+open+reading+frame+47+%28ORF47%29+protein+kinase+is+dispensable+for+viral+replication+and+is+not+required+for+phosphorylation+of+ORF63+protein%2C+the+VZV+homolog+of+herpes+simplex+virus+ICP22.&rft.au=Heineman%2C+T+C%3BCohen%2C+J+I&rft.aulast=Heineman&rft.aufirst=T&rft.date=1995-11-01&rft.volume=69&rft.issue=11&rft.spage=7367&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-01 N1 - Date created - 1995-12-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1994 Mar;68(3):1350-9 [8107200] Pharmacol Ther. 1993 Sep;59(3):343-89 [8309996] J Gen Virol. 1994 Feb;75 ( Pt 2):317-26 [8113753] J Virol. 1994 May;68(5):3317-23 [8151792] J Virol. 1994 Jul;68(7):4204-11 [8207795] J Biol Chem. 1975 May 25;250(10):4007-21 [236308] Infect Immun. 1978 Jan;19(1):199-203 [203532] Nucleic Acids Res. 1986 Feb 25;14(4):1765-77 [3005981] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] J Virol. 1989 Jan;63(1):450-5 [2535748] Nucleic Acids Res. 1989 Feb 11;17(3):1266 [2922271] J Gen Virol. 1989 May;70 ( Pt 5):1151-60 [2543772] J Gen Virol. 1992 Mar;73 ( Pt 3):521-30 [1312115] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7310-4 [1323829] Virology. 1992 Nov;191(1):9-18 [1329339] J Gen Virol. 1993 Mar;74 ( Pt 3):387-95 [8383174] Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6701-5 [8393574] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7376-80 [8394020] J Virol. 1994 Mar;68(3):1987-92 [8107260] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Processing of the envelope glycoprotein gp160 in immunotoxin-resistant cell lines chronically infected with human immunodeficiency virus type 1. AN - 77558708; 7474132 AB - We describe the isolation and characterization of variant cell lines which are chronically infected with the human immunodeficiency virus (HIV) and resistant to the action of immunotoxins directed against the HIV envelope protein. These variants all produce normal levels of HIV proteins, budding virions, and the envelope protein precursor gp160. Two of the variants, 10E and 11E, contain a mutation within the env gene which results in the production of a truncated precursor and altered processing and transport of the protein to the cell surface. Variants B9 and G4 are defective in gp160 cleavage and do not efficiently transport the envelope protein to the cell surface. There are no mutations in the expressed viruses of B9 and G4. These cell lines express higher levels of CD4 protein and mRNA than H9/NL4-3. Thus, 10E, 11E, B9, and G4 have escaped immunotoxin action by downmodulating the envelope protein from their cell surfaces. None of these variants produce infectious HIV. Two other immunotoxin-resistant variants, E9-3 and 41-17, produce normal levels of gp160, efficiently transport the cleaved and processed subunits to the cell surface, and secrete infectious HIV. These studies identify alterations in gp160 processing that underscore the importance of the relationship between HIV and the cell that it infects. JF - Journal of virology AU - Duensing, T D AU - Fang, H AU - Dorward, D W AU - Pincus, S H AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 7122 EP - 7131 VL - 69 IS - 11 SN - 0022-538X, 0022-538X KW - Antigens, CD KW - 0 KW - Antigens, CD4 KW - Gene Products, env KW - HIV Envelope Protein gp160 KW - Immunotoxins KW - Protein Precursors KW - RNA, Messenger KW - Index Medicus KW - AIDS/HIV KW - Antigens, CD -- biosynthesis KW - Genetic Variation KW - Virion -- genetics KW - Dose-Response Relationship, Drug KW - HeLa Cells KW - Humans KW - RNA, Messenger -- analysis KW - Cell Division -- drug effects KW - Drug Resistance KW - Virion -- physiology KW - RNA, Messenger -- biosynthesis KW - Virion -- ultrastructure KW - Genes, env KW - Antigens, CD4 -- biosynthesis KW - Cell Line KW - Microscopy, Electron, Scanning KW - HIV-1 -- genetics KW - Immunotoxins -- toxicity KW - Protein Precursors -- biosynthesis KW - Protein Processing, Post-Translational KW - HIV-1 -- physiology KW - Gene Products, env -- biosynthesis KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77558708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Processing+of+the+envelope+glycoprotein+gp160+in+immunotoxin-resistant+cell+lines+chronically+infected+with+human+immunodeficiency+virus+type+1.&rft.au=Duensing%2C+T+D%3BFang%2C+H%3BDorward%2C+D+W%3BPincus%2C+S+H&rft.aulast=Duensing&rft.aufirst=T&rft.date=1995-11-01&rft.volume=69&rft.issue=11&rft.spage=7122&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-01 N1 - Date created - 1995-12-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L42371; GENBANK N1 - SuppNotes - Cited By: FASEB J. 1994 Feb;8(2):201-8 [8119491] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):332-6 [8419938] J Gen Virol. 1994 Apr;75 ( Pt 4):857-65 [8151301] J Virol. 1995 Jan;69(1):75-81 [7983770] Virology. 1991 Sep;184(1):319-29 [1871974] AIDS Res Hum Retroviruses. 1991 Jun;7(6):501-10 [1931229] AIDS Res Hum Retroviruses. 1991 Aug;7(8):707-12 [1718346] J Virol. 1992 Jan;66(1):226-34 [1727486] J Virol. 1992 Feb;66(2):1207-9 [1731099] Virology. 1992 Apr;187(2):604-11 [1546456] Viral Immunol. 1992 Summer;5(2):163-72 [1319711] Antimicrob Agents Chemother. 1992 May;36(5):982-8 [1510424] J Virol. 1992 Dec;66(12):7193-200 [1433512] Nature. 1992 Nov 26;360(6402):358-61 [1360148] Science. 1985 May 31;228(4703):1091-4 [2986290] Science. 1985 Sep 27;229(4720):1402-5 [2994223] J Virol. 1986 Aug;59(2):284-91 [3016298] Science. 1986 Nov 28;234(4780):1123-7 [3095925] Nature. 1987 Nov 5-11;330(6143):74-7 [2959866] Cell. 1988 Apr 8;53(1):55-67 [2450679] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6944-8 [3413127] J Virol. 1988 Oct;62(10):3779-88 [3047430] Nature. 1988 Sep 22;335(6188):369-72 [2843774] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9248-52 [3264072] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] J Immunol. 1989 May 1;142(9):3070-5 [2540236] Proc Natl Acad Sci U S A. 1989 May;86(9):3384-8 [2541446] Intervirology. 1989;30(1):27-35 [2542177] J Virol. 1989 Jun;63(6):2452-6 [2542563] Proc Natl Acad Sci U S A. 1989 Dec;86(23):9539-43 [2480605] Virology. 1990 Jan;174(1):217-24 [2104682] Proc Natl Acad Sci U S A. 1990 Jan;87(2):648-52 [2300552] J Biol Chem. 1990 Feb 15;265(5):2640-9 [2406237] J Exp Med. 1990 Sep 1;172(3):745-57 [1696955] J Virol. 1990 Dec;64(12):6297-304 [2243395] J Infect Dis. 1991 Jan;163(1):64-70 [1984477] Virology. 1991 Mar;181(1):180-92 [1704656] J Virol. 1991 Apr;65(4):2047-55 [1900540] J Immunol. 1991 Jun 15;146(12):4315-24 [1710247] AIDS Res Hum Retroviruses. 1991 Mar;7(3):287-94 [1829617] Cancer Res. 1993 Jan 15;53(2):340-7 [8417828] J Virol. 1994 Apr;68(4):2570-7 [8139036] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence that flavivirus NS1-NS2A cleavage is mediated by a membrane-bound host protease in the endoplasmic reticulum. AN - 77547054; 7474145 AB - Previous deletion mutagenesis studies have shown that the flavivirus NS1-NS2A clevage requires the eight C-terminal residues of NS1, constituting the cleavage recognition sequence, and sequences in NS2A far downstream of the cleavage site. We now demonstrate that replacement of all of NS1 upstream of the cleavage recognition sequence with prM sequences still allows cleavage in vivo. Thus, other than the eight C-terminal residues, NS1 is dispensable for NS1-NS2A cleavage. However, deletion of the N-terminal signal sequence abrogated cleavage, suggesting that entry into the exocytic pathway is required. Cleavage in vivo was not blocked by brefeldin A, and cleavage could occur in vitro in the presence of dog pancreas microsomes, indicating that NS1-NS2A cleavage occurs in the endoplasmic reticulum. Four in-frame deletions in NS2A were cleavage defective in vitro, as were two mutants in which NS4A-NS4B sequences were substituted for NS2A, suggesting that most of NS2A is required. A series of substitution mutants were constructed in which all Asp, Cys, Glu, His, and Ser residues in NS2A were collectively replaced; all standard proteases require at least one of these residues in their active sites. No single mutant was cleavage defective, suggesting that NS2A is not a protease. Fractionation of the microsomes indicated that the lumenal contents were not required for NS1-NS2A cleavage. It seems most likely that NS1-NS2A cleavage is effected by a host membrane-bound endoplasmic reticulum-resident protease, quite possibly signalase, and that NS2A is required to present the cleavage recognition sequence in the correct conformation to the host enzyme for cleavage. JF - Journal of virology AU - Falgout, B AU - Markoff, L AD - Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 7232 EP - 7243 VL - 69 IS - 11 SN - 0022-538X, 0022-538X KW - Protein Sorting Signals KW - 0 KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Viral Nonstructural Proteins KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Endoplasmic Reticulum -- enzymology KW - Animals KW - Protein Sorting Signals -- metabolism KW - Humans KW - Amino Acid Sequence KW - Microsomes -- enzymology KW - Pancreas -- enzymology KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Recombinant Proteins -- metabolism KW - Restriction Mapping KW - Cercopithecus aethiops KW - Point Mutation KW - Dogs KW - Molecular Sequence Data KW - Substrate Specificity KW - Cell Line KW - Sequence Deletion KW - Endopeptidases -- metabolism KW - Flavivirus -- metabolism KW - Viral Nonstructural Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77547054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Evidence+that+flavivirus+NS1-NS2A+cleavage+is+mediated+by+a+membrane-bound+host+protease+in+the+endoplasmic+reticulum.&rft.au=Falgout%2C+B%3BMarkoff%2C+L&rft.aulast=Falgout&rft.aufirst=B&rft.date=1995-11-01&rft.volume=69&rft.issue=11&rft.spage=7232&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-01 N1 - Date created - 1995-12-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Enzymol. 1983;96:84-93 [6656655] J Biol Chem. 1983 Aug 10;258(15):9488-95 [6348046] Mol Cell Biol. 1985 Dec;5(12):3403-9 [3939316] Virology. 1986 Nov;155(1):77-88 [3022479] Virology. 1987 Aug;159(2):217-28 [3039728] J Gen Virol. 1988 Jan;69 ( Pt 1):23-34 [2826667] J Cell Biol. 1988 Apr;106(4):1035-42 [3283143] Virology. 1989 Mar;169(1):100-9 [2922923] J Virol. 1989 May;63(5):1852-60 [2522997] Virology. 1989 Apr;169(2):354-64 [2523178] Virology. 1989 Jul;171(1):302-5 [2525840] Virology. 1989 Jul;171(1):61-7 [2741348] Virology. 1990 Feb;174(2):450-8 [2154882] Virology. 1990 Jul;177(1):159-74 [2353452] J Membr Biol. 1990 May;115(3):195-201 [2197415] J Virol. 1990 Sep;64(9):4573-7 [2143546] Annu Rev Microbiol. 1990;44:649-88 [2174669] Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):517-21 [1846444] J Virol. 1991 May;65(5):2467-75 [2016768] Virology. 1991 Nov;185(1):505-8 [1926792] J Gen Virol. 1991 Nov;72 ( Pt 11):2727-32 [1658199] Experientia. 1992 Feb 15;48(2):118-29 [1740185] J Cell Biol. 1992 Mar;116(5):1071-80 [1740466] Biochem J. 1992 Mar 1;282 ( Pt 2):539-43 [1546969] J Biol Chem. 1992 Jul 5;267(19):13154-9 [1618816] Trends Biochem Sci. 1992 Nov;17(11):474-8 [1455520] J Cell Biol. 1993 Jan;120(1):95-102 [8416998] J Virol. 1993 Apr;67(4):2327-35 [8445732] Virology. 1993 Apr;193(2):888-99 [8460492] Cell. 1993 Jun 4;73(5):989-98 [8500184] Virology. 1993 Jan;192(1):38-51 [8517028] Cell. 1993 Nov 19;75(4):615-30 [8242738] Microbiol Rev. 1993 Dec;57(4):781-822 [8302216] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6218-22 [8392191] EMBO J. 1994 Feb 15;13(4):928-33 [8112307] Virology. 1994 Feb 15;199(1):114-23 [8116234] J Virol. 1994 Jun;68(6):3794-802 [8189517] J Virol. 1994 Sep;68(9):5765-71 [8057458] Virology. 1994 Nov 1;204(2):526-40 [7941319] J Gen Virol. 1995 Mar;76 ( Pt 3):573-80 [7897348] Science. 1995 Apr 28;268(5210):579-82 [7725107] J Gen Virol. 1995 Apr;76 ( Pt 4):979-84 [9049346] J Cell Biol. 1982 Apr;93(1):97-102 [7068762] Nucleic Acids Res. 1986 Jun 11;14(11):4683-90 [3714490] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p6Gag is required for particle production from full-length human immunodeficiency virus type 1 molecular clones expressing protease. AN - 77542395; 7474093 AB - The human immunodeficiency virus type 1 (HIV-1) Gag protein precursor, Pr55Gag, contains at its C-terminal end a proline-rich, 6-kDa domain designated p6. Two functions have been proposed for p6: incorporation of the HIV-1 accessory protein Vpr into virus particles and virus particle production. To characterize the role of p6 in the HIV-1 life cycle and to map functional domains within p6, we introduced a number of nonsense and single and multiple amino acid substitution mutations into p6. Following the introduction of the mutations into the full-length HIV-1 molecular clone pNL4-3, the effects on Gag protein expression and processing, virus particle production, and virus infectivity were analyzed. The production of mutant virus particles was also examined by transmission electron microscopy. The results indicate that (i) p6 is required for efficient virus particle production from a full-length HIV-1 molecular clone; (ii) a Pro-Thr-Ala-Pro sequence, located between residues 7 and 10 of p6, is critical for virus particle production; (iii) mutations outside the Pro-Thr-Ala-Pro motif have little or no effect on virus assembly and release; (iv) the p6 defect is manifested at a late stage in the budding process; and (v) mutations in p6 that severely reduce virion production in HeLa cells also block or significantly delay the establishment of a productive infection in the CEM (12D-7) T-cell line. We further demonstrate that mutational inactivation of the viral protease reverses the p6 defect, suggesting a functional linkage between p6 and the proteolytic processing of the Gag precursor protein during the budding of progeny virions. JF - Journal of virology AU - Huang, M AU - Orenstein, J M AU - Martin, M A AU - Freed, E O AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-0460, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 6810 EP - 6818 VL - 69 IS - 11 SN - 0022-538X, 0022-538X KW - Gene Products, gag KW - 0 KW - Gene Products, vpr KW - Recombinant Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - p6 gag protein, Human immunodeficiency virus 1 KW - vpr Gene Products, Human Immunodeficiency Virus KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Genes, pol KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Proteins -- metabolism KW - Gene Products, vpr -- metabolism KW - Kinetics KW - Point Mutation KW - Capsid -- biosynthesis KW - Molecular Sequence Data KW - Microscopy, Electron KW - Time Factors KW - Cell Line KW - Virus Replication KW - HIV-1 -- enzymology KW - Gene Products, gag -- biosynthesis KW - HIV-1 -- physiology KW - HIV Protease -- biosynthesis KW - Gene Products, gag -- metabolism KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77542395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=p6Gag+is+required+for+particle+production+from+full-length+human+immunodeficiency+virus+type+1+molecular+clones+expressing+protease.&rft.au=Huang%2C+M%3BOrenstein%2C+J+M%3BMartin%2C+M+A%3BFreed%2C+E+O&rft.aulast=Huang&rft.aufirst=M&rft.date=1995-11-01&rft.volume=69&rft.issue=11&rft.spage=6810&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-01 N1 - Date created - 1995-12-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1986 Nov;60(2):450-9 [2430109] Biochim Biophys Acta. 1987 Jul 8;907(2):93-123 [3036230] J Virol. 1988 Jan;62(1):139-47 [3257102] J Virol. 1988 Feb;62(2):479-87 [2826810] J Virol. 1988 May;62(5):1808-9 [3357211] J Virol. 1988 Sep;62(9):3217-23 [2841473] EMBO J. 1988 Jun;7(6):1777-83 [2458920] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8420-4 [3141927] Virology. 1994 Dec;205(2):496-502 [7975251] Cell. 1995 Jan 27;80(2):237-48 [7834743] J Virol. 1995 Mar;69(3):1778-84 [7853517] J Virol. 1995 Mar;69(3):1984-9 [7853546] Virology. 1995 Feb 1;206(2):854-65 [7856098] J Virol. 1995 May;69(5):2759-64 [7707498] J Virol. 1995 Jun;69(6):3407-19 [7745687] J Virol. 1988 Nov;62(11):3993-4002 [3262776] J Virol. 1978 Jun;26(3):750-61 [78989] J Virol. 1983 Nov;48(2):361-9 [6312093] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] J Virol. 1989 May;63(5):2370-3 [2649693] J Virol. 1989 Jun;63(6):2550-6 [2657099] Nature. 1989 Aug 3;340(6232):397-400 [2666861] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 [2788277] Cell. 1989 Oct 6;59(1):103-12 [2676191] Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 [2405382] Science. 1990 Jan 26;247(4941):454-6 [2405486] AIDS Res Hum Retroviruses. 1990 Jun;6(6):721-30 [2194551] J Virol. 1990 Aug;64(8):3995-4001 [2164607] Cell. 1990 Sep 7;62(5):875-87 [1975516] J Virol. 1990 Oct;64(10):4978-87 [2168981] J Virol. 1991 Feb;65(2):922-30 [1987379] EMBO J. 1991 Mar;10(3):535-46 [1705884] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3195-9 [2014240] J Virol. 1991 Jul;65(7):3804-12 [1710290] J Virol. 1991 Aug;65(8):4350-8 [2072454] Virology. 1991 Sep;184(1):319-29 [1871974] Virology. 1991 Sep;184(1):417-22 [1871977] AIDS. 1991 Jun;5(6):639-54 [1883539] J Gen Virol. 1991 Oct;72 ( Pt 10):2509-17 [1919528] Virology. 1992 Jan;186(1):25-39 [1727601] J Virol. 1992 Jul;66(7):4220-7 [1602542] J Virol. 1992 Jul;66(7):4479-87 [1318415] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Dec;66(12):7021-32 [1279197] J Gen Virol. 1992 Dec;73 ( Pt 12):3079-86 [1469349] Virology. 1993 Apr;193(2):661-71 [7681610] Virology. 1993 Apr;193(2):981-5 [8460500] J Virol. 1993 Jul;67(7):4050-5 [8510215] J Virol. 1993 Jul;67(7):4264-73 [7685414] J Virol. 1993 Sep;67(9):5550-61 [8394460] Biochim Biophys Acta. 1993 Sep 8;1182(2):157-61 [8357847] J Virol. 1993 Oct;67(10):6159-69 [8371356] J Virol. 1993 Nov;67(11):6387-94 [8411340] J Virol. 1993 Nov;67(11):6487-98 [8411352] J Virol. 1993 Nov;67(11):6542-50 [8411357] J Virol. 1993 Dec;67(12):7229-37 [8230445] J Virol. 1994 Jan;68(1):111-22 [8254720] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Apr;68(4):2503-12 [8139032] Virology. 1994 Aug 15;203(1):20-8 [8030280] J Virol. 1994 Aug;68(8):4927-36 [8035491] J Virol. 1994 Aug;68(8):5311-20 [8035531] J Virol. 1994 Oct;68(10):6161-9 [8083957] J Virol. 1994 Oct;68(10):6605-18 [8083996] J Virol. 1994 Oct;68(10):6782-6 [8084015] J Gen Virol. 1994 Nov;75 ( Pt 11):2985-97 [7964608] J Virol. 1994 Dec;68(12):8017-27 [7966591] J Virol. 1994 Dec;68(12):8180-7 [7966609] J Virol. 1984 Mar;49(3):918-24 [6199513] Proc Natl Acad Sci U S A. 1984 Jul;81(13):4149-53 [6330745] Virology. 1985 Sep;145(2):280-92 [2411050] J Virol. 1986 Aug;59(2):284-91 [3016298] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Herpes simplex virus trans-regulatory protein ICP27 stabilizes and binds to 3' ends of labile mRNA. AN - 77540066; 7474140 AB - Previous work demonstrated that a herpes simplex virus type 1 (HSV-1) immediate-early function up-regulates beta interferon but not chloramphenicol acetyltransferase reporter genes driven by the strong simian virus 40 (SV40) or cytomegalovirus promoter-enhancer regions in both transient assays and stable cell lines. The different 3' mRNA stabilization and RNA-processing signals from these two reporter genes appeared to be primarily responsible for this phenomenon. We now report that the HSV-1 ICP27 itself is sufficient to stimulate both steady-state accumulation and increased half-life of beta interferon reporter gene mRNA. Furthermore, the ability to respond directly to cotransfected ICP27 can be transferred to chloramphenicol acetyltransferase reporter genes by replacement of their SV40-derived splicing and poly(A) signals with the 3' AU-rich and poly(A) RNA-processing signals from the normally highly labile beta interferon and c-myc mRNA species. ICP27 expressed in bacteria bound specifically to in vitro-generated RNA from both the beta interferon and c-myc intronless AU-rich 3' RNA-processing regions, but not to the SV40-derived early-region splice signal and poly(A) sequences. By site-specific mutagenesis, we also show that individual ICP27 C-terminal amino acid residues that are positionally conserved in ICP27 homologs in other herpesviruses (D-357, E-358, H-479, C-400, C-483, and C-488) are critical for trans-regulatory activity. Importantly, several of these positions match mutations that are known to be essential for the role of ICP27 in the early-to-late switch during the virus lytic cycle. Therefore, our findings support the notion that HSV ICP27 modulates gene expression posttranscriptionally in part by targeting RNA. JF - Journal of virology AU - Brown, C R AU - Nakamura, M S AU - Mosca, J D AU - Hayward, G S AU - Straus, S E AU - Perera, L P AD - Medical Virology Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 7187 EP - 7195 VL - 69 IS - 11 SN - 0022-538X, 0022-538X KW - ICP27 protein, human herpesvirus 1 KW - 0 KW - Immediate-Early Proteins KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Trans-Activators KW - Viral Proteins KW - Interferon-beta KW - 77238-31-4 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Simian virus 40 -- genetics KW - Humans KW - Recombinant Fusion Proteins -- isolation & purification KW - Transcription, Genetic KW - Amino Acid Sequence KW - Protein Binding KW - Promoter Regions, Genetic KW - Conserved Sequence KW - Transfection KW - Enhancer Elements, Genetic KW - Glutathione Transferase -- biosynthesis KW - Cytomegalovirus -- genetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Species Specificity KW - Cell Line KW - Trans-Activators -- metabolism KW - Trans-Activators -- biosynthesis KW - RNA, Messenger -- metabolism KW - Simplexvirus -- genetics KW - Viral Proteins -- chemistry KW - Gene Expression KW - Viral Proteins -- metabolism KW - Viral Proteins -- biosynthesis KW - Simplexvirus -- metabolism KW - Interferon-beta -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77540066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Herpes+simplex+virus+trans-regulatory+protein+ICP27+stabilizes+and+binds+to+3%27+ends+of+labile+mRNA.&rft.au=Brown%2C+C+R%3BNakamura%2C+M+S%3BMosca%2C+J+D%3BHayward%2C+G+S%3BStraus%2C+S+E%3BPerera%2C+L+P&rft.aulast=Brown&rft.aufirst=T&rft.date=1996-10-01&rft.volume=16&rft.issue=5&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Nihon+shinkei+seishin+yakurigaku+zasshi+%3D+Japanese+journal+of+psychopharmacology&rft.issn=13402544&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-01 N1 - Date created - 1995-12-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1994 Jun;68(6):3943-54 [8189530] J Virol. 1994 Aug;68(8):4797-810 [8035480] Science. 1994 Jul 29;265(5172):615-21 [8036511] Virology. 1994 Oct;204(1):242-50 [8091655] Oncogene. 1994 Nov;9(11):3299-304 [7936654] J Virol. 1990 Apr;64(4):1704-15 [2157053] J Virol. 1990 Jul;64(7):3471-85 [2161950] J Virol. 1991 Jul;65(7):3656-66 [1645788] Virology. 1992 Jan;186(1):74-86 [1309283] Virology. 1992 Feb;186(2):573-8 [1733102] J Virol. 1981 Jul;39(1):150-61 [6268805] J Virol. 1983 Jan;45(1):397-407 [6296445] J Virol. 1983 May;46(2):371-7 [6302308] J Mol Biol. 1984 Nov 25;180(1):1-19 [6096556] J Virol. 1985 Mar;53(3):751-60 [2983086] Mol Cell Biol. 1985 May;5(5):957-63 [2987684] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] J Virol. 1985 Sep;55(3):796-805 [2991596] Proc Natl Acad Sci U S A. 1985 Aug;82(16):5265-9 [2991915] J Virol. 1985 Nov;56(2):558-70 [2997476] J Virol. 1985 Dec;56(3):723-33 [2999428] Cell. 1986 Aug 29;46(5):659-67 [3488815] J Virol. 1986 Oct;60(1):140-8 [3018281] J Virol. 1986 Oct;60(1):149-56 [3018282] Mol Cell Biol. 1985 Aug;5(8):1997-2008 [3018543] J Gen Virol. 1986 Nov;67 ( Pt 11):2507-13 [3023536] J Virol. 1987 Mar;61(3):819-28 [2433469] Cell. 1987 Feb 27;48(4):691-701 [3643816] EMBO J. 1986 Dec 1;5(12):3243-9 [3028777] J Cell Biol. 1987 Nov;105(5):2069-82 [2824525] Mol Cell Biol. 1987 Dec;7(12):4513-21 [3325826] J Gen Virol. 1988 Jul;69 ( Pt 7):1531-74 [2839594] J Virol. 1988 Sep;62(9):3250-7 [2841477] J Virol. 1988 Oct;62(10):3814-23 [2843677] J Virol. 1988 Dec;62(12):4510-22 [2846867] J Virol. 1989 Jan;63(1):18-27 [2535723] Virus Res. 1988 Nov;11(4):269-79 [2851895] Virology. 1989 Jun;170(2):496-504 [2543126] J Virol. 1989 Sep;63(9):3870-7 [2548002] J Virol. 1989 Nov;63(11):4590-602 [2552143] Genes Dev. 1992 May;6(5):848-63 [1315705] J Virol. 1992 Jun;66(6):3811-22 [1316484] Virology. 1992 Jul;189(1):377-84 [1318613] EMBO J. 1992 Jul;11(7):2655-64 [1628625] J Virol. 1992 Sep;66(9):5298-304 [1323696] Proc Natl Acad Sci U S A. 1990 Oct;87(20):7799-803 [2172963] J Virol. 1992 Sep;66(9):5363-72 [1323700] J Virol. 1994 Dec;68(12):7790-9 [7966568] J Virol. 1994 Dec;68(12):8158-68 [7966607] J Virol. 1995 Jan;69(1):476-91 [7983744] J Virol. 1995 Jan;69(1):49-59 [7983745] J Virol. 1995 Feb;69(2):935-47 [7529337] J Virol. 1989 Dec;63(12):5276-84 [2555554] Virology. 1989 Dec;173(2):750-4 [2556854] Cell. 1989 Dec 22;59(6):1093-105 [2557159] Nature. 1992 Sep 10;359(6391):162-5 [1522903] J Virol. 1992 Dec;66(12):6939-45 [1331504] J Virol. 1993 Feb;67(2):1105-9 [8380457] J Virol. 1993 Mar;67(3):1328-33 [8382298] J Virol. 1993 Apr;67(4):1778-87 [8383210] Biochem Biophys Res Commun. 1993 Feb 26;191(1):18-25 [8447821] J Virol. 1993 Aug;67(8):4676-87 [8392607] Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6701-5 [8393574] Virology. 1993 Sep;196(1):1-14 [8395110] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9056-60 [8415652] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9528-32 [8415735] J Virol. 1994 Feb;68(2):823-33 [8289386] J Virol. 1994 Apr;68(4):2468-77 [8139031] J Virol. 1994 May;68(5):3267-82 [8151788] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Viruses and human cancers: challenges for preventive strategies. AN - 21251459; 11701724 AB - Virus-associated human cancers provide unique opportunities for preventive strategies. The role of human papilloma viruses (HPV 16 and 18), hepatitis B virus (HBV), Epstein-Barr herpes virus (EBV), and retroviruses (human immunodeficiency virus [HIV] and human T-cell leukemia/lymphoma virus [HTLV]) in the development of common carcinomas and lymphomas represents a major cancer threat, particularly among individuals residing in developing countries, which account for 80% of the world's population. Even though these viruses are not the sole etiological agents of these cancers (as would be the case for infectious diseases), different approaches can be implemented to significantly decrease the incidence of virus-associated malignancies. The first approach is vaccination, which is available for HBV and possibly soon for EBV. The long delay between primary viral infection and development of associated tumors as well as the cost involved with administering vaccinations detracts from the feasibility of such an approach within developing countries. The second approach is to increase efforts to detect pre-cancerous lesions or early tumors using immunovirological means. This would allow early diagnosis and better treatment. The third strategy is linked to the existence of disease susceptibility genes, and suggests that counseling be provided for individuals carrying these genes to encourage them to modify their lifestyles and other conditions associated with increased cancer risks (predictive oncology). Specific recommendations include: a) increase international studies that explore the causes of the large variations in prevalence of common cancers throughout the world; b) conduct interdisciplinary studies involving laboratory investigation and social sciences, which may suggest hypotheses that may then be tested experimentally; and c) promote more preventive and health enhancement strategies in addition to curative and replacement therapies. JF - Environmental Health Perspectives AU - de The, G AD - Fogarty International Center, National Institutes of Health, Bethesda, Maryland and Institut Pasteur, Unit of Epidemiology of Oncogenic Viruses, Paris, France., dethe@pasteur.fr Y1 - 1995/11// PY - 1995 DA - Nov 1995 SP - 269 EP - 273 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 103 IS - Suppl 8 SN - 0091-6765, 0091-6765 KW - Virology & AIDS Abstracts; Risk Abstracts; Environment Abstracts; Immunology Abstracts KW - Human T-lymphotropic virus KW - Feasibility studies KW - Herpesvirus KW - Viruses KW - tumors KW - Oncology KW - hepatitis B KW - Infection KW - Herpes simplex KW - Leukemia KW - world population KW - Epstein-Barr virus KW - Malignancy KW - Retrovirus KW - Infectious diseases KW - infection KW - Lymphocytes T KW - Lesions KW - Papilloma KW - Lymphoma KW - Hepatitis B virus KW - Laboratory testing KW - Tumors KW - Vaccination KW - Cancer KW - Carcinoma KW - Human immunodeficiency virus KW - social sciences KW - lymphoma KW - Developing countries KW - Human papillomavirus KW - ENA 13:Population Planning & Control KW - V 22360:AIDS and HIV KW - R2 23060:Medical and environmental health KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21251459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Viruses+and+human+cancers%3A+challenges+for+preventive+strategies.&rft.au=de+The%2C+G&rft.aulast=de+The&rft.aufirst=G&rft.date=1995-11-01&rft.volume=103&rft.issue=Suppl+8&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Malignancy; Infectious diseases; Lymphocytes T; Oncology; Tumors; Infection; Papilloma; Herpes simplex; Developing countries; Vaccination; Lymphoma; Carcinoma; Feasibility studies; Laboratory testing; Viruses; tumors; hepatitis B; Cancer; world population; Leukemia; Human immunodeficiency virus; infection; Lesions; social sciences; lymphoma; Human T-lymphotropic virus; Epstein-Barr virus; Retrovirus; Hepatitis B virus; Herpesvirus; Human papillomavirus ER - TY - JOUR T1 - Who Comes to a Voluntary Depression Screening Program? AN - 1761700213; 199602342 AB - Survey data are used to describe 5,367 adult volunteers at 345 facilities offering a voluntary screening program on National Depression Screening Day in 1992. The prevalence of depression detected at the screening test & sociodemographic characteristics & treatment history of the respondents (Rs) are explored, & the % of Rs who would actually have a diagnosis of major depression is estimated. On the Zung Self-Rating Depression Scale, 76.6% of Rs had at least minimal depressive symptoms, 53.3% had at least moderate symptoms, & 22.6% had severe symptoms. Few of the depressed Rs were currently in treatment for a mental health problem. The positive predictive value of a screening test diagnosis of depression was 92.5%-95.5% when a cutoff score of 60 was used, & 88.7%-92.3% when a cutoff score of 50 was used. It is concluded that such voluntary screening tests provide a good opportunity for identifying previously unidentified & untreated individuals with depression. 5 Tables, 25 References. Adapted from the source document. JF - The American Journal of Psychiatry AU - Magruder, Kathryn M AU - Norquist, Grayson S AU - Feil, Michael B AU - Kopans, Barbara AU - Jacobs, Douglas AD - Division Epidemiology & Services Research Services Research Branch NIMH, 5600 Fishers Ln Room 10C-06 Rockville MD 20857 Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1615 EP - 1622 VL - 152 IS - 11 SN - 0002-953X, 0002-953X KW - voluntary depression screening, participant characteristics KW - scale data KW - Volunteers KW - Diagnosis KW - Depression (Psychology) KW - Client Characteristics KW - Tests KW - article KW - 6142: mental & emotional problems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1761700213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Psychiatry&rft.atitle=Who+Comes+to+a+Voluntary+Depression+Screening+Program%3F&rft.au=Magruder%2C+Kathryn+M%3BNorquist%2C+Grayson+S%3BFeil%2C+Michael+B%3BKopans%2C+Barbara%3BJacobs%2C+Douglas&rft.aulast=Magruder&rft.aufirst=Kathryn&rft.date=1995-11-01&rft.volume=152&rft.issue=11&rft.spage=1615&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2016-02-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Depression (Psychology); Diagnosis; Tests; Client Characteristics; Volunteers ER -