TY - JOUR T1 - Early onset and rapid progression of dominant nonsyndromic DFNA36 hearing loss. AN - 85376474; pmid-15354000 AB - To characterize the auditory and vestibular phenotype of autosomal dominant nonsyndromic DFNA36 hearing loss.Clinical evaluation of individuals with DFNA36 hearing loss linked to the D572N mutation of transmembrane channel-like gene 1 (TMC1). Medical history interviews, physical examinations, and pure-tone air conduction audiometry were performed in the field. Audiology and radiology reports were available and retrospectively reviewed for a subset of subjects.Primary, secondary, and tertiary referral centers (retrospectively reviewed studies); subjects' homes (prospective clinical evaluations).Thirteen affected members of a North American Caucasian family segregating DFNA36 hearing loss.Pure-tone audiometric thresholds and their rates of progression.Subjects had bilateral, symmetric, sensorineural hearing loss with a postlingual onset in the first decade of life. High frequencies were initially affected, followed by rapid progression (5.9 dB/yr for the 0.5/1/2/4-kHz pure-tone average) to profound deafness across all frequencies by the second decade of life. Two individuals had excellent auditory-verbal communication after rehabilitation with cochlear implants placed over two decades after total deafening.DFNA36 has one of the earliest onsets and most rapid rates of progression among the autosomal dominant non-syndromic hearing loss phenotypes. These distinctive features should facilitate its clinical detection and the development of clinical-molecular genetic diagnostic algorithms for dominant nonsyndromic hearing loss. JF - Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology AU - Makishima, Tomoko AU - Kurima, Kiyoto AU - Brewer, Carmen C AU - Griffith, Andrew J AD - Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA. Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 714 EP - 719 VL - 25 IS - 5 SN - 1531-7129, 1531-7129 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Age of Onset KW - Aged KW - Audiometry, Pure-Tone KW - *Auditory Threshold: physiology KW - Child KW - Child, Preschool KW - Cross-Sectional Studies KW - Disease Progression KW - Female KW - *Hearing Loss, Sensorineural: genetics KW - Humans KW - Male KW - Middle Aged KW - Pedigree KW - Phenotype KW - Regression Analysis KW - Retrospective Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85376474?accountid=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=Otology+%26+neurotology+%3A+official+publication+of+the+American+Otological+Society%2C+American+Neurotology+Society+%5Band%5D+European+Academy+of+Otology+and+Neurotology&rft.atitle=Early+onset+and+rapid+progression+of+dominant+nonsyndromic+DFNA36+hearing+loss.&rft.au=Makishima%2C+Tomoko%3BKurima%2C+Kiyoto%3BBrewer%2C+Carmen+C%3BGriffith%2C+Andrew+J&rft.aulast=Makishima&rft.aufirst=Tomoko&rft.date=2004-09-01&rft.volume=25&rft.issue=5&rft.spage=714&rft.isbn=&rft.btitle=&rft.title=Otology+%26+neurotology+%3A+official+publication+of+the+American+Otological+Society%2C+American+Neurotology+Society+%5Band%5D+European+Academy+of+Otology+and+Neurotology&rft.issn=15317129&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - HIV and the kidney: a status report after 20 years. AN - 67291924; 16091230 AB - The first association between HIV-1 infection and kidney disease was made in 1984 and much has been learned over the past 20 years. In recent years, more effective therapies for HIV-1 infection and its associated opportunistic infections have led to improved patient survival. However, with prolonged survival, morbidity associated with renal disease has also increased. Among the multiple glomerulopathies that can affect patients with HIV, focal segmental glomerulosclerosis (FSGS) is most common and frequently leads to end-stage renal disease. Although the precise mechanisms of HIV-associated FSGS remain to be elucidated, it appears that host genetic susceptibility, direct infection of the renal epithelium, and toxicity of one or more viral accessory protein contribute. Therapy for HIV-associated FSGS includes control of blood pressure and the use of angiotensin antagonist therapy. A randomized trial of angiotensin receptor blocker will be initiated shortly. Drug-related nephropathies are also common, manifesting as acute renal failure, nephrolithiasis, and interstitial nephritis. Tenofovir, a newer nucleoside analogue, has recently been implicated in causing tubular toxicity, although the incidence is low. Appropriate screening for renal dysfunction can minimize the likelihood of progressive renal injury in all patients with HIV-1 infection. JF - Current HIV/AIDS reports AU - Cho, Monique E AU - Kopp, Jeffrey B AD - Kidney Disease Section, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health/DHHS, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 109 EP - 115 VL - 1 IS - 3 SN - 1548-3568, 1548-3568 KW - Angiotensin-Converting Enzyme Inhibitors KW - 0 KW - Anti-HIV Agents KW - Antihypertensive Agents KW - Index Medicus KW - Kidney Failure, Chronic -- diagnosis KW - Hypertension, Renal -- etiology KW - Anti-HIV Agents -- therapeutic use KW - Angiotensin-Converting Enzyme Inhibitors -- therapeutic use KW - Kidney Failure, Chronic -- drug therapy KW - HIV Long-Term Survivors KW - Humans KW - Hypertension, Renal -- drug therapy KW - Prognosis KW - Anti-HIV Agents -- adverse effects KW - Kidney Failure, Chronic -- etiology KW - Glomerulosclerosis, Focal Segmental -- drug therapy KW - Glomerulosclerosis, Focal Segmental -- diagnosis KW - AIDS-Associated Nephropathy -- etiology KW - AIDS-Associated Nephropathy -- diagnosis KW - AIDS-Associated Nephropathy -- drug therapy KW - Glomerulosclerosis, Focal Segmental -- etiology KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67291924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+HIV%2FAIDS+reports&rft.atitle=HIV+and+the+kidney%3A+a+status+report+after+20+years.&rft.au=Cho%2C+Monique+E%3BKopp%2C+Jeffrey+B&rft.aulast=Cho&rft.aufirst=Monique&rft.date=2004-09-01&rft.volume=1&rft.issue=3&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Current+HIV%2FAIDS+reports&rft.issn=15483568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-25 N1 - Date created - 2005-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements. AN - 67286609; 15906159 AB - Huntington's disease (HD) is caused by a polyglutamine repeat expansion in the N-terminus of the huntingtin protein. Huntingtin is normally present in the cytoplasm where it may interact with structural and synaptic elements. The mechanism of HD pathogenesis remains unknown but studies indicate a toxic gain-of-function possibly through aberrant protein interactions. To investigate whether early degenerative changes in HD involve alterations of cytoskeletal and vesicular components, we examined early cellular changes in the frontal cortex of HD presymptomatic (PS), early pathological grade (grade 1) and late-stage (grade 3 and 4) patients as compared to age-matched controls. Morphologic analysis using silver impregnation revealed a progressive decrease in neuronal fiber density and organization in pyramidal cell layers beginning in presymptomatic HD cases. Immunocytochemical analyses for the cytoskeletal markers alpha -tubulin, microtubule-associated protein 2, and phosphorylated neurofilament demonstrated a concomitant loss of staining in early grade cases. Immunoblotting for synaptic proteins revealed a reduction in complexin 2, which was marked in some grade 1 HD cases and significantly reduced in all late stage cases. Interestingly, we demonstrate that two synaptic proteins, dynamin and PACSIN 1, which were unchanged by immunoblotting, showed a striking loss by immunocytochemistry beginning in early stage HD tissue suggesting abnormal distribution of these proteins. We propose that mutant huntingtin affects proteins involved in synaptic function and cytoskeletal integrity before symptoms develop which may influence early disease onset and/or progression. JF - Journal of neurocytology AU - DiProspero, Nicholas A AU - Chen, Er-Yun AU - Charles, Vinod AU - Plomann, Markus AU - Kordower, Jeffrey H AU - Tagle, Danilo A AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. diprospern@ninds.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 517 EP - 533 VL - 33 IS - 5 SN - 0300-4864, 0300-4864 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - Carrier Proteins KW - HTT protein, human KW - Huntingtin Protein KW - MAP2 protein, human KW - Microtubule-Associated Proteins KW - Nerve Tissue Proteins KW - Neurofilament Proteins KW - Nuclear Proteins KW - PACSIN1 protein, human KW - Tubulin KW - complexin II KW - Dynamins KW - EC 3.6.5.5 KW - Index Medicus KW - Microtubule-Associated Proteins -- metabolism KW - Carrier Proteins -- metabolism KW - Age of Onset KW - Humans KW - Pyramidal Cells -- metabolism KW - Tubulin -- metabolism KW - Neurofilament Proteins -- metabolism KW - Aged KW - Pyramidal Cells -- pathology KW - Dynamins -- metabolism KW - Aged, 80 and over KW - Adult KW - Nerve Tissue Proteins -- metabolism KW - Middle Aged KW - Nuclear Proteins -- metabolism KW - Immunohistochemistry KW - Male KW - Female KW - Huntington Disease -- physiopathology KW - Frontal Lobe -- physiopathology KW - Frontal Lobe -- pathology KW - Cytoskeleton -- metabolism KW - Presynaptic Terminals -- pathology KW - Cytoskeleton -- pathology KW - Huntington Disease -- pathology KW - Presynaptic Terminals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67286609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurocytology&rft.atitle=Early+changes+in+Huntington%27s+disease+patient+brains+involve+alterations+in+cytoskeletal+and+synaptic+elements.&rft.au=DiProspero%2C+Nicholas+A%3BChen%2C+Er-Yun%3BCharles%2C+Vinod%3BPlomann%2C+Markus%3BKordower%2C+Jeffrey+H%3BTagle%2C+Danilo+A&rft.aulast=DiProspero&rft.aufirst=Nicholas&rft.date=2004-09-01&rft.volume=33&rft.issue=5&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurocytology&rft.issn=03004864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-30 N1 - Date created - 2005-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapy for unresectable hepatocellular carcinoma: time for XRT? AN - 67047480; 15530257 JF - Cancer journal (Sudbury, Mass.) AU - Pingpank, James F AD - Surgery Branch, Center for Cancer Research, National CancerInstitute, National Institutes of Health, Bethesda, Maryland 20892, USA. james_pingpank@nih.gov PY - 2004 SP - 291 EP - 293 VL - 10 IS - 5 SN - 1528-9117, 1528-9117 KW - Mitomycin KW - 50SG953SK6 KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Radiotherapy, Adjuvant KW - Mitomycin -- adverse effects KW - Humans KW - Radiography KW - Cisplatin -- adverse effects KW - Mitomycin -- administration & dosage KW - Liver Failure -- epidemiology KW - Survival Analysis KW - Cisplatin -- administration & dosage KW - Chemoembolization, Therapeutic -- adverse effects KW - Carcinoma, Hepatocellular -- diagnostic imaging KW - Liver Neoplasms -- therapy KW - Chemoembolization, Therapeutic -- methods KW - Liver Neoplasms -- mortality KW - Carcinoma, Hepatocellular -- therapy KW - Liver Neoplasms -- diagnostic imaging KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Hepatocellular -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67047480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+journal+%28Sudbury%2C+Mass.%29&rft.atitle=Therapy+for+unresectable+hepatocellular+carcinoma%3A+time+for+XRT%3F&rft.au=Pingpank%2C+James+F&rft.aulast=Pingpank&rft.aufirst=James&rft.date=2004-09-01&rft.volume=10&rft.issue=5&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Cancer+journal+%28Sudbury%2C+Mass.%29&rft.issn=15289117&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-17 N1 - Date created - 2004-11-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Cancer J. 2004 Sep-Oct;10(5):307-16 [15530260] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insights into amyloid structural formation and assembly through computational approaches. AN - 67036428; 15523917 AB - Amyloids are long, insoluble ordered fibers. Due to their insolubility, to date the determination of an amyloid structure with an atomic scale resolution has proven to be a difficult task. Under such circumstances, computational approaches are a preferred option, providing the means to build likely models, test their stabilities and figure out the chemistry of their prevailing interactions. Computational models can be validated by targeted experiments, such as introducing mutations and testing for amyloid formation. Computations further provide vehicles for the comprehension of the mechanisms of amyloid seed formation and oligomer toxicity. Nevertheless, computations face an immense hurdle, the outcome of the time scales involved in amyloid formation and the immense sizes of the systems. In an attempt to overcome these, we adopt a strategy that encompasses (1) bioinformatics studies of native proteins containing beta-sheet structures; (2) simulations of shorter peptides; and finally (3) construction of potential oligomeric models and tests of their stabilities. The results are correlated with experimental data where available. Here, we describe the computational methods in simple terms and present an overview of the results. The systems derive from amyloidogenic, disease-related proteins, including gelsolin, beta2-microglobulin, and peptides derived from the prion, Alzheimer's Abeta, IAPP and human calcitonin. Ultimately, obtaining molecular structures should facilitate efforts to therapy and drug design. JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis AU - Zanuy, David AU - Gunasekaran, K AU - Ma, Buyong AU - Tsai, Hui-Hsu Gavin AU - Tsai, Chung-Jung AU - Nussinov, Ruth AD - Laboratory of Experimental and Computational Biology, NCI-Frederick, Bldg 469, Rm 151, Frederick, MD 21702, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 143 EP - 161 VL - 11 IS - 3 SN - 1350-6129, 1350-6129 KW - Amyloid KW - 0 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Humans KW - Protein Folding KW - Computational Biology KW - Protein Structure, Tertiary KW - Models, Molecular KW - Amyloid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67036428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Amyloid+%3A+the+international+journal+of+experimental+and+clinical+investigation+%3A+the+official+journal+of+the+International+Society+of+Amyloidosis&rft.atitle=Insights+into+amyloid+structural+formation+and+assembly+through+computational+approaches.&rft.au=Zanuy%2C+David%3BGunasekaran%2C+K%3BMa%2C+Buyong%3BTsai%2C+Hui-Hsu+Gavin%3BTsai%2C+Chung-Jung%3BNussinov%2C+Ruth&rft.aulast=Zanuy&rft.aufirst=David&rft.date=2004-09-01&rft.volume=11&rft.issue=3&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Amyloid+%3A+the+international+journal+of+experimental+and+clinical+investigation+%3A+the+official+journal+of+the+International+Society+of+Amyloidosis&rft.issn=13506129&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-03 N1 - Date created - 2004-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Does the sequence of gemcitabine and vinorelbine affect their efficacy in non-small cell lung cancer in vitro? AN - 67026159; 15517905 AB - We have recently completed a large phase III trial in advanced non-small cell lung cancer (NSCLC) in the elderly which showed that the combination of gemcitabine (GEM) plus vinorelbine (VNR), with GEM administered first, did not improve any outcome as compared with each single drug. The anti-tumor efficacy of different sequences of administration of GEM and VNR was investigated in a small panel of NSCLC cell lines, by using an in vitro cytotoxic assay and isobologram analysis. Treatment of lung cancer cells with GEM followed by VNR resulted in moderate synergism in one cell line (A549), and in antagonism in two cell lines (H838 and H1355). However, treatment of NSCLC cells with VNR followed by GEM resulted in antagonism in all cell lines. The results of this study show that the GEM/VNR combination is not superior to both single agents against NSCLC cells, independently of the schedule of administration of the drugs. JF - Anticancer research AU - De Luca, Antonella AU - Grassii, Michele AU - Maiello, Monica R AU - Di Maio, Massimo AU - Mancino, Mario AU - De Maio, Ermelinda AU - Gridelli, Cesare AU - Perrone, Francesco AU - Normanno, Nicola AD - Department of Experimental Oncology, National Cancer Institute, Fondazione Pascale, Naples, Italy. PY - 2004 SP - 2985 EP - 2989 VL - 24 IS - 5A SN - 0250-7005, 0250-7005 KW - Deoxycytidine KW - 0W860991D6 KW - Vinblastine KW - 5V9KLZ54CY KW - gemcitabine KW - B76N6SBZ8R KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line, Tumor KW - Inhibitory Concentration 50 KW - Vinblastine -- analogs & derivatives KW - Deoxycytidine -- analogs & derivatives KW - Lung Neoplasms -- drug therapy KW - Vinblastine -- administration & dosage KW - Deoxycytidine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67026159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Does+the+sequence+of+gemcitabine+and+vinorelbine+affect+their+efficacy+in+non-small+cell+lung+cancer+in+vitro%3F&rft.au=De+Luca%2C+Antonella%3BGrassii%2C+Michele%3BMaiello%2C+Monica+R%3BDi+Maio%2C+Massimo%3BMancino%2C+Mario%3BDe+Maio%2C+Ermelinda%3BGridelli%2C+Cesare%3BPerrone%2C+Francesco%3BNormanno%2C+Nicola&rft.aulast=De+Luca&rft.aufirst=Antonella&rft.date=2004-09-01&rft.volume=24&rft.issue=5A&rft.spage=2985&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 - 2004-12-10 N1 - Date created - 2004-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High throughput drug screening. AN - 67014172; 15512863 JF - Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases AU - Heemskerk, Jill AD - National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 19 EP - 21 VL - 5 Suppl 1 SN - 1466-0822, 1466-0822 KW - Neurotoxins KW - 0 KW - SOD1 protein, human KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Superoxide Dismutase-1 KW - Index Medicus KW - United States KW - Animals KW - Computer Simulation KW - Drug Therapy KW - Humans KW - National Institutes of Health (U.S.) KW - Apoptosis -- drug effects KW - Superoxide Dismutase -- genetics KW - Neurotoxins -- pharmacology KW - Drug Design KW - Combinatorial Chemistry Techniques -- methods KW - Drug Evaluation, Preclinical -- methods KW - Amyotrophic Lateral Sclerosis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67014172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Amyotrophic+lateral+sclerosis+and+other+motor+neuron+disorders+%3A+official+publication+of+the+World+Federation+of+Neurology%2C+Research+Group+on+Motor+Neuron+Diseases&rft.atitle=High+throughput+drug+screening.&rft.au=Heemskerk%2C+Jill&rft.aulast=Heemskerk&rft.aufirst=Jill&rft.date=2004-09-01&rft.volume=5+Suppl+1&rft.issue=&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Amyotrophic+lateral+sclerosis+and+other+motor+neuron+disorders+%3A+official+publication+of+the+World+Federation+of+Neurology%2C+Research+Group+on+Motor+Neuron+Diseases&rft.issn=14660822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-11 N1 - Date created - 2004-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted point mutagenesis of mouse Kcnq1: phenotypic analysis of mice with point mutations that cause Romano-Ward syndrome in humans. AN - 67010192; 15498462 AB - Inherited long QT syndrome is most frequently associated with mutations in KCNQ1, which encodes the primary subunit of a potassium channel. Patients with mutations in KCNQ1 may show only the cardiac defect (Romano-Ward syndrome or RWS) or may also have severe deafness (Jervell and Lange-Nielsen syndrome or JLNS). Targeted disruption of mouse Kcnq1 models JLNS in that mice are deaf and show abnormal ECGs. However, the phenotype is broader than that seen in patients. Most dramatically, the inner ear defects result in a severe hyperactivity/circling behavior, which may influence cardiac function. To understand the etiology of the cardiac phenotype in these mice and to generate a potentially more useful model system, we generated new mouse lines by introducing point mutations associated with RWS. The A340E line phenocopies RWS: the repolarization phenotype is inherited in a dominant manner and is observed independent of any inner ear defect. The T311I line phenocopies JLNS, with deafness associated with inner hair cell malfunction. JF - Genomics AU - Casimiro, Mathew C AU - Knollmann, Bjoern C AU - Yamoah, Ebenezer N AU - Nie, Liping AU - Vary, Jay C AU - Sirenko, Syevda G AU - Greene, Anne E AU - Grinberg, Alexander AU - Huang, Sing Ping AU - Ebert, Steven N AU - Pfeifer, Karl AD - Laboratory of Mammalian Genes and Development, NICHD/National Institutes of Health, Building 6B Room 2B-206, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 555 EP - 564 VL - 84 IS - 3 SN - 0888-7543, 0888-7543 KW - DNA Primers KW - 0 KW - KCNQ Potassium Channels KW - KCNQ1 Potassium Channel KW - Kcnq1 protein, mouse KW - Potassium Channels, Voltage-Gated KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Blotting, Northern KW - Evoked Potentials, Auditory, Brain Stem KW - Electrocardiography KW - Hair Cells, Auditory, Inner -- pathology KW - Deafness -- genetics KW - Phenotype KW - Potassium Channels, Voltage-Gated -- genetics KW - Romano-Ward Syndrome -- genetics KW - Mice -- genetics KW - Disease Models, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67010192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeted+point+mutagenesis+of+mouse+Kcnq1%3A+phenotypic+analysis+of+mice+with+point+mutations+that+cause+Romano-Ward+syndrome+in+humans.&rft.au=Casimiro%2C+Mathew+C%3BKnollmann%2C+Bjoern+C%3BYamoah%2C+Ebenezer+N%3BNie%2C+Liping%3BVary%2C+Jay+C%3BSirenko%2C+Syevda+G%3BGreene%2C+Anne+E%3BGrinberg%2C+Alexander%3BHuang%2C+Sing+Ping%3BEbert%2C+Steven+N%3BPfeifer%2C+Karl&rft.aulast=Casimiro&rft.aufirst=Mathew&rft.date=2004-09-01&rft.volume=84&rft.issue=3&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-24 N1 - Date created - 2004-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoradiation with gemcitabine for cervical cancer in patients with renal failure. AN - 66987126; 15494637 AB - The prognosis of cervical cancer patients with renal failure secondary to obstructive uropathy is poor. Our objective was to analyze our experience in the management with chemoradiation of untreated cervical cancer patients complicated by obstructive nephropathy and kidney dysfunction. Untreated patients with cervical cancer and renal failure as manifested by raised serum creatinine were treated with pelvic radiotherapy concurrently with weekly gemcitabine at 300 mg/m2. Response, toxicity and renal function pre- and post-therapy were evaluated. Eight FIGO stage IIIB and one IVB patients were treated. Pre-treatment serum creatinine ranged from 1.6 to 18.5 mg/100 ml (median 3.3, mean 6.8) and creatinine clearance varied from 4 to 57 mg/ml/min (median 17, mean 22.1). Four patients had a percutaneous nephrostomy placed and four patients had symptoms from kidney failure. All patient completed chemoradiation. Most patients had grade 3 leukopenia and neutropenia. Dermatitis, colitis and proctitis were common. All patients had improvement in creatinine clearance (pre-therapy 22.78, post-therapy 54.3 mg/ml/min) (p=0.0058) and all but one normalized serum creatinine. Eight (89%) of nine patients achieved complete response and one patient had persistence. At a median follow-up of 11 months (range 6-14), all patients are alive, one with pelvic and another with systemic disease. Ureteral obstruction causing any degree of renal insufficiency should not be a contraindication to receive chemoradiation to attempt cure. In this setting where cisplatin-based therapy is contraindicated, the use of gemcitabine may be considered. JF - Anti-cancer drugs AU - Cetina, Lucely AU - Rivera, Lesbia AU - Candelaria, Myrna AU - de la Garza, Jaime AU - Dueñas-González, Alfonso AD - Division of Clinical Research, National Cancer Institute/Institute of Biomedical Research, National Autonomous University of México. Mexico City, Mexico. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 761 EP - 766 VL - 15 IS - 8 SN - 0959-4973, 0959-4973 KW - Radiation-Sensitizing Agents KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - Creatinine KW - AYI8EX34EU KW - gemcitabine KW - B76N6SBZ8R KW - Index Medicus KW - Drug Administration Schedule KW - Neoplasm Staging KW - Injections, Intravenous KW - Humans KW - Carcinoma, Squamous Cell -- complications KW - Urethral Obstruction -- complications KW - Radiation-Sensitizing Agents -- therapeutic use KW - Creatinine -- blood KW - Kidney Function Tests -- methods KW - Mexico KW - Drug Evaluation -- methods KW - Treatment Outcome KW - Brachytherapy -- methods KW - Middle Aged KW - Follow-Up Studies KW - Time Factors KW - Radiation-Sensitizing Agents -- adverse effects KW - Carcinoma, Squamous Cell -- drug therapy KW - Carcinoma, Squamous Cell -- radiotherapy KW - Radiation-Sensitizing Agents -- administration & dosage KW - Female KW - Uterine Cervical Neoplasms -- complications KW - Deoxycytidine -- toxicity KW - Uterine Cervical Neoplasms -- drug therapy KW - Renal Insufficiency -- drug therapy KW - Deoxycytidine -- analogs & derivatives KW - Chemotherapy, Adjuvant -- methods KW - Deoxycytidine -- therapeutic use KW - Deoxycytidine -- administration & dosage KW - Radiotherapy, Adjuvant -- methods KW - Uterine Cervical Neoplasms -- radiotherapy KW - Renal Insufficiency -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66987126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Chemoradiation+with+gemcitabine+for+cervical+cancer+in+patients+with+renal+failure.&rft.au=Cetina%2C+Lucely%3BRivera%2C+Lesbia%3BCandelaria%2C+Myrna%3Bde+la+Garza%2C+Jaime%3BDue%C3%B1as-Gonz%C3%A1lez%2C+Alfonso&rft.aulast=Cetina&rft.aufirst=Lucely&rft.date=2004-09-01&rft.volume=15&rft.issue=8&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-16 N1 - Date created - 2004-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular cholesterol enrichment impairs T cell activation and chemotaxis. AN - 66986829; 15491683 AB - Human aging is associated with an increase in immune cell cholesterol levels, independent of circulating cholesterol levels. The effects of such an increase in membrane cholesterol on lipid raft-associated immune cell function have not been investigated. We sought to examine the effects of in vitro cholesterol loading on two known lipid raft-associated pathways of T cells, namely T cell activation and chemokine stimulation. Using beta-cyclodextrin (BCD) as a vehicle, we were able to rapidly load cholesterol onto human T cell lines and primary peripheral blood T cells without inducing significant cell toxicity. Loading of cholesterol to four-fold that of normal levels induced significant inhibition of intracellular calcium mobilization by both alphaCD3 and SDF-1alpha. Cholesterol-loaded peripheral T cells were completely unresponsive to alphaCD3/alphaCD28 stimulation, demonstrating no increase in IL-2, GM1 expression or cell size. T cell polarization of lipid rafts to alphaCD3/alphaCD28 beads was also impaired. In addition, cholesterol loading potently inhibited SDF-1alpha-induced chemotaxis. We propose that excess membrane cholesterol could potentially disrupt raft-related cell functions downstream of receptor triggering and that the loss of cholesterol regulation of aging immune cells could contribute to immune cell senescence. JF - Mechanisms of ageing and development AU - Nguyen, Dzung H AU - Espinoza, Juan C AU - Taub, Dennis D AD - Laboratory of Immunology, National Institute on Aging, NIH, Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA. taubd@grc.nia.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 641 EP - 650 VL - 125 IS - 9 SN - 0047-6374, 0047-6374 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD3 KW - CXCL12 protein, human KW - Chemokine CXCL12 KW - Chemokines, CXC KW - Protein Isoforms KW - Cholesterol KW - 97C5T2UQ7J KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Humans KW - Membrane Microdomains -- physiology KW - Jurkat Cells KW - Protein Isoforms -- physiology KW - Antibodies, Monoclonal -- pharmacology KW - Chemotaxis, Leukocyte KW - Microspheres KW - Protein Isoforms -- immunology KW - Antigens, CD3 -- immunology KW - Calcium -- metabolism KW - Chemokines, CXC -- physiology KW - Cell Polarity KW - Biological Transport -- physiology KW - Intracellular Membranes -- metabolism KW - Cell Line KW - Antigens, CD3 -- physiology KW - Lymphocyte Activation -- drug effects KW - T-Lymphocytes -- metabolism KW - Cholesterol -- metabolism KW - Cholesterol -- pharmacology KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Lymphocyte Activation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66986829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ageing+and+development&rft.atitle=Cellular+cholesterol+enrichment+impairs+T+cell+activation+and+chemotaxis.&rft.au=Nguyen%2C+Dzung+H%3BEspinoza%2C+Juan+C%3BTaub%2C+Dennis+D&rft.aulast=Nguyen&rft.aufirst=Dzung&rft.date=2004-09-01&rft.volume=125&rft.issue=9&rft.spage=641&rft.isbn=&rft.btitle=&rft.title=Mechanisms+of+ageing+and+development&rft.issn=00476374&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-26 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenous estrogen receptor beta is transcriptionally active in primary ovarian cells from estrogen receptor knockout mice. AN - 66944648; 15465114 AB - The estrogen receptor (ER) alpha is a hormone-inducible transcription factor that has a pivotal physiological role. Intriguingly, a clear and undisputed physiological function of the recently described ERbeta remains elusive, with the exception of the ovary where a cooperative role of ERalpha and ERbeta has been demonstrated. We have, therefore, investigated whether endogenous ERs, in particular ERbeta, act as ligand-inducible transcription factors in primary ovarian cells derived from wild-type, ERalpha or ERbeta knockout mice. Granulosa-enriched cell fractions naturally expressing ERbeta and thecal cell fractions that express ERalpha were analyzed in transactivation assays using the vitellogenin A2 consensus estrogen response element and potent ER agonists diethylstilbestrol and S-indenestrol A. We studied also the potency-selective ERbeta agonist R-indenestrol A, the pure ERalpha agonist and ERbeta antagonist R,R-diethyl-tetrahydrochrysene and the pure ERalpha agonist propylpyrazole-triol. Using ER subtype-specific physiological cell models and these ER subtype-specific structural probes, we analyzed trans-activation of ERalpha and ERbeta. This analysis revealed that endogenously expressed ERbeta is indeed functional as a transcription factor, that it responds to estrogens appropriately, and that the ligands used are true ER subtype-specific probes in primary ovarian cells. In conclusion, this study demonstrates that endogenously expressed ERbeta is capable of regulating gene transcription independent of ERalpha. JF - Steroids AU - Mueller, Stefan O AU - Katzenellenbogen, John A AU - Korach, Kenneth S AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 681 EP - 686 VL - 69 IS - 10 SN - 0039-128X, 0039-128X KW - 5,11-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol KW - 0 KW - Chrysenes KW - Estrogen Receptor alpha KW - Estrogen Receptor beta KW - Estrogens KW - Indenes KW - Phenols KW - Pyrazoles KW - Receptors, Estrogen KW - Recombinant Fusion Proteins KW - Vitellogenins KW - 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole KW - 0T83Y6JZPF KW - fulvestrant KW - 22X328QOC4 KW - indenestrol KW - 4A464K3BSI KW - Estradiol KW - 4TI98Z838E KW - Diethylstilbestrol KW - 731DCA35BT KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Chrysenes -- pharmacology KW - Vitellogenins -- genetics KW - Receptors, Estrogen -- physiology KW - Mice, Knockout KW - Recombinant Fusion Proteins -- metabolism KW - Indenes -- pharmacology KW - Recombinant Fusion Proteins -- genetics KW - Gene Expression Regulation -- drug effects KW - Response Elements -- genetics KW - Luciferases -- genetics KW - Estrogen Receptor alpha -- agonists KW - Receptors, Estrogen -- agonists KW - Luciferases -- metabolism KW - Mice KW - Transcriptional Activation KW - Pyrazoles -- pharmacology KW - Estrogen Receptor alpha -- genetics KW - Receptors, Estrogen -- genetics KW - Estrogens -- pharmacology KW - Ovary -- cytology KW - Transfection KW - Cells, Cultured KW - Diethylstilbestrol -- pharmacology KW - Mice, Inbred C57BL KW - Female KW - Estrogen Receptor beta -- agonists KW - Estradiol -- analogs & derivatives KW - Estradiol -- pharmacology KW - Estrogen Receptor beta -- physiology KW - Theca Cells -- metabolism KW - Granulosa Cells -- metabolism KW - Estrogen Receptor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66944648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Steroids&rft.atitle=Endogenous+estrogen+receptor+beta+is+transcriptionally+active+in+primary+ovarian+cells+from+estrogen+receptor+knockout+mice.&rft.au=Mueller%2C+Stefan+O%3BKatzenellenbogen%2C+John+A%3BKorach%2C+Kenneth+S&rft.aulast=Mueller&rft.aufirst=Stefan&rft.date=2004-09-01&rft.volume=69&rft.issue=10&rft.spage=681&rft.isbn=&rft.btitle=&rft.title=Steroids&rft.issn=0039128X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-15 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Euthanasia of mouse fetuses and neonates. AN - 66933151; 15461437 AB - We sought to determine whether any of the common methods of euthanasia for adult rodents would lead to an acceptable death for fetuses or neonates. We wanted to identify a method that was rapid, free of signs of pain or distress, reliable, and minimally distressful to the person performing the procedure and that minimized the amount of handling required to perform the procedure. We evaluated six methods of euthanasia, with and without anesthesia, in three age groups of mice: gravid mice (E14-20) and neonatal pups (P1-P7 and P8-P14). Euthanasia methods included: halothane inhalation, carbon dioxide inhalation, intraperitoneal sodium pentobarbital, intravenous potassium chloride, and cervical dislocation with and without anesthesia. Noninvasive echocardiography was used to assess heartbeat during euthanasia. With cardiac arrest as the definition of death, no method of euthanasia killed fetal mice. Halothane inhalation (5% by vaporizer) was not an acceptable method of euthanasia for mice of the age groups tested. Intraperitoneal administration of sodium pentobarbital for euthanasia required a higher dose than the previously established dose, and there is a risk of reduced efficacy in pregnant animals due to potential intrauterine injection. Carbon dioxide asphyxiation was the most efficient method of euthanasia for neonatal mouse pups P1-14. For pregnant adult mice, intravenous potassium chloride under anesthesia, carbon dioxide asphyxiation, and cervical dislocation alone or under anesthesia were excellent methods of euthanasia. Copyright 2004 American Association for Laboratory Animal Science JF - Contemporary topics in laboratory animal science AU - Klaunberg, Brenda A AU - O'malley, James AU - Clark, Terri AU - Davis, Judith A AD - 10 Center Drive, Bldg 10, Room B1D69, NMRF, DIR, NINDS, NIH, DHHS, Bethesda, Maryland 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 29 EP - 34 VL - 43 IS - 5 SN - 1060-0558, 1060-0558 KW - Carbon Dioxide KW - 142M471B3J KW - Potassium Chloride KW - 660YQ98I10 KW - Pentobarbital KW - I4744080IR KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Carbon Dioxide -- poisoning KW - Fetus KW - Animals, Newborn KW - Animals KW - Heart Arrest -- chemically induced KW - Spinal Injuries -- veterinary KW - Pentobarbital -- poisoning KW - Potassium Chloride -- poisoning KW - Halothane -- poisoning KW - Echocardiography -- veterinary KW - Laboratory Animal Science -- methods KW - Euthanasia, Animal -- methods KW - Animals, Laboratory -- physiology KW - Mice -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66933151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Contemporary+topics+in+laboratory+animal+science&rft.atitle=Euthanasia+of+mouse+fetuses+and+neonates.&rft.au=Klaunberg%2C+Brenda+A%3BO%27malley%2C+James%3BClark%2C+Terri%3BDavis%2C+Judith+A&rft.aulast=Klaunberg&rft.aufirst=Brenda&rft.date=2004-09-01&rft.volume=43&rft.issue=5&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Contemporary+topics+in+laboratory+animal+science&rft.issn=10600558&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-21 N1 - Date created - 2004-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessing the risk of birth defects associated with antiretroviral exposure during pregnancy. AN - 66932320; 15467577 AB - The purpose of this study was to examine teratogenic risk of antiretroviral (ARV) drugs. The Antiretroviral Pregnancy Registry (APR) monitors prenatal exposures to ARV drugs and pregnancy outcome through a prospective exposure-registration cohort. Statistical inference uses exact methods for binomial proportions. Through July 2003, APR has monitored 3583 live births exposed to ARV. Among 1391 first trimester exposures, there were 38 birth defects, prevalence of 2.7% (95% CI 1.9-3.7), not significantly higher than the CDC's population surveillance rate, 3.1 per 100 live births (95% CI 3.1-3.2). For lamivudine, nelfinavir, nevirapine, stavudine, and zidovudine, sufficient numbers of live births (>200) following first-trimester exposures have been monitored to allow detection of a 2-fold increase in risk of birth defects overall; no increases have been detected. APR data demonstrate no increase in prevalence of birth defects overall or among women exposed to lamivudine, nelfinavir, nevirapine, stavudine, and zidovudine. JF - American journal of obstetrics and gynecology AU - Watts, D Heather AU - Covington, Deborah L AU - Beckerman, Karen AU - Garcia, Patricia AU - Scheuerle, Angela AU - Dominguez, Kenneth AU - Ross, Brenda AU - Sacks, Susan AU - Chavers, Scott AU - Tilson, Hugh AD - Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Md 20892, USA. hw59i@nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 985 EP - 992 VL - 191 IS - 3 SN - 0002-9378, 0002-9378 KW - Anti-Retroviral Agents KW - 0 KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - Nevirapine KW - 99DK7FVK1H KW - Stavudine KW - BO9LE4QFZF KW - Nelfinavir KW - HO3OGH5D7I KW - Abridged Index Medicus KW - Index Medicus KW - Nevirapine -- adverse effects KW - Nelfinavir -- adverse effects KW - Prospective Studies KW - Zidovudine -- adverse effects KW - Risk Factors KW - Humans KW - Lamivudine -- adverse effects KW - Gestational Age KW - Stavudine -- adverse effects KW - Female KW - Pregnancy KW - Maternal-Fetal Exchange KW - Abnormalities, Drug-Induced -- epidemiology KW - Anti-Retroviral Agents -- adverse effects KW - Pregnancy Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66932320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+obstetrics+and+gynecology&rft.atitle=Assessing+the+risk+of+birth+defects+associated+with+antiretroviral+exposure+during+pregnancy.&rft.au=Watts%2C+D+Heather%3BCovington%2C+Deborah+L%3BBeckerman%2C+Karen%3BGarcia%2C+Patricia%3BScheuerle%2C+Angela%3BDominguez%2C+Kenneth%3BRoss%2C+Brenda%3BSacks%2C+Susan%3BChavers%2C+Scott%3BTilson%2C+Hugh&rft.aulast=Watts&rft.aufirst=D&rft.date=2004-09-01&rft.volume=191&rft.issue=3&rft.spage=985&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-06 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Picosecond time-resolved X-ray crystallography: probing protein function in real time. AN - 66920596; 15450293 AB - A detailed mechanistic understanding of how a protein functions requires knowledge not only of its static structure, but also how its conformation evolves as it executes its function. The recent development of picosecond time-resolved X-ray crystallography has allowed us to visualize in real time and with atomic detail the conformational evolution of a protein. Here, we report the photolysis-induced structural evolution of wild-type and L29F myoglobin over times ranging from 100 ps to 3 micros. The sub-ns structural rearrangements that accompany ligand dissociation in wild-type and the mutant form differ dramatically, and lead to vastly different ligand migration dynamics. The correlated protein displacements provide a structural explanation for the kinetic differences. Our observation of functionally important protein motion on the sub-ns time scale was made possible by the 150-ps time resolution of the measurement, and demonstrates that picosecond dynamics are relevant to protein function. To visualize subtle structural changes without modeling, we developed a novel method for rendering time-resolved electron density that depicts motion as a color gradient across the atom or group of atoms that move. A sequence of these time-resolved images have been stitched together into a movie, which allows one to literally "watch" the protein as it executes its function. JF - Journal of structural biology AU - Schotte, Friedrich AU - Soman, Jayashree AU - Olson, John S AU - Wulff, Michael AU - Anfinrud, Philip A AD - Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 235 EP - 246 VL - 147 IS - 3 SN - 1047-8477, 1047-8477 KW - Myoglobin KW - 0 KW - Proteins KW - carboxymyoglobin KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Structure, Secondary KW - Myoglobin -- chemistry KW - Models, Molecular KW - Kinetics KW - Myoglobin -- metabolism KW - Lasers KW - Amino Acid Substitution KW - Protein Conformation KW - Computer Systems KW - Proteins -- chemistry KW - Crystallography, X-Ray -- instrumentation KW - Crystallography, X-Ray -- methods KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66920596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+structural+biology&rft.atitle=Picosecond+time-resolved+X-ray+crystallography%3A+probing+protein+function+in+real+time.&rft.au=Schotte%2C+Friedrich%3BSoman%2C+Jayashree%3BOlson%2C+John+S%3BWulff%2C+Michael%3BAnfinrud%2C+Philip+A&rft.aulast=Schotte&rft.aufirst=Friedrich&rft.date=2004-09-01&rft.volume=147&rft.issue=3&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Journal+of+structural+biology&rft.issn=10478477&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-17 N1 - Date created - 2004-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential oblique angle spectroscopy of the oral epithelium. AN - 66914293; 15447016 AB - Increasing evidence suggests that inflammation may contribute to the process of carcinogenesis. This is the basis of several clinical trials evaluating potential chemopreventive drugs. These trials require quantitative assessments of inflammation, which, for the oral epithelium, are traditionally provided by histopathological evaluation. To reduce patient discomfort and morbidity of tissue biopsy procedures, we develop a noninvasive alternative using diffuse reflectance spectroscopy to measure epithelial thickness as an index of tissue inflammation. Although any optical system has the potential for probing near-surface structures, traditional methods of accounting for scattering of photons are generally invalid for typical epithelial thicknesses. We develop a single-scattering theory that is valid for typical epithelial thicknesses. The theory accurately predicts a distinctive feature that can be used to quantify epithelial thickness given intensity measurements with sources at two different angles relative to the tissue surface. This differential measure approach has acute sensitivity to small, layer-related changes in scattering coefficients. To assess the capability of our method to quantify epithelial thickness, detailed Monte Carlo simulations and measurements on phantom models of a two-layered structure are performed. The results show that the intensity ratio maximum feature can be used to quantify epithelial thickness with an error less than 30% despite fourfold changes in scattering coefficients and 10-fold changes in absorption coefficients. An initial study using a simple two-source, four-detector probe on patients shows that the technique has promise. We believe that this new method will perform well on patients with diverse tissue optical characteristics and therefore be of practical clinical value for quantifying epithelial thickness in vivo. (c) 2004 Society of Photo-Optical Instrumentation Engineers. JF - Journal of biomedical optics AU - Hattery, David AU - Hattery, Brenda AU - Chernomordik, Victor AU - Smith, Paul AU - Loew, Murray AU - Mulshine, James AU - Gandjbakhche, Amir AD - National Institutes of Health, National Institute of Child Health and Human Development, Laboratory of Integrative and Medical Biophysics, Building 9, Room B1E11, Bethesda, Maryland 20892-0924, USA. hattery@ieee.org PY - 2004 SP - 951 EP - 960 VL - 9 IS - 5 SN - 1083-3668, 1083-3668 KW - Index Medicus KW - Sensitivity and Specificity KW - Scattering, Radiation KW - Computer Simulation KW - Reproducibility of Results KW - Humans KW - Monte Carlo Method KW - Models, Biological KW - Image Interpretation, Computer-Assisted -- methods KW - Mouth Neoplasms -- diagnosis KW - Precancerous Conditions -- physiopathology KW - Mouth Mucosa -- pathology KW - Algorithms KW - Spectrum Analysis -- methods KW - Mouth Mucosa -- physiopathology KW - Precancerous Conditions -- diagnosis KW - Spectrum Analysis -- instrumentation KW - Mouth Neoplasms -- pathology KW - Precancerous Conditions -- pathology KW - Mouth Neoplasms -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66914293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+optics&rft.atitle=Differential+oblique+angle+spectroscopy+of+the+oral+epithelium.&rft.au=Hattery%2C+David%3BHattery%2C+Brenda%3BChernomordik%2C+Victor%3BSmith%2C+Paul%3BLoew%2C+Murray%3BMulshine%2C+James%3BGandjbakhche%2C+Amir&rft.aulast=Hattery&rft.aufirst=David&rft.date=2004-09-01&rft.volume=9&rft.issue=5&rft.spage=951&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomedical+optics&rft.issn=10833668&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-21 N1 - Date created - 2004-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulatory roles for the homeodomain and C2H2 zinc finger regions of Cryptococcus neoformans Ste12alphap. AN - 66903910; 15387817 AB - The STE12alpha gene of Cryptococcus neoformans encodes a protein containing both homeodomain and zinc finger regions. As homeodomains and zinc finger regions are important domains for the function of many transcription factors, we used site-specific mutagenesis to delineate the roles of these two domains. The homeodomain and zinc finger regions are each important for the function of Ste12alphap. DNA binding ability, mating frequency, and haploid fruiting capability were reduced in strains with mutations in the homeodomain, whereas virulence and capsule size in the mouse brain were increased. In contrast, mutations in the zinc fingers region resulted in decreased virulence, reduced capsule size in the mouse brain and decreased gene expression of capsule associated genes. In addition, phospholipase activity was increased in the zinc finger mutants. Taken together, most of the phenotypes previously observed in the ste12alpha deletion strains were reproduced in these two types of mutants. However, unlike mutations in the homeodomain/zinc finger region, complete deletion of STE12alpha caused a severe reduction in virulence and a decrease in phospholipase activity. These data suggest that region(s) other than the homeodomain and zinc finger regions of Ste12alphap contribute to the variable influences on the different phenotypes observed in C. neoformans. Copyright 2004 Blackwell Publishing Ltd JF - Molecular microbiology AU - Chang, Yun C AU - Wright, L C AU - Tscharke, R L AU - Sorrell, T C AU - Wilson, C F AU - Kwon-Chung, K J AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1385 EP - 1396 VL - 53 IS - 5 SN - 0950-382X, 0950-382X KW - Fungal Proteins KW - 0 KW - Homeodomain Proteins KW - Transcription Factors KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Gene Expression Regulation, Fungal KW - Animals KW - Survival Rate KW - Humans KW - Two-Hybrid System Techniques KW - Mice KW - Brain -- metabolism KW - Mice, Inbred BALB C KW - Female KW - Transcription Factors -- metabolism KW - Cryptococcus neoformans -- genetics KW - Cryptococcus neoformans -- metabolism KW - Fungal Proteins -- genetics KW - Cryptococcus neoformans -- growth & development KW - Transcription Factors -- genetics KW - Homeodomain Proteins -- chemistry KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- metabolism KW - Homeodomain Proteins -- genetics KW - Homeodomain Proteins -- metabolism KW - Transcription Factors -- chemistry KW - Zinc Fingers KW - Cryptococcus neoformans -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66903910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Regulatory+roles+for+the+homeodomain+and+C2H2+zinc+finger+regions+of+Cryptococcus+neoformans+Ste12alphap.&rft.au=Chang%2C+Yun+C%3BWright%2C+L+C%3BTscharke%2C+R+L%3BSorrell%2C+T+C%3BWilson%2C+C+F%3BKwon-Chung%2C+K+J&rft.aulast=Chang&rft.aufirst=Yun&rft.date=2004-09-01&rft.volume=53&rft.issue=5&rft.spage=1385&rft.isbn=&rft.btitle=&rft.title=Molecular+microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-24 N1 - Date created - 2004-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraocular lymphoma: update on diagnosis and management. AN - 66896529; 15377987 AB - Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) in which lymphoma cells initially invade the retina, vitreous, or optic nerve head, with or without concomitant CNS involvement. The incidence of this previously rare condition has increased dramatically. Given its nonspecific presentation and aggressive course, PIOL provides a diagnostic and therapeutic challenge. We review the current strategies for diagnosis and treatment of PIOL and present our own experience with PIOL. Recent developments in the diagnosis of PIOL include immunohistochemistry, flow cytometry, cytokine evaluation, and molecular analysis. However, definitive diagnosis still requires harvesting of tissue for histopathology. Optimal treatment for PIOL remains unclear. Initial therapeutic regimens should include methotrexate-based chemotherapy and radiotherapy to the brain and eye. In addition, promising results have been seen with intravitreal methotrexate and autologous stem cell transplantation for recurrent and refractory disease. Efforts to further determine the immunophenotype and molecular characteristics of PIOL will continue to assist in the diagnosis of PIOL. Future studies are required to determine the role of radiotherapy and optimal local and systemic chemotherapeutic regimens. JF - Cancer control : journal of the Moffitt Cancer Center AU - Chan, Chi-Chao AU - Wallace, Dana J AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. chanc@nei.nih.gov PY - 2004 SP - 285 EP - 295 VL - 11 IS - 5 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Stem Cell Transplantation -- methods KW - Injections, Intralymphatic KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Vitrectomy -- methods KW - Humans KW - Diagnostic Techniques, Neurological KW - Treatment Outcome KW - Radiotherapy -- methods KW - Diagnostic Techniques, Ophthalmological KW - Antineoplastic Agents -- therapeutic use KW - Methotrexate -- administration & dosage KW - Lymphoma -- therapy KW - Eye Neoplasms -- therapy KW - Eye Neoplasms -- diagnosis KW - Lymphoma -- diagnosis KW - Central Nervous System Neoplasms -- therapy KW - Central Nervous System Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66896529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+control+%3A+journal+of+the+Moffitt+Cancer+Center&rft.atitle=Intraocular+lymphoma%3A+update+on+diagnosis+and+management.&rft.au=Chan%2C+Chi-Chao%3BWallace%2C+Dana+J&rft.aulast=Chan&rft.aufirst=Chi-Chao&rft.date=2004-09-01&rft.volume=11&rft.issue=5&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Cancer+control+%3A+journal+of+the+Moffitt+Cancer+Center&rft.issn=1526-2359&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-09-28 N1 - Date created - 2004-09-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 2001 Jan 11;344(2):114-23 [11150363] J Clin Oncol. 2001 Feb 1;19(3):742-9 [11157026] Ophthalmology. 2001 Feb;108(2):386-99 [11158819] Ophthalmology. 2001 Mar;108(3):426-7 [11237883] Curr Opin Oncol. 2001 May;13(3):137-42 [11307054] Retina. 2001;21(3):281-4 [11421029] Surv Ophthalmol. 2001 May-Jun;45(6):463-71 [11425352] Onkologie. 2001 Oct;24(5):491-4 [11694778] Hematology Am Soc Hematol Educ Program. 2001;:194-220 [11722985] Blood. 2002 Feb 15;99(4):1136-43 [11830458] Retina. 2002 Feb;22(1):37-43 [11884876] Curr Mol Med. 2001 May;1(2):259-72 [11899075] Surv Ophthalmol. 2002 Mar-Apr;47(2):81-124 [11918892] Ann Oncol. 2002 Apr;13(4):531-8 [12056702] Eur J Cancer. 2002 Jul;38(10):1298-312 [12091059] J Neurooncol. 2002 Jun;58(2):175-8 [12164690] Leukemia. 2002 Sep;16(9):1852-6 [12200703] Ophthalmology. 2002 Sep;109(9):1709-16 [12208721] Curr Opin Ophthalmol. 2002 Dec;13(6):411-8 [12441846] J Clin Oncol. 2002 Dec 15;20(24):4643-8 [12488408] Blood. 2003 Jan 15;101(2):466-8 [12393404] J Neurol. 2002 Dec;249(12):1713-6 [12529795] Clin Cancer Res. 2003 Feb;9(2):711-5 [12576439] Ophthalmology. 2003 Feb;110(2):421-6 [12578791] Ophthalmology. 2003 Mar;110(3):595-9 [12623828] J Clin Oncol. 2003 Mar 15;21(6):1044-9 [12637469] Clin Cancer Res. 2003 Jun;9(6):2133-9 [12796378] Ophthalmology. 2003 Jun;110(6):1241-4 [12799254] Eye (Lond). 2003 May;17(4):513-21 [12802353] J Clin Oncol. 2003 Jun 15;21(12):2407-14 [12805341] Clin Lymphoma. 2003 Jun;4(1):22-9 [12837150] Curr Hematol Rep. 2003 Jan;2(1):13-22 [12901150] Ophthalmology. 2003 Aug;110(8):1671-2 [12917196] Onkologie. 2003 Aug;26(4):351-4 [12972702] Br J Cancer. 2003 Oct 20;89(8):1389-94 [14562003] Graefes Arch Clin Exp Ophthalmol. 2003 Oct;241(10):860-70 [14605902] J Clin Oncol. 2003 Nov 15;21(22):4151-6 [14615443] Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5235-41 [14638722] Ann Oncol. 2004 Jan;15(1):129-33 [14679132] Trans Am Ophthalmol Soc. 2003;101:275-92 [14971583] Arch Ophthalmol. 1975 Feb;93(2):123-4 [1090291] Surv Ophthalmol. 1979 Mar-Apr;23(5):279-96 [380030] Cancer. 1980 Feb 15;45(4):688-92 [6766795] Dev Ophthalmol. 1981;2:114-20 [7021249] N Engl J Med. 1982 Nov 11;307(20):1231-6 [7133054] Cancer. 1983 Sep 1;52(5):878-86 [6347357] Cancer. 1986 Apr 1;57(7):1273-5 [2418934] J Exp Med. 1986 Jul 1;164(1):315-20 [3014037] N Engl J Med. 1987 Nov 5;317(19):1185-9 [3657890] Br J Ophthalmol. 1987 Oct;71(10):748-52 [3314978] Ophthalmology. 1987 Dec;94(12):1631-9 [3323986] J Neurosurg. 1988 Jun;68(6):835-53 [3286832] N Engl J Med. 1988 Jun 23;318(25):1638-44 [3287162] Ophthalmology. 1988 May;95(5):625-30 [3050698] Br J Ophthalmol. 1988 Dec;72(12):905-11 [3067746] Cancer. 1989 May 15;63(10):1918-21 [2702565] Br J Ophthalmol. 1989 May;73(5):342-6 [2659067] Blood. 1990 Jul 1;76(1):131-5 [2194586] Nature. 1990 Nov 22;348(6299):334-6 [2250705] Am J Ophthalmol. 1991 Oct 15;112(4):472-4 [1928262] J Clin Oncol. 1992 Apr;10(4):635-43 [1548527] Ophthalmology. 1992 Feb;99(2):250-6 [1553217] Int J Radiat Oncol Biol Phys. 1992;23(1):9-17 [1572835] Retina. 1992;12(3 Suppl):S64-70 [1455086] Cancer. 1993 Aug 1;72(3):843-9 [8334638] Ophthalmology. 1993 Sep;100(9):1399-406 [8371930] Ophthalmology. 1994 May;101(5):850-5 [8190470] Mod Pathol. 1994 May;7(4):429-34 [8066071] Retina. 1995;15(2):125-9 [7624599] Int J Radiat Oncol Biol Phys. 1995 Oct 15;33(3):663-73 [7558957] Am J Ophthalmol. 1995 Nov;120(5):671-3 [7485372] Am J Ophthalmol. 1996 Apr;121(4):442-4 [8604740] Arch Pathol Lab Med. 1996 Apr;120(4):357-63 [8619747] Retina. 1996;16(1):47-56 [8927810] Leuk Lymphoma. 1996 Oct;23(3-4):339-45 [9031115] Retina. 1997;17(2):118-23 [9143039] Arch Ophthalmol. 1997 Sep;115(9):1152-6 [9298056] Arch Ophthalmol. 1997 Sep;115(9):1157-60 [9298057] Am J Ophthalmol. 1997 Sep;124(3):362-72 [9439362] J Clin Oncol. 1998 Mar;16(3):859-63 [9508166] J Clin Oncol. 1998 Sep;16(9):3000-6 [9738568] Ophthalmology. 1998 Sep;105(9):1664-9 [9754175] Blood. 1998 Nov 1;92(9):3152-62 [9787151] Blood. 1999 May 1;93(9):3081-7 [10216105] Br J Ophthalmol. 1999 Apr;83(4):448-51 [10434868] Ophthalmology. 1999 Sep;106(9):1805-10 [10485554] Arch Ophthalmol. 1999 Sep;117(9):1239-42 [10496399] Ocul Immunol Inflamm. 2000 Dec;8(4):243-50 [11262654] J Neurooncol. 1999 Jul;43(3):199-201 [10563423] J Neurooncol. 1999 Jul;43(3):203-8 [10563424] J Neurooncol. 1999 Jul;43(3):219-26 [10563426] J Neurooncol. 1999 Jul;43(3):249-57 [10563431] J Clin Oncol. 1999 Apr;17(4):1329 [10561199] Ophthalmology. 1999 Dec;106(12):2291-5 [10599659] J Neurosurg. 2000 Feb;92(2):261-6 [10659013] Curr Opin Neurol. 1999 Dec;12(6):687-91 [10676749] Blood. 2000 Mar 15;95(6):2084-92 [10706878] Oncology (Williston Park). 2000 Feb;14(2):228-34; discussion 237-42, 244 [10736810] Surv Ophthalmol. 2000 May-Jun;44(6):518-26 [10906383] Cytopathology. 2000 Aug;11(4):276-8 [10983729] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. AN - 66866452; 15356405 AB - There is now convincing evidence that usual hormone therapy for ovarian failure increases the risk for breast cancer. We have previously shown that ovarian androgens normally protect mammary epithelial cells from excessive estrogenic stimulation, and therefore we hypothesized that the addition of testosterone to usual hormone therapy might protect women from breast cancer. This was a retrospective, observational study that followed 508 postmenopausal women receiving testosterone in addition to usual hormone therapy in South Australia. Breast cancer status was ascertained by mammography at the initiation of testosterone treatment and biannually thereafter. The average age at the start of follow-up was 56.4 years, and the mean duration of follow-up was 5.8 years. Breast cancer incidence in this group was compared with that of untreated women and women using usual hormone therapy reported in the medical literature and to age-specific local population rates. There were seven cases of invasive breast cancer in this population of testosterone users, for an incidence of 238 per 100,000 woman-years. The rate for estrogen/progestin and testosterone users was 293 per 100,000 woman-years--substantially less than women receiving estrogen/pro-gestin in the Women's Health Initiative study (380 per 100,000 woman-years) or in the "Million Women" Study (521 per 100,000 woman-years). The breast cancer rate in our testosterone users was closest to that reported for hormone therapy never-users in the latter study (283 per 100,000 woman-years), and their age-standardized rate was the same as for the general population in South Australia. These observations suggest that the addition of testosterone to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population. JF - Menopause (New York, N.Y.) AU - Dimitrakakis, Constantine AU - Jones, Robert A AU - Liu, Aiyi AU - Bondy, Carolyn A AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2004 SP - 531 EP - 535 VL - 11 IS - 5 SN - 1072-3714, 1072-3714 KW - Testosterone KW - 3XMK78S47O KW - Index Medicus KW - Australia -- epidemiology KW - Humans KW - Retrospective Studies KW - Aged KW - Risk Assessment KW - Age Distribution KW - Drug Therapy, Combination KW - Aged, 80 and over KW - Adult KW - Cohort Studies KW - Incidence KW - Middle Aged KW - Female KW - Testosterone -- therapeutic use KW - Estrogen Replacement Therapy -- adverse effects KW - Estrogen Replacement Therapy -- methods KW - Testosterone -- adverse effects KW - Breast Neoplasms -- epidemiology KW - Breast Neoplasms -- chemically induced KW - Postmenopause -- physiology KW - Postmenopause -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66866452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Menopause+%28New+York%2C+N.Y.%29&rft.atitle=Breast+cancer+incidence+in+postmenopausal+women+using+testosterone+in+addition+to+usual+hormone+therapy.&rft.au=Dimitrakakis%2C+Constantine%3BJones%2C+Robert+A%3BLiu%2C+Aiyi%3BBondy%2C+Carolyn+A&rft.aulast=Dimitrakakis&rft.aufirst=Constantine&rft.date=2004-09-01&rft.volume=11&rft.issue=5&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=Menopause+%28New+York%2C+N.Y.%29&rft.issn=10723714&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-18 N1 - Date created - 2004-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Menopause. 2004 Sep-Oct;11(5):505-7 [15356402] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor in vitro enhances expression of other neurotrophic factors as well as cytokines and chemokines. AN - 66853470; 15352210 AB - Microarray analyses demonstrated that a variety of genes was affected by treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor (PEDF). The genes for neurotrophins, glial cell-derived neurotrophic factor (GDNF), and their receptors were regulated differentially in immature versus mature neurons; however, nerve growth factor (NGF), neurotrophin (NT)-3, and GDNF did not contribute to the protective effect of PEDF. Brain-derived neurotrophic factor (BDNF) seemed capable of inducing apoptosis, because a blocking antibody enhanced the protective effect of PEDF. In addition, PEDF exposure also stimulated expression of several cytokine and chemokine genes. Removal of the less than 1% of microglia in the cultures by treatment with L-leucine methyl ester, combined with enzyme-linked immunosorbent assays (ELISAs), demonstrated that the cerebellar granule cells constitutively produce three chemokines, macrophage inflammatory protein (MIP)-1alpha, MIP-2, and MIP-3alpha, whose production is enhanced further by treatment with PEDF. Blocking antibodies to each of the chemokines was protective under control conditions, suggesting that they may contribute to the "natural" apoptosis occurring in the cultures, and enhanced the effects of PEDF. Although PEDF enhanced production of all three chemokines, the blocking antibodies did not increase its protective effect against induced apoptosis. These results suggest that although PEDF enhances expression of other neurotrophic factors or chemokines, it does not exert its neuroprotective effect on cerebellar granule cells through their production. JF - Journal of neuroscience research AU - Yabe, Takeshi AU - Herbert, J Taylor AU - Takanohashi, Asako AU - Schwartz, Joan P AD - Neurotrophic Factors Section, NINDS, NIH, Bethesda, Maryland 20892, USA. Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 642 EP - 652 VL - 77 IS - 5 SN - 0360-4012, 0360-4012 KW - Antibodies KW - 0 KW - Chemokines KW - Cytokines KW - Eye Proteins KW - Nerve Growth Factors KW - RNA, Messenger KW - Serpins KW - pigment epithelium-derived factor KW - Index Medicus KW - Animals KW - Drug Interactions KW - Oligonucleotide Array Sequence Analysis -- methods KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - RNA, Messenger -- biosynthesis KW - Rats KW - Animals, Newborn KW - Enzyme-Linked Immunosorbent Assay -- methods KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Antibodies -- pharmacology KW - Apoptosis -- drug effects KW - Time Factors KW - Microglia -- drug effects KW - Microglia -- metabolism KW - Nerve Growth Factors -- metabolism KW - Neurons -- metabolism KW - Nerve Growth Factors -- pharmacology KW - Neurons -- drug effects KW - Cytokines -- immunology KW - Chemokines -- immunology KW - Cytokines -- metabolism KW - Eye Proteins -- pharmacology KW - Cerebellum -- cytology KW - Chemokines -- metabolism KW - Serpins -- pharmacology KW - Nerve Growth Factors -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66853470?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroscience+research&rft.atitle=Treatment+of+cerebellar+granule+cell+neurons+with+the+neurotrophic+factor+pigment+epithelium-derived+factor+in+vitro+enhances+expression+of+other+neurotrophic+factors+as+well+as+cytokines+and+chemokines.&rft.au=Yabe%2C+Takeshi%3BHerbert%2C+J+Taylor%3BTakanohashi%2C+Asako%3BSchwartz%2C+Joan+P&rft.aulast=Yabe&rft.aufirst=Takeshi&rft.date=2004-09-01&rft.volume=77&rft.issue=5&rft.spage=642&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-22 N1 - Date created - 2004-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indoor allergens, asthma, and asthma-related symptoms among adolescents in Wuhan, China. AN - 66847804; 15350953 AB - Information on indoor allergen exposures among non-Western populations, which have lower prevalence of atopic illness, is scant. We examined whether exposures to common indoor allergens were associated with doctor-diagnosed asthma and asthma-related symptoms among Chinese adolescents. A cross-sectional study of 4,185 ninth grade students was conducted at 22 randomly selected schools in Wuhan, China. Information on respiratory health and exposures to indoor allergens was obtained by a self-administered questionnaire completed in class. Having animals currently was associated with persistent cough [prevalence odds ratio (POR)=1.54, 95% confidence interval (CI ): 1.21-2.11] and wheeze (POR=1.41, 95% CI: 1.03-1.94). Early-life exposure to animals was also associated with doctor-diagnosed asthma (POR=1.95, 95% CI: 1.35-2.82). Associations with respiratory symptoms strengthened with higher levels of exposure and for exposure in both early childhood and in adolescence. Exposure to cockroaches and having mold/water damage in the home contributed especially to wheezing (POR=2.03, 95% CI: 1.41-2.90 for cockroaches; POR=2.49, 95% CI: 1.82-3.40 for mold/water damage). Indoor allergen exposures were positively associated with asthma diagnosis and persistent respiratory symptoms among Chinese adolescents. Neither early-life nor current exposure to animals was protective for asthma or asthma-related symptoms. JF - Annals of epidemiology AU - Salo, Päivi M AU - Xia, Jiang AU - Johnson, C Anderson AU - Li, Yan AU - Avol, Edward L AU - Gong, Jie AU - London, Stephanie J AD - National Institute of Environmental Health Sciences, Epidemiology Branch, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 543 EP - 550 VL - 14 IS - 8 SN - 1047-2797, 1047-2797 KW - Allergens KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Cross-Sectional Studies KW - China -- epidemiology KW - Cats KW - Surveys and Questionnaires KW - Dogs KW - Population KW - Adolescent KW - Female KW - Male KW - Animals, Domestic -- immunology KW - Prevalence KW - Allergens -- immunology KW - Asthma -- epidemiology KW - Air Pollution, Indoor -- adverse effects KW - Asthma -- etiology KW - Allergens -- classification KW - Allergens -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66847804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+the+role+of+ubiquitin-interacting+motifs+in+ubiquitin+binding+and+ubiquitylation.&rft.au=Miller%2C+Stephanie+L+H%3BMalotky%2C+Erica%3BO%27Bryan%2C+John+P&rft.aulast=Miller&rft.aufirst=Stephanie+L&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33528&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 - 2005-04-21 N1 - Date created - 2004-09-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Epidemiol. 1990 Dec;132(6):1176-84 [2260550] Clin Exp Allergy. 1994 Apr;24(4):353-8 [8039021] Curr Opin Allergy Clin Immunol. 2003 Feb;3(1):7-14 [12582308] Am J Epidemiol. 2002 Nov 15;156(10):977-83 [12419771] Lancet. 2002 Sep 7;360(9335):781-2 [12241839] Environ Health Perspect. 2002 Sep;110(9):961-7 [12204833] JAMA. 2002 Aug 28;288(8):963-72 [12190366] Clin Exp Allergy. 2002 Aug;32(8):1155-9 [12190651] Thorax. 1994 Dec;49(12):1205-10 [7878553] Clin Exp Allergy. 1997 May;27(5):540-5 [9179428] Ann Allergy Asthma Immunol. 1997 Jun;78(6):544-54; quiz 555-6 [9207717] J Allergy Clin Immunol. 1997 Dec;100(6 Pt 1):S2-24 [9438476] Allergy. 1998 Feb;53(2):120-8 [9534909] Int J Epidemiol. 1998 Feb;27(1):41-8 [9563692] Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1536-41 [9603135] Clin Exp Allergy. 1998 Apr;28 Suppl 1:2-7; discussion 32-6 [9641582] Eur Respir J. 1998 Aug;12(2):315-35 [9727780] Clin Exp Allergy. 1998 Oct;28(10):1178-81 [9824383] Clin Exp Allergy. 1998 Oct;28(10):1191-200 [9824385] Clin Exp Allergy. 1999 Jan;29(1):28-34 [10051699] Thorax. 1999 Mar;54(3):268-72 [10325905] Thorax. 1999 Jan;54(1):27-32 [10343627] Environ Health Perspect. 1999 Jun;107 Suppl 3:473-80 [10423390] Environ Health Perspect. 1999 Jun;107 Suppl 3:481-3 [10423391] Lancet. 1999 Sep;354 Suppl 2:SII12-5 [10507253] Clin Exp Allergy. 2000 Feb;30(2):187-93 [10651770] Clin Exp Allergy. 2000 Feb;30(2):194-200 [10651771] J Allergy Clin Immunol. 2000 Feb;105(2 Pt 2):S503-8 [10669532] Thorax. 2000 May;55(5):424-31 [10770825] Am J Respir Crit Care Med. 2000 May;161(5):1563-6 [10806155] Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):930-5 [10988108] Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 2):S128-33 [10988167] Clin Exp Allergy. 2000 Nov;30(11):1536-9 [11069560] Toxicology. 2000 Nov 2;152(1-3):47-52 [11090939] Environ Health Perspect. 2000 Nov;108(11):1023-8 [11102291] J Allergy Clin Immunol. 2001 Mar;107(3):455-60 [11240945] Lancet. 2001 Mar 10;357(9258):752-6 [11253969] Thorax. 2001 May;56(5):406-11 [11312411] Am J Respir Crit Care Med. 2001 Apr;163(5):1108-12 [11316644] Prev Med. 2001 May;32(5):437-45 [11330994] J Allergy Clin Immunol. 2001 May;107(5):790-6 [11344344] Clin Exp Allergy. 2001 Apr;31(4):570-5 [11359424] Pediatrics. 2001 Jun;107(6):E98 [11389296] Thorax. 2001 Sep;56 Suppl 2:ii58-63 [11514708] Clin Exp Allergy. 2001 Aug;31(8):1225-31 [11529892] J Allergy Clin Immunol. 2001 Oct;108(4):509-15 [11590373] Lancet. 2001 Oct 6;358(9288):1129-33 [11597666] Ann Allergy Asthma Immunol. 2001 Oct;87(4):296-302 [11686421] Clin Exp Allergy. 2001 Dec;31(12):1839-45 [11737034] Chest. 2002 Jan;121(1):6-8 [11796423] Clin Exp Allergy. 2002 Mar;32(3):361-6 [11940064] Curr Opin Allergy Clin Immunol. 2001 Oct;1(5):407-12 [11964720] Curr Opin Allergy Clin Immunol. 2002 Apr;2(2):133-9 [11964762] Epidemiology. 2002 May;13(3):288-95 [11964930] Clin Exp Allergy. 2002 May;32(5):714-20 [11994095] J Allergy Clin Immunol. 2002 May;109(5):784-8 [11994700] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. AN - 66846645; 15349906 AB - We analyzed global gene expression patterns of 91 human hepatocellular carcinomas (HCCs) to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with patient survival. This association was validated via 5 independent supervised learning methods. We also identified the genes most strongly associated with survival by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification, suggesting an etiological involvement of these processes in accelerating the progression of HCC. In conclusion, the biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g., HIF1a) for selective treatment of HCC patients. Supplementary material for this article can be found on the HEPATOLOGY Web site (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html) Copyright 2004 American Association for the Study of Liver Diseases JF - Hepatology (Baltimore, Md.) AU - Lee, Ju-Seog AU - Chu, In-Sun AU - Heo, Jeonghoon AU - Calvisi, Diego F AU - Sun, Zongtang AU - Roskams, Tania AU - Durnez, Anne AU - Demetris, Anthony J AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 667 EP - 676 VL - 40 IS - 3 SN - 0270-9139, 0270-9139 KW - Index Medicus KW - Humans KW - Liver -- metabolism KW - Gene Expression Profiling KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- mortality KW - Carcinoma, Hepatocellular -- classification KW - Liver Neoplasms -- classification KW - Carcinoma, Hepatocellular -- mortality KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66846645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Classification+and+prediction+of+survival+in+hepatocellular+carcinoma+by+gene+expression+profiling.&rft.au=Lee%2C+Ju-Seog%3BChu%2C+In-Sun%3BHeo%2C+Jeonghoon%3BCalvisi%2C+Diego+F%3BSun%2C+Zongtang%3BRoskams%2C+Tania%3BDurnez%2C+Anne%3BDemetris%2C+Anthony+J%3BThorgeirsson%2C+Snorri+S&rft.aulast=Lee&rft.aufirst=Ju-Seog&rft.date=2004-09-01&rft.volume=40&rft.issue=3&rft.spage=667&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 - 2004-09-23 N1 - Date created - 2004-09-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Liver Transpl. 2005 Apr;11(4):469-72 [15776402] Hepatology. 2004 Sep;40(3):521-3 [15349888] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro differentiation of rat liver derived stem cells results in sensitization to TNFalpha-mediated apoptosis. AN - 66846517; 15349897 AB - Hepatic stem cells are activated after liver damage and have a critical role in tissue homeostasis and repair. Characterization of molecular and cellular events accompanying the expansion and differentiation of liver stem cells is essential for understanding the basic biology of stem cells and for facilitating clinical application of the stem cells. We assessed whether in vitro differentiation of putative hepatic progenitor (rat liver epithelial [RLE]) cells toward hepatocytic lineage affects the response to TNFalpha-mediated cytotoxicity, a common determinant of liver injury. The data show that 50% of differentiated cells underwent apoptosis after 6 hours of TNFalpha treatment whereas control RLE cells were resistant. Both cell types displayed mitochondrial depolarization and release of cytochrome c but the TNFalpha treatment resulted in activation of caspases 9 and 3 and the execution of apoptosis only in differentiated RLE cells. Apoptotic death was associated with increased ROS production and depletion of glutathione. Antioxidants completely prevented both glutathione depletion and apoptosis induced by TNFalpha in differentiated RLE cells. Conversely, glutathione-depleting agents sensitized control RLE cells to TNFalpha induced apoptosis. In conclusion, efficient antioxidant defense system involving glutathione renders hepatic progenitor cells resistant to TNFalpha-mediated apoptosis and acquisition of sensitivity to death stimuli is an implicit feature of the differentiation process. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). Copyright 2004 American Association for the Study of Liver Diseases JF - Hepatology (Baltimore, Md.) AU - Sánchez, Aránzazu AU - Factor, Valentina M AU - Espinoza, Luis A AU - Schroeder, Insa S AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892-4258, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 590 EP - 599 VL - 40 IS - 3 SN - 0270-9139, 0270-9139 KW - Reactive Oxygen Species KW - 0 KW - Tumor Necrosis Factor-alpha KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Rats KW - Animals KW - Cell Lineage KW - Oxidative Stress KW - Glutathione -- physiology KW - Cell Differentiation KW - Mitochondria, Liver -- drug effects KW - Cell Line KW - Liver -- cytology KW - Stem Cells -- cytology KW - Liver -- drug effects KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Apoptosis -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66846517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+vitro+differentiation+of+rat+liver+derived+stem+cells+results+in+sensitization+to+TNFalpha-mediated+apoptosis.&rft.au=S%C3%A1nchez%2C+Ar%C3%A1nzazu%3BFactor%2C+Valentina+M%3BEspinoza%2C+Luis+A%3BSchroeder%2C+Insa+S%3BThorgeirsson%2C+Snorri+S&rft.aulast=S%C3%A1nchez&rft.aufirst=Ar%C3%A1nzazu&rft.date=2004-09-01&rft.volume=40&rft.issue=3&rft.spage=590&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 - 2004-09-23 N1 - Date created - 2004-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatitis C infection and injection drug use: the role of hepatologists in evolving treatment efforts. AN - 66845810; 15349886 AB - Treatment regimens for both substance abuse and hepatitis C infection are complex and evolving. New pharmacotherapy for opioid addiction allows for office-based treatment and, thus, an opportunity for expanded treatment in the context of hepatitis C infection. The current article addresses the newly evolving, complex issues in the medical management of hepatitis C and injection drug use. Copyright 2004 American Association for the Study of Liver Diseases JF - Hepatology (Baltimore, Md.) AU - Kresina, Thomas F AU - Seeff, Leonard B AU - Francis, Henry AD - Center on AIDS and other Medical Consequences of Drug Abuse, National Institute on Drug Abuse, Department of Health and Human Services, Bethesda, MD 20892, USA. tk13v@nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 516 EP - 519 VL - 40 IS - 3 SN - 0270-9139, 0270-9139 KW - Index Medicus KW - Humans KW - Hepatitis C -- drug therapy KW - Hepatitis C -- etiology KW - Substance Abuse, Intravenous -- therapy KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66845810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatitis+C+infection+and+injection+drug+use%3A+the+role+of+hepatologists+in+evolving+treatment+efforts.&rft.au=Kresina%2C+Thomas+F%3BSeeff%2C+Leonard+B%3BFrancis%2C+Henry&rft.aulast=Kresina&rft.aufirst=Thomas&rft.date=2004-09-01&rft.volume=40&rft.issue=3&rft.spage=516&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 - 2004-09-23 N1 - Date created - 2004-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biodistribution and radiation dosimetry of the serotonin transporter ligand 11C-DASB determined from human whole-body PET. AN - 66845262; 15347724 AB - 11C-Labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) is a selective radioligand for the in vivo quantitation of serotonin transporters (SERTs) using PET. The goal of this study was to provide dosimetry estimates for 11C-DASB based on human whole-body PET. Dynamic whole-body PET scans were acquired for 7 subjects after the injection of 669 +/- 97 MBq (18.1 +/- 2.6 mCi) of 11C-DASB. The acquisition for each subject was obtained at 14 time points for a total of 115 min after injection of the radioligand. Regions of interest were placed over compressed planar images of source organs that could be visually identified to generate time-activity curves. Radiation burden to the body was calculated from residence times of these source organs using the MIRDOSE3.1 program. The organs with high radiation burden included the lungs, urinary bladder wall, kidneys, gallbladder wall, heart wall, spleen, and liver. The activity peaked within 10 min after the injection of 11C-DASB for all these organs except two--the excretory organs gallbladder and urinary bladder wall, which had peak activities at 32 and 22 min, respectively. Monoexponential fitting of activity overlying the urinary bladder suggested that approximately 12% of activity was excreted via the urine. Simulations in which the urinary voiding interval was decreased from 4.8 to 0.6 h produced only modest effects on the dose to the urinary bladder wall. With a 2.4-h voiding interval, the calculated effective dose was 6.98 microGy/MBq (25.8 mrem/mCi). The estimated radiation burden of 11C-DASB is relatively modest and would allow multiple PET examinations of the same research subject per year. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Lu, Jian-Qiang AU - Ichise, Masanori AU - Liow, Jeih-San AU - Ghose, Subroto AU - Vines, Doug AU - Innis, Robert B AD - Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-0135, USA. lujq@intra.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1555 EP - 1559 VL - 45 IS - 9 SN - 0161-5505, 0161-5505 KW - 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile KW - 0 KW - Aniline Compounds KW - Carbon Radioisotopes KW - Carrier Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Radiopharmaceuticals KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Sulfides KW - Index Medicus KW - Carbon Radioisotopes -- pharmacokinetics KW - Radiopharmaceuticals -- pharmacokinetics KW - Radiation Dosage KW - Humans KW - Body Burden KW - Metabolic Clearance Rate KW - Organ Specificity KW - Brain -- metabolism KW - Tissue Distribution KW - Brain -- diagnostic imaging KW - Carrier Proteins -- metabolism KW - Sulfides -- pharmacokinetics KW - Aniline Compounds -- pharmacokinetics KW - Whole-Body Counting -- methods KW - Nerve Tissue Proteins -- metabolism KW - Risk Assessment -- methods KW - Radiometry -- methods KW - Tomography, Emission-Computed -- methods KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66845262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Biodistribution+and+radiation+dosimetry+of+the+serotonin+transporter+ligand+11C-DASB+determined+from+human+whole-body+PET.&rft.au=Lu%2C+Jian-Qiang%3BIchise%2C+Masanori%3BLiow%2C+Jeih-San%3BGhose%2C+Subroto%3BVines%2C+Doug%3BInnis%2C+Robert+B&rft.aulast=Lu&rft.aufirst=Jian-Qiang&rft.date=2004-09-01&rft.volume=45&rft.issue=9&rft.spage=1555&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-01 N1 - Date created - 2004-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Global expression profiling identifies signatures of tumor virulence in MMTV-PyMT-transgenic mice: correlation to human disease. AN - 66836784; 15342376 AB - FVB/N-Tg (MMTV-PyMT)(634Mul)-transgenic mice develop multifocal mammary tumors with a high incidence of pulmonary metastasis. We have demonstrated previously that mammary tumors derived from transgene-positive F1 progeny in particular inbred strains display altered latency, tumor growth rates, and metastatic rates when compared with the FVB/NJ homozygous parent. To identify genes with expression that might be critical in modifying the biological behavior of MMTV-PyMT tumors, we performed a detailed comparative analysis of expression profiles from mammary tumors arising in the parental FVB/NJ background and F1 progeny from crosses with I/LnJ, LP/J, MOLF/Ei, and NZB/B1NJ mice. Compared with normal mammary glands, gene expression profiles of tumors from all five strains exhibited up-regulation of genes involved in cell growth (e.g., Cks1 and CDC25C) and down-regulation of cell adhesion molecules, with many genes associated previously with human breast cancer such as STAT2, CD24 antigen, gelsolin, and lipocalin2. To identify genes with significant variation in expression between the five different genotypes, significance analysis of microarrays (SAM) and one-way ANOVA were used. Three definable groupings of tumors were identified: (a) tumors derived in the LP/J F1 and MOLF/Ei F1 strains in which tumor growth and dissemination are suppressed and latency prolonged; (b) the most aggressive tumors from the FVB/NJ parental strain and I/LnJ F1 genomic backgrounds; and (c) an intermediate virulence phenotype with tumors from NZB/B1NJ-F1 crosses. These array based assessments correlated well with a composite phenotype ranking using a "virulence" index. The gene expression signature that is associated with a high metastatic rate in the mouse contains the same 17 genes described recently as the signature gene set predictive of metastasis in human tumors (1) with 16 of the 17 genes exhibiting the same directional change in expression associated with human metastases. These results demonstrate that the genetic analysis of mouse models of tumorigenesis may be highly relevant to human cancer and that the metastatic phenotype of a tumor may be affected by the germline genetic configuration of the host. JF - Cancer research AU - Qiu, Ting Hu AU - Chandramouli, Gadisetti V R AU - Hunter, Kent W AU - Alkharouf, Nawal W AU - Green, Jeffrey E AU - Liu, Edison T AD - Laboratory of Cell Regulation and Carcinogenesis, Cancer Research Center, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 5973 EP - 5981 VL - 64 IS - 17 SN - 0008-5472, 0008-5472 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Index Medicus KW - Gene Expression Profiling KW - Animals KW - Cell Transformation, Neoplastic -- pathology KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Cell Transformation, Neoplastic -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- virology KW - Mammary Neoplasms, Experimental -- metabolism KW - Antigens, Polyomavirus Transforming -- genetics KW - Mammary Tumor Virus, Mouse -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66836784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Global+expression+profiling+identifies+signatures+of+tumor+virulence+in+MMTV-PyMT-transgenic+mice%3A+correlation+to+human+disease.&rft.au=Qiu%2C+Ting+Hu%3BChandramouli%2C+Gadisetti+V+R%3BHunter%2C+Kent+W%3BAlkharouf%2C+Nawal+W%3BGreen%2C+Jeffrey+E%3BLiu%2C+Edison+T&rft.aulast=Qiu&rft.aufirst=Ting&rft.date=2004-09-01&rft.volume=64&rft.issue=17&rft.spage=5973&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 - 2004-10-05 N1 - Date created - 2004-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bayesian multivariate logistic regression. AN - 66834007; 15339297 AB - Bayesian analyses of multivariate binary or categorical outcomes typically rely on probit or mixed effects logistic regression models that do not have a marginal logistic structure for the individual outcomes. In addition, difficulties arise when simple noninformative priors are chosen for the covariance parameters. Motivated by these problems, we propose a new type of multivariate logistic distribution that can be used to construct a likelihood for multivariate logistic regression analysis of binary and categorical data. The model for individual outcomes has a marginal logistic structure, simplifying interpretation. We follow a Bayesian approach to estimation and inference, developing an efficient data augmentation algorithm for posterior computation. The method is illustrated with application to a neurotoxicology study. JF - Biometrics AU - O'Brien, Sean M AU - Dunson, David B AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. obrien4@niehs.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 739 EP - 746 VL - 60 IS - 3 SN - 0006-341X, 0006-341X KW - Insecticides KW - 0 KW - Methoxychlor KW - RIA79UD69L KW - Index Medicus KW - Insecticides -- toxicity KW - Animals KW - Biometry KW - Methoxychlor -- administration & dosage KW - Insecticides -- administration & dosage KW - Algorithms KW - Monte Carlo Method KW - Pregnancy KW - Multivariate Analysis KW - Methoxychlor -- toxicity KW - Rats KW - Markov Chains KW - Motor Activity -- drug effects KW - Female KW - Male KW - Logistic Models KW - Bayes Theorem UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66834007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Bayesian+multivariate+logistic+regression.&rft.au=O%27Brien%2C+Sean+M%3BDunson%2C+David+B&rft.aulast=O%27Brien&rft.aufirst=Sean&rft.date=2004-09-01&rft.volume=60&rft.issue=3&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-01 N1 - Date created - 2004-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacogenomics and stomach cancer. AN - 66830646; 15335285 AB - In subgroups of gastric cancer patients, chemotherapy treatments carry a high risk of toxicity without any clear evidence of antitumor activity. Individualization of therapy is required to treat each patient with the optimal drug and dose. Genetic polymorphisms are the hereditary determinants for interindividual variations of drug effect and the genetic approach represents a new tool to design a tailored therapy. This review focuses on the relevance of the host polymorphisms involved in metabolism, cellular transport and interaction with molecular targets of the drugs used in gastric cancer in conventional or innovative chemotherapy regimens. Pharmacogenetic studies based on a single gene or multi-gene approach (pharmacogenomics) are promising to identify gastric cancer patients at risk for adverse toxicity, but larger and controlled studies are needed to justify changes in the chemotherapeutic strategies. JF - Pharmacogenomics AU - Toffoli, Giuseppe AU - Cecchin, Erika AD - Experimental and Clinical Pharmacology, CRO--National Cancer Institute, via Pedemontana Occidentale, 12, 33081 Aviano, Italy. gtoffoli@cro.it Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 627 EP - 641 VL - 5 IS - 6 SN - 1462-2416, 1462-2416 KW - Anthracyclines KW - 0 KW - Taxoids KW - irinotecan KW - 0H43101T0J KW - Cisplatin KW - Q20Q21Q62J KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Taxoids -- pharmacokinetics KW - Cisplatin -- pharmacokinetics KW - Anthracyclines -- pharmacology KW - Anthracyclines -- pharmacokinetics KW - Humans KW - Clinical Trials as Topic KW - Cisplatin -- pharmacology KW - Anthracyclines -- administration & dosage KW - Taxoids -- pharmacology KW - Taxoids -- administration & dosage KW - Cisplatin -- administration & dosage KW - Stomach Neoplasms -- drug therapy KW - Camptothecin -- pharmacology KW - Camptothecin -- pharmacokinetics KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Stomach Neoplasms -- genetics KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Pharmacogenetics KW - Camptothecin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66830646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Pharmacogenomics+and+stomach+cancer.&rft.au=Toffoli%2C+Giuseppe%3BCecchin%2C+Erika&rft.aulast=Toffoli&rft.aufirst=Giuseppe&rft.date=2004-09-01&rft.volume=5&rft.issue=6&rft.spage=627&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=14622416&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-08 N1 - Date created - 2004-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of painful temporomandibular joints with a cyclooxygenase-2 inhibitor: a randomized placebo-controlled comparison of celecoxib to naproxen. AN - 66815929; 15327804 AB - To compare the efficacy and adverse effects of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, with naproxen, a non-steroidal anti-inflammatory drug, and placebo in the treatment of painful temporomandibular joints (TMJs). In this randomized, double-blind, placebo-controlled trial, 68 subjects with painful TMJs secondary to disc-displacement with reduction, received celecoxib 100 mg twice a day; naproxen, 500 mg twice a day; or placebo for 6 weeks. Subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analogue scale, maximal comfortable mandibular opening, and quality of life (SF-36), at baseline (1 week after discontinuing previous analgesic therapy) and again after 6 weeks of drug treatment. Naproxen significantly reduced the symptoms of painful temporomandibular joint disc-displacement (TMJ DD) with reduction as determined by most efficacy measures. Significant improvement in pain intensity occurred within 3 weeks of treatment, and was sustained throughout the 6-week study. Clinically significant improvement in mandibular range of motion was observed for naproxen compared to celecoxib and placebo. Celecoxib showed slightly better pain reduction than placebo, but was not significantly effective for temporomandibular disorder pain. Celecoxib and naproxen were well tolerated, with similar number of reported adverse effects. Dual COX-1 and COX-2 inhibition with naproxen was demonstrated to be effective for the treatment of painful TMJs, as seen by significant improvement in clinical signs and symptoms of TMJ DD with reduction compared to celecoxib and placebo. Inhibition of both COX isozymes is needed to achieve effective analgesia for this type of musculoskeletal pain. JF - Pain AU - Ta, Lauren E AU - Dionne, Raymond A AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 Center Drive, Room 1N-103, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 13 EP - 21 VL - 111 IS - 1-2 SN - 0304-3959, 0304-3959 KW - Cyclooxygenase 2 Inhibitors KW - 0 KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Placebos KW - Pyrazoles KW - Sulfonamides KW - Naproxen KW - 57Y76R9ATQ KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Celecoxib KW - JCX84Q7J1L KW - Index Medicus KW - Range of Motion, Articular KW - Humans KW - Quality of Life KW - Isoenzymes -- antagonists & inhibitors KW - Adult KW - Treatment Outcome KW - Chronic Disease KW - Middle Aged KW - Female KW - Male KW - Cyclooxygenase Inhibitors -- adverse effects KW - Facial Pain -- etiology KW - Sulfonamides -- adverse effects KW - Temporomandibular Joint Disorders -- complications KW - Cyclooxygenase Inhibitors -- administration & dosage KW - Naproxen -- administration & dosage KW - Facial Pain -- drug therapy KW - Sulfonamides -- administration & dosage KW - Naproxen -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66815929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pain&rft.atitle=Treatment+of+painful+temporomandibular+joints+with+a+cyclooxygenase-2+inhibitor%3A+a+randomized+placebo-controlled+comparison+of+celecoxib+to+naproxen.&rft.au=Ta%2C+Lauren+E%3BDionne%2C+Raymond+A&rft.aulast=Ta&rft.aufirst=Lauren&rft.date=2004-09-01&rft.volume=111&rft.issue=1-2&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Pain&rft.issn=03043959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-09 N1 - Date created - 2004-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer risk associated with ovulation-stimulating drugs. AN - 66809233; 15217997 AB - Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored. JF - Human reproduction (Oxford, England) AU - Brinton, Louise A AU - Scoccia, Bert AU - Moghissi, Kamran S AU - Westhoff, Carolyn L AU - Althuis, Michelle D AU - Mabie, Jerome E AU - Lamb, Emmet J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. brinton@nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 2005 EP - 2013 VL - 19 IS - 9 SN - 0268-1161, 0268-1161 KW - Gonadotropins KW - 0 KW - Clomiphene KW - 1HRS458QU2 KW - Index Medicus KW - Neoplasm Invasiveness KW - Odds Ratio KW - Humans KW - Cohort Studies KW - Adult KW - Retrospective Studies KW - Female KW - Infertility, Female -- drug therapy KW - Gonadotropins -- adverse effects KW - Breast Neoplasms -- pathology KW - Breast Neoplasms -- chemically induced KW - Ovulation Induction -- adverse effects KW - Clomiphene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66809233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reproduction+%28Oxford%2C+England%29&rft.atitle=Breast+cancer+risk+associated+with+ovulation-stimulating+drugs.&rft.au=Brinton%2C+Louise+A%3BScoccia%2C+Bert%3BMoghissi%2C+Kamran+S%3BWesthoff%2C+Carolyn+L%3BAlthuis%2C+Michelle+D%3BMabie%2C+Jerome+E%3BLamb%2C+Emmet+J&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2004-09-01&rft.volume=19&rft.issue=9&rft.spage=2005&rft.isbn=&rft.btitle=&rft.title=Human+reproduction+%28Oxford%2C+England%29&rft.issn=02681161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-09 N1 - Date created - 2004-08-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Hum Reprod. 2005 Apr;20(4):1112; author reply 1112-3 [15788697] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p21Cip1 and p27Kip1 act in synergy to alter the sensitivity of naive T cells to TGF-beta-mediated G1 arrest through modulation of IL-2 responsiveness. AN - 66805094; 15322169 AB - Induction of G(1) arrest by TGF-beta correlates with the regulation of p21(Cip1) and p27(Kip1), members of the Cip/Kip family of cyclin-dependent kinase inhibitors (cki). However, no definitive evidence exists that these proteins play a causal role in TGF-beta(1)-induced growth arrest in lymphocytes. In this report we show the suppression of cell cycle progression by TGF-beta is diminished in T cells from mice deficient for both p21(Cip1) and p27(Kip1) (double-knockout (DKO)) only when activated under conditions of optimal costimulation. Although there is an IL-2-dependent enhanced proliferation of CD8(+) T cells from DKO mice, TGF-beta is able to maximally suppress the proliferation of DKO T cells when activated under conditions of low costimulatory strength. We also show that the induction of p15(Ink4b) in T cells stimulated in the presence of TGF-beta is not essential, as TGF-beta also efficiently suppressed proliferation of T cells from p15(Ink4b-/-) mice. Finally, although these cki are dispensable for the suppression of T cell proliferation by TGF-beta, we now describe a Smad3-dependent down-regulation of cdk4, suggesting a potential mechanism underlying to resistance of Smad3(-/-) T cells to the induction of growth arrest by TGF-beta. In summary, the growth suppressive effects of TGF-beta in naive T cells are a function of the strength of costimulation, and alterations in the expression of cki modify the sensitivity to TGF-beta by lowering thresholds for a maximal mitogenic response. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wolfraim, Lawrence A AU - Walz, Thomas M AU - James, Zakiya AU - Fernandez, Tania AU - Letterio, John J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wolfraim@tolergenics.com Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 3093 EP - 3102 VL - 173 IS - 5 SN - 0022-1767, 0022-1767 KW - Cdkn1a protein, mouse KW - 0 KW - Cdkn1b protein, mouse KW - Cdkn2b protein, mouse KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p15 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Interleukin-2 KW - Proto-Oncogene Proteins KW - Transforming Growth Factor beta KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Cdk4 protein, mouse KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Abridged Index Medicus KW - Index Medicus KW - Cyclin-Dependent Kinases -- metabolism KW - Animals KW - Cyclin-Dependent Kinases -- immunology KW - Immunologic Memory -- physiology KW - Mice KW - Lymphoid Tissue -- immunology KW - Mice, Knockout KW - Down-Regulation KW - Immunologic Memory -- immunology KW - Lymphoid Tissue -- cytology KW - Up-Regulation KW - Interleukin-2 -- metabolism KW - Cell Cycle Proteins -- immunology KW - Transforming Growth Factor beta -- immunology KW - Cell Cycle Proteins -- metabolism KW - G1 Phase -- immunology KW - Tumor Suppressor Proteins -- immunology KW - T-Lymphocytes -- metabolism KW - Tumor Suppressor Proteins -- metabolism KW - Cyclins -- metabolism KW - Cyclins -- immunology KW - Interleukin-2 -- immunology KW - Transforming Growth Factor beta -- metabolism KW - T-Lymphocytes -- immunology KW - G1 Phase -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66805094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p21Cip1+and+p27Kip1+act+in+synergy+to+alter+the+sensitivity+of+naive+T+cells+to+TGF-beta-mediated+G1+arrest+through+modulation+of+IL-2+responsiveness.&rft.au=Wolfraim%2C+Lawrence+A%3BWalz%2C+Thomas+M%3BJames%2C+Zakiya%3BFernandez%2C+Tania%3BLetterio%2C+John+J&rft.aulast=Wolfraim&rft.aufirst=Lawrence&rft.date=2004-09-01&rft.volume=173&rft.issue=5&rft.spage=3093&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 - 2004-09-21 N1 - Date created - 2004-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier. AN - 66801541; 15322232 AB - P-glycoprotein, an ATP-driven drug export pump, is a critical, selective component of the blood-brain barrier responsible for the poor penetration of many therapeutic drugs. In liver, ligand-activated, nuclear receptors are transcriptional regulators of drug metabolizing enzymes and drug export pumps, but only one, the pregnane X receptor (PXR in rodents, SXR in humans), regulates p-glycoprotein expression. We report for the first time that PXR is expressed in rat brain capillaries. Moreover, exposing isolated capillaries to the PXR ligands pregnenolone-16alpha-carbonitrile (PCN) and dexamethasone increased p-glycoprotein expression and p-glycoprotein-specific transport of a fluorescent cyclosporine A derivative into capillary lumens. Dosing rats with PCN and dexamethasone increased p-glycoprotein expression in liver plasma membranes and in brain capillaries and up-regulated specific transport in capillaries. This is the first evidence for PXR expression in brain and for regulation by nuclear receptors of a xenobiotic export pump at the blood-brain barrier. These results imply selective tightening of the barrier in patients exposed to the wide range of xenobiotics that are PXR/SXR ligands, including drugs, dietary constituents, and toxicants. JF - Molecular pharmacology AU - Bauer, Björn AU - Hartz, Anika M S AU - Fricker, Gert AU - Miller, David S AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 413 EP - 419 VL - 66 IS - 3 SN - 0026-895X, 0026-895X KW - P-Glycoprotein KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Steroid KW - Xenobiotics KW - pregnane X receptor KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Xenobiotics -- pharmacology KW - Gene Expression KW - Biological Transport KW - Up-Regulation KW - Immunohistochemistry KW - Male KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Blood-Brain Barrier -- drug effects KW - P-Glycoprotein -- physiology KW - P-Glycoprotein -- genetics KW - Receptors, Steroid -- physiology KW - P-Glycoprotein -- metabolism KW - Blood-Brain Barrier -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptors, Steroid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66801541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pregnane+X+receptor+up-regulation+of+P-glycoprotein+expression+and+transport+function+at+the+blood-brain+barrier.&rft.au=Bauer%2C+Bj%C3%B6rn%3BHartz%2C+Anika+M+S%3BFricker%2C+Gert%3BMiller%2C+David+S&rft.aulast=Bauer&rft.aufirst=Bj%C3%B6rn&rft.date=2004-09-01&rft.volume=66&rft.issue=3&rft.spage=413&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 - 2004-11-03 N1 - Date created - 2004-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catecholamine metabolism: a contemporary view with implications for physiology and medicine. AN - 66799563; 15317907 AB - This article provides an update about catecholamine metabolism, with emphasis on correcting common misconceptions relevant to catecholamine systems in health and disease. Importantly, most metabolism of catecholamines takes place within the same cells where the amines are synthesized. This mainly occurs secondary to leakage of catecholamines from vesicular stores into the cytoplasm. These stores exist in a highly dynamic equilibrium, with passive outward leakage counterbalanced by inward active transport controlled by vesicular monoamine transporters. In catecholaminergic neurons, the presence of monoamine oxidase leads to formation of reactive catecholaldehydes. Production of these toxic aldehydes depends on the dynamics of vesicular-axoplasmic monoamine exchange and enzyme-catalyzed conversion to nontoxic acids or alcohols. In sympathetic nerves, the aldehyde produced from norepinephrine is converted to 3,4-dihydroxyphenylglycol, not 3,4-dihydroxymandelic acid. Subsequent extraneuronal O-methylation consequently leads to production of 3-methoxy-4-hydroxyphenylglycol, not vanillylmandelic acid. Vanillylmandelic acid is instead formed in the liver by oxidation of 3-methoxy-4-hydroxyphenylglycol catalyzed by alcohol and aldehyde dehydrogenases. Compared to intraneuronal deamination, extraneuronal O-methylation of norepinephrine and epinephrine to metanephrines represent minor pathways of metabolism. The single largest source of metanephrines is the adrenal medulla. Similarly, pheochromocytoma tumor cells produce large amounts of metanephrines from catecholamines leaking from stores. Thus, these metabolites are particularly useful for detecting pheochromocytomas. The large contribution of intraneuronal deamination to catecholamine turnover, and dependence of this on the vesicular-axoplasmic monoamine exchange process, helps explain how synthesis, release, metabolism, turnover, and stores of catecholamines are regulated in a coordinated fashion during stress and in disease states. JF - Pharmacological reviews AU - Eisenhofer, Graeme AU - Kopin, Irwin J AU - Goldstein, David S AD - Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Dr., MSC-1620, Bethesda, MD 20892-1620, USA. ge@box-g.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 331 EP - 349 VL - 56 IS - 3 SN - 0031-6997, 0031-6997 KW - Catecholamines KW - 0 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Biological Transport, Active -- physiology KW - Humans KW - Models, Biological KW - Catecholamines -- pharmacokinetics KW - Catecholamines -- metabolism KW - Catecholamines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66799563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+reviews&rft.atitle=Catecholamine+metabolism%3A+a+contemporary+view+with+implications+for+physiology+and+medicine.&rft.au=Eisenhofer%2C+Graeme%3BKopin%2C+Irwin+J%3BGoldstein%2C+David+S&rft.aulast=Eisenhofer&rft.aufirst=Graeme&rft.date=2004-09-01&rft.volume=56&rft.issue=3&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=00316997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-09 N1 - Date created - 2004-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In utero exposure to polychlorinated biphenyls and sensorineural hearing loss in 8-year-old children. AN - 66797540; 15315812 AB - Early-life exposure to polychlorinated biphenyls (PCBs), a ubiquitous environmental contaminant, increases the hearing threshold at selected frequencies in rats. Among humans from the Faroe Islands with unusually high early-life PCB exposure, exposure was directly associated with increased hearing thresholds at two frequencies, although the deficits were present in the left ear but not the right. We examined PCB levels in maternal pregnancy serum in relation with audiometrically determined hearing thresholds among offspring when they were of school age. Complete data were available for 195 children with sensorineural hearing loss (SNHL) and 615 children selected at random, all of whom were born in 1959-1966 in the Collaborative Perinatal Project (CPP) U.S. cohort. The median exposure among those selected at random, as reflected by the mother's third trimester serum total PCB concentration, was 2.8 microg/l, about twofold higher than recent background levels in the United States. Based on the average hearing threshold across the frequencies essential for speech recognition in the "worst ear," the maternal serum PCB level was unrelated to the adjusted odds of SNHL or to adjusted mean hearing threshold. Overall, an adverse effect of early-life, background-level PCB exposure on SNHL was not supported by these data. JF - Neurotoxicology and teratology AU - Longnecker, Matthew P AU - Hoffman, Howard J AU - Klebanoff, Mark A AU - Brock, John W AU - Zhou, Haibo AU - Needham, Larry AU - Adera, Tilahun AU - Guo, Xuguang AU - Gray, Kimberly A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, MD A3-05, Research Triangle Park, NC 27709, USA. longnecker@niehs.nih.gov PY - 2004 SP - 629 EP - 637 VL - 26 IS - 5 SN - 0892-0362, 0892-0362 KW - Environmental Pollutants KW - 0 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Audiometry -- methods KW - Humans KW - Adult KW - Retrospective Studies KW - Follow-Up Studies KW - Child KW - Birth Weight -- drug effects KW - Male KW - Female KW - Body Height -- drug effects KW - Pregnancy KW - Hearing Loss, Sensorineural -- chemically induced KW - Polychlorinated Biphenyls -- blood KW - Environmental Pollutants -- poisoning KW - Polychlorinated Biphenyls -- poisoning KW - Environmental Pollutants -- blood KW - Maternal Exposure KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66797540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+teratology&rft.atitle=In+utero+exposure+to+polychlorinated+biphenyls+and+sensorineural+hearing+loss+in+8-year-old+children.&rft.au=Longnecker%2C+Matthew+P%3BHoffman%2C+Howard+J%3BKlebanoff%2C+Mark+A%3BBrock%2C+John+W%3BZhou%2C+Haibo%3BNeedham%2C+Larry%3BAdera%2C+Tilahun%3BGuo%2C+Xuguang%3BGray%2C+Kimberly+A&rft.aulast=Longnecker&rft.aufirst=Matthew&rft.date=2004-09-01&rft.volume=26&rft.issue=5&rft.spage=629&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology+and+teratology&rft.issn=08920362&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-09 N1 - Date created - 2004-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary supplementation with 2-deoxy-D-glucose improves cardiovascular and neuroendocrine stress adaptation in rats. AN - 66796579; 15317676 AB - Dietary restriction and physical exercise can enhance stress resistance and reduce the risk of cardiovascular disease. We investigated the effects of dietary supplementation with 2-deoxy-d-glucose (2-DG), a glucose analog that limits glucose availability at the cellular level, on cardiovascular and neuroendocrine responses to stress in rats. Young adult male Sprague-Dawley rats were implanted with telemetry probes to monitor blood pressure (BP), heart rate, body temperature, and body movements. These variables were measured at designated times during a 6-mo period in rats fed control and 2-DG-supplemented (0.4% 2-DG, fed ad libitum on a schedule of 2 days on the diet and 1 day off the diet) diets during unperturbed conditions and during and after immobilization stress or cold-water swim stress. Rats fed the 2-DG diet exhibited significant reductions in resting BP, attenuated BP responses during stress, and accelerated recovery to baseline after stress. Plasma concentrations of ACTH and corticosterone were elevated under nonstress conditions in rats fed the 2-DG diet and exhibited differential responses to single (enhanced response) and multiple (reduced response) stress sessions compared with rats fed control rat chow ad libitum. The 2-DG diet improved glucose metabolism, as indicated by decreased concentrations of blood glucose and insulin under nonstress conditions, but glucose and insulin responses to stress were maintained. We conclude that improvements in some cardiovascular risk factors and stress adaptation in rats maintained on a 2-DG-supplemented diet are associated with reduced neuroendocrine responses to the stressors. JF - American journal of physiology. Heart and circulatory physiology AU - Wan, Ruiqian AU - Camandola, Simonetta AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - H1186 EP - H1193 VL - 287 IS - 3 SN - 0363-6135, 0363-6135 KW - Antimetabolites KW - 0 KW - Blood Glucose KW - Insulin KW - Deoxyglucose KW - 9G2MP84A8W KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Heart Rate -- drug effects KW - Insulin -- blood KW - Glucose -- metabolism KW - Rest KW - Blood Pressure -- drug effects KW - Blood Glucose -- analysis KW - Male KW - Antimetabolites -- pharmacology KW - Cardiovascular System -- physiopathology KW - Dietary Supplements KW - Adaptation, Physiological KW - Deoxyglucose -- pharmacology KW - Stress, Physiological -- physiopathology KW - Neurosecretory Systems -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66796579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Heart+and+circulatory+physiology&rft.atitle=Dietary+supplementation+with+2-deoxy-D-glucose+improves+cardiovascular+and+neuroendocrine+stress+adaptation+in+rats.&rft.au=Wan%2C+Ruiqian%3BCamandola%2C+Simonetta%3BMattson%2C+Mark+P&rft.aulast=Wan&rft.aufirst=Ruiqian&rft.date=2004-09-01&rft.volume=287&rft.issue=3&rft.spage=H1186&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Heart+and+circulatory+physiology&rft.issn=03636135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disregulation of E-cadherin in transgenic mouse models of liver cancer. AN - 66790523; 15220935 AB - E-cadherin is a cell-cell adhesion molecule that plays a pivotal role in the development and maintenance of cell polarity. Disruption of E-cadherin-mediated adhesion represents a key step toward the invasive phenotype in a variety of solid tumors, including hepatocellular carcinoma (HCC). Here, we investigate whether deregulation of E-cadherin occurs along the multistep process of hepatocarcinogenesis in transgenic mouse models, including c-Myc, E2F1, c-Myc/TGF-alpha and c-Myc/E2F1 mice. Liver tumors from the transgenic mouse lines could be divided into two categories based on E-cadherin levels. Of 28, 20 (71.4%) c-Myc HCCs showed marked reduction of E-cadherin expression when compared with wild-type livers. In contrast, all of c-Myc/TGF-alpha and the majority of E2F1 and c-myc/E2F1 preneoplastic and neoplastic lesions exhibited overexpression of E-cadherin. Downregulation of E-cadherin was associated with promoter hypermethylation in seven of 20 c-Myc HCCs (35%), while no loss of heterozygosity at the E-cadherin locus was detected. Nuclear accumulation of beta-catenin did not correlate with E-cadherin downregulation. Furthermore, c-Myc HCCs with reduced E-cadherin displayed upregulation of hypoxia-inducible factor-1alpha and vascular endothelial growth factor proteins. Importantly, loss of E-cadherin was associated with increased cell proliferation and higher microvessel density in c-Myc tumors. Taken together, these data suggest that loss of E-cadherin might favor tumor progression in relatively more benign HCC from c-Myc transgenic mice by stimulating neoplastic proliferation and angiogenesis under hypoxic conditions. JF - Laboratory investigation; a journal of technical methods and pathology AU - Calvisi, Diego F AU - Ladu, Sara AU - Conner, Elizabeth A AU - Factor, Valentina M AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1137 EP - 1147 VL - 84 IS - 9 SN - 0023-6837, 0023-6837 KW - Cadherins KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Polymerase Chain Reaction KW - Microsatellite Repeats KW - Mice, Inbred Strains KW - Animals KW - Blotting, Western KW - Microcirculation -- pathology KW - Apoptosis KW - Disease Models, Animal KW - Mice KW - DNA, Neoplasm -- analysis KW - Neovascularization, Pathologic KW - Immunohistochemistry KW - Gene Expression Regulation, Neoplastic KW - Liver Neoplasms -- pathology KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Cadherins -- metabolism KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Mice, Transgenic KW - Cadherins -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66790523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Disregulation+of+E-cadherin+in+transgenic+mouse+models+of+liver+cancer.&rft.au=Calvisi%2C+Diego+F%3BLadu%2C+Sara%3BConner%2C+Elizabeth+A%3BFactor%2C+Valentina+M%3BThorgeirsson%2C+Snorri+S&rft.aulast=Calvisi&rft.aufirst=Diego&rft.date=2004-09-01&rft.volume=84&rft.issue=9&rft.spage=1137&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 - 2004-09-28 N1 - Date created - 2004-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term exposure to elevated levels of circulating TIMP-1 but not mammary TIMP-1 suppresses growth of mammary carcinomas in transgenic mice. AN - 66789572; 15166086 AB - Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates matrix metalloproteinase activity, acts as a growth stimulator and inhibits apoptosis. We developed transgenic mice to evaluate the relevance of circulating versus mammary TIMP-1 in mammary carcinogenesis. The transgene was placed under the control of the albumin (Alb) promoter for the production of large amounts of TIMP-1 in the liver and release into the systemic circulation to achieve chronically elevated blood levels. The initial 7,12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis study showed greatly decreased tumor incidence in heterozygous Alb-TIMP-1 mice (25%), compared with their wild-type (wt) littermates (83.3%). Metastatic mammary carcinomas were induced in the Alb-TIMP-1 mice through breeding with mice expressing the polyomavirus Middle T antigen (MT) under the control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Both the mammary tumor burden and the incidence of lung metastases were lower in the Alb-TIMP-1/MMTV-MT mice than their MMTV-MT littermates. Analysis of the Alb-TIMP-1/MMTV-MT tumors showed evidence of decreased proliferative activity and inhibition of apoptosis, whereas microvascular density was not affected. Transgenic expression of TIMP-1 in mammary epithelial cells was accomplished by using MMTV-LTR. In contrast to the Alb-TIMP-1 mice, there was insignificant difference in the growth of both DMBA- and MT-induced mammary tumors between heterozygous MMTV-TIMP-1 mice and their wt littermates. The MT-induced mammary tumors of the MMTV-TIMP-1 mice were separated into 'low' and 'high' TIMP-1 expressing groups. The 'high' TIMP-1 expressing tumors exhibited significantly higher proliferative activity than the tumors of the MMTV-MT only mice, whereas the number of apoptotic cells and microvascular density were not different. The findings of this study show that circulating TIMP-1, but not mammary-derived TIMP-1, has growth suppressive effects on DMBA and MT-induced mammary carcinomas. JF - Carcinogenesis AU - Yamazaki, Masaharu AU - Akahane, Takemi AU - Buck, Todd AU - Yoshiji, Hitoshi AU - Gomez, Daniel E AU - Schoeffner, Daniel J AU - Okajima, Eijiro AU - Harris, Steven R AU - Bunce, Opal R AU - Thorgeirsson, Snorri S AU - Thorgeirsson, Unnur P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1735 EP - 1746 VL - 25 IS - 9 SN - 0143-3334, 0143-3334 KW - Albumins KW - 0 KW - Antigens, Polyomavirus Transforming KW - Tissue Inhibitor of Metalloproteinase-1 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Animals KW - Mice, Inbred CBA KW - Terminal Repeat Sequences -- genetics KW - Apoptosis KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Transgenes KW - Mice, Inbred C57BL KW - Mice KW - Mice, Transgenic KW - Antigens, Polyomavirus Transforming -- genetics KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- blood KW - Tissue Inhibitor of Metalloproteinase-1 -- metabolism KW - Lung Neoplasms -- secondary KW - Albumins -- genetics KW - Mammary Neoplasms, Experimental -- prevention & control KW - Mammary Neoplasms, Experimental -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66789572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Long-term+exposure+to+elevated+levels+of+circulating+TIMP-1+but+not+mammary+TIMP-1+suppresses+growth+of+mammary+carcinomas+in+transgenic+mice.&rft.au=Yamazaki%2C+Masaharu%3BAkahane%2C+Takemi%3BBuck%2C+Todd%3BYoshiji%2C+Hitoshi%3BGomez%2C+Daniel+E%3BSchoeffner%2C+Daniel+J%3BOkajima%2C+Eijiro%3BHarris%2C+Steven+R%3BBunce%2C+Opal+R%3BThorgeirsson%2C+Snorri+S%3BThorgeirsson%2C+Unnur+P&rft.aulast=Yamazaki&rft.aufirst=Masaharu&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1735&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-05 N1 - Date created - 2004-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo analysis of the 3' untranslated region of GB virus B after in vitro mutagenesis of an infectious cDNA clone: persistent infection in a transfected tamarin. AN - 66785127; 15308733 AB - GB virus B (GBV-B), the virus most closely related to hepatitis C virus (HCV), infects tamarins and causes acute hepatitis. The 3' untranslated region (UTR) of an infectious GBV-B clone (pGBB) has a proximal short sequence followed by a poly(U) tract and a 3' terminal sequence. Our investigators previously demonstrated that the 3' terminal sequence was critical for in vivo infectivity. Here, we tested the effect of deleting the short sequence and/or the poly(U) tract from pGBB; infectivity of each mutant was tested by intrahepatic transfection of two tamarins with transcribed RNA. A mutant lacking both regions was not viable. However, mutants lacking either the short sequence or the poly(U) tract were viable. All four tamarins had a wild-type-like acute infection and developed acute hepatitis. Whereas we found that five tamarins transfected with the wild-type clone pGBB had acute resolving infection, one tamarin transfected with the poly(U) deletion mutant became persistently infected. This animal had viremia and hepatitis until its death at week 90. The genomes recovered at weeks 2, 7, 15, 20, 60, and 90 lacked the poly(U) stretch. Eight amino acid changes were identified at week 90. One change, in the putative p7 protein, was dominant at week 15. Thus, persistence of GBV-B, like persistence of HCV, was associated with the emergence of virus variants. Four tamarins inoculated with serum collected at weeks 2 and 90 from the tamarin with persistent infection had an acute resolving infection. Nonetheless, the demonstration that GBV-B can persist in tamarins strengthens its relevance as a surrogate model for the study of HCV. JF - Journal of virology AU - Nam, Jae-Hwan AU - Faulk, Kristina AU - Engle, Ronald E AU - Govindarajan, Sugantha AU - St Claire, Marisa AU - Bukh, Jens AD - Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8009, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 9389 EP - 9399 VL - 78 IS - 17 SN - 0022-538X, 0022-538X KW - 3' Untranslated Regions KW - 0 KW - DNA, Complementary KW - Luminescent Proteins KW - Polyproteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Poly U KW - 27416-86-0 KW - Index Medicus KW - Virus Replication KW - Animals KW - DNA, Complementary -- genetics KW - Genome, Viral KW - Cloning, Molecular KW - Hepatitis, Viral, Animal -- virology KW - Poly U -- genetics KW - Base Sequence KW - Transfection KW - Sequence Deletion -- genetics KW - Molecular Sequence Data KW - Polyproteins -- genetics KW - Time Factors KW - Luminescent Proteins -- genetics KW - Flaviviridae Infections -- virology KW - GB virus B -- genetics KW - Saguinus -- virology KW - Genetic Engineering KW - GB virus B -- physiology KW - GB virus B -- pathogenicity KW - Mutagenesis -- genetics KW - 3' Untranslated Regions -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66785127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+vivo+analysis+of+the+3%27+untranslated+region+of+GB+virus+B+after+in+vitro+mutagenesis+of+an+infectious+cDNA+clone%3A+persistent+infection+in+a+transfected+tamarin.&rft.au=Nam%2C+Jae-Hwan%3BFaulk%2C+Kristina%3BEngle%2C+Ronald+E%3BGovindarajan%2C+Sugantha%3BSt+Claire%2C+Marisa%3BBukh%2C+Jens&rft.aulast=Nam&rft.aufirst=Jae-Hwan&rft.date=2004-09-01&rft.volume=78&rft.issue=17&rft.spage=9389&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 - 2004-09-16 N1 - Date created - 2004-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Virol. 2001 Oct;82(Pt 10):2437-48 [11562537] J Virol. 1999 Apr;73(4):3317-25 [10074186] J Med Virol. 2001 Dec;65(4):694-7 [11745933] J Virol. 2002 Jun;76(11):5326-38 [11991961] Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14416-21 [12391335] Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15661-8 [12441397] J Virol. 2003 Mar;77(6):3557-68 [12610131] Virology. 2003 Jun 20;311(1):72-80 [12832204] Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9962-7 [12907703] Virology. 1999 Sep 1;261(2):216-26 [10497107] J Gen Virol. 1999 Sep;80 ( Pt 9):2337-41 [10501485] Virology. 1999 Sep 30;262(2):470-8 [10502525] J Virol. 2000 Jan;74(2):773-83 [10623739] J Virol. 2000 Feb;74(4):2046-51 [10644379] J Virol. 2000 May;74(9):4291-301 [10756044] J Gen Virol. 2000 Sep;81(Pt 9):2183-8 [10950975] J Viral Hepat. 2000 Sep;7(5):335-42 [10971821] J Virol. 2000 Dec;74(24):11764-72 [11090176] J Virol. 1999 Dec;73(12):10546-50 [10559376] Methods Mol Biol. 2003;226:173-8 [12958498] Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3401-5 [7724574] J Med Virol. 1995 May;46(1):81-90 [7623012] J Virol. 1995 Sep;69(9):5621-30 [7637008] Biochem Biophys Res Commun. 1995 Oct 13;215(2):744-9 [7488017] J Virol. 1996 Jun;70(6):3363-71 [8648666] J Clin Microbiol. 1996 Dec;34(12):3085-91 [8940452] Virology. 1997 Mar 17;229(2):429-36 [9126255] J Virol. 1997 Jul;71(7):4985-9 [9188562] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8738-43 [9238047] Virology. 1998 Apr 25;244(1):161-72 [9581788] Arch Virol. 1998;143(12):2493-503 [9930205] Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2291-5 [10051634] Gastroenterology. 2001 Nov;121(5):1226-33 [11677216] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody. AN - 66782934; 15308718 AB - The identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in our understanding of the mechanisms of virus entry and neutralization and in the development of entry inhibitors and vaccines. For enhanced selection of broadly cross-reactive antibodies, soluble HIV-1 envelope glycoproteins (Envs proteins) from two isolates complexed with two-domain soluble CD4 (sCD4) were alternated during panning of a phage-displayed human antibody library; these two Env proteins (89.6 and IIIB gp140s), and one additional Env (JR-FL gp120) alone and complexed with sCD4 were used for screening. An antibody with relatively long HCDR3 (17 residues), designated m14, was identified that bound to all antigens and neutralized heterologous HIV-1 isolates in multiple assay formats. Fab m14 potently neutralized selected well-characterized subtype B isolates, including JRCSF, 89.6, IIIB, and Yu2. Immunoglobulin G1 (IgG1) m14 was more potent than Fab m14 and neutralized 7 of 10 other clade B isolates; notably, although the potency was on average significantly lower than that of IgG1 b12, IgG1 m14 neutralized two of the isolates with significantly lower 50% inhibitory concentrations than did IgG1 b12. IgG1 m14 neutralized four of four selected clade C isolates with potency higher than that of IgG1 b12. It also neutralized 7 of 17 clade C isolates from southern Africa that were difficult to neutralize with other hMAbs and sCD4. IgG1 m14 neutralized four of seven primary HIV-1 isolates from other clades (A, D, E, and F) much more efficiently than did IgG1 b12; for the other three isolates, IgG b12 was much more potent. Fab m14 bound with high (nanomolar range) affinity to gp120 and gp140 from various isolates; its binding was reduced by soluble CD4 and antibodies recognizing the CD4 binding site (CD4bs) on gp120, and its footprint as defined by alanine-scanning mutagenesis overlaps that of b12. These results suggest that m14 is a novel CD4bs cross-reactive HIV-1-neutralizing antibody that exhibits a different inhibitory profile compared to the only known potent broadly neutralizing CD4bs human antibody, b12, and may have implications for our understanding of the mechanisms of immune evasion and for the development of inhibitors and vaccines. JF - Journal of virology AU - Zhang, Mei-Yun AU - Xiao, Xiaodong AU - Sidorov, Igor A AU - Choudhry, Vidita AU - Cham, Fatim AU - Zhang, Peng Fei AU - Bouma, Peter AU - Zwick, Michael AU - Choudhary, Anil AU - Montefiori, David C AU - Broder, Christopher C AU - Burton, Dennis R AU - Quinnan, Gerald V AU - Dimitrov, Dimiter S AD - Human Immunovirology Group, Laboratory of Experimental and Computational Biology, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, Maryland 21702-1201, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 9233 EP - 9242 VL - 78 IS - 17 SN - 0022-538X, 0022-538X KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD4 KW - Epitopes KW - Gene Products, env KW - HIV Antibodies KW - HIV Envelope Protein gp120 KW - Immunoglobulin Fab Fragments KW - Immunoglobulin G KW - Peptide Library KW - env Gene Products, Human Immunodeficiency Virus KW - gp140 envelope protein, Human immunodeficiency virus 1 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Epitopes -- genetics KW - Humans KW - Immunoglobulin Fab Fragments -- genetics KW - Antigens, CD4 -- immunology KW - Biosensing Techniques KW - HIV Envelope Protein gp120 -- immunology KW - Alanine -- metabolism KW - Molecular Sequence Data KW - Alanine -- genetics KW - Immunoglobulin Fab Fragments -- immunology KW - Epitopes -- chemistry KW - Immunoglobulin G -- isolation & purification KW - Bacteriophages -- genetics KW - Amino Acid Sequence KW - Mutagenesis -- genetics KW - Immunoglobulin G -- immunology KW - Base Sequence KW - Immunoglobulin G -- genetics KW - Kinetics KW - Neutralization Tests KW - Gene Products, env -- immunology KW - Immunoglobulin Fab Fragments -- isolation & purification KW - Epitopes -- immunology KW - Cell Line KW - Genomics KW - HIV-1 -- immunology KW - HIV Antibodies -- isolation & purification KW - Antibodies, Monoclonal -- isolation & purification KW - HIV Antibodies -- immunology KW - Antibodies, Monoclonal -- genetics KW - HIV Antibodies -- genetics KW - HIV-1 -- classification KW - Cross Reactions -- immunology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66782934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+and+characterization+of+a+new+cross-reactive+human+immunodeficiency+virus+type+1-neutralizing+human+monoclonal+antibody.&rft.au=Zhang%2C+Mei-Yun%3BXiao%2C+Xiaodong%3BSidorov%2C+Igor+A%3BChoudhry%2C+Vidita%3BCham%2C+Fatim%3BZhang%2C+Peng+Fei%3BBouma%2C+Peter%3BZwick%2C+Michael%3BChoudhary%2C+Anil%3BMontefiori%2C+David+C%3BBroder%2C+Christopher+C%3BBurton%2C+Dennis+R%3BQuinnan%2C+Gerald+V%3BDimitrov%2C+Dimiter+S&rft.aulast=Zhang&rft.aufirst=Mei-Yun&rft.date=2004-09-01&rft.volume=78&rft.issue=17&rft.spage=9233&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 - 2004-09-16 N1 - Date created - 2004-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2002 May 14;99(10):6913-8 [11997472] Biochemistry. 2002 Jun 4;41(22):7176-82 [12033952] J Virol. 2002 Jul;76(14):7293-305 [12072528] J Virol. 2002 Jul;76(14):7306-21 [12072529] Curr Opin Immunol. 2002 Aug;14(4):495-502 [12088685] Nat Rev Immunol. 2002 Sep;2(9):706-13 [12209139] AIDS. 2002 Oct 18;16(15):2019-25 [12370500] J Gen Virol. 2002 Nov;83(Pt 11):2723-32 [12388808] J Virol. 2003 Jan;77(1):560-70 [12477860] J Virol. 2003 Jan;77(1):642-58 [12477867] J Virol. 1991 Jan;65(1):489-93 [1702163] J Immunol. 1991 Jun 15;146(12):4325-32 [1710248] J Virol. 1991 Sep;65(9):4832-8 [1714520] AIDS Res Hum Retroviruses. 1998 May 1;14(7):545-50 [9591708] Science. 1998 Jun 19;280(5371):1884-8 [9632381] J Virol. 1998 Sep;72(9):7099-107 [9696803] J Virol. 1999 May;73(5):4009-18 [10196297] AIDS Res Hum Retroviruses. 1999 Apr 10;15(6):561-70 [10221533] J Virol. 1999 Jun;73(6):5225-30 [10233993] J Virol. 1999 Jul;73(7):5707-13 [10364321] Nat Med. 2000 Feb;6(2):200-6 [10655110] Nat Med. 2000 Feb;6(2):207-10 [10655111] J Virol. 2000 May;74(9):4183-91 [10756031] J Virol. 1991 Nov;65(11):6188-93 [1717717] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10134-7 [1719545] Res Virol. 1991 Jul-Aug;142(4):247-59 [1724568] J Virol. 1992 Sep;66(9):5635-41 [1380099] J Virol. 1992 Dec;66(12):7538-42 [1433529] J Mol Biol. 1993 Apr 5;230(3):812-23 [8478936] J Virol. 1993 Jul;67(7):3978-88 [7685405] J Virol. 1993 Nov;67(11):6642-7 [7692082] J Virol. 1994 Jun;68(6):4001-8 [7514683] J Virol. 1994 Aug;68(8):4821-8 [7518527] AIDS Res Hum Retroviruses. 1994 Apr;10(4):359-69 [7520721] J Virol. 1994 Nov;68(11):6994-7000 [7933081] Science. 1994 Nov 11;266(5187):1024-7 [7973652] AIDS Res Hum Retroviruses. 1994 Dec;10(12):1651-8 [7888224] AIDS. 1995 Jun;9(6):F1-6 [7662189] AIDS. 1995 Aug;9(8):867-74 [7576320] J Virol. 1996 Feb;70(2):1100-8 [8551569] J Virol. 1996 Mar;70(3):1863-72 [8627711] J Virol. 1996 Oct;70(10):6751-8 [8794312] AIDS Res Hum Retroviruses. 1996 Jul 1;12(10):911-24 [8798976] J Virol. 1996 Dec;70(12):9046-50 [8971041] J Mol Biol. 1997 Apr 4;267(3):684-95 [9126846] J Infect Dis. 1997 May;175(5):1056-62 [9129066] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10018-23 [9294155] AIDS. 1997;11 Suppl A:S87-98 [9451972] AIDS Res Hum Retroviruses. 1998 Jan 20;14(2):151-5 [9462925] J Infect Dis. 2000 Jul;182(1):326-9 [10882617] J Virol. 2001 Jun;75(11):4964-72 [11333875] Science. 2001 Aug 10;293(5532):1155-9 [11498595] J Virol. 2001 Nov;75(22):10892-905 [11602729] J Virol. 2002 Jan;76(2):644-55 [11752155] Vaccine. 2002 Dec 19;20 Suppl 4:A61-5 [12477430] Virology. 2003 Jan 5;305(1):124-37 [12504547] AIDS. 2003 Feb 14;17(3):301-9 [12556683] J Virol. 2003 Mar;77(5):3119-30 [12584337] Nat Med. 2003 Mar;9(3):343-6 [12579198] J Antimicrob Chemother. 2003 Apr;51(4):757-9 [12654737] J Virol. 2003 May;77(10):5863-76 [12719580] J Virol. 2003 Jul;77(14):8061-71 [12829845] Vaccine. 2003 Jul 28;21(24):3370-3 [12850342] J Virol. 2003 Oct;77(19):10557-65 [12970440] J Immunol Methods. 2003 Dec;283(1-2):17-25 [14659896] J Mol Biol. 2004 Jan 2;335(1):209-19 [14659751] J Virol. 2004 Jan;78(1):146-57 [14671096] J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):169-77 [14722451] Antimicrob Agents Chemother. 2004 Feb;48(2):423-9 [14742190] Antiviral Res. 2004 Mar;61(3):161-4 [15168796] AIDS Res Hum Retroviruses. 2001 Dec 10;17(18):1757-65 [11788027] AIDS. 2002 Jan 25;16(2):227-33 [11807307] J Virol. 2002 Mar;76(5):2233-44 [11836401] J Biol Chem. 2002 May 10;277(19):17291-9 [11782464] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - United States nuclear industry perspective on useful improvements to radiation protection principles. AN - 66774904; 15303064 AB - The current radiation protection framework provides an adequate basis for protecting workers, the public and the environment. Nevertheless, international and national radiation protection organizations are presently engaged in updating, clarifying and enhancing radiation protection principles-and rightly so, given our culture of pursuing excellence in radiation safety through a process of continuous improvement. Accordingly, the nuclear energy industry appreciates the opportunity to provide its perspective on this effort. The nuclear energy industry's perspective is shaped in several ways-as an operator, we carry out a primary responsibility for protecting human health and safety and the environment; as a licensee, we are responsible for complying with government regulations; and as an energy producer, we are responsible for the safe, reliable, and economic generation of electricity for consumers. Our objective in regard to improving radiation protection principles is to help promote an outcome that has a clearly articulated basis in science, is flexible in regard to how it might be applied to a very wide range of current and future regulated activities, and is practical and cost-effective in terms of how it can be implemented and maintained. JF - Health physics AU - Andersen, Ralph L AD - Nuclear Energy Institute, 1776 I Street, NW, Suite 400, Washington, DC 20006-3700, USA. rla@nei.org Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 282 EP - 285 VL - 87 IS - 3 SN - 0017-9078, 0017-9078 KW - Index Medicus KW - United States KW - Occupational Exposure KW - Radiation Dosage KW - Humans KW - Government Agencies KW - Environmental Exposure KW - International Agencies KW - Radiation Protection KW - Nuclear Energy KW - Industry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66774904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=United+States+nuclear+industry+perspective+on+useful+improvements+to+radiation+protection+principles.&rft.au=Andersen%2C+Ralph+L&rft.aulast=Andersen&rft.aufirst=Ralph&rft.date=2004-09-01&rft.volume=87&rft.issue=3&rft.spage=282&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 - 2004-09-14 N1 - Date created - 2004-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluorescein-methotrexate transport in rat choroid plexus analyzed using confocal microscopy. AN - 66770568; 15126245 AB - One function of the vertebrate choroid plexus (CP) is removal of potentially toxic metabolites and xenobiotics from cerebrospinal fluid (CSF) to blood for subsequent excretion in urine and bile. We have used confocal microscopy and quantitative image analysis to follow transport of the large organic anion fluorescein-methotrexate (FL-MTX) from bath (CSF side) to blood vessels in intact rat CP and found concentrative transport from CSF to blood. With 2 microM FL-MTX in the bath, steady-state fluorescence in the subepithelium and vascular spaces exceeded bath levels by 5- to 10-fold, but fluorescence in epithelial cells was below bath levels. FL-MTX accumulation in subepithelium and vascular spaces was reduced by NaCN, Na removal, and by other organic anions, e.g., MTX, probenecid, and estrone sulfate. Increasing medium K 10-fold had no effect. None of these treatments affected cellular accumulation. However, two observations indicated that apical FL-MTX uptake was indeed mediated: first, cellular accumulation was a saturable function of medium substrate concentration; and second, digoxin and MK-571 reduced FL-MTX accumulation in the subepithelial/vascular spaces but also increased cellular accumulation severalfold. In the presence of digoxin and MK-571, cellular accumulation was concentrative, specific, and Na dependent. Thus transepithelial FL-MTX transport involved the following two mediated steps: Na-dependent uptake at the apical membrane and electroneutral efflux at the basolateral membrane, possibly on Oatp2 and Mrp1. JF - American journal of physiology. Renal physiology AU - Breen, Christopher M AU - Sykes, Destiny B AU - Baehr, Carsten AU - Fricker, Gert AU - Miller, David S AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - F562 EP - F569 VL - 287 IS - 3 SN - 1931-857X, 1931-857X KW - Bronchodilator Agents KW - 0 KW - Enzyme Inhibitors KW - Fluoresceins KW - Organic Anion Transporters KW - Propionates KW - Quinolines KW - fluorescein-methotrexate KW - verlukast KW - 5Q9O54P0H7 KW - Digoxin KW - 73K4184T59 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Animals KW - Bronchodilator Agents -- pharmacology KW - Propionates -- pharmacology KW - Biological Transport -- drug effects KW - Epithelial Cells -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Quinolines -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Biological Transport -- physiology KW - Organic Anion Transporters -- metabolism KW - Digoxin -- pharmacology KW - Male KW - Methotrexate -- pharmacokinetics KW - Methotrexate -- analogs & derivatives KW - Choroid Plexus -- metabolism KW - Fluoresceins -- pharmacokinetics KW - Microscopy, Confocal -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66770568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Renal+physiology&rft.atitle=Fluorescein-methotrexate+transport+in+rat+choroid+plexus+analyzed+using+confocal+microscopy.&rft.au=Breen%2C+Christopher+M%3BSykes%2C+Destiny+B%3BBaehr%2C+Carsten%3BFricker%2C+Gert%3BMiller%2C+David+S&rft.aulast=Breen&rft.aufirst=Christopher&rft.date=2004-09-01&rft.volume=287&rft.issue=3&rft.spage=F562&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Renal+physiology&rft.issn=1931857X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-28 N1 - Date created - 2004-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences between AGAP1, ASAP1 and Arf GAP1 in substrate recognition: interaction with the N-terminus of Arf1. AN - 66646669; 15212764 AB - The Arf GAPs are a structurally diverse group of proteins that catalyze the hydrolysis of GTP bound to Arf1. Here, we directly compare the role of amino acids 2-17 of Arf1, a GTP- and phospholipid-sensitive switch, for interaction with three Arf GAPs: Arf GAP1, AGAP1 and ASAP1. Sequestration of amino acids 2-17 with an antibody inhibited interaction with the three tested Arf GAPs. Examination of Arf1 mutants also indicated that [2-17]Arf1 is a critical structural determinant of interaction with all three Arf GAPs; however, the effect of specific mutations differed among the GAPs. Compared to wild-type Arf1, Arf1 with the amino terminal 13 ([Delta13]Arf1) and 17 amino acids ([Delta17]Arf1) deleted had 200- and 4000-fold reduced interaction with ASAP1 and 150-fold reduced interaction with AGAP1. In contrast, deletion of the amino terminus of Arf reduced interaction with Arf GAP1 by 5-fold. By analysis of point mutants, we found that lysines 15 and 16 had a greater contribution to productive interaction between Arf1, ASAP1 and AGAP1 than between Arf1 and Arf GAP1. Leucine 8 contributed to the interaction with Arf GAP1 but not with ASAP1 and AGAP1. Amino acids 2-17 of Arf1, isolated from the protein, inhibited GAP activity of Arf GAP1, ASAP1 and AGAP1 and bound directly to ASAP1. Taken together, our results indicate that (i) Arf GAPs interact with amino acids 2-17 of Arf1 and (ii) each subgroup of Arf GAPs has a unique interface with Arf1. JF - Cellular signalling AU - Yoon, Hye-Young AU - Jacques, Kerry AU - Nealon, Beth AU - Stauffer, Stacey AU - Premont, Richard T AU - Randazzo, Paul A AD - Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Building 37, Room 4118, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1033 EP - 1044 VL - 16 IS - 9 SN - 0898-6568, 0898-6568 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Arfgap1 protein, mouse KW - Arfgap3 protein, mouse KW - GTPase-Activating Proteins KW - Immune Sera KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Animals KW - Base Sequence KW - GTP Phosphohydrolases -- metabolism KW - Enzyme Activation -- drug effects KW - Mice KW - Substrate Specificity KW - Protein Binding KW - NIH 3T3 Cells KW - Immune Sera -- pharmacology KW - Protein Transport KW - Mutagenesis KW - Adaptor Proteins, Signal Transducing -- metabolism KW - ADP-Ribosylation Factors -- genetics KW - GTPase-Activating Proteins -- genetics KW - GTPase-Activating Proteins -- metabolism KW - ADP-Ribosylation Factor 1 -- immunology KW - ADP-Ribosylation Factors -- metabolism KW - ADP-Ribosylation Factor 1 -- metabolism KW - ADP-Ribosylation Factor 1 -- genetics KW - Adaptor Proteins, Signal Transducing -- genetics KW - ADP-Ribosylation Factor 1 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differences+between+AGAP1%2C+ASAP1+and+Arf+GAP1+in+substrate+recognition%3A+interaction+with+the+N-terminus+of+Arf1.&rft.au=Yoon%2C+Hye-Young%3BJacques%2C+Kerry%3BNealon%2C+Beth%3BStauffer%2C+Stacey%3BPremont%2C+Richard+T%3BRandazzo%2C+Paul+A&rft.aulast=Yoon&rft.aufirst=Hye-Young&rft.date=2004-09-01&rft.volume=16&rft.issue=9&rft.spage=1033&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 - 2005-01-07 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Does class size in first grade relate to children's academic and social performance or observed classroom processes? AN - 37948901; 2847269 JF - Developmental psychology Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 651 EP - 664 VL - 40 IS - 5 SN - 0012-1649, 0012-1649 KW - Sociology KW - Education KW - Academic achievement KW - Child psychology KW - Psychology KW - Child development KW - Developmental psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37948901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+psychology&rft.atitle=Does+class+size+in+first+grade+relate+to+children%27s+academic+and+social+performance+or+observed+classroom+processes%3F&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2004-09-01&rft.volume=40&rft.issue=5&rft.spage=651&rft.isbn=&rft.btitle=&rft.title=Developmental+psychology&rft.issn=00121649&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 3518 10404; 10404; 2205 2212 10404; 2197 2212 6075 3483; 501 542 8322; 4049 ER - TY - JOUR T1 - Use of microarray for screening radiation induced molecular targets AN - 21268734; 6184266 JF - International Journal of Radiation Oncology, Biology, & Physics AU - Citrin, D AU - Beecken, W AU - Scott, T AU - Goley, E AU - Sproull, M AU - Tofilon, P AU - Camphausen, K AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, MD Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - S360 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 60 IS - 1 SN - 0360-3016, 0360-3016 KW - Biotechnology and Bioengineering Abstracts KW - Radiation KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21268734?accountid=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=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Use+of+microarray+for+screening+radiation+induced+molecular+targets&rft.au=Citrin%2C+D%3BBeecken%2C+W%3BScott%2C+T%3BGoley%2C+E%3BSproull%2C+M%3BTofilon%2C+P%3BCamphausen%2C+K&rft.aulast=Citrin&rft.aufirst=D&rft.date=2004-09-01&rft.volume=60&rft.issue=1&rft.spage=S360&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/10.1016%2Fj.ijrobp.2004.07.201 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-03-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Radiation DO - http://dx.doi.org/10.1016/j.ijrobp.2004.07.201 ER - TY - JOUR T1 - Multiplex bead array assays for detection of soluble cytokines: Comparisons of sensitivity and quantitative values among kits from multiple manufacturers AN - 20378641; 7760273 AB - Background Multiplex bead array assays permit simultaneous cytometric quantitation of multiple cytokines in solution by capturing these to spectrally distinct beads. Because several manufacturers offer reagents to quantitate the same cytokines on a single instrument, a comparison should be made to determine whether these kits yield similar data and whether these data are comparable to enzyme-linked immunosorbent assay (ELISA). Methods This study compared cytokine detection kits by using Luminex 100. Twenty-six serum samples from seven subjects were analyzed for interferon-, interleukins 1, 6, and 8, and tumor necrosis factor- by using multiplex kits from LINCO Research, Bio-Rad Laboratories, R&D Systems, and BioSource International. Each assay was performed according to the manufacturers' specifications. Standard curves were generated by using reference concentrations supplied by each manufacturer. ELISAs for interleukin-8 were performed by using kits from R&D and BioSource. Results Cytokine levels followed similar patterns, although absolute concentrations differed among kits. ELISA and Luminex values for interleukin-8 were similar in kits from the same manufacturer. Conclusions Because relative cytokine measurements are often valuable when performed serially, it may be possible to make interlaboratory comparisons by using different kits. When comparison of absolute values is crucial, kits from the same supplier should be used. Within-vendor, bead array, and ELISA values appear comparable. JF - Cytometry Part B AU - Khan, Sameena S AU - Smith, Meghan S AU - Reda, Debra AU - Suffredini, Anthony F AU - McCoy Jr, J Philip AD - National Heart, Lung, and Blood Institute, Flow Cytometry Core Facility, National Institutes of Health, Bethesda, Maryland, mccoyj@nhlbi.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 35 EP - 39 PB - John Wiley & Sons, Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 61B IS - 1 SN - 1552-4949, 1552-4949 KW - Biotechnology and Bioengineering Abstracts KW - Interferon KW - Enzyme-linked immunosorbent assay KW - Interleukin 1 KW - Cytokines KW - Quantitation KW - Cytometry KW - Interleukin 8 KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20378641?accountid=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=Cytometry+Part+B&rft.atitle=Multiplex+bead+array+assays+for+detection+of+soluble+cytokines%3A+Comparisons+of+sensitivity+and+quantitative+values+among+kits+from+multiple+manufacturers&rft.au=Khan%2C+Sameena+S%3BSmith%2C+Meghan+S%3BReda%2C+Debra%3BSuffredini%2C+Anthony+F%3BMcCoy+Jr%2C+J+Philip&rft.aulast=Khan&rft.aufirst=Sameena&rft.date=2004-09-01&rft.volume=61B&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+B&rft.issn=15524949&rft_id=info:doi/10.1002%2Fcyto.b.20021 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Enzyme-linked immunosorbent assay; Cytokines; Interleukin 8; Cytometry; Interleukin 1; Interferon; Quantitation DO - http://dx.doi.org/10.1002/cyto.b.20021 ER - TY - JOUR T1 - Mass spectrometric measurement of differential reactivity of cysteine to localize protein-ligand binding sites. AN - 20326681; 7536351 AB - A new method for localizing binding sites of noncovalent drugs on proteins is presented. We have developed an accurate and high-throughput method based on the mass spectrometric measurement of differential reaction yield of cysteine alkylation (MS-DRC). This method, essentially a semiquantitative footprinting approach, is applicable to any type of ligand targeting cysteine-rich proteins because the method measures the reactivity change of each cysteine toward an alkylating agent instead of monitoring the drug itself. Thus, no modification of the drug is needed. In this study, the method is evaluated using tubulin as a model system. Tubulin and drug-treated tubulin were alkylated separately with several alkylating reagents, followed by proteolysis and high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) and HPLC-MS. Relative alkylation yields of each cysteine toward the reagents were measured by mass spectrometric quantitation. The reaction yields of each cysteine of two samples were compared to detect a particular cysteine (or cysteines) for which reaction yield was markedly decreased following drug binding. Monobromobimane (mBrB) showed the highest differential.Thus, the MS-DRC method with mBrB was evaluated with various tubulin agents, including the covalent agent T138067 and the noncovalent agents colchicine, podophyllotoxin, and 2-methoxyestradiol. Conformational changes induced by drug binding, as well as sites of direct binding, may be identified. JF - Analytical Biochemistry AU - Kim, Yeoun Jin AU - Pannell, Lewis K AU - Sackett, Dan L AD - National Institute of Diabetes, Digestive, Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA, sackettd@mail.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 376 EP - 383 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 332 IS - 2 SN - 0003-2697, 0003-2697 KW - Biotechnology and Bioengineering Abstracts KW - Cysteine KW - Reactivity KW - Drug binding KW - Tubulin KW - Mass spectrometry KW - HPLC-MS KW - HPLC-MS/MS KW - Monobromobimane KW - Alkylation KW - T138067 KW - Colchicine KW - Podophyllotoxin KW - High-performance liquid chromatography KW - Proteolysis KW - Alkylating agents KW - Footprinting KW - Mass spectroscopy KW - Drugs KW - Quantitation KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20326681?accountid=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=Analytical+Biochemistry&rft.atitle=Mass+spectrometric+measurement+of+differential+reactivity+of+cysteine+to+localize+protein-ligand+binding+sites.&rft.au=Kim%2C+Yeoun+Jin%3BPannell%2C+Lewis+K%3BSackett%2C+Dan+L&rft.aulast=Kim&rft.aufirst=Yeoun&rft.date=2004-09-01&rft.volume=332&rft.issue=2&rft.spage=376&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2Fj.ab.2004.06.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-09-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Alkylating agents; Proteolysis; High-performance liquid chromatography; Footprinting; Cysteine; Podophyllotoxin; Colchicine; Tubulin; Quantitation; Drugs; Mass spectroscopy; Alkylation DO - http://dx.doi.org/10.1016/j.ab.2004.06.033 ER - TY - JOUR T1 - Isolation and characterization of mammalian cells that are undergoing apoptosis by a bovine serum albumin density gradient AN - 20326638; 7536333 AB - When cells are treated with cytotoxic agents, they enter apoptosis asynchronously to yield cells at various stages of cellular deterioration. This mixture makes it difficult to study the biochemical pathways leading to cell death. We have fractionated apoptotic mammalian cells in a simple discontinuous bovine serum albumin (BSA) density gradient centrifugation into five layers, each containing cells at different stages of apoptosis, (1) nonapoptotic, (2) undergoing apoptosis, and (3) mature apoptotic cells, as judged by light and electron microscopy of chromatin condensation and by the extent of DNA fragmentation. Modifications of apoptosis markers including c-Jun N-terminal kinase/stress-activated protein kinase and procaspase 3 cleavage were apparent in those cells that are undergoing apoptosis. Apoptosis-specific histone H2B phosphorylation was highly elevated and DNA fragmentation activity in the cytoplasm was observed in those cells that are undergoing apoptosis, but not much was observed in the cells of other fractions. Results show that apoptotic cells can be fractionated easily by the BSA gradient method, and this method will be invaluable for studying the biochemical processes that drive apoptosis. JF - Analytical Biochemistry AU - Ajiro, Kozo AU - Th'ng, John AU - Yau, Jonathan AU - Nishi, Yoshimi AD - Laboratory of Cell Biology, Research Institute, Aichi Cancer Center, Nagoya, 464-8681, Japan, ajiro@niehs.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 226 EP - 233 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 332 IS - 2 SN - 0003-2697, 0003-2697 KW - Biotechnology and Bioengineering Abstracts KW - MAP kinase KW - c-Jun amino-terminal kinase KW - Apoptosis KW - Chromatin KW - Cytotoxic agents KW - Centrifugation KW - DNA fragmentation KW - Bovine serum albumin KW - Mammalian cells KW - Density gradients KW - Phosphorylation KW - Cytoplasm KW - Histone H2B KW - Condensation KW - Electron microscopy KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20326638?accountid=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=Analytical+Biochemistry&rft.atitle=Isolation+and+characterization+of+mammalian+cells+that+are+undergoing+apoptosis+by+a+bovine+serum+albumin+density+gradient&rft.au=Ajiro%2C+Kozo%3BTh%27ng%2C+John%3BYau%2C+Jonathan%3BNishi%2C+Yoshimi&rft.aulast=Ajiro&rft.aufirst=Kozo&rft.date=2004-09-01&rft.volume=332&rft.issue=2&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2Fj.ab.2004.05.035 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-09-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - MAP kinase; Apoptosis; c-Jun amino-terminal kinase; Chromatin; Cytotoxic agents; DNA fragmentation; Centrifugation; Phosphorylation; Density gradients; Mammalian cells; Bovine serum albumin; Cytoplasm; Condensation; Histone H2B; Electron microscopy DO - http://dx.doi.org/10.1016/j.ab.2004.05.035 ER - TY - JOUR T1 - CYP1A1 and GSTM1 polymorphisms in relation to lung cancer risk in Chinese women AN - 20189407; 6021243 AB - We examined CYP1A1 (I462V) and GSTM1 null polymorphisms in 200 female cases and 144 female controls selected from a population-based case-control study of lung cancer conducted in northeast China, where the rates of lung cancer among Chinese women are especially high. The CYP1A1 codon 462 point mutation in exon 7 (I462V) causes an Ile-Val substitution near the heme binding site. This mutation correlates with inducibility of aryl hydrocarbon hydrolase (AHH) activity, which activates polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke and in indoor air pollution from coal-burning stoves, a risk factor for lung cancer in this study population. We found that the CYP1A1 I462V genotype (combined ile/val and val/val) was significantly associated with lung cancer risk. The odds ratio (OR) was 2.5 (95% confidence interval [CI], 1.55-4.03) after adjustment for significant risk factors such as age, ever smoking status, family history of cancer, and eye irritation when cooking. The association was more pronounced among non-smokers (OR=3.67; 95% CI, 1.85-7.28) than among smokers (OR=1.74, 95% CI, 0.85-3.54). In contrast, we did not find a significant association with the GSTM1 null genotype. In summary, our case-control study of lung cancer among women in northeast China revealed an elevated risk associated with the CYP1A1 I462V genotype, but no interaction with smoking or indoor air pollution was found. JF - Cancer Letters AU - Yang, X R AU - Wacholder, S AU - Xu, Z AU - Dean, M AU - Clark, V AU - Gold, B AU - Brown, L M AU - Stone, B J AU - Fraumeni, JF Jr AU - Caporaso, N E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, Bethesda MD 20892, USA, royang@mail.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 197 EP - 204 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 213 IS - 2 SN - 0304-3835, 0304-3835 KW - Pollution Abstracts KW - CYP1A1 I462V KW - GSTM1 KW - Lung cancer KW - Chinese women KW - Age KW - Eye KW - Indoor air pollution KW - Genotypes KW - Cancer KW - Smoke KW - Genetics KW - Smoking KW - Tobacco KW - polycyclic aromatic hydrocarbons KW - cooking KW - China, People's Rep. KW - Females KW - Mutation KW - aromatic hydrocarbons KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20189407?accountid=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=Cancer+Letters&rft.atitle=CYP1A1+and+GSTM1+polymorphisms+in+relation+to+lung+cancer+risk+in+Chinese+women&rft.au=Yang%2C+X+R%3BWacholder%2C+S%3BXu%2C+Z%3BDean%2C+M%3BClark%2C+V%3BGold%2C+B%3BBrown%2C+L+M%3BStone%2C+B+J%3BFraumeni%2C+JF+Jr%3BCaporaso%2C+N+E&rft.aulast=Yang&rft.aufirst=X&rft.date=2004-09-01&rft.volume=213&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Cancer+Letters&rft.issn=03043835&rft_id=info:doi/10.1016%2Fj.canlet.2004.06.040 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-09-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Age; Eye; Indoor air pollution; Genotypes; Cancer; Smoke; Smoking; Genetics; Tobacco; polycyclic aromatic hydrocarbons; cooking; Females; Mutation; aromatic hydrocarbons; Lung cancer; China, People's Rep. DO - http://dx.doi.org/10.1016/j.canlet.2004.06.040 ER - TY - JOUR T1 - Inhibition of Growth by p205: A Nuclear Protein and Putative Tumor Suppressor Expressed during Myeloid Cell Differentiation AN - 19952703; 6006442 AB - p205 belongs to a family of interferon-inducible proteins called the IFI-200 family, which have been implicated in the regulation of cell growth and differentiation. While p205 is induced in hematopoietic stem cells during myeloid cell differentiation, its function is not known. Therefore, the aim of this study was to determine the role of p205 in regulating proliferation in hematopoietic progenitor cells and in nonhematopoietic cell lines. We found that p205 localizes to the nucleus in hematopoietic and nonhematopoietic cell lines. Transient expression of p205 in murine IL-3-dependent BaF3 and 32D-C123 progenitor cell lines inhibited IL-3-induced growth and proliferation. The closely related IFI-200 family members, p204 and p202, similarly inhibited IL-3- dependent progenitor cell proliferation. p205 also inhibited the proliferation and growth of normal hematopoietic progenitor cells. In nonhematopoietic cell lines, p205 and p204 expression inhibited NIH3T3 cell colony formation in vitro, and microinjection of p205 expression vectors into NIH3T3 fibroblasts inhibited serum-induced proliferation. We have determined the functional domains of p205 necessary for activity, which were identified as the N-terminal domain in apoptosis and interferon response (DAPIN)/PYRIN domain, and the C-terminal retinoblastoma protein (Rb)-binding motif. In addition, we have demonstrated that a putative ataxia telangiectasia, mutated (ATM) kinase phosphorylation site specifically regulates the activity of p205. Taken together, these data suggest that p205 is a potent cell growth regulator whose activity is mediated by its protein-binding domains. We propose that during myelomonocytic cell differentiation, induction of p205 expression contributes to cell growth arrest, thus allowing progenitor cells to differentiate. JF - Stem Cells AU - Dermott, Jonathan M AU - Gooya, John M AU - Asefa, Benyam AU - Weiler, Sarah R AU - Smith, Mark AU - Keller, Jonathan R AD - Laboratory of Molecular Immunoregulation and Basic Research Program, Science Applications International Corporation (SAIC)-Frederick, Inc., Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 832 EP - 848 VL - 22 IS - 5 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts; Oncogenes & Growth Factors Abstracts; Immunology Abstracts KW - Tumor suppressor genes KW - Apoptosis KW - Data processing KW - Lymphocytes B KW - Retinoblastoma protein KW - Myeloid cells KW - Microinjection KW - Fibroblasts KW - Pyrin protein KW - Expression vectors KW - Interferon KW - Ataxia telangiectasia mutated protein KW - Differentiation KW - Stem cells KW - Colonies KW - Phosphorylation KW - Growth regulators KW - interferon-inducible protein KW - Hemopoiesis KW - Nuclei KW - Cell proliferation KW - W 30905:Medical Applications KW - B 26670:Tumor Suppressors KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19952703?accountid=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+Cell+Biology&rft.atitle=Membrane+insertion+of+anthrax+protective+antigen+and+cytoplasmic+delivery+of+lethal+factor+occur+at+different+stages+of+the+endocytic+pathway&rft.au=Abrami%2C+Laurence%3BLindsay%2C+Margaret%3BParton%2C+Robert+G%3BLeppla%2C+Stephen+H%3BVan+Der+Goot%2C+FGisou&rft.aulast=Abrami&rft.aufirst=Laurence&rft.date=2004-08-30&rft.volume=166&rft.issue=5&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cell+Biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-08-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Tumor suppressor genes; Data processing; Apoptosis; Lymphocytes B; Retinoblastoma protein; Microinjection; Myeloid cells; Fibroblasts; Expression vectors; Pyrin protein; Differentiation; Ataxia telangiectasia mutated protein; Interferon; Colonies; Stem cells; Growth regulators; Phosphorylation; interferon-inducible protein; Hemopoiesis; Cell proliferation; Nuclei ER - TY - JOUR T1 - PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis AN - 19807585; 5985929 AB - Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenzaanthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA- mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis. JF - Carcinogenesis AU - Nicol, Christopher J AU - Yoon, Michung AU - Ward, Jerrold M AU - Yamashita, Masamichi AU - Fukamachi, Katsumi AU - Peters, Jeffrey M AU - Gonzalez, Frank J AD - Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1747 EP - 1755 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 25 IS - 9 SN - 0143-3334, 0143-3334 KW - Toxicology Abstracts KW - Macrophages KW - Granulosa cells KW - Skin KW - Data processing KW - Peroxisome proliferator-activated receptors KW - Mammary gland KW - Nuclear receptors KW - Tumors KW - Colon cancer KW - Inflammation KW - Diabetes mellitus KW - Metastases KW - Differentiation KW - 9,10-Dimethyl-1,2-benzanthracene KW - Adipocytes KW - Carcinogenesis KW - haploinsufficiency KW - Breast cancer KW - Ovarian carcinoma KW - Adenocarcinoma KW - Papilloma KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19807585?accountid=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=PPARgamma+influences+susceptibility+to+DMBA-induced+mammary%2C+ovarian+and+skin+carcinogenesis&rft.au=Nicol%2C+Christopher+J%3BYoon%2C+Michung%3BWard%2C+Jerrold+M%3BYamashita%2C+Masamichi%3BFukamachi%2C+Katsumi%3BPeters%2C+Jeffrey+M%3BGonzalez%2C+Frank+J&rft.aulast=Nicol&rft.aufirst=Christopher&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1747&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Macrophages; Granulosa cells; Data processing; Skin; Peroxisome proliferator-activated receptors; Mammary gland; Nuclear receptors; Colon cancer; Tumors; Inflammation; Metastases; Diabetes mellitus; Differentiation; Adipocytes; 9,10-Dimethyl-1,2-benzanthracene; haploinsufficiency; Carcinogenesis; Breast cancer; Ovarian carcinoma; Papilloma; Adenocarcinoma ER - TY - JOUR T1 - Biological pre-treatment of wastewater containing sulfate using anaerobic immobilized cells AN - 19673492; 6021286 AB - Biological reduction of sulfate to sulfide using sulfate reducing bacteria (SRB) was investigated. A respirometer was used to study the sulfide toxicity in the systems fed glucose, the results showed that sulfide would start to inhibit methanogens when the dissolved sulfide and total sulfide concentrations were 276.4 and 304.6 mg/L, respectively. When chemostats were used to study the Monod kinetic coefficients, Y, k sub(d), K sub(s), and k were 0.36 mg VSS (volatile suspended solids) using SRB/mg SO sub(4)-S, 0.05/day, 147.30 mg SO sub(4)- S/L, and 6.50 mg SO sub(4)-S/mg VSS using SRB-d, respectively. Using pure cultural techniques, SRB were found to be 29.45% of the VSS in the chemostats. Sulfate removal using an upflow anaerobic filter packed with immobilized cells was also investigated. Under sulfate loading rates of 0.2 and 0.4 g SO sub(4)-S/L day, and a hydraulic retention time (HRT) of 2 days, a sulfate removal efficiency greater than 93% could be achieved. When the filter was operated under COD (chemical oxygen demand)/S from 10/1 to 5/1 and HRTs of 2, 1 and 0.5 days, sulfate removal efficiency was between 98.1 and 70.9%. It is believed that protection by the immobilized cell structure caused the microbial cells in the filter to tolerate higher dissolved sulfide (447.8 mg/L) and total sulfide (940.3 mg/L) levels, allowing a much higher biomass concentration (13.2-13.5 g VSS/L) to be reached. JF - Journal of Hazardous Materials AU - Kuo, W-C AU - Shu, T-Y AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Nei Pu, Pingtung 91207, Taiwan, ROC, xwck@mail.npust.edu.tw Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 147 EP - 155 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 113 IS - 1-3 SN - 0304-3894, 0304-3894 KW - Toxicology Abstracts; Water Resources Abstracts KW - Sulfide toxicity KW - Sulfate reduction KW - Bubble respirometer KW - Immobilized cells KW - Methane production KW - Sulfates KW - Hydraulics KW - Glucose KW - Chemical Oxygen Demand KW - Hazardous Materials KW - Chemostats KW - Suspended Solids KW - Retention Time KW - Sulfides KW - Sulfur Bacteria KW - Protection KW - Chemical oxygen demand KW - Toxicity KW - Methanogenic bacteria KW - Biomass KW - Sulfate KW - Filters KW - Hydraulic Loading KW - Sulfide KW - Volatiles KW - Structure KW - Kinetics KW - Load Distribution KW - Waste water KW - Wastewater Treatment KW - SW 3040:Wastewater treatment processes KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19673492?accountid=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+Hazardous+Materials&rft.atitle=Biological+pre-treatment+of+wastewater+containing+sulfate+using+anaerobic+immobilized+cells&rft.au=Kuo%2C+W-C%3BShu%2C+T-Y&rft.aulast=Kuo&rft.aufirst=W-C&rft.date=2004-09-01&rft.volume=113&rft.issue=1-3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Hazardous+Materials&rft.issn=03043894&rft_id=info:doi/10.1016%2Fj.jhazmat.2004.05.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Hydraulics; Glucose; Immobilized cells; Chemical oxygen demand; Toxicity; Biomass; Methanogenic bacteria; Sulfate; Filters; Sulfide; Chemostats; Volatiles; Kinetics; Waste water; Sulfates; Retention Time; Sulfur Bacteria; Sulfides; Protection; Chemical Oxygen Demand; Hydraulic Loading; Hazardous Materials; Suspended Solids; Structure; Load Distribution; Wastewater Treatment DO - http://dx.doi.org/10.1016/j.jhazmat.2004.05.033 ER - TY - JOUR T1 - Eating Disorder or Disordered Eating? Non-normative Eating Patterns in Obese Individuals AN - 19413015; 6042996 AB - Binge eating disorder (BED) and night eating syndrome (NES) are putative eating disorders frequently seen in obese individuals. Data suggest that BED fulfills criteria for a mental disorder. Criteria for NES are evolving but at present do not require distress or functional impairment. It remains unclear whether BED and NES, as they are currently defined, are optimally useful for characterizing distinct patient subgroups. We propose that a distinction be made between "eating disorders" and "non-normative" eating patterns without associated distress or impairment. Although non-normative eating patterns may not be considered mental disorders, they may be very important in terms of their impact on body weight and health. More precise behavioral and metabolic characterization of subgroups with eating disorders and non-normative eating behaviors has important implications for understanding the etiology, pathophysiology, and treatment of obesity. Ultimately, better understanding of the many pathways to increased energy intake may lead to targeted strategies for prevention of overweight and obesity in at-risk individuals and populations. JF - Obesity Research AU - Tanofsky-Kraff, Marian AU - Yanovski, Susan Z AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development and. Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Department of Health and Human Services, Bethesda, Maryland. Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1361 EP - 1366 PB - North American Association for the Study of Obesity, 1090 Amsterdam Ave., Ste. 14K New York NY 10025 USA, [mailto:helener@mindspring.com], [URL:http://www.naaso.org] VL - 12 IS - 9 SN - 1071-7323, 1071-7323 KW - Physical Education Index KW - Obesity KW - Eating disorders KW - Preventive health KW - Strategy KW - Diet (weight control) KW - Patients KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19413015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Obesity+Research&rft.atitle=Eating+Disorder+or+Disordered+Eating%3F+Non-normative+Eating+Patterns+in+Obese+Individuals&rft.au=Tanofsky-Kraff%2C+Marian%3BYanovski%2C+Susan+Z&rft.aulast=Tanofsky-Kraff&rft.aufirst=Marian&rft.date=2004-09-01&rft.volume=12&rft.issue=9&rft.spage=1361&rft.isbn=&rft.btitle=&rft.title=Obesity+Research&rft.issn=10717323&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Obesity; Preventive health; Eating disorders; Strategy; Diet (weight control); Patients ER - TY - JOUR T1 - Differential Monocyte Activation Underlies Strain-Specific Mycobacterium tuberculosis Pathogenesis AN - 18063724; 5992276 AB - In vitro infection of monocytes with Mycobacterium tuberculosis HN878 and related W/Beijing isolates preferentially induced interleukin-4 (IL-4) and IL- 13, which characterize Th2 polarized immunity. In contrast, CDC1551 induced more IL-12 and other molecules associated with phagocyte activation and Th1 protective immunity. The differential cytokine-chemokine response was mediated by extracted lipids, suggesting that these molecules regulate host responses to infection. JF - Infection and Immunity AU - Manca, Claudia AU - Reed, Michael B AU - Freeman, Sherry AU - Mathema, Barun AU - Kreiswirth, Barry AU - Barry, Clifton E AU - Kaplan, Gilla AD - Laboratory of Mycobacterial Immunity and Pathogenesis. Tuberculosis Center, Public Health Research Institute, International Center for Public Health, Newark, New Jersey. Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 5511 EP - 5514 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 9 SN - 0019-9567, 0019-9567 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Interleukin 4 KW - Lipids KW - Helper cells KW - Infection KW - Cell activation KW - Interleukin 12 KW - Phagocytes KW - Lymphocytes T KW - Monocytes KW - Mycobacterium tuberculosis KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18063724?accountid=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=Differential+Monocyte+Activation+Underlies+Strain-Specific+Mycobacterium+tuberculosis+Pathogenesis&rft.au=Manca%2C+Claudia%3BReed%2C+Michael+B%3BFreeman%2C+Sherry%3BMathema%2C+Barun%3BKreiswirth%2C+Barry%3BBarry%2C+Clifton+E%3BKaplan%2C+Gilla&rft.aulast=Manca&rft.aufirst=Claudia&rft.date=2004-09-01&rft.volume=72&rft.issue=9&rft.spage=5511&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 - Mycobacterium tuberculosis; Interleukin 4; Lymphocytes T; Monocytes; Helper cells; Interleukin 12; Lipids; Cell activation; Phagocytes; Infection ER - TY - JOUR T1 - Level of Maternal IgG Anti-Group B Streptococcus Type III Antibody Correlated with Protection of Neonates against Early-Onset Disease Caused by This Pathogen AN - 18053620; 6008414 AB - The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of greater than or equal to 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had greater than or equal to 10 mu g/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of <2 mu g/mL. A vaccine that induces IgG anti-GBS type III levels of greater than or equal to 10 mu g/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen. JF - Journal of Infectious Diseases AU - Lin, Feng-Ying C AU - Weisman, LE AU - Azimi, PH AU - Philips, JB III AU - Clark, P AU - Regan, J AU - Rhoads, G G AU - Frasch, CE AU - Gray, B M AU - Troendle, J AU - Brenner, R A AU - Moyer, P AU - Clemens, J D AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 928 EP - 934 VL - 190 IS - 5 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Enzyme-linked immunosorbent assay KW - Infectious diseases KW - Guillain-Barre syndrome KW - Gestation KW - Immunoglobulin G KW - Vaccines KW - Neonates KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18053620?accountid=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+Infectious+Diseases&rft.atitle=Level+of+Maternal+IgG+Anti-Group+B+Streptococcus+Type+III+Antibody+Correlated+with+Protection+of+Neonates+against+Early-Onset+Disease+Caused+by+This+Pathogen&rft.au=Lin%2C+Feng-Ying+C%3BWeisman%2C+LE%3BAzimi%2C+PH%3BPhilips%2C+JB+III%3BClark%2C+P%3BRegan%2C+J%3BRhoads%2C+G+G%3BFrasch%2C+CE%3BGray%2C+B+M%3BTroendle%2C+J%3BBrenner%2C+R+A%3BMoyer%2C+P%3BClemens%2C+J+D&rft.aulast=Lin&rft.aufirst=Feng-Ying&rft.date=2004-09-01&rft.volume=190&rft.issue=5&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&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; Neonates; Immunoglobulin G; Guillain-Barre syndrome; Infectious diseases; Gestation; Enzyme-linked immunosorbent assay; Vaccines ER - TY - JOUR T1 - Agricultural pesticide use and adenocarcinomas of the stomach and oesophagus AN - 18034737; 5992648 AB - AIMS: To evaluate the risk of the stomach and oesophageal adenocarcinomas associated with farming and agricultural pesticide use. METHODS: Population based case-control study in eastern Nebraska. Telephone interviews were conducted with men and women diagnosed with adenocarcinoma of the stomach (n = 170) or oesophagus (n = 137) between 1988 and 1993, and controls (n = 502) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds on reaction with nitrite). Non-farmers were used as the reference category for all analyses. RESULTS: Ever living or working on a farm, duration of farming, and size of the farm were not associated with stomach or oesophageal adenocarcinomas. There was no association for either cancer with ever-use of insecticides (stomach OR 0.9, 95% CI 0.6 to 1.4; oesophagus OR 0.7, 95% CI 0.4 to 1.1) or herbicides (stomach OR 0.9, 95% CI 0.5 to 1.4; oesophagus OR 0.7, 95% CI 0.4 to 1.2). Likewise, individual pesticides, including individual nitrosatable pesticides, were not significantly associated with risk. CONCLUSIONS: No significant associations were found between specific agricultural pesticide exposures and the risk of stomach or oesophageal adenocarcinomas among Nebraska farmers. JF - Occupational and Environmental Medicine AU - Lee, W J AU - Lijinsky, W AU - Heineman, E F AU - Markin, R S AU - Weisenburger, D D AU - Ward, M H AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 743 EP - 749 PB - B M J Publishing Group, B.M.A. House Tavistock Sq. London WC1H 9JR UK VL - 61 IS - 9 SN - 1351-0711, 1351-0711 KW - man KW - Health & Safety Science Abstracts; Toxicology Abstracts; Risk Abstracts KW - Risk assessment KW - Esophagus KW - Farms KW - Agrochemicals KW - Cancer KW - Pesticides KW - USA, Nebraska KW - Adenocarcinoma KW - Occupational exposure KW - Stomach KW - R2 23080:Industrial and labor KW - X 24134:Pathology KW - H 5000:Pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18034737?accountid=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+and+Environmental+Medicine&rft.atitle=Agricultural+pesticide+use+and+adenocarcinomas+of+the+stomach+and+oesophagus&rft.au=Lee%2C+W+J%3BLijinsky%2C+W%3BHeineman%2C+E+F%3BMarkin%2C+R+S%3BWeisenburger%2C+D+D%3BWard%2C+M+H&rft.aulast=Lee&rft.aufirst=W&rft.date=2004-09-01&rft.volume=61&rft.issue=9&rft.spage=743&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Esophagus; Farms; Pesticides; Adenocarcinoma; Cancer; Stomach; Occupational exposure; Risk assessment; Agrochemicals; USA, Nebraska ER - TY - JOUR T1 - Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: implications for arsenic hepatocarcinogenesis AN - 18028003; 5985932 AB - Inorganic arsenic is a human carcinogen that can target the liver, but its carcinogenic mechanisms are still unknown. Global DNA hypomethylation occurs during arsenic-induced malignant transformation in rodent liver cells. DNA hypomethylation can increase gene expression, particularly when occurring in the promoter region CpG sites, and may be a non-genotoxic mechanism of carcinogenesis. Thus, in the present study liver samples of male mice exposed to 0 (control) or 45 p.p.m. arsenic (as NaAsO sub(2)) in the drinking water for 48 weeks were analyzed for gene expression and DNA methylation. Chronic arsenic exposure caused hepatic steatosis, a lesion also linked to consumption of methyl-deficient diets. Microarray analysis of liver samples showed arsenic induced aberrant gene expression including steroid-related genes, cytokines, apoptosis-related genes and cell cycle-related genes. In particular, the expression of the estrogen receptor-alpha (ER-alpha), and cyclin D1 genes were markedly increased. RT-PCR and immunohistochemistry confirmed arsenic-induced increases in hepatic ER-alpha and cyclin D1 transcription and translation products, respectively. Arsenic induced hepatic global DNA hypomethylation, as evidenced by 5-methylcytosine content of DNA and by the methyl acceptance assay. Arsenic also markedly reduced the methylation within the ER-alpha gene promoter region, as assessed by methylation-specific PCR, and this reduction was statistically significant in 8 of 13 CpG sites within the promoter region. Overall, in controls 28.3% of the ER-alpha promoter region CpG sites were methylated, but only 2.9% were methylated after chronic arsenic exposure. Thus, long-term exposure of mice to arsenic in the drinking water can induce aberrant gene expression, global DNA hypomethylation, and the hypomethylation of the ER- alpha gene promoter, all of which could potentially contribute to arsenic hepatocarcinogenesis. JF - Carcinogenesis AU - Chen, Hua AU - Li, Shuanfang AU - Liu, Jie AU - Diwan, Bhalchandra A AU - Barrett, JCarl AU - Waalkes, Michael P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institutes of Environmental Health Sciences, Research Triangle Park, North Carolina, Laboratory of Biosystems and Cancer, National Cancer Institute, Bethesda, Maryland and Basic Research Program, SAIC-Frederick, Frederick, Maryland, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1779 EP - 1786 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 25 IS - 9 SN - 0143-3334, 0143-3334 KW - mice KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Gene expression KW - Arsenic KW - Carcinogenesis KW - Liver KW - DNA KW - DNA methylation KW - Drinking water KW - Methylation KW - Estrogen receptors KW - cyclin D1 KW - X 24165:Biochemistry KW - X 24162:Chronic exposure KW - N 14550:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18028003?accountid=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=Chronic+inorganic+arsenic+exposure+induces+hepatic+global+and+individual+gene+hypomethylation%3A+implications+for+arsenic+hepatocarcinogenesis&rft.au=Chen%2C+Hua%3BLi%2C+Shuanfang%3BLiu%2C+Jie%3BDiwan%2C+Bhalchandra+A%3BBarrett%2C+JCarl%3BWaalkes%2C+Michael+P&rft.aulast=Chen&rft.aufirst=Hua&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1779&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Gene expression; Arsenic; Carcinogenesis; DNA methylation; DNA; Liver; Drinking water; Estrogen receptors; Methylation; cyclin D1 ER - TY - JOUR T1 - Development of a Noninvasive Method for Detecting and Monitoring the Time Course of Helicobacter pylori Infection AN - 18025181; 5992131 AB - Helicobacter pylori infection status following experimental inoculation of mice presently requires euthanasia. The purpose of this study was to develop a method for following the time course of H. pylori infection in live experimental animals. Twenty-six C57BL/6, Helicobacter-free female mice were inoculated with H. pylori Sydney strain 1, and 16 mice were sham inoculated. The mice were repeatedly tested during a period of about 1 year with an H. pylori species- specific primer-based PCR analysis of DNA extracted from fecal pellets of mice. The mice were euthanized at 6 months (n = 15) and 10 months (n = 15) to determine their infection status by histology, culture, and PCR of gastric specimens. H. pylori-inoculated mice were tested via the PCR method at 6 and 10 months prior to necropsy. Nine of 13 (69%) and 10 of 13 (77%) mice tested at 6 and 10 months, respectively, were positive. All sham-inoculated mice were negative. These two PCR results suggested a specificity of 100% with a sensitivity range between 69 and 77%. In contrast, sensitivity and specificity rose to 90 and 100% if groups of mice were tested once daily for 4 days. Seventy-seven to 85% of the experimental mice were also positive for H. pylori by culture. The histopathology demonstrated mild to severe gastritis. These findings demonstrate that the persistence or transience of H. pylori infection in live mice can be repeatedly evaluated over time. This method could allow the determination of the time course of infection and the efficacy of medications and/or vaccine without necropsy. JF - Infection and Immunity AU - Nyan, Dougbeh C AU - Welch, Anthony R AU - Dubois, Andre AU - Coleman, William G AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda. Diagnon Corporation, Gaithersburg, Maryland Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 5358 EP - 5364 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 9 SN - 0019-9567, 0019-9567 KW - mice KW - Microbiology Abstracts B: Bacteriology KW - Helicobacter pylori KW - Gastrointestinal tract diseases KW - Animal models KW - Histopathology KW - Polymerase chain reaction KW - Primers KW - Feces KW - Persistent infection KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18025181?accountid=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=Development+of+a+Noninvasive+Method+for+Detecting+and+Monitoring+the+Time+Course+of+Helicobacter+pylori+Infection&rft.au=Nyan%2C+Dougbeh+C%3BWelch%2C+Anthony+R%3BDubois%2C+Andre%3BColeman%2C+William+G&rft.aulast=Nyan&rft.aufirst=Dougbeh&rft.date=2004-09-01&rft.volume=72&rft.issue=9&rft.spage=5358&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 - Helicobacter pylori; Gastrointestinal tract diseases; Animal models; Feces; Polymerase chain reaction; Primers; Histopathology; Persistent infection ER - TY - JOUR T1 - Risk factors for completed suicides: a case-control study from Bangalore, India AN - 17810733; 6220644 AB - Suicides are a hidden and unrecognized epidemic in the Indian region, affecting predominantly younger age groups. Information on causative risk factors and mechanisms is not available in the country, which is crucial for designing intervention programmes. To identify and quantify risk factors for completed suicides in the city of Bangalore. A case-control study was conducted with the families of 269 completed suicides and 269 living controls within the broader population of the city using psychological autopsy methods. The study has shown that several factors in the areas of family, marriage, education, occupation, general health, mental health and absence of protective factors contribute significantly for suicides. The cumulative and repetitive interaction of several factors in a complex manner results in suicides. The significant factors were presence of previous suicidal attempt in self (odds ratio (OR) = 42.62), interpersonal conflicts and marital disharmony with spouse (OR = 27.98), alcoholism in self (OR = 23.38), presence of a mental illness (OR = 11.07), sudden economic bankruptcy (OR = 7.1), domestic violence (OR = 6.82) and unemployment (OR = 6.15). Individuals completing suicides did not have a positive outlook towards life, problem-solving approaches and coping skills. The observed findings are at variance with suicidal causation in the West in some areas operating in a different sociocultural and economic environment. The intervention strategies should include prioritized macro and micro level efforts aimed at individual, family and society. JF - Injury Control and Safety Promotion AU - Gururaj, G AU - Isaac, M K AU - Subbakrishna, D K AU - Ranjani, R AD - Department of Epidemiology, WHO Collaborating Centre for Injury Prevention and Safety Promotion, National Institute of Mental Health and Neuro Sciences, PO Box No. 2900, Bangalore-560 029, India, guru@nimhans.kar.nic.in Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 183 EP - 191 VL - 11 IS - 3 SN - 1566-0974, 1566-0974 KW - Risk Abstracts KW - Age KW - Psychology KW - domestic violence KW - Family studies KW - India KW - Education KW - Economics KW - suicide KW - Urban areas KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17810733?accountid=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=Injury+Control+and+Safety+Promotion&rft.atitle=Risk+factors+for+completed+suicides%3A+a+case-control+study+from+Bangalore%2C+India&rft.au=Gururaj%2C+G%3BIsaac%2C+M+K%3BSubbakrishna%2C+D+K%3BRanjani%2C+R&rft.aulast=Gururaj&rft.aufirst=G&rft.date=2004-09-01&rft.volume=11&rft.issue=3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Injury+Control+and+Safety+Promotion&rft.issn=15660974&rft_id=info:doi/10.1080%2F156609704%2F233%2F289706 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - India; suicide; Economics; Urban areas; Psychology; domestic violence; Education; Family studies; Age DO - http://dx.doi.org/10.1080/156609704/233/289706 ER - TY - JOUR T1 - Antimicrobial susceptibility trends among Escherichia coli and Shigella spp. isolated from rural Egyptian paediatric populations with diarrhoea between 1995 and 2000 AN - 17794950; 6012230 AB - Antimicrobial susceptibility testing was performed on 3627 isolates of Escherichia coli and 180 isolates of Shigella spp. collected in rural locations from 875 Egyptian children with diarrhoea between 1995 and 2000. The cumulative rates of resistance for E. coli and Shigella spp. were high (respectively, 68.2% and 54.8% for ampicillin, 24.2% and 23.5% for ampicillin-sulbactam, 57.2% and 42.5% for trimethoprim-sulphamethoxazole, and 50.9% and 75.4% for tetracycline). Non-enterotoxigenic E. coli (NETEC) isolates had a consistently higher level of antimicrobial resistance than did enterotoxigenic E. coli (ETEC) isolates. Trend testing showed significant decreases in resistance to ampicillin, ampicillin-sulbactam and tetracycline among all E. coli isolates. Increasing rates of resistance were observed for trimethoprim-sulphamethoxazole in ETEC isolates and Shigella spp., but not in NETEC isolates. Low levels of resistance were observed for all other antimicrobial agents tested. Overall, high levels, but decreasing trends, of resistance to commonly used antimicrobial agents were detected among isolates of E. coli and Shigella spp. from children in rural Egypt. JF - Clinical Microbiology and Infection AU - Putnam, S D AU - Riddle AU - Wierzba, T F AU - Pittner, B T AU - Elyazeed, R A AU - El-Gendy, A AU - Rao, M R AU - Clemens, J D AU - Frenck, R W AD - Enteric Disease Department, Naval Medical Research Center, Silver Spring, MD, USA, Enteric Disease Research Program, Naval Medical Research Unit No. 3, Cairo, Egypt, EPI and Polio Eradication, World Health Organization, Katmandu, Nepal, Department of Immunology, Mayo Clinic, Rochester, MN, Epidemiology Branch, National Institute of Child Health and Human Development, Bethesda, MD, USA and International Vaccine Institute, Seoul, South Korea, putnam@namruz.019 Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 804 EP - 810 PB - Blackwell Science Ltd VL - 10 IS - 9 SN - 1198-743X, 1198-743X KW - Microbiology Abstracts B: Bacteriology KW - Egypt, Arab Rep. KW - Diarrhea KW - Pediatrics KW - Drug resistance KW - Escherichia coli KW - Ampicillin KW - Shigella KW - Children KW - Tetracyclines KW - Antibiotic resistance KW - Antimicrobial agents KW - J 02795:Antibiotic resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17794950?accountid=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=American+journal+of+physiology.+Renal+physiology&rft.atitle=Fluorescein-methotrexate+transport+in+rat+choroid+plexus+analyzed+using+confocal+microscopy.&rft.au=Breen%2C+Christopher+M%3BSykes%2C+Destiny+B%3BBaehr%2C+Carsten%3BFricker%2C+Gert%3BMiller%2C+David+S&rft.aulast=Breen&rft.aufirst=Christopher&rft.date=2004-09-01&rft.volume=287&rft.issue=3&rft.spage=F562&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Renal+physiology&rft.issn=1931857X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Diarrhea; Pediatrics; Drug resistance; Ampicillin; Tetracyclines; Children; Antibiotic resistance; Antimicrobial agents; Escherichia coli; Shigella; Egypt, Arab Rep. DO - http://dx.doi.org/10.1111/j.1469-0691.2004.00927.x ER - TY - JOUR T1 - Probabilities of Death From Breast Cancer and Other Causes Among Female Breast Cancer Patients AN - 17794625; 6006835 AB - BACKGROUND: Among cancer patients, probabilities of death from that cancer and other causes in the presence of competing risks are optimal measures of prognosis and of mortality across demographic groups. We used data on breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) Program in a competing-risk analysis. METHODS: We determined vital status and cause of death for 395 251 white and 35 259 black female patients with breast cancer diagnosed from January 1, 1973, through December 31, 2000, by use of SEER data. We calculated probabilities of death from breast cancer and other causes according to stage, race, and age at diagnosis; for cases diagnosed from January 1, 1990, to December 31, 2000, we also calculated some such probabilities according to tumor size and estrogen receptor (ER) status. All statistical tests were two-sided. RESULTS: The probability of death from breast cancer after nearly 28 years of follow-up ranged from 0.03 to 0.10 for patients with in situ disease to 0.70 to 0.85 for patients with distant disease, depending on race and age. The probability of death from breast cancer at the end of the follow-up period generally declined with age at diagnosis; the probability among the oldest (=>70 years) compared with the youngest (70 years). Among patients with localized or regional disease and known ER status, the probability of death from breast cancer after nearly 11 years of follow-up ranged from 0.04 to 0.11 for patients with localized ER-positive tumors of 2 cm or less to 0.37 to 0.53 for patients with regional ER-negative tumors. CONCLUSIONS: The probability of death from breast cancer versus other causes varied substantially according to stage, tumor size, ER status, and age at diagnosis in both white and black patients. JF - Journal of the National Cancer Institute AU - Schairer, Catherine AU - Mink, Pamela J AU - Carroll, Leslie AU - Devesa, Susan S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (CS, SSD) Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 1311 EP - 1321 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 96 IS - 17 SN - 0027-8874, 0027-8874 KW - Risk Abstracts KW - Mortality KW - Age KW - Demographics KW - Breast cancer KW - Females KW - Ethnic groups KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17794625?accountid=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=Journal+of+the+National+Cancer+Institute&rft.atitle=Probabilities+of+Death+From+Breast+Cancer+and+Other+Causes+Among+Female+Breast+Cancer+Patients&rft.au=Schairer%2C+Catherine%3BMink%2C+Pamela+J%3BCarroll%2C+Leslie%3BDevesa%2C+Susan+S&rft.aulast=Schairer&rft.aufirst=Catherine&rft.date=2004-09-01&rft.volume=96&rft.issue=17&rft.spage=1311&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Females; Mortality; Age; Ethnic groups; Breast cancer; Demographics ER - TY - JOUR T1 - Long-Term Interferon- gamma Therapy for Patients with Chronic Granulomatous Disease AN - 17791419; 6056715 AB - Background. Chronic granulomatous disease (CGD) is a rare disorder of phagocytes in which absent production of superoxide and hydrogen peroxide in phagocytes predisposes patients to bacterial and fungal infections. Infections are dramatically reduced by prophylaxis with antibiotics, antifungals, and interferon- gamma (IFN- gamma ). Methods. Seventy-six patients with CGD were enrolled in an uncontrolled, open-label follow-up study to assess the long-term clinical safety and efficacy of IFN- gamma therapy. Patients received IFN- gamma subcutaneously 3 times per week. Results. We observed patients for up to 9 years, for a total observation period of 328.4 patient-years. The incidence of serious infections was 0.30 infections per patient-year; for serious bacterial infections, the incidence was 0.18 cases per patient-year, and for serious fungal infections, it was 0.12 cases per patient-year. Thirty-seven percent of patients reported an adverse event, the most common of which was fever. Twenty-six patients withdrew from the study (3 because of adverse events, 15 because of patient preference, and 8 because of transfer to another trial). There were no life-threatening IFN- gamma -related adverse events and no discernible effects on growth. The overall mortality rate was 1.5% per patient-year. Conclusion. IFN- gamma prophylaxis for CGD appears to be effective and well tolerated over a prolonged period of time. JF - Clinical Infectious Diseases AU - Marciano, B E AU - Wesley, R AU - De Carlo, ES AU - Anderson, V L AU - Barnhart, LA AU - Darnell, D AU - Malech, H L AU - Gallin, JI AU - Holland, S M AD - Laboratories of Host Defenses and Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, and Warren G. Magnuson Clinical Center, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 692 EP - 699 VL - 39 IS - 5 SN - 1058-4838, 1058-4838 KW - Microbiology Abstracts B: Bacteriology KW - Fever KW - Mortality KW - Hydrogen peroxide KW - Phagocytes KW - ^g-Interferon KW - Superoxide KW - Chronic infection KW - Prophylaxis KW - Antibiotics KW - Chronic granulomatous disease KW - Clinical trials KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17791419?accountid=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=Clinical+Infectious+Diseases&rft.atitle=Long-Term+Interferon-+gamma+Therapy+for+Patients+with+Chronic+Granulomatous+Disease&rft.au=Marciano%2C+B+E%3BWesley%2C+R%3BDe+Carlo%2C+ES%3BAnderson%2C+V+L%3BBarnhart%2C+LA%3BDarnell%2C+D%3BMalech%2C+H+L%3BGallin%2C+JI%3BHolland%2C+S+M&rft.aulast=Marciano&rft.aufirst=B&rft.date=2004-09-01&rft.volume=39&rft.issue=5&rft.spage=692&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 - ^g-Interferon; Chronic granulomatous disease; Phagocytes; Prophylaxis; Fever; Hydrogen peroxide; Superoxide; Mortality; Chronic infection; Antibiotics; Clinical trials ER - TY - JOUR T1 - Rapid grouping of monoclonal antibodies based on their topographical epitopes by a label-free competitive immunoassay AN - 17755338; 6144551 AB - Topography of epitopes of monoclonal antibodies (MAbs), identified as the mutual competition of the MAbs, can be valuable indicators for the biological functions of MAbs. However, the determination of topographical epitopes is not performed before the functional screening of MAbs, because the requirement for purifying and labeling of MAbs makes the mapping experiment difficult, particularly in the early stage of MAb production. Here we describe a new label-free competitive enzyme-linked immunosorbent assay (LFC-ELISA) for the rapid grouping of MAbs based on the topography of their epitopes. In the LFC-ELISA, the immune complex formed by a competitor, MAb#2, and an antigen is challenged by an indicator, MAb#1 that had been captured on the ELISA plate through a secondary antibody. The MAb#2-antigen immune complex is trapped by MAb#1 only if MAb#1 reacts with an epitope different from that of MAb#2. The immune complex (MAb#2-antigen-MAb#1) is detected with an enzyme-labeled reagent specific to a tag on the antigen. Our experiments using different anti-CD30 MAbs and a CD30-Fc fusion protein as the antigen revealed that the LFC-ELISA performed well with MAbs of different isotypes (IgG1, IgG2a, and IgG2b), and in a practical range of MAb concentrations (0.3-10 mu g/ml) and affinities (0.9-13 nM of Kd). We obtained pairwise competition data from all 26 anti-CD30 MAbs. We then utilized a cluster analysis and a bootstrap method to analyze the competition data for grouping of the MAbs. This objective and automated analysis identified eight distinct topographical epitopes on CD30. The reactivity of the anti-CD30 MAbs in immunoblot, and their inhibiting activity on CD30-CD30-ligand binding correlated with the topographical epitopes. The results show that the LFC-ELISA combined with cluster analysis is a useful new method for grouping MAbs based on their topographical epitopes and can be used in the early stage of MAb production. One useful application is to identify MAbs reacting with different epitopes from a large number of MAbs so that the most appropriate MAbs can be selected for therapeutic use. JF - Journal of Immunological Methods AU - Nagata, S AU - Numata, Y AU - Onda, M AU - Ise, T AU - Hahn, Y AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4264, USA, pastani@mail.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 141 EP - 155 VL - 292 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Enzyme-linked immunosorbent assay KW - Monoclonal antibodies KW - Immunoassays KW - Epitopes KW - Topography KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17755338?accountid=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=Rapid+grouping+of+monoclonal+antibodies+based+on+their+topographical+epitopes+by+a+label-free+competitive+immunoassay&rft.au=Nagata%2C+S%3BNumata%2C+Y%3BOnda%2C+M%3BIse%2C+T%3BHahn%2C+Y%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Nagata&rft.aufirst=S&rft.date=2004-09-01&rft.volume=292&rft.issue=1-2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2Fj.jim.2004.06.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Monoclonal antibodies; Immunoassays; Topography; Enzyme-linked immunosorbent assay; Epitopes DO - http://dx.doi.org/10.1016/j.jim.2004.06.009 ER - TY - JOUR T1 - Marijuana and cannabinoid regulation of brain reward circuits AN - 17708393; 6089852 AB - The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta super(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta super(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta super(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA. JF - British Journal of Pharmacology AU - Lupica, C R AU - Riegel, A C AU - Hoffman, A F AD - Neurophysiology Section, Cellular Neurobiology Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, U.S. Department of Health and Human Services, Baltimore, MD 21224, USA, clupica@intra.nida.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 227 EP - 234 VL - 143 IS - 2 SN - 0007-1188, 0007-1188 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Drug abuse KW - Anxiolytics KW - Environmental effects KW - Reinforcement KW - Cannabis KW - Self-administration KW - Cannabinoid CB1 receptors KW - Drug addiction KW - Nucleus accumbens KW - ventral tegmentum KW - Tetrahydrocannabinol KW - Reviews 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/17708393?accountid=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=British+Journal+of+Pharmacology&rft.atitle=Marijuana+and+cannabinoid+regulation+of+brain+reward+circuits&rft.au=Lupica%2C+C+R%3BRiegel%2C+A+C%3BHoffman%2C+A+F&rft.aulast=Lupica&rft.aufirst=C&rft.date=2004-09-01&rft.volume=143&rft.issue=2&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Pharmacology&rft.issn=00071188&rft_id=info:doi/10.1038%2Fsj.bjp.0705931 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cannabis; Reinforcement; Tetrahydrocannabinol; Drug abuse; Drug addiction; Anxiolytics; Nucleus accumbens; ventral tegmentum; Self-administration; Environmental effects; Cannabinoid CB1 receptors; Reviews DO - http://dx.doi.org/10.1038/sj.bjp.0705931 ER - TY - JOUR T1 - Absolute Myocardial Perfusion in Canines Measured by Using Dual-Bolus First- Pass MR Imaging AN - 17688168; 6002801 AB - PURPOSE: To compare fluorescent microsphere measurements of myocardial blood flow (MBF) with qualitative, semiquantitative, and fully quantitative measurements of first-pass perfusion at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Coronary artery occlusion or intracoronary adenosine infusion was successfully performed in 16 beagles; both procedures were performed simultaneously in one animal. MBF was assessed at microsphere analysis. First-pass myocardial perfusion MR imaging was performed during a dual-bolus administration of gadopentetate dimeglumine (0.0025 mmol/kg followed by 0.10 mmol/kg). The absolute myocardial perfusion at MR imaging was calculated by using Fermi function deconvolution methods. Qualitative, semiquantitative, and absolute myocardial perfusion MR imaging measurements were compared with microsphere MBF measurements by using paired t tests, linear correlation, and Bland-Altman analysis. RESULTS: Fully quantitative (ie, absolute) analysis of MBF at MR imaging correlated with microsphere MBF measurement (r = 0.95, P 5.0 mL/min/g). Similar close correlations were observed in endocardial and epicardial segments (representing approximately 0.85 g of the myocardium). With modest increases in MBF, qualitative measurements plateaued in the hyperemic zones. Semiquantitative measurements did not correlate with MBF as well (r = 0.69-0.89); they plateaued around 3.0 mL/min/g. CONCLUSION: Dual-bolus MR imaging enabled accurate measurement of absolute epicardial and endocardial perfusion across a wide range of blood flow rates (0 to >5.0 mL/min/g). Use of qualitative MR imaging measures such as the contrast enhancement ratio led to substantially underestimated hyperemic blood flow measurements. RSNA, 2004 JF - Radiology AU - Christian, Timothy F AU - Rettmann, Dan W AU - Aletras, Anthony H AU - Liao, Steve L AU - Taylor, Joni L AU - Balaban, Robert S AU - Arai, Andrew E AD - Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bldg 10, Rm B1D416, MSC 1061, 10 Center Dr, Bethesda, MD Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 677 EP - 684 PB - Radiological Society of North America, 820 Jorie Blvd. Oak Brook Illinois 60523-2251 USA VL - 232 IS - 3 SN - 0033-8419, 0033-8419 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17688168?accountid=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=Radiology&rft.atitle=Absolute+Myocardial+Perfusion+in+Canines+Measured+by+Using+Dual-Bolus+First-+Pass+MR+Imaging&rft.au=Christian%2C+Timothy+F%3BRettmann%2C+Dan+W%3BAletras%2C+Anthony+H%3BLiao%2C+Steve+L%3BTaylor%2C+Joni+L%3BBalaban%2C+Robert+S%3BArai%2C+Andrew+E&rft.aulast=Christian&rft.aufirst=Timothy&rft.date=2004-09-01&rft.volume=232&rft.issue=3&rft.spage=677&rft.isbn=&rft.btitle=&rft.title=Radiology&rft.issn=00338419&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Neonatal abstinence syndrome in methadone-exposed infants is altered by level of prenatal tobacco exposure AN - 17544878; 6418506 AB - Maternal tobacco consumption during pregnancy has been associated with lower birth weight infants, preterm births, intrauterine growth retardation, smaller head circumference and increase in morbidity, yet few studies have examined the role tobacco has on the opiate neonatal abstinence syndrome (NAS). This study examined the effect of prenatal tobacco exposure on NAS for infants born to mothers maintained on methadone during gestation. Twenty-nine pregnant women and their newborn infants participated in this study. Tobacco exposure was based on maternal self-report with 16 women reporting cigarette consumption of 10 or less per day and 13 reporting smoking 20 cigarettes or more a day. The onset, peak, and duration of NAS were examined. Results showed that infants born to mothers who reported smoking 20 or more cigarettes per day had significantly higher NAS peak scores of 9.8 versus 4.8, and took longer to peak (113.0 h versus 37.8 h), than light smokers of 10 or fewer cigarettes per day. We concluded that tobacco use in conjunction with methadone plays an important role in the timing and severity of NAS in prenatally exposed infants. JF - Drug and Alcohol Dependence AU - Choo, R E AU - Huestis, MA AU - Schroeder, J R AU - Shin, A S AU - Jones, HE AD - Chemistry and Drug Metabolism Section, Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institute of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224-6823, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 253 EP - 260 VL - 75 IS - 3 SN - 0376-8716, 0376-8716 KW - Toxicology Abstracts KW - Birth weight KW - Tobacco smoking KW - Opiates KW - Prenatal experience KW - Pregnancy KW - Birth KW - Methadone KW - Drug dependence KW - Gestation KW - Cigarette smoking KW - Neonates KW - Infants KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17544878?accountid=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=Drug+and+Alcohol+Dependence&rft.atitle=Neonatal+abstinence+syndrome+in+methadone-exposed+infants+is+altered+by+level+of+prenatal+tobacco+exposure&rft.au=Choo%2C+R+E%3BHuestis%2C+MA%3BSchroeder%2C+J+R%3BShin%2C+A+S%3BJones%2C+HE&rft.aulast=Choo&rft.aufirst=R&rft.date=2004-09-01&rft.volume=75&rft.issue=3&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Dependence&rft.issn=03768716&rft_id=info:doi/10.1016%2Fj.drugalcdep.2004.03.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tobacco smoking; Infants; Cigarette smoking; Prenatal experience; Neonates; Drug dependence; Methadone; Birth weight; Gestation; Birth; Pregnancy; Opiates DO - http://dx.doi.org/10.1016/j.drugalcdep.2004.03.012 ER - TY - JOUR T1 - Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers AN - 17494023; 6282040 AB - Rationale: Although numerous studies have documented that nicotine can function as an effective reinforcer of intravenous self-administration behavior in animals, it has not been clearly shown to maintain intravenous self-administration behavior above vehicle placebo levels in humans. Objectives: To compare the reinforcing effectiveness of nicotine versus saline placebo in human research volunteers responding under fixed-ratio (FR) schedules of intravenous drug self-administration while systematically increasing response requirements. Methods: Eight male cigarette smokers resided in an inpatient research unit. During 3-h sessions, intravenous injections of nicotine and saline were available concurrently and were contingent on responding (pulling a lever). Nicotine dose (0.75, 1.5, 3.0 mg/injection), time out (TO) value after each injection (1-20 min) and FR response requirement (10-1600) were varied in different subjects over consecutive sessions. Results: Number of nicotine injections/session significantly decreased as dose/injection increased and the number of self-administered nicotine injections was significantly greater than the number of self-administered saline injections across conditions. When FR value was progressively increased over sessions, response rates for nicotine, but not saline, injections increased, with maximal rates at the highest FR values. Rates of responding and injections/session were markedly and significantly higher for nicotine than for saline at FR values of 200 and above. Subjects rated effects of nicotine as both significantly more positive and more negative than saline placebo, with positive ratings significantly higher than negative ratings. Conclusions: Nicotine functioned as a prototypic drug of abuse, serving as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers. Subjects adjusted their responding to response requirements in a way that maintained relatively constant levels of nicotine injections per session. JF - Psychopharmacology AU - Harvey, Deon M AU - Yasar, Sevil AU - Heishman, Stephen J AU - Panlilio, Leigh V AU - Henningfield, Jack E AU - Goldberg, Steven R AD - DHHS, 5500 Nathan Shock Drive, Baltimore, MD, 21224, USA, sgoldber@intra.nida.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 134 EP - 142 PB - Springer-Verlag (Berlin), Heidelberger Platz 3 Berlin 14197 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 175 IS - 2 SN - 0033-3158, 0033-3158 KW - Toxicology Abstracts KW - Intravenous administration KW - Nicotine KW - Cigarette smoking KW - Reinforcement KW - Self-administration KW - Drug abuse KW - Drug self-administration KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17494023?accountid=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=Psychopharmacology&rft.atitle=Nicotine+serves+as+an+effective+reinforcer+of+intravenous+drug-taking+behavior+in+human+cigarette+smokers&rft.au=Harvey%2C+Deon+M%3BYasar%2C+Sevil%3BHeishman%2C+Stephen+J%3BPanlilio%2C+Leigh+V%3BHenningfield%2C+Jack+E%3BGoldberg%2C+Steven+R&rft.aulast=Harvey&rft.aufirst=Deon&rft.date=2004-09-01&rft.volume=175&rft.issue=2&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/10.1007%2Fs00213-004-1818-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nicotine; Intravenous administration; Reinforcement; Cigarette smoking; Self-administration; Drug abuse; Drug self-administration DO - http://dx.doi.org/10.1007/s00213-004-1818-6 ER - TY - JOUR T1 - Enhanced spectral resolution in RNA HCP spectra for measurement of super(3)J sub(C2'P) and super(3)J sub(C4'P) couplings and super(31)P chemical shift changes upon weak alignment AN - 17296949; 6056213 AB - The `out-and-back' 3D HCP experiment, using gradient- and sensitivity-enhanced detection, provides a convenient method for assignment of the super(31)P NMR spectra and accurate measurement of the super(31)P chemical shifts of ribonucleic acids. The super(13)C resolution in such spectra can be doubled, at the cost of a 50% reduction in sensitivity, by combining super(13)C evolution during the super(13)C-\ super(31)P\ de- and rephasing periods. The multiple connectivities observable for a given super(31)P, including correlations to the intranucleotide C5'H sub(2) and C4'H groups, and the C2'H, C3'H and C4'H groups of the preceding nucleotide, permit independent measurements of the super(31)P shift. The super(13)C spectrum of these groups is typically crowded for an RNA molecule in isotropic solution and overlap becomes more problematic in media used to achieve partial alignment. However, many of these correlations are resolvable in the combined-evolution HCP spectrum. The difference in super(31)P chemical shift between isotropic solution and a medium containing liquid crystalline Pf1 provides information on the orientation of phosphate groups. The intensities measured in the 3D HCP spectrum, obtained for an isotropic sample, yield values for the super(3)J sub(C2'P) and super(3)J sub(C4'P) couplings, thereby providing important restraints for the backbone torsion angles epsilon and beta . The experiments are illustrated for a uniformly super(13)C-enriched, 24-residue stem-loop RNA sequence, and results for the helical stem region show close agreement between observed Delta delta ( super(31)P) values and those predicted for a model A-form RNA helix when using a uniform super(31)P CSA tensor. This confirms that Delta delta ( super(31)P) values can be used directly as restraints in refining nucleic acid structures. JF - Journal of Biomolecular NMR AU - O'Neil-Cabello, E AU - Wu, Z AU - Bryce, D L AU - Nikonowicz, E P AU - Bax, A AD - Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, MD 20892-0520, U.S.A. Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 61 EP - 70 PB - Kluwer Academic Publishers VL - 30 IS - 1 SN - 0925-2738, 0925-2738 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17296949?accountid=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+Biomolecular+NMR&rft.atitle=Enhanced+spectral+resolution+in+RNA+HCP+spectra+for+measurement+of+super%283%29J+sub%28C2%27P%29+and+super%283%29J+sub%28C4%27P%29+couplings+and+super%2831%29P+chemical+shift+changes+upon+weak+alignment&rft.au=O%27Neil-Cabello%2C+E%3BWu%2C+Z%3BBryce%2C+D+L%3BNikonowicz%2C+E+P%3BBax%2C+A&rft.aulast=O%27Neil-Cabello&rft.aufirst=E&rft.date=2004-09-01&rft.volume=30&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+NMR&rft.issn=09252738&rft_id=info:doi/10.1023%2FB%3AJNMR.0000042952.66982.38 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1023/B:JNMR.0000042952.66982.38 ER - TY - JOUR T1 - Detection and quantitation of parvovirus B19 AN - 17275485; 6045406 JF - Journal of Clinical Virology AU - Brown, KE AD - Virus Discovery Group, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10/Room 7C218, 9000 Rockville Pike, Bethesda, MD 20892-1652 USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1 EP - 4 PB - Elsevier B.V. VL - 31 IS - 1 SN - 1386-6532, 1386-6532 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Parvovirus B19 KW - Detection KW - Quantitation KW - A 01114:Viruses KW - V 22022:Virus assay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17275485?accountid=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+Virology&rft.atitle=Detection+and+quantitation+of+parvovirus+B19&rft.au=Brown%2C+KE&rft.aulast=Brown&rft.aufirst=KE&rft.date=2004-09-01&rft.volume=31&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Virology&rft.issn=13866532&rft_id=info:doi/10.1016%2Fj.jcv.2004.05.001 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Detection; Quantitation; Parvovirus B19 DO - http://dx.doi.org/10.1016/j.jcv.2004.05.001 ER - TY - JOUR T1 - The solubilizing detergents, Tween 80 and Triton X-100 non-competitively inhibit alpha 7-nicotinic acetylcholine receptor function in Xenopus oocytes. AN - 66724100; 15262057 AB - Because many studies rely upon detergents to solubilize lipophilic agents such as cannabinoid drugs, we examined the effect of commonly employed detergents on the function of the cloned alpha(7) subunit of the nicotinic ACh receptor. Homomeric alpha(7) receptors were expressed in Xenopus oocytes and the two-microelectrode voltage-clamp technique was used to assess their electrophysiological properties. The detergents Tween 80 and Triton X-100 reversibly inhibited ACh (100 microM)-induced inward currents in a concentration-dependent manner, with IC(50) values of 610 nM and 1.4 microM, respectively. The effects of these detergents were independent of membrane potential, and they were not mediated by endogenous Ca(2+)-dependent Cl(-) channels, since they were unaffected by intracellularly injected BAPTA, and recorded in Ca(2+)-free bathing solution containing 2 mM Ba(2+). Both detergents also decreased the maximal effect of ACh, without significantly affecting its EC(50), indicating a non-competitive interaction with the nACh alpha(7) receptors. In contrast to the effects of these detergents, we found that cholic acid (10 microM), DMSO (10 microM) and Tocrisol (0.01% v/v) did not cause a significant effect on nicotinic responses. In conclusion, we demonstrate that the detergents Tween 80 and Triton X-100 are potent inhibitors of neuronal nACh alpha(7) receptors expressed in Xenopus oocytes, and we suggest that studies utilizing these detergents to solubilize lipophilic drugs should be scrutinized for such effects. JF - Journal of neuroscience methods AU - Oz, Murat AU - Spivak, Charles E AU - Lupica, Carl R AD - National Institute on Drug Abuse, NIH/DHHS, Intramural Research Program, Cellular Neurobiology Branch, Cellular Neurophysiology Section, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2004/08/30/ PY - 2004 DA - 2004 Aug 30 SP - 167 EP - 173 VL - 137 IS - 2 SN - 0165-0270, 0165-0270 KW - Chelating Agents KW - 0 KW - Detergents KW - Muscarinic Antagonists KW - Polysorbates KW - RNA, Complementary KW - Receptors, Nicotinic KW - alpha7 Nicotinic Acetylcholine Receptor KW - Barium KW - 24GP945V5T KW - Egtazic Acid KW - 526U7A2651 KW - Atropine KW - 7C0697DR9I KW - Octoxynol KW - 9002-93-1 KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid KW - K22DDW77C0 KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Patch-Clamp Techniques -- methods KW - Animals KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Acetylcholine -- pharmacology KW - RNA, Complementary -- metabolism KW - RNA, Complementary -- chemistry KW - Cloning, Molecular KW - Xenopus laevis KW - Chelating Agents -- pharmacology KW - Chickens KW - Muscarinic Antagonists -- pharmacology KW - Membrane Potentials -- drug effects KW - Atropine -- pharmacology KW - Barium -- pharmacology KW - Female KW - Octoxynol -- pharmacology KW - Egtazic Acid -- analogs & derivatives KW - Polysorbates -- pharmacology KW - Oocytes -- drug effects KW - Receptors, Nicotinic -- drug effects KW - Neural Inhibition -- drug effects KW - Receptors, Nicotinic -- physiology KW - Detergents -- pharmacology KW - Egtazic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66724100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroscience+methods&rft.atitle=The+solubilizing+detergents%2C+Tween+80+and+Triton+X-100+non-competitively+inhibit+alpha+7-nicotinic+acetylcholine+receptor+function+in+Xenopus+oocytes.&rft.au=Oz%2C+Murat%3BSpivak%2C+Charles+E%3BLupica%2C+Carl+R&rft.aulast=Oz&rft.aufirst=Murat&rft.date=2004-08-30&rft.volume=137&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+methods&rft.issn=01650270&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-08 N1 - Date created - 2004-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway AN - 17822387; 6002472 AB - The protective antigen (PA) of anthrax toxin binds to a cell surface receptor, undergoes heptamerization, and binds the enzymatic subunits, the lethal factor (LF) and the edema factor (EF). The resulting complex is then endocytosed. Via mechanisms that depend on the vacuolar ATPase and require membrane insertion of PA, LF and EF are ultimately delivered to the cytoplasm where their targets reside. Here, we show that membrane insertion of PA already occurs in early endosomes, possibly only in the multivesicular regions, but that subsequent delivery of LF to the cytoplasm occurs preferentially later in the endocytic pathway and relies on the dynamics of internal vesicles of multivesicular late endosomes. JF - Journal of Cell Biology AU - Abrami, Laurence AU - Lindsay, Margaret AU - Parton, Robert G AU - Leppla, Stephen H AU - Van Der Goot, FGisou AD - Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland 1211. Institute for Molecular Bioscience, Centre for Microscopy and Microanalysis, and Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia 4072. Microbial Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Y1 - 2004/08/30/ PY - 2004 DA - 2004 Aug 30 SP - 645 EP - 651 PB - Rockefeller University Press, 1114 First Avenue New York NY 10021-8325 USA, [mailto:Bruce.Lyons@rockefeller.edu], [URL:http://www.rockefeller.edu/rupress] VL - 166 IS - 5 SN - 0021-9525, 0021-9525 KW - Microbiology Abstracts B: Bacteriology KW - Cell surface KW - endosomes KW - Adenosinetriphosphatase KW - Lethal factor KW - protective antigen KW - Edema KW - Anthrax KW - Vesicles KW - Bacillus anthracis KW - Toxins KW - J 02832:Antigenic properties and virulence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17822387?accountid=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+Cell+Biology&rft.atitle=Membrane+insertion+of+anthrax+protective+antigen+and+cytoplasmic+delivery+of+lethal+factor+occur+at+different+stages+of+the+endocytic+pathway&rft.au=Abrami%2C+Laurence%3BLindsay%2C+Margaret%3BParton%2C+Robert+G%3BLeppla%2C+Stephen+H%3BVan+Der+Goot%2C+FGisou&rft.aulast=Abrami&rft.aufirst=Laurence&rft.date=2004-08-30&rft.volume=166&rft.issue=5&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cell+Biology&rft.issn=00219525&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 - Bacillus anthracis; protective antigen; Anthrax; endosomes; Lethal factor; Adenosinetriphosphatase; Vesicles; Cell surface; Toxins; Edema ER - TY - JOUR T1 - Retention of aggregated LDL by cultured human coronary artery endothelial cells. AN - 66864359; 15358167 AB - Aggregated LDL (AgLDL) accumulates within the subendothelial space of developing atherosclerotic lesions. We were interested to learn whether endothelial cells can interact with AgLDL. Incubation of endothelial cells with AgLDL resulted in apparent cholesterol retention. Microscopic examination revealed that cholesterol retention resulted mainly from endothelial cell surface attachment of AgLDL. Little AgLDL entered endothelial cells consistent with the small amount of endothelial cell degradation of AgLDL. Although endothelial cell retention of AgLDL was inhibited by LDL, AgLDL retention was not blocked by lactoferrin, C7 anti-LDL receptor monoclonal antibody, or receptor-associated protein, suggesting that LDL receptor family members did not mediate this retention. Surface retention of AgLDL depended on microtubule function and could be regulated by the protein kinase C activator, PMA. Treatment of endothelial cells with PMA either before or during, but not after incubation with AgLDL, inhibited retention of AgLDL. Our findings show that endothelial cells can retain AgLDL but internalize and metabolize little of this AgLDL. Thus, it is unlikely that endothelial cells can transport AgLDL out of atherosclerotic lesions, but it is likely that retention of AgLDL affects endothelial function. JF - Biochemical and biophysical research communications AU - Zhao, Bin AU - Huang, Wei AU - Zhang, Wei-Yang AU - Ishii, Itsuko AU - Kruth, Howard S AD - Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/08/27/ PY - 2004 DA - 2004 Aug 27 SP - 728 EP - 735 VL - 321 IS - 3 SN - 0006-291X, 0006-291X KW - Cholesterol, LDL KW - 0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Macrophages -- cytology KW - Animals KW - Tetradecanoylphorbol Acetate -- metabolism KW - Cells, Cultured KW - Humans KW - Macrophages -- metabolism KW - Arteries -- metabolism KW - Arteries -- anatomy & histology KW - Endothelial Cells -- ultrastructure KW - Coronary Vessels -- metabolism KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- cytology KW - Cholesterol, LDL -- metabolism KW - Coronary Vessels -- anatomy & histology KW - Endothelial Cells -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66864359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mass+spectrometric+measurement+of+differential+reactivity+of+cysteine+to+localize+protein-ligand+binding+sites.&rft.au=Kim%2C+Yeoun+Jin%3BPannell%2C+Lewis+K%3BSackett%2C+Dan+L&rft.aulast=Kim&rft.aufirst=Yeoun&rft.date=2004-09-01&rft.volume=332&rft.issue=2&rft.spage=376&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2Fj.ab.2004.06.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-03 N1 - Date created - 2004-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx. AN - 66817613; 15327778 AB - The mechanism(s) involved in agonist-stimulation of TRPC3 channels is not yet known. Here we demonstrate that TRPC3-N terminus interacts with VAMP2 and alphaSNAP. Further, endogenous and exogenously expressed TRPC3 colocalized and coimmunoprecipitated with SNARE proteins in neuronal and epithelial cells. Imaging of GFP-TRPC3 revealed its localization in the plasma membrane region and in mobile intracellular vesicles. Recovery of TRPC3-GFP fluorescence after photobleaching of the plasma membrane region was decreased by brefeldin-A or BAPTA-AM. Cleavage of VAMP2 with tetanus toxin (TeNT) did not prevent delivery of TRPC3 to the plasma membrane region but reduced its surface expression. TeNT also decreased carbachol and OAG, but not thapsigargin, stimulated Ca2+ influx. Importantly, carbachol, not thapsigargin, increased surface expression of TRPC3 that was attenuated by TeNT and not by BAPTA. In aggregate, these data suggest that VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to carbachol-stimulation of Ca2+ influx. JF - Molecular cell AU - Singh, Brij B AU - Lockwich, Timothy P AU - Bandyopadhyay, Bidhan C AU - Liu, Xibao AU - Bollimuntha, Sunitha AU - Brazer, So-Ching AU - Combs, Christian AU - Das, Sunit AU - Leenders, A G Miriam AU - Sheng, Zu-Hang AU - Knepper, Mark A AU - Ambudkar, Suresh V AU - Ambudkar, Indu S AD - Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA. Y1 - 2004/08/27/ PY - 2004 DA - 2004 Aug 27 SP - 635 EP - 646 VL - 15 IS - 4 SN - 1097-2765, 1097-2765 KW - Carrier Proteins KW - 0 KW - Cholinergic Agonists KW - Ion Channels KW - Membrane Proteins KW - Protein Synthesis Inhibitors KW - R-SNARE Proteins KW - Recombinant Fusion Proteins KW - SNARE Proteins KW - Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins KW - TRPC Cation Channels KW - TRPC3 cation channel KW - Tetanus Toxin KW - Vesicular Transport Proteins KW - Brefeldin A KW - 20350-15-6 KW - Carbachol KW - 8Y164V895Y KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Carrier Proteins -- metabolism KW - Neurons -- metabolism KW - Humans KW - Two-Hybrid System Techniques KW - Cholinergic Agonists -- metabolism KW - Carbachol -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Protein Synthesis Inhibitors -- metabolism KW - Fluorescence Recovery After Photobleaching KW - Brefeldin A -- metabolism KW - Hippocampus -- cytology KW - Neurons -- cytology KW - Tetanus Toxin -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Cytoplasmic Vesicles -- physiology KW - Vesicular Transport Proteins -- metabolism KW - Cell Line KW - Exocytosis -- physiology KW - Calcium -- metabolism KW - Membrane Proteins -- metabolism KW - Membrane Proteins -- genetics KW - Cell Membrane -- metabolism KW - Ion Channels -- genetics KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66817613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell&rft.atitle=VAMP2-dependent+exocytosis+regulates+plasma+membrane+insertion+of+TRPC3+channels+and+contributes+to+agonist-stimulated+Ca2%2B+influx.&rft.au=Singh%2C+Brij+B%3BLockwich%2C+Timothy+P%3BBandyopadhyay%2C+Bidhan+C%3BLiu%2C+Xibao%3BBollimuntha%2C+Sunitha%3BBrazer%2C+So-Ching%3BCombs%2C+Christian%3BDas%2C+Sunit%3BLeenders%2C+A+G+Miriam%3BSheng%2C+Zu-Hang%3BKnepper%2C+Mark+A%3BAmbudkar%2C+Suresh+V%3BAmbudkar%2C+Indu+S&rft.aulast=Singh&rft.aufirst=Brij&rft.date=2004-08-27&rft.volume=15&rft.issue=4&rft.spage=635&rft.isbn=&rft.btitle=&rft.title=Molecular+cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-19 N1 - Date created - 2004-08-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Identifying novel homozygous deletions by microsatellite analysis and characterization of tumor suppressor candidate 1 gene, TUSC1, on chromosome 9p in human lung cancer. AN - 66817580; 15208665 AB - Loss of heterozygosity (LOH) studies indicate that genetic alterations of chromosome 9p occur in numerous tumor types, suggesting the presence of tumor suppressor genes (TSGs) on chromosome 9p critical in carcinogenesis. Our previous LOH analyses in primary lung tumors led us to propose that chromosome 9p harbors other TSGs important in lung tumorigenesis. In this study, 30 non-small-cell lung cancer and 12 small-cell lung cancer cell lines were screened with 55 markers to identify new regions of homozygous deletion (HD) on chromosome 9p. Three novel noncontiguous homozygously deleted regions were detected and ranged in size from 840 kb to 7.4 Mb. One gene identified in the deletion at D9S126, TUSC1 (tumor suppressor candidate 1), is an intronless gene. Multiplex polymerase chain reaction and Southern blot confirmed the HD of TUSC1. Northern blot analysis of TUSC1 demonstrated two transcripts of approximately 2 and 1.5 kb that are likely generated by alternative polyadenylation signals. Both transcripts are expressed in several human tissues and share an open-reading frame encoding a peptide of 209 amino acids. Analysing cell line cDNAs by reverse transcriptase (RT)-PCR demonstrated downregulation of TUSC1 in cell lines with or without HDs, suggesting that TUSC1 may play a role in lung tumorigenesis. JF - Oncogene AU - Shan, Zhihong AU - Parker, Tracy AU - Wiest, Jonathan S AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4258, USA. Y1 - 2004/08/26/ PY - 2004 DA - 2004 Aug 26 SP - 6612 EP - 6620 VL - 23 IS - 39 SN - 0950-9232, 0950-9232 KW - DNA, Complementary KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Sequence Deletion KW - Microsatellite Repeats -- genetics KW - Homozygote KW - Genes, Tumor Suppressor KW - Lung Neoplasms -- genetics KW - Chromosomes, Human, Pair 9 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66817580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Indoor+allergens%2C+asthma%2C+and+asthma-related+symptoms+among+adolescents+in+Wuhan%2C+China.&rft.au=Salo%2C+P%C3%A4ivi+M%3BXia%2C+Jiang%3BJohnson%2C+C+Anderson%3BLi%2C+Yan%3BAvol%2C+Edward+L%3BGong%2C+Jie%3BLondon%2C+Stephanie+J&rft.aulast=Salo&rft.aufirst=P%C3%A4ivi&rft.date=2004-09-01&rft.volume=14&rft.issue=8&rft.spage=543&rft.isbn=&rft.btitle=&rft.title=Annals+of+epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-08-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY168647; GENBANK; AY546089 N1 - SuppNotes - Cited By: Genes Chromosomes Cancer. 2000 Mar;27(3):308-18 [10679921] Trends Genet. 2000 Apr;16(4):168-74 [10729832] Adv Cancer Res. 1998;72:141-96 [9338076] Leukemia. 1997 Oct;11(10):1636-40 [9324282] Int J Cancer. 1997 Apr 10;71(2):213-7 [9139845] Cancer Res. 1997 Jan 1;57(1):1-6 [8988029] Br J Cancer. 1999 May;80(3-4):468-76 [10408855] Nat Genet. 1999 Feb;21(2):163-7 [9988266] Genes Chromosomes Cancer. 1998 Jul;22(3):232-40 [9624535] Cancer Res. 1997 Nov 1;57(21):4868-75 [9354451] Cancer Res. 2001 Feb 1;61(3):1154-61 [11221846] Cancer Res. 2002 Jun 1;62(11):3207-13 [12036935] Nat Rev Genet. 2002 Jun;3(6):415-28 [12042769] Gene. 2003 Jan 16;303:55-61 [12559566] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] Cancer Res. 1993 Oct 15;53(20):4761-3 [8402655] Nature. 1993 Dec 16;366(6456):704-7 [8259215] Cancer Res. 1994 Jan 15;54(2):344-8 [8275465] Oncogene. 1994 May;9(5):1361-5 [8152796] Science. 1994 Apr 15;264(5157):436-40 [8153634] Cancer Res. 1995 Jul 15;55(14):2968-71 [7606711] Nat Genet. 1995 Oct;11(2):210-2 [7550353] Nat Med. 1995 Jul;1(7):686-92 [7585152] Cell. 1995 Dec 15;83(6):993-1000 [8521522] Genes Chromosomes Cancer. 1996 Sep;17(1):14-20 [8889502] Glycoconj J. 1996 Oct;13(5):741-7 [8910001] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evodiamine functions as an agonist for the vanilloid receptor TRPV1. AN - 66778723; 15305207 AB - Evodiamine, a quinozole alkaloid constituent of Evodia rutaecarpa, has been reported previously to induce several responses comparable to capsaicin in animal systems. Here, we characterize evodiamine as an agonist for rat TRPV1 expressed heterologously in CHO cells. Evodiamine bound to rat TRPV1 with a Ki of 5.95 +/- 0.87 microM, as measured by inhibition of [3H] RTX binding (capsaicin, Ki = 1.8 +/- 0.3 microM). Evodiamine was a full agonist for induction of 45Ca2+ uptake, with an EC50 of 856 +/- 43 nM (capsaicin, EC50 = 45 +/- 4 nM) and was competitively antagonized by capsazepine, as revealed by a Schild plot. The pattern of cellular response, as determined by calcium imaging, was similar to that with capsaicin and yielded an EC(50) of 1.03 +/- 0.21 [micro sign]M. Molecular modeling suggested a consistent pattern of overlap between evodiamine and TRPV1 agonists. We conclude that evodiamine represents a novel class of agonists for rat TRPV1, albeit 3-19-fold less potent than capsaicin, and thus represents a new potential class of lead molecules for drug development. JF - Organic & biomolecular chemistry AU - Pearce, Larry V AU - Petukhov, Pavel A AU - Szabo, Tamas AU - Kedei, Noemi AU - Bizik, Fero AU - Kozikowski, Alan P AU - Blumberg, Peter M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Building 37, Room 4048, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA. blumberp@dc37a.nci.nih.gov Y1 - 2004/08/21/ PY - 2004 DA - 2004 Aug 21 SP - 2281 EP - 2286 VL - 2 IS - 16 SN - 1477-0520, 1477-0520 KW - Cations, Divalent KW - 0 KW - Diterpenes KW - Ligands KW - Plant Extracts KW - Quinazolines KW - TRPV Cation Channels KW - resiniferatoxin KW - A5O6P1UL4I KW - evodiamine KW - C01825BVNL KW - capsazepine KW - LFW48MY844 KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Molecular Structure KW - Animals KW - Capsaicin -- chemistry KW - Calcium -- chemistry KW - Models, Biological KW - Capsaicin -- pharmacology KW - Diterpenes -- chemistry KW - Calcium -- metabolism KW - CHO Cells KW - Molecular Conformation KW - Capsaicin -- analogs & derivatives KW - Cations, Divalent -- chemistry KW - Cricetinae KW - TRPV Cation Channels -- agonists KW - TRPV Cation Channels -- metabolism KW - Plant Extracts -- pharmacology KW - Quinazolines -- chemistry KW - Plant Extracts -- chemistry KW - Quinazolines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66778723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Organic+%26+biomolecular+chemistry&rft.atitle=Evodiamine+functions+as+an+agonist+for+the+vanilloid+receptor+TRPV1.&rft.au=Pearce%2C+Larry+V%3BPetukhov%2C+Pavel+A%3BSzabo%2C+Tamas%3BKedei%2C+Noemi%3BBizik%2C+Fero%3BKozikowski%2C+Alan+P%3BBlumberg%2C+Peter+M&rft.aulast=Pearce&rft.aufirst=Larry&rft.date=2004-08-21&rft.volume=2&rft.issue=16&rft.spage=2281&rft.isbn=&rft.btitle=&rft.title=Organic+%26+biomolecular+chemistry&rft.issn=14770520&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-06-09 N1 - Date created - 2004-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - UvsX recombinase and Dda helicase rescue stalled bacteriophage T4 DNA replication forks in vitro. AN - 66788372; 15194689 AB - The rescue of stalled replication forks via a series of steps that include fork regression, template switching, and fork restoration often has been proposed as a major mechanism for accurately bypassing non-coding DNA lesions. Bacteriophage T4 encodes almost all of the proteins required for its own DNA replication, recombination, and repair. Both recombination and recombination repair in T4 rely on UvsX, a RecA-like recombinase. We show here that UvsX plus the T4-encoded helicase Dda suffice to rescue stalled T4 replication forks in vitro. This rescue is based on two sequential template-switching reactions that allow DNA replication to bypass a non-coding DNA lesion in a non-mutagenic manner. JF - The Journal of biological chemistry AU - Kadyrov, Farid A AU - Drake, John W AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 2004/08/20/ PY - 2004 DA - 2004 Aug 20 SP - 35735 EP - 35740 VL - 279 IS - 34 SN - 0021-9258, 0021-9258 KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - Membrane Proteins KW - UvsX protein, Enterobacteria phage T4 KW - Viral Proteins KW - DNA Helicases KW - EC 3.6.4.- KW - dda DNA helicase protein, Bacteriophage T4 KW - EC 3.6.4.12 KW - Index Medicus KW - DNA, Viral -- biosynthesis KW - Base Sequence KW - Recombination, Genetic KW - Molecular Sequence Data KW - DNA, Viral -- genetics KW - Viral Proteins -- genetics KW - DNA Helicases -- metabolism KW - Membrane Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - DNA Helicases -- genetics KW - Bacteriophage T4 -- metabolism KW - Viral Proteins -- metabolism KW - Bacteriophage T4 -- genetics KW - Membrane Proteins -- genetics KW - DNA Replication KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66788372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=UvsX+recombinase+and+Dda+helicase+rescue+stalled+bacteriophage+T4+DNA+replication+forks+in+vitro.&rft.au=Kadyrov%2C+Farid+A%3BDrake%2C+John+W&rft.aulast=Kadyrov&rft.aufirst=Farid&rft.date=2004-08-20&rft.volume=279&rft.issue=34&rft.spage=35735&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 - 2005-02-15 N1 - Date created - 2004-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeting of Scavenger Receptor Class B Type I by Synthetic Amphipathic alpha-Helical-containing Peptides Blocks Lipopolysaccharide (LPS) Uptake and LPS-induced Pro-inflammatory Cytokine Responses in THP-1 Monocyte Cells AN - 18041237; 5986365 AB - Human scavenger receptor class B type I, CLA-1, mediates lipopolysaccharide (LPS) binding and internalization. Because one of the recognition motifs in SR-B1 ligands is the anionic amphipathic alpha-helix, we analyzed the effects of model amphipathic alpha-helical-containing peptides on LPS uptake and LPS-stimulated cytokine production. The L-37pA model peptide, containing two class A amphipathic helices, bound with high affinity (K sub(d) = 0.94 mu g/ml) to CLA-1-expressing HeLa cells with a 10-fold increased capacity when compared with mock transfected HeLa cells. Both LPS and L-37pA colocalized with anti-CLA-1 antibody and directly bound CLA-1 as determined by cross- linking. SR-BI/CLA-1 ligands such as HDL, apoA-I, and L-37pA efficiently competed against iodinated L-37pA. Bacterial LPS, lipoteichoic acid, and hsp60 also competed against iodinated L-37pA. Model peptides blocked uptake of iodinated LPS in both mock transfected and CLA-1-overexpressing HeLa cells. Bound and internalized Alexa-L-37pA and BODIPY-LPS colocalized at the cell surface and perinuclear compartment. Both ligands were predominantly transported to the Golgi complex, colocalizing with the Golgi markers bovine serum albumin- ceramide, anti-Golgin97 antibody, and cholera toxin subunit B. A 100-fold excess of L-37pA nearly eliminated BODIPY-LPS binding and internalization. L-37pA and its D-amino acid analogue, D-37pA peptide were similarly effective in blocking LPS, Gram-positive bacterial wall component lipoteichoic acid and bacterial heat shock protein Gro-EL-stimulated cytokine secretion in THP-1 cells. In the same culture media used for the cytokine stimulation study, neither L-37pA nor D-37pA affected the Limulus amebocyte lysate activity of LPS, indicating that LPS uptake and cytokine stimulation were blocked independently of LPS neutralization. These results demonstrate that amphipathic helices of exchangeable apolipoproteins may represent a general host defense mechanism against inflammation. JF - Journal of Biological Chemistry AU - Bocharov, Alexander V AU - Baranova, Irina N AU - Vishnyakova, Tatyana G AU - Remaley, Alan T AU - Csako, Gyorgy AU - Thomas, Fairwell AU - Patterson, Amy P AU - Eggerman, Thomas L AD - Department of Laboratory Medicine, W. G. Magnuson Clinical Center, NHLBI, and the Division of Diabetes, Endocrinology and Metabolic Diseases, NIDDK, the National Institutes of Health, Bethesda, Maryland Y1 - 2004/08/20/ PY - 2004 DA - 2004 Aug 20 SP - 36072 EP - 36082 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 34 SN - 0021-9258, 0021-9258 KW - man KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Golgi apparatus KW - Gram-positive bacteria KW - Lipopolysaccharides KW - Cytokines KW - Monocytes KW - scavenger receptors KW - Inflammation KW - F 06733:General KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18041237?accountid=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=Targeting+of+Scavenger+Receptor+Class+B+Type+I+by+Synthetic+Amphipathic+alpha-Helical-containing+Peptides+Blocks+Lipopolysaccharide+%28LPS%29+Uptake+and+LPS-induced+Pro-inflammatory+Cytokine+Responses+in+THP-1+Monocyte+Cells&rft.au=Bocharov%2C+Alexander+V%3BBaranova%2C+Irina+N%3BVishnyakova%2C+Tatyana+G%3BRemaley%2C+Alan+T%3BCsako%2C+Gyorgy%3BThomas%2C+Fairwell%3BPatterson%2C+Amy+P%3BEggerman%2C+Thomas+L&rft.aulast=Bocharov&rft.aufirst=Alexander&rft.date=2004-08-20&rft.volume=279&rft.issue=34&rft.spage=36072&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 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Golgi apparatus; Gram-positive bacteria; Cytokines; Lipopolysaccharides; Monocytes; scavenger receptors; Inflammation ER - TY - JOUR T1 - Detection of HIV-1 and HCV Infections among Antibody-Negative Blood Donors by Nucleic Acid-Amplification Testing AN - 223941326; 15317889 AB - Background Testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA by means of nucleic acid amplification was introduced in the United States as an investigational screening test in mid-1999 to identify donations made during the window period before seroconversion. Methods We analyzed all antibody-nonreactive donations that were confirmed to be positive for HIV-1 and HCV RNA on nucleic acid-amplification testing of "minipools" (pools of 16 to 24 donations) by the main blood-collection programs in the United States during the first three years of nucleic acid screening. Results Among 37,164,054 units screened, 12 were confirmed to be positive for HIV-1 RNA -- or 1 in 3.1 million donations -- only 2 of which were detected by HIV-1 p24 antigen testing. For HCV, of 39,721,404 units screened, 170 were confirmed to be positive for HCV RNA, or 1 in 230,000 donations (or 1 in 270,000 on the basis of 139 donations confirmed to be positive for HCV RNA with the use of a more sensitive HCV-antibody test). The respective rates of positive HCV and HIV-1 nucleic acid-amplification tests were 3.3 and 4.1 times as high among first-time donors as among donors who gave blood repeatedly. Follow-up studies of 67 HCV RNA-positive donors demonstrated that seroconversion occurred a median of 35 days after the index donation, followed by a low rate of resolution of viremia; three cases of long-term immunologically silent HCV infection were documented. Conclusions Minipool nucleic acid-amplification testing has helped prevent the transmission of approximately 5 HIV-1 infections and 56 HCV infections annually and has reduced the residual risk of transfusion-transmitted HIV-1 and HCV to approximately 1 in 2 million blood units. JF - The New England Journal of Medicine AU - Stramer, Susan L, PhD AU - Glynn, Simone A, MD, MPH AU - Kleinman, Steven H, MD AU - Strong, D Michael, PhD AU - Caglioti, Sally, MT (ASCP), SBB AU - Wright, David J, PhD AU - Dodd, Roger Y, PhD AU - Busch, Michael P, MD, PhD Y1 - 2004/08/19/ PY - 2004 DA - 2004 Aug 19 SP - 760 EP - 8 CY - Boston PB - Massachusetts Medical Society VL - 351 IS - 8 SN - 00284793 KW - Medical Sciences KW - HIV Antibodies KW - Hepatitis C Antibodies KW - RNA, Viral KW - Alanine Transaminase KW - FDA approval KW - Hepatitis KW - Human immunodeficiency virus--HIV KW - Blood & organ donations KW - Acids KW - United States--US KW - Alanine Transaminase -- blood KW - Hepatitis C -- transmission KW - HIV Infections -- transmission KW - HIV Infections -- blood KW - HIV Antibodies -- blood KW - Hepatitis C -- blood KW - Humans KW - Hepatitis C Antibodies -- blood KW - RNA, Viral -- analysis KW - Viremia -- diagnosis KW - Hepatitis C -- diagnosis KW - HIV-1 -- isolation & purification KW - Nucleic Acid Amplification Techniques KW - Hepacivirus -- isolation & purification KW - Blood Donors KW - HIV Infections -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/223941326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Detection+of+HIV-1+and+HCV+Infections+among+Antibody-Negative+Blood+Donors+by+Nucleic+Acid-Amplification+Testing&rft.au=Stramer%2C+Susan+L%2C+PhD%3BGlynn%2C+Simone+A%2C+MD%2C+MPH%3BKleinman%2C+Steven+H%2C+MD%3BStrong%2C+D+Michael%2C+PhD%3BCaglioti%2C+Sally%2C+MT+%28ASCP%29%2C+SBB%3BWright%2C+David+J%2C+PhD%3BDodd%2C+Roger+Y%2C+PhD%3BBusch%2C+Michael+P%2C+MD%2C+PhD&rft.aulast=Stramer&rft.aufirst=Susan&rft.date=2004-08-19&rft.volume=351&rft.issue=8&rft.spage=760&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Pharmacology&rft.issn=00071188&rft_id=info:doi/10.1038%2Fsj.bjp.0705931 LA - English DB - ProQuest Central N1 - Name - Food & Drug Administration--FDA N1 - Copyright - Copyright © 2004 Massachusetts Medical Society. All rights reserved. N1 - Document feature - Tables; Graphs; References N1 - Last updated - 2014-04-21 N1 - CODEN - NEJMAG N1 - SubjectsTermNotLitGenreText - United States--US ER - TY - JOUR T1 - Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma. AN - 66789547; 15266310 AB - The WWOX (WW-domain containing oxidoreductase) is a candidate tumour suppressor gene spanning the same chromosome region, 16q23, as the second most common fragile site (FS), FRA16D. Deletions detected by comparative genomic hybridisation (CGH) and loss of heterozygosity at microsatellite markers on chromosome 16q are common in many human cancers including hepatocellular carcinoma (HCC). The development of human HCC is closely associated with exposure to oncogenic viruses and chemical carcinogens, agents known to frequently target common FS. We examined the status of WWOX genomic DNA, RNA and protein in 18 cell lines derived from human HCC and found recurrent alterations of the gene. Loss of DNA copy-number confined to band 16q23 was detected by CGH in several cell lines. Although homozygous deletions of the WWOX gene were not detected, WWOX mRNA expression was absent or lower in 60% of cell lines. The occurrence of aberrant WWOX reverse transcription-PCR products with deletion of exons 6-8 correlated significantly with altered WWOX expression. All of the cell lines showing mRNA downregulation had a decreased or undetectable level of WWOX protein as demonstrated by Western blotting with antibody to WWOX. Furthermore, 13 out of the 18 cell lines expressed decreased levels or no WWOX protein when compared with normal liver. These results show that WWOX gene is frequently altered in HCC and raise the possibility that this gene is implicated in hepatocarcinogenesis. JF - British journal of cancer AU - Park, S-W AU - Ludes-Meyers, J AU - Zimonjic, D B AU - Durkin, M E AU - Popescu, N C AU - Aldaz, C M AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4262, USA. Y1 - 2004/08/16/ PY - 2004 DA - 2004 Aug 16 SP - 753 EP - 759 VL - 91 IS - 4 SN - 0007-0920, 0007-0920 KW - Tumor Suppressor Proteins KW - 0 KW - Oxidoreductases KW - EC 1.- KW - WWOX protein, human KW - EC 1.1.1.- KW - Index Medicus KW - Microsatellite Repeats KW - Loss of Heterozygosity KW - Apoptosis KW - Tumor Cells, Cultured KW - Down-Regulation KW - Humans KW - Chromosome Fragile Sites KW - Reverse Transcriptase Polymerase Chain Reaction KW - Gene Expression Regulation, Neoplastic KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Oxidoreductases -- biosynthesis KW - Liver Neoplasms -- genetics KW - Gene Deletion KW - Chromosomes, Human, Pair 16 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66789547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Frequent+downregulation+and+loss+of+WWOX+gene+expression+in+human+hepatocellular+carcinoma.&rft.au=Park%2C+S-W%3BLudes-Meyers%2C+J%3BZimonjic%2C+D+B%3BDurkin%2C+M+E%3BPopescu%2C+N+C%3BAldaz%2C+C+M&rft.aulast=Park&rft.aufirst=S-W&rft.date=2004-08-16&rft.volume=91&rft.issue=4&rft.spage=753&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 - 2004-09-14 N1 - Date created - 2004-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 2000 Apr 15;60(8):2140-5 [10786676] Cancer Res. 2000 Feb 15;60(4):1049-53 [10706123] Oncogene. 2001 Aug 23;20(37):5232-8 [11526514] Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11417-22 [11572989] Cancer Res. 2001 Nov 15;61(22):8068-73 [11719429] Nat Rev Cancer. 2001 Dec;1(3):214-21 [11902576] Oncogene. 2002 Mar 14;21(12):1832-40 [11896615] Cancer Res. 2002 Apr 15;62(8):2258-60 [11956080] Cancer Res. 2002 Jul 15;62(14):4054-60 [12124341] Nat Genet. 2002 Aug;31(4):339-46 [12149612] Hepatology. 2002 Nov;36(5):1214-20 [12395332] Int J Oncol. 1998 Jan;12(1):187-96 [9454904] Cell. 2002 Dec 13;111(6):779-89 [12526805] Oncogene. 2003 Jan 23;22(3):445-50 [12545165] J Mol Diagn. 2003 Feb;5(1):48-53 [12552080] Cancer Res. 2003 Feb 15;63(4):878-81 [12591741] Cancer Lett. 2003 Mar 20;192(1):1-17 [12637148] Int J Oncol. 2003 Jul;23(1):133-7 [12792785] Cytogenet Genome Res. 2003;100(1-4):92-100 [14526169] Cytogenet Genome Res. 2003;100(1-4):101-10 [14526170] Cytogenet Genome Res. 2003;101(1):8-16 [14571130] Genes Chromosomes Cancer. 2004 Jan;39(1):71-6 [14603443] Mol Cancer Res. 2003 Nov;1(13):940-7 [14638866] Neoplasia. 2003 Sep-Oct;5(5):390-6 [14670176] Cancer Res. 2003 Dec 15;63(24):8629-33 [14695174] Oncogene. 2004 Feb 12;23(6):1308-13 [14647417] Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4401-6 [15070730] Hum Genet. 1984;67(2):136-42 [6430783] Science. 1987 Jan 16;235(4786):305-11 [3541204] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] Nat Genet. 1997 Apr;15 Spec No:417-74 [9140409] Hum Mol Genet. 1998 Apr;7(4):755-61 [9499431] Hepatology. 1999 Apr;29(4):1208-14 [10094966] Cancer Genet Cytogenet. 1999 May;111(1):37-44 [10326589] J Clin Oncol. 1999 May;17(5):1618-24 [10334551] Cell. 2000 Jan 7;100(1):57-70 [10647931] Genes Chromosomes Cancer. 2001 Mar;30(3):245-53 [11170281] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome. AN - 66824695; 15334433 AB - To screen for potential efficacy and assess feasibility and safety of dehydroepiandrosterone (DHEA) as a treatment for Sjögren's syndrome (SS). A 24-week randomized, double-blinded, pilot trial of oral DHEA (200 mg/day) versus placebo was conducted. The primary comparison was to a hypothesized 20% placebo response rate. If 14 consecutive subjects on DHEA did not respond, a Phase III trial would be considered futile. A placebo group of 14 subjects was planned to verify placebo response rate and estimate sample size required for a definitive trial. Response criteria required 20% improvement in at least 2 of 3 domains. Analysis of covariance was used to adjust for baseline differences and for stratified randomization. Outcome measures included visual analog scale questionnaires for dry eye and dry mouth symptoms, lissamine green ocular dye staining and Schirmer I tests, stimulated salivary flow, IgG, and erythrocyte sedimentation rate (ESR). Randomization resulted in 14 DHEA and 14 placebo group subjects. At baseline, mean +/- SD for DHEA versus placebo groups were Schirmer I tests 4.5 +/- 4.5 versus 5.4 +/- 6.1 mm/5 minutes; Van Bijsterveld score 5.3 +/- 2.1 versus 5.5 +/- 2.2; unstimulated saliva 0.03 +/- 0.05 versus 0.04 +/- 0.10 ml/minute; IgG 1,699 +/- 749 versus 1,712 +/- 621 g/dl; and ESR 40 +/- 31 versus 44 +/- 28 mm/hour. Apart from changes over the trial in dry mouth symptoms, no significant differences were noted between the DHEA and placebo groups for dry eye symptoms, objective measures of ocular dryness, stimulated salivary flow; IgG, or ESR. Four DHEA and one placebo group patient dropped out because of adverse effects. Although 7 subjects met response criteria in the DHEA group, 5 met the criteria in the placebo group, and there was no significant difference between groups. DHEA showed no evidence of efficacy in SS. Without evidence for efficacy, patients with SS should avoid using unregulated DHEA supplements, since long-term adverse consequences of exposure to this hormone are unknown. JF - Arthritis and rheumatism AU - Pillemer, Stanley R AU - Brennan, Michael T AU - Sankar, Vidya AU - Leakan, Rose Anne AU - Smith, Janine A AU - Grisius, Margaret AU - Ligier, Sophie AU - Radfar, Lida AU - Kok, Marc R AU - Kingman, Albert AU - Fox, Philip C AD - National Institute of Dental and Craniofacial Research, Bethesda, Maryland 28092, USA. PillemerS@medimmune.com Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 601 EP - 604 VL - 51 IS - 4 SN - 0004-3591, 0004-3591 KW - Adjuvants, Immunologic KW - 0 KW - Placebos KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Treatment Outcome KW - Pilot Projects KW - Middle Aged KW - Female KW - Adjuvants, Immunologic -- administration & dosage KW - Sjogren's Syndrome -- drug therapy KW - Dehydroepiandrosterone -- adverse effects KW - Adjuvants, Immunologic -- adverse effects KW - Dehydroepiandrosterone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66824695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Pilot+clinical+trial+of+dehydroepiandrosterone+%28DHEA%29+versus+placebo+for+Sj%C3%B6gren%27s+syndrome.&rft.au=Pillemer%2C+Stanley+R%3BBrennan%2C+Michael+T%3BSankar%2C+Vidya%3BLeakan%2C+Rose+Anne%3BSmith%2C+Janine+A%3BGrisius%2C+Margaret%3BLigier%2C+Sophie%3BRadfar%2C+Lida%3BKok%2C+Marc+R%3BKingman%2C+Albert%3BFox%2C+Philip+C&rft.aulast=Pillemer&rft.aufirst=Stanley&rft.date=2004-08-15&rft.volume=51&rft.issue=4&rft.spage=601&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-20 N1 - Date created - 2004-08-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arthritis Rheum. 2005 Aug 15;53(4):626 [16082652] Arthritis Rheum. 2005 Aug 15;53(4):626-7 [16082644] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Poliovirus vaccination during pregnancy, maternal seroconversion to simian virus 40, and risk of childhood cancer. AN - 66763424; 15286015 AB - Before 1963, poliovirus vaccine produced in the United States was contaminated with simian virus 40 (SV40), which causes cancer in animals. To examine whether early-life SV40 infection can cause human cancer, the authors studied 54,796 children enrolled in the US-based Collaborative Perinatal Project (CPP) in 1959-1966, 52 of whom developed cancer by their eighth birthday. Those children whose mothers had received pre-1963 poliovirus vaccine during pregnancy (22.5% of the children) had an increased incidence of neural tumors (hazard ratio = 2.6, 95% confidence interval: 1.0, 6.7; 18 cases) and hematologic malignancies (hazard ratio = 2.8, 95% confidence interval: 1.2, 6.4; 22 cases). For 50 CPP children with cancer and 200 CPP control children, the authors tested paired maternal serum samples from pregnancy for SV40 antibodies using a virus-like particle enzyme immunoassay and a plaque neutralization assay. Overall, mothers exhibited infrequent, low-level SV40 antibody reactivity, and only six case mothers seroconverted by either assay. Using the two SV40 assays, maternal SV40 seroconversion during pregnancy was not consistently related to children's case/control status or mothers' receipt of pre-1963 vaccine. The authors conclude that an increased cancer risk in CPP children whose mothers received pre-1963 poliovirus vaccine was unlikely to have been due to SV40 infection transmitted from mothers to their children. JF - American journal of epidemiology AU - Engels, E A AU - Chen, J AU - Viscidi, R P AU - Shah, K V AU - Daniel, R W AU - Chatterjee, N AU - Klebanoff, M A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA. engelse@exchange.nih.gov Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 306 EP - 316 VL - 160 IS - 4 SN - 0002-9262, 0002-9262 KW - Antibodies, Viral KW - 0 KW - Poliovirus Vaccines KW - Index Medicus KW - Causality KW - Drug Contamination KW - Maternal Exposure -- statistics & numerical data KW - Humans KW - Seroepidemiologic Studies KW - Child KW - Pregnancy KW - Child, Preschool KW - Infant KW - BK Virus -- immunology KW - Vaccination -- statistics & numerical data KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Nervous System Neoplasms -- epidemiology KW - Incidence KW - Fibrosarcoma -- epidemiology KW - Hematologic Neoplasms -- epidemiology KW - United States -- epidemiology KW - Male KW - Female KW - Poliomyelitis -- immunology KW - Antibodies, Viral -- blood KW - Pregnancy Complications, Infectious -- prevention & control KW - Pregnancy Complications, Infectious -- immunology KW - Poliomyelitis -- prevention & control KW - Neoplasms -- classification KW - Poliovirus Vaccines -- adverse effects KW - Neoplasms -- epidemiology KW - Simian virus 40 -- immunology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66763424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Poliovirus+vaccination+during+pregnancy%2C+maternal+seroconversion+to+simian+virus+40%2C+and+risk+of+childhood+cancer.&rft.au=Engels%2C+E+A%3BChen%2C+J%3BViscidi%2C+R+P%3BShah%2C+K+V%3BDaniel%2C+R+W%3BChatterjee%2C+N%3BKlebanoff%2C+M+A&rft.aulast=Engels&rft.aufirst=E&rft.date=2004-08-15&rft.volume=160&rft.issue=4&rft.spage=306&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 completed - 2004-09-21 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. AN - 66757118; 15100158 AB - Recently, there have been several reports using various superparamagnetic iron oxide (SPIO) nanoparticles to label mammalian cells for monitoring their temporal and spatial migration in vivo by magnetic resonance imaging (MRI). The purpose of this study was to evaluate the efficiency and toxicity of labeling cells using 2 commercially available Food and Drug Administration (FDA)-approved agents, ferumoxides, a suspension of dextran-coated SPIO used as an MRI contrast agent, and protamine sulfate, conventionally used to reverse heparin anticoagulation but also used ex vivo as a cationic transfection agent. After labeling of human mesenchymal stem cells (MSCs) and hematopoietic (CD34+) stem cells and other mammalian cells with ferumoxides-protamine sulfate complexes (FE-Pro), cellular toxicity, functional capacity, and quantitative cellular iron incorporation were determined. FE-Pro-labeled cells demonstrated no short- or long-term toxicity, changes in differentiation capacity of the stem cells, or changes in phenotype when compared with unlabeled cells. Efficient labeling with FE-Pro was observed with iron content per cell varying between 2.01 +/- 0.1 pg for CD34+ cells and 10.94 +/- 1.86 pg for MSCs with 100% of cells labeled. Cell labeling using these agents should facilitate the translation of this method to clinical trials for evaluation of trafficking of infused or transplanted cells by MRI. JF - Blood AU - Arbab, Ali S AU - Yocum, Gene T AU - Kalish, Heather AU - Jordan, Elaine K AU - Anderson, Stasia A AU - Khakoo, Aarif Y AU - Read, Elizabeth J AU - Frank, Joseph A AD - Laboratory of Diagnostic Radiology Research, National Institutes of Health, Building 10, Room no. B1N256, Bethesda, MD 20892, USA. saali@cc.nih.gov Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 1217 EP - 1223 VL - 104 IS - 4 SN - 0006-4971, 0006-4971 KW - Dextrans KW - 0 KW - Magnetite Nanoparticles KW - Molecular Probes KW - Oxides KW - Protamines KW - Iron KW - E1UOL152H7 KW - ferumoxides KW - G6N3J05W84 KW - Ferrosoferric Oxide KW - XM0M87F357 KW - Abridged Index Medicus KW - Index Medicus KW - Cell Movement KW - Cell Proliferation -- drug effects KW - Magnetic Resonance Imaging KW - Animals KW - Protamines -- toxicity KW - Humans KW - Mice KW - Molecular Probes -- pharmacokinetics KW - Drug Evaluation KW - Cell Survival -- drug effects KW - Molecular Probes -- toxicity KW - Protamines -- pharmacokinetics KW - Mesenchymal Stromal Cells -- drug effects KW - Neoplasms -- pathology KW - Iron -- analysis KW - Hematopoietic Stem Cells -- cytology KW - Iron -- pharmacokinetics KW - Oxides -- pharmacokinetics KW - Oxides -- toxicity KW - Iron -- toxicity KW - Molecular Probe Techniques KW - Mesenchymal Stromal Cells -- cytology KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66757118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficient+magnetic+cell+labeling+with+protamine+sulfate+complexed+to+ferumoxides+for+cellular+MRI.&rft.au=Arbab%2C+Ali+S%3BYocum%2C+Gene+T%3BKalish%2C+Heather%3BJordan%2C+Elaine+K%3BAnderson%2C+Stasia+A%3BKhakoo%2C+Aarif+Y%3BRead%2C+Elizabeth+J%3BFrank%2C+Joseph+A&rft.aulast=Arbab&rft.aufirst=Ali&rft.date=2004-08-15&rft.volume=104&rft.issue=4&rft.spage=1217&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-09 N1 - Date created - 2004-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Blood. 2004 Nov 15;104(10):3410-2; author reply 3412-3 [15525839] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV transmission risk behavior among men and women living with HIV in 4 cities in the United States. AN - 66694418; 15247559 AB - Determining rates of HIV transmission risk behavior among HIV-positive individuals is a public health priority, especially as infected persons live longer because of improved medical treatments. Few studies have assessed the potential for transmission to the partners of HIV-positive persons who engage in high-risk activities. A total of 3723 HIV-infected persons (1918 men who have sex with men [MSM], 978 women, and 827 heterosexual men) were interviewed in clinics and community-based agencies in Los Angeles, Milwaukee, New York City, and San Francisco from June 2000 to January 2002 regarding sexual and drug use behaviors that confer risk for transmitting HIV. Less than one quarter of women and heterosexual men had 2 or more sexual partners, whereas 59% of MSM reported having multiple partners. Most unprotected vaginal and anal sexual activity took place in the context of relationships with other HIV-positive individuals. Approximately 19% of women, 15.6% of MSM, and 13.1% of heterosexual men engaged in unprotected vaginal or anal intercourse with partners who were HIV-negative or whose serostatus was unknown. The majority of sexually active participants disclosed their serostatus to all partners with whom they engaged in unprotected intercourse. An estimated 30.4 new infections (79.7% as a result of sexual interactions with MSM) would be expected among the sex partners of study participants during the 3-month reporting period. Eighteen percent of 304 participants who injected drugs in the past 3 months reported lending their used injection equipment to others. In addition to the more traditional approaches of HIV test counseling and of focusing on persons not infected, intensive prevention programs for persons with HIV infection are needed to stem the future spread of the virus. JF - Journal of acquired immune deficiency syndromes (1999) AU - Weinhardt, Lance S AU - Kelly, Jeffrey A AU - Brondino, Michael J AU - Rotheram-Borus, Mary Jane AU - Kirshenbaum, Sheri B AU - Chesney, Margaret A AU - Remien, Robert H AU - Morin, Stephen F AU - Lightfoot, Marguerita AU - Ehrhardt, Anke A AU - Johnson, Mallory O AU - Catz, Sheryl L AU - Pinkerton, Steven D AU - Benotsch, Eric G AU - Hong, Daniel AU - Gore-Felton, Cheryl AU - National Institute of Mental Health Healthy Living Project Team AD - Center for AIDS Intervention Research, Medical College of Wisconsin, Milwaukee, WI 53202, USA. lsw@mcw.edu ; National Institute of Mental Health Healthy Living Project Team Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 1057 EP - 1066 VL - 36 IS - 5 SN - 1525-4135, 1525-4135 KW - Index Medicus KW - AIDS/HIV KW - Risk-Taking KW - Humans KW - Aged KW - Models, Statistical KW - Sexual Partners KW - Sexual Behavior KW - Aged, 80 and over KW - Needle Sharing KW - Adult KW - Middle Aged KW - Substance Abuse, Intravenous -- complications KW - United States -- epidemiology KW - Female KW - Male KW - HIV Infections -- transmission KW - HIV Infections -- complications KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66694418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%281999%29&rft.atitle=HIV+transmission+risk+behavior+among+men+and+women+living+with+HIV+in+4+cities+in+the+United+States.&rft.au=Weinhardt%2C+Lance+S%3BKelly%2C+Jeffrey+A%3BBrondino%2C+Michael+J%3BRotheram-Borus%2C+Mary+Jane%3BKirshenbaum%2C+Sheri+B%3BChesney%2C+Margaret+A%3BRemien%2C+Robert+H%3BMorin%2C+Stephen+F%3BLightfoot%2C+Marguerita%3BEhrhardt%2C+Anke+A%3BJohnson%2C+Mallory+O%3BCatz%2C+Sheryl+L%3BPinkerton%2C+Steven+D%3BBenotsch%2C+Eric+G%3BHong%2C+Daniel%3BGore-Felton%2C+Cheryl%3BNational+Institute+of+Mental+Health+Healthy+Living+Project+Team&rft.aulast=Weinhardt&rft.aufirst=Lance&rft.date=2004-08-15&rft.volume=36&rft.issue=5&rft.spage=1057&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.issn=15254135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-13 N1 - Date created - 2005-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repacking of hydrophobic residues in a stable mutant of apocytochrome b562 selected by phage-display and proteolysis. AN - 66670982; 15229877 AB - To test a hydrophobic core-directed protein design approach, we previously have used phage-display and proteolysis to select stably folded proteins from a library of mutants of apocytochrome b562. The consensus sequence of the selected mutants has hydrophilic residues at two of the three positions that are designed to form a hydrophobic core. To understand this unexpected result, we determined the high-resolution structure of one of the selected mutants using multi-dimensional nuclear magnetic resonance (NMR). The structure shows that the two hydrophilic residues in the consensus sequence were on the surface of the structure. Instead, two of their neighboring hydrophobic residues reorganized their side-chain conformations and formed the hydrophobic core. This result suggests that the hydrophobic core-directed protein design by phage-display and proteolysis is a valid method in general but alternative hydrophobic packing needs to be considered in the initial design. The unexpected repacking of the hydrophobic residues also highlights the plastic nature of protein structures. Copyright 2004 Wiley-Liss, Inc. JF - Proteins AU - Feng, Hanqiao AU - Bai, Yawen AD - Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 426 EP - 429 VL - 56 IS - 3 KW - Cytochrome b Group KW - 0 KW - Peptide Library KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Hydrophobic and Hydrophilic Interactions KW - Protein Structure, Secondary KW - Protein Engineering KW - Computer Simulation KW - Models, Molecular KW - Nuclear Magnetic Resonance, Biomolecular KW - Protein Folding KW - Consensus Sequence KW - Protein Structure, Tertiary KW - Hydrolysis KW - Hydrogen Bonding KW - Cytochrome b Group -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66670982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins&rft.atitle=Repacking+of+hydrophobic+residues+in+a+stable+mutant+of+apocytochrome+b562+selected+by+phage-display+and+proteolysis.&rft.au=Feng%2C+Hanqiao%3BBai%2C+Yawen&rft.aulast=Feng&rft.aufirst=Hanqiao&rft.date=2004-08-15&rft.volume=56&rft.issue=3&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Proteins&rft.issn=1097-0134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-20 N1 - Date created - 2004-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activity of Staphylococcus epidermidis Phenol-Soluble Modulin Peptides Expressed in Staphylococcus carnosus AN - 18041997; 5990609 AB - Staphylococcus epidermidis releases a group of peptides termed phenol-soluble modulin (PSM) that stimulate macrophages. The structure of 3 peptides (PSM alpha , PSM beta , and PSM gamma ) have been described. We report a fourth peptide (PSM delta ), which is a 23mer with the structure fMSIVSTIIEVVKTIVDIVKKFKK. The gene for each of the 4 peptides was introduced singly into Staphylococcus carnosus, and the PSM-like activity of culture medium and bacterial extract were significantly greater than those of the parent strain. PSM peptides from each of the S. carnosus-expressing strains were purified and analyzed by liquid chromatography-mass spectrometry. The products, which appeared to form aggregates, were active in the activation of human immunodeficiency virus type 1 long-terminal repeat and the production of tumor necrosis factor- alpha by the macrophage cell line THP-1. These findings suggest that PSM peptides are responsible, in part, for the modulin-like activity of staphylococci and may contribute to the development of severe staphylococcal sepsis. JF - Journal of Infectious Diseases AU - Otto, M AU - O'Mahoney, D S AU - Guina, T AU - Klebanoff, S J AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 748 EP - 755 VL - 190 IS - 4 SN - 0022-1899, 0022-1899 KW - modulin KW - Microbiology Abstracts B: Bacteriology KW - Macrophages KW - Sepsis KW - Tumor necrosis factor-^a KW - Staphylococcus carnosus KW - Cell lines KW - Staphylococcus epidermidis KW - Phenols KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18041997?accountid=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+Infectious+Diseases&rft.atitle=Activity+of+Staphylococcus+epidermidis+Phenol-Soluble+Modulin+Peptides+Expressed+in+Staphylococcus+carnosus&rft.au=Otto%2C+M%3BO%27Mahoney%2C+D+S%3BGuina%2C+T%3BKlebanoff%2C+S+J&rft.aulast=Otto&rft.aufirst=M&rft.date=2004-08-15&rft.volume=190&rft.issue=4&rft.spage=748&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&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 carnosus; Staphylococcus epidermidis; Phenols; Tumor necrosis factor-^a; Cell lines; Macrophages; Sepsis ER - TY - JOUR T1 - Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections AN - 18016175; 5982709 AB - Molecular factors that contribute to the emergence of new virulent bacterial subclones and epidemics are poorly understood. We hypothesized that analysis of a population-based strain sample of serotype M3 group A Streptococcus (GAS) recovered from patients with invasive infection by using genome-wide investigative methods would provide new insight into this fundamental infectious disease problem. Serotype M3 GAS strains (n = 255) cultured from patients in Ontario, Canada, over 11 years and representing two distinct infection peaks were studied. Genetic diversity was indexed by pulsed-field gel electrophoresis, DNA-DNA microarray, whole-genome PCR scanning, prophage genotyping, targeted gene sequencing, and single-nucleotide polymorphism genotyping. All variation in gene content was attributable to acquisition or loss of prophages, a molecular process that generated unique combinations of proven or putative virulence genes. Distinct serotype M3 genotypes experienced rapid population expansion and caused infections that differed significantly in character and severity. Molecular genetic analysis, combined with immunologic studies, implicated a 4-aa duplication in the extreme N terminus of M protein as a factor contributing to an epidemic wave of serotype M3 invasive infections. This finding has implications for GAS vaccine research. Genome-wide analysis of population-based strain samples cultured from clinically well defined patients is crucial for understanding the molecular events underlying bacterial epidemics. JF - Proceedings of the National Academy of Sciences, USA AU - Beres, Stephen B AU - Sylva, Gail L AU - Sturdevant, Daniel E AU - Granville, Chanel N AU - Liu, Mengyao AU - Ricklefs, Stacy M AU - Whitney, Adeline R AU - Parkins, Larye D AU - Hoe, Nancy P AU - Adams, Gerald J AU - Low, Donald E AU - Deleo, Frank R AU - Mcgeer, Allison AU - Musser, James M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT Y1 - 2004/08/10/ PY - 2004 DA - 2004 Aug 10 SP - 11833 EP - 11838 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 32 SN - 0027-8424, 0027-8424 KW - streptococci KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Streptococcus KW - Serotypes KW - Genetic diversity KW - Genotypes KW - Infection KW - Virulence KW - Epidemiology KW - J 02855:Human Bacteriology: Others KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18016175?accountid=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=Carcinogenesis&rft.atitle=PPARgamma+influences+susceptibility+to+DMBA-induced+mammary%2C+ovarian+and+skin+carcinogenesis&rft.au=Nicol%2C+Christopher+J%3BYoon%2C+Michung%3BWard%2C+Jerrold+M%3BYamashita%2C+Masamichi%3BFukamachi%2C+Katsumi%3BPeters%2C+Jeffrey+M%3BGonzalez%2C+Frank+J&rft.aulast=Nicol&rft.aufirst=Christopher&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1747&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 - Streptococcus; Virulence; Serotypes; Infection; Genetic diversity; Genotypes; Epidemiology ER - TY - JOUR T1 - Clastogenic effect for cigarette smoking but not areca quid chewing as measured by micronuclei in exfoliated buccal mucosal cells. AN - 66755882; 15279828 AB - The objective of this study was to use the micronuclei from exfoliated buccal mucosal cells to investigate the clastogenic effects of areca quid chewing and cigarette smoking, as well as the interaction between the two. The study population was selected from residents of seven villages recruited for a community-cohort study. A total of 141 subjects were recruited based on the regular consumption of cigarettes and betel quid. Salient personal characteristics were collected from interview using a specially designed questionnaire. Micronuclei were scored on Feulgen/fast green-stained smear preparations of exfoliated cells obtained by scraping the surface of the buccal mucosa. There was no significant interaction between the chewing of betel nut and cigarette smoking. Heavy smoking was positively associated with MN frequency, with areca quid chewing negatively associated. A significant positive trend was demonstrated for the relationship between MN frequency and either daily cigarette consumption or cumulative smoking pack-years. By contrast, negative trends were demonstrated for the analogous relationships with areca quid chewing. These results indicate that heavy smoking, but not areca quid chewing, increases MN formation. These findings suggest that the carcinogenesis of the oral cancers induced by areca quid chewing in Taiwan may be through a pathway other than genotoxicity. JF - Mutation research AU - Wu, Ping-An AU - Loh, Ching-Hui AU - Hsieh, Ling-Ling AU - Liu, Tsung-Yun AU - Chen, Chien-Jen AU - Liou, Saou-Hsing AD - Graduate Institute of Medical Sciences, National Defense Medical Center, National Defense University, Nei-Hu, Taipei, Taiwan, ROC. Y1 - 2004/08/08/ PY - 2004 DA - 2004 Aug 08 SP - 27 EP - 38 VL - 562 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Areca KW - Tobacco KW - Mouth Mucosa -- cytology KW - Smoking -- genetics KW - Micronuclei, Chromosome-Defective UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66755882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+inorganic+arsenic+exposure+induces+hepatic+global+and+individual+gene+hypomethylation%3A+implications+for+arsenic+hepatocarcinogenesis&rft.au=Chen%2C+Hua%3BLi%2C+Shuanfang%3BLiu%2C+Jie%3BDiwan%2C+Bhalchandra+A%3BBarrett%2C+JCarl%3BWaalkes%2C+Michael+P&rft.aulast=Chen&rft.aufirst=Hua&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1779&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Mutat Res. 2005 Apr 4;582(1-2):163-4; author reply 165-7 [15781221] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inter-rater agreement on chromosome 5 breakage in FISH-based mutagen sensitivity assays (MSAs). AN - 66754707; 15279836 AB - In chromosome breakage assays, validated, universal criteria for selection of cells and classification of chromosome aberrations may enhance their utility for cancer susceptibility screening. To standardize a fluorescence in situ hybridization (FISH) modification of the mutagen sensitivity assay (MSA), scoring criteria were evaluated by web-based validation. Two hundred digital FISH images were assigned random identification numbers. With this set of images, criteria for inclusion of cells and measurement of the frequency of abnormal cells were evaluated by eight observers, all of whom had five or more years of experience. Observers included doctoral and MS/BS level cytogeneticists, and were drawn from a randomized pool of 54 volunteers. Questions addressed were: (1) how uniformly were criteria applied to analysis of a standard digital FISH image set and (2) did concordance vary with educational level? These data suggest inter-rater agreement within a factor of 2 for average breakage frequency, but revealed greater variability in cell selection. These results aid in estimating the components of assay variance due to definitions, technical parameters and biological variables. JF - Mutation research AU - Barker, Peter E AU - Wang, Wendy AU - Wagner, Paul D AU - Pinsky, Paul AD - DNA Technologies Group, Biotechnology Division, Chemical Sciences and Technology Laboratory, NIST-NCI Biomarkers Validation Project, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899-8311, USA. peter.barker@nist.gov Y1 - 2004/08/08/ PY - 2004 DA - 2004 Aug 08 SP - 133 EP - 142 VL - 562 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Index Medicus KW - Humans KW - In Situ Hybridization, Fluorescence KW - Chromosome Aberrations KW - Mutagens -- toxicity KW - Observer Variation KW - Chromosomes, Human, Pair 5 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66754707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inter-rater+agreement+on+chromosome+5+breakage+in+FISH-based+mutagen+sensitivity+assays+%28MSAs%29.&rft.au=Barker%2C+Peter+E%3BWang%2C+Wendy%3BWagner%2C+Paul+D%3BPinsky%2C+Paul&rft.aulast=Barker&rft.aufirst=Peter&rft.date=2004-08-08&rft.volume=562&rft.issue=1-2&rft.spage=133&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 - 2004-09-16 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endoplasmic reticulum (ER) stress induced by a neurovirulent mouse retrovirus is associated with prolonged BiP binding and retention of a viral protein in the ER. AN - 66766043; 15178688 AB - Some murine retroviruses cause a spongiform neurodegenerative disease exhibiting pathology resembling that observed in transmissible spongiform encephalopathies. The neurovirulence of these "spongiogenic retroviruses" is determined by the sequence of their respective envelope proteins, although the mechanisms of neurotoxicity are not understood. We have studied a highly neurovirulent virus called FrCasE that causes a rapidly progressive form of this disease. Recently, transcriptional markers of endoplasmic reticulum (ER) stress were detected during the early preclinical period in the brains of FrCasE-infected mice. In contrast, ER stress was not observed in mice infected with an avirulent virus, F43, which carries a different envelope gene, suggesting a role for ER stress in disease pathogenesis. Here we have examined in NIH 3T3 cells the cause of this cellular stress response. The envelope protein of F43 bound BiP, a major ER chaperone, transiently and was processed normally through the secretory pathway. In contrast, the envelope protein of FrCasE bound to BiP for a prolonged period, was retained in the ER, and was degraded by the proteasome. Furthermore, engagement of the FrCasE envelope protein by ER quality control pathways resulted in decreased steady-state levels of this protein, relative to that of F43, both in NIH 3T3 cells and in the brains of infected mice. Thus, the ER stress induced by FrCasE appears to be initiated by inefficient folding of its viral envelope protein, suggesting that the neurodegenerative disease caused by this virus represents a protein misfolding disorder. JF - The Journal of biological chemistry AU - Dimcheff, Derek E AU - Faasse, Mark A AU - McAtee, Frank J AU - Portis, John L AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA. Y1 - 2004/08/06/ PY - 2004 DA - 2004 Aug 06 SP - 33782 EP - 33790 VL - 279 IS - 32 SN - 0021-9258, 0021-9258 KW - Heat-Shock Proteins KW - 0 KW - Molecular Chaperones KW - Multienzyme Complexes KW - RNA, Messenger KW - RNA, Viral KW - Viral Envelope Proteins KW - molecular chaperone GRP78 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Animals KW - Multienzyme Complexes -- metabolism KW - RNA, Messenger -- analysis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - NIH 3T3 Cells KW - Microscopy, Fluorescence KW - Mice, Inbred Strains KW - Cysteine Endopeptidases -- metabolism KW - Kinetics KW - Protein Folding KW - Brain -- ultrastructure KW - Cell Line KW - RNA, Viral -- analysis KW - Heat-Shock Proteins -- metabolism KW - Endoplasmic Reticulum -- metabolism KW - Endoplasmic Reticulum -- chemistry KW - Endoplasmic Reticulum -- virology KW - Viral Envelope Proteins -- chemistry KW - Molecular Chaperones -- metabolism KW - Prion Diseases -- virology KW - Retroviridae -- physiology KW - Viral Envelope Proteins -- metabolism KW - Retroviridae Infections -- metabolism KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66766043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endoplasmic+reticulum+%28ER%29+stress+induced+by+a+neurovirulent+mouse+retrovirus+is+associated+with+prolonged+BiP+binding+and+retention+of+a+viral+protein+in+the+ER.&rft.au=Dimcheff%2C+Derek+E%3BFaasse%2C+Mark+A%3BMcAtee%2C+Frank+J%3BPortis%2C+John+L&rft.aulast=Dimcheff&rft.aufirst=Derek&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33782&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 - 2004-10-25 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the role of ubiquitin-interacting motifs in ubiquitin binding and ubiquitylation. AN - 66765953; 15155768 AB - The ubiquitin-interacting motif (UIM) is a short peptide motif with the dual function of binding ubiquitin and promoting ubiquitylation. This motif is conserved throughout eukaryotes and is present in numerous proteins involved in a wide variety of cellular processes including endocytosis, protein trafficking, and signal transduction. We previously reported that the UIMs of epsin were both necessary and sufficient for its ubiquitylation. In this study, we found that many, but not all, UIM-containing proteins were ubiquitylated. When expressed as chimeric fusion proteins, most UIMs promoted ubiquitylation of the chimera. In contrast to previous studies, we found that UIMs do not exclusively promote monoubiquitylation but rather a mixture of mono-, multi-, and polyubiquitylation. However, UIM-dependent polyubiquitylation does not lead to degradation of the modified protein. UIMs also bind polyubiquitin chains of varying lengths and to different degrees, and this activity is required for UIM-dependent ubiquitylation. Mutational analysis of the UIM revealed specific amino acids that are important for both polyubiquitin binding and ubiquitin conjugation. Finally we provide evidence that UIM-dependent ubiquitylation inhibits the interaction of UIM-containing proteins with other ubiquitylated cellular proteins. Our results suggest a new model for the ubiquitylation of UIM-containing proteins. JF - The Journal of biological chemistry AU - Miller, Stephanie L H AU - Malotky, Erica AU - O'Bryan, John P AD - Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/08/06/ PY - 2004 DA - 2004 Aug 06 SP - 33528 EP - 33537 VL - 279 IS - 32 SN - 0021-9258, 0021-9258 KW - ANKIB1 protein, human KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - DNAJB2 protein, human KW - Endosomal Sorting Complexes Required for Transport KW - HSP40 Heat-Shock Proteins KW - Heat-Shock Proteins KW - Molecular Chaperones KW - Nerve Tissue Proteins KW - Nuclear Proteins KW - Oligopeptides KW - Peptide Fragments KW - Peptides KW - Phosphoproteins KW - Proteins KW - Recombinant Fusion Proteins KW - Repressor Proteins KW - Ubiquitin KW - Vesicular Transport Proteins KW - epsin KW - hepatocyte growth factor-regulated tyrosine kinase substrate KW - FLAG peptide KW - 98849-88-8 KW - MAP Kinase Kinase Kinase 1 KW - EC 2.7.11.25 KW - MAP Kinase Kinase Kinases KW - MAP3K1 protein, human KW - ATXN3 protein, human KW - EC 3.4.19.12 KW - Ataxin-3 KW - Index Medicus KW - Molecular Chaperones -- genetics KW - Molecular Chaperones -- metabolism KW - Humans KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Molecular Sequence Data KW - Embryo, Mammalian KW - Signal Transduction KW - Phosphoproteins -- metabolism KW - Heat-Shock Proteins -- metabolism KW - Vesicular Transport Proteins -- genetics KW - Phosphoproteins -- genetics KW - MAP Kinase Kinase Kinases -- genetics KW - Amino Acid Sequence KW - Nerve Tissue Proteins -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - Protein Binding KW - Structure-Activity Relationship KW - Binding Sites KW - MAP Kinase Kinase Kinases -- metabolism KW - Polymerase Chain Reaction KW - Endocytosis KW - Conserved Sequence KW - Transfection KW - Kidney KW - Nerve Tissue Proteins -- metabolism KW - Vesicular Transport Proteins -- metabolism KW - Peptides -- genetics KW - Heat-Shock Proteins -- genetics KW - Cell Line KW - Ubiquitin -- metabolism KW - Peptide Fragments -- chemistry KW - Peptide Fragments -- genetics KW - Peptide Fragments -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66765953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+the+role+of+ubiquitin-interacting+motifs+in+ubiquitin+binding+and+ubiquitylation.&rft.au=Miller%2C+Stephanie+L+H%3BMalotky%2C+Erica%3BO%27Bryan%2C+John+P&rft.aulast=Miller&rft.aufirst=Stephanie+L&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33528&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 - 2004-10-25 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A protein sequestering system reveals control of cellular programs by the transcriptional coactivator HCF-1. AN - 66764238; 15190068 AB - The mammalian transcriptional coactivator HCF-1 is a critical component of the multiprotein herpes simplex virus immediate early gene enhancer core complex. The protein has also been implicated in basic cellular processes such as cell-cycle progression, transcriptional coactivation, and mRNA processing. Functions have been attributed to HCF-1 primarily from analyses of protein-protein interactions and from the cell-cycle-arrested phenotype of an HCF-1 temperature-sensitive mutant. However, neither the mechanisms involved nor specific cellular transcriptional targets have been identified. As the protein is essential for cell viability and proliferation, a genetic system was developed to specifically sequester the nuclear factor in the cell cytoplasm in a regulated manner. This approach exhibits no significant cell toxicity yet clearly demonstrates the requirement of available nuclear HCF-1 for herpes simplex virus immediate early gene expression during productive infection. Additionally, cellular transcriptional events were identified that contribute to understanding the functions ascribed to the protein and implicate the protein in events that impact the regulation of critical cellular processes. JF - The Journal of biological chemistry AU - Khurana, Bharat AU - Kristie, Thomas M AD - Laboratory of Viral Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/08/06/ PY - 2004 DA - 2004 Aug 06 SP - 33673 EP - 33683 VL - 279 IS - 32 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - HCFC1 protein, human KW - Host Cell Factor C1 KW - Recombinant Fusion Proteins KW - Transcription Factors KW - Viral Proteins KW - Index Medicus KW - Virus Replication KW - Viral Proteins -- genetics KW - Oligonucleotide Array Sequence Analysis KW - HeLa Cells KW - Cell Nucleus -- metabolism KW - Humans KW - Temperature KW - Transcription, Genetic KW - Amino Acid Sequence KW - Binding Sites KW - Cell Survival KW - Actins -- genetics KW - Cells -- virology KW - Transfection KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Enhancer Elements, Genetic -- genetics KW - Cells -- ultrastructure KW - Mutation KW - Cells -- metabolism KW - Fluorescent Antibody Technique KW - Cell Division KW - Transcription Factors -- physiology KW - Gene Expression Regulation -- physiology KW - Cell Physiological Phenomena KW - Transcription Factors -- chemistry KW - Herpesvirus 1, Human -- physiology KW - Genes, Immediate-Early -- genetics KW - Transcription Factors -- genetics KW - Herpesvirus 1, Human -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66764238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+protein+sequestering+system+reveals+control+of+cellular+programs+by+the+transcriptional+coactivator+HCF-1.&rft.au=Khurana%2C+Bharat%3BKristie%2C+Thomas+M&rft.aulast=Khurana&rft.aufirst=Bharat&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33673&rft.isbn=&rft.btitle=&rft.title=Contemporary+topics+in+laboratory+animal+science&rft.issn=10600558&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-25 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CbpA, a DnaJ Homolog, Is a DnaK Co-chaperone, and Its Activity Is Modulated by CbpM AN - 18017104; 5963689 AB - The DnaK chaperone system, consisting of DnaK, DnaJ, and GrpE, remodels and refolds proteins during both normal growth and stress conditions. CbpA, one of several DnaJ analogs in Escherichia coli, is known to function as a multicopy suppressor for dnaJ mutations and to bind nonspecifically to DNA and preferentially to curved DNA. We found that CbpA functions as a DnaJ-like co- chaperone in vitro. CbpA acted in an ATP-dependent reaction with DnaK and GrpE to remodel inactive dimers of plasmid P1 RepA into monomers active in P1 DNA binding. Additionally, CbpA participated with DnaK in an ATP-dependent reaction to prevent aggregation of denatured rhodanese. The cbpA gene is in an operon with an open reading frame, yccD, which encodes a protein that has some homology to DafA of Thermus thermophilus. DafA is a protein required for the assembly of ring-like particles that contain trimers each of T. thermophilus DnaK, DnaJ, and DafA. The E. coli YccD was isolated because of its potential functional relationship to CbpA. Purified YccD specifically inhibited both the co-chaperone activity and the DNA binding activity of CbpA, suggesting that YccD modulates the activity of CbpA. We named the product of the yccD gene CbpM for "CbpA modulator." JF - Journal of Biological Chemistry AU - Chae, Chi AU - Sharma, Suveena AU - Hoskins, Joel R AU - Wickner, Sue AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland Y1 - 2004/08/06/ PY - 2004 DA - 2004 Aug 06 SP - 33147 EP - 33153 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 32 SN - 0021-9258, 0021-9258 KW - CbpM protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Suppressors KW - Escherichia coli KW - DnaK protein KW - Chaperones KW - Plasmids KW - CbpA protein KW - J 02726:RNA and ribosomes KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18017104?accountid=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=CbpA%2C+a+DnaJ+Homolog%2C+Is+a+DnaK+Co-chaperone%2C+and+Its+Activity+Is+Modulated+by+CbpM&rft.au=Chae%2C+Chi%3BSharma%2C+Suveena%3BHoskins%2C+Joel+R%3BWickner%2C+Sue&rft.aulast=Chae&rft.aufirst=Chi&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33147&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 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Suppressors; DnaK protein; Chaperones; CbpA protein; Plasmids; Escherichia coli ER - TY - JOUR T1 - Loss of Smad3 in acute T-cell lymphoblastic leukemia. AN - 66759392; 15295048 AB - The receptors for transforming growth factor beta (TGF-beta) and their signaling intermediates make up an important tumor-suppressor pathway. The role of one of these intermediates--Smad3--in the pathogenesis of lymphoid neoplasia is unknown. We measured Smad3 messenger RNA (mRNA) and protein in leukemia cells obtained at diagnosis from 19 children with acute leukemia, including 10 with T-cell acute lymphoblastic leukemia (ALL), 7 with pre-B-cell ALL, and 2 with acute nonlymphoblastic leukemia (ANLL). All nine exons of the SMAD3 gene (MADH3) were sequenced. Mice in which one or both alleles of Smad3 were inactivated were used to evaluate the role of Smad3 in the response of normal T cells to TGF-beta and in the susceptibility to spontaneous leukemogenesis in mice in which both alleles of the tumor suppressor p27Kip1 were deleted. Smad3 protein was absent in T-cell ALL but present in pre-B-cell ALL and ANLL. No mutations were found in the MADH3 gene in T-cell ALL, and Smad3 mRNA was present in T-cell ALL and normal T cells at similar levels. In mice, the loss of one allele for Smad3 impairs the inhibitory effect of TGF-beta on the proliferation of normal T cells and works in tandem with the homozygous inactivation of p27Kip1 to promote T-cell leukemogenesis. Loss of Smad3 protein is a specific feature of pediatric T-cell ALL. A reduction in Smad3 expression and the loss of p27Kip1 work synergistically to promote T-cell leukemogenesis in mice. Copyright 2004 Massachusetts Medical Society JF - The New England journal of medicine AU - Wolfraim, Lawrence A AU - Fernandez, Tania M AU - Mamura, Mizuko AU - Fuller, Walter L AU - Kumar, Rajesh AU - Cole, Diane E AU - Byfield, Stacey AU - Felici, Angelina AU - Flanders, Kathleen C AU - Walz, Thomas M AU - Roberts, Anita B AU - Aplan, Peter D AU - Balis, Frank M AU - Letterio, John J AD - Laboratory of Cell Regulation and Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md, USA. Y1 - 2004/08/05/ PY - 2004 DA - 2004 Aug 05 SP - 552 EP - 559 VL - 351 IS - 6 KW - Cdkn1b protein, mouse KW - 0 KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - Interleukin-2 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - SMAD3 protein, human KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Exons KW - Humans KW - Leukemia, Myeloid, Acute -- metabolism KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Gene Expression KW - Interleukin-2 -- biosynthesis KW - Child KW - Mice KW - Sequence Analysis, DNA KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- genetics KW - Mice, Knockout KW - Gene Deletion KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- metabolism KW - Leukemia, Myeloid, Acute -- genetics KW - Adult KW - Signal Transduction KW - Leukemia, T-Cell -- genetics KW - Trans-Activators -- metabolism KW - Leukemia-Lymphoma, Adult T-Cell -- metabolism KW - Leukemia, T-Cell -- metabolism KW - Tumor Suppressor Proteins -- genetics KW - DNA-Binding Proteins -- genetics KW - Leukemia-Lymphoma, Adult T-Cell -- genetics KW - Cell Cycle Proteins -- metabolism KW - T-Lymphocytes -- metabolism KW - Cell Cycle Proteins -- genetics KW - Trans-Activators -- genetics KW - Tumor Suppressor Proteins -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66759392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+Smad3+in+acute+T-cell+lymphoblastic+leukemia.&rft.au=Wolfraim%2C+Lawrence+A%3BFernandez%2C+Tania+M%3BMamura%2C+Mizuko%3BFuller%2C+Walter+L%3BKumar%2C+Rajesh%3BCole%2C+Diane+E%3BByfield%2C+Stacey%3BFelici%2C+Angelina%3BFlanders%2C+Kathleen+C%3BWalz%2C+Thomas+M%3BRoberts%2C+Anita+B%3BAplan%2C+Peter+D%3BBalis%2C+Frank+M%3BLetterio%2C+John+J&rft.aulast=Wolfraim&rft.aufirst=Lawrence&rft.date=2004-08-05&rft.volume=351&rft.issue=6&rft.spage=552&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-10 N1 - Date created - 2004-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2004 Aug 5;351(6):528-30 [15295044] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular and Cellular Determinants of Skeletal Muscle Atrophy and Hypertrophy AN - 19947536; 5969558 AB - The maintenance of adult skeletal muscle mass is ensured by physical exercise. Accordingly, physiological and pathological situations characterized by either impaired motor neuron activity, reduced gravity (microgravity during space flights), or reduced physical activity result in loss of muscle mass. Furthermore, a plethora of clinical conditions, including cancer, sepsis, diabetes, and AIDS, are associated with varying degrees of muscle atrophy. The cellular and molecular pathways responsible for maintaining the skeletal muscle mass are not well defined. Nonetheless, studies aimed at the understanding of the mechanisms underlying either muscular atrophy or hypertrophy have begun to identify the physiological determinants and clarify the molecular pathways responsible for the maintenance of muscle mass. JF - Signal Transduction Knowledge Environment AU - Sartorelli, Vittorio AU - Fulco, Marcella AD - Muscle Gene Expression Group Laboratory of Muscle Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD Y1 - 2004/08/03/ PY - 2004 DA - 2004 Aug 03 SP - re11 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 USA, [mailto:membership@aaas.org], [URL:http://www.aaas.org] VL - 2004 IS - 244 SN - 1525-8882, 1525-8882 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Space flight KW - Gravity KW - Physical activity KW - Cancer KW - Physical training KW - Diabetes mellitus KW - Motor neurons KW - Microgravity KW - Sepsis KW - Hypertrophy KW - Atrophy KW - Skeletal muscle KW - V 22360:AIDS and HIV KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19947536?accountid=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=Cytometry+Part+B&rft.atitle=Multiplex+bead+array+assays+for+detection+of+soluble+cytokines%3A+Comparisons+of+sensitivity+and+quantitative+values+among+kits+from+multiple+manufacturers&rft.au=Khan%2C+Sameena+S%3BSmith%2C+Meghan+S%3BReda%2C+Debra%3BSuffredini%2C+Anthony+F%3BMcCoy+Jr%2C+J+Philip&rft.aulast=Khan&rft.aufirst=Sameena&rft.date=2004-09-01&rft.volume=61B&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+B&rft.issn=15524949&rft_id=info:doi/10.1002%2Fcyto.b.20021 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-06-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Acquired immune deficiency syndrome; Space flight; Gravity; Physical activity; Cancer; Physical training; Diabetes mellitus; Microgravity; Motor neurons; Hypertrophy; Sepsis; Skeletal muscle; Atrophy ER - TY - JOUR T1 - Neural stem cells redefined. A FACS perspective AN - 856761486; 13859493 AB - Using the generally accepted ontogenetic definition, neural stem cells (NSCs) are characterized as undifferentiated cells originating from the neuroectoderm that have the capacity both to perpetually self-renew without differentiating and to generate multiple types of lineage-restricted progenitors (LRP). LRPs can themselves undergo limited self-renewal, then ultimately differentiate into highly specialized cells that compose the nervous system. However, this physiologically delimited definition of NSCs has been increasingly blurred in the current state of the field, as the great majority of studies have retrospectively inferred the existence of NSCs based on their deferred functional capability rather than prospectively identifying the actual cells that created the outcome. Further complicating the matter is the use of a wide variety of neuroepithelial or neurosphere preparations as a source of putative NSCs, without due consideration that these preparations are themselves composed of heterogeneous populations of both NSCs and LRPs. This article focuses on recent attempts using FACS strategies to prospectively isolate NSCs from different types of LRPs as they appear in vivo and reveals the contrasting differences among these populations at molecular, phenotypic, and functional levels. Thus, the strategies presented here provide a framework for more precise studies of NSC and LRP cell biology in the future. JF - Molecular Neurobiology AU - Maric, Dragan AU - Barker, Jeffery L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 20892, Bethesda, MD, maricd@ninds.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 49 EP - 76 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 30 IS - 1 SN - 0893-7648, 0893-7648 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Flow cytometry KW - Nervous system KW - Neuroectoderm KW - Ontogeny KW - neurospheres KW - Neural stem cells KW - N3 11007:Neurobiology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856761486?accountid=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=Molecular+Neurobiology&rft.atitle=Neural+stem+cells+redefined.+A+FACS+perspective&rft.au=Maric%2C+Dragan%3BBarker%2C+Jeffery+L&rft.aulast=Maric&rft.aufirst=Dragan&rft.date=2004-08-01&rft.volume=30&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Molecular+Neurobiology&rft.issn=08937648&rft_id=info:doi/10.1385%2FMN%3A30%3A1%3A049 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Flow cytometry; Nervous system; Neuroectoderm; Ontogeny; neurospheres; Neural stem cells DO - http://dx.doi.org/10.1385/MN:30:1:049 ER - TY - JOUR T1 - Toxicity of commonly-used antimalarial drugs. AN - 734180898; 17291978 JF - Travel medicine and infectious disease AU - Berman, Jonathan AD - Office of Clinical and Regulatory Affairs, National Center for Complementary and Alternative Medicine, National Institutes of Health, 6707 Democracy Boulevard, Suite 401, Bethesda, MD 20892, USA. PY - 2004 SP - 171 EP - 184 VL - 2 IS - 3-4 SN - 1477-8939, 1477-8939 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/734180898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Travel+medicine+and+infectious+disease&rft.atitle=Toxicity+of+commonly-used+antimalarial+drugs.&rft.au=Berman%2C+Jonathan&rft.aulast=Berman&rft.aufirst=Jonathan&rft.date=2004-08-01&rft.volume=2&rft.issue=3-4&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Travel+medicine+and+infectious+disease&rft.issn=14778939&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2012-10-02 N1 - Date created - 2007-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic potential of interleukin-6 in preventing obesity- and alcohol-associated fatty liver transplant failure. AN - 67243330; 15670667 AB - Donor organ shortage significantly hinders orthotopic liver transplantation therapy, the only effective treatment for chronic end-stage liver disease and acute liver failure. Further complicating this matter is the prevalence of steatosis in 13% to 50% of donor livers obtained from obese and alcoholic individuals. When transplanted, these livers are associated with primary nonfunction and an elevated risk of dysfunction. New therapeutic approaches to render marginal fatty livers worthy for clinical transplantation are actively being sought. Study findings obtained from my group show that in vitro treatment with interleukin-6 (IL-6) dramatically reduces mortality, liver injury, and necrapoptosis in steatotic Zucker rat liver isografts. Findings of additional studies indicate that IL-6 induces hepatoprotection of steatotic liver isografts by preventing sinusoidal endothelial cell damage and, consequently, the amelioration of hepatic microcirculation, and by protecting against hepatocyte death, which is likely mediated through activation of signal transducer and activator of transcription 3/Bcl-x(L). Finally, in vitro IL-6 treatment also prevents mortality associated with alcoholic fatty liver transplants. Relative to the protective effect of IL-6 on steatotic Zucker rat liver, IL-6 is less effective in alcoholic fatty livers, which may be due to the inhibitory effects of ethanol on IL-6 activation of signal transducer and activator of transcription 3 in hepatocytes and sinusoidal endothelial cells. Collectively, these results support the assertion that in vitro IL-6 treatment of steatotic livers may render allografts usable for clinical transplantation, thereby decreasing the gap between the short supply of cadaver liver allografts and high demands for replacement livers. Higher concentrations of IL-6 may be required to protect against alcoholic fatty liver isograft injury because alcohol inhibits IL-6 signaling in the liver. JF - Alcohol (Fayetteville, N.Y.) AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Park Building Room 120, 12420 Parklawn Drive, MSC 8115, Bethesda, MD 20892, USA. bgao@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 59 EP - 65 VL - 34 IS - 1 SN - 0741-8329, 0741-8329 KW - Interleukin-6 KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Prevalence KW - Obesity -- drug therapy KW - Fatty Liver, Alcoholic -- surgery KW - Interleukin-6 -- therapeutic use KW - Fatty Liver, Alcoholic -- epidemiology KW - Obesity -- surgery KW - Graft Rejection -- metabolism KW - Obesity -- epidemiology KW - Liver Transplantation -- adverse effects KW - Graft Rejection -- prevention & control KW - Fatty Liver, Alcoholic -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67243330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Therapeutic+potential+of+interleukin-6+in+preventing+obesity-+and+alcohol-associated+fatty+liver+transplant+failure.&rft.au=Gao%2C+Bin&rft.aulast=Gao&rft.aufirst=Bin&rft.date=2004-08-01&rft.volume=34&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-09 N1 - Date created - 2005-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenocarcinoma of ethmoid sinus: an occupational disease. AN - 67242639; 15688904 AB - Sinonasal tumours, particularly those of ethmoidal origin, are rare neoplasms, of which adenocarcinoma is the most frequent histotype in Europe. The association between sinonasal malignancies and exposure to wood or leather dusts has been widely documented, however, the precise tumour site and histology has seldom been reported. In the present study, exposure to wood or leather dusts was investigated in 499 patients diagnosed with sinonasal tumours, who were treated at the Head and Neck Surgery Department of the National Cancer Institute of Milan, Italy, between 1987 and 2001. The original tumour site and histology were carefully assessed. Of the 499 patients evaluated, 249 had ethmoidal tumours; 124 of which adenocarcinomas, affecting 115 males; 9 females. Of the males with adenocarcinoma, 90.4% had been exposed to wood or leather dusts; 16.3% of these had only been exposed for a short time and long before onset of the disease (median exposure 11 years; median latency 31 years). Of the remaining 125 patients with ethmoidal tumours other than adenocarcinomas, only 2 (1.6%) had ever been exposed to these dusts. Non-ethmoidal sinonasal tumours were seen in 250 cases; 17 of these (6.8%) were adenocarcinomas; no exposure to wood or leather dusts was reported in any of these patients. Ethmoid proved to be the sinonasal site affected by adenocarcinomas induced by exposure to wood or leather dusts. Even brief exposure, which may have occurred a very long time before onset of the disease, seems to be sufficient to increase the incidence of this tumour type. No significant correlation was observed between exposure and either non-ethmoidal sinonasal neoplasms or ethmoidal tumours other than adenocarcinomas. JF - Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale AU - Bimbi, G AU - Saraceno, M Squadrelli AU - Riccio, S AU - Gatta, G AU - Licitra, L AU - Cantù, G AD - Head and Neck Surgery Department, National Cancer Institute, Milan, Italy. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 199 EP - 203 VL - 24 IS - 4 SN - 0392-100X, 0392-100X KW - Dust KW - 0 KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Paranasal Sinus Neoplasms -- pathology KW - Adenocarcinoma -- etiology KW - Occupational Diseases -- etiology KW - Occupational Exposure -- adverse effects KW - Ethmoid Sinus -- pathology KW - Paranasal Sinus Neoplasms -- surgery KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67242639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+otorhinolaryngologica+Italica+%3A+organo+ufficiale+della+Societa+italiana+di+otorinolaringologia+e+chirurgia+cervico-facciale&rft.atitle=Adenocarcinoma+of+ethmoid+sinus%3A+an+occupational+disease.&rft.au=Bimbi%2C+G%3BSaraceno%2C+M+Squadrelli%3BRiccio%2C+S%3BGatta%2C+G%3BLicitra%2C+L%3BCant%C3%B9%2C+G&rft.aulast=Bimbi&rft.aufirst=G&rft.date=2004-08-01&rft.volume=24&rft.issue=4&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Acta+otorhinolaryngologica+Italica+%3A+organo+ufficiale+della+Societa+italiana+di+otorinolaringologia+e+chirurgia+cervico-facciale&rft.issn=0392100X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-16 N1 - Date created - 2005-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Role of fatty liver, dietary fatty acid supplements, and obesity in the progression of alcoholic liver disease: introduction and summary of the symposium. AN - 67226544; 15670659 AB - Alcoholic liver disease is a major cause of illness and death in the United States. In the initial stages of the disease, fat accumulation in hepatocytes leads to the development of fatty liver (steatosis), which is a reversible condition. If alcohol consumption is continued, steatosis may progress to hepatitis and fibrosis, which may lead to liver cirrhosis. Alcoholic fatty liver has long been considered benign; however, increasing evidence supports the idea that it is a pathologic condition. Blunting of the accumulation of fat within the liver during alcohol consumption may block or delay the progression of fatty liver to hepatitis and fibrosis. To achieve this goal, it is important to understand the underlying biochemical and molecular mechanisms by which chronic alcohol consumption leads to fat accumulation in the liver and fatty liver progresses to hepatitis and fibrosis. In addition to alcohol consumption, dietary fatty acids and obesity have been shown to affect the degree of fat accumulation within the liver. Again, it is important to know how these factors modulate the progression of alcoholic liver disease. The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on "Role of Fatty Liver, Dietary Fatty Acid Supplements, and Obesity in the Progression of Alcoholic Liver Disease" in Bethesda, Maryland, USA, October 2003. The following is a summary of the symposium. Alcoholic fatty liver is a pathologic condition that may predispose the liver to further injury (hepatitis and fibrosis) by cytochrome P450 2E1 induction, free radical generation, lipid peroxidation, nuclear factor-kappa B activation, and increased transcription of proinflammatory mediators, including tumor necrosis factor-alpha. Increased acetaldehyde production and lipopolysaccharide-induced Kupffer cell activation may further exacerbate liver injury. Acetaldehyde may promote hepatic fat accumulation by impairing the ability of peroxisome proliferator-activated receptor alpha to bind DNA, and by increasing the synthesis of sterol regulatory binding protein-1. Unsaturated fatty acids (corn oil, fish oil) exacerbate alcoholic liver injury by accentuating oxidative stress, whereas saturated fatty acids are protective. Polyenylphosphatidylcholine may prevent liver injury by down-regulating cytochrome P450 2E1 activity, attenuating oxidative stress, reducing the number of activated hepatic stellate cells, and up-regulating collagenase activity. Nonalcoholic steatohepatitis may develop through several mechanisms, such as oxidative stress, mitochondrial dysfunction and associated impaired fat metabolism, dysregulated cytokine metabolism, insulin resistance, and altered methionine/S-adenosylmethionine/homocysteine metabolism. Obesity (adipose tissue) may contribute to the development of alcoholic liver disease by generating free radicals, increasing tumor necrosis factor-alpha production, inducing insulin resistance, and producing fibrogenic agents, such as angiotensin II, norepinephrine, neuropeptide Y, and leptin. Finally, alcoholic fatty liver transplant failure may be linked to oxidative stress. In vitro treatment of fatty livers with interleukin-6 may render allografts safer for clinical transplantation. JF - Alcohol (Fayetteville, N.Y.) AU - Purohit, Vishnudutt AU - Russo, Denise AU - Coates, Paul M Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 3 EP - 8 VL - 34 IS - 1 KW - Fatty Acids KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Disease Progression KW - Fatty Liver, Alcoholic -- complications KW - Obesity -- pathology KW - Fatty Acids -- adverse effects KW - Fatty Acids -- physiology KW - Fatty Liver, Alcoholic -- pathology KW - Dietary Supplements -- adverse effects KW - Obesity -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67226544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Role+of+fatty+liver%2C+dietary+fatty+acid+supplements%2C+and+obesity+in+the+progression+of+alcoholic+liver+disease%3A+introduction+and+summary+of+the+symposium.&rft.au=Purohit%2C+Vishnudutt%3BRusso%2C+Denise%3BCoates%2C+Paul+M&rft.aulast=Purohit&rft.aufirst=Vishnudutt&rft.date=2004-08-01&rft.volume=34&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-09 N1 - Date created - 2005-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical applications of genetics in sporadic cancers. AN - 66985085; 15491025 AB - To describe how genetic information shapes our understanding of carcinogenesis; how genetic information influences recommendations for cancer screening, prevention, diagnosis, and treatment; and how genetic information may affect the prognosis of patients with cancer and the monitoring of anticancer treatment. Medical and nursing literature, textbooks, Internet websites. The Human Genome Project has taken oncology one step further toward accurate diagnosis and treatment of many forms of cancer. There are many genetic traits that can be associated with increased cancer risk, diagnosis, and selection of treatments. Oncology nursing practice is directly affected by the developments of medical genetics. The information gained can be used by nurses at all stages of the cancer continuum when administering these new therapies. JF - Seminars in oncology nursing AU - Kwitkowski, Virginia E AU - Daub, Janine R AD - National Cancer Institute, Center for Cancer Research, Medical Oncology Clinical Research Unit, Bethesda, MD 20892-1906, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 155 EP - 163 VL - 20 IS - 3 SN - 0749-2081, 0749-2081 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Nursing KW - Nursing Methodology Research KW - Nursing Assessment KW - Risk Factors KW - Humans KW - Databases, Genetic KW - Antineoplastic Agents -- therapeutic use KW - Neoplasms -- diagnosis KW - Neoplasms -- nursing KW - Oncology Nursing -- standards KW - Human Genome Project -- organization & administration KW - Neoplasms -- genetics KW - Oncology Nursing -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66985085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology+nursing&rft.atitle=Clinical+applications+of+genetics+in+sporadic+cancers.&rft.au=Kwitkowski%2C+Virginia+E%3BDaub%2C+Janine+R&rft.aulast=Kwitkowski&rft.aufirst=Virginia&rft.date=2004-08-01&rft.volume=20&rft.issue=3&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology+nursing&rft.issn=07492081&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-23 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic effect of root extract of Tiliacora racemosa and oil of Semecarpus anacardium nut in human tumour cells. AN - 66984206; 15476314 AB - Tiliacora racemosa and Semecarpus anacardium, the two plants frequently used in Ayurvedic medicine for the treatment of cancerous diseases, have been selected to examine their action in four human tumour cell lines: acute myeloblastic leukaemia (HL-60), chronic myelogenic leukaemia (K-562), breast adenocarcinoma (MCF-7) and cervical epithelial carcinoma (HeLa). In cells grown in appropriate media the ethanol extract of T. racemosa root, the total alkaloids isolated from this organ and S. anacardium nut oil prepared according to the Ayurvedic principle were found to have cytotoxic activity. The alkaloid fraction from T. racemosa had maximum cytotoxicity and was effective against all four cell lines. S. anacardium oil was cytotoxic only in leukaemic cells. These herbal preparations were not cytotoxic towards normal human lymphocytes, suggesting their action is specific for tumour cells. On microscopic examination the cells treated with these agents exhibited characteristic morphological features of apoptosis, such as cell shrinkage, and the formation of apoptotic bodies. Fluorescent staining with propidium iodide revealed distinct chromatin condensation and nuclear fragmentation. The apoptotic index paralleled the cytotoxic parameters, and fragmented DNA extracted free of genomic DNA from treated cells displayed a typical ladder pattern on gel electrophoresis. Apoptosis induced by alkaloids and phenolics, the active principles present in T. racemosa and S. anacardium, respectively, was found to be mediated by the activation of caspases. Copyright (c) 2004 John Wiley & Sons, Ltd. JF - Phytotherapy research : PTR AU - Chakraborty, Sutapa AU - Roy, Madhumita AU - Taraphdar, Amit K AU - Bhattacharya, R K AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 595 EP - 600 VL - 18 IS - 8 SN - 0951-418X, 0951-418X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Plant Extracts KW - Plant Oils KW - Index Medicus KW - Plant Roots KW - HeLa Cells -- drug effects KW - HL-60 Cells -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Apoptosis -- drug effects KW - DNA Fragmentation -- drug effects KW - Cell Line, Tumor -- drug effects KW - Fruit KW - K562 Cells -- drug effects KW - Medicine, Ayurvedic KW - Plant Oils -- therapeutic use KW - Plant Extracts -- pharmacology KW - Phytotherapy KW - Semecarpus KW - Plant Oils -- pharmacology KW - Plants, Medicinal KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Plant Oils -- administration & dosage KW - Plant Extracts -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Plant Extracts -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66984206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Phytotherapy+research+%3A+PTR&rft.atitle=Cytotoxic+effect+of+root+extract+of+Tiliacora+racemosa+and+oil+of+Semecarpus+anacardium+nut+in+human+tumour+cells.&rft.au=Chakraborty%2C+Sutapa%3BRoy%2C+Madhumita%3BTaraphdar%2C+Amit+K%3BBhattacharya%2C+R+K&rft.aulast=Chakraborty&rft.aufirst=Sutapa&rft.date=2004-08-01&rft.volume=18&rft.issue=8&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Phytotherapy+research+%3A+PTR&rft.issn=0951418X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-02 N1 - Date created - 2004-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetics and oncology nursing. AN - 66982253; 15491027 AB - To review oncology nursing practice in the genetic era, how genetic information is used across the cancer care continuum, practice guidelines, and opportunities for genetic nursing education. Published articles. Genetic information in oncology health care is used not only to predict risk but to elucidate disease biology, explain individual variation in vulnerability to environmental carcinogens, diagnose and characterize malignancies, design treatment regimens specific to a cancer's genetic fingerprint, develop new, therapeutic modalities, and clarify modulators of drug metabolism, efficacy, and interactions. With current and emerging genetic discoveries, all oncology nurses will use genetic information in their practice. JF - Seminars in oncology nursing AU - Calzone, Kathleen A AU - Masny, Agnes AD - National Cancer Institute/Center for Cancer Research/Genetics Branch, Bethesda, MD 20883-5105, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 178 EP - 185 VL - 20 IS - 3 SN - 0749-2081, 0749-2081 KW - Index Medicus KW - Nursing KW - Nursing Methodology Research KW - Education, Nursing, Continuing -- standards KW - Nursing Assessment KW - Human Genome Project KW - Risk Factors KW - Humans KW - Practice Guidelines as Topic KW - Nurse-Patient Relations KW - Clinical Competence KW - Neoplasms -- diagnosis KW - Neoplasms -- nursing KW - Oncology Nursing -- standards KW - Nurse's Role KW - Neoplasms -- genetics KW - Oncology Nursing -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66982253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology+nursing&rft.atitle=Genetics+and+oncology+nursing.&rft.au=Calzone%2C+Kathleen+A%3BMasny%2C+Agnes&rft.aulast=Calzone&rft.aufirst=Kathleen&rft.date=2004-08-01&rft.volume=20&rft.issue=3&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology+nursing&rft.issn=07492081&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-23 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of the current population survey to characterize subpopulations of continued smokers: a national perspective on the "hardcore" smoker phenomenon. AN - 66884421; 15370158 AB - The existence of "hardcore" smokers, those most likely to have substantial difficulty quitting, may have far reaching impact on how to best allocate cessation resources. It has been suggested that hardcore smokers make up only a small fraction of current smokers and therefore do not represent a significant public health problem. However, little is known about the prevalence and nature of this subgroup of smokers in the United States. Based on a national sample, the 1998-1999 Tobacco Use Supplement to the Current Population Survey, we categorized, based on smoking pattern, groups of current smokers who were over age 25 years (N=33,568). We compared hardcore smokers with other groups of current smokers on demographic, environmental, and smoking variables to assess whether hardcore smokers represent a unique group. Hardcore smokers were defined as established daily smokers, consuming 15 or more cigarettes per day with no reported history of quit attempts. Hardcore smokers represent 13.7% of all current smokers and 17.6% of all established smokers. They are more likely to be male, unmarried, not in the work force, and have lower education. They also are more likely to have started smoking at a younger age, smoke more, and are less likely to report contact with smoking restrictions. This analysis suggests that hardcore smokers are distinct from other groups of smokers. These results also indicate that hardcore smokers account for a substantial proportion of smokers and as such may represent a significant public health challenge that needs to be addressed. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Augustson, Erik AU - Marcus, Stephen AD - Tobacco Control and Research Branch, DCCPS National Cancer Institute, Bethesda, MD 20892-8318, USA. augustse@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 621 EP - 629 VL - 6 IS - 4 SN - 1462-2203, 1462-2203 KW - Index Medicus KW - Severity of Illness Index KW - Age of Onset KW - Risk Factors KW - Humans KW - Smoking Cessation KW - Health Surveys KW - Adult KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Tobacco Use Disorder -- epidemiology KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66884421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Use+of+the+current+population+survey+to+characterize+subpopulations+of+continued+smokers%3A+a+national+perspective+on+the+%22hardcore%22+smoker+phenomenon.&rft.au=Augustson%2C+Erik%3BMarcus%2C+Stephen&rft.aulast=Augustson&rft.aufirst=Erik&rft.date=2004-08-01&rft.volume=6&rft.issue=4&rft.spage=621&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-02 N1 - Date created - 2004-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Management of patients receiving antithymocyte globulin for aplastic anemia and myelodysplastic syndrome. AN - 66854243; 15354924 AB - Antithymocyte globulin (ATG) is used commonly in patients with severe aplastic anemia and those undergoing renal transplant. Its utility also is being explored in the treatment of myelodysplastic syndrome, conditioning regimens for hematopoietic stem cell transplant, and prophylaxis of graft-versus-host disease. As indications for ATG expand, knowledge regarding its administration and management of associated toxicities is needed. These toxicities range from life-threatening anaphylaxis associated with the infusion to flu-like symptoms that occur one to two weeks after the infusion. Adverse effects are classified according to the severity and system impacted. Mild toxicities respond to comfort measures and include fever, chills, urticarial rash, and vomiting. Moderate toxicities require acute interventions and include fluid-responsive hypotension, nonischemic chest pain, and reversible oxygen desaturation. Severe toxicities require intensive support and include those refractory to earlier intervention. Management of these toxicities usually is limited to fluid resuscitation and noninvasive monitoring. Occurrence of infusion-related toxicities may require premature discontinuation of therapy. Therefore, an educated healthcare team and interdisciplinary clinical management guidelines are important to ensure the safe administration and complete course of ATG. JF - Clinical journal of oncology nursing AU - Bevans, Margaret F AU - Shalabi, Reem A AD - Clinical Center, National Institutes of Health, Bethesda, MD, USA. mbevans@cc.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 377 EP - 382 VL - 8 IS - 4 SN - 1092-1095, 1092-1095 KW - Antilymphocyte Serum KW - 0 KW - Immunosuppressive Agents KW - Nursing KW - Patient Education as Topic KW - Infusions, Intravenous KW - Humans KW - Drug Monitoring KW - Adult KW - Desensitization, Immunologic KW - Child KW - Drug Hypersensitivity -- therapy KW - Antilymphocyte Serum -- adverse effects KW - Drug Hypersensitivity -- etiology KW - Anemia, Aplastic -- drug therapy KW - Myelodysplastic Syndromes -- drug therapy KW - Immunosuppressive Agents -- therapeutic use KW - Antilymphocyte Serum -- therapeutic use KW - Immunosuppressive Agents -- adverse effects KW - Drug Hypersensitivity -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66854243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+journal+of+oncology+nursing&rft.atitle=Management+of+patients+receiving+antithymocyte+globulin+for+aplastic+anemia+and+myelodysplastic+syndrome.&rft.au=Bevans%2C+Margaret+F%3BShalabi%2C+Reem+A&rft.aulast=Bevans&rft.aufirst=Margaret&rft.date=2004-08-01&rft.volume=8&rft.issue=4&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Clinical+journal+of+oncology+nursing&rft.issn=10921095&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-28 N1 - Date created - 2004-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin J Oncol Nurs. 2004 Dec;8(6):583; author reply 583 [15637953] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Marine toxins and nonmarine toxins: convergence or symbiotic organisms? AN - 66826222; 15332834 AB - Bioactive marine natural products occur only rarely in nonmarine sources. The converse also is true. Divergent evolutionary pathways for the biosynthesis of bioactive secondary metabolites seem to be the rule. Marine biosynthetic pathways lead to a wide variety of different structural classes, among which polyethers, macrolides, terpenes, unusual amino acids/peptides, and alkaloids are notable. Nonmarine biosynthetic pathways also lead to a similar wide variety of structural classes. However, the structures are usually quite different from the marine analogues. The alkaloids of plants are notable, but again there appears little convergence between the marine and nonmarine alkaloids. However, tetrodotoxin, a remarkable, highly polar, marine alkaloid, does occur in various amphibians. The occurrence and possible origin of tetrodotoxin and congeners, including chiriquitoxin, and of the saxitoxin analogue zetekitoxin in amphibians are reviewed. JF - Journal of natural products AU - Daly, John W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, Maryland 20892-0820, USA. jdaly@nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 1211 EP - 1215 VL - 67 IS - 8 SN - 0163-3864, 0163-3864 KW - Alkaloids KW - 0 KW - Amphibian Venoms KW - Fish Venoms KW - Marine Toxins KW - Quinazolines KW - Toxins, Biological KW - zetekitoxin AB KW - tetrodonic acid KW - 3270-35-7 KW - Saxitoxin KW - 35523-89-8 KW - Tetrodotoxin KW - 4368-28-9 KW - chiriquitoxin KW - 61132-15-8 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Tetrodotoxin -- chemistry KW - Quinazolines -- chemistry KW - Saxitoxin -- analogs & derivatives KW - Saxitoxin -- chemistry KW - Fish Venoms -- chemistry KW - Amphibian Venoms -- chemistry KW - Alkaloids -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66826222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+natural+products&rft.atitle=Marine+toxins+and+nonmarine+toxins%3A+convergence+or+symbiotic+organisms%3F&rft.au=Daly%2C+John+W&rft.aulast=Daly&rft.aufirst=John&rft.date=2004-08-01&rft.volume=67&rft.issue=8&rft.spage=1211&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 completed - 2004-10-18 N1 - Date created - 2004-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ovarian cancer risk associated with varying causes of infertility. AN - 66773545; 15302291 AB - To evaluate the risk of ovarian cancer as related to underlying causes of infertility. Retrospective observational cohort study. Five large reproductive endocrinology practices. A total of 12,193 women evaluated for infertility between 1965 and 1988. None. Ovarian cancer ascertained through 1999. With 45 identified ovarian cancers, this cohort of infertility patients demonstrated a significantly higher rate of ovarian cancer than the general female population (standardized incidence ratio [SIR] = 1.98; 95% confidence interval [CI], 1.4-2.6). The risk was higher for patients with primary infertility (SIR = 2.73) than for those with secondary infertility (SIR = 1.44), and it was particularly high for patients who never subsequently conceived (SIR = 3.33). Women with endometriosis had the highest risk (SIR = 2.48; 95% CI, 1.3-4.2), with a further elevated risk among those with primary infertility (4.19, 2.0-7.7). Comparisons among the infertile women, which allowed calculation of rate ratios (RRs) after adjustment for multiple factors, also showed links with endometriosis. Compared with women with secondary infertility without endometriosis, patients with primary infertility and endometriosis had a RR of 2.72 (95% CI, 1.1-6.7). Determination of ovarian cancer risk should take into account the type of infertility (primary vs. secondary) and underlying causes. Further study of endometriosis may provide insights into ovarian carcinogenesis. JF - Fertility and sterility AU - Brinton, Louise A AU - Lamb, Emmet J AU - Moghissi, Kamran S AU - Scoccia, Bert AU - Althuis, Michelle D AU - Mabie, Jerome E AU - Westhoff, Carolyn L AD - Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, Bethesda, MD 20852, USA. Brinton@nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 405 EP - 414 VL - 82 IS - 2 SN - 0015-0282, 0015-0282 KW - Index Medicus KW - Medical Records KW - Risk Factors KW - Humans KW - Cohort Studies KW - Retrospective Studies KW - Follow-Up Studies KW - Time Factors KW - Female KW - Survival Analysis KW - Ovarian Neoplasms -- mortality KW - Infertility, Female -- complications KW - Ovarian Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66773545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fertility+and+sterility&rft.atitle=Ovarian+cancer+risk+associated+with+varying+causes+of+infertility.&rft.au=Brinton%2C+Louise+A%3BLamb%2C+Emmet+J%3BMoghissi%2C+Kamran+S%3BScoccia%2C+Bert%3BAlthuis%2C+Michelle+D%3BMabie%2C+Jerome+E%3BWesthoff%2C+Carolyn+L&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2004-08-01&rft.volume=82&rft.issue=2&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Fertility+and+sterility&rft.issn=00150282&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-15 N1 - Date created - 2004-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of the cyclin-dependent kinase inhibitor flavopiridol in combination with docetaxel in patients with metastatic breast cancer. AN - 66772237; 15297405 AB - The purpose of this study was to determine the toxicities and characterize the pharmacokinetics of docetaxel and flavopiridol in patients with metastatic breast cancer. Docetaxel was administered at an initial dose of 60 mg/m(2) followed in 24 hours by a 72-hour infusion of flavopiridol at 50 mg/m(2)/d every 3 weeks. Because dose-limiting myelosuppression occurred, the schedule was amended to docetaxel, 50 mg/m(2), followed by escalating doses of flavopiridol (starting dose, 26 mg/m(2)/d) as a 1-hour infusion daily for 3 days. Pharmacokinetic studies were performed. Ki67, p53, and phosphorylated retinoblastoma protein (phospho-Rb) in paired tumor and buccal mucosa biopsies (obtained pre- and posttreatment) were examined by immunohistochemistry. Eleven patients were enrolled. Five patients received docetaxel and 72-hour flavopiridol. Dose-limiting toxicity was grade 4 neutropenia. Six patients received docetaxel and 1-hour flavopiridol, and the dose-limiting toxicity was grade 3 hypotension. Pharmacokinetics of flavopiridol and docetaxel were consistent with historical data. Nuclear staining with p53 increased and phospho-Rb decreased in 10 pairs of buccal mucosa biopsies posttreatment (P = 0.002 and P = 0.04, respectively). No significant changes in Ki67, p53, or phospho-Rb were detected in six paired tumors. Two patients sustained stable disease for >3 months (72-hour flavopiridol), and one partial response was observed (1-hour flavopiridol). Docetaxel combined with 72-hour flavopiridol was not feasible because of dose-limiting neutropenia. Dose escalation of a 1-hour infusion of flavopiridol with docetaxel was also not possible. The changes in p53 and phospho-Rb in buccal mucosa suggest that a biological effect with flavopiridol was achieved. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Tan, Antoinette R AU - Yang, Xiaowei AU - Berman, Arlene AU - Zhai, Suoping AU - Sparreboom, Alex AU - Parr, Allyson L AU - Chow, Catherine AU - Brahim, Jaime S AU - Steinberg, Seth M AU - Figg, William D AU - Swain, Sandra M AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20889, USA. Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 5038 EP - 5047 VL - 10 IS - 15 SN - 1078-0432, 1078-0432 KW - Biomarkers, Tumor KW - 0 KW - Enzyme Inhibitors KW - Flavonoids KW - Ki-67 Antigen KW - Piperidines KW - Retinoblastoma Protein KW - Taxoids KW - Tumor Suppressor Protein p53 KW - docetaxel KW - 15H5577CQD KW - alvocidib KW - 45AD6X575G KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Ki-67 Antigen -- biosynthesis KW - Area Under Curve KW - Mouth Mucosa -- pathology KW - Humans KW - Clinical Trials as Topic KW - Aged KW - Retinoblastoma Protein -- biosynthesis KW - Biopsy KW - Tumor Suppressor Protein p53 -- metabolism KW - Biomarkers, Tumor -- metabolism KW - Phosphorylation KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Mucous Membrane -- pathology KW - Time Factors KW - Immunohistochemistry KW - Female KW - Breast Neoplasms -- drug therapy KW - Enzyme Inhibitors -- administration & dosage KW - Breast Neoplasms -- pathology KW - Flavonoids -- adverse effects KW - Taxoids -- adverse effects KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Breast Neoplasms -- metabolism KW - Piperidines -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Piperidines -- adverse effects KW - Taxoids -- administration & dosage KW - Flavonoids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66772237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+trial+of+the+cyclin-dependent+kinase+inhibitor+flavopiridol+in+combination+with+docetaxel+in+patients+with+metastatic+breast+cancer.&rft.au=Tan%2C+Antoinette+R%3BYang%2C+Xiaowei%3BBerman%2C+Arlene%3BZhai%2C+Suoping%3BSparreboom%2C+Alex%3BParr%2C+Allyson+L%3BChow%2C+Catherine%3BBrahim%2C+Jaime+S%3BSteinberg%2C+Seth+M%3BFigg%2C+William+D%3BSwain%2C+Sandra+M&rft.aulast=Tan&rft.aufirst=Antoinette&rft.date=2004-08-01&rft.volume=10&rft.issue=15&rft.spage=5038&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 - 2005-03-07 N1 - Date created - 2004-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro combination treatment with perifosine and UCN-01 demonstrates synergism against prostate (PC-3) and lung (A549) epithelial adenocarcinoma cell lines. AN - 66771415; 15297428 AB - Antineoplastic agents often achieve antitumor activity at the expense of close to unacceptable toxicity. One potential avenue to improve therapeutic index might combine agents targeting distinct components of the same growth regulatory pathway. This might lead to more complete modulation of the target pathway at concentrations lower than those associated with limiting adventitious toxicities from either agent alone. The protein kinase antagonist UCN-01 is currently used in Phase I/II trials and has recently been demonstrated to inhibit potently PDK1. We have recently documented that the alkylphospholipid perifosine potently also inhibits Akt kinase (PKB) activation by interfering with membrane localization of Akt. This leads to the hypothesis that these two agents might act synergistically through distinct mechanisms in the PI3K/Akt proliferation and survival-related signaling pathway. The synergistic effects of UCN-01 and perifosine, on two cell lines (A-549 and PC-3), were examined using various long-term in vitro assays for cell growth, cell cycle distribution, clonogenicity, survival morphology, and apoptosis. Along with Western blotting experiments were performed to determine whether this synergistic combination of two drugs has significant effect on their downstream targets and on biochemical markers of apoptosis. After 72 h, perifosine at concentrations of 1.5 and 10 microM UCN-01 at 40 and 250 nM did not significantly affect the growth of PC-3 and A459 cells, respectively. However, in combination at the same respective individual concentrations (1.5 microM and 40 nM of perifosine and UCN-01, respectively, in PC-3 cells and 10 microM perifosine and 0.25 microM UCN-01 in the somewhat more resistant A549 cells), virtually complete growth inhibition of both the cell lines resulted. Supra-additive inhibition of growth was also demonstrated in independent clonogenic assays. Mechanistic studies in cell culture models suggest enhanced depletion of the S-phase population in cells treated by the combination. This correlated with enhanced inactivation of Akt along with activation of caspases 3 and 9 and poly(ADP-ribose) polymerase cleavage. Evidence of synergy was formally demonstrated and occurred across a wide range of drug concentrations and was largely independent of the order or sequence of drug addition. As the concentrations of UCN-01 and perifosine causing synergistic inhibition of cell growth are clinically achievable without prominent toxicity, these data support the development of clinical studies with this combination. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Dasmahapatra, Girija P AU - Didolkar, Parijat AU - Alley, Michael C AU - Ghosh, Somiranjan AU - Sausville, Edward A AU - Roy, Krishnendu K AD - Clinical Trials Unit, Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 5242 EP - 5252 VL - 10 IS - 15 SN - 1078-0432, 1078-0432 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - Enzyme Inhibitors KW - Phosphorylcholine KW - 107-73-3 KW - perifosine KW - 2GWV496552 KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Immunoblotting KW - Apoptosis KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line, Tumor KW - Antimetabolites, Antineoplastic -- pharmacology KW - Blotting, Western KW - Bromodeoxyuridine -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Time Factors KW - Antineoplastic Agents -- pharmacology KW - Cell Cycle KW - Signal Transduction KW - Male KW - Female KW - Staurosporine -- administration & dosage KW - Phosphorylcholine -- administration & dosage KW - Lung Neoplasms -- drug therapy KW - Phosphorylcholine -- pharmacology KW - Prostatic Neoplasms -- drug therapy KW - Drug Synergism KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Staurosporine -- analogs & derivatives KW - Phosphorylcholine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66771415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+combination+treatment+with+perifosine+and+UCN-01+demonstrates+synergism+against+prostate+%28PC-3%29+and+lung+%28A549%29+epithelial+adenocarcinoma+cell+lines.&rft.au=Dasmahapatra%2C+Girija+P%3BDidolkar%2C+Parijat%3BAlley%2C+Michael+C%3BGhosh%2C+Somiranjan%3BSausville%2C+Edward+A%3BRoy%2C+Krishnendu+K&rft.aulast=Dasmahapatra&rft.aufirst=Girija&rft.date=2004-08-01&rft.volume=10&rft.issue=15&rft.spage=5242&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 - 2005-03-07 N1 - Date created - 2004-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of paxillin tyrosines 31 and 118 controls polarization and motility of lymphoid cells and is PMA-sensitive. AN - 66765511; 15252114 AB - Tyrosine phosphorylation of paxillin regulates actin cytoskeleton-dependent changes in cell morphology and motility in adherent cells. In this report we investigated the involvement of paxillin tyrosine phosphorylation in the regulation of actin cytoskeleton-dependent polarization and motility of a non-adherent IL-3-dependent murine pre-B lymphocytic cell line Baf3. We also assessed the effect of phorbol myristate acetate (PMA), a phorbol ester analogous to those currently in clinical trials for the treatment of leukemia, on paxillin phosphorylation. Using tyrosine-to-phenylalanine phosphorylation mutants of paxillin and phosphospecific antibody we demonstrated that IL-3 stimulated phosphorylation of paxillin tyrosine residues 31 and 118, whereas the tyrosines 40 and 181 were constitutively phosphorylated. Phosphorylation of paxillin residues 31 and 118 was required for cell polarization and motility. In the presence of IL-3, PMA dramatically reduced the phosphorylation of residues 31 and 118, which was accompanied by inhibition of cell polarization and motility. This PMA effect was partially recapitulated by expression of exogenous tyrosine 31 and 118 mutants of paxillin. We also demonstrated that PMA inhibited the IL-3-induced and activation-dependent tyrosine phosphorylation of focal adhesion kinase. Thus, our results indicate that phosphorylation of paxillin tyrosine residues 31 and 118 regulates actin-dependent polarization and motility of pre-B Baf3 cells, both of which could be inhibited by PMA. They also suggest that inhibition of upstream signaling by PMA contributes to the decrease of paxillin phosphorylation and subsequent changes in cell morphology. JF - Journal of cell science AU - Romanova, Larisa Y AU - Hashimoto, Shigeru AU - Chay, Kee-Oh AU - Blagosklonny, Mikhail V AU - Sabe, Hisataka AU - Mushinski, J Frederic AD - Molecular Genetics Section, Laboratory of Genetics, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. iromanova@partners.org Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 3759 EP - 3768 VL - 117 SN - 0021-9533, 0021-9533 KW - Actins KW - 0 KW - Cytoskeletal Proteins KW - Interleukin-3 KW - PXN protein, human KW - Paxillin KW - Phosphoproteins KW - Pxn protein, mouse KW - Tyrosine KW - 42HK56048U KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Cell Movement KW - Animals KW - Humans KW - Immunoprecipitation KW - Actins -- metabolism KW - Mice KW - Cell Line, Tumor KW - Lymphocytes KW - B-Lymphocytes -- metabolism KW - Phosphoric Monoester Hydrolases -- metabolism KW - Microscopy, Fluorescence KW - Blotting, Western KW - Phosphorylation KW - Genetic Vectors KW - Interleukin-3 -- metabolism KW - Mutation KW - Immunohistochemistry KW - Cell Line KW - Tyrosine -- chemistry KW - Phosphoproteins -- chemistry KW - Cytoskeletal Proteins -- chemistry KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cytoskeletal Proteins -- metabolism KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66765511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+science&rft.atitle=Phosphorylation+of+paxillin+tyrosines+31+and+118+controls+polarization+and+motility+of+lymphoid+cells+and+is+PMA-sensitive.&rft.au=Romanova%2C+Larisa+Y%3BHashimoto%2C+Shigeru%3BChay%2C+Kee-Oh%3BBlagosklonny%2C+Mikhail+V%3BSabe%2C+Hisataka%3BMushinski%2C+J+Frederic&rft.aulast=Romanova&rft.aufirst=Larisa&rft.date=2004-08-01&rft.volume=117&rft.issue=&rft.spage=3759&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-04 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bone marrow-derived immune cells regulate vascular disease through a p27(Kip1)-dependent mechanism. AN - 66765028; 15286808 AB - The cyclin-dependent kinase inhibitors are key regulators of cell cycle progression. Although implicated in carcinogenesis, they inhibit the proliferation of a variety of normal cell types, and their role in diverse human diseases is not fully understood. Here, we report that p27(Kip1) plays a major role in cardiovascular disease through its effects on the proliferation of bone marrow-derived (BM-derived) immune cells that migrate into vascular lesions. Lesion formation after mechanical arterial injury was markedly increased in mice with homozygous deletion of p27(Kip1), characterized by prominent vascular infiltration by immune and inflammatory cells. Vascular occlusion was substantially increased when BM-derived cells from p27(-/-) mice repopulated vascular lesions induced by mechanical injury in p27(+/+) recipients, in contrast to p27(+/+) BM donors. To determine the contribution of immune cells to vascular injury, transplantation was performed with BM derived from RAG(-/-) and RAG(+/+) mice. RAG(+/+) BM markedly exacerbated vascular proliferative lesions compared with what was found in RAG(-/-) donors. Taken together, these findings suggest that vascular repair and regeneration is regulated by the proliferation of BM-derived hematopoietic and nonhematopoietic cells through a p27(Kip1)-dependent mechanism and that immune cells largely mediate these effects. JF - The Journal of clinical investigation AU - Boehm, Manfred AU - Olive, Michelle AU - True, Andrea L AU - Crook, Martin F AU - San, Hong AU - Qu, Xuan AU - Nabel, Elizabeth G AD - Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 419 EP - 426 VL - 114 IS - 3 SN - 0021-9738, 0021-9738 KW - Cell Cycle Proteins KW - 0 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Thymectomy KW - Cell Cycle -- physiology KW - Femoral Artery -- injuries KW - Mice KW - Mice, Knockout KW - Gene Deletion KW - Neutrophils -- metabolism KW - Mice, Inbred Strains KW - T-Lymphocytes -- metabolism KW - Cell Division -- immunology KW - Time Factors KW - Bone Marrow Transplantation KW - Cell Cycle -- drug effects KW - Female KW - Male KW - Macrophages -- metabolism KW - Vascular Diseases -- pathology KW - Cell Cycle Proteins -- genetics KW - Gene Expression Regulation -- immunology KW - Vascular Diseases -- genetics KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Bone Marrow Cells -- immunology KW - Cell Cycle Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66765028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bone+marrow-derived+immune+cells+regulate+vascular+disease+through+a+p27%28Kip1%29-dependent+mechanism.&rft.au=Boehm%2C+Manfred%3BOlive%2C+Michelle%3BTrue%2C+Andrea+L%3BCrook%2C+Martin+F%3BSan%2C+Hong%3BQu%2C+Xuan%3BNabel%2C+Elizabeth+G&rft.aulast=Boehm&rft.aufirst=Manfred&rft.date=2004-08-01&rft.volume=114&rft.issue=3&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+NMR&rft.issn=09252738&rft_id=info:doi/10.1023%2FB%3AJNMR.0000042952.66982.38 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-25 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 2001 Jan 1;166(1):304-12 [11123306] Nat Med. 2000 Nov;6(11):1235-40 [11062534] J Immunol. 2000 Dec 1;165(11):6270-7 [11086062] Science. 2000 Dec 1;290(5497):1779-82 [11099419] Cell. 2001 Feb 23;104(4):503-16 [11239408] Nat Med. 2001 Apr;7(4):382-3 [11283635] Nat Med. 2001 Jun;7(6):693-8 [11385506] Nat Med. 2001 Jun;7(6):738-41 [11385513] J Clin Invest. 2001 Jun;107(11):1411-22 [11390423] J Biol Chem. 2001 Jun 15;276(24):21976-83 [11297537] J Clin Invest. 2001 Jul;108(2):251-9 [11457878] Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1948-54 [11742869] Circulation. 2002 Mar 5;105(9):1135-43 [11877368] Nat Med. 2002 Apr;8(4):403-9 [11927948] Nature. 2002 Jul 4;418(6893):41-9 [12077603] Circ Res. 2002 Aug 23;91(4):281-91 [12193460] Nat Med. 2002 Nov;8(11):1218-26 [12411948] Nat Med. 2002 Nov;8(11):1249-56 [12411952] N Engl J Med. 2002 Nov 14;347(20):1557-65 [12432042] Mol Cell Biol. 2003 Jan;23(1):359-69 [12482987] Nature. 2002 Dec 19-26;420(6917):868-74 [12490960] Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4754-9 [12665618] N Engl J Med. 2003 Oct 2;349(14):1307-9 [14523135] Blood. 2004 Jan 1;103(1):158-61 [14504088] J Clin Invest. 2004 May;113(9):1258-65 [15124016] Cell. 1992 Mar 6;68(5):869-77 [1547488] Cell. 1994 Jul 15;78(1):59-66 [8033212] Circ Res. 1995 Mar;76(3):412-7 [7532117] Cell. 1996 May 31;85(5):707-20 [8646779] Cell. 1996 May 31;85(5):721-32 [8646780] Cell. 1996 May 31;85(5):733-44 [8646781] J Clin Invest. 1996 Nov 15;98(10):2277-83 [8941644] Science. 1997 Feb 14;275(5302):964-7 [9020076] Exp Hematol. 1999 Feb;27(2):203-9 [10029157] Genes Dev. 1999 Jun 15;13(12):1501-12 [10385618] Nat Med. 2000 Mar;6(3):290-7 [10700231] Nature. 2000 Nov 2;408(6808):92-6 [11081514] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of and risk factors for depressive symptoms among young adolescents. AN - 66763989; 15289248 AB - To determine the prevalence, risk factors, and risk behaviors associated with depressive symptoms in a nationally representative, cross-sectional sample of young adolescents. A school-based survey collected through self-administered questionnaires in grades 6, 8, and 10 in 1996. Schools in the United States. 9863 students in grades 6, 8, and 10 (average ages, 11, 13, and 15). Depressive symptoms, substance use, somatic symptoms, scholastic behaviors, and involvement in bullying. Eighteen percent of youths reported symptoms of depression. A higher proportion of females (25%) reported depressive symptoms than males (10%). Prevalence of depressive symptoms increased by age for both males and females. Among American Indian youths, 29% reported depressive symptoms, as compared with 22% of Hispanic, 18% of white, 17% of Asian American, and 15% of African American youths. Youths who were frequently involved in bullying, either as perpetrators or as victims, were more than twice as likely to report depressive symptoms than those who were not involved in bullying. A significantly higher percentage of youths who reported using substances reported depressive symptoms as compared with other youths. Similarly, youths who reported experiencing somatic symptoms also reported significantly higher proportions of depressive symptoms than other youths. Depression is a substantial and largely unrecognized problem among young adolescents that warrants an increased need and opportunity for identification and intervention at the middle school level. Understanding differences in prevalence between males and females and among racial/ethnic groups may be important to the recognition and treatment of depression among youths. JF - Archives of pediatrics & adolescent medicine AU - Saluja, Gitanjali AU - Iachan, Ronaldo AU - Scheidt, Peter C AU - Overpeck, Mary D AU - Sun, Wenyu AU - Giedd, Jay N AD - National Institute of Child Health and Human Development, Rockville, MD 20892-7510, USA. salujag@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 760 EP - 765 VL - 158 IS - 8 SN - 1072-4710, 1072-4710 KW - Abridged Index Medicus KW - Index Medicus KW - Violence -- statistics & numerical data KW - Humans KW - Child KW - Comorbidity KW - Ethnic Groups -- statistics & numerical data KW - Age Distribution KW - Cross-Sectional Studies KW - Risk Factors KW - Health Surveys KW - Psychophysiologic Disorders -- epidemiology KW - Adolescent KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Substance-Related Disorders -- epidemiology KW - Prevalence KW - Adolescent Behavior KW - Depression -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66763989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prevalence+of+and+risk+factors+for+depressive+symptoms+among+young+adolescents.&rft.au=Saluja%2C+Gitanjali%3BIachan%2C+Ronaldo%3BScheidt%2C+Peter+C%3BOverpeck%2C+Mary+D%3BSun%2C+Wenyu%3BGiedd%2C+Jay+N&rft.aulast=Saluja&rft.aufirst=Gitanjali&rft.date=2004-08-01&rft.volume=158&rft.issue=8&rft.spage=760&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 - 2004-08-31 N1 - Date created - 2004-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical-induced DNA damage and human cancer risk. AN - 66763860; 15286742 JF - Nature reviews. Cancer AU - Poirier, Miriam C AD - Carcinogen-DNA Interactions Section, LCCTP, Building 37 Room 4032, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC-4255, Bethesda, Maryland 20892-4255, USA. poirierm@exchange.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 630 EP - 637 VL - 4 IS - 8 SN - 1474-175X, 1474-175X KW - Carcinogens KW - 0 KW - DNA Adducts KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - Humans KW - China KW - Cell Transformation, Neoplastic KW - Risk Assessment KW - Esophageal Neoplasms -- prevention & control KW - Esophageal Neoplasms -- chemically induced KW - DNA Damage KW - Esophageal Neoplasms -- physiopathology KW - Neoplasms -- physiopathology KW - Environmental Exposure KW - Carcinogens -- toxicity KW - Polycyclic Aromatic Hydrocarbons -- poisoning KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66763860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reviews.+Cancer&rft.atitle=Chemical-induced+DNA+damage+and+human+cancer+risk.&rft.au=Poirier%2C+Miriam+C&rft.aulast=Poirier&rft.aufirst=W-C&rft.date=2004-09-01&rft.volume=113&rft.issue=1-3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Hazardous+Materials&rft.issn=03043894&rft_id=info:doi/10.1016%2Fj.jhazmat.2004.05.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-24 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Nat Rev Cancer. 2004 Sep;4(9):747 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. AN - 66761968; 15289279 AB - Uncertainties exist about the prevalence and comorbidity of substance use disorders and independent mood and anxiety disorders. To present nationally representative data on the prevalence and comorbidity of DSM-IV alcohol and drug use disorders and independent mood and anxiety disorders (including only those that are not substance induced and that are not due to a general medical condition). Face-to-face survey. The United States. Household and group quarters' residents. Prevalence and associations of substance use disorders and independent mood and anxiety disorders. The prevalences of 12-month DSM-IV independent mood and anxiety disorders in the US population were 9.21% (95% confidence interval [CI], 8.78%-9.64%) and 11.08% (95% CI, 10.43%-11.73%), respectively. The rate of substance use disorders was 9.35% (95% CI, 8.86%-9.84%). Only a few individuals with mood or anxiety disorders were classified as having only substance-induced disorders. Associations between most substance use disorders and independent mood and anxiety disorders were positive and significant (P<.05). Substance use disorders and mood and anxiety disorders that develop independently of intoxication and withdrawal are among the most prevalent psychiatric disorders in the United States. Associations between most substance use disorders and independent mood and anxiety disorders were overwhelmingly positive and significant, suggesting that treatment for a comorbid mood or anxiety disorder should not be withheld from individuals with substance use disorders. JF - Archives of general psychiatry AU - Grant, Bridget F AU - Stinson, Frederick S AU - Dawson, Deborah A AU - Chou, S Patricia AU - Dufour, Mary C AU - Compton, Wilson AU - Pickering, Roger P AU - Kaplan, Kenneth AD - Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9304, USA. bgrant@willco.niaaa.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 807 EP - 816 VL - 61 IS - 8 SN - 0003-990X, 0003-990X KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Diagnosis, Dual (Psychiatry) KW - Aged KW - Comorbidity KW - Depressive Disorder -- epidemiology KW - Psychiatric Status Rating Scales KW - Adult KW - Depressive Disorder -- diagnosis KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Diagnostic and Statistical Manual of Mental Disorders KW - Female KW - Male KW - Prevalence KW - Substance-Related Disorders -- diagnosis KW - Mood Disorders -- diagnosis KW - Anxiety Disorders -- diagnosis KW - Mood Disorders -- epidemiology KW - Anxiety Disorders -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66761968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prevalence+and+co-occurrence+of+substance+use+disorders+and+independent+mood+and+anxiety+disorders%3A+results+from+the+National+Epidemiologic+Survey+on+Alcohol+and+Related+Conditions.&rft.au=Grant%2C+Bridget+F%3BStinson%2C+Frederick+S%3BDawson%2C+Deborah+A%3BChou%2C+S+Patricia%3BDufour%2C+Mary+C%3BCompton%2C+Wilson%3BPickering%2C+Roger+P%3BKaplan%2C+Kenneth&rft.aulast=Grant&rft.aufirst=Bridget&rft.date=2004-08-01&rft.volume=61&rft.issue=8&rft.spage=807&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 - 2004-08-17 N1 - Date created - 2004-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Natural history of lipid abnormalities and fat redistribution among human immunodeficiency virus-infected children receiving long-term, protease inhibitor-containing, highly active antiretroviral therapy regimens. AN - 66761430; 15286262 AB - To characterize the type and frequency of biochemical lipid abnormalities and physical changes in body composition associated with the use of protease inhibitor (PI)-containing antiretroviral therapy among human immunodeficiency virus-infected children treated for up to 6 years. A retrospective study of human immunodeficiency virus-infected pediatric patients enrolled in research protocols between August 1995 and December 2001 was performed. All patients who had received a PI for > or =2 years as part of their investigational antiretroviral treatment regimens during the study period were eligible. Of the 110 patients identified as having received PI therapy, 94 met the study criteria. Of the 94 patients evaluated, 9 patients (10%) developed fat redistribution as well as dyslipidemia, 49 patients (52%) developed dyslipidemia without associated physical changes, and 36 patients (38%) exhibited no elevation of lipid levels or physical signs of fat redistribution. For all 9 patients with fat redistribution, the onset of the physical changes was closely associated with changes during pubertal development. Fat redistribution was also associated with lower viral loads and higher, more sustained levels of dyslipidemia. The onset of dyslipidemia and fat redistribution peaked between 10 and 15 years of age. Among pediatric patients receiving PI therapy, there seems to be an age range in which children are at greater risk of developing hypercholesterolemia and subsequent fat redistribution, suggesting that unidentified physiologic changes associated with puberty may predispose pediatric patients treated with PI therapy to developing lipodystrophy. JF - Pediatrics AU - Taylor, Perdita AU - Worrell, Carol AU - Steinberg, Seth M AU - Hazra, Rohan AU - Jankelevich, Shirley AU - Wood, Lauren V AU - Zwerski, Sheryl AU - Yarchoan, Robert AU - Zeichner, Steven AD - Pediatric HIV Working Group, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - e235 EP - e242 VL - 114 IS - 2 KW - HIV Protease Inhibitors KW - 0 KW - Lipids KW - Abridged Index Medicus KW - Index Medicus KW - Lipids -- blood KW - Age Factors KW - Analysis of Variance KW - Humans KW - Retrospective Studies KW - Child KW - Child, Preschool KW - Infant KW - Risk Factors KW - Adolescent KW - Female KW - Male KW - Puberty KW - HIV-Associated Lipodystrophy Syndrome -- etiology KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - HIV Infections -- complications KW - HIV Infections -- blood KW - Hypercholesterolemia -- etiology 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/66761430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Natural+history+of+lipid+abnormalities+and+fat+redistribution+among+human+immunodeficiency+virus-infected+children+receiving+long-term%2C+protease+inhibitor-containing%2C+highly+active+antiretroviral+therapy+regimens.&rft.au=Taylor%2C+Perdita%3BWorrell%2C+Carol%3BSteinberg%2C+Seth+M%3BHazra%2C+Rohan%3BJankelevich%2C+Shirley%3BWood%2C+Lauren+V%3BZwerski%2C+Sheryl%3BYarchoan%2C+Robert%3BZeichner%2C+Steven&rft.aulast=Taylor&rft.aufirst=Perdita&rft.date=2004-08-01&rft.volume=114&rft.issue=2&rft.spage=e235&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-27 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discovery of new potentially defective alleles of human CYP2C9. AN - 66758479; 15284535 AB - CYP2C9 is a clinically important enzyme, responsible for the metabolism of numerous clinically important therapeutic drugs. In the present study, we discovered 38 single nucleotide polymorphisms in CYP2C9 by resequencing of genomic DNA from 92 individuals from three different racial groups. Haplotype analysis predicted that there are at least 21 alleles of CYP2C9 in this group of individuals. Six new alleles were identified that contained coding changes: L19I (CYP2C9*7), R150H (CYP2C9*8), H251R (CYP2C9*9), E272G (CYP2C9*10), R335W(CYP2C9*11) and P489S (CYP2C9*12). When expressed in a bacterial cDNA expression system, several alleles exhibited altered catalytic activity. CYP2C9*11 appeared to be a putative poor metabolizer allele, exhibiting a three-fold increase in the Km and more than a two-fold decrease in the intrinsic clearance for tolbutamide. Examination of the crystal structure of human CYP2C9 reveals that R335 is located in the turn between the J and J' helices and forms a hydrogen-bonding ion pair with D341 from the J' helix. Abolishing this interaction in CYP2C9*11 individuals could destabilize the secondary structure and alter the substrate affinity. This new putative poor metabolizer (PM) allele was found in Africans. A second potentially PM allele CYP2C9*12 found in a racially unidentified sample also exhibited a modest decrease in the Vmax and the intrinsic clearance for tolbutamide in a recombinant system. Further clinical studies are needed to determine the effect of these new polymorphisms on the metabolism of CYP2C9 substrates. JF - Pharmacogenetics AU - Blaisdell, Joyce AU - Jorge-Nebert, Lucia F AU - Coulter, Sherry AU - Ferguson, Stephen S AU - Lee, Su-Jun AU - Chanas, Brian AU - Xi, Tina AU - Mohrenweiser, Harvey AU - Ghanayem, Burhan AU - Goldstein, Joyce A AD - Laboratory of Pharmacology and Chemistry, Human Metabolism Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA, DNA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 527 EP - 537 VL - 14 IS - 8 SN - 0960-314X, 0960-314X KW - Recombinant Proteins KW - 0 KW - Tolbutamide KW - 982XCM1FOI 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 - Index Medicus KW - Models, Molecular KW - Humans KW - Recombinant Proteins -- genetics KW - Asian Continental Ancestry Group KW - Genotype KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Alleles KW - Haplotypes -- genetics KW - Transfection KW - Recombinant Proteins -- metabolism KW - European Continental Ancestry Group KW - African Continental Ancestry Group KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Tolbutamide -- metabolism KW - Aryl Hydrocarbon Hydroxylases -- genetics KW - Polymorphism, Single Nucleotide -- genetics KW - Ethnic Groups -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66758479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Discovery+of+new+potentially+defective+alleles+of+human+CYP2C9.&rft.au=Blaisdell%2C+Joyce%3BJorge-Nebert%2C+Lucia+F%3BCoulter%2C+Sherry%3BFerguson%2C+Stephen+S%3BLee%2C+Su-Jun%3BChanas%2C+Brian%3BXi%2C+Tina%3BMohrenweiser%2C+Harvey%3BGhanayem%2C+Burhan%3BGoldstein%2C+Joyce+A&rft.aulast=Blaisdell&rft.aufirst=Joyce&rft.date=2004-08-01&rft.volume=14&rft.issue=8&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-10 N1 - Date created - 2004-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia. AN - 66754774; 15258572 AB - Progressive external ophthalmoplegia (PEO) is a mitochondrial disorder associated with mutations in the POLG gene encoding the mitochondrial DNA polymerase (pol gamma). Four autosomal dominant mutations that cause PEO encode the amino acid substitutions G923D, R943H, Y955C and A957S in the polymerase domain of pol gamma. A homology model of the pol gamma catalytic domain in complex with DNA was developed to investigate the effects of these mutations. Two mutations causing the most severe disease phenotype, Y955C and R943H, change residues that directly interact with the incoming dNTP. Polymerase mutants exhibit 0.03-30% wild-type polymerase activity and a 2- to 35-fold decrease in nucleotide selectivity in vitro. The reduced selectivity and catalytic efficiency of the autosomal dominant PEO mutants predict in vivo dysfunction, and the extent of biochemical defects correlates with the clinical severity of the disease. JF - Nature structural & molecular biology AU - Graziewicz, Maria A AU - Longley, Matthew J AU - Bienstock, Rachelle J AU - Zeviani, Massimo AU - Copeland, William C AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 770 EP - 776 VL - 11 IS - 8 SN - 1545-9993, 1545-9993 KW - Bacterial Proteins KW - 0 KW - Nucleotides KW - Tyrosine KW - 42HK56048U KW - DNA KW - 9007-49-2 KW - DNA polymerase gamma KW - EC 2.7.7.- KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Glycine -- chemistry KW - Models, Molecular KW - DNA -- metabolism KW - Humans KW - Catalytic Domain KW - Nucleotides -- chemistry KW - RNA-Directed DNA Polymerase -- metabolism KW - Protein Binding KW - Structure-Activity Relationship KW - Tyrosine -- chemistry KW - Mutagenesis, Site-Directed KW - Amino Acid Motifs KW - Bacterial Proteins -- chemistry KW - Genes, Dominant KW - Kinetics KW - Protein Folding KW - DNA -- chemistry KW - Crystallography, X-Ray KW - Mutation KW - Mitochondria -- enzymology KW - Ophthalmoplegia, Chronic Progressive External -- genetics KW - Ophthalmoplegia, Chronic Progressive External -- enzymology 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/66754774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+structural+%26+molecular+biology&rft.atitle=Structure-function+defects+of+human+mitochondrial+DNA+polymerase+in+autosomal+dominant+progressive+external+ophthalmoplegia.&rft.au=Graziewicz%2C+Maria+A%3BLongley%2C+Matthew+J%3BBienstock%2C+Rachelle+J%3BZeviani%2C+Massimo%3BCopeland%2C+William+C&rft.aulast=Graziewicz&rft.aufirst=Maria&rft.date=2004-08-01&rft.volume=11&rft.issue=8&rft.spage=770&rft.isbn=&rft.btitle=&rft.title=Nature+structural+%26+molecular+biology&rft.issn=15459993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1D8Y; PDB; 1T7P; 2KTQ; 3DBP N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The transcription factor NRF2 protects against pulmonary fibrosis. AN - 66752968; 15208274 AB - The molecular mechanisms of pulmonary fibrosis are poorly understood, although reactive oxygen species are thought to have an important role. NRF2 is a transcription factor that protects cells and tissues from oxidative stress by activating protective antioxidant and detoxifying enzymes. We hypothesized that NRF2 protects lungs from injury and fibrosis induced by bleomycin, an anti-neoplastic agent that causes pulmonary fibrosis in susceptible patients. To test this hypothesis, mice with targeted deletion of Nrf2 (Nrf2-/-) and wild-type (Nrf2+/+) mice were treated with bleomycin or vehicle, and pulmonary injury and fibrotic responses were compared. Bleomycin-induced increases in lung weight, epithelial cell death, and inflammation were significantly greater in Nrf2-/- mice than in Nrf2+/+ mice. Indices of lung fibrosis (hydroxyproline content, collagen accumulation, fibrotic score, cell proliferation) were significantly greater in bleomycin-treated Nrf2-/- mice, compared with Nrf2+/+ mice. NRF2 expression and activity were elevated in Nrf2+/+ mice by bleomycin. Bleomycin caused greater up-regulation of several NRF2-inducible antioxidant enzyme genes and protein products in Nrf2+/+ mice compared with Nrf2-/- mice. Further, bleomycin-induced transcripts and protein levels of lung injury and fibrosis markers were significantly attenuated in Nrf2+/+ mice compared with Nrf2-/- mice. Results demonstrated that NRF2 has a critical role in protection against pulmonary fibrosis, presumably through enhancement of cellular antioxidant capacity. This study has important implications for the development of intervention strategies against fibrosis. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Cho, Hye-Youn AU - Reddy, Sekhar P M AU - Yamamoto, Masayuki AU - Kleeberger, Steven R AD - Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. cho2@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 1258 EP - 1260 VL - 18 IS - 11 KW - Biomarkers KW - 0 KW - Tenascin KW - Tissue Inhibitor of Metalloproteinase-1 KW - Bleomycin KW - 11056-06-7 KW - RNA KW - 63231-63-0 KW - Collagen KW - 9007-34-5 KW - Hydroxyproline KW - RMB44WO89X KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Lung -- chemistry KW - Cell Division -- drug effects KW - Collagen -- analysis KW - Bleomycin -- toxicity KW - Mice KW - Lung -- pathology KW - Organ Size KW - RNA -- biosynthesis KW - Mice, Knockout KW - Hydroxyproline -- analysis KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Enzyme Induction -- drug effects KW - Tenascin -- analysis KW - Lung -- drug effects KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Male KW - Tissue Inhibitor of Metalloproteinase-1 -- biosynthesis KW - Pulmonary Fibrosis -- chemically induced KW - Pulmonary Fibrosis -- prevention & control KW - Pulmonary Fibrosis -- metabolism KW - Pulmonary Fibrosis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66752968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+transcription+factor+NRF2+protects+against+pulmonary+fibrosis.&rft.au=Cho%2C+Hye-Youn%3BReddy%2C+Sekhar+P+M%3BYamamoto%2C+Masayuki%3BKleeberger%2C+Steven+R&rft.aulast=Cho&rft.aufirst=Hye-Youn&rft.date=2004-08-01&rft.volume=18&rft.issue=11&rft.spage=1258&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-08 N1 - Date created - 2004-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prolonged fever of unknown origin and hemophagocytosis evolving into acute lymphoblastic leukemia. AN - 66750483; 15282670 AB - Hemophagocytic syndrome (HPS) is an unusual acute syndrome presenting with fever, hepatosplenomegaly, and cytopenias. The hallmark of HPS is the accumulation of activated macrophages that engulf hematopoietic cells in the reticuloendothelial system. Most cases of HPS in adults are secondary to infection or malignancy, and thus investigation of the underlying disease is necessary. We describe a patient with prolonged fever, HPS, and chromosomal abnormalities in the bone marrow who underwent thorough evaluation for the cause of his symptoms. A final diagnosis of acute lymphoblastic leukemia (ALL) was established in a fourth, repeated bone marrow biopsy performed more than 2 months after the first presenting symptom appeared. This unusual case demonstrates the importance of cytogenetic abnormalities found in cases of HPS and the importance of repeated testing when an underlying disease is suspected. Copyright 2004 Wiley-Liss, Inc. JF - American journal of hematology AU - Goldschmidt, Neta AU - Gural, Alexander AU - Kornberg, Abraham AU - Spectre, Galia AU - Shopen, Andrei AU - Paltiel, Ora AD - Department of Hematology, Hadassah Medical Center, Jerusalem, Israel. goldschn@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 364 EP - 367 VL - 76 IS - 4 SN - 0361-8609, 0361-8609 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Cytarabine KW - 04079A1RDZ KW - Rituximab KW - 4F4X42SYQ6 KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Karyotyping KW - Bone Marrow -- pathology KW - Humans KW - Vincristine -- administration & dosage KW - Disease Progression KW - Doxorubicin -- administration & dosage KW - Cytarabine -- administration & dosage KW - Antibodies, Monoclonal -- administration & dosage KW - Splenomegaly -- etiology KW - Chromosome Aberrations KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Pancytopenia -- etiology KW - Methotrexate -- administration & dosage KW - Prednisone -- administration & dosage KW - Male KW - Remission Induction KW - Histiocytosis, Non-Langerhans-Cell -- pathology KW - Histiocytosis, Non-Langerhans-Cell -- etiology KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- pathology KW - Fever of Unknown Origin -- etiology KW - Histiocytosis, Non-Langerhans-Cell -- genetics KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- complications KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66750483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prolonged+fever+of+unknown+origin+and+hemophagocytosis+evolving+into+acute+lymphoblastic+leukemia.&rft.au=Goldschmidt%2C+Neta%3BGural%2C+Alexander%3BKornberg%2C+Abraham%3BSpectre%2C+Galia%3BShopen%2C+Andrei%3BPaltiel%2C+Ora&rft.aulast=Goldschmidt&rft.aufirst=Neta&rft.date=2004-08-01&rft.volume=76&rft.issue=4&rft.spage=364&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 - 2004-09-16 N1 - Date created - 2004-07-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Hematol. 2005 Mar;78(3):246-7 [15726603] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice. AN - 66743874; 15276424 AB - Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity. JF - Toxicology and applied pharmacology AU - Patterson, Rachel AU - Vega, Libia AU - Trouba, Kevin AU - Bortner, Carl AU - Germolec, Dori AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 434 EP - 443 VL - 198 IS - 3 SN - 0041-008X, 0041-008X KW - Arsenites KW - 0 KW - Cytokines KW - Enzyme Inhibitors KW - Sodium Compounds KW - sodium arsenite KW - 48OVY2OC72 KW - Dinitrofluorobenzene KW - D241E059U6 KW - Index Medicus KW - Lymph Nodes -- metabolism KW - Animals KW - Dinitrofluorobenzene -- toxicity KW - Mice KW - Flow Cytometry KW - Mice, Inbred BALB C KW - Lymph Nodes -- drug effects KW - Female KW - Sodium Compounds -- therapeutic use KW - Sodium Compounds -- pharmacology KW - Arsenites -- pharmacology KW - Enzyme Inhibitors -- therapeutic use KW - Dermatitis, Contact -- prevention & control KW - Cytokines -- biosynthesis KW - Dermatitis, Contact -- immunology KW - Enzyme Inhibitors -- pharmacology KW - Arsenites -- therapeutic use KW - Immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66743874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Arsenic-induced+alterations+in+the+contact+hypersensitivity+response+in+Balb%2Fc+mice.&rft.au=Patterson%2C+Rachel%3BVega%2C+Libia%3BTrouba%2C+Kevin%3BBortner%2C+Carl%3BGermolec%2C+Dori&rft.aulast=Patterson&rft.aufirst=Rachel&rft.date=2004-08-01&rft.volume=198&rft.issue=3&rft.spage=434&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 - 2004-09-14 N1 - Date created - 2004-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxicity of oxidized low-density lipoprotein in cultured RPE cells is dependent on the formation of 7-ketocholesterol. AN - 66742567; 15277510 AB - To determine which components present in oxidized LDL are responsible for the cytotoxicity associated with its internalization by culture ARPE19 cells. ARPE19 cells were grown in 24-well and 96-well plates. Cell viability was measured by MTT and/or adenosine triphosphate (ATP) content. LDL was oxidized with Cu(+2) and oxysterol content analyzed by a novel HPLC method. OxLDL showed increased cytotoxicity with prolonged oxidation. Analysis of the oxLDL showed a predominance of the 7-oxygenated products, 7 alpha-hydroxycholesterol (7 alpha HCh), 7 beta-hydroxycholesterol (7 beta HCh), and 7-ketocholesterol (7kCh). Addition of these oxysterols to the ARPE19 cell in free form indicated that 7kCh is the most cytotoxic of the oxysterols but at physiologically unrealistic concentrations. Partitioning of individual oxysterols into nonoxidized LDL at concentrations similar to those found in the oxLDL also indicated that 7kCh is the most cytotoxic of the oxysterols. Transition metals are tightly bound by LDL and play an important role in the oxidation of LDL, but do not seem to enhance its cytotoxicity directly. Prolonged oxidation of LDL increases the levels of 7kCh due to further oxidation of 7 alpha HCh and 7 beta HCh. The formation of 7KCh seems to be responsible for most of the cytotoxicity associated with oxLDL internalization in ARPE19 cells. JF - Investigative ophthalmology & visual science AU - Rodriguez, Ignacio R AU - Alam, Shahabuddin AU - Lee, Jung Wha AD - Laboratory of Retinal Cell and Molecular Biology, Section on Mechanisms of Retinal Diseases, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. rodriguezi@nei.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 2830 EP - 2837 VL - 45 IS - 8 SN - 0146-0404, 0146-0404 KW - Hydroxycholesterols KW - 0 KW - Ketocholesterols KW - Lipoproteins, LDL KW - Tetrazolium Salts KW - Thiazoles KW - Transition Elements KW - oxidized low density lipoprotein KW - cholest-5-en-3 beta,7 alpha-diol KW - 566-26-7 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - thiazolyl blue KW - EUY85H477I KW - 7-ketocholesterol KW - O7676FE78M KW - Index Medicus KW - Oxidation-Reduction KW - Hydroxycholesterols -- metabolism KW - Transition Elements -- toxicity KW - Thiazoles -- metabolism KW - Cells, Cultured KW - Humans KW - Adenosine Triphosphate -- metabolism KW - Drug Synergism KW - Time Factors KW - Tetrazolium Salts -- metabolism KW - Chromatography, High Pressure Liquid KW - Cell Survival KW - Pigment Epithelium of Eye -- drug effects KW - Pigment Epithelium of Eye -- metabolism KW - Lipoproteins, LDL -- toxicity KW - Ketocholesterols -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66742567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytotoxicity+of+oxidized+low-density+lipoprotein+in+cultured+RPE+cells+is+dependent+on+the+formation+of+7-ketocholesterol.&rft.au=Rodriguez%2C+Ignacio+R%3BAlam%2C+Shahabuddin%3BLee%2C+Jung+Wha&rft.aulast=Rodriguez&rft.aufirst=Ignacio&rft.date=2004-08-01&rft.volume=45&rft.issue=8&rft.spage=2830&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 - 2004-08-31 N1 - Date created - 2004-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cannabinoid antagonist SR-141716 inhibits endotoxic hypotension by a cardiac mechanism not involving CB1 or CB2 receptors. AN - 66741803; 15059774 AB - Endocannabinoids and CB1 receptors have been implicated in endotoxin (LPS)-induced hypotension: LPS stimulates the synthesis of anandamide in macrophages, and the CB1 antagonist SR-141716 inhibits the hypotension induced by treatment of rats with LPS or LPS-treated macrophages. Recent evidence indicates the existence of cannabinoid receptors distinct from CB1 or CB2 that are inhibited by SR-141716 but not by other CB1 antagonists such as AM251. In pentobarbital-anesthetized rats, intravenous injection of 10 mg/kg LPS elicited hypotension associated with profound decreases in cardiac contractility, moderate tachycardia, and an increase in lower body vascular resistance. Pretreatment with 3 mg/kg SR-141716 prevented the hypotension and decrease in cardiac contractility, slightly attenuated the increase in peripheral resistance, and had no effect on the tachycardia caused by LPS, whereas pretreatment with 3 mg/kg AM251 did not affect any of these responses. SR-141716 also elicited an acute reversal of the hypotension and decreased contractility when administered after the response to LPS had fully developed. The LPS-induced hypotension and its inhibition by SR-141716 were similar in pentobarbital-anesthetized wild-type, CB1(-/-), and CB1(-/-)/CB2(-/-) mice. We conclude that SR-141716 inhibits the acute hemodynamic effects of LPS by interacting with a cardiac receptor distinct from CB1 or CB2 that mediates negative inotropy and may be activated by anandamide or a related endocannabinoid released during endotoxemia. JF - American journal of physiology. Heart and circulatory physiology AU - Bátkai, Sándor AU - Pacher, Pál AU - Járai, Zoltán AU - Wagner, Jens A AU - Kunos, George AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-8115, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - H595 EP - H600 VL - 287 IS - 2 SN - 0363-6135, 0363-6135 KW - Cannabinoids KW - 0 KW - Endotoxins KW - Piperidines KW - Pyrazoles KW - Receptor, Cannabinoid, CB1 KW - Receptor, Cannabinoid, CB2 KW - AM 251 KW - 3I4FA44MAI KW - rimonabant KW - RML78EN3XE KW - Index Medicus KW - Receptor, Cannabinoid, CB2 -- metabolism KW - Hemodynamics -- drug effects KW - Animals KW - Receptor, Cannabinoid, CB1 -- metabolism KW - Vascular Resistance -- drug effects KW - Mice KW - Myocardial Contraction -- drug effects KW - Receptor, Cannabinoid, CB2 -- deficiency KW - Mice, Knockout KW - Rats KW - Heart Rate -- drug effects KW - Rats, Sprague-Dawley KW - Male KW - Receptor, Cannabinoid, CB1 -- deficiency KW - Piperidines -- pharmacology KW - Hypotension -- chemically induced KW - Pyrazoles -- pharmacology KW - Hypotension -- prevention & control KW - Hypotension -- physiopathology KW - Heart -- physiopathology KW - Cannabinoids -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66741803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Heart+and+circulatory+physiology&rft.atitle=Cannabinoid+antagonist+SR-141716+inhibits+endotoxic+hypotension+by+a+cardiac+mechanism+not+involving+CB1+or+CB2+receptors.&rft.au=B%C3%A1tkai%2C+S%C3%A1ndor%3BPacher%2C+P%C3%A1l%3BJ%C3%A1rai%2C+Zolt%C3%A1n%3BWagner%2C+Jens+A%3BKunos%2C+George&rft.aulast=B%C3%A1tkai&rft.aufirst=S%C3%A1ndor&rft.date=2004-08-01&rft.volume=287&rft.issue=2&rft.spage=H595&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Heart+and+circulatory+physiology&rft.issn=03636135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-03 N1 - Date created - 2004-07-27 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Pharmacol Exp Ther. 2003 Jan;304(1):179-84 [12490589] Biochem Pharmacol. 2002 Dec 15;64(12):1785-91 [12445868] Circulation. 2003 Feb 18;107(6):896-904 [12591762] Mol Pharmacol. 2003 Mar;63(3):699-705 [12606780] J Cardiovasc Pharmacol. 2003 Apr;41(4):657-64 [12658069] Br J Pharmacol. 2003 Apr;138(7):1320-32 [12711633] J Biol Chem. 2003 Nov 7;278(45):45034-9 [12949078] Clin Pharmacol Ther. 1975 Sep;18(3):287-97 [1164818] Circulation. 1976 Apr;53(4):703-7 [1253395] Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932-6 [2308954] J Crit Care. 1993 Jun;8(2):117-27 [8102078] Nature. 1993 Sep 2;365(6441):61-5 [7689702] FEBS Lett. 1994 Aug 22;350(2-3):240-4 [8070571] Eur J Pharmacol. 1995 May 24;278(3):279-83 [7589169] Br J Pharmacol. 1996 Aug;118(8):2023-8 [8864538] Am J Physiol. 1997 Feb;272(2 Pt 2):H843-50 [9124447] J Pharmacol Exp Ther. 1997 Jun;281(3):1030-7 [9190833] Naunyn Schmiedebergs Arch Pharmacol. 1997 Aug;356(2):197-202 [9272725] Life Sci. 1997;61(14):PL 191-7 [9335234] Nature. 1997 Dec 4;390(6659):518-21 [9394002] J Cardiovasc Pharmacol. 1998 Apr;31(4):479-83 [9554792] FASEB J. 1998 Aug;12(11):1035-44 [9707176] Science. 1999 Jan 15;283(5400):401-4 [9888857] Am J Physiol. 1999 Jun;276(6 Pt 2):H2085-93 [10362691] J Cardiovasc Pharmacol. 1999 Jul;34(1):64-9 [10413069] Nature. 1999 Jul 29;400(6743):452-7 [10440374] Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1393-8 [12538878] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14136-41 [10570211] Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14228-33 [10588688] Br J Pharmacol. 1999 Dec;128(8):1772-8 [10588933] Hypertension. 2000 Feb;35(2):679-84 [10679517] Biochem J. 2000 Mar 15;346 Pt 3:835-40 [10698714] J Pharmacol Exp Ther. 2000 Jul;294(1):27-32 [10871291] Jpn J Pharmacol. 2000 Mar;82(3):261-4 [10887957] Shock. 2000 Oct;14(4):441-6 [11049107] Chem Phys Lipids. 2000 Nov;108(1-2):159-68 [11106789] Naunyn Schmiedebergs Arch Pharmacol. 2001 Mar;363(3):267-75 [11284440] Nature. 2001 Apr 12;410(6830):822-5 [11298451] Crit Care Med. 2001 Mar;29(3):609-17 [11373429] Anal Biochem. 2001 Jul 1;294(1):73-82 [11412008] Nat Med. 2001 Jul;7(7):827-32 [11433348] J Am Coll Cardiol. 2001 Dec;38(7):2048-54 [11738314] Anesthesiology. 2001 Dec;95(6):1396-405 [11748398] Gastroenterology. 2002 Jan;122(1):85-93 [11781284] Br J Pharmacol. 2002 Mar;135(5):1191-8 [11877326] Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H2046-54 [12003810] Br J Pharmacol. 2002 Jun;136(4):581-7 [12055136] J Am Coll Cardiol. 2002 Sep 4;40(5):1006-16 [12225730] Neuropharmacology. 2002 Sep;43(4):503-10 [12367597] Behav Pharmacol. 2002 Sep;13(5-6):451-63 [12394421] Comment In: Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H451; author reply H451-2 [15598874] N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Mouse susceptibility to anthrax lethal toxin is influenced by genetic factors in addition to those controlling macrophage sensitivity. AN - 66737458; 15271901 AB - Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages (M phi) derived from certain inbred strains. We used nine inbred strains and two inducible nitric oxide synthase (iNOS) knockout C57BL/6J strains polymorphic for the LT M phi sensitivity Kif1C locus to analyze the role of M phi sensitivity (to lysis) in LT-mediated cytokine responses and lethality. LT-mediated induction of cytokines KC, MCP-1/JE, MIP-2, eotaxin, and interleukin-1 beta occurred only in mice having LT-sensitive M phi. However, while iNOS knockout C57BL/6J mice having LT-sensitive M phi were much more susceptible to LT than the knockout mice with LT-resistant M phi, a comparison of susceptibilities to LT in the larger set of inbred mouse strains showed a lack of correlation between M phi sensitivity and animal susceptibility to toxin. For example, C3H/HeJ mice, harboring LT-sensitive M phi and having the associated LT-mediated cytokine response, were more resistant than mice with LT-resistant M phi and no cytokine burst. Toll-like receptor 4 (Tlr4)-deficient, lipopolysaccharide-nonresponsive mice were not more resistant to LT. We also found that CAST/Ei mice are uniquely sensitive to LT and may provide an economical bioassay for toxin-directed therapeutics. The data indicate that while the cytokine response to LT in mice requires M phi lysis and while M phi sensitivity in the C57BL/6J background is sufficient for BALB/cJ-like mortality of that strain, the contribution of M phi sensitivity and cytokine response to animal susceptibility to LT differs among other inbred strains. Thus, LT-mediated lethality in mice is influenced by genetic factors in addition to those controlling M phi lysis and cytokine response and is independent of Tlr4 function. JF - Infection and immunity AU - Moayeri, Mahtab AU - Martinez, Nathaniel W AU - Wiggins, Jason AU - Young, Howard A AU - Leppla, Stephen H AD - Microbial Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 4439 EP - 4447 VL - 72 IS - 8 SN - 0019-9567, 0019-9567 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - anthrax toxin KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Disease Susceptibility KW - Nitric Oxide Synthase -- genetics KW - Mice, Inbred C57BL KW - Mice KW - Mice, Knockout KW - Macrophages, Peritoneal -- physiology KW - Antigens, Bacterial -- toxicity KW - Bacillus anthracis -- pathogenicity KW - Macrophages, Peritoneal -- drug effects KW - Bacterial Toxins -- toxicity KW - Antigens, Bacterial -- immunology KW - Genetic Predisposition to Disease KW - Bacterial Toxins -- immunology KW - Anthrax -- mortality KW - Anthrax -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66737458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Mouse+susceptibility+to+anthrax+lethal+toxin+is+influenced+by+genetic+factors+in+addition+to+those+controlling+macrophage+sensitivity.&rft.au=Moayeri%2C+Mahtab%3BMartinez%2C+Nathaniel+W%3BWiggins%2C+Jason%3BYoung%2C+Howard+A%3BLeppla%2C+Stephen+H&rft.aulast=Moayeri&rft.aufirst=Mahtab&rft.date=2004-08-01&rft.volume=72&rft.issue=8&rft.spage=4439&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 completed - 2004-08-20 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 Jun;87(12):4828-32 [2191302] J Biol Chem. 2003 Feb 28;278(9):7413-21 [12488448] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10198-201 [8234277] Ann N Y Acad Sci. 1995 Jul 21;762:499-501 [7668571] Mol Med. 1998 Feb;4(2):87-95 [9508786] Mol Microbiol. 1998 Jul;29(2):581-91 [9720874] Behav Brain Res. 1998 Sep;95(1):135-42 [9754885] J Bacteriol. 1962 Jun;83:1274-80 [13866126] J Clin Invest. 2003 Sep;112(5):670-82 [12952916] Am J Pathol. 2003 Nov;163(5):1735-41 [14578173] J Infect Dis. 1966 Apr;116(2):123-38 [4956203] J Infect Dis. 1966 Jun;116(3):377-89 [4957317] J Infect Dis. 1968 Feb;118(1):114-24 [5640983] Infect Immun. 1986 Mar;51(3):795-800 [3081444] Science. 1962 Dec 21;138(3547):1331-3 [14033353] Curr Biol. 2001 Oct 2;11(19):1503-11 [11591317] Science. 2002 Sep 20;297(5589):2048-51 [12202685] Infect Immun. 1993 Jan;61(1):245-52 [8380282] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular repair of oxidatively induced DNA base lesions is defective in prostate cancer cell lines, PC-3 and DU-145. AN - 66736484; 15044326 AB - Mutagenic oxidative DNA base damage increases with age in prostatic tissue. Various factors may influence this increase including: increased production of reactive oxygen species, increased susceptibility to oxidative stress, alterations in detoxifying enzyme levels or defects in DNA repair. Using liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry, we show increased levels of oxidative DNA base lesions, 8-hydroxyguanine (8-oxoG), 8-hydroxyadenine (8-oxoA) and 5-hydroxycytosine (5OHC) over the baseline in PC-3 and DU-145 prostate cancer cells following exposure to ionizing radiation and a repair period. Nuclear extracts from PC-3 and DU-145 prostate cancer cell lines are defective in the incision of 8-oxoG, 5OHC and thymine glycol (TG) relative to the non-malignant prostate cell line. Consistent with reduced expression of OGG1 2a, incision of 8-oxoG is reduced in PC-3 and DU-145 mitochondrial extracts. We also show a correlation between severely defective incision of TG and 5OHC and reduced levels of NTH1 in PC-3 mitochondria. The antioxidant enzymes, glutathione peroxidase (GPx), catalase and superoxide dismutases (SOD1, SOD2), have altered expression patterns in these cancer cell lines. Genetic analysis of the OGG1 gene reveals that both PC-3 and DU-145 cell lines harbor polymorphisms associated with a higher susceptibility to certain cancers. These data suggest that the malignant phenotype in PC-3 and DU-145 cell lines may be associated with defects in base excision repair and alterations in expression of antioxidant enzymes. JF - Carcinogenesis AU - Trzeciak, Andrzej R AU - Nyaga, Simon G AU - Jaruga, Pawel AU - Lohani, Althaf AU - Dizdaroglu, Miral AU - Evans, Michele K AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 1359 EP - 1370 VL - 25 IS - 8 SN - 0143-3334, 0143-3334 KW - Antioxidants KW - 0 KW - 8-hydroxyadenine KW - 21149-26-8 KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - 5-hydroxycytosine KW - 75321-30-1 KW - Cytosine KW - 8J337D1HZY KW - DNA KW - 9007-49-2 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 - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Adenine KW - JAC85A2161 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Comet Assay KW - Polymorphism, Genetic KW - Cell Nucleus -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Superoxide Dismutase -- metabolism KW - Cell Line, Tumor KW - Catalase -- metabolism KW - Blotting, Western KW - Glutathione Peroxidase -- metabolism KW - Antioxidants -- pharmacology KW - Kinetics KW - Gas Chromatography-Mass Spectrometry KW - Mitochondria -- metabolism KW - Electron Transport Complex IV -- metabolism KW - Time Factors KW - Male KW - Cell Division KW - DNA Damage KW - Cytosine -- pharmacology KW - Oxygen -- metabolism KW - Prostatic Neoplasms -- genetics KW - DNA -- chemistry KW - Guanine -- analogs & derivatives KW - Cytosine -- analogs & derivatives KW - Adenine -- analogs & derivatives KW - Guanine -- pharmacology KW - Adenine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66736484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+repair+of+oxidatively+induced+DNA+base+lesions+is+defective+in+prostate+cancer+cell+lines%2C+PC-3+and+DU-145.&rft.au=Trzeciak%2C+Andrzej+R%3BNyaga%2C+Simon+G%3BJaruga%2C+Pawel%3BLohani%2C+Althaf%3BDizdaroglu%2C+Miral%3BEvans%2C+Michele+K&rft.aulast=Trzeciak&rft.aufirst=Andrzej&rft.date=2004-08-01&rft.volume=25&rft.issue=8&rft.spage=1359&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raloxifene and its role in breast cancer prevention. AN - 66733533; 15270657 AB - Raloxifene (Evista, Eli Lilly), a selective estrogen receptor modulator (SERM) and ligand for the estrogen receptor (ER), competes with endogenous estrogen for ER binding. Raloxifene is approved for the prevention and treatment of osteoporosis, and shows promise as a breast cancer prevention drug. Raloxifene may be a preferred agent over tamoxifen due to its side-effect profile; in particular, it does not stimulate the endometrium and is not associated with endometrial cancer. The mechanisms for the differential tissue effects of raloxifene compared with other SERMs are not completely understood; the roles of ERalpha and -beta, classic and alternative signaling pathways, and drug conformation are discussed in this review. The utility of raloxifene will depend on the outcome of trials that are now underway, as well as acceptance by high-risk women and their healthcare practitioners. JF - Expert review of anticancer therapy AU - Eng-Wong, Jennifer AU - Zujewski, Jo Anne AD - National Cancer Institute, Medical Oncology Clinical Research Unit, Bldg 10, Rm 12N226, Bethesda, MD 20892, USA. engwongj@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 523 EP - 532 VL - 4 IS - 4 SN - 1473-7140, 1473-7140 KW - Estrogen Antagonists KW - 0 KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Index Medicus KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Chemoprevention KW - Signal Transduction KW - Female KW - Osteoporosis -- prevention & control KW - Estrogen Antagonists -- pharmacology KW - Raloxifene Hydrochloride -- pharmacology KW - Estrogen Antagonists -- adverse effects KW - Raloxifene Hydrochloride -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Raloxifene Hydrochloride -- adverse effects KW - Estrogen Antagonists -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66733533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+review+of+anticancer+therapy&rft.atitle=Raloxifene+and+its+role+in+breast+cancer+prevention.&rft.au=Eng-Wong%2C+Jennifer%3BZujewski%2C+Jo+Anne&rft.aulast=Eng-Wong&rft.aufirst=Jennifer&rft.date=2004-08-01&rft.volume=4&rft.issue=4&rft.spage=523&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+anticancer+therapy&rft.issn=14737140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-21 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Severe disabling sensory-motor polyneuropathy during oxaliplatin-based chemotherapy. AN - 66729629; 15269607 AB - Oxaliplatin-based combination chemotherapy is an option for first-line therapy of metastatic colorectal cancer. It is associated with acute hyperexcitability of motor and sensory nerves, and a cumulative sensory axonal neuropathy. We describe a 56-year-old male with metastatic colorectal cancer treated with oxaliplatin and capecitabine who developed a rapidly ascending motor and sensory neuropathy, which rendered him wheelchair-bound. Heightened clinical suspicion for possible oxaliplatin-induced motor neuropathies may be warranted. JF - Anti-cancer drugs AU - Leonard, Gregory D AU - Wagner, Michael R AU - Quinn, Mary G AU - Grem, Jean L AD - National Cancer Institute-Navy Medical Oncology, Bethesda, MD, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 733 EP - 735 VL - 15 IS - 7 SN - 0959-4973, 0959-4973 KW - Organoplatinum Compounds KW - 0 KW - oxaliplatin KW - 04ZR38536J KW - Deoxycytidine KW - 0W860991D6 KW - Capecitabine KW - 6804DJ8Z9U KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Severity of Illness Index KW - Organoplatinum Compounds -- adverse effects KW - Organoplatinum Compounds -- administration & dosage KW - Humans KW - Fluorouracil -- analogs & derivatives KW - Middle Aged KW - Disabled Persons KW - Male KW - Deoxycytidine -- adverse effects KW - Deoxycytidine -- analogs & derivatives KW - Colonic Neoplasms -- drug therapy KW - Deoxycytidine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Polyneuropathies -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66729629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Severe+disabling+sensory-motor+polyneuropathy+during+oxaliplatin-based+chemotherapy.&rft.au=Leonard%2C+Gregory+D%3BWagner%2C+Michael+R%3BQuinn%2C+Mary+G%3BGrem%2C+Jean+L&rft.aulast=Leonard&rft.aufirst=Gregory&rft.date=2004-08-01&rft.volume=15&rft.issue=7&rft.spage=733&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-15 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-1beta-induced mucin production in human airway epithelium is mediated by cyclooxygenase-2, prostaglandin E2 receptors, and cyclic AMP-protein kinase A signaling. AN - 66728441; 15266025 AB - We reported recently that interleukin (IL)-1beta exposure resulted in a prolonged increase in MUC5AC mucin production in normal, well differentiated, human tracheobronchial epithelial (NHTBE) cell cultures, without significantly increasing MUC5AC mRNA (Am J Physiol 286:L320-L330, 2004). The goal of the present study was to elucidate the signaling pathways involved in IL-1beta-induced MUC5AC production. We found that IL-1beta increased cyclooxygenase-2 (COX-2) mRNA expression and prostaglandin (PG) E(2) production and that the COX-2 inhibitor celecoxib suppressed IL-1beta-induced MUC5AC production. Addition of exogenous PGE(2) to NHTBE cultures also increased MUC5AC production and IL-1beta-induced Muc5ac hypersecretion in tracheas from wild-type but not from COX-2-/- mice. NHTBE cells expressed all four E-prostanoid (EP) receptor subtypes and misoprostol, an EP2 and EP4 agonist, increased MUC5AC production, whereas sulprostone, an EP1 and EP3 agonist, did not. Furthermore, specific protein kinase A (PKA) inhibitors blocked IL-1beta and PGE(2)-induced MUC5AC production. However, neither inhibition of epidermal growth factor receptor (EGFR) activation with the tyrosine kinase inhibitor 4-(3-chloroanilino)-6,7-dimethoxyquinazoline HCl (AG-1478) or EGFR blocking antibody nor inhibition of extracellular signal-regulated kinase/P-38 mitogen activated protein kinases with specific inhibitors blocked IL-1beta stimulation of MUC5AC mucin production. We also observed that tumor necrosis factor (TNF)-alpha, platelet activating factor (PAF), and lipopolysaccharide (LPS) induced COX-2 and increased MUC5AC production that was blocked by celecoxib, suggesting a common signaling pathway of inflammatory mediator-induced MUC5AC production in NHTBE cells. We conclude that the induction of MUC5AC by IL-1beta, TNF-alpha, PAF, and LPS involves COX-2- generated PGE(2), activation of EP2 and/or EP4 receptor(s), and cAMP-PKA-mediated signaling. JF - Molecular pharmacology AU - Gray, Thomas AU - Nettesheim, Paul AU - Loftin, Charles AU - Koo, Ja-Seok AU - Bonner, James AU - Peddada, Shyamal AU - Langenbach, Robert AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. grayt@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 337 EP - 346 VL - 66 IS - 2 SN - 0026-895X, 0026-895X KW - Interleukin-1 KW - 0 KW - Isoenzymes KW - Lipopolysaccharides KW - Membrane Proteins KW - Mucins KW - PTGER1 protein, human KW - PTGER2 protein, human KW - PTGER3 protein, human KW - PTGER4 protein, human KW - Ptger1 protein, mouse KW - Ptger2 protein, mouse KW - Ptger3 protein, mouse KW - Ptger4 protein, mouse KW - Receptors, Prostaglandin E KW - Receptors, Prostaglandin E, EP1 Subtype KW - Receptors, Prostaglandin E, EP2 Subtype KW - Receptors, Prostaglandin E, EP3 Subtype KW - Receptors, Prostaglandin E, EP4 Subtype KW - Tumor Necrosis Factor-alpha KW - Cyclic AMP KW - E0399OZS9N KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Receptor, Epidermal Growth Factor -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Bronchi -- cytology KW - Cells, Cultured KW - Dinoprostone -- metabolism KW - Cyclic AMP -- metabolism KW - Trachea -- metabolism KW - Trachea -- drug effects KW - Receptors, Prostaglandin E -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Signal Transduction -- physiology KW - Interleukin-1 -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Epithelium -- metabolism KW - Mucins -- biosynthesis KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Epithelium -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66728441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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-1beta-induced+mucin+production+in+human+airway+epithelium+is+mediated+by+cyclooxygenase-2%2C+prostaglandin+E2+receptors%2C+and+cyclic+AMP-protein+kinase+A+signaling.&rft.au=Gray%2C+Thomas%3BNettesheim%2C+Paul%3BLoftin%2C+Charles%3BKoo%2C+Ja-Seok%3BBonner%2C+James%3BPeddada%2C+Shyamal%3BLangenbach%2C+Robert&rft.aulast=Gray&rft.aufirst=Thomas&rft.date=2004-08-01&rft.volume=66&rft.issue=2&rft.spage=337&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 - 2004-08-30 N1 - Date created - 2004-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of cysteines and charged amino acids in extracellular loops of the human Ca(2+) receptor in cell surface expression and receptor activation processes. AN - 66727651; 15117879 AB - The Ca(2+) receptor is a plasma-membrane bound G protein-coupled receptor stimulated by extracellular calcium [Ca(2+)](o) and other di- and poly-cations. We investigated the role in receptor activation of all the charged amino acid residues and cysteines in the three extracellular loops (EL1, 2, and 3) of the human Ca(2+) receptor by alanine-scanning mutagenesis. The mutant receptors were transiently expressed in HEK-293 cells, and cell surface expression patterns were analyzed by endoglycosidase-H digestion, immunoblotting, intact cell ELISA, and hydrolysis of phosphoinositides (PI) induced by [Ca(2+)](o.) The mutation of Cys677 and Cys765 located in EL1 and EL2, respectively, ablated PI hydrolysis completely, showed less than 5% cell surface expression of the wild-type receptor, and were not properly glycosylated. Replacement of the charged residues by using a single mutation or multiple alanine mutations in EL1, 2, and 3 produced only minor changes in receptor activation, except for Glu767 and Lys831. The E767A and K831A mutations in EL2 and EL3, respectively, showed gain-of-function by significantly enhancing apparent [Ca(2+)](o) affinity. E767A and K831A exhibited EC(50) values of 2.1 and 2.8 mm, respectively, for [Ca(2+)](o)-stimulated PI hydrolysis as opposed to EC(50) value of 4.2 mm for the wild-type receptor. Like E767A, substitutions of Glu767 with Gln and Lys was similarly activating, whereas Asp substitution displayed wild-type [Ca(2+)](o) sensitivity. Substitution of Lys831 with Glu but not with Gln showed similar activating effect as Ala replacement. A double-mutant E767K/K831E in which charged residues were switched positions showed impaired cell surface expression and failed to respond to [Ca(2+)](o.) Taken together, these results suggest that in ELs, two cysteines form critical disulfide links, and the side chains of Glu767 and Lys831 are probably involved in ionic interactions with other prospective oppositely charged residues. Some of these interactions could be important for receptor folding and also may contribute to keep the Ca(2+) receptor transmembrane helix bundle in an inactive conformation. JF - Endocrinology AU - Ray, Kausik AU - Ghosh, Sanchita P AU - Northup, John K AD - Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA. rayk@nidcd.nih.gov. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 3892 EP - 3903 VL - 145 IS - 8 SN - 0013-7227, 0013-7227 KW - Receptors, Calcium-Sensing KW - 0 KW - Cysteine KW - K848JZ4886 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Calcium -- metabolism KW - Cells, Cultured KW - Humans KW - Protein Folding KW - Signal Transduction KW - Molecular Weight KW - Structure-Activity Relationship KW - Receptors, Calcium-Sensing -- chemistry KW - Receptors, Calcium-Sensing -- physiology KW - Cysteine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66727651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+role+of+cysteines+and+charged+amino+acids+in+extracellular+loops+of+the+human+Ca%282%2B%29+receptor+in+cell+surface+expression+and+receptor+activation+processes.&rft.au=Ray%2C+Kausik%3BGhosh%2C+Sanchita+P%3BNorthup%2C+John+K&rft.aulast=Ray&rft.aufirst=Kausik&rft.date=2004-08-01&rft.volume=145&rft.issue=8&rft.spage=3892&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-17 N1 - Date created - 2004-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nkx2.1 transcription factor in lung cells and a transforming growth factor-beta1 heterozygous mouse model of lung carcinogenesis. AN - 66720233; 15264213 AB - The Nkx2.1 homeobox gene and transforming growth factor-beta1 (TGF-beta1) are essential for organogenesis and differentiation of the mouse lung. NKX2.1 is a marker of human lung carcinomas, but it is not known whether this gene participates in early tumorigenesis. Addition of TGF-beta1 to TGF-beta1-responsive nontumorigenic mouse lung cells cotransfected with a NKX2.1Luc luciferase reporter and either a Sp1 or Sp3 plasmid showed a significant increase or decrease, respectively, in NKX2.1Luc transcription. Cotransfection of Sp3 and dominant-negative TGF-beta type II receptor plasmids negated the effect of Sp1. Cotransfected Sp1 plasmid with either dominant-negative Smad2 or Smad3 or Smad4 plasmids significantly decreased NKX2.1Luc transcription. Electrophoretic mobility shift assays revealed binding of Sp1 and Smad4 to the NKX2.1 promoter. With a TGF-beta1 heterozygous mouse model, Nkx2.1 mRNA and protein in lungs of TGF-beta1 heterozygous mice were significantly lower compared to wildtype (WT) littermates. Competitive reverse transcription (RT)-polymerase chain reaction (PCR) and immunostaining showed that Nkx2.1 mRNA and protein decreased significantly in adenomas and adenocarcinomas compared to normal lung tissue. Our in vitro data showed that regulation of Nkx2.1 by TGF-beta1 occurs through TGF-beta type II receptor and Smad signaling, with Sp1 and Sp3 in lung cells. Our in vivo data showed reduced Nkx2.1 in lungs of TGF-beta1 heterozygous mice compared to WT mice, that is detectable in adenomas, and that is further reduced in carcinogenesis, and that correlates with reduction of Sp1, Sp3, and Smads in lung adenocarcinomas. Our findings suggest that reduced Nkx2.1 and TGF-beta1 signaling components may contribute to tumorigenesis in the lungs of TGF-beta1 heterozygous mice. JF - Molecular carcinogenesis AU - Kang, Yang AU - Hebron, Haroun AU - Ozbun, Laurent AU - Mariano, Jennifer AU - Minoo, Parviz AU - Jakowlew, Sonia B AD - National Cancer Institute, Cell and Cancer Biology Branch, Rockville, Maryland 20850, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 212 EP - 231 VL - 40 IS - 4 SN - 0899-1987, 0899-1987 KW - Nuclear Proteins KW - 0 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transcription Factors KW - Transforming Growth Factor beta KW - thyroid nuclear factor 1 KW - Tritium KW - 10028-17-8 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Thymidine -- metabolism KW - Receptors, Transforming Growth Factor beta -- genetics KW - Animals KW - Blotting, Northern KW - Tritium -- metabolism KW - RNA, Messenger -- metabolism KW - Gene Expression Regulation, Neoplastic -- physiology KW - Disease Models, Animal KW - Mice KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - Immunohistochemistry KW - Lung Neoplasms -- etiology KW - Nuclear Proteins -- genetics KW - Transcription Factors -- metabolism KW - Cell Transformation, Neoplastic -- metabolism KW - Lung Neoplasms -- genetics KW - Lung -- metabolism KW - Transforming Growth Factor beta -- genetics KW - Nuclear Proteins -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Transcription Factors -- genetics KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66720233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nkx2.1+transcription+factor+in+lung+cells+and+a+transforming+growth+factor-beta1+heterozygous+mouse+model+of+lung+carcinogenesis.&rft.au=Kang%2C+Yang%3BHebron%2C+Haroun%3BOzbun%2C+Laurent%3BMariano%2C+Jennifer%3BMinoo%2C+Parviz%3BJakowlew%2C+Sonia+B&rft.aulast=Kang&rft.aufirst=Yang&rft.date=2004-08-01&rft.volume=40&rft.issue=4&rft.spage=212&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 - 2004-09-17 N1 - Date created - 2004-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substrate specificity of Xenopus matrix metalloproteinase stromelysin-3. AN - 66706793; 15254771 AB - The matrix metalloproteinase stromelysin-3 (ST3 or MMP11) was initially identified as a breast carcinoma associated protease and has since been shown to be highly expressed in diverse carcinomas and in developmental processes that involve extensive cell death (apoptosis) and tissue remodeling. Unlike other MMPs, purified ST3 has little activity toward known extracellular matrix (ECM) proteins in vitro but cleaves strongly a few non-ECM, extracellular proteins, including human alpha1-proteinase inhibitor (alpha1-PI). To investigate the possibility of alpha1-PI as a conserved physiological substrate for ST3 during vertebrate development, we analyzed the ability of Xenopus laevis ST3 catalytic domain to cleave frog alpha1-PI. Surprisingly, we found the ST3 failed to recognize the site in alpha1-PI equivalent to the major cleavage site in human alpha1-PI by mammalian ST3. Sequence and mutagenic analysis revealed that multiple substitutions at P2-P3' positions between human and Xenopus alpha1-PI contributed to the inability of Xenopus alpha1-PI to be cleaved by ST3. Our studies showed that (A)(G/A)(A)(M)(F/A)(L) (P3-P3') as a preferred cleavage site for ST3. We further demonstrated that mutations in the cleavage sites affected cleavage by ST3 differently from several other MMPs. These findings, together with earlier reports on ST3, showed that ST3 has distinct substrate specificities compared to other MMPs. Our results further suggest that alpha1-PI is unlikely to be a physiological substrate for ST3, at least with regard to evolutionarily conserved developmental processes. JF - International journal of molecular medicine AU - Amano, Tosikazu AU - Fu, Liezhen AU - Sahu, Shelley AU - Markey, Meghan AU - Shi, Yun-Bo AD - Section on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 233 EP - 239 VL - 14 IS - 2 SN - 1107-3756, 1107-3756 KW - alpha 1-Antitrypsin KW - 0 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Matrix Metalloproteinase 11 KW - EC 3.4.24.- KW - Metalloendopeptidases KW - Index Medicus KW - Animals KW - alpha 1-Antitrypsin -- chemistry KW - Extracellular Matrix -- metabolism KW - alpha 1-Antitrypsin -- metabolism KW - DNA Mutational Analysis KW - Humans KW - Catalytic Domain KW - Protein Binding KW - Evolution, Molecular KW - Binding Sites KW - Mutagenesis KW - Mutagenesis, Site-Directed KW - Xenopus KW - Substrate Specificity KW - Protein Structure, Tertiary KW - Green Fluorescent Proteins -- metabolism KW - Metalloendopeptidases -- metabolism KW - Metalloendopeptidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66706793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+molecular+medicine&rft.atitle=Substrate+specificity+of+Xenopus+matrix+metalloproteinase+stromelysin-3.&rft.au=Amano%2C+Tosikazu%3BFu%2C+Liezhen%3BSahu%2C+Shelley%3BMarkey%2C+Meghan%3BShi%2C+Yun-Bo&rft.aulast=Amano&rft.aufirst=Tosikazu&rft.date=2004-08-01&rft.volume=14&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=International+journal+of+molecular+medicine&rft.issn=11073756&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-04 N1 - Date created - 2004-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional reconstitution of gamma-secretase through coordinated expression of presenilin, nicastrin, Aph-1, and Pen-2. AN - 66697934; 15248287 AB - The gamma-secretase complex has emerged as an unusual membrane-bound aspartyl protease with the ability to cleave certain substrate proteins at peptide bonds believed to be buried within the hydrophobic environment of the lipid bilayer. This cleavage is responsible for a key biochemical step in signaling from several different cell-surface receptors, and it is also crucial in generating the neurotoxic amyloid peptides that are central to the pathogenesis of Alzheimer's disease. Active gamma-secretase is a multimeric protein complex consisting of at least four different proteins, presenilin, nicastrin, Aph-1, and Pen-2, with presenilin serving as the catalytically active core of the aspartyl protease. Presenilin itself undergoes endoproteolytic maturation, a process that is tightly regulated during the assembly and maturation of gamma-secretase, and that depends on the three cofactors nicastrin, Aph-1, and Pen-2. Recent studies have demonstrated that presenilin and its three cofactors are likely to be the major proteins needed for functional reconstitution of active gamma-secretase and have begun to elucidate the specific functions of the cofactors in the ordered assembly of gamma-secretase. Published 2004 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Periz, Goran AU - Fortini, Mark E AD - Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, Maryland 21701, USA. Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 309 EP - 322 VL - 77 IS - 3 SN - 0360-4012, 0360-4012 KW - Macromolecular Substances KW - 0 KW - Membrane Glycoproteins KW - Membrane Proteins KW - PSEN1 protein, human KW - PSENEN protein, human KW - Presenilin-1 KW - nicastrin protein KW - APH1A protein, human KW - EC 3.4.- KW - Amyloid Precursor Protein Secretases KW - Endopeptidases KW - Peptide Hydrolases KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - BACE1 protein, human KW - EC 3.4.23.46 KW - Index Medicus KW - Animals KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Membrane Glycoproteins -- biosynthesis KW - Membrane Glycoproteins -- physiology KW - Membrane Proteins -- biosynthesis KW - Endopeptidases -- metabolism KW - Endopeptidases -- physiology KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66697934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroscience+research&rft.atitle=Functional+reconstitution+of+gamma-secretase+through+coordinated+expression+of+presenilin%2C+nicastrin%2C+Aph-1%2C+and+Pen-2.&rft.au=Periz%2C+Goran%3BFortini%2C+Mark+E&rft.aulast=Periz&rft.aufirst=Goran&rft.date=2004-08-01&rft.volume=77&rft.issue=3&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-09 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic alcohol consumption accelerates liver injury in T cell-mediated hepatitis: alcohol disregulation of NF-kappaB and STAT3 signaling pathways. AN - 66691603; 15064234 AB - Alcohol consumption is a major risk factor accelerating the progression of liver disease in patients with chronic hepatitis virus infection. However, the mechanism underlying the enhanced susceptibility of alcoholics to liver injury is not fully understood. Here, we demonstrate that chronic ethanol consumption increases the susceptibility of C57BL/6 mice to concanavalin A (Con A)-induced T cell-mediated hepatitis. Injection of a low dose of Con A (5 microg/g) causes severe liver damage in ethanol-fed mice as evidenced by a significant elevation of serum alanine aminotransaminase levels, massive necrosis, and infiltration of leukocytes but only slightly induces liver injury in control pair-fed mice. In ethanol-fed mice, the activation and cytotoxicity of natural killer T cells, cells that play key roles in Con A-induced T cell hepatitis, are not significantly enhanced relative to pair-fed mice. Moreover, Con A-induced activation of hepatic NF-kappaB is increased, whereas activation of STAT1 and STAT3 is attenuated in ethanol-fed mice. Consistent with this result, the expression of chemokines and adhesion molecules [such as ICAM-1, macrophage inflammatory protein (MIP)-1, MIP-2, and MCP-1] controlled by NF-kappaB is upregulated, whereas STAT1-controlled expression of chemokines (such as MIG and IP-10) is downregulated in ethanol-fed mice compared with pair-fed mice. In conclusion, chronic alcohol consumption accelerates T cell-mediated hepatitis via upregulation of the NF-kappaB signaling pathway and subsequently enhances expression of chemokines/adhesive molecules and recruitment of leukocytes into the liver. Downregulation of the antiapoptotic STAT3 signal may also contribute to alcohol potentiation of T cell hepatitis. JF - American journal of physiology. Gastrointestinal and liver physiology AU - Jaruga, Barbara AU - Hong, Feng AU - Kim, Won-Ho AU - Sun, Rui AU - Fan, Saijun AU - Gao, Bin AD - Section on Liver Biology, NIAAA/NIH, Park Bldg. Rm. 120, 12420 Parklawn Dr., MSC 8115, Bethesda, MD 20892, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - G471 EP - G479 VL - 287 IS - 2 SN - 0193-1857, 0193-1857 KW - Cell Adhesion Molecules KW - 0 KW - Chemokines KW - DNA-Binding Proteins KW - NF-kappa B KW - STAT3 Transcription Factor KW - Stat3 protein, mouse KW - Trans-Activators KW - Concanavalin A KW - 11028-71-0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals KW - Chemokines -- metabolism KW - Concanavalin A -- adverse effects KW - Hepatocytes KW - Leukocytes -- pathology KW - Mice, Inbred C57BL KW - Cell Adhesion Molecules -- metabolism KW - Mice KW - Monocytes KW - Time Factors KW - Male KW - Killer Cells, Natural -- drug effects KW - T-Lymphocytes KW - Trans-Activators -- metabolism KW - Liver -- physiopathology KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Ethanol -- pharmacology KW - Signal Transduction -- drug effects KW - Alcohol Drinking KW - NF-kappa B -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66691603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Gastrointestinal+and+liver+physiology&rft.atitle=Chronic+alcohol+consumption+accelerates+liver+injury+in+T+cell-mediated+hepatitis%3A+alcohol+disregulation+of+NF-kappaB+and+STAT3+signaling+pathways.&rft.au=Jaruga%2C+Barbara%3BHong%2C+Feng%3BKim%2C+Won-Ho%3BSun%2C+Rui%3BFan%2C+Saijun%3BGao%2C+Bin&rft.aulast=Jaruga&rft.aufirst=Barbara&rft.date=2004-08-01&rft.volume=287&rft.issue=2&rft.spage=G471&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Gastrointestinal+and+liver+physiology&rft.issn=01931857&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-30 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A population-based study of vaginal human papillomavirus infection in hysterectomized women. AN - 66687159; 15243917 AB - We compared point prevalences and determinants of human papillomavirus (HPV) DNA detection by testing enrollment vaginal specimens from hysterectomized women (n=569) and enrollment cervical specimens from nonhysterectomized women (n=6098) >or=30 years old, using MY09/MY11 L1 consensus-primer polymerase chain reaction. The subjects were participating in a population-based cohort study (n=10,049) in Guanacaste, Costa Rica, that was initiated in 1993. Non-cancer-associated HPV types, especially types 61, 71, and 72, were detected more frequently in the vaginal specimens from hysterectomized women (23.7% [95% confidence interval [CI], 20.3%-27.4%]) than in the cervical specimens from nonhysterectomized women (16.7% [95% CI, 15.7%-17.6%]) (P=.0001). There was no difference between the prevalences of cancer-associated HPV types in hysterectomized women and those in nonhysterectomized women; in both groups, the prevalence of HPV DNA was greater in women with multiple lifetime sex partners. We infer from our data that the cervical transformation zone may not be needed for cancer-associated HPV infection but may be uniquely susceptible to HPV-induced carcinogenesis; we also infer that specific phylogenetic groups of HPV (i.e., A3/A4/A15) may have a predilection for vaginal epithelium. JF - The Journal of infectious diseases AU - Castle, Philip E AU - Schiffman, Mark AU - Bratti, M Concepcion AU - Hildesheim, Allan AU - Herrero, Rolando AU - Hutchinson, Martha L AU - Rodriguez, Ana Cecilia AU - Wacholder, Sholom AU - Sherman, Mark E AU - Kendall, Hortense AU - Viscidi, Raphael P AU - Jeronimo, Jose AU - Schussler, John E AU - Burk, Robert D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-7234, USA. castlep@mail.nih.gov Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 458 EP - 467 VL - 190 IS - 3 SN - 0022-1899, 0022-1899 KW - Antibodies, Viral KW - 0 KW - DNA, Viral KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Aged KW - Antibodies, Viral -- blood KW - Polymerase Chain Reaction KW - Uterine Cervical Neoplasms -- epidemiology KW - Aged, 80 and over KW - DNA, Viral -- analysis KW - Adult KW - Cohort Studies KW - Vagina -- virology KW - Cervix Uteri -- virology KW - Middle Aged KW - Female KW - Uterine Cervical Neoplasms -- virology KW - Prevalence KW - Vaginal Diseases -- virology KW - Papillomavirus Infections -- epidemiology KW - Vaginal Diseases -- epidemiology KW - Papillomaviridae -- classification KW - Hysterectomy KW - Papillomaviridae -- isolation & purification KW - Papillomavirus Infections -- virology KW - Papillomaviridae -- genetics KW - Papillomaviridae -- immunology KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66687159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+population-based+study+of+vaginal+human+papillomavirus+infection+in+hysterectomized+women.&rft.au=Castle%2C+Philip+E%3BSchiffman%2C+Mark%3BBratti%2C+M+Concepcion%3BHildesheim%2C+Allan%3BHerrero%2C+Rolando%3BHutchinson%2C+Martha+L%3BRodriguez%2C+Ana+Cecilia%3BWacholder%2C+Sholom%3BSherman%2C+Mark+E%3BKendall%2C+Hortense%3BViscidi%2C+Raphael+P%3BJeronimo%2C+Jose%3BSchussler%2C+John+E%3BBurk%2C+Robert+D&rft.aulast=Castle&rft.aufirst=Philip&rft.date=2004-08-01&rft.volume=190&rft.issue=3&rft.spage=458&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 - 2004-08-24 N1 - Date created - 2004-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulated expression of pathogen-associated molecular pattern molecules in Staphylococcus epidermidis: quorum-sensing determines pro-inflammatory capacity and production of phenol-soluble modulins. AN - 66679322; 15236642 AB - Phenol-soluble modulin (PSM) is a peptide complex produced by the nosocomial pathogen Staphylococcus epidermidis that has a strong capacity to activate the human innate immune response. We developed a novel method based on liquid chromatography-mass spectrometry (LC-MS) to quantify the production of the individual PSM components. Each PSM peptide was abundant in most of the 76 S epidermidis strains tested. Importantly, none of the PSM components were secreted by an agr mutant strain, indicating that PSM synthesis is regulated strictly by the agr quorum-sensing system. Furthermore, the agr mutant strain failed to elicit production of TNFalpha by human myeloid cells and induced significantly less neutrophil chemotaxis compared with the wild-type strain. Thus, quorum-sensing in S. epidermidis dramatically influenced activation of human host defence. We propose that an agr quorum-sensing mechanism facilitates growth and survival in infected hosts by adapting production of the pro-inflammatory PSMs to the stage of infection. JF - Cellular microbiology AU - Vuong, Cuong AU - Dürr, Manuela AU - Carmody, Aaron B AU - Peschel, Andreas AU - Klebanoff, Seymour J AU - Otto, Michael AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, 903 S 4th Street, Hamilton, MT 59840, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 753 EP - 759 VL - 6 IS - 8 SN - 1462-5814, 1462-5814 KW - Bacterial Toxins KW - 0 KW - staphylococcal delta toxin KW - Index Medicus KW - Virulence KW - Mass Spectrometry KW - Humans KW - Inflammation -- etiology KW - Chromatography, Liquid KW - Mutation KW - Inflammation -- pathology KW - Bacterial Toxins -- metabolism KW - Bacterial Toxins -- analysis KW - Staphylococcus epidermidis -- metabolism KW - Staphylococcus epidermidis -- physiology KW - Staphylococcus epidermidis -- pathogenicity KW - Bacterial Toxins -- toxicity KW - Staphylococcal Infections -- microbiology KW - Staphylococcal Infections -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66679322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Regulated+expression+of+pathogen-associated+molecular+pattern+molecules+in+Staphylococcus+epidermidis%3A+quorum-sensing+determines+pro-inflammatory+capacity+and+production+of+phenol-soluble+modulins.&rft.au=Vuong%2C+Cuong%3BD%C3%BCrr%2C+Manuela%3BCarmody%2C+Aaron+B%3BPeschel%2C+Andreas%3BKlebanoff%2C+Seymour+J%3BOtto%2C+Michael&rft.aulast=Vuong&rft.aufirst=Cuong&rft.date=2004-08-01&rft.volume=6&rft.issue=8&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=Cellular+microbiology&rft.issn=14625814&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-05 N1 - Date created - 2004-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fmoc-based chemical synthesis and selective binding to supercoiled DNA of the p53 C-terminal segment and its phosphorylated and acetylated derivatives AN - 21157353; 11338236 AB - The C-terminal domain of p53 comprises a linker, the tetramerization domain and the regulatory domain, and contains at least seven sites of potential post-translational modification. An improved strategy was developed for the synthesis of large peptides that contain phosphorylated amino acids and p53(303-393), a 91-amino acid peptide, and three post-translationally modified derivatives were synthesized through the sequential condensation of three partially protected segments. Peptide thiolesters were prepared using the sulfonamide-based safety-catch resin approach and employing Fmoc-based solid-phase peptide synthesis. At the N-terminus of the middle building block, a photolabile protecting group, 3,4-dimethoxy-6-nitrobenzyloxycarbonyl, was incorporated to differentiate the N-terminal amino group from the side-chain amino groups. Two sequential couplings were accomplished following this protection strategy. The synthetic products, p53(303-393) and its phosphorylated or acetylated derivatives, exhibited the ability to bind specifically to supercoiled DNA, which is one of the characteristics of this domain. Published in 2004 by the European Peptide Society and John Wiley & Sons, Ltd. JF - Journal of Peptide Science AU - Teruya, Kenta AU - Murphy, Angela C AU - Burlin, Tom AU - Appella, Ettore AU - Mazur, Sharlyn J AD - National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD 20892, USA, mazurs@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 479 EP - 493 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 10 IS - 8 SN - 1075-2617, 1075-2617 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Amino groups KW - Resins KW - Amino acids KW - Post-translation KW - DNA KW - Condensation KW - thiolesters KW - Peptide synthesis KW - Protecting groups KW - p53 protein KW - N-Terminus KW - W 30940:Products KW - N 14835:Protein-Nucleic Acids Association UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21157353?accountid=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+Peptide+Science&rft.atitle=Fmoc-based+chemical+synthesis+and+selective+binding+to+supercoiled+DNA+of+the+p53+C-terminal+segment+and+its+phosphorylated+and+acetylated+derivatives&rft.au=Teruya%2C+Kenta%3BMurphy%2C+Angela+C%3BBurlin%2C+Tom%3BAppella%2C+Ettore%3BMazur%2C+Sharlyn+J&rft.aulast=Teruya&rft.aufirst=Kenta&rft.date=2004-08-01&rft.volume=10&rft.issue=8&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Journal+of+Peptide+Science&rft.issn=10752617&rft_id=info:doi/10.1002%2Fpsc.552 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Resins; Amino groups; Amino acids; Post-translation; DNA; thiolesters; Condensation; Peptide synthesis; Protecting groups; N-Terminus; p53 protein DO - http://dx.doi.org/10.1002/psc.552 ER - TY - JOUR T1 - Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients AN - 20859737; 6650339 AB - The purpose of this study was to perform exploratory relationships between the pharmacokinetics of the farnesyl transferase inhibitor, tipifarnib (R115777, Zarnestra) and allelic variants of genes coding for ATP binding-cassette transporters and drug-metabolizing enzymes. Twenty-eight patients with advanced solid tumors were treated with tipifarnib administered orally at a dose of 200 or 300 mg. Blood samples were collected for pharmacokinetics and genotyping of 10 variants in genes encoding P-glycoprotein (ABCB1), cytochrome P450 isozymes CYP3A4 and CYP3A5, and UDP glucuronosyltransferase isozyme UGT1A1. The homozygous T-allele of ABCB1*8 (1236C > T) was associated with a trend for a higher area under the curve of tipifarnib as compared to patients with only one or no variant alleles [mean ( plus or minus SD), 5,303 plus or minus 1,620 ng.h/mL vs. 3,619 plus or minus 1,275 ng.h/mL; P = 0.047). No statistically significant differences were observed with any other genetic variant (P > 0.15). Overall, this study indicates that ABCB1 genotype might be correlated with tipifarnib pharmacokinetics, although considerable overlap in exposure measures between genotype groups was observed. JF - Investigational New Drugs AU - Sparreboom, Alex AU - Marsh, Sharon AU - Mathijssen, Ron HJ AU - Verweij, Jaap AU - McLeod, Howard L AD - National Cancer Institute, Bethesda, MD, USA Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 285 EP - 289 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 22 IS - 3 SN - 0167-6997, 0167-6997 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Glucuronosyltransferase KW - Solid tumors KW - Genotyping KW - Statistical analysis KW - Enzymes KW - ATP KW - Genotypes KW - Pharmacogenetics KW - Pharmacokinetics KW - P-Glycoprotein KW - Isoenzymes KW - Cytochrome P450 KW - Metabolism KW - G 07880:Human Genetics KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20859737?accountid=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=Investigational+New+Drugs&rft.atitle=Pharmacogenetics+of+tipifarnib+%28R115777%29+transport+and+metabolism+in+cancer+patients&rft.au=Sparreboom%2C+Alex%3BMarsh%2C+Sharon%3BMathijssen%2C+Ron+HJ%3BVerweij%2C+Jaap%3BMcLeod%2C+Howard+L&rft.aulast=Sparreboom&rft.aufirst=Alex&rft.date=2004-08-01&rft.volume=22&rft.issue=3&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Investigational+New+Drugs&rft.issn=01676997&rft_id=info:doi/10.1023%2FB%3ADRUG.0000026254.97350.fe LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-09-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Glucuronosyltransferase; Solid tumors; Genotyping; Statistical analysis; ATP; Enzymes; Genotypes; Pharmacokinetics; Pharmacogenetics; P-Glycoprotein; Isoenzymes; Cytochrome P450; Metabolism DO - http://dx.doi.org/10.1023/B:DRUG.0000026254.97350.fe ER - TY - JOUR T1 - Bioeconomics of Managing the Spread of Exotic Pest Species with Barrier Zones AN - 20133638; 6120793 AB - Exotic pests are serious threats to North American ecosystems; thus, economic analysis of decisions about eradication, stopping, or slowing their spread may be critical to ecosystem management. The proposed bioeconomic model assumes that the rate of population expansion can be reduced (even to negative values in a case of eradication) if certain management actions are taken along the population front. The area of management can be viewed as a dynamic barrier zone that moves together with the population front. The lower is the target rate of spread, the higher would be both benefits and costs of the project. The problem is to find the optimal target rate of spread at which the present value of net benefits from managing population spread reaches its maximum value. If a population spreads along an infinite habitat strip, the target rate of spread is optimal if the slope of the cost function versus the rate of spread is equal to the ratio of the average pest-related damage per unit time and unit area to the discount rate. In a more complex model where the potential area of expansion is limited, two local maxima of net benefits may exist: one for eradication and another for slowing the spread. If both maxima are present, their heights are compared and the strategy that corresponds to a higher value of net benefits is selected. The optimal strategy changes from eradication to slowing the spread and finally to doing nothing as the area occupied by the species increases. The model shows that slowing the spread of pest species generates economic benefits even if a relatively small area remains uninfested. The cost of slowing the spread can be estimated from a model of population expansion via establishment of isolated colonies beyond the moving front. The model is applied to managing the spread of the gypsy moth (Lymantria dispar) populations in the United States. JF - Risk Analysis AU - Sharov, A A AD - National Institute on Aging, Baltimore, MD, USA, Sharoval@grc.nia.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 879 EP - 892 VL - 24 IS - 4 SN - 0272-4332, 0272-4332 KW - Gypsy Moth KW - Entomology Abstracts; Sustainability Science Abstracts; ASFA 1: Biological Sciences & Living Resources KW - North America KW - population levels KW - Barriers KW - Ecosystems KW - Habitat preferences KW - Pest control KW - Habitat KW - Nearctic Region KW - Models KW - USA KW - Lymantriidae KW - pests KW - Infestation KW - Colonies KW - Economics KW - Ecosystem management KW - Economic analysis KW - Introduced species KW - Economic benefits KW - Lymantria dispar KW - economic analysis KW - M3 1010:Issues in Sustainable Development KW - Z 05350:Medical, Veterinary, and Agricultural Entomology KW - Q1 08485:Species interactions: pests and control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20133638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Assamodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Risk+Analysis&rft.atitle=Bioeconomics+of+Managing+the+Spread+of+Exotic+Pest+Species+with+Barrier+Zones&rft.au=Sharov%2C+A+A&rft.aulast=Sharov&rft.aufirst=A&rft.date=2004-08-01&rft.volume=24&rft.issue=4&rft.spage=879&rft.isbn=&rft.btitle=&rft.title=Risk+Analysis&rft.issn=02724332&rft_id=info:doi/10.1111%2Fj.0272-4332.2004.00486.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Barriers; Economic analysis; Ecosystem management; Introduced species; Economic benefits; Colonies; Infestation; Economics; Habitat preferences; Pest control; Models; pests; population levels; Ecosystems; Habitat; economic analysis; Lymantriidae; Lymantria dispar; North America; USA; Nearctic Region DO - http://dx.doi.org/10.1111/j.0272-4332.2004.00486.x ER - TY - JOUR T1 - Global Gene Expression Profile of Nasopharyngeal Carcinoma by Laser Capture Microdissection and Complementary DNA Microarrays AN - 19937671; 5969439 AB - A number of genetic and epigenetic changes underlying the development of nasopharyngeal carcinomas have recently been identified. However, there is still limited information on the nature of the genes and gene products whose aberrant expression and activity promote the malignant conversion of nasopharyngeal epithelium. Here, we have performed a genome-wide transcriptome analysis by probing cDNA microarrays with fluorescent-labeled amplified RNA derived from laser capture microdissected cells procured from normal nasopharyngeal epithelium and areas of metaplasia-dysplasia and carcinoma from EBV-associated nasopharyngeal carcinomas. This approach enabled the identification of genes differentially expressed in each cell population, as well as numerous genes whose expression can help explain the aggressive clinical nature of this tumor type. For example, genes indicating cell cycle aberrations (cyclin D2, cyclin B1, activator of S-phase kinase, and the cell cycle checkpoint kinase, CHK1) and invasive-metastatic potential (matrix metalloproteinase 11, v-Ral, and integrin beta sub(4)) were highly expressed in tumor cells. In contrast, genes underexpressed in tumors included genes involved in apoptosis (B-cell CLL/lymphoma 6, secretory leukocyte protease inhibitor, and calpastatin), cell structure (keratin 7 and carcinoembryonic antigen-related cell adhesion molecule 6), and putative tumor suppressor genes (H-Ras-like suppressor 3, retinoic acid receptor responder 1, and growth arrested specific 8) among others. Gene expression patterns also suggested alterations in the Wnt/ beta -catenin and transforming growth factor beta pathways in nasopharyngeal carcinoma. Thus, expression profiles indicate that aberrant expression of growth, survival, and invasion-promoting genes may contribute to the molecular pathogenesis of nasopharyngeal carcinoma. Ultimately, this approach may facilitate the identification of clinical useful markers of disease progression and novel potential therapeutic targets for nasopharyngeal carcinoma. JF - Clinical Cancer Research AU - Sriuranpong, Virote AU - Mutirangura, Apiwat AU - Gillespie, John W AU - Patel, Vyomesh AU - Amornphimoltham, Panomwat AU - Molinolo, Alfredo A AU - Kerekhanjanarong, Veerachai AU - Supanakorn, Siripornchai AU - Supiyaphun, Pakpoom AU - Rangdaeng, Samreung AU - Voravud, Narin AU - Gutkind, JSilvio AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, and Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 4944 EP - 4958 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 10 IS - 15 SN - 1078-0432, 1078-0432 KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Tumor suppressor genes KW - Apoptosis KW - Wnt protein KW - Cell cycle KW - Survival KW - Matrix metalloproteinase KW - DNA microarrays KW - Tumor cells KW - Gene expression KW - epigenetics KW - Cyclin B1 KW - Cytology KW - Epithelium KW - cyclin D2 KW - Lymphoma KW - Retinoic acid receptors KW - Lymphocytes B KW - Proteinase inhibitors KW - Leukocytes KW - Tumors KW - catenin KW - Keratin KW - Nasopharyngeal carcinoma KW - RNA KW - Transforming growth factor- beta KW - Lasers KW - CHK1 protein KW - Chronic lymphatic leukemia KW - Calpastatin KW - Cell adhesion molecules KW - W 30915:Pharmaceuticals & Vaccines KW - G 07730:Development & Cell Cycle KW - N 14825:Gene Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19937671?accountid=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+Cancer+Research&rft.atitle=Global+Gene+Expression+Profile+of+Nasopharyngeal+Carcinoma+by+Laser+Capture+Microdissection+and+Complementary+DNA+Microarrays&rft.au=Sriuranpong%2C+Virote%3BMutirangura%2C+Apiwat%3BGillespie%2C+John+W%3BPatel%2C+Vyomesh%3BAmornphimoltham%2C+Panomwat%3BMolinolo%2C+Alfredo+A%3BKerekhanjanarong%2C+Veerachai%3BSupanakorn%2C+Siripornchai%3BSupiyaphun%2C+Pakpoom%3BRangdaeng%2C+Samreung%3BVoravud%2C+Narin%3BGutkind%2C+JSilvio&rft.aulast=Sriuranpong&rft.aufirst=Virote&rft.date=2004-08-01&rft.volume=10&rft.issue=15&rft.spage=4944&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-06-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Tumor suppressor genes; Wnt protein; Apoptosis; Cell cycle; Matrix metalloproteinase; Survival; Tumor cells; DNA microarrays; Gene expression; Cyclin B1; epigenetics; Cytology; Epithelium; cyclin D2; Lymphoma; Retinoic acid receptors; Lymphocytes B; Leukocytes; Proteinase inhibitors; Tumors; Nasopharyngeal carcinoma; Keratin; catenin; RNA; Transforming growth factor- beta; CHK1 protein; Lasers; Calpastatin; Chronic lymphatic leukemia; Cell adhesion molecules ER - TY - JOUR T1 - Prevalence of multiple chronic disease risk factors 2001 National Health Interview Survey AN - 19637312; 8790683 AB - Background: Four common factors-cigarette smoking, risky drinking of alcoholic beverages, physical inactivity, and overweight-contribute substantially to chronic disease prevalence. Methods We used data from the 2001 National Health Interview Survey to provide an up-to-date picture of multiple risk factor prevalence and clustering in the U.S. population. We conducted a multinomial logit analysis to examine the independent association between each covariate and the dependent ordinal risk factor variable with three levels (none or one risk factor, two risk factors, and three or four risk factors). Results Seventeen percent of the sample of 29,183 subjects had three or more risk factors. For the entire sample, the mean number of risk factors was 1.68 (95% confidence interval [CI]=1.66-1.70). Many demographic and health factors were significantly associated with the mean number of risk factors including gender, age, ethnic/racial categories, education, martial status, presence of chronic diseases, level of mental distress, country of birth, and presence and type of health insurance. Using the risk factor score as the ordinal dependent variable, adjusted odds for having a risk score of three or four versus zero or one were as follows: men aged <65, 2.49 (95% CI=2.29-2.72); education attainment of high school graduate or less, 3.24 (95% CI=2.86-3.67); and individuals with high levels of mental distress, 2.06 (95% CI=1.65-2.58). Conclusions Our analyses confirm earlier reports of the high prevalence of multiple, clustered behavioral risk factors and underline the challenge this presents for primary care and public health systems. JF - American Journal of Preventive Medicine AU - Fine, Lawrence J AU - Philogene, G Stephane AU - Gramling, Robert AU - Coups, Elliot J AU - Sinha, Sarbajit AD - Office of Behavioral and Social Sciences Research, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA, FineL@od.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 18 EP - 24 PB - Elsevier Science, The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 27 IS - 2 SN - 0749-3797, 0749-3797 KW - Risk Abstracts KW - demography KW - Age KW - Insurance KW - Public health KW - Smoking KW - Education KW - USA KW - Gender KW - physical activity KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19637312?accountid=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+Preventive+Medicine&rft.atitle=Prevalence+of+multiple+chronic+disease+risk+factors+2001+National+Health+Interview+Survey&rft.au=Fine%2C+Lawrence+J%3BPhilogene%2C+G+Stephane%3BGramling%2C+Robert%3BCoups%2C+Elliot+J%3BSinha%2C+Sarbajit&rft.aulast=Fine&rft.aufirst=Lawrence&rft.date=2004-08-01&rft.volume=27&rft.issue=2&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Preventive+Medicine&rft.issn=07493797&rft_id=info:doi/10.1016%2Fj.amepre.2004.04.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-02-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - USA; Education; Insurance; Gender; physical activity; Public health; Smoking; demography; Age DO - http://dx.doi.org/10.1016/j.amepre.2004.04.017 ER - TY - JOUR T1 - Patterns of Pesticide Use and Their Determinants Among Wives of Farmer Pesticide Applicators in the Agricultural Health Study AN - 18060808; 6019973 AB - Pesticide exposure among farmers' wives is poorly characterized. Using questionnaire data from a cohort study of licensed pesticide applicators and their spouses, we investigated patterns of pesticide use among farmers' wives (n = 31,173). Wives reported a wide range of pesticide use: 36% never used pesticides during their lifetimes, whereas the heaviest pesticide users (10%) reported lifetime use of 3 or more agricultural pesticides plus commonly used residential pesticides. We identified 5 ordinal pesticide-use categories and studied factors associated with each category through polytomous logistic regression. Engaging in field work and household hygiene practices that could increase exposure were associated with pesticide use, and associations appeared to strengthen with increasing pesticide use category. Farm women reporting the heaviest pesticide use could exacerbate their exposure by engaging in practices that could increase pesticide contact. JF - Journal of Occupational and Environmental Medicine AU - Kirrane, E F AU - Hoppin, JA AU - Umbach, D M AU - Samanic, C AU - Sandler, D P AD - Epidemiology Branch, NIH, MD A3 05, Box 12233, Research Triangle Park, NC 27709, USA, hoppin1@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 856 EP - 865 VL - 46 IS - 8 SN - 1076-2752, 1076-2752 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Farms KW - Agrochemicals KW - Exposure KW - Pesticides KW - Residential areas KW - Hygiene KW - Occupational exposure KW - H 5000:Pesticides KW - X 24222:Analytical procedures KW - X 24136:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18060808?accountid=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+Occupational+and+Environmental+Medicine&rft.atitle=Patterns+of+Pesticide+Use+and+Their+Determinants+Among+Wives+of+Farmer+Pesticide+Applicators+in+the+Agricultural+Health+Study&rft.au=Kirrane%2C+E+F%3BHoppin%2C+JA%3BUmbach%2C+D+M%3BSamanic%2C+C%3BSandler%2C+D+P&rft.aulast=Kirrane&rft.aufirst=E&rft.date=2004-08-01&rft.volume=46&rft.issue=8&rft.spage=856&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/10.1097%2F01.jom.0000135521.15169.3e LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Residential areas; Pesticides; Agrochemicals; Hygiene; Exposure; Farms DO - http://dx.doi.org/10.1097/01.jom.0000135521.15169.3e ER - TY - JOUR T1 - Animal models for arsenic carcinogenesis: inorganic arsenic is a transplacental carcinogen in mice AN - 18054701; 6045937 AB - Inorganic arsenic is a known human carcinogen causing tumors of the skin, urinary bladder, lung, liver, kidney, and possibly other organs. However, the animal models for inorganic arsenic carcinogenesis have been limited and development has been problematic. Gestation is often a period of high sensitivity to carcinogenesis so we investigated inorganic arsenite as a transplacental carcinogen in mice. Pregnant C3H mice were exposed to sodium arsenite (0, 42.5, and 85 ppm as arsenic) in the drinking water for a brief period during gestation (from gestation day 8 to 18), with no further arsenic exposure or other treatments. The offsprings were monitored up to 90 weeks. Transplacental inorganic arsenic exposure produced a dose-dependent induction of tumors in the liver, adrenal, lung, and ovary in the offsprings after they had reached adulthood. This included hepatocellular carcinoma (HCC), a tumor associated with arsenic exposure in humans. These tumors occurred when mice became adults in the absence of any other treatments and well after arsenic exposure had ended. Genomic analysis of liver tumors and tumor-surrounding tissues revealed several patterns of aberrant gene expression associated with transplacental arsenic carcinogenesis. This animal model demonstrated that inorganic arsenic could act as a 'complete' transplacental carcinogen in mice. In addition, other important animal models for inorganic arsenic as a skin tumor co-promoter or as a co-carcinogen are discussed. The development of these animal models should advance our understanding of the mechanisms of inorganic arsenic carcinogenesis. JF - Toxicology and Applied Pharmacology AU - Waalkes, M P AU - Liu, J AU - Ward, J M AU - Diwan, BA AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, waalkes@niehs.nih.gov Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 377 EP - 384 PB - Elsevier Inc. VL - 198 IS - 3 SN - 0041-008X, 0041-008X KW - mice KW - Toxicology Abstracts KW - Arsenic KW - Sodium arsenite KW - Skin KW - Urinary bladder KW - Animal models KW - Offspring KW - Carcinogens KW - Gene expression KW - Lung KW - Genomic analysis KW - Gestation KW - Carcinogenesis KW - Kidney KW - Ovaries KW - Hepatocellular carcinoma KW - X 24165:Biochemistry KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18054701?accountid=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=Animal+models+for+arsenic+carcinogenesis%3A+inorganic+arsenic+is+a+transplacental+carcinogen+in+mice&rft.au=Waalkes%2C+M+P%3BLiu%2C+J%3BWard%2C+J+M%3BDiwan%2C+BA&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2004-08-01&rft.volume=198&rft.issue=3&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1016%2Fj.taap.2003.10.028 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arsenic; Carcinogenesis; Animal models; Carcinogens; Gestation; Offspring; Skin; Lung; Sodium arsenite; Ovaries; Gene expression; Hepatocellular carcinoma; Urinary bladder; Genomic analysis; Kidney DO - http://dx.doi.org/10.1016/j.taap.2003.10.028 ER - TY - JOUR T1 - Translation repression by an RNA polymerase elongation complex AN - 18054361; 6003910 AB - Bacteriophage lambda N and bacterial Nus proteins together with a unique site NUT in the leader of the early viral N gene transcript bind RNA polymerase (RNAP) and form a highly processive antitermination complex; N bound at NUT also represses N translation. In this study, we investigate whether N and NUT cause N translation repression as part of the antitermination complex by testing conditions that inhibit the formation of the N-modified transcription complex for their effect on N-mediated translation repression. We show that nus and nut mutations that in combination destabilize multiple interactions in the antitermination complex prevent N-mediated translation repression. Likewise, transcription of the nut-N region by T7 RNAP, which does not lead to the assembly of an effective antitermination complex when N is supplied, eliminates translation repression. We also demonstrate that a unique mutant beta subunit of RNAP reduces N-mediated translation repression, and that overexpression of transcription factor NusA suppresses this defect. We conclude that the N-modified RNAP transcription complex is necessary to repress N translation. JF - Molecular Microbiology AU - Wilson, H R AU - Zhou, J AU - Yu, D AU - Court, D L AD - Molecular Control and Genetics Section, Gene Regulation and Chromosome Biology, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA., court@ncifcrf.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 821 EP - 828 PB - Blackwell Science Ltd VL - 53 IS - 3 SN - 0950-382X, 0950-382X KW - antitermination KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Phages KW - Translation KW - Elongation KW - double prime N gene KW - Bacteria KW - DNA-directed RNA polymerase KW - Transcription factors KW - Transcription KW - Mutation KW - Gene silencing KW - J 02726:RNA and ribosomes KW - V 22070:Phage-host interactions including lysogeny & transduction KW - N 14551:Virus & phage infections UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18054361?accountid=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=Translation+repression+by+an+RNA+polymerase+elongation+complex&rft.au=Wilson%2C+H+R%3BZhou%2C+J%3BYu%2C+D%3BCourt%2C+D+L&rft.aulast=Wilson&rft.aufirst=H&rft.date=2004-08-01&rft.volume=53&rft.issue=3&rft.spage=821&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04170.x LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Phages; Bacteria; double prime N gene; Elongation; Translation; DNA-directed RNA polymerase; Transcription factors; Transcription; Mutation; Gene silencing DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04170.x ER - TY - JOUR T1 - High-resolution genome-wide mapping of histone modifications AN - 18019482; 5993744 AB - The expression patterns of eukaryotic genomes are controlled by their chromatin structure, consisting of nucleosome subunits in which DNA of approximately 146 bp is wrapped around a core of 8 histone molecules. Post-translational histone modifications play an essential role in modifying chromatin structure. Here we apply a combination of SAGE and chromatin immunoprecipitation (ChIP) protocols to determine the distribution of hyperacetylated histones H3 and H4 in the Saccharomyces cerevisiae genome. We call this approach genome-wide mapping technique (GMAT). Using GMAT, we find that the highest acetylation levels are detected in the 5' end of a gene's coding region, but not in the promoter. Furthermore, we show that the histone acetyltransferase, GCN5p, regulates H3 acetylation in the promoter and 5' end of the coding regions. These findings indicate that GMAT should find valuable applications in mapping target sites of chromatin-modifying enzymes. JF - Nature Biotechnology AU - Roh, T-Y AU - Ngau, W C AU - Cui, K AU - Landsman, D AU - Zhao, K AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA, zhaok@nhlbi.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1013 EP - 1016 VL - 22 IS - 8 SN - 1087-0156, 1087-0156 KW - budding yeast KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - Histones KW - Serial analysis of gene expression KW - Chromatin KW - Saccharomyces cerevisiae KW - Acetylation KW - DNA KW - Gene mapping KW - N 14040:Genome/chromosome structure & maintenance KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18019482?accountid=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=High-resolution+genome-wide+mapping+of+histone+modifications&rft.au=Roh%2C+T-Y%3BNgau%2C+W+C%3BCui%2C+K%3BLandsman%2C+D%3BZhao%2C+K&rft.aulast=Roh&rft.aufirst=T-Y&rft.date=2004-08-01&rft.volume=22&rft.issue=8&rft.spage=1013&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt990 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Saccharomyces cerevisiae; Serial analysis of gene expression; Histones; Chromatin; Acetylation; DNA; Gene mapping DO - http://dx.doi.org/10.1038/nbt990 ER - TY - JOUR T1 - Application of a Statistical Dynamic Model Investigating the Short-Term Cellular Kinetics Induced by Riddelliine, a Hepatic Endothelial Carcinogen AN - 18007981; 5945833 AB - In recent studies, riddelliine, a pyrrolizidine alkaloid, was found to increase rates of replication and apoptosis and induce hemangiosarcoma in the liver of rats and mice. To analyze DNA replication and apoptosis data taken from the same animals, we have developed a predictive mathematical model for describing BrdU labeling and apoptotic processes. The model allows the incorporation of simple diurnal patterns in cellular kinetics and is applied to data on hepatocytes and endothelial cells taken from riddelliine exposed rats. Predictions from the model were used with multivariable nonlinear regression techniques to estimate replication and apoptotic rate constants for both cell types and all treatment groups. Hypothesis tests were used with the predicted rates to separate the competing effects of riddelliine on replication and apoptosis of hepatocytes and endothelial cells as well as compare replication rates between cell types. That estimated replication rates were found to be significantly higher for endothelial cells supports the supposition of induction of hemangiosarcoma by riddelliine in the liver. JF - Toxicological Sciences AU - Smith, Marjo V AU - Nyska, Abraham AU - Portier, Chris AD - Constella Health Sciences, 2605 Meridian Parkway, Durham, North Carolina 27713 and National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27713 Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 258 EP - 267 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 80 IS - 2 SN - 1096-6080, 1096-6080 KW - hemangiosarcoma KW - mice KW - pyrrolizidine alkaloid KW - rats KW - riddelliine KW - Toxicology Abstracts KW - Prediction KW - Endothelial cells KW - DNA biosynthesis KW - Alkaloids KW - Mathematical models KW - Apoptosis KW - Replication KW - Hepatocytes KW - DNA KW - Liver KW - X 24173:Animals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18007981?accountid=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=Toxicological+Sciences&rft.atitle=Application+of+a+Statistical+Dynamic+Model+Investigating+the+Short-Term+Cellular+Kinetics+Induced+by+Riddelliine%2C+a+Hepatic+Endothelial+Carcinogen&rft.au=Smith%2C+Marjo+V%3BNyska%2C+Abraham%3BPortier%2C+Chris&rft.aulast=Smith&rft.aufirst=Marjo&rft.date=2004-08-01&rft.volume=80&rft.issue=2&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Endothelial cells; Prediction; DNA biosynthesis; Alkaloids; Apoptosis; Mathematical models; Hepatocytes; Replication; Liver; DNA ER - TY - JOUR T1 - Three-Dimensional Electron Microscopic Imaging of Membrane Invaginations in Escherichia coli Overproducing the Chemotaxis Receptor Tsr AN - 17991438; 5952582 AB - Electron tomography is a powerful method for determining the three- dimensional structures of large macromolecular assemblies, such as cells, organelles, and multiprotein complexes, when crystallographic averaging methods are not applicable. Here we used electron tomographic imaging to determine the molecular architecture of Escherichia coli cells engineered to overproduce the bacterial chemotaxis receptor Tsr. Tomograms constructed from fixed, cryosectioned cells revealed that overproduction of Tsr led to formation of an extended internal membrane network composed of stacks and extended tubular structures. We present an interpretation of the tomogram in terms of the packing arrangement of Tsr using constraints derived from previous X-ray and electron- crystallographic studies of receptor clusters. Our results imply that the interaction between the cytoplasmic ends of Tsr is likely to stabilize the presence of the membrane networks in cells overproducing Tsr. We propose that membrane invaginations that are potentially capable of supporting axial interactions between receptor clusters in apposing membranes could also be present in wild-type E. coli and that such receptor aggregates could play an important role in signal transduction during bacterial chemotaxis. JF - Journal of Bacteriology AU - Lefman, Jonathan AU - Zhang, Peijun AU - Hirai, Teruhisa AU - Weis, Robert M AU - Juliani, Jemma AU - Bliss, Donald AU - Kessel, Martin AU - Bos, Erik AU - Peters, Peter J AU - Subramaniam, Sriram AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 5052 EP - 5061 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 15 SN - 0021-9193, 0021-9193 KW - Tsr protein KW - Microbiology Abstracts B: Bacteriology KW - Cell membranes KW - Escherichia coli KW - Receptors KW - Tomography KW - Invaginations KW - Chemotaxis KW - Signal transduction KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17991438?accountid=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=Three-Dimensional+Electron+Microscopic+Imaging+of+Membrane+Invaginations+in+Escherichia+coli+Overproducing+the+Chemotaxis+Receptor+Tsr&rft.au=Lefman%2C+Jonathan%3BZhang%2C+Peijun%3BHirai%2C+Teruhisa%3BWeis%2C+Robert+M%3BJuliani%2C+Jemma%3BBliss%2C+Donald%3BKessel%2C+Martin%3BBos%2C+Erik%3BPeters%2C+Peter+J%3BSubramaniam%2C+Sriram&rft.aulast=Lefman&rft.aufirst=Jonathan&rft.date=2004-08-01&rft.volume=186&rft.issue=15&rft.spage=5052&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Cell membranes; Receptors; Tomography; Invaginations; Chemotaxis; Signal transduction; Escherichia coli ER - TY - JOUR T1 - Age and gender affect ventricular-vascular coupling during aerobic exercise AN - 17883635; 6086755 AB - Objectives The goal of this study was to examine the age-associated differences in ventricular-vascular coupling, defined by the ratio of arterial elastance (EaI) to left ventricular systolic elastance (E sub(LV)I), and its components, at rest and during exercise. Background Ejection fraction (EF) increases during exercise, but the EF reserve decreases with aging. Ejection fraction is inversely related to EaI/E sub(LV)I, an index of the interaction between arterial and ventricular properties, which is an important determinant of cardiac performance. Thus, age differences in EaI/E sub(LV)I during exercise, due to age differences in EaI, E sub(LV)I, or both, may help to explain the age deficit in EF reserve. Methods We noninvasively characterized EaI/E sub(LV)I = end-systolic volume index (ESVI)/stroke volume index (SVI) and its two determinants EaI = end-systolic pressure/SVI, and E sub(LV)I = end-systolic pressure/ESVI, at rest and during exercise in 239 healthy men and women (age range, 21 to 87 years). Blood pressures were assessed with cuff sphygomanometry, and cardiac volumes with gated blood pool scintingraphy. Results Resting EaI/E sub(LV)I was not age related in men or women. In both sexes, EaI/E sub(LV)I decreased during exercise and declined to a lesser extent in older subjects. There were gender differences in the components of EaI/E sub(LV)I during exercise: EaI was greater in older versus young women (p = 0.01) but was unaffected by age in men. Left ventricular systolic elastance increased to a greater extent in young versus older subjects (p = 0.0001 for men, P = 0.07 for women). Conclusions Age-associated differences in EaI/E sub(LV)I occur in both genders during exercise. Sub-optimal ventricular-vascular coupling helps to explain the age-associated blunting of maximal exercise EF, and its underlying mechanisms appear to differ between men and women. JF - Journal of the American College of Cardiology AU - Najjar, S S AU - Schulman, S P AU - Gerstenblith, G AU - Fleg, J L AU - Kass, DA AU - O'Connor, F AU - Becker, L C AU - Lakatta, E G AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive,, Baltimore, Maryland 21224,, USA Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 611 EP - 617 VL - 44 IS - 3 SN - 0735-1097, 0735-1097 KW - Physical Education Index KW - Age KW - Aerobics KW - Heart (stroke volume) KW - Gerontology KW - Stress KW - Adults KW - Exercise KW - Sex differences KW - Blood pressure KW - Blood KW - Cardiac output KW - Rest KW - Performance KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17883635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+College+of+Cardiology&rft.atitle=Age+and+gender+affect+ventricular-vascular+coupling+during+aerobic+exercise&rft.au=Najjar%2C+S+S%3BSchulman%2C+S+P%3BGerstenblith%2C+G%3BFleg%2C+J+L%3BKass%2C+DA%3BO%27Connor%2C+F%3BBecker%2C+L+C%3BLakatta%2C+E+G&rft.aulast=Najjar&rft.aufirst=S&rft.date=2004-08-01&rft.volume=44&rft.issue=3&rft.spage=611&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Cardiology&rft.issn=07351097&rft_id=info:doi/10.1016%2Fj.jacc.2004.04.041 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Exercise; Adults; Gerontology; Sex differences; Age; Rest; Stress; Performance; Blood; Aerobics; Heart (stroke volume); Blood pressure; Cardiac output DO - http://dx.doi.org/10.1016/j.jacc.2004.04.041 ER - TY - JOUR T1 - RNAi quashes polyQ AN - 17881341; 5994264 AB - RNA interference in the brain inhibits neurodegeneration in a polyglutamine disease, SCA1. Is this now the way forward for the clinical treatment of certain genetic disorders?. JF - Nature Medicine AU - Caplen, N J AD - Gene Silencing Section, Office of Science and Technology Partnerships, Office of the Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, ncaplen@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 775 VL - 10 IS - 8 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - polyglutamine diseases KW - Hereditary diseases KW - Brain KW - ataxin KW - Neurodegeneration KW - Neurodegenerative diseases KW - Movement disorders KW - Reviews KW - Polyglutamine KW - RNA-mediated interference KW - Spinocerebellar ataxia KW - N 14100:Reviews KW - W3 33243:Molecular methods KW - N3 11011:Motor systems and movement disorders KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17881341?accountid=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+Medicine&rft.atitle=RNAi+quashes+polyQ&rft.au=Caplen%2C+N+J&rft.aulast=Caplen&rft.aufirst=N&rft.date=2004-08-01&rft.volume=10&rft.issue=8&rft.spage=775&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&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 - ataxin; RNA-mediated interference; Hereditary diseases; Brain; Neurodegenerative diseases; Polyglutamine; Reviews; Movement disorders; Spinocerebellar ataxia; Neurodegeneration; polyglutamine diseases ER - TY - JOUR T1 - Simultaneous Quantification of Opiates, Cocaine, and Metabolites in Hair by LC-APCI-MS/MS AN - 17825522; 6129970 AB - A quantitative LC-APCI-MS/MS method for simultaneous measurement of opiates, cocaine, and metabolites in hair was developed and validated. Cocaine and opiates were extracted from pulverized hair via sonication in methanol at 37 degree C for 3 h. Samples were cleaned up using solid-phase extraction. LC separation was achieved in 20 min with identification and quantification by selected reaction monitoring. Calibration by linear regression analysis utilized deuterated internal standards and a weighting factor of 1/x (R super(2) > 0.998). Limits of quantification (LOQ) ranged from 17 to 50 pg/mg for cocaine and metabolites and were 83 pg/mg for opiates. Standard curves were linear from the LOQ to 5000 pg/mg for cocaine and metabolites, except benzoylecgonine (2500 pg/mg). Opiate standard curves were linear from the LOQ to 12500 pg/mg. Accuracy ranged from 84 to 115% for all quantitative analytes. Precision, % relative standard deviation, was less than 11.0% for all analytes. Methanolic sonication produced less than 5% hydrolysis of cocaine and 6-acetylmorphine. The method should be useful for studying cocaine and opiate distribution into hair. JF - Analytical Chemistry (Washington) AU - Scheidweiler, K B AU - Huestis, MA AD - Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 4358 EP - 4363 VL - 76 IS - 15 SN - 0003-2700, 0003-2700 KW - Toxicology Abstracts KW - Opiates KW - Standard deviation KW - Methanol KW - Regression analysis KW - Metabolites KW - Cocaine KW - Hair KW - Hydrolysis KW - Sonication KW - X 24222:Analytical procedures KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17825522?accountid=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=Analytical+Chemistry+%28Washington%29&rft.atitle=Simultaneous+Quantification+of+Opiates%2C+Cocaine%2C+and+Metabolites+in+Hair+by+LC-APCI-MS%2FMS&rft.au=Scheidweiler%2C+K+B%3BHuestis%2C+MA&rft.aulast=Scheidweiler&rft.aufirst=K&rft.date=2004-08-01&rft.volume=76&rft.issue=15&rft.spage=4358&rft.isbn=&rft.btitle=&rft.title=Analytical+Chemistry+%28Washington%29&rft.issn=00032700&rft_id=info:doi/10.1021%2Fac049555t LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Standard deviation; Opiates; Methanol; Regression analysis; Metabolites; Cocaine; Hydrolysis; Hair; Sonication DO - http://dx.doi.org/10.1021/ac049555t ER - TY - JOUR T1 - Stress Dose of Hydrocortisone Is Not Beneficial in Patients with Classic Congenital Adrenal Hyperplasia Undergoing Short-Term, High-Intensity Exercise AN - 17820736; 5964659 AB - Classic congenital adrenal hyperplasia (CAH) is associated with impaired function of the adrenal cortex and medulla leading to decreased production of cortisol and epinephrine. As a result, the normal exercise-induced rise in blood glucose is markedly blunted in such individuals. We examined whether an extra dose of hydrocortisone, similar to that given during other forms of physical stress such as intercurrent illness, would normalize blood glucose levels during exercise in patients with CAH. We studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with classic CAH. Patients were assigned to receive either an additional morning dose of hydrocortisone or placebo, in addition to their usual glucocorticoid and mineralocorticoid replacement in a randomized, double-blind, crossover design 1 h before exercising. Although plasma cortisol levels approximately doubled after administration of the additional hydrocortisone dose compared with the usual single dose, fasting and exercise-induced blood glucose levels did not differ. In addition, no differences were observed in the serum concentrations of the glucose-modulating hormones epinephrine, insulin, glucagon, and GH and of the metabolic parameters lactate and free fatty acids. Although maximal heart rate was slightly higher after stress dosing (193 +/- 3 vs. 191 +/- 3 beats/min, mean +/- SEM, P < 0.05), this did not affect exercise performance or perceived exertion. We conclude that patients with classic CAH do not benefit from additional hydrocortisone during short-term, high-intensity exercise. Although this has not been tested with long-term exercise, a high degree of caution should be used when considering the frequent use of additional hydrocortisone administration with exercise, given the adverse side effects of glucocorticoid excess. JF - Journal of Clinical Endocrinology and Metabolism AU - Weise, Martina AU - Drinkard, Bart AU - Mehlinger, Sarah L AU - Holzer, Stuart M AU - Eisenhofer, Graeme AU - Charmandari, Evangelia AU - Chrousos, George P AU - Merke, Deborah P AD - Pediatric and Reproductive Endocrinology Branch (S.L.M., S.M.H., E.C., G.P.C., D.P.M.), Developmental Endocrinology Branch (M.W.), National Institute of Child Health and Human Development, The Warren Grant Magnuson Clinical Center (B.D., D.P.M.) and Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke (G.E.), National Institutes of Health, Bethesda, Maryland Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 3679 EP - 3684 PB - Endocrine Society, 4350 East West Highway Suite 500 Bethesda MD 20814-4426 USA, [mailto:societyservices@endo-society.org], [URL:http://www.endo-society.org/] VL - 89 IS - 8 SN - 0021-972X, 0021-972X KW - Physical Education Index KW - Perceived exertion KW - Lipids KW - Adolescence KW - Heart rate KW - Stress KW - Blood glucose KW - Patients KW - Illness KW - Hormones KW - Physical stress KW - Exercise (intensity) KW - Lactic acid KW - Cardiorespiratory KW - Performance KW - Endocrine system KW - Metabolism KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17820736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.atitle=Stress+Dose+of+Hydrocortisone+Is+Not+Beneficial+in+Patients+with+Classic+Congenital+Adrenal+Hyperplasia+Undergoing+Short-Term%2C+High-Intensity+Exercise&rft.au=Weise%2C+Martina%3BDrinkard%2C+Bart%3BMehlinger%2C+Sarah+L%3BHolzer%2C+Stuart+M%3BEisenhofer%2C+Graeme%3BCharmandari%2C+Evangelia%3BChrousos%2C+George+P%3BMerke%2C+Deborah+P&rft.aulast=Weise&rft.aufirst=Martina&rft.date=2004-08-01&rft.volume=89&rft.issue=8&rft.spage=3679&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Patients; Endocrine system; Hormones; Blood glucose; Stress; Metabolism; Heart rate; Adolescence; Lipids; Cardiorespiratory; Performance; Physical stress; Exercise (intensity); Illness; Perceived exertion; Lactic acid ER - TY - JOUR T1 - Perspectives on alcohol consumption: liver polyunsaturated fatty acids and essential fatty acid metabolism AN - 17796664; 6141277 AB - In this article, subjects diagnosed with alcoholic liver disease are shown to have lower concentrations of several polyunsaturated fatty acids (PUFAs), including 18:2n6, 18:3n6, 20:3n6, 18:3n3, 22:5n3, and 22:6n3, but not 20:4n6 and 22:4n6, nor 22:5n6, in the total lipid extracts of their livers compared with findings for specimens obtained from patients diagnosed with primary biliary cirrhosis and from control subjects. Findings of studies in animals have demonstrated that prolonged alcohol consumption reduces liver polyunsaturate content. However, the effect of ethanol on the elongation/desaturation of essential fatty acids is complex, as in vitro study results indicate that the direction of the effect of alcohol may be related to the dose of alcohol. Findings of studies in hepatocyte cell culture indicate that ethanol increased delta-5 and delta-6 desaturase activities throughout a broad concentration range. In contrast, lower liver desaturase activity has been reported in animals consuming high concentrations of alcohol (36%-40% energy) over a period of several months. Findings from in vivo isotope tracers studies in nonhuman primates and felines indicate that prolonged periods of moderate (mean consumption 2.6 g kg super(-1) d super(-1) and 1.2 g kg super(-1) d super(-1), respectively) alcohol consumption had no effect on the uptake of either linoleic (18:2n6) or alpha-linolenic (18:3n3) acids into the plasma and lead to an increased incorporation of these deuterated precursors into 20:4n6 and 22:6n3. Thus, this likely reflects a stimulated, rather than an inhibited, production of long-chain PUFAs. In numerous studies in various species, investigators have documented that alcohol consumption can increase the level of lipid peroxidation in tissues, and sustained periods of ethanol-induced peroxidation can deplete tissues of PUFAs. A hypothesis to rationalize the long-term effects of alcohol consumption on liver PUFA concentration that takes into consideration the effect of ethanol on essential fatty acid metabolism is presented. JF - Alcohol AU - Salem, N AD - Section of Nutritional Neuroscience, Laboratory of Membrane Biochemistry and Biophysics, Division of Intramural Clinical and Biological Research, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 3C-07, Rockville, MD 20852, USA, nsalem@niaaa.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 27 EP - 33 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 34 IS - 1 SN - 0741-8329, 0741-8329 KW - Toxicology Abstracts KW - Fatty liver KW - Essential fatty acids KW - Human beings KW - Animals KW - Docosahexaenoic acid KW - Arachidonic acid KW - Fatty acid desaturation KW - Metabolism KW - Ethanol KW - Isotopes KW - Liver diseases KW - Peroxidation KW - Hepatocytes KW - Lipids KW - Cell culture KW - Alcoholics KW - Lipid peroxidation KW - Long-term effects KW - Elongation KW - Tracers KW - Fatty acids KW - Polyunsaturated fatty acids KW - desaturase KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17796664?accountid=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=Alcohol&rft.atitle=Perspectives+on+alcohol+consumption%3A+liver+polyunsaturated+fatty+acids+and+essential+fatty+acid+metabolism&rft.au=Salem%2C+N&rft.aulast=Salem&rft.aufirst=N&rft.date=2004-08-01&rft.volume=34&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Alcohol&rft.issn=07418329&rft_id=info:doi/10.1016%2Fj.alcohol.2004.07.009 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Isotopes; Liver diseases; Peroxidation; Hepatocytes; Lipids; Cell culture; Lipid peroxidation; Alcoholics; Long-term effects; Tracers; Elongation; Fatty acids; Polyunsaturated fatty acids; Fatty liver; desaturase; Metabolism; Ethanol DO - http://dx.doi.org/10.1016/j.alcohol.2004.07.009 ER - TY - JOUR T1 - Biokinetics and Subchronic Toxic Effects of Oral Arsenite, Arsenate, Monomethylarsonic Acid, and Dimethylarsinic Acid in v-Ha-ras Transgenic (Tg.AC) Mice AN - 17757486; 6047506 AB - Previous research demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment increased the number of skin papillomas in v-Ha-ras transgenic (Tg.AC) mice that had received sodium arsenite [(As(III)] in drinking water, indicating that this model is useful for studying the toxic effects of arsenic in vivo. Because the liver is a known target of arsenic, we examined the pathophysiologic and molecular effects of inorganic and organic arsenical exposure on Tg.AC mouse liver in this study. Tg.AC mice were provided drinking water containing As(III), sodium arsenate [As(V)], monomethylarsonic acid [(MMA(V)], and 1,000 ppm dimethylarsinic acid [DMA(V)] at dosages of 150, 200, 1,500, or 1,000 ppm as arsenic, respectively, for 17 weeks. Control mice received unaltered water. Four weeks after initiation of arsenic treatment, TPA at a dose of 1.25 mu g/200 mu L acetone was applied twice a week for 2 weeks to the shaved dorsal skin of all mice, including the controls not receiving arsenic. In some cases arsenic exposure reduced body weight gain and caused mortality (including moribundity). Arsenical exposure resulted in a dose-dependent accumulation of arsenic in the liver that was unexpectedly independent of chemical species and produced hepatic global DNA hypomethylation. cDNA microarray and reverse transcriptase-polymerase chain reaction analysis revealed that all arsenicals altered the expression of numerous genes associated with toxicity and cancer. However, organic arsenicals [MMA(V) and DMA(V)] induced a pattern of gene expression dissimilar to that of inorganic arsenicals. In summary, subchronic exposure of Tg.AC mice to inorganic or organic arsenicals resulted in toxic manifestations, hepatic arsenic accumulation, global DNA hypomethylation, and numerous gene expression changes. These effects may play a role in arsenic-induced hepatotoxicity and carcinogenesis and may be of particular toxicologic relevance. JF - Environmental Health Perspectives AU - Xie, Yaxiong AU - Trouba, K J AU - Liu, J AU - Waalkes, M P AU - Germolec AD - Environmental Immunology, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop C1-03, Research Triangle Park, NC 27709, USA, germolec@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1255 EP - 1263 VL - 112 IS - 12 SN - 0091-6765, 0091-6765 KW - monomethylarsonic acid KW - Toxicology Abstracts KW - Mortality KW - Arsenic KW - Sodium arsenite KW - Skin KW - Animal models KW - Toxicity KW - Transgenic mice KW - sodium arsenate KW - DNA microarrays KW - TPA KW - Cancer KW - 12-O-Tetradecanoylphorbol-13-acetate KW - Carcinogenesis KW - DNA KW - Liver KW - Polymerase chain reaction KW - Papilloma KW - Drinking water KW - Body weight gain KW - dimethylarsinic acid KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17757486?accountid=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=Biokinetics+and+Subchronic+Toxic+Effects+of+Oral+Arsenite%2C+Arsenate%2C+Monomethylarsonic+Acid%2C+and+Dimethylarsinic+Acid+in+v-Ha-ras+Transgenic+%28Tg.AC%29+Mice&rft.au=Xie%2C+Yaxiong%3BTrouba%2C+K+J%3BLiu%2C+J%3BWaalkes%2C+M+P%3BGermolec&rft.aulast=Xie&rft.aufirst=Yaxiong&rft.date=2004-08-01&rft.volume=112&rft.issue=12&rft.spage=1255&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Ftxg.7152 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Mortality; Arsenic; Skin; Sodium arsenite; Animal models; Toxicity; sodium arsenate; Transgenic mice; DNA microarrays; 12-O-Tetradecanoylphorbol-13-acetate; Cancer; TPA; Carcinogenesis; Liver; DNA; Polymerase chain reaction; Body weight gain; Drinking water; Papilloma; dimethylarsinic acid DO - http://dx.doi.org/10.1289/txg.7152 ER - TY - JOUR T1 - Gene Interaction Network Suggests Dioxin Induces a Significant Linkage between Aryl Hydrocarbon Receptor and Retinoic Acid Receptor Beta AN - 17757455; 6047503 AB - Gene expression arrays (gene chips) have enabled researchers to roughly quantify the level of mRNA expression for a large number of genes in a single sample. Several methods have been developed for the analysis of gene array data including clustering, outlier detection, and correlation studies. Most of these analyses are aimed at a qualitative identification of what is different between two samples and/or the relationship between two genes. We propose a quantitative, statistically sound methodology for the analysis of gene regulatory networks using gene expression data sets. The method is based on Bayesian networks for direct quantification of gene expression networks. Using the gene expression changes in HPL1A lung airway epithelial cells after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin at levels of 0.1, 1.0, and 10.0 nM for 24 hr, a gene expression network was hypothesized and analyzed. The method clearly demonstrates support for the assumed network and the hypothesis linking the usual dioxin expression changes to the retinoic acid receptor system. Simulation studies demonstrated the method works well, even for small samples. JF - Environmental Health Perspectives AU - Toyoshiba, Hiroyoshi AU - Yamanaka, Takeharu AU - Sone, Hideko AU - Parham, F M AU - Walker, N J AU - Martinez, J AU - Portier, C J AD - National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA, portier@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1217 EP - 1224 VL - 112 IS - 12 SN - 0091-6765, 0091-6765 KW - Toxicology Abstracts KW - Gene expression KW - Epithelial cells KW - Retinoic acid receptors KW - Bayesian analysis KW - Lung KW - Sound KW - Aryl hydrocarbon receptors KW - Dioxin KW - Respiratory tract KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17757455?accountid=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=Gene+Interaction+Network+Suggests+Dioxin+Induces+a+Significant+Linkage+between+Aryl+Hydrocarbon+Receptor+and+Retinoic+Acid+Receptor+Beta&rft.au=Toyoshiba%2C+Hiroyoshi%3BYamanaka%2C+Takeharu%3BSone%2C+Hideko%3BParham%2C+F+M%3BWalker%2C+N+J%3BMartinez%2C+J%3BPortier%2C+C+J&rft.aulast=Toyoshiba&rft.aufirst=Hiroyoshi&rft.date=2004-08-01&rft.volume=112&rft.issue=12&rft.spage=1217&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Ftxg.7020 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Gene expression; Epithelial cells; Retinoic acid receptors; Lung; Bayesian analysis; Sound; Aryl hydrocarbon receptors; Dioxin; Respiratory tract DO - http://dx.doi.org/10.1289/txg.7020 ER - TY - JOUR T1 - Prediction equations for resting energy expenditure in overweight and normal-weight black and white children AN - 17738647; 6086679 AB - Background: Accurate estimation of children's resting energy expenditure (REE) is important for planning dietary therapy. Objective: Our objective was to compare the utility of 5 REE prediction equations in a diverse sample of young children. Design: REE was obtained in 502 black and white girls and boys aged 6-11 y by using indirect calorimetry at 4 US sites. Measured REE and REE predicted from the equations were compared. Results: None of the equations provided both accurate and unbiased estimates of REE. Two new sets of sex-specific equations including race as a factor were generated and evaluated. One set used easily measured variables--females: REE = 0.046 x weight - 4.492 x 1/height super(2) - 0.151 x race + 5.841; males: REE = 0.037 x weight - 4.67 x 1/height super(2) - 0.159 x race + 6.792--and accounted for 72% and 69%, respectively, of REE variance. The other set used body-composition variables--females: REE = 0.101 x fat-free mass + 0.025 x fat mass + 0.293 x height super(3) - 0.185 x race + 1.643; males: REE = 0.078 x fat-free mass + 0.026 x fat mass - 2.646 x 1/height super(2) - 0.244 x race + 4.8--and accounted for 75% and 71%, respectively, of REE variance. When split by race and adiposity, the small bias generated could be corrected to within 0.25 MJ (60 kcal) of the mean measured value. Conclusion: Sex-specific equations must take race into account to predict REE adequately in children. JF - American Journal of Clinical Nutrition AU - McDuffie, J R AU - Adler-Wailes, D C AU - Elberg, J AU - Steinberg, EN AU - Fallon, E M AU - Tershakovec, A M AU - Arslanian, SA AU - Delany, J P AU - Bray, G A AU - Yanovski, JA AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 365 EP - 373 VL - 80 IS - 2 SN - 0002-9165, 0002-9165 KW - Physical Education Index KW - Ethnic differences KW - Energy cost KW - Obesity KW - Nutrition (effects) KW - Children KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17738647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Clinical+Nutrition&rft.atitle=Prediction+equations+for+resting+energy+expenditure+in+overweight+and+normal-weight+black+and+white+children&rft.au=McDuffie%2C+J+R%3BAdler-Wailes%2C+D+C%3BElberg%2C+J%3BSteinberg%2C+EN%3BFallon%2C+E+M%3BTershakovec%2C+A+M%3BArslanian%2C+SA%3BDelany%2C+J+P%3BBray%2C+G+A%3BYanovski%2C+JA&rft.aulast=McDuffie&rft.aufirst=J&rft.date=2004-08-01&rft.volume=80&rft.issue=2&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Clinical+Nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Energy cost; Children; Ethnic differences; Obesity; Nutrition (effects) ER - TY - JOUR T1 - Prevalence of Overweight among Inner City Hispanic-American Children and Adolescents AN - 17712913; 6024873 AB - OBJECTIVE: National surveys have pointed to a particularly high risk of pediatric overweight among U.S. Hispanics. However, the data have been primarily from the Mexican-American community. We studied the prevalence of overweight and clinical comorbidities in children and youth of predominantly El Salvadoran ancestry. RESEARCH METHODS AND PROCEDURES: A sample of 309 Hispanic youth, 6-18 years was surveyed from two inner city Washington, DC, clinics. BMI; triceps skinfold (TSF) and subscapular skinfold thickness (SSSF); bioelectrical impedance analysis (BIA); and blood pressure measures were obtained, along with information regarding physical activity, sedentary behavior, dietary history, family, and personal medical history. RESULTS: Thirty-eight percent were overweight (BMI => 95th percentile) and 22% at risk for overweight (BMI 85-94th percentile). Thirty-four percent had TSF => 90th percentile and 29% had SSSF => 90th percentile. Fifty-one percent of males and 70% of females had body fat > 30%. Compared to their nonoverweight counterparts, overweight youth had significantly higher systolic blood pressure (111.4 +/- 1.3 vs. 104.5 +/- 0.9 mm Hg, p < 0.0001). Among children younger than 11 years, overweight was associated with onset of adrenarche (23% vs. 10%, p = 0.01). Participation in one or more sports teams was negatively correlated with overweight) p = 0.04). DISCUSSION: The prevalence of overweight and at risk for overweight in this sample was twice the national average for U.S. children and 1.7 times greater than that of Mexican-American children in national surveys. Overweight was associated with advanced pubertal development, high body fat, elevated blood pressure, and decreased sports participation. JF - Obesity Research AU - Mirza, Nazrat M AU - Kadow, Kathleen AU - Palmer, Matilde AU - Solano, Heidi AU - Rosche, Claire AU - Yanovski, Jack A AD - Children's National Medical Center, Washington, DC. Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1298 EP - 1310 PB - North American Association for the Study of Obesity, 1090 Amsterdam Ave., Ste. 14K New York NY 10025 USA, [mailto:helener@mindspring.com], [URL:http://www.naaso.org] VL - 12 IS - 8 SN - 1071-7323, 1071-7323 KW - Hispanics KW - Risk Abstracts; Physical Education Index KW - Obesity KW - Physical activity KW - Adolescence KW - Surveys KW - Children KW - Blood pressure KW - Sports (participation) KW - Ethnic groups KW - Adolescents KW - Urban areas KW - Urban environment KW - R2 23060:Medical and environmental health KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17712913?accountid=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=Obesity+Research&rft.atitle=Prevalence+of+Overweight+among+Inner+City+Hispanic-American+Children+and+Adolescents&rft.au=Mirza%2C+Nazrat+M%3BKadow%2C+Kathleen%3BPalmer%2C+Matilde%3BSolano%2C+Heidi%3BRosche%2C+Claire%3BYanovski%2C+Jack+A&rft.aulast=Mirza&rft.aufirst=Nazrat&rft.date=2004-08-01&rft.volume=12&rft.issue=8&rft.spage=1298&rft.isbn=&rft.btitle=&rft.title=Obesity+Research&rft.issn=10717323&rft_id=info:doi/ LA - English DB - Physical Education Index; ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Obesity; Children; Adolescence; Blood pressure; Sports (participation); Urban environment; Surveys; Urban areas; Adolescents; Ethnic groups; Physical activity ER - TY - JOUR T1 - Gene Therapy Progress and Prospects. Downregulating gene expression: the impact of RNA interference AN - 17711855; 5994586 AB - The control and maintenance of gene expression is critical for cell development and differentiation. Over the last 2 years, our understanding of the role of RNA as a regulator of gene expression has significantly increased. Small RNA molecules are key elements of a machinery that trigger chromosomal modifications, post-transcriptional gene silencing and protein translational blockade depending on the source, the RNA and the nature of the interaction with the target nucleic acid. Currently, the best characterized of this group of RNA-mediated gene regulation pathways is the post-transcriptional gene silencing mechanism known as RNA interference. RNAi is triggered by double-stranded RNA (dsRNA), which induces the formation of a ribonucleoprotein complex that mediates sequence-specific cleavage of the transcript cognate with the input dsRNA. RNAi has been adapted as a functional genomics tool and it has potential as a therapeutic approach. This review will summarize our current understanding of the RNAi mechanism and the various applications of RNAi-based technologies. JF - Gene Therapy AU - Caplen, N J AD - Gene Silencing Section, Office of the Director, Center for Cancer Research, National Cancer Institute, Building 37, Room 3128B, Bethesda, MD 20892, USA Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1241 EP - 1248 VL - 11 IS - 16 SN - 0969-7128, 0969-7128 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Double-stranded RNA KW - Gene expression KW - Gene regulation KW - Reviews KW - Ribonucleoproteins KW - RNA-mediated interference KW - Post-transcription KW - Gene silencing KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17711855?accountid=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=Gene+Therapy&rft.atitle=Gene+Therapy+Progress+and+Prospects.+Downregulating+gene+expression%3A+the+impact+of+RNA+interference&rft.au=Caplen%2C+N+J&rft.aulast=Caplen&rft.aufirst=N&rft.date=2004-08-01&rft.volume=11&rft.issue=16&rft.spage=1241&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fsj.gt.3302324 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - RNA-mediated interference; Gene expression; Gene therapy; Gene silencing; Ribonucleoproteins; Reviews; Double-stranded RNA; Gene regulation; Post-transcription DO - http://dx.doi.org/10.1038/sj.gt.3302324 ER - TY - JOUR T1 - Human Mesenchymal Progenitor Cell-Based Tissue Engineering of a Single-Unit Osteochondral Construct AN - 17701426; 6072194 AB - A desirable strategy for articular cartilage repair is to surgically replace the damaged area with an in vitro-engineered osteochondral plug. We report here the development of a novel osteochondral construct using human trabecular bone-derived mesenchymal progenitor cells and a biodegradable poly-D,L-lactic acid scaffold. The cartilage layer was fabricated by press-coating a chondrifying high-density cell pellet onto the scaffold, which was then loaded with cells previously initiated to undergo osteogenesis. The composite was then cultured in a cocktail medium formulated to maintain both chondrogenesis and osteogenesis. Macroscopically, the construct consisted of a cartilage-like layer adherent to, and overlying, a dense bone-like component. RT-PCR, immunohistochemistry, and histology revealed hyaline-like cartilage and bone with an interface resembling the native osteochondral junction. All parameters, including mechanical properties, improved with increased culture time. The single-cell source nature of the construct, which minimizes handling while maximizing biocompatibility, suggests applicability for articular cartilage repair. JF - Tissue Engineering AU - Tuli, R AU - Nandi, S AU - Li, W-J AU - Tuli, S AU - Huang, X AU - Manner, P A AU - Laquerriere, P AU - Noeth, U AU - Hall, D J AU - Tuan, R S AD - Cartilage Biology and Orthopedics Branch, National Institute of Arthritis, and Musculoskeletal, and Skin Diseases, National Institutes of Health, Building 50, Room 1503, 50 South Drive, MSC 8022, Bethesda, MD 20892-8022, USA, tuanr@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1169 EP - 1179 VL - 10 IS - 7-8 SN - 1076-3279, 1076-3279 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cell culture KW - biocompatibility KW - Stem cells KW - Polymerase chain reaction KW - Cartilage (articular) KW - Mechanical properties KW - Osteogenesis KW - Tissue engineering KW - poly-D,L-lactic acid KW - scaffolds KW - Immunohistochemistry KW - Chondrogenesis KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17701426?accountid=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=Tissue+Engineering&rft.atitle=Human+Mesenchymal+Progenitor+Cell-Based+Tissue+Engineering+of+a+Single-Unit+Osteochondral+Construct&rft.au=Tuli%2C+R%3BNandi%2C+S%3BLi%2C+W-J%3BTuli%2C+S%3BHuang%2C+X%3BManner%2C+P+A%3BLaquerriere%2C+P%3BNoeth%2C+U%3BHall%2C+D+J%3BTuan%2C+R+S&rft.aulast=Tuli&rft.aufirst=R&rft.date=2004-08-01&rft.volume=10&rft.issue=7-8&rft.spage=1169&rft.isbn=&rft.btitle=&rft.title=Tissue+Engineering&rft.issn=10763279&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; scaffolds; Cartilage (articular); Tissue engineering; Osteogenesis; Mechanical properties; biocompatibility; Immunohistochemistry; Chondrogenesis; Polymerase chain reaction; poly-D,L-lactic acid; Cell culture ER - TY - JOUR T1 - Physical activity and risk of coronary heart disease in India AN - 17559629; 6406893 AB - Background Physical exercise has been inversely associated with coronary heart disease (CHD) risk in Western populations; however, the association has not been examined in India where physical inactivity levels in urban areas are now comparable with the West. Methods We conducted a hospital-based case-control study and collected data from 350 cases of acute myocardial infarction and 700 controls matched on age, gender, and hospital in New Delhi and Bangalore. We used conditional logistic regression to control for the matching and other risk factors. Results Of the controls, 48% participated in some form of leisure-time exercise compared with 38% of cases. In age- and sex-adjusted analyses, people in the highest level of leisure-time exercise (>145 metabolic equivalents [MET]-minutes per day, equivalent to 36 minutes of brisk walking per day) had a relative risk of 0.45 (95% CI: 0.31, 0.66) compared with non-exercisers. Multivariate adjustment for other risk factors did not substantially alter the association. We observed a positive association between non-work sedentary activity and CHD risk; people with >3.6 hours per day of sedentary activity (for example, television viewing) had an elevated risk of 1.88 (95% CI: 1.09, 3.20) compared with <70 minutes per day in multivariate analysis. Conclusion Leisure-time exercise, including as much as 35-40 minutes per day of brisk walking, was protective for CHD risk and sedentary lifestyles were positively associated with risk of CHD. Given limited resources for care of CHD in India and the important role of physical exercise in disease risk in urban India, improvements in physical activity should be promoted. JF - International Journal of Epidemiology AU - Rastogi, T AU - Vaz, M AU - Spiegelman, D AU - Reddy, K S AU - Bharathi, A V AU - Stampfer, MJ AU - Willett, W C AU - Ascherio, A AD - NEB, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, EPS 320, Rockville MD 20852 USA, trastogi@post.harvard.edu Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 759 EP - 767 VL - 33 IS - 4 SN - 0300-5771, 0300-5771 KW - Risk Abstracts; Physical Education Index KW - Age KW - Physical activity KW - Promotion KW - Walking KW - Exercise KW - India KW - Risk factors KW - Analysis KW - Gender KW - Television KW - Cardiovascular diseases KW - Health promotion KW - Urban areas KW - Hospitals KW - Heart diseases KW - Urban environment KW - R2 23060:Medical and environmental health KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17559629?accountid=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=International+Journal+of+Epidemiology&rft.atitle=Physical+activity+and+risk+of+coronary+heart+disease+in+India&rft.au=Rastogi%2C+T%3BVaz%2C+M%3BSpiegelman%2C+D%3BReddy%2C+K+S%3BBharathi%2C+A+V%3BStampfer%2C+MJ%3BWillett%2C+W+C%3BAscherio%2C+A&rft.aulast=Rastogi&rft.aufirst=T&rft.date=2004-08-01&rft.volume=33&rft.issue=4&rft.spage=759&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Epidemiology&rft.issn=03005771&rft_id=info:doi/10.1093%2Fije%2Fdyh042 LA - English DB - Physical Education Index; ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Urban environment; Exercise; Analysis; Heart diseases; Risk factors; Walking; Hospitals; Television; Promotion; Age; Gender; India; Urban areas; Physical activity; Cardiovascular diseases; Health promotion DO - http://dx.doi.org/10.1093/ije/dyh042 ER - TY - JOUR T1 - Imaging of myocardial infarction for diagnosis and intervention using real-time interactive MRI without ECG-gating or breath-holding AN - 17380507; 6494140 AB - Current methods for MRI of infarcted myocardium require ECG-gating and breath-holding during contrast-enhanced segmented k-space inversion-recovery (IR) imaging. However, ECG-gating can be problematic in MRI, and breath-holding can be difficult for some patients. This work demonstrates that infarcted tissue can be visualized without ECG-gating or breath-holding with the use of intermittent inversion pulses during real-time (RT) interactive imaging with steady-state free precession (SSFP). The sequence generates a RT image stream containing a myocardium-nulled image every few frames, which allows nearly simultaneous observation of both infarcted regions and wall motion. First-pass perfusion and wall motion can be simultaneously observed with minor parameter modifications. This method may reduce diagnostic scan time, expand the target population, improve patient comfort, and facilitate targeted, interventional treatment of infarcted myocardium. Supplementary material for this article can be found on the MRM website at http://www.interscience.wiley.com/jpages/0740-3194/suppmat/index.h tml. JF - Magnetic Resonance in Medicine AU - Guttman, Michael A AU - Dick, Alexander J AU - Raman, Venkatesh K AU - Arai, Andrew E AU - Lederman, Robert J AU - McVeigh, Elliot R AD - NIH/NHLBI, 10 Center Dr., Building 10, Room B1D416, Bethesda, MD 20892-1061, USA, mguttman@nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 354 EP - 361 PB - John Wiley & Sons, Ltd. VL - 52 IS - 2 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Heart KW - Perfusion KW - Magnetic resonance imaging KW - N.M.R. KW - Myocardial infarction KW - Myocardium KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17380507?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Imaging+of+myocardial+infarction+for+diagnosis+and+intervention+using+real-time+interactive+MRI+without+ECG-gating+or+breath-holding&rft.au=Guttman%2C+Michael+A%3BDick%2C+Alexander+J%3BRaman%2C+Venkatesh+K%3BArai%2C+Andrew+E%3BLederman%2C+Robert+J%3BMcVeigh%2C+Elliot+R&rft.aulast=Guttman&rft.aufirst=Michael&rft.date=2004-08-01&rft.volume=52&rft.issue=2&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20174 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Myocardium; N.M.R.; Perfusion; Heart; Myocardial infarction DO - http://dx.doi.org/10.1002/mrm.20174 ER - TY - JOUR T1 - Sensitivity of femoral orientation estimates to condylar surface and MR image plane location AN - 17378668; 6482101 AB - Purpose To define the femoral anatomic region that provides the most reliable reference for measuring femoral orientation, from which patellofemoral and tibiofemoral orientation can be measured. Materials and Methods After a three-dimensional image-based osteo-alignment procedure, two independent estimates of distal femoral orientation, the anterior (AFA) and posterior femoral angles (PFA), were acquired. These sets were comprised of 31 axial femoral orientation estimates each (obtained across a region 10 mm above to. JF - Journal of Magnetic Resonance Imaging AU - Shibanuma, N AU - Sheehan, F T AU - Lipsky, P E AU - Stanhope, S J AD - Building 10, Room 6s235, MSC 1604, National Institutes of Health, Bethesda, MD 20892-1604, USA, fsheehan@cc.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 300 EP - 305 VL - 20 IS - 2 SN - 1053-1807, 1053-1807 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Magnetic resonance imaging KW - Femur KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17378668?accountid=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+Magnetic+Resonance+Imaging&rft.atitle=Sensitivity+of+femoral+orientation+estimates+to+condylar+surface+and+MR+image+plane+location&rft.au=Shibanuma%2C+N%3BSheehan%2C+F+T%3BLipsky%2C+P+E%3BStanhope%2C+S+J&rft.aulast=Shibanuma&rft.aufirst=N&rft.date=2004-08-01&rft.volume=20&rft.issue=2&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-07-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Femur ER - TY - JOUR T1 - Measures of Accuracy for Active Shoulder Movements at 3 Different Speeds With Kinesthetic and Visual Feedback AN - 17337589; 6384854 AB - To compare measures of end point accuracy (EPA) for 2 feedback conditions: (1) visual and kinesthetic feedback and (2) kinesthetic feedback alone, during shoulder movements, at 3 different speeds. Shoulder joint kinesthesia is typically reported with EPA measures, such as constant error. Reporting multiple measures of EPA, such as variable error and absolute error, could provide a more detailed description of performance. Subjects were seated with the shoulder abducted 90 degree in the scapular plane and externally rotated 75 degree , with the forearm placed in a custom shoulder wheel. Subjects internally rotated the shoulder 27 degree to a target position at 48 degree of shoulder external rotation for both conditions. Motion analysis was used to determine peak angular velocity and 3 EPA measures for shoulder movements. Each EPA measure was compared between the 2 feedback conditions and among the 3 speeds with a separate 2-way analysis of variance. Movements performed with kinesthetic feedback alone, measured by constant error (P<.01), variable error (P<.01), and absolute error (P<.01), were less accurate than movements performed with visual and kinesthetic feedback. Faster movements were less accurate when measured by constant error (P = .01) and absolute error (P<.01) than slower movements. Subjects tended to overshoot the target in the absence of visual feedback; however, movement speed played minimal role in the overshooting. Multiple measures of EPA, such as constant, variable, and absolute error during simple restricted shoulder movements may provide additional information regarding the evaluation of a motor performance or identify different central nervous system control mechanisms for joint kinesthesia. JF - Journal of Orthopaedic & Sports Physical Therapy AU - Brindle, T J AU - Nitz, A J AU - Uhl, T L AU - Kifer, E AU - Shapiro, R AD - Physical Disabilities Branch, National Institutes of Health, Bethesda, MD, USA Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 468 EP - 478 VL - 34 IS - 8 SN - 0190-6011, 0190-6011 KW - Physical Education Index KW - PE 100:Kinesiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17337589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Orthopaedic+%26+Sports+Physical+Therapy&rft.atitle=Measures+of+Accuracy+for+Active+Shoulder+Movements+at+3+Different+Speeds+With+Kinesthetic+and+Visual+Feedback&rft.au=Brindle%2C+T+J%3BNitz%2C+A+J%3BUhl%2C+T+L%3BKifer%2C+E%3BShapiro%2C+R&rft.aulast=Brindle&rft.aufirst=T&rft.date=2004-08-01&rft.volume=34&rft.issue=8&rft.spage=468&rft.isbn=&rft.btitle=&rft.title=Journal+of+Orthopaedic+%26+Sports+Physical+Therapy&rft.issn=01906011&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-03-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Radio frequency continuous-wave and time-domain EPR imaging and Overhauser-enhanced magnetic resonance imaging of small animals: instrumental developments and comparison of relative merits for functional imaging AN - 17122147; 6755180 AB - Electron paramagnetic resonance (EPR) imaging in the continuous wave (CW) and time-domain modes, as well as Overhauser-enhanced magnetic resonance imaging in vivo is described. The review is based mainly on the CW and time-domain EPR instrumentation at 300 MHz developed in our laboratory, and the relative merits of these methods for functional in vivo imaging of small animals to assess hypoxia and tissue redox status are described. Overhauser imaging of small animals at magnetic fields in the range 10-15 mT that is being carried out in our laboratory for tumor imaging and the evaluation of tumor hypoxia based on quantitative evaluation of Overhauser enhancement is also described. Alternate approaches to spectral-spatial imaging using the transverse decay constants to infer in situ line widths and hence in vivo pO sub(2) using CW and time-domain EPR imaging are also discussed. The nature of the spin probes used, the quality of the images obtained in all the three methods, the achievable resolution, limitations and possible future directions in small animal functional imaging with these modalities are summarized. JF - NMR in Biomedicine AU - Subramanian, Sankaran AU - Matsumoto, Ken-Ichiro AU - Mitchell, James B AU - Krishna, Murali C AD - Biomedical Imaging Section, Radiation Biology Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA, murali@helix.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 263 EP - 294 PB - John Wiley & Sons, Ltd. VL - 17 IS - 5 SN - 0952-3480, 0952-3480 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - E.S.R. KW - Magnetic fields KW - Hypoxia KW - Reviews KW - Magnetic resonance imaging KW - N.M.R. KW - Nuclear Overhauser effect KW - Spin probes KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17122147?accountid=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=NMR+in+Biomedicine&rft.atitle=Radio+frequency+continuous-wave+and+time-domain+EPR+imaging+and+Overhauser-enhanced+magnetic+resonance+imaging+of+small+animals%3A+instrumental+developments+and+comparison+of+relative+merits+for+functional+imaging&rft.au=Subramanian%2C+Sankaran%3BMatsumoto%2C+Ken-Ichiro%3BMitchell%2C+James+B%3BKrishna%2C+Murali+C&rft.aulast=Subramanian&rft.aufirst=Sankaran&rft.date=2004-08-01&rft.volume=17&rft.issue=5&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=NMR+in+Biomedicine&rft.issn=09523480&rft_id=info:doi/10.1002%2Fnbm.897 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-05-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - E.S.R.; Magnetic fields; Reviews; Hypoxia; Magnetic resonance imaging; N.M.R.; Nuclear Overhauser effect; Spin probes DO - http://dx.doi.org/10.1002/nbm.897 ER - TY - JOUR T1 - Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required. AN - 66743064; 15161912 AB - Inorganic arsenic is an established human carcinogen, but its metabolism is incompletely defined. The ATP binding cassette protein, multidrug resistance protein (MRP1/ABCC1), transports conjugated organic anions (e.g. leukotriene C(4)) and also co-transports certain unmodified xenobiotics (e.g. vincristine) with glutathione (GSH). MRP1 also confers resistance to arsenic in association with GSH; however, the mechanism and the species of arsenic transported are unknown. Using membrane vesicles prepared from the MRP1-overexpressing lung cancer cell line, H69AR, we found that MRP1 transports arsenite (As(III)) only in the presence of GSH but does not transport arsenate (As(V)) (with or without GSH). The non-reducing GSH analogs L-gamma-glutamyl-L-alpha-aminobutyryl glycine and S-methyl GSH did not support As(III) transport, indicating that the free thiol group of GSH is required. GSH-dependent transport of As(III) was 2-fold higher at pH 6.5-7 than at a more basic pH, consistent with the formation and transport of the acid-stable arsenic triglutathione (As(GS)(3)). Immunoblot analysis of H69AR vesicles revealed the unexpected membrane association of GSH S-transferase P1-1 (GSTP1-1). Membrane vesicles from an MRP1-transfected HeLa cell line lacking membrane-associated GSTP1-1 did not transport As(III) even in the presence of GSH but did transport synthetic As(GS)(3). The addition of exogenous GSTP1-1 to HeLa-MRP1 vesicles resulted in GSH-dependent As(III) transport. The apparent K(m) of As(GS)(3) for MRP1 was 0.32 microM, suggesting a remarkably high relative affinity. As(GS)(3) transport by MRP1 was osmotically sensitive and was inhibited by several conjugated organic anions (MRP1 substrates) as well as the metalloid antimonite (K(i) 2.8 microM). As(GS)(3) transport experiments using MRP1 mutants with substrate specificities differing from wild-type MRP1 suggested a commonality in the substrate binding pockets of As(GS)(3) and leukotriene C(4). Finally, human MRP2 also transported As(GS)(3). In conclusion, MRP1 transports inorganic arsenic as a tri-GSH conjugate, and GSTP1-1 may have a synergistic role in this process. JF - The Journal of biological chemistry AU - Leslie, Elaine M AU - Haimeur, Anass AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07/30/ PY - 2004 DA - 2004 Jul 30 SP - 32700 EP - 32708 VL - 279 IS - 31 SN - 0021-9258, 0021-9258 KW - Anions KW - 0 KW - Antibodies, Monoclonal KW - Carcinogens KW - Multidrug Resistance-Associated Proteins KW - Oligopeptides KW - Protein Isoforms KW - Sulfhydryl Compounds KW - Aspartic Acid KW - 30KYC7MIAI KW - ophthalmic acid KW - 3A60475Q1Q KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Glutathione KW - GAN16C9B8O KW - Leucine KW - GMW67QNF9C KW - Cadmium Chloride KW - J6K4F9V3BA KW - Lysine KW - K3Z4F929H6 KW - Arsenic KW - N712M78A8G KW - multidrug resistance-associated protein 1 KW - Y49M64GZ4Q KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - Humans KW - Hydrogen-Ion Concentration KW - Biological Transport KW - Drug Resistance KW - Leucine -- chemistry KW - Aspartic Acid -- chemistry KW - Genetic Vectors KW - Time Factors KW - Immunoblotting KW - Lysine -- chemistry KW - Dose-Response Relationship, Drug KW - Antibodies, Monoclonal -- metabolism KW - HeLa Cells KW - Cadmium Chloride -- pharmacology KW - Glutathione Transferase -- metabolism KW - Cell Line, Tumor KW - Mice KW - Antibodies, Monoclonal -- chemistry KW - Osmosis KW - Transfection KW - Kinetics KW - Oligopeptides -- pharmacology KW - Substrate Specificity KW - Cell Membrane -- metabolism KW - Mutation KW - Cell Line KW - Arsenic -- pharmacokinetics KW - Arsenic -- metabolism KW - Glutathione -- metabolism KW - Multidrug Resistance-Associated Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66743064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Arsenic+transport+by+the+human+multidrug+resistance+protein+1+%28MRP1%2FABCC1%29.+Evidence+that+a+tri-glutathione+conjugate+is+required.&rft.au=Leslie%2C+Elaine+M%3BHaimeur%2C+Anass%3BWaalkes%2C+Michael+P&rft.aulast=Leslie&rft.aufirst=Elaine&rft.date=2004-07-30&rft.volume=279&rft.issue=31&rft.spage=32700&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 - 2004-09-10 N1 - Date created - 2004-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional redundancy of the human CCL4 and CCL4L1 chemokine genes. AN - 66682860; 15240137 AB - CCL4 and CCL4L1 are two CC chemokine genes located at chromosome 17q21 whose mature proteins differ at only a single amino acid. Abundant functional information exists for CCL4, however, CCL4L1 has only recently been recognized as a distinct gene, thus information describing it is wanting. The CCL4L1 protein was synthesized in Escherichia coli and compared with the CCL4 protein. Competitive binding studies using HEK-293/CCR5 cells produced comparable EC50 values for the two proteins. Similarly, chemotaxis assays with cells expressing CCR1, CCR3, or CCR5 revealed no substantial differences. CCL4L1 was somewhat more effective at inhibiting HIV-1 replication in PBMCs than was CCL4, however the difference was not statistically significant. These data combined with the observation of individual variation in CCL4L1 gene copy number [Eur. J. Immunol. 32 (2002) 3016, Genomics 83 (2004) 735] support the contention that the CCL4 and CCL4L1 proteins have redundant functions. JF - Biochemical and biophysical research communications AU - Howard, O M Zack AU - Turpin, Jim A AU - Goldman, Robert AU - Modi, William S AD - Laboratory of Molecular Immunoregulation, NCI-Frederick, Frederick, MD 21702, USA. Y1 - 2004/07/30/ PY - 2004 DA - 2004 Jul 30 SP - 927 EP - 931 VL - 320 IS - 3 SN - 0006-291X, 0006-291X KW - CCL4 protein, human KW - 0 KW - CCL4L1 protein, human KW - Chemokine CCL4 KW - Chemokines KW - Chemokines, CC KW - Macrophage Inflammatory Proteins KW - Proteins KW - Receptors, CCR5 KW - Index Medicus KW - Chemokines -- metabolism KW - Chemokines -- chemistry KW - Chemokines -- pharmacology KW - Chemokines -- genetics KW - Virus Replication -- drug effects KW - Humans KW - Molecular Sequence Data KW - Lethal Dose 50 KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Structure-Activity Relationship KW - Kidney -- metabolism KW - Chemotaxis -- physiology KW - Kidney -- drug effects KW - Chemokines, CC -- genetics KW - Proteins -- genetics KW - Proteins -- metabolism KW - Proteins -- pharmacology KW - Chemokines, CC -- metabolism KW - Proteins -- chemistry KW - Chemokines, CC -- pharmacology KW - HIV-1 -- growth & development KW - HIV-1 -- drug effects KW - Receptors, CCR5 -- metabolism KW - Chemokines, CC -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66682860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+redundancy+of+the+human+CCL4+and+CCL4L1+chemokine+genes.&rft.au=Howard%2C+O+M+Zack%3BTurpin%2C+Jim+A%3BGoldman%2C+Robert%3BModi%2C+William+S&rft.aulast=Howard&rft.aufirst=O+M&rft.date=2004-07-30&rft.volume=320&rft.issue=3&rft.spage=927&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 - 2004-08-26 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Investigating the Role of the Little Finger Domain of Y-family DNA Polymerases in Low Fidelity Synthesis and Translesion Replication AN - 17999938; 5964061 AB - Dpo4 and Dbh are Y-family polymerases that originate from two closely related strains of Sulfolobaceae: Quite surprisingly, however, the two polymerases exhibit different enzymatic properties in vitro. For example, Dpo4 can replicate past a variety of DNA lesions, yet Dbh does so with a much lower efficiency. When replicating undamaged DNA, Dpo4 is prone to make base pair substitutions, whereas Dbh predominantly makes single-base deletions. Overall, the two proteins are 54% identical, but the greatest divergence is found in their respective little finger (LF) domains, which are only 41% identical. To investigate the role of the LF domain in the fidelity and lesion-bypassing abilities of Y-family polymerases, we have generated chimeras of Dpo4 and Dbh in which their LF domains have been interchanged. Interestingly, by replacing the LF domain of Dbh with that of Dpo4, the enzymatic properties of the chimeric enzyme are more Dpo4-like in that the enzyme is more processive, can bypass an abasic site and a thymine-thymine cyclobutane pyrimidine dimer, and predominantly makes base pair substitutions when replicating undamaged DNA. The converse is true for the Dpo4-LF-Dbh chimera, which is more Dbh-like in its processivity and ability to bypass DNA adducts and generate single-base deletion errors. Our studies indicate that the unique but variable LF domain of Y-family polymerases plays a major role in determining the enzymatic and biological properties of each individual Y-family member. JF - Journal of Biological Chemistry AU - Boudsocq, Francois AU - Kokoska, Robert J AU - Plosky, Brian S AU - Vaisman, Alexandra AU - Ling, Hong AU - Kunkel, Thomas A AU - Yang, Wei AU - Woodgate, Roger AD - Section on DNA Replication, Repair, and Mutagenesis, Laboratory of Genomic Integrity, NICHD, National Institutes of Health, Bethesda, Maryland Y1 - 2004/07/30/ PY - 2004 DA - 2004 Jul 30 SP - 32932 EP - 32940 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 31 SN - 0021-9258, 0021-9258 KW - Dpo4 protein KW - LF domain KW - Dbh protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Replication KW - DNA-directed DNA polymerase KW - Enzymatic activity KW - Sulfolobaceae KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17999938?accountid=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=Investigating+the+Role+of+the+Little+Finger+Domain+of+Y-family+DNA+Polymerases+in+Low+Fidelity+Synthesis+and+Translesion+Replication&rft.au=Boudsocq%2C+Francois%3BKokoska%2C+Robert+J%3BPlosky%2C+Brian+S%3BVaisman%2C+Alexandra%3BLing%2C+Hong%3BKunkel%2C+Thomas+A%3BYang%2C+Wei%3BWoodgate%2C+Roger&rft.aulast=Boudsocq&rft.aufirst=Francois&rft.date=2004-07-30&rft.volume=279&rft.issue=31&rft.spage=32932&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 - Sulfolobaceae; Enzymatic activity; Replication; DNA-directed DNA polymerase ER - TY - JOUR T1 - Interaction of noncompetitive inhibitors with an immobilized alpha3beta4 nicotinic acetylcholine receptor investigated by affinity chromatography, quantitative-structure activity relationship analysis, and molecular docking. AN - 66733329; 15267239 AB - A large number of drug substances act as noncompetitive inhibitors (NCIs) of the nicotinic acetylcholine receptor (nAChR) by blocking the ion flux through the channel. An affinity chromatography technique has been developed for investigating the interactions between NCIs and the alpha3beta4 subtype of neuronal nAChR. The data obtained from the chromatographic study were used to construct QSAR models of the NCI-nAChR binding with both electronic and steric parameters observed as important descriptors. A molecular model of the transmembrane domain of the alpha3beta4 subtype of nAChR was constructed and used to simulate the docking of a series of NCIs. A key aspect of the model was the discovery of the cleft produced by the incorporation of the bulky phenylalanine moiety into the nonpolar section of the lumen by the beta4 subunit. Quantitatively, the results of docking simulations modeled the experimental affinity data better than QSAR results. The computational approach, combined with the modeling of NCI-nAChR interaction by affinity chromatography, can be used to predict possible toxicities and adverse interactions. JF - Journal of medicinal chemistry AU - Jozwiak, Krzysztof AU - Ravichandran, Sarangan AU - Collins, Jack R AU - Wainer, Irving W AD - Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA. Y1 - 2004/07/29/ PY - 2004 DA - 2004 Jul 29 SP - 4008 EP - 4021 VL - 47 IS - 16 SN - 0022-2623, 0022-2623 KW - Ligands KW - 0 KW - Nicotinic Antagonists KW - Protein Subunits KW - Receptors, Nicotinic KW - Dextromethorphan KW - 7355X3ROTS KW - Index Medicus KW - Chromatography, Affinity KW - Sequence Alignment KW - Quantitative Structure-Activity Relationship KW - Dextromethorphan -- chemistry KW - Neurons -- chemistry KW - Models, Molecular KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Molecular Conformation KW - Protein Subunits -- chemistry KW - Nicotinic Antagonists -- chemistry KW - Receptors, Nicotinic -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66733329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+of+noncompetitive+inhibitors+with+an+immobilized+alpha3beta4+nicotinic+acetylcholine+receptor+investigated+by+affinity+chromatography%2C+quantitative-structure+activity+relationship+analysis%2C+and+molecular+docking.&rft.au=Jozwiak%2C+Krzysztof%3BRavichandran%2C+Sarangan%3BCollins%2C+Jack+R%3BWainer%2C+Irving+W&rft.aulast=Jozwiak&rft.aufirst=Krzysztof&rft.date=2004-07-29&rft.volume=47&rft.issue=16&rft.spage=4008&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 - 2004-08-24 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of ABCG2: role of the GXXXG motif. AN - 66720746; 15260487 AB - ABCG2 (BCRP/MXR/ABCP) is a half-transporter associated with multidrug resistance that presumably homodimerizes for function. It has a conserved GXXXG motif in its first transmembrane segment, a motif that has been linked with dimerization in other proteins, e.g., glycophorin A. We substituted either or both glycines of this GXXXG motif with leucines to evaluate the impact on drug transport, ATP hydrolysis, cross-linking, and susceptibility to degradation. All mutants also carried the R482G gain-of-function mutation, and all migrated to the cell surface. The mutations resulted in lost transport for rhodamine 123 and impaired mitoxantrone, pheophorbide a, and BODIPY-prazosin transport, particularly in the double leucine mutant (G406L/G410L). Basal ATPase activity of the G406L/G410L mutant was comparable to the empty vector transfected cells with no substrate induction. Despite impaired function, the mutants retained susceptibility to cross-linking using either disuccinimidyl suberate (DSS) or the reducible dithiobis(succinimidyl propionate) (DSP) and demonstrated a high molecular weight complex under nonreducing conditions. Mutations to alanine at the same positions yielded fully functional transporters. Finally, we exposed cells to mitoxantrone to promote folding and processing of the mutant proteins, which in the leucine mutants resulted in increased amounts detected on immunoblot and by immunofluorescence. These studies support a hypothesis that the GXXXG motif promotes proper packing of the transmembrane segments in the functional ABCG2 homodimer, although it does not solely arbitrate dimerization. JF - Biochemistry AU - Polgar, Orsolya AU - Robey, Robert W AU - Morisaki, Kuniaki AU - Dean, Michael AU - Michejda, Christopher AU - Sauna, Zuben E AU - Ambudkar, Suresh V AU - Tarasova, Nadya AU - Bates, Susan E AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. Y1 - 2004/07/27/ PY - 2004 DA - 2004 Jul 27 SP - 9448 EP - 9456 VL - 43 IS - 29 SN - 0006-2960, 0006-2960 KW - ABCG2 protein, human KW - 0 KW - ATP Binding Cassette Transporter, Sub-Family G, Member 2 KW - Neoplasm Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Humans KW - Molecular Sequence Data KW - Flow Cytometry KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Amino Acid Motifs KW - Neoplasm Proteins -- genetics KW - ATP-Binding Cassette Transporters -- genetics KW - ATP-Binding Cassette Transporters -- chemistry KW - Neoplasm Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66720746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+ABCG2%3A+role+of+the+GXXXG+motif.&rft.au=Polgar%2C+Orsolya%3BRobey%2C+Robert+W%3BMorisaki%2C+Kuniaki%3BDean%2C+Michael%3BMichejda%2C+Christopher%3BSauna%2C+Zuben+E%3BAmbudkar%2C+Suresh+V%3BTarasova%2C+Nadya%3BBates%2C+Susan+E&rft.aulast=Polgar&rft.aufirst=Orsolya&rft.date=2004-07-27&rft.volume=43&rft.issue=29&rft.spage=9448&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-20 N1 - Date created - 2004-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MRI detection of single particles for cellular imaging AN - 17681959; 5963847 AB - There is rapid growth in the use of MRI for molecular and cellular imaging. Much of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran-coated iron oxide particles. Typically, millions of dextran-coated ultrasmall iron oxide particles must be loaded into cells for efficient detection. Here we show that single, micrometer-sized iron oxide particles (MPIOs) can be detected by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos. Experiments studying effects of MRI resolution and particle size from 0.76 to 1.63 mu m indicated that effects can be readily detected from single MPIOs at 50- mu m resolution and significant signal effects could be detected at resolutions as low as 200 mu m. Cultured cells were labeled with fluorescent MPIOs such that single particles were present in individual cells. These single particles in single cells could be detected both by MRI and fluorescence microscopy. Finally, single particles injected into single-cell-stage mouse embryos could be detected at embryonic day 11.5, demonstrating that even after many cell divisions, daughter cells still carry individual particles. These results demonstrate that MRI can detect single particles and indicate that single-particle detection will be useful for cellular imaging. JF - Proceedings of the National Academy of Sciences, USA AU - Shapiro, Erik M AU - Skrtic, Stanko AU - Sharer, Kathryn AU - Hill, Jonathan M AU - Dunbar, Cynthia E AU - Koretsky, Alan P AD - Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke and Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD Y1 - 2004/07/27/ PY - 2004 DA - 2004 Jul 27 SP - 10901 EP - 10906 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 30 SN - 0027-8424, 0027-8424 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17681959?accountid=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=MRI+detection+of+single+particles+for+cellular+imaging&rft.au=Shapiro%2C+Erik+M%3BSkrtic%2C+Stanko%3BSharer%2C+Kathryn%3BHill%2C+Jonathan+M%3BDunbar%2C+Cynthia+E%3BKoretsky%2C+Alan+P&rft.aulast=Shapiro&rft.aufirst=Erik&rft.date=2004-07-27&rft.volume=101&rft.issue=30&rft.spage=10901&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 - 2006-04-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Myocardial protection at a crossroads: the need for translation into clinical therapy. AN - 66739977; 15271864 AB - Over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The National Heart, Lung, and Blood Institute convened a working group to discuss the reasons for the failure to translate potential therapies for protecting the heart from ischemia and reperfusion and to recommend new approaches to accomplish this goal. The Working Group concluded that cardioprotection in the setting of acute myocardial infarction, cardiac surgery, and cardiac arrest is at a crossroads. Present basic research approaches to identify cardioprotective therapies are inefficient and counterproductive. For 3 decades, significant resources have been invested in single-center studies that have often yielded inconclusive results. A new paradigm is needed to obviate many of the difficulties associated with translation of basic science findings. The Working Group urged a new focus on translational research that emphasizes efficacy and clinically relevant outcomes, and recommended the establishment of a system for rigorous preclinical testing of promising cardioprotective agents with clinical trial-like approaches (ie, blinded, randomized, multicenter, and adequately powered studies using standardized methods). A national preclinical research consortium would enable rational translation of important basic science findings into clinical use. The Working Group recommended that the National Institutes of Health proactively intervene to remedy current problems that impede translation of cardioprotective therapies. Their specific recommendations include the establishment of a preclinical consortium and the performance of 2 clinical studies that are likely to demonstrate effectiveness (phase III clinical trials of adenosine in acute myocardial infarction and cardiac surgery). JF - Circulation research AU - Bolli, Roberto AU - Becker, Lance AU - Gross, Garrett AU - Mentzer, Robert AU - Balshaw, David AU - Lathrop, David A AU - NHLBI Working Group on the Translation of Therapies for Protecting the Heart from Ischemia AD - Heart Research Program, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health & Human Services, Bethesda, Md 20892, USA. ; NHLBI Working Group on the Translation of Therapies for Protecting the Heart from Ischemia Y1 - 2004/07/23/ PY - 2004 DA - 2004 Jul 23 SP - 125 EP - 134 VL - 95 IS - 2 KW - Cardiotonic Agents KW - 0 KW - Guanidines KW - Sodium-Hydrogen Antiporter KW - Sulfones KW - cariporide KW - 7E3392891K KW - eniporide KW - 7IGF9182QU KW - Index Medicus KW - Myocardial Infarction -- pathology KW - Animals KW - Clinical Trials, Phase III as Topic KW - Guanidines -- administration & dosage KW - Humans KW - Clinical Trials as Topic KW - Drug Utilization KW - Sulfones -- administration & dosage KW - Sulfones -- adverse effects KW - Prospective Studies KW - Guanidines -- therapeutic use KW - Sulfones -- therapeutic use KW - Coronary Artery Bypass KW - Treatment Outcome KW - Sodium-Hydrogen Antiporter -- antagonists & inhibitors KW - Guanidines -- adverse effects KW - Drug Evaluation, Preclinical KW - Myocardial Infarction -- drug therapy KW - Myocardial Ischemia -- surgery KW - Myocardial Ischemia -- drug therapy KW - Myocardial Reperfusion Injury -- drug therapy KW - Cardiotonic Agents -- therapeutic use KW - Myocardial Ischemia -- prevention & control KW - Myocardial Reperfusion Injury -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66739977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Myocardial+protection+at+a+crossroads%3A+the+need+for+translation+into+clinical+therapy.&rft.au=Bolli%2C+Roberto%3BBecker%2C+Lance%3BGross%2C+Garrett%3BMentzer%2C+Robert%3BBalshaw%2C+David%3BLathrop%2C+David+A%3BNHLBI+Working+Group+on+the+Translation+of+Therapies+for+Protecting+the+Heart+from+Ischemia&rft.aulast=Bolli&rft.aufirst=Roberto&rft.date=2004-07-23&rft.volume=95&rft.issue=2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Circulation+research&rft.issn=1524-4571&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-08 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of DNA structure on DNA polymerase beta active site function: extension of mutagenic DNA intermediates. AN - 66717877; 15145936 AB - In the ternary substrate complex of DNA polymerase (pol) beta, the nascent base pair (templating and incoming nucleotides) is sandwiched between the duplex DNA terminus and polymerase. To probe molecular interactions in the dNTP-binding pocket, we analyzed the kinetic behavior of wild-type pol beta on modified DNA substrates that alter the structure of the DNA terminus and represent mutagenic intermediates. The DNA substrates were modified to 1) alter the sequence of the duplex terminus (matched and mismatched), 2) introduce abasic sites near the nascent base pair, and 3) insert extra bases in the primer or template strands to mimic frameshift intermediates. The results indicate that the nucleotide insertion efficiency (k(cat)/K(m), dGTP-dC) is highly dependent on the sequence identity of the matched (i.e. Watson-Crick base pair) DNA terminus (template/primer, G/C approximately A/T > T/A approximately C/G). Mismatches at the primer terminus strongly diminish correct nucleotide insertion efficiency but do not affect DNA binding affinity. Transition intermediates are generally extended more easily than transversions. Most mismatched primer termini decrease the rate of insertion and binding affinity of the incoming nucleotide. In contrast, the loss of catalytic efficiency with homopurine mismatches at the duplex DNA terminus is entirely due to the inability to insert the incoming nucleotide, since K(d)((dGTP)) is not affected. Abasic sites and extra nucleotides in and around the duplex terminus decrease catalytic efficiency and are more detrimental to the nascent base pair binding pocket when situated in the primer strand than the equivalent position in the template strand. JF - The Journal of biological chemistry AU - Beard, William A AU - Shock, David D AU - Wilson, Samuel H AD - Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07/23/ PY - 2004 DA - 2004 Jul 23 SP - 31921 EP - 31929 VL - 279 IS - 30 SN - 0021-9258, 0021-9258 KW - DNA KW - 9007-49-2 KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Frameshift Mutation KW - Base Sequence KW - Kinetics KW - Humans KW - Base Pair Mismatch KW - In Vitro Techniques KW - Binding, Competitive KW - Catalytic Domain KW - Substrate Specificity KW - Mutagenesis KW - DNA -- metabolism KW - DNA Polymerase beta -- chemistry KW - DNA -- genetics KW - DNA -- chemistry KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66717877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Influence+of+DNA+structure+on+DNA+polymerase+beta+active+site+function%3A+extension+of+mutagenic+DNA+intermediates.&rft.au=Beard%2C+William+A%3BShock%2C+David+D%3BWilson%2C+Samuel+H&rft.aulast=Beard&rft.aufirst=William&rft.date=2004-07-23&rft.volume=279&rft.issue=30&rft.spage=31921&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 - 2004-09-21 N1 - Date created - 2004-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The trihelical bundle subdomain of the GGA proteins interacts with multiple partners through overlapping but distinct sites. AN - 66716689; 15143060 AB - The Golgi-localized, gamma-adaptin ear-containing, ARF-binding (GGA) proteins are monomeric clathrin adaptors that mediate the sorting of cargo at the trans-Golgi network and endosomes. The GGAs contain four different domains named Vps27, Hrs, Stam (VHS); GGAs and TOM1 (GAT); hinge; and gamma-adaptin ear (GAE). The VHS domain recognizes transmembrane cargo, whereas the hinge and GAE regions bind clathrin and accessory proteins, respectively. The GAT domain is a polyfunctional module that interacts with various partners including the small GTPase ARF, the endosomal fusion regulator Rabaptin-5, ubiquitin, and the product of the tumor susceptibility gene 101 (TSG101). Previous x-ray crystallographic analyses showed that the GAT region is composed of two subdomains, an N-terminal helix-loop-helix containing the ARF binding site, and a C-terminal triple alpha-helical (trihelical) bundle. In this study, we define the Rabaptin-5 binding site on the GGA1-GAT domain and its relationship to the binding sites for ubiquitin and TSG101. Our observations show that Rabaptin-5, ubiquitin, and TSG101 bind to overlapping but distinct binding sites on the trihelical bundle. The different GAT binding partners engage in both competitive and cooperative interactions that may be important for the function of the GGAs in protein sorting. JF - The Journal of biological chemistry AU - Mattera, Rafael AU - Puertollano, Rosa AU - Smith, William J AU - Bonifacino, Juan S AD - Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/23/ PY - 2004 DA - 2004 Jul 23 SP - 31409 EP - 31418 VL - 279 IS - 30 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Vesicular Transport KW - 0 KW - Carrier Proteins KW - GGA adaptor proteins KW - RABEP1 protein, human KW - Recombinant Proteins KW - Vesicular Transport Proteins KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - rab GTP-Binding Proteins KW - Index Medicus KW - Vesicular Transport Proteins -- genetics KW - Models, Molecular KW - ADP-Ribosylation Factor 1 -- genetics KW - Humans KW - Two-Hybrid System Techniques KW - ADP-Ribosylation Factor 1 -- chemistry KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - rab GTP-Binding Proteins -- genetics KW - rab GTP-Binding Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - ADP-Ribosylation Factor 1 -- metabolism KW - In Vitro Techniques KW - Molecular Sequence Data KW - Vesicular Transport Proteins -- metabolism KW - Recombinant Proteins -- chemistry KW - Binding Sites -- genetics KW - rab GTP-Binding Proteins -- metabolism KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Vesicular Transport Proteins -- chemistry KW - Amino Acid Substitution KW - ADP-Ribosylation Factors -- genetics KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - ADP-Ribosylation Factors -- metabolism KW - Carrier Proteins -- genetics KW - ADP-Ribosylation Factors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66716689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+trihelical+bundle+subdomain+of+the+GGA+proteins+interacts+with+multiple+partners+through+overlapping+but+distinct+sites.&rft.au=Mattera%2C+Rafael%3BPuertollano%2C+Rosa%3BSmith%2C+William+J%3BBonifacino%2C+Juan+S&rft.aulast=Mattera&rft.aufirst=Rafael&rft.date=2004-07-23&rft.volume=279&rft.issue=30&rft.spage=31409&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 - 2004-09-21 N1 - Date created - 2004-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome AN - 223939921; 15269312 AB - Background Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. Methods We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. Results Mean (±SD) PEEP values on days 1 through 4 were 8.3±3.2 cm of water in the lower-PEEP group and 13.2±3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5±10.4 days in the lower-PEEP group and 13.8±10.6 days in the higher-PEEP group (P=0.50). Conclusions These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used. JF - The New England Journal of Medicine AU - Brower, R G AU - Lanken, P N AU - MacIntyre, N AU - Matthay MA AU - Morris, A AU - Ancukiewicz, M AU - Schoenfeld, D AU - Thompson, B T AU - National Heart, Lung, and Blood Institute ARDS Clinical Trials Network AD - National Heart, Lung, and Blood Institute ARDS Clinical Trials Network Y1 - 2004/07/22/ PY - 2004 DA - 2004 Jul 22 SP - 327 EP - 36 CY - Boston PB - Massachusetts Medical Society VL - 351 IS - 4 SN - 00284793 KW - Medical Sciences KW - Biological Markers KW - Interleukin-6 KW - Pulmonary Surfactant-Associated Protein D KW - Intercellular Adhesion Molecule-1 KW - Ventilators KW - Lungs KW - Injuries KW - Respiratory distress syndrome KW - Mortality KW - Proteins KW - Respiratory Distress Syndrome, Adult -- mortality KW - Intercellular Adhesion Molecule-1 -- blood KW - Humans KW - Pulmonary Surfactant-Associated Protein D -- blood KW - Aged KW - Respiratory Physiological Phenomena KW - Biological Markers -- blood KW - Interleukin-6 -- blood KW - Respiratory Distress Syndrome, Adult -- blood KW - Hospital Mortality KW - Adult KW - Treatment Outcome KW - Respiratory Distress Syndrome, Adult -- physiopathology KW - Middle Aged KW - Female KW - Male KW - Positive-Pressure Respiration -- methods KW - Respiratory Distress Syndrome, Adult -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/223939921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Higher+versus+Lower+Positive+End-Expiratory+Pressures+in+Patients+with+the+Acute+Respiratory+Distress+Syndrome&rft.au=Brower%2C+R+G%3BLanken%2C+P+N%3BMacIntyre%2C+N%3BMatthay+MA%3BMorris%2C+A%3BAncukiewicz%2C+M%3BSchoenfeld%2C+D%3BThompson%2C+B+T%3BNational+Heart%2C+Lung%2C+and+Blood+Institute+ARDS+Clinical+Trials+Network&rft.aulast=Brower&rft.aufirst=R&rft.date=2004-07-22&rft.volume=351&rft.issue=4&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=The+New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright © 2004 Massachusetts Medical Society. All rights reserved. N1 - Document feature - Tables; Graphs; Diagrams; References N1 - Last updated - 2014-04-21 N1 - CODEN - NEJMAG ER - TY - JOUR T1 - Neural activity protects hypothalamic magnocellular neurons against axotomy-induced programmed cell death. AN - 66732014; 15269267 AB - Axotomy typically leads to retrograde neuronal degeneration in the CNS. Studies in the hypothalamo-neurohypophysial system (HNS) have suggested that neural activity is supportive of magnocellular neuronal (MCN) survival after axotomy. In this study, we directly test this hypothesis by inhibiting neural activity in the HNS, both in vivo and in vitro, by the use of tetrodotoxin (TTX). After median eminence compression to produce axonal injury, unilateral superfusion of 3 microM TTX into the rat supraoptic nucleus (SON), delivered with the use of a miniature osmotic pump for 2 weeks in vivo, produced a decrease in the number of surviving MCNs in the TTX-treated SON, compared with the contralateral untreated side of the SON. In vitro application of 2.5 microM TTX for 2 weeks to the SON in organotypic culture produced a 73% decrease in the surviving MCNs, compared with untreated control cultures. Raising the extracellular KCl in the culture medium to 25 mM rescued the MCNs from the axotomy- and TTX-induced cell death. These data support the proposal that after axotomy, neural activity is neuroprotective in the HNS. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Shahar, Tal AU - House, Shirley B AU - Gainer, Harold AD - Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4130, USA. Y1 - 2004/07/21/ PY - 2004 DA - 2004 Jul 21 SP - 6553 EP - 6562 VL - 24 IS - 29 KW - Tetrodotoxin KW - 4368-28-9 KW - Potassium Chloride KW - 660YQ98I10 KW - Index Medicus KW - Animals KW - Axotomy KW - Synaptic Transmission -- drug effects KW - Potassium Chloride -- pharmacology KW - Rats KW - Tetrodotoxin -- toxicity KW - Rats, Sprague-Dawley KW - Neurites -- ultrastructure KW - Cell Survival -- drug effects KW - Neurites -- drug effects KW - Median Eminence -- surgery KW - Organ Culture Techniques KW - Male KW - Apoptosis KW - Supraoptic Nucleus -- cytology KW - Nerve Degeneration -- physiopathology KW - Neurons -- cytology KW - Nerve Degeneration -- pathology KW - Neurons -- physiology KW - Supraoptic Nucleus -- physiopathology KW - Supraoptic Nucleus -- drug effects KW - Neurons -- pathology KW - Nerve Degeneration -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66732014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neural+activity+protects+hypothalamic+magnocellular+neurons+against+axotomy-induced+programmed+cell+death.&rft.au=Shahar%2C+Tal%3BHouse%2C+Shirley+B%3BGainer%2C+Harold&rft.aulast=Shahar&rft.aufirst=Tal&rft.date=2004-07-21&rft.volume=24&rft.issue=29&rft.spage=6553&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-21 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Neurosci. 2004 Aug 4;24(31):1 p following 7014 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynamic characterization of a DNA repair enzyme: NMR studies of [methyl-13C]methionine-labeled DNA polymerase beta. AN - 66702336; 15248749 AB - Crystallographic characterization of DNA polymerase beta (pol beta) has suggested that multiple-domain and subdomain motions occur during substrate binding and catalysis. NMR studies of [methyl-(13)C]methionine-labeled pol beta were conducted to characterize the structural and dynamic response to ligand binding. The enzyme contains seven methionine residues, one of which is at the amino terminus and is partially removed by the expression system. Three of the methyl resonances were readily assigned using site-directed mutants. Assignment of the resonances of Met155, Met158, and Met191 was more difficult due to the spatial proximity of these residues, so that assignments were based on NOESY-HSQC data and on the response to paramagnetic Co(2+) addition, as well as shift perturbations observed for the site-directed mutants. The response of the methyl resonances to substrate binding was evaluated by the serial addition of a template oligonucleotide, a downstream 5'-phosphorylated oligonucleotide, and a primer oligonucleotide to create a two-nucleotide-gapped DNA substrate. Addition of the single-stranded template DNA resulted in selective broadening of the methyl resonance of Met18 in the 8 kDa lyase domain, and this resonance then shifted and sharpened upon addition of a 5'-phosphate-terminated downstream complementary oligonucleotide. Conversion of the two-nucleotide-gapped DNA substrate to a single-nucleotide-gapped substrate by incorporation of ddCMP produced a small perturbation of the Met236 resonance, which makes contact with the primer strand in the crystal structure. The addition of a second equivalent of ddCTP to form the pol beta-DNA-ddCTP ternary complex resulted in significant shifts for the resonances corresponding to Met155, Met191, Met236, and Met282. The Met155 methyl resonance is severely broadened, while the Met191 and Met282 resonances exhibit significant but less extreme broadening. Since only Met236 makes contact with the substrate, the effects on Met155, Met236, and Met282 result from indirect conformational and dynamic perturbations. Previous crystallographic characterization of this abortive complex indicated that a polymerase subdomain or segment (alpha-helix N) repositions itself to form one face of the binding pocket for the nascent base pair. Met282 serves as a probe for motion in this segment. Addition of Mg(2+)-dATP to pol beta in the absence of DNA produced qualitatively similar but much smaller effects on Met191 and Met155, but did not strongly perturb Met282, leading to the conclusion that Mg(2+)-dATP alone is insufficient to produce the large conformational changes that are observed in the abortive complex involving the gapped DNA with a blocked primer and ddNTP. Thus, the NMR data indicate that the nucleotide-DNA interaction appears to be essential for conformational activation. JF - Biochemistry AU - Bose-Basu, Bidisha AU - DeRose, Eugene F AU - Kirby, Thomas W AU - Mueller, Geoffrey A AU - Beard, William A AU - Wilson, Samuel H AU - London, Robert E AD - Laboratory of Structural Biology, NIEHS, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07/20/ PY - 2004 DA - 2004 Jul 20 SP - 8911 EP - 8922 VL - 43 IS - 28 SN - 0006-2960, 0006-2960 KW - Carbon Isotopes KW - 0 KW - Deoxycytosine Nucleotides KW - Oligonucleotides KW - DNA Polymerase beta KW - EC 2.7.7.- KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Molecular Structure KW - Animals KW - Motion KW - Oligonucleotides -- pharmacology KW - Deoxycytosine Nucleotides -- chemistry KW - Protein Conformation -- drug effects KW - Mutation, Missense KW - Protein Binding KW - Rats KW - Mutagenesis, Site-Directed KW - Deoxycytosine Nucleotides -- pharmacology KW - Oligonucleotides -- chemistry KW - Nuclear Magnetic Resonance, Biomolecular -- methods KW - DNA Polymerase beta -- chemistry KW - DNA Repair Enzymes -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66702336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dynamic+characterization+of+a+DNA+repair+enzyme%3A+NMR+studies+of+%5Bmethyl-13C%5Dmethionine-labeled+DNA+polymerase+beta.&rft.au=Bose-Basu%2C+Bidisha%3BDeRose%2C+Eugene+F%3BKirby%2C+Thomas+W%3BMueller%2C+Geoffrey+A%3BBeard%2C+William+A%3BWilson%2C+Samuel+H%3BLondon%2C+Robert+E&rft.aulast=Bose-Basu&rft.aufirst=Bidisha&rft.date=2004-07-20&rft.volume=43&rft.issue=28&rft.spage=8911&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-09 N1 - Date created - 2004-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis of a bromotyrosine-derived natural product inhibitor of mycothiol-S-conjugate amidase. AN - 66643258; 15203162 AB - Recently we described the structures of two new bromotyrosine-derived alkaloids that inhibit the detoxification enzyme mycothiol-S-conjugate amidase (MCA) from Mycobacterium tuberculosis. Here we describe a concise total synthesis of bromotyrosine oxime 1. The six-step synthesis of 1 utilized a trifluoromethyloxazole intermediate, whose hydrolysis product underwent alkylation and coupling to agmatine to give the inhibitor in approximately 40% overall yield. Oxime 1 inhibited MCA and its homolog AcGI deacetylase with IC(50) values of 30 and 150 microM, respectively. JF - Bioorganic & medicinal chemistry letters AU - Fetterolf, Brandon AU - Bewley, Carole A AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0820, USA. Y1 - 2004/07/16/ PY - 2004 DA - 2004 Jul 16 SP - 3785 EP - 3788 VL - 14 IS - 14 SN - 0960-894X, 0960-894X KW - Anti-Infective Agents KW - 0 KW - Bacterial Proteins KW - Hydrocarbons, Fluorinated KW - Oxazoles KW - Oximes KW - bromotyrosine KW - Tyrosine KW - 42HK56048U KW - Amidohydrolases KW - EC 3.5.- KW - N-acetyl-1-D-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase KW - EC 3.5.1.- KW - mycothiol S-conjugate amidase KW - Index Medicus KW - Hydrocarbons, Fluorinated -- chemistry KW - Kinetics KW - Oxazoles -- chemistry KW - Inhibitory Concentration 50 KW - Oximes -- chemistry KW - Hydrolysis KW - Structure-Activity Relationship KW - Alkylation KW - Amidohydrolases -- metabolism KW - Mycobacterium tuberculosis -- enzymology KW - Tyrosine -- pharmacology KW - Anti-Infective Agents -- pharmacology KW - Amidohydrolases -- antagonists & inhibitors KW - Tyrosine -- analogs & derivatives KW - Mycobacterium tuberculosis -- drug effects KW - Anti-Infective Agents -- chemical synthesis KW - Tyrosine -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66643258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+letters&rft.atitle=Synthesis+of+a+bromotyrosine-derived+natural+product+inhibitor+of+mycothiol-S-conjugate+amidase.&rft.au=Fetterolf%2C+Brandon%3BBewley%2C+Carole+A&rft.aulast=Fetterolf&rft.aufirst=Brandon&rft.date=2004-07-16&rft.volume=14&rft.issue=14&rft.spage=3785&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-07 N1 - Date created - 2004-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma. AN - 66733837; 15269145 AB - P-glycoprotein (Pgp) inhibitors have been under clinical evaluation for drug resistance reversal for over a decade. Valspodar (PSC 833) inhibits Pgp-mediated efflux but delays drug clearance, requiring reduction of anticancer drug dosage. We designed an infusional schedule for valspodar and vinblastine to mimic infusional vinblastine alone. The study was designed to determine the maximally tolerated dose of vinblastine, while attempting to understand the pharmacokinetic interactions between vinblastine and valspodar and to determine the response rate in patients with metastatic renal cell cancer. Thirty-nine patients received continuous infusion valspodar and vinblastine. Vinblastine was administered for 3 days to compensate for the expected delay in clearance and the required dose reduction. Valspodar was administered initially at a dose of 10 mg/kg/d; the dose of vinblastine varied. The maximum-tolerated dose of vinblastine was 1.3 mg/m(2)/d. As suggested previously, serum valspodar concentrations exceeded those needed for Pgp inhibition. Consequently, the dose of valspodar was reduced to 5 mg/kg, allowing a vinblastine dose of 2.1 mg/m(2)/d to be administered. Pharmacodynamic studies demonstrated continued inhibition of Pgp at lower valspodar doses by functional assay in Pgp-expressing CD56+ cells and by (99m)Tc-sestamibi imaging. A 15-fold range in cytochrome p450 activity was observed, as measured by midazolam clearance. No major responses were observed. These results suggest that the pharmacokinetic impact of cytochrome P450 inhibition by valspodar can be reduced although not eliminated, while preserving Pgp inhibition, thus separating the pharmacokinetic and pharmacodynamic activities of valspodar. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Bates, Susan E AU - Bakke, Susan AU - Kang, Min AU - Robey, Robert W AU - Zhai, Suoping AU - Thambi, Paul AU - Chen, Clara C AU - Patil, Sheela AU - Smith, Tom AU - Steinberg, Seth M AU - Merino, Maria AU - Goldspiel, Barry AU - Meadows, Beverly AU - Stein, Wilfred D AU - Choyke, Peter AU - Balis, Frank AU - Figg, William D AU - Fojo, Tito AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. sebates@helix.nih.gov Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 4724 EP - 4733 VL - 10 IS - 14 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Cyclosporins KW - P-Glycoprotein KW - Vinblastine KW - 5V9KLZ54CY KW - valspodar KW - Q7ZP55KF3X KW - Index Medicus KW - Infusions, Intravenous KW - Area Under Curve KW - Dose-Response Relationship, Drug KW - Humans KW - Fatigue -- chemically induced KW - Metabolic Clearance Rate KW - Aged KW - Constipation -- chemically induced KW - P-Glycoprotein -- antagonists & inhibitors KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Male KW - Female KW - Cyclosporins -- adverse effects KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- drug therapy KW - Carcinoma, Renal Cell -- metabolism KW - Cyclosporins -- pharmacokinetics KW - Vinblastine -- pharmacokinetics KW - Kidney Neoplasms -- metabolism KW - Vinblastine -- administration & dosage KW - Carcinoma, Renal Cell -- drug therapy KW - Vinblastine -- adverse effects KW - Cyclosporins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66733837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+phase+I%2FII+study+of+infusional+vinblastine+with+the+P-glycoprotein+antagonist+valspodar+%28PSC+833%29+in+renal+cell+carcinoma.&rft.au=Bates%2C+Susan+E%3BBakke%2C+Susan%3BKang%2C+Min%3BRobey%2C+Robert+W%3BZhai%2C+Suoping%3BThambi%2C+Paul%3BChen%2C+Clara+C%3BPatil%2C+Sheela%3BSmith%2C+Tom%3BSteinberg%2C+Seth+M%3BMerino%2C+Maria%3BGoldspiel%2C+Barry%3BMeadows%2C+Beverly%3BStein%2C+Wilfred+D%3BChoyke%2C+Peter%3BBalis%2C+Frank%3BFigg%2C+William+D%3BFojo%2C+Tito&rft.aulast=Bates&rft.aufirst=Susan&rft.date=2004-07-15&rft.volume=10&rft.issue=14&rft.spage=4724&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 - 2005-01-19 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using germ-line genetic variation to investigate and treat cancer. AN - 66689887; 15239980 AB - For many years, there has been spirited debate as to the relative importance of environmental and genetic factors in the pathogenesis of cancer. Current efforts to annotate the human genome for germ-line genetic variants should establish the foundation for dissecting the contribution of genetics to the risk for cancer susceptibility. Population-based studies should be conducted to determine the influence of germline genetic variation on cancer outcomes, including the efficacy of anti-cancer drugs and the risk for life-threatening toxicities. Although we are early in the investigation of the influence of germline genetics on cancer outcomes, it is likely that, in the future, it will be possible to individualize therapeutic interventions. In turn, knowledge of genetic risk factors could afford opportunities for prevention, early intervention and minimization of deleterious toxicities associated with cancer therapy. JF - Drug discovery today AU - Savage, Sharon A AU - Chanock, Stephen J AD - Section of Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 610 EP - 618 VL - 9 IS - 14 SN - 1359-6446, 1359-6446 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Microsatellite Repeats -- genetics KW - Genome, Human KW - Antineoplastic Agents -- therapeutic use KW - Polymorphism, Single Nucleotide -- genetics KW - Polymorphism, Single Nucleotide -- physiology KW - Neoplasms -- genetics KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66689887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+discovery+today&rft.atitle=Using+germ-line+genetic+variation+to+investigate+and+treat+cancer.&rft.au=Savage%2C+Sharon+A%3BChanock%2C+Stephen+J&rft.aulast=Savage&rft.aufirst=Sharon&rft.date=2004-07-15&rft.volume=9&rft.issue=14&rft.spage=610&rft.isbn=&rft.btitle=&rft.title=Drug+discovery+today&rft.issn=13596446&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-31 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2-amino-O4-benzylpteridine derivatives: potent inactivators of O6-alkylguanine-DNA alkyltransferase. AN - 66686363; 15239666 AB - 2-amino-O4-benzylpteridine (1), 2-amino-O4-benzyl-6,7-dimethylpteridine (2), 2-amino-O4-benzyl-6-hydroxymethylpteridine (4), 2-amino-O4-benzylpteridine-6-carboxylic acid (5), 2-amino-O4-benzyl-6-formylpteridine (6), and O4-benzylfolic acid (7) are shown to be as potent or more potent inactivators of the human DNA repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase) in vitro than O6-benzylguanine, the prototype alkyltransferase inactivator currently in clinical trials. Additionally, the negatively charged (at physiological pH) inactivators 2-amino-O4-benzylpteridine-6-carboxylic acid (5) and O4-benzylfolate (7) are far more water soluble than O6-benzylguanine. The activity of O4-benzylfolic acid (7) is particularly noteworthy because it is roughly 30 times more active than O6-benzylguanine against the wild-type alkyltransferase and is even capable of inactivating the P140K mutant alkyltransferase that is resistant to inactivation by O6-benzylguanine. All the pteridine derivatives except 2-amino-O4-benzylpteridine-6-carboxylic acid are effective in enhancing cell killing by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). However, the effectiveness of O4-benzylfolate as an adjuvant for cell killing by BCNU appears to be a function of a cell's alpha-folate receptor expression. Thus, O4-benzylfolate is least effective as an adjuvant in A549 cells (which express little if any receptor), is moderately effective in HT29 cells (which express low levels of the receptor), but is very effective in KB cells (which are known to express high levels of the alpha-folate receptor). Therefore, O4-benzylfolic acid shows promise as an agent for possible tumor-selective alkyltransferase inactivation, which suggests it may prove to be superior to O6-benzylguanine as a chemotherapy adjuvant. JF - Journal of medicinal chemistry AU - Nelson, Michael E AU - Loktionova, Natalia A AU - Pegg, Anthony E AU - Moschel, Robert C AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, P.O. Box B, Building 538, Frederick, MD 21702, USA. Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 3887 EP - 3891 VL - 47 IS - 15 SN - 0022-2623, 0022-2623 KW - Pteridines KW - 0 KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Humans KW - Cell Line, Tumor KW - Chemotherapy, Adjuvant KW - Structure-Activity Relationship KW - Pteridines -- chemistry KW - Pteridines -- pharmacology KW - O(6)-Methylguanine-DNA Methyltransferase -- antagonists & inhibitors KW - O(6)-Methylguanine-DNA Methyltransferase -- chemistry KW - Pteridines -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66686363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=2-amino-O4-benzylpteridine+derivatives%3A+potent+inactivators+of+O6-alkylguanine-DNA+alkyltransferase.&rft.au=Nelson%2C+Michael+E%3BLoktionova%2C+Natalia+A%3BPegg%2C+Anthony+E%3BMoschel%2C+Robert+C&rft.aulast=Nelson&rft.aufirst=Michael&rft.date=2004-07-15&rft.volume=47&rft.issue=15&rft.spage=3887&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 - 2004-08-12 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cholera toxin prevents Th1-mediated autoimmune disease by inducing immune deviation. AN - 66685294; 15240661 AB - Cholera toxin (CT), a major enterotoxin produced by Vibrio cholerae, is known for its properties as a mucosal adjuvant that promotes Th2 or mixed Th1 + Th2 responses. In this study, we explore the ability of CT to act as a systemic adjuvant to counteract the Th1 response leading to experimental autoimmune uveitis. We report that susceptible B10.RIII mice immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein could be protected from disease by a single systemic injection of as little as 2 micro g of CT at the time of immunization. The protected mice were not immunosuppressed, but rather displayed evidence of immune deviation. Subsequent adaptive responses to interphotoreceptor retinoid-binding protein showed evidence of Th2 enhancement, as indicated by reduced delayed-type hypersensitivity in the context of enhanced Ag-specific lymphocyte proliferation and IL-4 production. Ag-specific production of several other cytokines, including IFN-gamma, was not appreciably altered. The inhibitory effect of CT was dependent on the enzymatic A subunit of CT, because the cell-binding B subunit alone could not block disease development. Mice given CT displayed detectable IL-4 levels in their serum within hours of CT administration. This innate IL-4 production was critical for protection, as infusion of neutralizing Ab against IL-4 to mice, given a uveitogenic immunization and treated with CT, counteracted immune deviation and abrogated protection. Our data indicate that systemic administration of CT inhibits experimental autoimmune uveitis by skewing the response to the uveitogenic autoantigen to a nonpathogenic phenotype. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Su, Shao-Bo AU - Silver, Phyllis B AU - Wang, Peng AU - Chan, Chi-Chao AU - Caspi, Rachel R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 755 EP - 761 VL - 173 IS - 2 SN - 0022-1767, 0022-1767 KW - Adjuvants, Immunologic KW - 0 KW - Autoantigens KW - Cholera Toxin KW - 9012-63-9 KW - Abridged Index Medicus KW - Index Medicus KW - Uveitis -- prevention & control KW - Animals KW - Uveitis -- pathology KW - Autoantigens -- immunology KW - Uveitis -- immunology KW - Mice KW - Autoimmune Diseases -- prevention & control KW - Th1 Cells -- drug effects KW - Autoimmune Diseases -- pathology KW - Cholera Toxin -- pharmacology KW - Adjuvants, Immunologic -- pharmacology KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66685294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cholera+toxin+prevents+Th1-mediated+autoimmune+disease+by+inducing+immune+deviation.&rft.au=Su%2C+Shao-Bo%3BSilver%2C+Phyllis+B%3BWang%2C+Peng%3BChan%2C+Chi-Chao%3BCaspi%2C+Rachel+R&rft.aulast=Su&rft.aufirst=Shao-Bo&rft.date=2004-07-15&rft.volume=173&rft.issue=2&rft.spage=755&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 - 2004-08-27 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethics and Standard of Care in Clinical Trials/From the Authors AN - 199644921; 15242856 JF - American Journal of Respiratory and Critical Care Medicine AU - Brower, Roy G AU - Gordon, Bernard AU - Morris, Alan AU - Miller, Franklin G AU - Silverman, Henry J Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 198 EP - 9; author reply 199 CY - New York PB - American Thoracic Society VL - 170 IS - 2 SN - 1073449X KW - Medical Sciences--Respiratory Diseases KW - Pulmonary Medicine -- standards KW - Humans KW - Respiratory Distress Syndrome, Adult -- therapy KW - Clinical Trials as Topic -- standards KW - Clinical Trials as Topic -- ethics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/199644921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.atitle=Ethics+and+Standard+of+Care+in+Clinical+Trials%2FFrom+the+Authors&rft.au=Brower%2C+Roy+G%3BGordon%2C+Bernard%3BMorris%2C+Alan%3BMiller%2C+Franklin+G%3BSilverman%2C+Henry+J&rft.aulast=Brower&rft.aufirst=Roy&rft.date=2004-07-15&rft.volume=170&rft.issue=2&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.issn=1073449X&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Thoracic Society Jul 15, 2004 N1 - Last updated - 2017-01-07 ER - TY - JOUR T1 - Immunization of Patients with the hTERT:540-548 Peptide Induces Peptide-Reactive T Lymphocytes That Do Not Recognize Tumors Endogenously Expressing Telomerase AN - 19400415; 5956877 AB - PURPOSE: Telomerase is an attractive target antigen for cancer immunotherapies because it is expressed in >85% of human tumors but is rarely found in normal tissues. A HLA-A*0201-restricted T-cell epitope was previously identified within telomerase reverse transcriptase hTERT:540-548. This peptide was reported to induce CTL that recognized tumor cells and transfectants that endogenously expressed telomerase. Therefore, we initiated a clinical protocol to evaluate the therapeutic and immunological efficacy of this peptide. Experimental Design: Fourteen patients with metastatic cancers were vaccinated with hTERT:540-548 emulsified in incomplete Freund's adjuvant. RESULTS: In 7 patients, peripheral blood mononuclear cells collected after immunization recognized hTERT:540-548, whereas those collected before vaccination did not. However, none of these CTLs recognized tumors that endogenously expressed telomerase, and none of the patients had an objective clinical response. Several highly avid T-cell clones were generated that recognized T2 cells pulsed with <1 nM hTERT:540-548, but none of these recognized HLA-A*0201 super(+) hTERT super(+) tumors or cells transduced with the human telomerase reverse transcriptase (hTERT) gene. Also, an antibody specific for hTERT:540-548/HLA-A*0201 complexes stained peptide-pulsed cells but not telomerase super(+) tumors. CONCLUSIONS: Our results are discordant with previous studies and those of a clinical trial that claimed peripheral blood mononuclear cells from patients vaccinated with peptide-pulsed dendritic cells lysed hTERT super(+) tumors. However, our findings are consistent with a previous study that demonstrated that the hTERT:540-548 peptide is cleaved in the proteasome. These results suggest that hTERT:540-548 is not presented on the surfaces of tumor cells in the context of HLA-A*0201 and will not be useful for the immunotherapy of patients with cancer. JF - Clinical Cancer Research AU - Parkhurst, Maria R AU - Riley, John P AU - Igarashi, Takehito AU - Li, Yong AU - Robbins, Paul F AU - Rosenberg, Steven A AD - National Cancer Institute, Surgery Branch and National Heart, Lung, and Blood Institute, Hematology Branch, NIH, Bethesda, Maryland Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 4688 EP - 4698 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 10 IS - 14 SN - 1078-0432, 1078-0432 KW - Genetics Abstracts; Immunology Abstracts; Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Histocompatibility antigen HLA KW - Immunotherapy KW - proteasomes KW - Tumors KW - telomerase reverse transcriptase KW - Clinical trials KW - Tumor cells KW - Vaccination KW - Cancer KW - Metastases KW - Dendritic cells KW - Antibodies KW - Cytotoxicity KW - Peripheral blood mononuclear cells KW - Lymphocytes T KW - Freund's adjuvant KW - Telomerase reverse transcriptase KW - Epitopes KW - G 07880:Human Genetics KW - F 06915:Cancer Immunology KW - N 14835:Protein-Nucleic Acids Association KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19400415?accountid=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+Cancer+Research&rft.atitle=Immunization+of+Patients+with+the+hTERT%3A540-548+Peptide+Induces+Peptide-Reactive+T+Lymphocytes+That+Do+Not+Recognize+Tumors+Endogenously+Expressing+Telomerase&rft.au=Parkhurst%2C+Maria+R%3BRiley%2C+John+P%3BIgarashi%2C+Takehito%3BLi%2C+Yong%3BRobbins%2C+Paul+F%3BRosenberg%2C+Steven+A&rft.aulast=Parkhurst&rft.aufirst=Maria&rft.date=2004-07-15&rft.volume=10&rft.issue=14&rft.spage=4688&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Histocompatibility antigen HLA; Immunotherapy; proteasomes; telomerase reverse transcriptase; Tumors; Vaccination; Tumor cells; Clinical trials; Cancer; Metastases; Dendritic cells; Peripheral blood mononuclear cells; Cytotoxicity; Antibodies; Lymphocytes T; Freund's adjuvant; Telomerase reverse transcriptase; Epitopes ER - TY - JOUR T1 - Engagement of the Pathogen Survival Response Used by Group A Streptococcus to Avert Destruction by Innate Host Defense AN - 18038963; 5945914 AB - Neutrophils are a critical component of human innate host defense and efficiently kill the vast majority of invading microorganisms. However, bacterial pathogens such as group A Streptococcus (GAS) successfully avert destruction by neutrophils to cause human infections. Relatively little is known about how pathogens detect components of the innate immune system to respond and survive within the host. In this study, we show that inactivation of a two- component gene regulatory system designated Ihk-Irr significantly attenuates streptococcal virulence in mouse models of soft tissue infection and bacteremia. Microarray analysis of wild-type and irr-negative mutant (irr mutant) GAS strains revealed that Ihk-Irr influenced expression of 20% of all transcripts in the pathogen genome. Notably, at least 11 genes involved in cell wall synthesis, turnover, and/or modification were down-regulated in the irr mutant strain. Compared with the wild-type strain, significantly more of the irr mutant strain was killed by human neutrophil components that destroy bacteria by targeting the cell envelope (cell wall and/or membrane). Unexpectedly, expression of ihk and irr was dramatically increased in the wild-type strain exposed to these same neutrophil products under conditions that favored cell envelope damage. We report a GAS mechanism for detection of innate host defense that initiates the pathogen survival response, in which cell wall synthesis is critical. Importantly, our studies identify specific genes in the pathogen survival response as potential targets to control human infections. JF - Journal of Immunology AU - Voyich, Jovanka M AU - Braughton, Kevin R AU - Sturdevant, Daniel E AU - Vuong, Cuong AU - Kobayashi, Scott D AU - Porcella, Stephen F AU - Otto, Michael AU - Musser, James M AU - DeLeo, Frank R AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840 Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 1194 EP - 1201 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 173 IS - 2 SN - 0022-1767, 0022-1767 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Cell survival KW - Streptococcus KW - Bacteria KW - Immune system KW - Cell envelopes KW - Animal models KW - Leukocytes (neutrophilic) KW - Bacteremia KW - Pathogens KW - DNA microarrays KW - Streptococcus pyogenes KW - Virulence KW - Soft tissues KW - Cell walls KW - J 02833:Immune response and immune mechanisms KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18038963?accountid=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+Immunology&rft.atitle=Engagement+of+the+Pathogen+Survival+Response+Used+by+Group+A+Streptococcus+to+Avert+Destruction+by+Innate+Host+Defense&rft.au=Voyich%2C+Jovanka+M%3BBraughton%2C+Kevin+R%3BSturdevant%2C+Daniel+E%3BVuong%2C+Cuong%3BKobayashi%2C+Scott+D%3BPorcella%2C+Stephen+F%3BOtto%2C+Michael%3BMusser%2C+James+M%3BDeLeo%2C+Frank+R&rft.aulast=Voyich&rft.aufirst=Jovanka&rft.date=2004-07-15&rft.volume=173&rft.issue=2&rft.spage=1194&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Streptococcus; Pathogens; Leukocytes (neutrophilic); Cell walls; Cell envelopes; DNA microarrays; Bacteremia; Immune system; Soft tissues; Virulence; Bacteria; Cell survival; Animal models ER - TY - JOUR T1 - Divinyl Sulfone as a Postdigestion Modifier for Enhancing the a sub(1) Ion in MS/MS and Postsource Decay: Potential Applications in Proteomics AN - 17302675; 6129556 AB - Divinyl sulfone reacts at pH 8-9 with the alpha -amino groups of N-terminal residues, proline, the epsilon -amino groups of lysine, and the histidine side chains of peptides. This reaction leads to great enhancement of the abundance of the normally weak or missing "a sub(1)" fragment ion in MS/MS analysis defining the N-terminal residue of a peptide in a digest. This provides "one-step Edman-like" information that, together with a fairly accurately determined mass, often enables one to correctly identify a protein or family of proteins. The applicability of this procedure in proteomics was demonstrated with several peptides and tryptic digests of protein mixtures by LC-MS/MS experiments using a QTOF and MALDI-PSD analyses. Advantages of this approach are its simple chemistry, retention of charge multiplicity, and possibly, shortening of database search time. Used with other MS/MS data, it provides higher confidence in the scores and identification of a protein found in peptide mass fingerprinting. Moreover, this approach has an advantage in "de novo" sequencing due to its ability to decipher the first amino acid of a peptide whose information is normally unavailable in MS/MS spectra. JF - Analytical Chemistry (Washington) AU - Boja, E S AU - Sokoloski, E A AU - Fales, H M AD - Laboratory of Biophysical Chemistry, NHLBI, NIH, 50 South Drive, Bethesda, Maryland 20892-8014, USA Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 3958 EP - 3970 VL - 76 IS - 14 SN - 0003-2700, 0003-2700 KW - Divinyl sulfone KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17302675?accountid=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=Analytical+Chemistry+%28Washington%29&rft.atitle=Divinyl+Sulfone+as+a+Postdigestion+Modifier+for+Enhancing+the+a+sub%281%29+Ion+in+MS%2FMS+and+Postsource+Decay%3A+Potential+Applications+in+Proteomics&rft.au=Boja%2C+E+S%3BSokoloski%2C+E+A%3BFales%2C+H+M&rft.aulast=Boja&rft.aufirst=E&rft.date=2004-07-15&rft.volume=76&rft.issue=14&rft.spage=3958&rft.isbn=&rft.btitle=&rft.title=Analytical+Chemistry+%28Washington%29&rft.issn=00032700&rft_id=info:doi/10.1021%2Fac049774e LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1021/ac049774e ER - TY - JOUR T1 - Direct action of estradiol on gonadotropin-releasing hormone-1 neuronal activity via a transcription-dependent mechanism. AN - 66713414; 15254088 AB - Pulsatile secretion of gonadotropin-releasing hormone-1 (GnRH-1) is essential for reproduction. GnRH-1 induces gonadotropin release and is regulated by 17beta-estradiol (E2). Although a subpopulation of GnRH-1 neurons expresses estrogen receptor (ER) beta, it is unclear whether E2 acts directly on GnRH-1 neurons or indirectly through interneuronal connections. To test the hypothesis that E2 acts directly on GnRH-1 neurons to regulate neuronal activity, we used calcium imaging to monitor intracellular calcium oscillations in GnRH-1 neurons maintained in nasal explants. TTX was used to minimize synaptic input from other cells. Consistent with previous studies, TTX reduced the activity of individual GnRH-1 neurons to a basal level, while the population of cells maintained synchronized calcium oscillations. Exposure of GnRH-1 cells to TTX plus E2 increased the number of calcium peaks/cell, percentage of cells with > or =10 peaks, mean peak amplitude, and percentage of cells that contributed to each calcium pulse in explants maintained in vitro for 7 d (7 div) compared with TTX alone. These effects were induced within 30 min and were not mimicked by 17alpha-estradiol, E2 conjugated to BSA (which does not cross the plasma membrane), or seen at 21 div, when the percentage of GnRH-1 cells expressing ERbeta transcripts declines. In addition, these effects were inhibited by the ER antagonist ICI 182,780 and prevented by inhibition of gene transcription. These data suggest that, via ERbeta, E2 can rapidly act as a hormone-activated transcription complex and are the first to show that E2 directly increases GnRH-1 neuronal activity and synchronization. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Temple, Jennifer L AU - Laing, Eric AU - Sunder, Anushka AU - Wray, Susan AD - Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/14/ PY - 2004 DA - 2004 Jul 14 SP - 6326 EP - 6333 VL - 24 IS - 28 KW - Estrogen Receptor Modulators KW - 0 KW - Estrogen Receptor beta KW - Fluorescent Dyes KW - Organic Chemicals KW - Sodium Channel Blockers KW - calcium green KW - 138067-55-7 KW - fulvestrant KW - 22X328QOC4 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Estradiol KW - 4TI98Z838E KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Fluorescent Dyes -- analysis KW - Animals KW - Transcription, Genetic -- drug effects KW - Calcium -- analysis KW - Humans KW - Estrogen Receptor beta -- drug effects KW - Mice KW - Nasal Mucosa -- cytology KW - Secretory Rate KW - Adenocarcinoma -- pathology KW - Breast Neoplasms -- pathology KW - Sodium Channel Blockers -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Organ Culture Techniques KW - Calcium Signaling KW - Female KW - Estrogen Receptor Modulators -- pharmacology KW - Estradiol -- analogs & derivatives KW - Neurons -- drug effects KW - Estradiol -- pharmacology KW - Gonadotropin-Releasing Hormone -- secretion KW - Neurons -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66713414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Direct+action+of+estradiol+on+gonadotropin-releasing+hormone-1+neuronal+activity+via+a+transcription-dependent+mechanism.&rft.au=Temple%2C+Jennifer+L%3BLaing%2C+Eric%3BSunder%2C+Anushka%3BWray%2C+Susan&rft.aulast=Temple&rft.aufirst=Jennifer&rft.date=2004-07-14&rft.volume=24&rft.issue=28&rft.spage=6326&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-13 N1 - Date created - 2004-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subunit-specific regulation of NMDA receptor endocytosis. AN - 66713084; 15254094 AB - At excitatory synapses, both NMDA and AMPA receptors are localized to the postsynaptic density (PSD). However, unlike AMPA receptors, synaptic NMDA receptors are stable components of the PSD. Even so, surface-expressed NMDA receptors undergo endocytosis, which is more robust early in development and declines during synaptic development. We investigated the subunit-specific contributions to NMDA receptor endocytosis, specifically defining the endocytic motifs and endocytic pathways preferred by the NR2A and NR2B subunits. We find that NR2A and NR2B have distinct endocytic motifs encoded in their distal C termini and that these interact with clathrin adaptor complexes with differing affinities. We also find that NR2A and NR2B sort into different intracellular pathways after endocytosis, with NR2B preferentially trafficking through recycling endosomes. In mature cultures, we find that NR2B undergoes more robust endocytosis than NR2A, consistent with previous studies showing that NR2A is more highly expressed at stable synaptic sites. Our findings demonstrate fundamental differences between NR2A and NR2B that help clarify developmental changes in NMDA receptor trafficking and surface expression. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Lavezzari, Gabriela AU - McCallum, Jennifer AU - Dewey, Colleen M AU - Roche, Katherine W AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/14/ PY - 2004 DA - 2004 Jul 14 SP - 6383 EP - 6391 VL - 24 IS - 28 KW - Adaptor Protein Complex 2 KW - 0 KW - Membrane Glycoproteins KW - NR2A NMDA receptor KW - NR2B NMDA receptor KW - Nerve Tissue Proteins KW - Protein Subunits KW - Receptors, N-Methyl-D-Aspartate KW - Recombinant Fusion Proteins KW - TGOLN2 protein, human KW - Tgoln2 protein, rat KW - postsynaptic density proteins KW - Index Medicus KW - Animals KW - Neurons -- metabolism KW - Cerebral Cortex -- metabolism KW - HeLa Cells KW - Humans KW - Two-Hybrid System Techniques KW - Endosomes -- metabolism KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Mutagenesis, Site-Directed KW - Rats, Sprague-Dawley KW - Protein Interaction Mapping KW - Amino Acid Motifs KW - Transfection KW - Hippocampus -- growth & development KW - Hippocampus -- cytology KW - Nerve Tissue Proteins -- metabolism KW - Synapses -- metabolism KW - Protein Transport KW - Adaptor Protein Complex 2 -- metabolism KW - Membrane Glycoproteins -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, N-Methyl-D-Aspartate -- chemistry KW - Endocytosis -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66713084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Subunit-specific+regulation+of+NMDA+receptor+endocytosis.&rft.au=Lavezzari%2C+Gabriela%3BMcCallum%2C+Jennifer%3BDewey%2C+Colleen+M%3BRoche%2C+Katherine+W&rft.aulast=Lavezzari&rft.aufirst=Gabriela&rft.date=2004-07-14&rft.volume=24&rft.issue=28&rft.spage=6383&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-13 N1 - Date created - 2004-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Export from the endoplasmic reticulum of assembled N-methyl-d-aspartic acid receptors is controlled by a motif in the c terminus of the NR2 subunit. AN - 66682090; 15102836 AB - Functional N-methyl-d-aspartic acid (NMDA) receptors are formed from the assembly of NR1 and NR2 subunits. When expressed alone, the major NR1 splice variant and the NR2 subunits are retained in the endoplasmic reticulum (ER), reflecting a quality control mechanism found in many complex multisubunit proteins to ensure that only fully assembled and properly folded complexes reach the cell surface. Recent studies have identified an RRR motif in the C terminus of the NR1 subunit, which controls the ER retention of the unassembled subunit. Here we investigated the mechanisms controlling the ER retention of the NR2 subunit and the export of the assembled complex from the ER. We found that Tac chimeras of the C terminus of the NR2B subunit show that an ER retention signal is also present in the NR2B subunit. In assembled complexes, ER retention signals on the individual subunits must be overcome to allow the complex to leave the ER. One common mechanism involves mutual masking of the signals on the individual subunits. Our data do not support such a mechanism for regulating the release of assembled NMDA receptors from the ER. We found that the motif, HLFY, immediately following transmembrane domain 4 of the NR2 subunit, is required for the assembled complex to exit from the ER. Mutation of this motif allowed the assembly of NR1 and NR2 subunits into a complex that was functional, based on MK-801 binding, but it is retained in the ER. These results are consistent with HLFY functioning as a signal that is necessary for the release of the assembled functional NMDA receptor complex from the ER. JF - The Journal of biological chemistry AU - Hawkins, Lynda M AU - Prybylowski, Kate AU - Chang, Kai AU - Moussan, Caroline AU - Stephenson, F Anne AU - Wenthold, Robert J AD - Laboratory of Neurochemistry, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/09/ PY - 2004 DA - 2004 Jul 09 SP - 28903 EP - 28910 VL - 279 IS - 28 SN - 0021-9258, 0021-9258 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Protein Sorting Signals KW - Protein Subunits KW - Receptors, N-Methyl-D-Aspartate KW - Recombinant Fusion Proteins KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Index Medicus KW - Animals KW - Excitatory Amino Acid Antagonists -- metabolism KW - Dizocilpine Maleate -- metabolism KW - Humans KW - Amino Acid Sequence KW - Mice KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Amino Acid Motifs KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Cell Line KW - Protein Transport -- physiology KW - Endoplasmic Reticulum -- metabolism KW - Protein Subunits -- genetics KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Protein Subunits -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- genetics KW - Receptors, N-Methyl-D-Aspartate -- chemistry KW - Protein Subunits -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66682090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Export+from+the+endoplasmic+reticulum+of+assembled+N-methyl-d-aspartic+acid+receptors+is+controlled+by+a+motif+in+the+c+terminus+of+the+NR2+subunit.&rft.au=Hawkins%2C+Lynda+M%3BPrybylowski%2C+Kate%3BChang%2C+Kai%3BMoussan%2C+Caroline%3BStephenson%2C+F+Anne%3BWenthold%2C+Robert+J&rft.aulast=Hawkins&rft.aufirst=Lynda&rft.date=2004-07-09&rft.volume=279&rft.issue=28&rft.spage=28903&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 - 2004-08-24 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mixed lineage kinase 3 (MLK3)-activated p38 MAP kinase mediates transforming growth factor-beta-induced apoptosis in hepatoma cells. AN - 66679929; 15069087 AB - Although transforming growth factor beta1 (TGF-beta1) acts via the Smad signaling pathway to initiate de novo gene transcription, the TGF-beta1-induced MAPK kinase activation that is involved in the regulation of apoptosis is less well understood. Even though the p38 MAP kinase and c-Jun NH(2)-terminal kinases (JNKs) are involved in TGF-beta1-induced cell death in hepatoma cells, the upstream mediators of these kinases remain to be defined. We show here that the members of the mixed lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper-bearing kinase (DLK)) are expressed in FaO rat hepatoma cells and are likely to act between p38 and TGF-beta receptor kinase in death signaling. TGF-beta1 treatment leads to an increase in MLK3 activity. Overexpression of MLK3 enhances TGF-beta1-induced apoptotic death in FaO cells and Hep3B human hepatoma cells, whereas expression of the dominant-negative forms of MLK3 suppresses cell death induced by TGF-beta1. The dominant-negative forms of MLK1 and -2 also suppress TGF-beta1-induced cell death. In MLK3-overexpressing cells, ERK, JNKs, and p38 MAP kinases were further activated in response to TGF-beta1 compared with the control cells. In contrast, overexpression of the dominant-negative MLK3 resulted in suppression of TGF-beta1-induced MAP kinase activation and TGF-beta1-induced caspase-3 activation. We also show that only the inhibition of the p38 pathway suppressed TGF-beta1-induced apoptosis. These observations support a role for MLKs in the TGF-beta1-induced cell death mechanism. JF - The Journal of biological chemistry AU - Kim, Ki-Yong AU - Kim, Byung-Chul AU - Xu, Zhiheng AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/09/ PY - 2004 DA - 2004 Jul 09 SP - 29478 EP - 29484 VL - 279 IS - 28 SN - 0021-9258, 0021-9258 KW - Enzyme Inhibitors KW - 0 KW - Proteins KW - Recombinant Fusion Proteins KW - TGFB1 protein, human KW - Tgfb1 protein, rat KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Sprk protein, rat KW - EC 2.7.1.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - MAP Kinase Kinase Kinases KW - EC 2.7.11.25 KW - mitogen-activated protein kinase kinase kinase 11 KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Casp3 protein, rat KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Humans KW - Transcription, Genetic KW - Cell Line, Tumor KW - Caspases -- metabolism KW - Rats KW - Recombinant Fusion Proteins -- metabolism KW - Signal Transduction -- physiology KW - Phosphorylation KW - Recombinant Fusion Proteins -- genetics KW - Enzyme Inhibitors -- metabolism KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Apoptosis -- physiology KW - Protein-Serine-Threonine Kinases -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66679929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mixed+lineage+kinase+3+%28MLK3%29-activated+p38+MAP+kinase+mediates+transforming+growth+factor-beta-induced+apoptosis+in+hepatoma+cells.&rft.au=Kim%2C+Ki-Yong%3BKim%2C+Byung-Chul%3BXu%2C+Zhiheng%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Ki-Yong&rft.date=2004-07-09&rft.volume=279&rft.issue=28&rft.spage=29478&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 - 2004-08-24 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Captured Folding Intermediate Involved in Dimerization and Domain-swapping of GB1 AN - 19806388; 5962010 AB - Immunoglobulin binding domain B1 of streptococcal protein G (GB1), a small (56 residues), stable, single domain protein, is one of the most extensively used model systems in the area of protein folding and design. The recently determined NMR structure of a quadruple mutant (HS#124 super(F26A), L5V/F30V/Y33F/A34F) revealed a domain-swapped dimer that dissociated into a partially folded, monomeric species at low micromolar protein concentrations. Here, we have characterized this monomeric, partially folded species by NMR and show that extensive conformational heterogeneity for a substantial portion of the polypeptide chain exists. Exchange between the conformers within the monomer ensemble on the microsecond to millisecond timescale renders the majority of backbone amide resonances broadened beyond detection. Despite these extensive temporal and spatial fluctuations, the overall architecture of the monomeric mutant protein resembles that of wild-type GB1 and not the monomer unit of the domain-swapped dimer. JF - Journal of Molecular Biology AU - Byeon, IL AU - Louis, J M AU - Gronenborn, A M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA, gronenborn@nih.gov Y1 - 2004/07/09/ PY - 2004 DA - 2004 Jul 09 SP - 615 EP - 625 PB - Elsevier Ltd VL - 340 IS - 3 SN - 0022-2836, 0022-2836 KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Monomers KW - Protein folding KW - streptococcal protein G KW - N.M.R. KW - amides KW - Immunoglobulins KW - J 02310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19806388?accountid=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+Molecular+Biology&rft.atitle=A+Captured+Folding+Intermediate+Involved+in+Dimerization+and+Domain-swapping+of+GB1&rft.au=Byeon%2C+IL%3BLouis%2C+J+M%3BGronenborn%2C+A+M&rft.aulast=Byeon&rft.aufirst=IL&rft.date=2004-07-09&rft.volume=340&rft.issue=3&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2Fj.jmb.2004.04.069 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Monomers; Protein folding; streptococcal protein G; N.M.R.; amides; Immunoglobulins; Streptococcus DO - http://dx.doi.org/10.1016/j.jmb.2004.04.069 ER - TY - JOUR T1 - Increased Susceptibility of Mice Lacking Clara Cell 10-kDa Protein to Lung Tumorigenesis by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a Potent Carcinogen in Cigarette Smoke AN - 17998338; 5944147 AB - Ninety percent of all human lung cancers are related to cigarette smoking. Both tobacco smoke and lung tumorigenesis are associated with drastically reduced levels of Clara cell 10-kDa protein (CC10), a multifunctional secreted protein, naturally produced by the airway epithelia of virtually all mammals. We previously reported that the expression of CC10 is markedly reduced in animals exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK, a potent carcinogen in tobacco smoke. Furthermore, it has been reported that CC10 expression, induced in certain tumor cells, reverses the transformed phenotype. We demonstrate here that NNK exposure of CC10-knock-out (CC10-KO) mice causes a significantly higher incidence of airway epithelial hyperplasia and lung adenomas compared with wild type (WT) littermates (30% CC10-KO versus 5% WT, p = 0.041). We also found that compared with NNK-treated WT mice, CC10-KO mice manifest increased frequency of K-ras mutation, elevated level of Fas ligand (FasL) expression, and increased MAPK/Erk phosphorylation, all of which are considered predisposing events in NNK-induced lung tumorigenesis. We propose that CC10 has a protective role against NNK-induced lung tumorigenesis mediated via down-regulation of the above-mentioned predisposing events. JF - Journal of Biological Chemistry AU - Yang, Y AU - Zhang, Z AU - Mukherjee, AB AU - Linnoila, R I AD - Cell and Cancer Biology Branch, Center for Cancer Research, NCI, National Institutes of Health, Rockville, Maryland, yongpiny@mail.nih.gov Y1 - 2004/07/09/ PY - 2004 DA - 2004 Jul 09 SP - 29336 EP - 29340 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 28 SN - 0021-9258, 0021-9258 KW - Clara cell KW - Clara cells KW - mice KW - Genetics Abstracts; Toxicology Abstracts KW - Transformation KW - Tumorigenesis KW - FasL protein KW - Cigarette smoke KW - Tumor cells KW - Phenotypes KW - Cancer KW - Hyperplasia KW - Phosphorylation KW - Lung KW - Carcinogenesis KW - Tobacco KW - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone KW - Proteins KW - Epithelium KW - Expression KW - CC10 protein KW - Adenoma KW - X 24180:Social poisons & drug abuse KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17998338?accountid=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=Increased+Susceptibility+of+Mice+Lacking+Clara+Cell+10-kDa+Protein+to+Lung+Tumorigenesis+by+4-%28Methylnitrosamino%29-1-%283-pyridyl%29-1-butanone%2C+a+Potent+Carcinogen+in+Cigarette+Smoke&rft.au=Yang%2C+Y%3BZhang%2C+Z%3BMukherjee%2C+AB%3BLinnoila%2C+R+I&rft.aulast=Yang&rft.aufirst=Y&rft.date=2004-07-09&rft.volume=279&rft.issue=28&rft.spage=29336&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.C400162200 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Transformation; FasL protein; Tumorigenesis; Cigarette smoke; Phenotypes; Tumor cells; Cancer; Hyperplasia; Phosphorylation; Lung; Carcinogenesis; Tobacco; Proteins; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone; Expression; Epithelium; CC10 protein; Adenoma DO - http://dx.doi.org/10.1074/jbc.C400162200 ER - TY - JOUR T1 - The challenge of emerging and re-emerging infectious diseases AN - 21292583; 5941597 AB - Infectious diseases have for centuries ranked with wars and famine as major challenges to human progress and survival. They remain among the leading causes of death and disability worldwide. Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. Studies of these emerging infections reveal the evolutionary properties of pathogenic microorganisms and the dynamic relationships between microorganisms, their hosts and the environment. JF - Nature AU - Morens, David M AU - Folkers, Gregory K AU - Fauci, Anthony S AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892- 2520, USA, afauciniaid.nih.gov Y1 - 2004/07/08/ PY - 2004 DA - 2004 Jul 08 SP - 242 EP - 249 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 430 IS - 6996 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Famine KW - Epidemics KW - Infectious diseases KW - War KW - Microorganisms KW - Survival KW - Infection KW - Evolution KW - A 01450:Environmental Pollution & Waste Treatment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21292583?accountid=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=Nature&rft.atitle=The+challenge+of+emerging+and+re-emerging+infectious+diseases&rft.au=Morens%2C+David+M%3BFolkers%2C+Gregory+K%3BFauci%2C+Anthony+S&rft.aulast=Morens&rft.aufirst=David&rft.date=2004-07-08&rft.volume=430&rft.issue=6996&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2Fnature02759 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-03-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Famine; Epidemics; Infectious diseases; War; Microorganisms; Survival; Infection; Evolution DO - http://dx.doi.org/10.1038/nature02759 ER - TY - JOUR T1 - A chlamydial type III translocated protein is tyrosine-phosphorylated at the site of entry and associated with recruitment of actin AN - 17823883; 5943511 AB - The obligate intracellular bacterium Chlamydia trachomatis rapidly induces its own entry into host cells. Initial attachment is mediated by electrostatic interactions to heparan sulfate moieties on the host cell, followed by irreversible binding to an unknown secondary receptor. This secondary binding leads to the recruitment of actin to the site of attachment, formation of an actin-rich, pedestallike structure, and finally internalization of the bacteria. How chlamydiae induce this process is unknown. We have identified a high-molecular-mass tyrosine-phosphorylated protein that is rapidly phosphorylated on attachment to the host cell. Immunoelectron microscopy studies revealed that this tyrosine-phosphorylated protein is localized to the cytoplasmic face of the plasma membrane at the site of attachment of surface- associated chlamydiae. The phosphoprotein was isolated by immunoprecipitation with the antiphosphotyrosine antibody 4G10 and identified as the chlamydial protein CT456, a hypothetical protein with unknown function. The chlamydial protein (Tarp) appears to be translocated into the host cell by type III secretion because it is exported in a Yersinia heterologous expression assay. Phosphotyrosine signaling across the plasma membrane preceded the recruitment of actin to the site of chlamydial attachment and may represent the initial signal transduced from pathogen to the host cell. These results suggest that C. trachomatis internalization is mediated by a chlamydial type III- secreted effector protein. JF - Proceedings of the National Academy of Sciences, USA AU - Clifton AU - Fields, KA AU - Grieshaber, S S AU - Dooley, CA AU - Fischer, E R AU - Mead, D J AU - Carabeo, R A AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, thackstadt@niaid.nih.gov Y1 - 2004/07/06/ PY - 2004 DA - 2004 Jul 06 SP - 10166 EP - 10171 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 27 SN - 0027-8424, 0027-8424 KW - Tarp protein KW - Microbiology Abstracts B: Bacteriology KW - Microbiology KW - Receptor mechanisms KW - Chlamydia trachomatis KW - Pathogens KW - Immunoelectron microscopy KW - Yersinia KW - Heparan sulfate KW - phosphotyrosine KW - Databases KW - Antibodies KW - Plasma membranes KW - Phosphoproteins KW - Actin KW - Signal transduction KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17823883?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+chlamydial+type+III+translocated+protein+is+tyrosine-phosphorylated+at+the+site+of+entry+and+associated+with+recruitment+of+actin&rft.au=Clifton%3BFields%2C+KA%3BGrieshaber%2C+S+S%3BDooley%2C+CA%3BFischer%2C+E+R%3BMead%2C+D+J%3BCarabeo%2C+R+A%3BHackstadt%2C+T&rft.aulast=Clifton&rft.aufirst=&rft.date=2004-07-06&rft.volume=101&rft.issue=27&rft.spage=10166&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0402829101 LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - The sequence reported in this paper has been deposited in the GenBank database (accession no. AY623902). N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Databases; Antibodies; Phosphoproteins; Receptor mechanisms; Plasma membranes; Actin; Immunoelectron microscopy; Pathogens; Heparan sulfate; phosphotyrosine; Signal transduction; Chlamydia trachomatis; Yersinia DO - http://dx.doi.org/10.1073/pnas.0402829101 ER - TY - JOUR T1 - Herp stabilizes neuronal Ca2+ homeostasis and mitochondrial function during endoplasmic reticulum stress. AN - 66661351; 15102845 AB - In response to endoplasmic reticulum (ER) stress, cells launch homeostatic and protective responses, but can also activate cell death cascades. A 54 kDa integral ER membrane protein called Herp was identified as a stress-responsive protein in non-neuronal cells. We report that Herp is present in neurons in the developing and adult brain, and that it is regulated in neurons by ER stress; sublethal levels of ER stress increase Herp levels, whereas higher doses decrease Herp levels and induce apoptosis. The decrease in Herp protein levels following a lethal ER stress occurs prior to mitochondrial dysfunction and cell death, and is mediated by caspases which generate a 30-kDa proteolytic Herp fragment. Mutagenesis of the caspase cleavage site in Herp enhances its neuroprotective function during ER stress. While suppression of Herp induction by RNA interference sensitizes neural cells to apoptosis induced by ER stress, overexpression of Herp promotes survival by a mechanism involving stabilization of ER Ca(2+) levels, preservation of mitochondrial function and suppression of caspase 3 activation. ER stress-induced activation of JNK/c-Jun and caspase 12 are reduced by Herp, whereas induction of major ER chaperones is unaffected. Herp prevents ER Ca(2+) overload under conditions of ER stress and agonist-induced ER Ca(2+) release is attenuated by Herp suggesting a role for Herp in regulating neuronal Ca(2+) signaling. By stabilizing ER Ca(2+) homeostasis and mitochondrial functions, Herp serves a neuroprotective function under conditions of ER stress. JF - The Journal of biological chemistry AU - Chan, Sic L AU - Fu, Weiming AU - Zhang, Peisu AU - Cheng, Aiwu AU - Lee, Jaewon AU - Kokame, Koichi AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. chanst@grc.nia.nih.gov Y1 - 2004/07/02/ PY - 2004 DA - 2004 Jul 02 SP - 28733 EP - 28743 VL - 279 IS - 27 SN - 0021-9258, 0021-9258 KW - Amyloid beta-Peptides KW - 0 KW - Membrane Proteins KW - RNA, Small Interfering KW - RNA KW - 63231-63-0 KW - Cytochromes c KW - 9007-43-6 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Casp12 protein, rat KW - EC 3.4.22.- KW - Casp3 protein, rat KW - Caspase 12 KW - Caspase 3 KW - Caspases KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cytochromes c -- metabolism KW - Apoptosis KW - Brain -- metabolism KW - RNA, Small Interfering -- metabolism KW - Caspases -- metabolism KW - Mutagenesis KW - Rats KW - RNA -- metabolism KW - RNA Interference KW - Time Factors KW - Signal Transduction KW - Plasmids -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Enzyme Activation KW - Amyloid beta-Peptides -- chemistry KW - Precipitin Tests KW - Reverse Transcriptase Polymerase Chain Reaction KW - Rats, Sprague-Dawley KW - Transfection KW - Cell Death KW - Subcellular Fractions -- metabolism KW - PC12 Cells KW - Endoplasmic Reticulum -- metabolism KW - Calcium -- metabolism KW - Neurons -- metabolism KW - Membrane Proteins -- chemistry KW - Membrane Proteins -- metabolism KW - Mitochondria -- metabolism KW - Cell Membrane -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66661351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Herp+stabilizes+neuronal+Ca2%2B+homeostasis+and+mitochondrial+function+during+endoplasmic+reticulum+stress.&rft.au=Chan%2C+Sic+L%3BFu%2C+Weiming%3BZhang%2C+Peisu%3BCheng%2C+Aiwu%3BLee%2C+Jaewon%3BKokame%2C+Koichi%3BMattson%2C+Mark+P&rft.aulast=Chan&rft.aufirst=Sic&rft.date=2004-07-02&rft.volume=279&rft.issue=27&rft.spage=28733&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 - 2004-08-11 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activin receptor-like kinase-7 induces apoptosis through activation of MAPKs in a Smad3-dependent mechanism in hepatoma cells. AN - 66658013; 15107418 AB - Activin receptor-like kinase (ALK)7 is a type I serine/threonine kinase receptor of the transforming growth factor (TGF)-beta family of proteins that has similar properties to other type I receptors when activated. To see whether ALK7 can induce apoptosis as can some of the other ALK proteins, we infected the FaO rat hepatoma cell line with adenovirus expressing a constitutively active form of the ALK7. Cells infected with active ALK7 adenovirus showed an apoptotic-positive phenotype, as opposed to those that were infected with a control protein. DNA fragmentation assays and fluorescence-activated cell sorter analysis also indicated that ALK7 infection induced apoptosis in FaO cells. We also confirmed this finding in Hep3B human hepatoma cells by transiently transfecting the constitutively active form of ALK7, ALK7(T194D). Investigation into the downstream targets and mechanisms involved in ALK7-induced apoptosis revealed that the TGF-beta signaling intermediates, Smad2 and -3, were activated, as well as the MAPKs JNK and p38. In addition, caspase-3 and -9 were also activated, and cytochrome c release from the mitochondria was observed. Short interfering RNA-mediated inhibition of Smad3 markedly suppressed ALK7-induced caspase-3 activation. Treatment with protein synthesis inhibitors or the expression of the dominant-negative form of the stress-activated protein/extracellular signal-regulated kinase 1 abolished not only JNK activation but apoptosis as well. Taken together, these results suggest that ALK7 induces apoptosis through activation of the traditional TGF-beta pathway components, thus resulting in new gene transcription and JNK and p38 activation that initiates cross-talk with the cellular stress death pathway and ultimately leads to apoptosis. JF - The Journal of biological chemistry AU - Kim, Byung-Chul AU - van Gelder, Howard AU - Kim, Tae Aug AU - Lee, Ho-Jae AU - Baik, Kim G AU - Chun, Hyun Hye AU - Lee, David A AU - Choi, Kyeong Sook AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. Y1 - 2004/07/02/ PY - 2004 DA - 2004 Jul 02 SP - 28458 EP - 28465 VL - 279 IS - 27 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Madh2 protein, rat KW - Madh3 protein, rat KW - RNA, Small Interfering KW - SMAD2 protein, human KW - SMAD3 protein, human KW - Smad2 Protein KW - Smad3 Protein KW - TGFB1 protein, human KW - Tgfb1 protein, rat KW - Trans-Activators KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Cytochromes c KW - 9007-43-6 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - ACVR1C protein, human KW - EC 2.7.11.30 KW - Activin Receptors, Type I KW - Acvr1c protein, rat KW - CASP3 protein, human KW - EC 3.4.22.- KW - CASP9 protein, human KW - Casp3 protein, rat KW - Casp9 protein, rat KW - Caspase 3 KW - Caspase 9 KW - Caspases KW - Index Medicus KW - Animals KW - Cytochromes c -- metabolism KW - Humans KW - Cell Separation KW - RNA, Small Interfering -- metabolism KW - Caspases -- metabolism KW - Cell Survival KW - Rats KW - Genes, Dominant KW - Genetic Vectors KW - Flow Cytometry KW - DNA Fragmentation KW - Adenoviridae -- metabolism KW - Plasmids -- metabolism KW - Dose-Response Relationship, Drug KW - Mitogen-Activated Protein Kinases -- metabolism KW - Cell Line, Tumor KW - Adenoviridae -- genetics KW - Blotting, Western KW - Transfection KW - Transforming Growth Factor beta -- metabolism KW - Cell Line KW - Trans-Activators -- metabolism KW - MAP Kinase Signaling System KW - Carcinoma, Hepatocellular -- metabolism KW - Apoptosis KW - Carcinoma, Hepatocellular -- pathology KW - Activin Receptors, Type I -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66658013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activin+receptor-like+kinase-7+induces+apoptosis+through+activation+of+MAPKs+in+a+Smad3-dependent+mechanism+in+hepatoma+cells.&rft.au=Kim%2C+Byung-Chul%3Bvan+Gelder%2C+Howard%3BKim%2C+Tae+Aug%3BLee%2C+Ho-Jae%3BBaik%2C+Kim+G%3BChun%2C+Hyun+Hye%3BLee%2C+David+A%3BChoi%2C+Kyeong+Sook%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Byung-Chul&rft.date=2004-07-02&rft.volume=279&rft.issue=27&rft.spage=28458&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 - 2004-08-11 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. AN - 66657762; 15117964 AB - Among gastrointestinal distributed isozymes encoded at the UGT1 locus, UDP-glucuronosyltransferase 1A10 (UGT1A10) metabolizes a number of important chemicals. Similar to broad conversion of phytoestrogens (Basu, N. K., Ciotti, M., Hwang, M. S., Kole, L., Mitra, P. S., Cho, J. W., and Owens, I. S. (2004) J. Biol. Chem. 279, 1429-1441), UGT1A10 metabolized estrogens and their derivatives, whereas UGT1A1, -1A3, -1A7, and -1A8 differentially exhibited reduced activity toward the same. UGT1A10 compared with UGT1A7, -1A8, and -1A3 generally exhibited high activity toward acidic nonsteroidal anti-inflammatory drugs and natural benzaldehyde derivatives, while UGT1A3 metabolized most efficiently aromatic transcinnamic acids known to be generated from flavonoid glycosides by microflora in the lower gastrointestinal tract. Finally UGT1A10, -1A7, -1A8, and -1A3 converted plant-based salicylic acids; methylsalicylic acid was transformed at high levels, and acetylsalicylic (aspirin) and salicylic acid were transformed at moderate to low levels. Atypically UGT1A10 transformed estrogens between pH 6 and 8 but acidic structures preferentially at pH 6.4. Furthermore evidence indicates UGT1A10 expressed in COS-1 cells depends upon phosphorylation; UGT1A10 versus its single, double, and triple mutants at three predicted protein kinase C phosphorylation sites incorporated [(33)P]-orthophosphate and showed a progressive decrease with no detectable label or activity for the triple T73A/T202A/S432G-1A10 mutant. Single and double mutants revealed either null/full activity or null/additive activity, respectively. Additionally UGT1A10-expressing cultures glucuronidated 17beta-[(14)C]estradiol, whereas cultures containing null mutants at protein kinase C sites showed no estrogen conversion. Importantly UGT1A10 in cells supported 10-fold higher glucuronidation of 17beta-estradiol than UGT1A1. In summary, our results suggest gastrointestinally distributed UGT1A10 is important for detoxifying estrogens/phytoestrogens and aromatic acids with complementary activity by UGT1A7, -1A8, -1A3, and/or -1A1 evidently dependent upon phosphorylation. JF - The Journal of biological chemistry AU - Basu, Nikhil K AU - Kubota, Shigeki AU - Meselhy, Meselhy R AU - Ciotti, Marco AU - Chowdhury, Bhabadeb AU - Hartori, Masao AU - Owens, Ida S AD - Heritable Disorders Branch, National Institute of Child Health & Human Development, National Institutes of Health, Room 9S-21, Building 10, Bethesda, MD 20892, USA. Y1 - 2004/07/02/ PY - 2004 DA - 2004 Jul 02 SP - 28320 EP - 28329 VL - 279 IS - 27 SN - 0021-9258, 0021-9258 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cinnamates KW - DNA, Complementary KW - Estrogens KW - Salicylates KW - Estradiol KW - 4TI98Z838E KW - UDP-glucuronosyltransferase, UGT1A3 KW - EC 2.4.1.- KW - bilirubin uridine-diphosphoglucuronosyl transferase 1A10 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - UDP-glucuronosyltransferase, UGT1A7 KW - UDP-glucuronosyltransferase, UGT1A8 KW - Protein Kinase C KW - EC 2.7.11.13 KW - cinnamic acid KW - U14A832J8D KW - Index Medicus KW - Cinnamates -- chemistry KW - Animals KW - COS Cells KW - Dose-Response Relationship, Drug KW - Humans KW - Hydrogen-Ion Concentration KW - Tissue Distribution KW - Binding Sites KW - Estradiol -- metabolism KW - Protein Kinase C -- metabolism KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Phosphorylation KW - Transfection KW - Microsomes -- metabolism KW - DNA, Complementary -- metabolism KW - Kinetics KW - Models, Chemical KW - Mutation KW - Salicylates -- metabolism KW - Cell Line KW - Estrogens -- metabolism KW - Glucuronosyltransferase -- metabolism KW - Digestive System -- enzymology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66657762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gastrointestinally+distributed+UDP-glucuronosyltransferase+1A10%2C+which+metabolizes+estrogens+and+nonsteroidal+anti-inflammatory+drugs%2C+depends+upon+phosphorylation.&rft.au=Basu%2C+Nikhil+K%3BKubota%2C+Shigeki%3BMeselhy%2C+Meselhy+R%3BCiotti%2C+Marco%3BChowdhury%2C+Bhabadeb%3BHartori%2C+Masao%3BOwens%2C+Ida+S&rft.aulast=Basu&rft.aufirst=Nikhil&rft.date=2004-07-02&rft.volume=279&rft.issue=27&rft.spage=28320&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 - 2004-08-11 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Biol Chem. 2004 Dec 24;279(52):54972 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-Linguistic Analysis of Vocabulary in Young Children: Spanish, Dutch, French, Hebrew, Italian, Korean, and American English AN - 85624506; 200504882 AB - The composition of young children's vocabularies in seven contrasting linguistic communities was investigated. Mothers of 269 20-month-olds in Argentina, Belgium, France, Israel, Italy, the Republic of Korea, & the United States completed comparable vocabulary checklists for their children. In each language & vocabulary size grouping (except for children just learning to talk), children's vocabularies contained relatively greater proportions of nouns than other word classes. Each word class was consistently positively correlated with every other class in each language & for children with smaller & larger vocabularies. Noun prevalence in the vocabularies of young children & the merits of several theories that may account for this pattern are discussed. 6 Tables, 1 Appendix, 151 References. Adapted from the source document JF - Child Development AU - Bornstein, Marc H AU - Cote, Linda R AD - National Instit Child Health & Human Development, Bethesda Marc_H_Bornstein@nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1115 EP - 1139 VL - 75 IS - 4 SN - 0009-3920, 0009-3920 KW - Italy (39100) KW - France (25500) KW - Form Classes (25250) KW - Lexicon (47150) KW - Belgium (07990) KW - Nouns (59650) KW - Argentina (03950) KW - Language Acquisition (41600) KW - United States of America (92750) KW - Comparative Linguistics (13850) KW - Korea (40945) KW - Israel (38800) KW - Children (11850) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85624506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Cross-Linguistic+Analysis+of+Vocabulary+in+Young+Children%3A+Spanish%2C+Dutch%2C+French%2C+Hebrew%2C+Italian%2C+Korean%2C+and+American+English&rft.au=Bornstein%2C+Marc+H%3BCote%2C+Linda+R&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2004-07-01&rft.volume=75&rft.issue=4&rft.spage=1115&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2005-05-01 N1 - Last updated - 2016-09-27 N1 - CODEN - CHDEAW N1 - SubjectsTermNotLitGenreText - Children (11850); Language Acquisition (41600); Lexicon (47150); Form Classes (25250); Nouns (59650); Comparative Linguistics (13850); Argentina (03950); Belgium (07990); France (25500); Israel (38800); Italy (39100); Korea (40945); United States of America (92750) ER - TY - JOUR T1 - The new-generation positron emission tomography/computed tomography scanners: implications for cardiac imaging AN - 754558334; 13337650 AB - The exceptionally rapid increase in the number of PET/CT scanners (often 3D only) for oncology may well facilitate an increase in cardiac PET imaging. However, there is only limited literature available as to how 3D acquisitions, especially with the new generation of scanners, will affect cardiac imaging. This situation will undoubtedly change very soon. Similarly, several aspects of CT-based attenuation correction for cardiac imaging remain to be investigated. Although, at the moment, 2D imaging with Ge-68 (or Cs-137) attenuation correction may remain the safest alternative for cardiac imaging, the new-generation PET/CT scanners hold great promise for the future of cardiac PET. JF - Journal of Nuclear Cardiology AU - Bacharach, Stephen L AD - Department of Nuclear Medicine, National Institutes of Health, Bldg 10, Room 1C401, 20892, Bethesda, Md., steve-bacharach@nih.gov. Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 388 EP - 392 PB - Mosby, Inc., New York VL - 11 IS - 4 SN - 1071-3581, 1071-3581 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Computed tomography KW - Positron emission tomography KW - Oncology KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/754558334?accountid=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+Nuclear+Cardiology&rft.atitle=The+new-generation+positron+emission+tomography%2Fcomputed+tomography+scanners%3A+implications+for+cardiac+imaging&rft.au=Bacharach%2C+Stephen+L&rft.aulast=Bacharach&rft.aufirst=Stephen&rft.date=2004-07-01&rft.volume=11&rft.issue=4&rft.spage=388&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nuclear+Cardiology&rft.issn=10713581&rft_id=info:doi/10.1016%2Fj.nuclcard.2004.04.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-08-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Heart; Computed tomography; Positron emission tomography; Oncology DO - http://dx.doi.org/10.1016/j.nuclcard.2004.04.008 ER - TY - JOUR T1 - Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo. AN - 72016666; 15194782 AB - Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4(+) T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4(+) T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4(+) T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus. JF - Journal of virology AU - Fitzgerald, Wendy AU - Sylwester, Andrew W AU - Grivel, Jean-Charles AU - Lifson, Jeffrey D AU - Margolis, Leonid B AD - Laboratory of Cellular and Molecular Biophysics and NASA/NIH Center for Three-Dimensional Tissue Culture, National Institutes of child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 7061 EP - 7068 VL - 78 IS - 13 SN - 0022-538X, 0022-538X KW - Culture Media, Conditioned KW - 0 KW - Disulfides KW - HIV Antibodies KW - Oxidants KW - Receptors, CCR5 KW - Receptors, CXCR4 KW - 2,2'-dipyridyl disulfide KW - 2127-03-9 KW - 2,2'-Dipyridyl KW - 551W113ZEP KW - Index Medicus KW - Culture Media, Conditioned -- pharmacology KW - B-Lymphocytes -- drug effects KW - B-Lymphocytes -- virology KW - Oxidants -- pharmacology KW - HIV Antibodies -- immunology KW - Disulfides -- pharmacology KW - Cells, Cultured KW - Humans KW - B-Lymphocytes -- immunology KW - Culture Media, Conditioned -- metabolism KW - Receptors, CCR5 -- metabolism KW - HIV-1 -- metabolism KW - HIV-1 -- immunology KW - Virion -- pathogenicity KW - HIV-1 -- pathogenicity KW - HIV Infections -- immunology KW - Receptors, CXCR4 -- metabolism KW - Palatine Tonsil -- immunology KW - 2,2'-Dipyridyl -- analogs & derivatives KW - Virion -- immunology KW - HIV-1 -- drug effects KW - 2,2'-Dipyridyl -- pharmacology KW - Virion -- drug effects KW - Palatine Tonsil -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72016666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Noninfectious+X4+but+not+R5+human+immunodeficiency+virus+type+1+virions+inhibit+humoral+immune+responses+in+human+lymphoid+tissue+ex+vivo.&rft.au=Fitzgerald%2C+Wendy%3BSylwester%2C+Andrew+W%3BGrivel%2C+Jean-Charles%3BLifson%2C+Jeffrey+D%3BMargolis%2C+Leonid+B&rft.aulast=Fitzgerald&rft.aufirst=Wendy&rft.date=2004-07-01&rft.volume=78&rft.issue=13&rft.spage=7061&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 - 2004-07-15 N1 - Date created - 2004-06-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Med Primatol. 2002 Aug;31(4-5):205-16 [12390543] Nat Med. 1999 Mar;5(3):344-6 [10086394] Proc Natl Acad Sci U S A. 2003 May 13;100(10):6057-62 [12730375] J Virol. 2003 Aug;77(15):8280-9 [12857897] J Acquir Immune Defic Syndr. 2003 Sep 1;34(1):7-19 [14501788] J Virol. 2001 Feb;75(3):1152-64 [11152488] Nat Med. 2001 Mar;7(3):344-9 [11231634] AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1003-8 [11485617] Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10362-7 [11504927] J Immunol Methods. 2002 Feb 1;260(1-2):219-34 [11792391] J Virol. 2002 Mar;76(6):2936-51 [11861860] AIDS. 2002 Jul 5;16(10):1319-29 [12131208] J Infect Dis. 2004 Feb 1;189(3):506-14 [14745709] N Engl J Med. 1983 Aug 25;309(8):453-8 [6224088] J Clin Invest. 1984 Jan;73(1):191-201 [6228564] Ann Intern Med. 1984 Dec;101(6):757-63 [6388451] Proc Natl Acad Sci U S A. 1985 Dec;82(23):8198-202 [2999797] Clin Immunol Immunopathol. 1986 Jun;39(3):359-67 [2938858] J Immunol. 1987 Jun 1;138(11):3720-4 [2953790] Clin Exp Immunol. 1987 Jun;68(3):479-87 [3652522] Clin Immunol Immunopathol. 1988 Jan;46(1):37-54 [3257177] J Clin Invest. 1988 Dec;82(6):1908-14 [2974045] Lancet. 1989 May 6;1(8645):983-5 [2565516] Cell Immunol. 1989 Jul;121(2):336-48 [2786762] Science. 1989 Dec 22;246(4937):1606-8 [2556795] AIDS. 1990 Apr;4(4):307-15 [2190605] N Engl J Med. 1991 Dec 26;325(26):1837-42 [1683682] J Virol. 1992 Mar;66(3):1354-60 [1738194] Eur J Immunol. 1992 Oct;22(10):2729-32 [1396975] AIDS. 1992 Dec;6(12):1465-9 [1492931] J Virol. 1993 Apr;67(4):2182-90 [8445728] Science. 1993 Mar 19;259(5102):1749-54 [8096089] Cell. 1994 Jan 28;76(2):241-51 [7904900] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6594-8 [7912830] Cell Immunol. 1995 Apr 1;161(2):236-43 [7697734] J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):139-49 [7552477] Nat Med. 1995 Dec;1(12):1320-2 [7489416] Ann Intern Med. 1996 Apr 1;124(7):654-63 [8607594] Immunol Lett. 1995 Nov;48(1):39-44 [8847089] Microbiol Rev. 1996 Jun;60(2):386-406 [8801439] J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Aug 15;12(5):442-50 [8757420] J Biol Regul Homeost Agents. 1995 Jul-Sep;9(3):88-90 [8782013] J Clin Microbiol. 1997 Jan;35(1):41-7 [8968878] AIDS Res Hum Retroviruses. 1997 Apr 10;13(6):461-71 [9100987] J Leukoc Biol. 1997 Jun;61(6):654-66 [9201256] Nature. 1998 Jan 15;391(6664):240 [9440686] Nat Med. 1998 Mar;4(3):346-9 [9500611] Virology. 1998 Feb 15;241(2):181-8 [9499793] J Biol Regul Homeost Agents. 1996 Oct-Dec;10(4):83-91 [9604776] J Exp Med. 1998 Jul 20;188(2):233-45 [9670036] Dev Immunol. 1998;6(1-2):61-70 [9716906] AIDS. 1998 Aug 20;12(12):1437-49 [9727564] J Virol. 1998 Oct;72(10):7992-8001 [9733838] Nature. 1998 Sep 10;395(6698):189-94 [9744279] J Virol. 1998 Nov;72(11):9345-7 [9765486] AIDS Res Hum Retroviruses. 1998 Oct;14 Suppl 3:S311-9 [9814959] J Immunol. 2003 Mar 1;170(5):2449-55 [12594269] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression profiling of rat livers reveals indicators of potential adverse effects. AN - 72003008; 15084756 AB - This study tested the hypothesis that gene expression profiling can reveal indicators of subtle injury to the liver induced by a low dose of a substance that does not cause overt toxicity as defined by conventional criteria of toxicology (e.g., abnormal clinical chemistry and histopathology). For the purpose of this study we defined this low dose as subtoxic, i.e., a dose that elicits effects which are below the detection of conventional toxicological parameters. Acetaminophen (APAP) was selected as a model hepatotoxicant because (1) considerable information exists concerning the mechanism of APAP hepatotoxicity that can occur following high doses, (2) intoxication with APAP is the leading cause of emergency room visits involving acute liver failure within the United States, and (3) conventional clinical markers have poor predictive value. Rats treated with a single dose of 0, 50, 150, or 1500 mg/kg APAP were examined at 6, 24, or 48 h after exposure for conventional toxicological parameters and for gene expression alterations. Patterns of gene expression were found which indicated cellular energy loss as a consequence of APAP toxicity. Elements of these patterns were apparent even after exposure to subtoxic doses. With increasing dose, the magnitude of changes increased and additional members of the same biological pathways were differentially expressed. The energy loss suggested by gene expression changes was confirmed at the 1500 mg/kg dose exposure by measuring ATP levels. Only by ultrastructural examination could any indication of toxicity be identified after exposure to a subtoxic dose of APAP and that was occasional mitochondrial damage. In conclusion, this study provides evidence that supports the hypothesis that gene expression profiling may be a sensitive means of identifying indicators of potential adverse effects in the absence of the occurrence of overt toxicity. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Heinloth, Alexandra N AU - Irwin, Richard D AU - Boorman, Gary A AU - Nettesheim, Paul AU - Fannin, Rickie D AU - Sieber, Stella O AU - Snell, Michael L AU - Tucker, Charles J AU - Li, Leping AU - Travlos, Gregory S AU - Vansant, Gordon AU - Blackshear, Pamela E AU - Tennant, Raymond W AU - Cunningham, Michael L AU - Paules, Richard S AD - National Center for Toxicogenomics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 193 EP - 202 VL - 80 IS - 1 SN - 1096-6080, 1096-6080 KW - Analgesics, Non-Narcotic KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Mitochondria, Liver -- metabolism KW - Mitochondria, Liver -- ultrastructure KW - Adenosine Triphosphate -- metabolism KW - Microarray Analysis KW - Toxicity Tests -- methods KW - Male KW - Gene Expression Profiling KW - Analgesics, Non-Narcotic -- adverse effects KW - Acetaminophen -- administration & dosage KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury -- etiology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Liver -- drug effects KW - Acetaminophen -- adverse effects KW - Liver -- metabolism KW - Analgesics, Non-Narcotic -- administration & dosage KW - Chemical and Drug Induced Liver Injury -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72003008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Gene+expression+profiling+of+rat+livers+reveals+indicators+of+potential+adverse+effects.&rft.au=Heinloth%2C+Alexandra+N%3BIrwin%2C+Richard+D%3BBoorman%2C+Gary+A%3BNettesheim%2C+Paul%3BFannin%2C+Rickie+D%3BSieber%2C+Stella+O%3BSnell%2C+Michael+L%3BTucker%2C+Charles+J%3BLi%2C+Leping%3BTravlos%2C+Gregory+S%3BVansant%2C+Gordon%3BBlackshear%2C+Pamela+E%3BTennant%2C+Raymond+W%3BCunningham%2C+Michael+L%3BPaules%2C+Richard+S&rft.aulast=Heinloth&rft.aufirst=Alexandra&rft.date=2004-07-01&rft.volume=80&rft.issue=1&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-25 N1 - Date created - 2004-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The schedule-dependent enhanced cytotoxic activity of 7-ethyl-10-hydroxy-camptothecin (SN-38) in combination with Gefitinib (Iressa, ZD1839). AN - 72001641; 15183125 AB - The combination of the topoisomerase I (Topo I) inhibitor CPT-11 with the anti-epidermal growth factor receptor (EGFR) agent Gefitinib (Iressa, ZD1839) represents a promising medical approach for colorectal cancer patients. In this report, we provide pre-clinical evidences for their optimal combination schedule in HT-29 and LoVo human colon cancer cell lines. We analyzed the different effects that three different combination schedules of SN-38 (the active CPT-11 metabolite) and Gefitinib (Gefitinib before; Gefitinib simultaneously; Gefitinib after SN-38) have on cell growth, cell cycle, apoptosis, and expression/phosphorylation of EGFR, Topo I and some steps of the signal transduction pathway. We first determined the IC(50) of each drug choosing the 5 days exposure for Gefitinib (0.6 and 3.8 microM for LoVo and HT-29 cells, respectively) and 1 day exposure for SN-38 (0.31 and 0.5 microM for LoVo and HT-29 cells, respectively). The different drug combination schedules were tested in various concentrations by using equiactive concentrations of the two drugs. The cytotoxicity of Gefitinib and SN-38 combination was schedule- and concentration-dependent but not cell line-specific. The most synergistic schedule was Gefitinib given after SN-38, with combination indexes (CI) of 0.007 and 0.454 in HT-29 and LoVo, respectively. Analysis of bio-molecular targets showed that Gefitinib was able to modulate SN-38 ability to inhibit Topo I, to accumulate cells in S-phase, and to induce apoptosis. Interestingly, SN-38 was able to activate EGFR and its signal transduction pathway. Confirming preliminary clinical experience of Gefitinib with other cytotoxic drugs, it seems that Gefitinib after SN-38 represents the best cytotoxic combination schedule but the biomolecular basis for this synergism remain to be completely elucidated. JF - Biochemical pharmacology AU - Azzariti, Amalia AU - Xu, Jian-Ming AU - Porcelli, Letizia AU - Paradiso, Angelo AD - Clinical Experimental Oncology Laboratory, National Cancer Institute, Bari, Italy. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 135 EP - 144 VL - 68 IS - 1 SN - 0006-2952, 0006-2952 KW - Antineoplastic Agents KW - 0 KW - Quinazolines KW - irinotecan KW - 0H43101T0J KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - gefitinib KW - S65743JHBS KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Signal Transduction -- physiology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Tumor Cells, Cultured KW - Humans KW - Signal Transduction -- drug effects KW - Cell Division -- drug effects KW - HT29 Cells KW - Drug Synergism KW - Colonic Neoplasms -- pathology KW - DNA Topoisomerases, Type I -- metabolism KW - Cell Cycle -- drug effects KW - Quinazolines -- administration & dosage KW - Apoptosis KW - Camptothecin -- pharmacology KW - Antineoplastic Agents -- administration & dosage KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Agents -- pharmacology KW - Quinazolines -- pharmacology KW - Camptothecin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72001641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+schedule-dependent+enhanced+cytotoxic+activity+of+7-ethyl-10-hydroxy-camptothecin+%28SN-38%29+in+combination+with+Gefitinib+%28Iressa%2C+ZD1839%29.&rft.au=Azzariti%2C+Amalia%3BXu%2C+Jian-Ming%3BPorcelli%2C+Letizia%3BParadiso%2C+Angelo&rft.aulast=Azzariti&rft.aufirst=Amalia&rft.date=2004-07-01&rft.volume=68&rft.issue=1&rft.spage=135&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 - 2004-07-19 N1 - Date created - 2004-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - L-Carnitine and acetyl-L-carnitine in the treatment of complications associated with HIV infection and antiretroviral therapy. AN - 67303845; 16120381 AB - L-Carnitine (LC) and acetyl-L-carnitine (ALC) play major roles in cell energy and lipid metabolism. Supplementation with these nutrients, which are highly popular in USA, has been associated with favorable effects, including anti-oxidant action, neuro- and cardioprotection, immunomodulation, and cognitive enhancement. Patients with HIV infection and undergoing highly active antiretroviral therapy (HAART) often develop complications, such as polyneuropathy, skeletal myopathy, dyslipidemia and lipodystrophy, which have been linked to mitochondrial dysfunction. Moreover, these patients are often LC-deficient. Thus, they may benefit from LC and ALC supplementation. Indeed, oral, i.v., or i.m. administration of large doses of LC and/or ALC to HIV positive subjects untreated/treated with HAART was shown to: (1) increase the number of CD4 cells and reduce lymphocyte apoptosis; (2) improve symptoms of polyneuropathy; (3) prevent cardiovascular damage from wasting and diarrhea syndromes; (4) decrease serum levels of triglycerides and TNFalpha. No significant toxicities were associated with LC and ALC treatment. Although promising, most of these findings derive from small uncontrolled clinical trials. Further research is warranted to prove the efficacy and safety of LC and ALC supplementation in patients with complications of HIV infection and HAART. JF - Mitochondrion AU - Ilias, Ioannis AU - Manoli, Irini AU - Blackman, Marc R AU - Gold, Philip W AU - Alesci, Salvatore AD - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 163 EP - 168 VL - 4 IS - 2-3 SN - 1567-7249, 1567-7249 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67303845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mitochondrion&rft.atitle=L-Carnitine+and+acetyl-L-carnitine+in+the+treatment+of+complications+associated+with+HIV+infection+and+antiretroviral+therapy.&rft.au=Ilias%2C+Ioannis%3BManoli%2C+Irini%3BBlackman%2C+Marc+R%3BGold%2C+Philip+W%3BAlesci%2C+Salvatore&rft.aulast=Ilias&rft.aufirst=Ioannis&rft.date=2004-07-01&rft.volume=4&rft.issue=2-3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Mitochondrion&rft.issn=15677249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-24 N1 - Date created - 2005-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular insights into NRTI inhibition and mitochondrial toxicity revealed from a structural model of the human mitochondrial DNA polymerase. AN - 67291190; 16120386 AB - NRTI-based therapy used to treat AIDS can cause mitochondrial toxicity resulting from the incorporation of NRTIs into mitochondrial DNA by DNA polymerase gamma (pol gamma). Pol gamma has poor discrimination against many of the currently used NRTIs resulting in aborted DNA synthesis and subsequent depletion of mtDNA. Pol gamma readily incorporates ddCTP, ddITP and D4T-TP with an efficiency similar to the incorporation of normal nucleotides, whereas AZT-TP, CBV-TP, 3TC-TP and PMPApp act as moderate inhibitors to DNA synthesis. We have sought a structural explanation for the unique selection for NRTIs by the human pol gamma. A structural model of the human pol gamma was developed to ascertain the role of active site amino acids. One residue in particular, Y951 in motif B, is primarily responsible for the selection of dideoxynucleotides and D4T-TP. Our structural model of the human pol gamma should assist in rational design of antiviral nucleoside analogs with higher specificity for HIV-RT and minimal selection and incorporation into mitochondrial DNA. JF - Mitochondrion AU - Bienstock, Rachelle J AU - Copeland, Willliam C AD - Scientific Computing Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, NC 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 203 EP - 213 VL - 4 IS - 2-3 SN - 1567-7249, 1567-7249 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67291190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mitochondrion&rft.atitle=Molecular+insights+into+NRTI+inhibition+and+mitochondrial+toxicity+revealed+from+a+structural+model+of+the+human+mitochondrial+DNA+polymerase.&rft.au=Bienstock%2C+Rachelle+J%3BCopeland%2C+Willliam+C&rft.aulast=Bienstock&rft.aufirst=Rachelle&rft.date=2004-07-01&rft.volume=4&rft.issue=2-3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Mitochondrion&rft.issn=15677249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-24 N1 - Date created - 2005-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beyond human papillomavirus: the cervix, exogenous secondary factors, and the development of cervical precancer and cancer. AN - 67278711; 15874868 AB - Human papillomavirus (HPV) is the necessary but probably not sufficient cause of cervical precancer and cancer. Secondary exogenous and endogenous factors, HPV cofactors, may contribute to the probability of a cancer-associated (oncogenic) HPV infection progressing to cervical precancer and cancer. For these cofactors to influence the natural history of HPV infection, they must act on cervical tissue to promote viral persistence, progression to precancer or cancer given viral persistence, or both. The aim of this review was to examine briefly the impact these factors may have on carcinogenesis of the cervix. Specifically, the roles of the cervical transformation zone, cervical immunity, inflammation and coinfection, and exposure to the main HPV cofactors (smoking, oral contraceptive use, and multiparity) are discussed. JF - Journal of lower genital tract disease AU - Castle, Philip E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. castlep@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 224 EP - 230 VL - 8 IS - 3 SN - 1089-2591, 1089-2591 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67278711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lower+genital+tract+disease&rft.atitle=Beyond+human+papillomavirus%3A+the+cervix%2C+exogenous+secondary+factors%2C+and+the+development+of+cervical+precancer+and+cancer.&rft.au=Castle%2C+Philip+E&rft.aulast=Castle&rft.aufirst=Philip&rft.date=2004-07-01&rft.volume=8&rft.issue=3&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Journal+of+lower+genital+tract+disease&rft.issn=10892591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-19 N1 - Date created - 2005-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynamic balancing of the dual nature of HIF-1alpha for cell survival. AN - 67061539; 15190211 AB - In hypoxic cells, HIF-1alpha escapes from oxygen-dependent proteolysis and binds to the hypoxia-responsive element (HRE) for transcriptional activation of target genes involved in angiogenesis and glycolysis. We recently demonstrated that the G(1) checkpoint gene p21(cip1)is activated by HIF-1alpha with a novel mechanism that involves the HIF-1alpha PAS domains to displace Myc binding from p21(cip1) promoter. This HIF-1alpha-Myc pathway may account for up- and down-regulation of other hypoxia-responsive genes that lack the HRE. Moreover, the role of HIF-1alpha in cell cycle control indicates a dual, yet seemingly conflicting, nature of HIF-1alpha: promoting cell growth and arrest in concomitance. We speculate that a dynamic balance between the two processes is achieved by a "stop-and-go" strategy to maintain cell growth and survival. Tumor cells may adopt such scheme to evade the killing by chemotherapeutic agents. JF - Cell cycle (Georgetown, Tex.) AU - Koshiji, Minori AU - Huang, L Eric AD - Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 853 EP - 854 VL - 3 IS - 7 KW - Cell Cycle Proteins KW - 0 KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - MYC protein, human KW - Proto-Oncogene Proteins c-myc KW - Index Medicus KW - Animals KW - Adaptation, Physiological -- physiology KW - Humans KW - Cell Division -- physiology KW - Drug Resistance, Neoplasm -- physiology KW - Cell Enlargement -- drug effects KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Hypoxia-Inducible Factor 1, alpha Subunit -- genetics KW - Cell Cycle Proteins -- genetics KW - Cell Hypoxia -- physiology KW - Hypoxia-Inducible Factor 1, alpha Subunit -- metabolism KW - Cell Survival -- physiology KW - Cell Cycle Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67061539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cycle+%28Georgetown%2C+Tex.%29&rft.atitle=Dynamic+balancing+of+the+dual+nature+of+HIF-1alpha+for+cell+survival.&rft.au=Koshiji%2C+Minori%3BHuang%2C+L+Eric&rft.aulast=Koshiji&rft.aufirst=Minori&rft.date=2004-07-01&rft.volume=3&rft.issue=7&rft.spage=853&rft.isbn=&rft.btitle=&rft.title=Cell+cycle+%28Georgetown%2C+Tex.%29&rft.issn=1551-4005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-04-14 N1 - Date created - 2004-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Applications of magnetic resonance microscopy. AN - 67009411; 15503663 AB - Magnetic resonance imaging (MRI) has enjoyed enormous clinical success since the first demonstration of the method more than 30 years ago. An increasing number of pharmaceutical manufacturers seeking new biomarkers for assessing drug efficacy and toxicity are turning to MRI. A specific application of MRI promises to revolutionize pathology for the basic scientist in the same way MRI has forever altered the standard of care in the clinical domain. More specifically, this application is the use of magnetic resonance microscopy (MRM) in conjunction with new staining methodologies that now make MRM routinely available to the widest range of investigators. JF - Toxicologic pathology AU - Maronpot, Robert R AU - Sills, Robert C AU - Johnson, G Allan AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Maronpot@niehs.nih.gov PY - 2004 SP - 42 EP - 48 VL - 32 Suppl 2 SN - 0192-6233, 0192-6233 KW - Sulfur Oxides KW - 0 KW - carbonyl sulfide KW - 871UI0ET21 KW - Urate Oxidase KW - EC 1.7.3.3 KW - Index Medicus KW - Urate Oxidase -- genetics KW - Imaging, Three-Dimensional KW - Fetus KW - Animals KW - Sulfur Oxides -- metabolism KW - Urate Oxidase -- metabolism KW - Humans KW - Teratology KW - Brain -- metabolism KW - Image Processing, Computer-Assisted KW - Magnetic Resonance Imaging KW - Microscopy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67009411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Applications+of+magnetic+resonance+microscopy.&rft.au=Maronpot%2C+Robert+R%3BSills%2C+Robert+C%3BJohnson%2C+G+Allan&rft.aulast=Maronpot&rft.aufirst=Robert&rft.date=2004-07-01&rft.volume=32+Suppl+2&rft.issue=&rft.spage=42&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 - 2005-01-31 N1 - Date created - 2004-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological modulation of GABA(B) receptors affects cocaine-induced seizures in mice. AN - 66933090; 14985936 AB - Previous data have demonstrated that the convulsant effects of cocaine can be modulated by compounds that increase levels of endogenous gamma-aminobutyric acid (GABA) or that directly stimulate GABA(A) receptors. To determine whether the convulsant effects of cocaine can be modulated by ligands selective for GABA(B) receptors in mice. Effects of the GABA(B) receptor agonist ((+/-)-baclofen), antagonist (phaclofen), and their combination were tested against clonic seizures induced by cocaine (75 mg/kg). Enantiomers of baclofen were used to confirm stereospecificity of (+/-)-baclofen's effects. Pharmacological specificity of (+/-)-baclofen's effects was tested by comparison against seizures induced by GBR 12909 (monoamine transporter inhibitor), pentylenetetrazole (GABA(A) antagonist), N-methyl-D-aspartate (NMDA agonist), and aminophylline (A1/A2 adenosine antagonist). Additionally, effects of (+/-)-baclofen on kindled seizures induced by repeated administration of cocaine (60 mg/kg every 24 h for 6 days) were evaluated. The inverted screen test was used to assess behavioral side effects of baclofen. (+/-)-Baclofen dose-dependently inhibited acute (ED50=4.1 mg/kg) and kindled (6.4 mg/kg) seizures induced by cocaine at doses somewhat lower than those producing behavioral side effects (11.5 mg/kg), and these effects were stereospecific. (+/-)-Baclofen suppressed seizures induced by GBR 12909 but not by pentylenetetrazole, NMDA, and aminophylline, suggesting selectivity of its anticonvulsant effects for monoamine-related mechanisms. Finally, phaclofen dose-dependently enhanced the convulsant effects of a threshold dose of cocaine (60 mg/kg). Modulation of GABA(B) receptors can affect seizures induced by cocaine. This molecular mechanism may be involved in seizures induced by cocaine or, alternatively, may function as an independent inhibitory mechanism against seizures arising from blockade of monoamine uptake. JF - Psychopharmacology AU - Gasior, Maciej AU - Kaminski, Rafal AU - Witkin, Jeffrey M AD - Drug Development Group, Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. GasiorM@ninds.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 211 EP - 219 VL - 174 IS - 2 SN - 0033-3158, 0033-3158 KW - Dopamine Uptake Inhibitors KW - 0 KW - GABA-A Receptor Agonists KW - GABA-A Receptor Antagonists KW - GABA-B Receptor Agonists KW - GABA-B Receptor Antagonists KW - Piperazines KW - Receptors, GABA-A KW - Receptors, GABA-B KW - phaclofen KW - 108351-35-5 KW - vanoxerine KW - 90X28IKH43 KW - Baclofen KW - H789N3FKE8 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Piperazines -- antagonists & inhibitors KW - Animals KW - Kindling, Neurologic -- drug effects KW - Mice KW - Piperazines -- toxicity KW - Male KW - Seizures -- chemically induced KW - Dopamine Uptake Inhibitors -- toxicity KW - Dopamine Uptake Inhibitors -- antagonists & inhibitors KW - Cocaine -- toxicity KW - Baclofen -- analogs & derivatives KW - Seizures -- prevention & control KW - Baclofen -- therapeutic use KW - Baclofen -- pharmacology KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66933090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pharmacological+modulation+of+GABA%28B%29+receptors+affects+cocaine-induced+seizures+in+mice.&rft.au=Gasior%2C+Maciej%3BKaminski%2C+Rafal%3BWitkin%2C+Jeffrey+M&rft.aulast=Gasior&rft.aufirst=Maciej&rft.date=2004-07-01&rft.volume=174&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-19 N1 - Date created - 2004-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drugs and driving: the nuances. AN - 66885140; 15372862 JF - Journal of the American Pharmacists Association : JAPhA AU - Wick, Jeannette Y AU - Zanni, Guido R AD - National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD , USA. PY - 2004 SP - 430 EP - 433 VL - 44 IS - 4 SN - 1544-3191, 1544-3191 KW - Index Medicus KW - United States KW - Drug Interactions KW - Patient Education as Topic -- methods KW - Professional Role KW - Humans KW - Automobile Driving -- education KW - Accidents, Traffic -- statistics & numerical data KW - Accidents, Traffic -- mortality KW - Drug Prescriptions -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66885140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Pharmacists+Association+%3A+JAPhA&rft.atitle=Drugs+and+driving%3A+the+nuances.&rft.au=Wick%2C+Jeannette+Y%3BZanni%2C+Guido+R&rft.aulast=Wick&rft.aufirst=Jeannette&rft.date=2004-07-01&rft.volume=44&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Pharmacists+Association+%3A+JAPhA&rft.issn=15443191&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-06 N1 - Date created - 2004-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allium vegetables in cancer prevention: an overview. AN - 66883348; 15373701 AB - The Allium genus includes approximately 500 species. Commonly used allium vegetables include garlic, onion, leeks, chives, scallions which are used all over the world in different delicacies. Some allium vegetables have been employed for millenia in the traditional medical practice to treat cardiovascular diseases. They have been shown to have applications as antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic agents. In recent years, extensive research has focused on the anticarcinogenic potential of allium vegetables and their constituents, viz., allylsulfides and flavonoids (particularly quercetin which is present abundantly in onion). Epidemiological studies have shown that higher intake of allium products is associated with reduced risk of several types of cancers. These epidemiological findings are well correlated with laboratory investigations. Organosulfur compounds present in Allium vegetables, are considered to be responsible for the beneficial effects of these herbs. Several mechanisms have been proposed to explain the cancer-preventive effects of Allium vegetables and related organosulfur compounds. These include inhibition of mutagenesis, modulation of enzyme activities, inhibition of DNA adduct formation, free-radical scavenging, and effects on cell proliferation and tumor growth. Although there is a large body of evidence supporting these mechanisms, they are still speculative, and further research is needed to support causality between such properties and cancer-preventive activity in experimental animals. This article reviews current knowledge concerning allium vegetables and cancer prevention. JF - Asian Pacific journal of cancer prevention : APJCP AU - Sengupta, Archana AU - Ghosh, Samit AU - Bhattacharjee, Shamee AD - Dept. of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata-700026, India. archana_sen@yahoo.com PY - 2004 SP - 237 EP - 245 VL - 5 IS - 3 SN - 1513-7368, 1513-7368 KW - Anticarcinogenic Agents KW - 0 KW - DNA Adducts KW - Free Radical Scavengers KW - Index Medicus KW - Plant Structures KW - Epidemiologic Studies KW - DNA Damage KW - Humans KW - Cell Division KW - Vegetables -- chemistry KW - Anticarcinogenic Agents -- pharmacology KW - Allium -- chemistry KW - Neoplasms -- prevention & control KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66883348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Allium+vegetables+in+cancer+prevention%3A+an+overview.&rft.au=Sengupta%2C+Archana%3BGhosh%2C+Samit%3BBhattacharjee%2C+Shamee&rft.aulast=Sengupta&rft.aufirst=Archana&rft.date=2004-07-01&rft.volume=5&rft.issue=3&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-26 N1 - Date created - 2004-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Asian Pac J Cancer Prev. 2004 Jul-Sep;5(3):229-30 [15373700] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [HCV infection among narcotics/methamphetamine abusers]. AN - 66863509; 15359814 JF - Nihon rinsho. Japanese journal of clinical medicine AU - Wada, Kiyoshi AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 326 EP - 329 VL - 62 Suppl 7 SN - 0047-1852, 0047-1852 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Risk KW - Needle Sharing -- statistics & numerical data KW - Needle-Exchange Programs KW - Methamphetamine -- adverse effects KW - Humans KW - Substance-Related Disorders KW - Needle Sharing -- adverse effects KW - Prevalence KW - Hepatitis C -- prevention & control KW - Amphetamine-Related Disorders -- epidemiology KW - Opioid-Related Disorders -- epidemiology KW - Opioid-Related Disorders -- psychology KW - Hepatitis C -- transmission KW - Amphetamine-Related Disorders -- psychology KW - Hepatitis C -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66863509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+rinsho.+Japanese+journal+of+clinical+medicine&rft.atitle=%5BHCV+infection+among+narcotics%2Fmethamphetamine+abusers%5D.&rft.au=Wada%2C+Kiyoshi&rft.aulast=Wada&rft.aufirst=Kiyoshi&rft.date=2004-07-01&rft.volume=62+Suppl+7&rft.issue=&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Nihon+rinsho.+Japanese+journal+of+clinical+medicine&rft.issn=00471852&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-18 N1 - Date created - 2004-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antidepressant-withdrawal mania:a critical review and synthesis of the literature. AN - 66767618; 15291689 AB - Hypomania or mania have rarely been reported to develop shortly after the discontinuation of an antidepressant drug. The true incidence of this discontinuation syndrome is unknown because it may be underreported as a consequence of underrecognition or misattribution. This article examines the possible etiology, nosology, mechanisms, and other aspects of the syndrome. A PubMed search was conducted in May 2003 and repeated in January 2004 using the search terms antidepressant and mania. Relevant articles containing adequate descriptions for presentation were retrieved, and their reference lists were hand-searched for further pertinent material. Hand-searches of the indexes of leading psychiatry journals were also performed for the years 1998-2003. Twenty-three articles were identified for review. Antidepressant-withdrawal hypomania or mania may occur rarely with almost any antidepressant drug after sudden withdrawal, tapered discontinuation, or even merely a decrease in dose. The syndrome may be self-limiting, may abate with the reinstitution of the antidepressant drug, or may require specific anti-manic treatments; mood stabilizers do not necessarily protect against the syndrome. The true incidence of the syndrome is unknown. Narrow and broad diagnostic criteria are proposed for the syndrome, and a synthesis of literature is provided. JF - The Journal of clinical psychiatry AU - Andrade, Chittaranjan AD - Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India. andrade@nimhans.kar.nic.in Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 987 EP - 993 VL - 65 IS - 7 SN - 0160-6689, 0160-6689 KW - Antidepressive Agents KW - 0 KW - Antimanic Agents KW - Index Medicus KW - Diagnosis, Differential KW - Syndrome KW - PubMed -- statistics & numerical data KW - Humans KW - Incidence KW - Depressive Disorder -- drug therapy KW - Antimanic Agents -- therapeutic use KW - Bipolar Disorder -- diagnosis KW - Substance Withdrawal Syndrome -- etiology KW - Bipolar Disorder -- epidemiology KW - Antidepressive Agents -- therapeutic use KW - Antidepressive Agents -- adverse effects KW - Bipolar Disorder -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66767618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antidepressant-withdrawal+mania%3Aa+critical+review+and+synthesis+of+the+literature.&rft.au=Andrade%2C+Chittaranjan&rft.aulast=Andrade&rft.aufirst=Chittaranjan&rft.date=2004-07-01&rft.volume=65&rft.issue=7&rft.spage=987&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 - 2004-09-13 N1 - Date created - 2004-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical proteomics: Applications for prostate cancer biomarker discovery and detection. AN - 66764442; 15283891 AB - The science of proteomics comprises much more than simply generating lists of proteins that change in expression as a cause of or consequence of pathophysiology. The goal of proteomics should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. Serum proteomic pattern diagnostics is a new type of proteomic concept in which patterns of ion signatures generated from high dimensional mass spectrometry data are used as diagnostic classifiers. This recent approach has exciting potential for clinical utility of diagnostic patterns because low molecular weight metabolites, peptides, and protein fragments may have higher accuracy than traditional biomarkers of cancer detection. Intriguingly, we now have discovered that this diagnostic information exists in a bound state, complexed with circulating highly abundant carrier proteins. These diagnostic fragments may one day be harvested by circulating nanoparticles, designed to absorb, enrich, and amplify the repertoire of diagnostic biomarkers generated-even at the critical, initial stages of carcinogenesis. Copyright 2004 Elsevier Inc. JF - Urologic oncology AU - Petricoin, Emanuel F AU - Ornstein, David K AU - Liotta, Lance A AD - FDA-NCI Clinical Proteomics Program, Office of Cell and Gene Therapies, Center for Biologic Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. petricoin@cber.fda.gov PY - 2004 SP - 322 EP - 328 VL - 22 IS - 4 SN - 1078-1439, 1078-1439 KW - Biomarkers, Tumor KW - 0 KW - Index Medicus KW - Protein Array Analysis KW - Mass Spectrometry KW - Diagnosis, Differential KW - Humans KW - Male KW - Gene Expression Profiling KW - Prostatic Neoplasms -- diagnosis KW - Proteomics -- trends KW - Biomarkers, Tumor -- analysis KW - Prostatic Neoplasms -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66764442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urologic+oncology&rft.atitle=Clinical+proteomics%3A+Applications+for+prostate+cancer+biomarker+discovery+and+detection.&rft.au=Petricoin%2C+Emanuel+F%3BOrnstein%2C+David+K%3BLiotta%2C+Lance+A&rft.aulast=Petricoin&rft.aufirst=Emanuel&rft.date=2004-07-01&rft.volume=22&rft.issue=4&rft.spage=322&rft.isbn=&rft.btitle=&rft.title=Urologic+oncology&rft.issn=10781439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-26 N1 - Date created - 2004-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eradication of HIV in infected patients: some potential approaches. AN - 66746257; 15232518 AB - Although at present, highly active antiretroviral therapy (HAART) has greatly reduced the number of viral copies to an undetectable level and has slowed down the progress of the disease in patients with human immunodeficiency virus (HIV) infection, the HIV-infected cells are not eradicated by this therapy. Virus replication rebounds once the drug therapy is terminated, regardless of duration of the therapy, primarily due to the establishment of a viral reservoir. Therefore, viral suppressive therapy is a lifelong task and may be accompanied by many as yet unidentified serious side effects. In addition, the maximum therapeutic benefits of HAART appear to have been reached recently in the U. S, and the incidences of multi-drug resistant viral strain infections are slowly but steadily increasing. Without an effective vaccine, which has already proved to be very difficult to develop, for the protection of the uninfected population and a feasible eradication strategy to cure infected patients, the number of HIV-infected persons will inevitably continue to rise. While the vast majority of endeavors are focused on developing new drugs that target different steps of HIV replication for suppressive therapy, researchers need to find a therapeutic strategy that directly aims at HIV-infected cells to cure the disease. In this article, I review and discuss some potential approaches to eradicate HIV-infected cells from the patients. JF - Medical science monitor : international medical journal of experimental and clinical research AU - Yang, Quan-en AD - SAIC-Frederick, Inc, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. yangq@dtpax2.ncifcrf.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - RA155 EP - RA165 VL - 10 IS - 7 SN - 1234-1010, 1234-1010 KW - Anti-HIV Agents KW - 0 KW - Immunotoxins KW - RNA, Small Interfering KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Genetic Therapy KW - T-Lymphocytes, Cytotoxic -- immunology KW - Virus Replication -- physiology KW - Transplantation, Homologous KW - RNA, Small Interfering -- therapeutic use KW - Bone Marrow Transplantation -- immunology KW - Virus Latency -- physiology KW - Anti-HIV Agents -- therapeutic use KW - Virus Replication -- drug effects KW - Virus Latency -- drug effects KW - Antiretroviral Therapy, Highly Active KW - Immunotoxins -- therapeutic use KW - RNA, Small Interfering -- pharmacology KW - Immunotoxins -- pharmacology KW - HIV -- physiology KW - HIV Infections -- virology KW - HIV Infections -- therapy KW - HIV Infections -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66746257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+science+monitor+%3A+international+medical+journal+of+experimental+and+clinical+research&rft.atitle=Eradication+of+HIV+in+infected+patients%3A+some+potential+approaches.&rft.au=Yang%2C+Quan-en&rft.aulast=Yang&rft.aufirst=Quan-en&rft.date=2004-07-01&rft.volume=10&rft.issue=7&rft.spage=RA155&rft.isbn=&rft.btitle=&rft.title=Medical+science+monitor+%3A+international+medical+journal+of+experimental+and+clinical+research&rft.issn=12341010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-14 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monanchorin, a bicyclic alkaloid from the sponge Monanchora ungiculata. AN - 66741397; 15270573 AB - Monanchorin, a guanidine alkaloid with an unusual bicyclic skeleton, together with the known pentacyclic alkaloid crambescidin acid have been isolated from the aqueous extract of the sponge Monanchoraungiculata. JF - Journal of natural products AU - Meragelman, Karina M AU - McKee, Tawnya C AU - McMahon, James B AD - Molecular Targets Development Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1165 EP - 1167 VL - 67 IS - 7 SN - 0163-3864, 0163-3864 KW - Alkaloids KW - 0 KW - Bridged Bicyclo Compounds, Heterocyclic KW - Guanidines KW - monanchorin KW - Guanidine KW - JU58VJ6Y3B KW - Index Medicus KW - Molecular Structure KW - Animals KW - Nuclear Magnetic Resonance, Biomolecular KW - Pacific Ocean KW - Mice KW - Inhibitory Concentration 50 KW - Mast Cells -- drug effects KW - Bridged Bicyclo Compounds, Heterocyclic -- chemistry KW - Alkaloids -- chemistry KW - Bridged Bicyclo Compounds, Heterocyclic -- pharmacology KW - Porifera -- chemistry KW - Bridged Bicyclo Compounds, Heterocyclic -- isolation & purification KW - Alkaloids -- isolation & purification KW - Guanidines -- isolation & purification KW - Guanidines -- pharmacology KW - Guanidines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66741397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+natural+products&rft.atitle=Monanchorin%2C+a+bicyclic+alkaloid+from+the+sponge+Monanchora+ungiculata.&rft.au=Meragelman%2C+Karina+M%3BMcKee%2C+Tawnya+C%3BMcMahon%2C+James+B&rft.aulast=Meragelman&rft.aufirst=Karina&rft.date=2004-07-01&rft.volume=67&rft.issue=7&rft.spage=1165&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 completed - 2004-09-08 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perspectives on familial chronic lymphocytic leukemia: genes and the environment. AN - 66737256; 15269880 AB - Chronic lymphocytic leukemia (CLL) comprises a substantial proportion of leukemias in adults in the western hemisphere. Male gender, increasing age, ethnicity (high in Caucasians, lowest in Asians), and family history are risk factors. Although no specific extrinsic etiologic factors have been established, farming and pesticide exposure are associated with increased risk. Migration studies confirm that ethnic groups retain the risk associated with their origin rather than their new location, favoring a role for heredity. Kindreds with multiple cases of CLL have been well described in the literature and studies in large populations confirm that lymphoproliferative malignancies and especially CLL occur together at a rate that cannot be attributed to chance. Since environmental factors cannot readily explain the familial aggregations, a hereditary factor that affects susceptibility to CLL is likely. The identification of clones that are immunophenotypically identical to CLL in healthy individuals from CLL kindreds (14% to 18%) as well as in the general population (3.5% in age bracket >65 years) suggests a possible precursor condition, but longitudinal studies will be necessary to establish significance in the general population. Family (linkage) and population (candidate gene) studies to date have been too small to identify the specific genes that account for increased susceptibility; larger studies including planned consortia to identify additional high-risk kindreds for genetic studies, as well as the application of advanced technologies such as genomics, cytogenetic, expression, and proteomics, are widely expected to advance understanding over the next few years. JF - Seminars in hematology AU - Caporaso, Neil AU - Marti, Gerald E AU - Goldin, Lynn AD - Genetic Epideimology Branch, Division of Cancer Epideiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 201 EP - 206 VL - 41 IS - 3 SN - 0037-1963, 0037-1963 KW - Index Medicus KW - Genetic Linkage KW - Animals KW - Risk Factors KW - Humans KW - Adult KW - Siblings KW - Male KW - Female KW - Leukemia, Lymphocytic, Chronic, B-Cell -- genetics KW - Leukemia, Lymphocytic, Chronic, B-Cell -- epidemiology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- etiology KW - Environmental Exposure -- adverse effects KW - Family Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66737256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Perspectives+on+familial+chronic+lymphocytic+leukemia%3A+genes+and+the+environment.&rft.au=Caporaso%2C+Neil%3BMarti%2C+Gerald+E%3BGoldin%2C+Lynn&rft.aulast=Caporaso&rft.aufirst=Neil&rft.date=2004-07-01&rft.volume=41&rft.issue=3&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=00371963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-25 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins for the treatment of haematological malignancies. AN - 66731057; 15268678 AB - Recombinant immunotoxins are fusion proteins which contain a ligand derived from the immune system fused to a toxin. The protein toxin is truncated to delete its binding domain, allowing selective ligand-directed binding. Growth factor fusion toxins are often considered immunotoxins. One of these molecules, containing the truncated diphtheria toxin and human IL-2 (Ontak), Ligand Pharmaceuticals), has been approved for the treatment of cutaneous T-cell lymphoma. Recombinant immunotoxins have also been produced containing the variable domains (Fv fragment) of monoclonal antibodies fused to toxins. These agents are relatively versatile with respect to the range of antigens possible. Several of these recombinant immunotoxins have showed clinical effectiveness in Phase I testing against haematological malignancies. One of these molecules, BL22, targets CD22 on hairy-cell leukaemia and has enabled patients to achieve complete remissions despite previous treatment and resistance to chemotherapy. JF - Expert opinion on biological therapy AU - Kreitman, Robert J AD - Clinical Immunotherapy Section, Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1115 EP - 1128 VL - 4 IS - 7 KW - Antineoplastic Agents KW - 0 KW - Immunoglobulin Fragments KW - Immunotoxins KW - Neoplasm Proteins KW - Recombinant Fusion Proteins KW - Index Medicus KW - Molecular Structure KW - Animals KW - Macaca fascicularis KW - Antineoplastic Agents -- administration & dosage KW - Clinical Trials, Phase II as Topic KW - Combined Modality Therapy KW - Neoplasm Proteins -- immunology KW - Humans KW - Mice KW - Drug Design KW - Immunoglobulin Fragments -- therapeutic use KW - Immunoglobulin Fragments -- administration & dosage KW - Clinical Trials, Phase I as Topic KW - Treatment Outcome KW - Xenograft Model Antitumor Assays KW - Cell Line, Tumor -- drug effects KW - Forecasting KW - Antineoplastic Agents -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use KW - Drug Evaluation, Preclinical KW - Remission Induction KW - Immunotoxins -- chemistry KW - Hematologic Neoplasms -- drug therapy KW - Immunotoxins -- therapeutic use KW - Hematologic Neoplasms -- immunology KW - Immunotoxins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66731057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+biological+therapy&rft.atitle=Recombinant+immunotoxins+for+the+treatment+of+haematological+malignancies.&rft.au=Kreitman%2C+Robert+J&rft.aulast=Kreitman&rft.aufirst=Robert&rft.date=2004-07-01&rft.volume=4&rft.issue=7&rft.spage=1115&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+biological+therapy&rft.issn=1744-7682&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-23 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin A toxicity and vitamin E deficiency in a rabbit colony. AN - 66725536; 15264766 AB - Vitamin A toxicosis and vitamin E deficiency was diagnosed in a commercial rabbit-breeding colony and was associated with reproductive abnormalities, abortions, and poor survivability of kits in the breeding colony. Paresis and muscular dystrophy were noted in juvenile rabbits. Another group of New Zealand White rabbits from the same commercial colony was used to assess the effect of vitamin E-based therapy on clinical signs, reproduction, and vitamin A and E serum and liver levels. Blood samples were taken before and after dietary changes and vitamin E therapy. Serum vitamin E remained low after feeding a diet containing the recommended levels of vitamin E. Administration of vitamin E for 2 weeks lowered the serum vitamin A levels and increased the vitamin E serum and liver levels. In conclusion, vitamin E therapy appears to be an effective treatment for hypervitaminosis A. Copyright 2004 American Association for Laboratory Animal Science JF - Contemporary topics in laboratory animal science AU - St Claire, Mark B AU - Kennett, Mary J AU - Besch-Williford, Cynthia L AD - Department of Health and Humane Services, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 26 EP - 30 VL - 43 IS - 4 SN - 1060-0558, 1060-0558 KW - Vitamin A KW - 11103-57-4 KW - Vitamin E KW - 1406-18-4 KW - Index Medicus KW - Animals KW - Vitamin A -- blood KW - Fetal Death -- etiology KW - Vitamin A -- administration & dosage KW - Liver -- metabolism KW - Rabbits KW - Vitamin E -- blood KW - Pregnancy KW - Animals, Newborn KW - Abortion, Veterinary -- etiology KW - Liver -- drug effects KW - Diet KW - Vitamin E -- administration & dosage KW - Female KW - Male KW - Vitamin E Deficiency -- complications KW - Hypervitaminosis A -- veterinary KW - Vitamin E Deficiency -- diagnosis KW - Hypervitaminosis A -- diagnosis KW - Hypervitaminosis A -- complications KW - Animal Husbandry KW - Vitamin E Deficiency -- veterinary KW - Musculoskeletal Abnormalities -- etiology KW - Animals, Laboratory KW - Musculoskeletal Abnormalities -- veterinary KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66725536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Contemporary+topics+in+laboratory+animal+science&rft.atitle=Vitamin+A+toxicity+and+vitamin+E+deficiency+in+a+rabbit+colony.&rft.au=St+Claire%2C+Mark+B%3BKennett%2C+Mary+J%3BBesch-Williford%2C+Cynthia+L&rft.aulast=St+Claire&rft.aufirst=Mark&rft.date=2004-07-01&rft.volume=43&rft.issue=4&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Contemporary+topics+in+laboratory+animal+science&rft.issn=10600558&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-24 N1 - Date created - 2004-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro evaluation of dimethane sulfonate analogues with potential alkylating activity and selective renal cell carcinoma cytotoxicity. AN - 66705096; 15252146 AB - We identified five structurally related dimethane sulfonates with putative selective cytotoxicity in renal cancer cell lines. These compounds have a hydrophobic moiety linked to a predicted alkylating group. A COMPARE analysis with the National Cancer Institute Anticancer Drug Screen standard agent database found significant correlations between the IC50 of the test compounds and the IC50 of alkylating agents (e.g., r = 0.68, P < 0.00001 for chlorambucil). In this report, we examined whether these compounds had activities similar to those of conventional alkylating agents. In cytotoxicity studies, chlorambucil-resistant Walker rat carcinoma cells were 4- to 11-fold cross-resistant to the test compounds compared with 14-fold resistant to chlorambucil. To determine effects on cell cycle progression, renal cell carcinoma (RCC) line 109 was labeled with bromodeoxyuridine prior to drug treatment. Complete cell cycle arrest occurred in cells treated with an IC90 dose of NSC 268965. p53 protein levels increased as much as 5.7-fold in RCC line 109 and as much as 20.4-fold in breast cancer line MCF-7 following an 18-hour drug exposure. Finally, DNA-protein cross-links were found following a 6-hour pretreatment with all compounds. Thus, the dimethane sulfonate analogues have properties expected of some alkylating agents but, unlike conventional alkylating agents, appear to possess activity against RCC. JF - Molecular cancer therapeutics AU - Mertins, Susan D AU - Myers, Timothy G AU - Holbeck, Susan L AU - Medina-Perez, Wilma AU - Wang, Elaine AU - Kohlhagen, Glenda AU - Pommier, Yves AU - Bates, Susan E AD - Cancer Therapeutics Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA. smertins@mail.ncifcrf.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 849 EP - 860 VL - 3 IS - 7 SN - 1535-7163, 1535-7163 KW - Alkylating Agents KW - 0 KW - Mesylates KW - Tumor Suppressor Protein p53 KW - Busulfan KW - G1LN9045DK KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Carmustine KW - U68WG3173Y KW - Index Medicus KW - Animals KW - DNA Damage KW - Humans KW - Tumor Suppressor Protein p53 -- metabolism KW - Rats KW - Tumor Suppressor Protein p53 -- analysis KW - Busulfan -- analogs & derivatives KW - Carmustine -- analogs & derivatives KW - Bromodeoxyuridine -- analysis KW - Inhibitory Concentration 50 KW - Yeasts -- drug effects KW - Drug Evaluation, Preclinical KW - Cell Cycle -- drug effects KW - Drug Resistance, Neoplasm -- drug effects KW - Alkylating Agents -- therapeutic use KW - Kidney Neoplasms -- drug therapy KW - Alkylating Agents -- chemistry KW - Carcinoma, Renal Cell -- drug therapy KW - Alkylating Agents -- toxicity KW - Mesylates -- toxicity KW - Mesylates -- therapeutic use KW - Mesylates -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66705096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+therapeutics&rft.atitle=In+vitro+evaluation+of+dimethane+sulfonate+analogues+with+potential+alkylating+activity+and+selective+renal+cell+carcinoma+cytotoxicity.&rft.au=Mertins%2C+Susan+D%3BMyers%2C+Timothy+G%3BHolbeck%2C+Susan+L%3BMedina-Perez%2C+Wilma%3BWang%2C+Elaine%3BKohlhagen%2C+Glenda%3BPommier%2C+Yves%3BBates%2C+Susan+E&rft.aulast=Mertins&rft.aufirst=Susan&rft.date=2004-07-01&rft.volume=3&rft.issue=7&rft.spage=849&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-28 N1 - Date created - 2004-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional signature of flavopiridol-induced tumor cell death. AN - 66705079; 15252147 AB - Flavopiridol has been shown to inhibit the proliferation of a variety of human tumor cells and is currently undergoing clinical evaluation in cancer treatment. Although the antiproliferative effect of flavopiridol has been attributed to the inhibition of cyclin-dependent kinases 2 and 4, recent reports indicate that the mechanism responsible for the cell death induced by this agent is more complex. To provide insight into the molecular processes mediating flavopiridol-induced cytotoxicity and to investigate the availability of markers indicative of its activity, we have applied cDNA microarray technology. Gene expression profiles were determined for four human tumor cell lines (prostate carcinomas PC3 and DU145 and gliomas SF359 and U251) following exposure to selected concentrations of flavopiridol. Treatment of these cell lines with a concentration of flavopiridol sufficient to reduce survival to 10% resulted in the identification of a set of 209 genes, the expression of which were altered in each of the cell lines. This common set of 209 gene expression changes suggested that flavopiridol-induced cell death can be defined in terms of a specific transcriptome. The flavopiridol death transcriptome consisted primarily of down-regulated genes; however, there were also a significant number of genes with increased expression. Whereas causal relationships were not established, these data suggest molecular events/processes that may be associated with flavopiridol-induced tumor cell death. Moreover, the identification of a set of gene expression changes in four human tumor cell lines suggests that such a transcriptome may be applicable to investigations of flavopiridol pharmacodynamics. JF - Molecular cancer therapeutics AU - Lü, Xing AU - Burgan, William E AU - Cerra, Michael A AU - Chuang, Eric Y AU - Tsai, Mong-Hsun AU - Tofilon, Philip J AU - Camphausen, Kevin AD - Molecular Radiation Therapeutics Branch, National Cancer Institute, Bethesda, Maryland 20892-1002, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 861 EP - 872 VL - 3 IS - 7 SN - 1535-7163, 1535-7163 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Piperidines KW - RNA, Messenger KW - RNA, Neoplasm KW - alvocidib KW - 45AD6X575G KW - Index Medicus KW - Gene Expression Profiling KW - RNA, Messenger -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Cell Death -- genetics KW - Cell Line, Tumor KW - Neoplasms -- genetics KW - Neoplasms -- metabolism KW - Piperidines -- pharmacology KW - Transcription, Genetic -- drug effects KW - Piperidines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Flavonoids -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - RNA, Neoplasm -- metabolism KW - Flavonoids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66705079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+therapeutics&rft.atitle=Transcriptional+signature+of+flavopiridol-induced+tumor+cell+death.&rft.au=L%C3%BC%2C+Xing%3BBurgan%2C+William+E%3BCerra%2C+Michael+A%3BChuang%2C+Eric+Y%3BTsai%2C+Mong-Hsun%3BTofilon%2C+Philip+J%3BCamphausen%2C+Kevin&rft.aulast=L%C3%BC&rft.aufirst=Xing&rft.date=2004-07-01&rft.volume=3&rft.issue=7&rft.spage=861&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-28 N1 - Date created - 2004-07-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Mol Cancer Ther. 2004 Jul;3(7):873-5 [15252148] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis. AN - 66687703; 15248218 AB - Pulse cyclophosphamide is the treatment of choice for severe lupus nephritis. However, not all patients respond to this therapy, and gonadal toxicity is of particular concern. Cyclophosphamide is a prodrug that requires activation by cytochrome P450 (CYP) enzymes. We conducted a retrospective cohort study to test whether genetic polymorphisms of these enzymes are associated with the toxicity of, and clinical response to, cyclophosphamide in patients with lupus nephritis. Sixty-two patients with proliferative lupus nephritis treated with cyclophosphamide were genotyped for common variant alleles of CYP2B6, 2C19, 2C9, and 3A5. We examined the association between these genotypes and the following clinical end points: development of premature ovarian failure, end-stage renal disease (ESRD), doubling of serum creatinine level, and achievement of complete renal response. The observed frequencies of the variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%, 25.0%, 4.0%, and 75.8%, respectively. Patients who were either heterozygous or homozygous for CYP2C19*2 had a significantly lower risk of developing premature ovarian failure (relative risk 0.10; 95% confidence interval 0.02-0.52), after adjustment for age and total number of cyclophosphamide pulses received. In a survival analysis, patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n = 4) had a higher probability of reaching ESRD (P = 0.0005) and of doubling the creatinine level (P = 0.0005) as well as a trend toward a lower probability of achieving a complete renal response (P = 0.051). Determination of selected cytochrome P450 enzyme genotypes may be valuable for predicting the risk of premature ovarian failure in lupus nephritis patients treated with cyclophosphamide. The association of these genotypes with renal response needs further validation. JF - Arthritis and rheumatism AU - Takada, Kazuki AU - Arefayene, Million AU - Desta, Zeruesenay AU - Yarboro, Cheryl H AU - Boumpas, Dimitrios T AU - Balow, James E AU - Flockhart, David A AU - Illei, Gabor G AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 2202 EP - 2210 VL - 50 IS - 7 SN - 0004-3591, 0004-3591 KW - Antirheumatic Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Abridged Index Medicus KW - Index Medicus KW - Genetic Variation KW - Homozygote KW - Pulse Therapy, Drug KW - Gene Frequency KW - Humans KW - Retrospective Studies KW - Predictive Value of Tests KW - Kidney Failure, Chronic -- etiology KW - Primary Ovarian Insufficiency -- chemically induced KW - Genotype KW - Alleles KW - Risk Factors KW - Adult KW - Cohort Studies KW - Treatment Outcome KW - Middle Aged KW - Female KW - Male KW - Cyclophosphamide -- administration & dosage KW - Lupus Nephritis -- drug therapy KW - Polymorphism, Genetic KW - Cytochrome P-450 Enzyme System -- genetics KW - Antirheumatic Agents -- administration & dosage KW - Antirheumatic Agents -- adverse effects KW - Lupus Nephritis -- complications KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66687703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Cytochrome+P450+pharmacogenetics+as+a+predictor+of+toxicity+and+clinical+response+to+pulse+cyclophosphamide+in+lupus+nephritis.&rft.au=Takada%2C+Kazuki%3BArefayene%2C+Million%3BDesta%2C+Zeruesenay%3BYarboro%2C+Cheryl+H%3BBoumpas%2C+Dimitrios+T%3BBalow%2C+James+E%3BFlockhart%2C+David+A%3BIllei%2C+Gabor+G&rft.aulast=Takada&rft.aufirst=Kazuki&rft.date=2004-07-01&rft.volume=50&rft.issue=7&rft.spage=2202&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-13 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: results from the National Survey of Lead and Allergens in Housing. AN - 66686314; 15241352 AB - Exposures to dog and cat allergens are believed to play important roles in the etiology of asthma; however, the levels of these allergens have never been assessed in a representative sample of US homes. The objective of this study was to estimate and characterize exposures to Can f 1 (dog allergen) and Fel d 1 (cat allergen) in US homes. Data were obtained from the National Survey of Lead and Allergens in Housing, a nationally representative survey of 831 US homes. Vacuumed-collected dust samples from the bed, bedroom floor, living room floor, and living room sofa were analyzed for concentrations of Can f 1 and Fel d 1 (micrograms of allergen per gram of dust). Although a dog or cat had lived in only 49.1% of homes in the previous 6 months, Can f 1 and Fel d 1 were detected in 100% and 99.9% of homes, respectively. Averaged over the sampled sites, geometric mean concentrations (microg/g) were 4.69 for Can f 1 and 4.73 for Fel d 1. Among homes with an indoor dog and cat, respectively, geometric mean concentrations were 69 for Can f 1 and 200 for Fel d 1. Among homes without the indoor pet, geometric mean concentrations were above 1.0. The independent predictors of elevated concentrations in homes without pets were all demographic variables that were also linked to a higher prevalence of pet ownership. Can f 1 and Fel d 1 are universally present in US homes. Levels that have been associated with an increased risk of allergic sensitization were found even in homes without pets. Because of the transportability of these allergens on clothing, elevated levels in homes without pets, particularly among demographic groups in which pet ownership is more prevalent, implicate the community as an important source of these pet allergens. JF - The Journal of allergy and clinical immunology AU - Arbes, Samuel J AU - Cohn, Richard D AU - Yin, Ming AU - Muilenberg, Michael L AU - Friedman, Warren AU - Zeldin, Darryl C AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 111 EP - 117 VL - 114 IS - 1 SN - 0091-6749, 0091-6749 KW - Allergens KW - 0 KW - Antigens, Plant KW - Glycoproteins KW - allergen Can f I KW - Fel d 1 protein, Felis domesticus KW - G408EE88II KW - Abridged Index Medicus KW - Index Medicus KW - Cross-Sectional Studies KW - Animals KW - Humans KW - Cats KW - Dogs KW - Residence Characteristics -- statistics & numerical data KW - United States -- epidemiology KW - Glycoproteins -- analysis KW - Environmental Exposure -- analysis KW - Allergens -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66686314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dog+allergen+%28Can+f+1%29+and+cat+allergen+%28Fel+d+1%29+in+US+homes%3A+results+from+the+National+Survey+of+Lead+and+Allergens+in+Housing.&rft.au=Arbes%2C+Samuel+J%3BCohn%2C+Richard+D%3BYin%2C+Ming%3BMuilenberg%2C+Michael+L%3BFriedman%2C+Warren%3BZeldin%2C+Darryl+C&rft.aulast=Arbes&rft.aufirst=Samuel&rft.date=2004-07-01&rft.volume=114&rft.issue=1&rft.spage=111&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 - 2004-09-28 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense protein kinase A RIalpha inhibits 7,12-dimethylbenz(a)anthracene-induction of mammary cancer: blockade at the initial phase of carcinogenesis. AN - 66684482; 15240549 AB - There are two types of cyclic AMP (cAMP)-dependent protein kinase (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunit but contain distinct regulatory (R) subunits, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RIalpha) correlates with tumorigenesis and tumor growth. We investigated the effect of sequence-specific inhibition of RIalpha gene expression at the initial phase of 7,12-dimethylbenz(alphaa)anthracene (DMBA)-induced mammary carcinogenesis. Antisense RIalpha oligodeoxynucleotide (ODN) targeted against PKA RIalpha was administered (0.1 mg/day/rat, i.p.) 1 day before DMBA intubation and during the first 9 days post-DMBA intubation to determine the anticarcinogenic effects. Antisense RIalpha, in a sequence-specific manner, inhibited the tumor production. At 90 days after DMBA intubation, untreated controls and RIalpha-antisense-treated rats exhibited an average mean number of tumors per rat of 4.2 and 1.8, respectively, and 90% of control and 45% of antisense-treated animals had tumors. The antisense also delayed the first tumor appearance. An increase in RIalpha and PKA-I levels in the mammary gland and liver preceded DMBA-induced tumor production, and antisense down-regulation of RIalpha restored normal levels of PKA-I and PKA-II in these tissues. Antisense RIalpha in the liver induced the phase II enzymes, glutathione S-transferase and quinone oxidoreductase, c-fos protein, and activator protein 1 (AP-1)- and cAMP response element (CRE)-directed transcription. In the mammary glands, antisense RIalpha promoted DNA repair processes. In contrast, the CRE transcription-factor decoy could not mimic these effects of antisense RIalpha. The results demonstrate that RIalpha antisense produces dual anticarcinogenic effects: (a) increasing DMBA detoxification in the liver by increasing phase II enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and Ap-1-directed transcription; and (b) activating DNA repair processes in the mammary gland by down-regulating PKA-I. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Nesterova, Maria V AU - Cho-Chung, Yoon S AD - Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 4568 EP - 4577 VL - 10 IS - 13 SN - 1078-0432, 1078-0432 KW - Carcinogens KW - 0 KW - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit KW - Ethanolamines KW - Oligonucleotides, Antisense KW - Prkar1a protein, mouse KW - Prkar1a protein, rat KW - Proto-Oncogene Proteins c-fos KW - Transcription Factor AP-1 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cyclic AMP KW - E0399OZS9N KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - NADPH Dehydrogenase KW - EC 1.6.99.1 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Cyclic AMP-Dependent Protein Kinase Type II KW - EC 2.7.11.11 KW - Cyclic AMP-Dependent Protein Kinases KW - 2-diethylaminoethanol KW - S6DL4M053U KW - Index Medicus KW - Carcinogens -- pharmacology KW - Animals KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Catalytic Domain KW - Liver -- metabolism KW - Transcription, Genetic KW - NAD(P)H Dehydrogenase (Quinone) -- metabolism KW - Rats KW - NADPH Dehydrogenase -- metabolism KW - Down-Regulation KW - Phosphorylation KW - Time Factors KW - DNA Repair KW - Ethanolamines -- pharmacology KW - Dose-Response Relationship, Drug KW - Glutathione Transferase -- metabolism KW - Immunoprecipitation KW - Mice KW - Protein Binding KW - Rats, Sprague-Dawley KW - Mammary Glands, Animal -- metabolism KW - Cyclic AMP -- metabolism KW - Female KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Mammary Neoplasms, Animal -- pathology KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Oligonucleotides, Antisense -- pharmacology KW - Mammary Neoplasms, Animal -- metabolism KW - Mammary Neoplasms, Animal -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66684482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antisense+protein+kinase+A+RIalpha+inhibits+7%2C12-dimethylbenz%28a%29anthracene-induction+of+mammary+cancer%3A+blockade+at+the+initial+phase+of+carcinogenesis.&rft.au=Nesterova%2C+Maria+V%3BCho-Chung%2C+Yoon+S&rft.aulast=Nesterova&rft.aufirst=Maria&rft.date=2004-07-01&rft.volume=10&rft.issue=13&rft.spage=4568&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 - 2005-01-31 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What is the rationale for new treatment strategies in Alzheimer's disease? AN - 66683434; 15241294 AB - Alzheimer's disease (AD) is characterized by the abnormal extracellular accumulation of amyloid beta-peptide (Abeta) into neuritic plaques and the intraneuronal aggregation of the microtubule-associated protein tau to form neurofibrillary tangles. These molecular events are implicated in the selective damage to neural systems critical for the brain functions that are impaired in AD. Impairment of cholinergic neurotransmission may be an important factor underlying the defects in cognition and memory that characterize AD. Cholinesterase (ChE) inhibitors, such as donepezil, rivastigmine, and galantamine, cause symptomatic improvement by inhibiting the breakdown of the neurotransmitter acetylcholine to increase its synaptic availability and, in the case of galantamine, by also allosterically potentiating nicotinic cholinergic receptors. Other agents, including vitamin E, monoamine oxidase inhibitors, and statins, have shown some benefit in epidemiological studies and clinical trials although compelling evidence of their efficacy is lacking. Memantine, shown to cause cognitive and functional improvement, is not an ChE inhibitor and does not interact with marketed ChE inhibitors. While the mechanism of action of memantine in AD is not known, the principal pharmacologic actions at therapeutic dose are inhibition of ionotropic neurotransmitter receptors, specifically N-methyl-D-aspartate (NMDA), 5-HT3, and nicotinic receptors. Like other NMDA antagonists, memantine causes behavioral activation associated with enhanced cerebral glucose utilization. Studies have shown that memantine can reverse the decreased metabolic activity associated with AD, possibly accounting for its beneficial effects on cognition and global functioning. Memantine also has neuroprotective properties and can inhibit Abeta-induced neurodegeneration. JF - CNS spectrums AU - Rogawski, Michael A AD - Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892, USA. michael.rogawski@nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 6 EP - 12 VL - 9 IS - 7 Suppl 5 SN - 1092-8529, 1092-8529 KW - Cholinesterase Inhibitors KW - 0 KW - Excitatory Amino Acid Antagonists KW - Nootropic Agents KW - Receptors, N-Methyl-D-Aspartate KW - Acetylcholine KW - N9YNS0M02X KW - Memantine KW - W8O17SJF3T KW - Index Medicus KW - Acetylcholine -- physiology KW - Memantine -- therapeutic use KW - Brain -- drug effects KW - Cholinesterase Inhibitors -- therapeutic use KW - Humans KW - Cholinergic Fibers -- physiology KW - Memantine -- adverse effects KW - Brain -- physiopathology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Cholinesterase Inhibitors -- adverse effects KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Excitatory Amino Acid Antagonists -- adverse effects KW - Cholinergic Fibers -- drug effects KW - Cognition Disorders -- diagnosis KW - Cognition Disorders -- drug therapy KW - Alzheimer Disease -- physiopathology KW - Alzheimer Disease -- drug therapy KW - Nootropic Agents -- therapeutic use KW - Nootropic Agents -- adverse effects KW - Cognition Disorders -- physiopathology KW - Alzheimer Disease -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66683434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=CNS+spectrums&rft.atitle=What+is+the+rationale+for+new+treatment+strategies+in+Alzheimer%27s+disease%3F&rft.au=Rogawski%2C+Michael+A&rft.aulast=Rogawski&rft.aufirst=Michael&rft.date=2004-07-01&rft.volume=9&rft.issue=7+Suppl+5&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=CNS+spectrums&rft.issn=10928529&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-18 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiviral prophylaxis of smallpox. AN - 66681129; 15163655 AB - Proof-of-concept studies suggest that current defences against smallpox could be strengthened by supplementing vaccination with antiviral drug prophylaxis, based on aerosolized or orally available forms of the long-acting medication cidofovir. Delivery of aerosolized cidofovir to mice results in its prolonged retention in respiratory tissues and protection against lethal intranasal or aerosol poxviral challenge. Although cidofovir itself is not orally available, the addition of an alkoxyalkanol ether side-chain allows it to be absorbed from the gastrointestinal tract. This also markedly increases its antiviral activity and lengthens its intracellular half-life from roughly 3 to 8-10 days. Oral treatment also protected mice against lethal poxviral challenge. These results suggest that a single aerosol dose of cidofovir (or an alkoxyalkanol-ether derivative) could provide prolonged protection against initiation of smallpox infection, whereas oral treatment could prevent both initiation of infection and internal dissemination of virus. Both approaches may avoid the nephrotoxicity that occasionally results from intravenous cidofovir therapy. JF - The Journal of antimicrobial chemotherapy AU - Bray, Mike AU - Roy, Chad J AD - Biodefense Clinical Research Branch, Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mbray@niaid.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1 EP - 5 VL - 54 IS - 1 SN - 0305-7453, 0305-7453 KW - Antiviral Agents KW - 0 KW - Organophosphonates KW - Organophosphorus Compounds KW - Smallpox Vaccine KW - Cytosine KW - 8J337D1HZY KW - cidofovir KW - JIL713Q00N KW - Index Medicus KW - Organophosphorus Compounds -- therapeutic use KW - Combined Modality Therapy KW - Humans KW - Smallpox Vaccine -- therapeutic use KW - Organophosphorus Compounds -- administration & dosage KW - Vaccination KW - Antiviral Agents -- therapeutic use KW - Antiviral Agents -- administration & dosage KW - Cytosine -- therapeutic use KW - Cytosine -- administration & dosage KW - Smallpox -- prevention & control KW - Cytosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66681129?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+antimicrobial+chemotherapy&rft.atitle=Antiviral+prophylaxis+of+smallpox.&rft.au=Bray%2C+Mike%3BRoy%2C+Chad+J&rft.aulast=Bray&rft.aufirst=Mike&rft.date=2004-07-01&rft.volume=54&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+antimicrobial+chemotherapy&rft.issn=03057453&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-27 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hybridization buffer systems impact the quality of filter array data. AN - 66680929; 15233970 AB - cDNA microarray technology has greatly facilitated mechanistic studies in pharmacology and toxicology. A clean hybridization with minimal background is critical for successful microarray analysis and is highly desired. However, clean hybridization alone is not enough; verification is needed. Total RNA was isolated from the livers of acetaminophen-intoxicated mice and was subjected to cDNA microarray analyses using ExpressHyb, ULTRArrayHyb or MicroHyb on nylon membranes. Real-time RT-PCR analyses were performed for verification. We have demonstrated in this paper that hybridization systems can significantly impact the quality of array data. MicroHyb produced very clean hybridizations, but some results could not be confirmed by real-time RT-PCR and in accord with biological responses. The hybridization images from ExpressHyb were not always clean, but were reliable. The sensitivity of ULTRArrayHyb was moderate. This study has indicated the importance of selecting hybridization buffers in membrane arrays and recommended real-time RT-PCR for follow-up analysis. Gene expression changes should also be correlated with biological significance. JF - Journal of pharmacological and toxicological methods AU - Liu, Jie AU - Walker, Nigel AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, LCC, NCI at NIEHS, 111 Alexander Drive, RTP, NC 27709, USA. Liu6@niehs.nih.gov PY - 2004 SP - 67 EP - 71 VL - 50 IS - 1 SN - 1056-8719, 1056-8719 KW - Analgesics, Non-Narcotic KW - 0 KW - Buffers KW - DNA Primers KW - RNA, Messenger KW - Acetaminophen KW - 362O9ITL9D KW - Index Medicus KW - Animals KW - RNA, Messenger -- metabolism KW - Analgesics, Non-Narcotic -- toxicity KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Male KW - Acetaminophen -- toxicity KW - Liver -- drug effects KW - Nucleic Acid Hybridization -- methods KW - Oligonucleotide Array Sequence Analysis -- methods KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66680929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacological+and+toxicological+methods&rft.atitle=Hybridization+buffer+systems+impact+the+quality+of+filter+array+data.&rft.au=Liu%2C+Jie%3BWalker%2C+Nigel%3BWaalkes%2C+Michael+P&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2004-07-01&rft.volume=50&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmacological+and+toxicological+methods&rft.issn=10568719&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-25 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of antiangiogenic therapy with bevacizumab and thalidomide in patients with metastatic renal cell carcinoma. AN - 66679439; 15235386 AB - The use of antiangiogenic agents represents a promising strategy for the treatment of patients with metastatic renal cell carcinoma. Objective responses to single-agent thalidomide have been described, and a randomized study showed that bevacizumab (a neutralizing antibody against vascular endothelial growth factor) delayed time to progression of metastatic renal cancer. A pilot study combining these two agents was performed. Sequential cohorts of 10 and 12 patients (crossing over from placebo therapy in the aforementioned randomized bevacizuamab trial) were treated with low-dose bevacizumab alone or bevacizumab plus the maximum tolerated dose of thalidomide as determined by intrapatient escalation. Toxicity, objective responses, and time to progression were the endpoints of this study. Patients tolerated thalidomide and bevacizumab well, with more than 50% of patients escalating to at least 500 mg/d thalidomide. Grades 1 and 2 sensory neuropathy limited thalidomide dose escalation in 3 of 12 patients. The incidence of grades 3 and 4 toxicity was not different between patients treated with bevacizumab alone versus bevacizumab plus thalidomide. There were no objective responses and no difference in progression-free survival between the groups (2.4 months for bevacizumab alone, 3.0 months for bevacizumab plus thalidomide). Combination antiangiogenic therapy with bevacizumab plus thalidomide in patients with renal cell carcinoma is associated with similar toxicity and progression-free survival compared with bevacizumab alone. This study illustrates a clinical trial design for rapidly testing the feasibility and safety of combining antiangiogenic agents, an approach that will be necessary for rapidly evaluating the many potential combinations of antiangiogenic agents. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Elaraj, Dina M AU - White, Donald E AU - Steinberg, Seth M AU - Haworth, Leah AU - Rosenberg, Steven A AU - Yang, James C AD - Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2004 SP - 259 EP - 264 VL - 27 IS - 4 SN - 1524-9557, 1524-9557 KW - Angiogenesis Inhibitors KW - 0 KW - Antibodies, Monoclonal KW - Antibodies, Monoclonal, Humanized KW - Bevacizumab KW - 2S9ZZM9Q9V KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - Survival Rate KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Aged KW - Pilot Projects KW - Middle Aged KW - Male KW - Female KW - Carcinoma, Renal Cell -- pathology KW - Angiogenesis Inhibitors -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols KW - Thalidomide -- administration & dosage KW - Carcinoma, Renal Cell -- drug therapy KW - Thalidomide -- therapeutic use KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use KW - Angiogenesis Inhibitors -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66679439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=A+pilot+study+of+antiangiogenic+therapy+with+bevacizumab+and+thalidomide+in+patients+with+metastatic+renal+cell+carcinoma.&rft.au=Elaraj%2C+Dina+M%3BWhite%2C+Donald+E%3BSteinberg%2C+Seth+M%3BHaworth%2C+Leah%3BRosenberg%2C+Steven+A%3BYang%2C+James+C&rft.aulast=Elaraj&rft.aufirst=Dina&rft.date=2004-07-01&rft.volume=27&rft.issue=4&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-04 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1999 Nov 18;341(21):1565-71 [10564685] Ann Surg. 1998 Sep;228(3):307-19 [9742914] Br J Cancer. 2000 Feb;82(4):812-7 [10732751] Oncology (Williston Park). 2000 Dec;14(12 Suppl 13):33-6 [11204672] J Clin Oncol. 2001 Feb 1;19(3):843-50 [11157038] J Clin Oncol. 2002 Jan 1;20(1):302-6 [11773183] J Clin Oncol. 2002 Mar 1;20(5):1368-74 [11870181] Ann Oncol. 2002 Jul;13(7):1029-35 [12176780] Invest New Drugs. 2002 Nov;20(4):389-93 [12448656] CA Cancer J Clin. 2003 Jan-Feb;53(1):5-26 [12568441] Ann Intern Med. 1988 Apr;108(4):518-23 [3258138] Cancer Res. 1988 Dec 15;48(24 Pt 1):7310-3 [3056613] Urology. 1989 Oct;34(4 Suppl):80-3; discussion 87-96 [2678687] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4082-5 [7513432] Nat Genet. 1994 May;7(1):85-90 [7915601] Graefes Arch Clin Exp Ophthalmol. 1998 Jun;236(6):461-6 [9646092] J Clin Oncol. 1999 Aug;17(8):2530-40 [10561319] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Associations between plasma DDE levels and immunologic measures in African-American farmers in North Carolina. AN - 66676891; 15238281 AB - Experimental studies in rodents demonstrate evidence of immunosuppressive effects of dietary exposure to DDT [2,2-bis((italic)p(/italic)-chlorophenyl)-1,1,1-trichloroethane], but human data pertaining to immunomodulating effects of DDT exposure are limited. In this study we examined the association between the persistent organochlorine breakdown product 1,1-dichloro-2,2,bis(p-chlorophenyl)ethylene p,p'-DDE) and immunologic measures using blood samples in a relatively highly exposed population of farmers in the United States. Levels of serum immunoglobulin A (IgA) and IgG and the prevalence of antinuclear antibodies in relation to plasma p,p'-DDE levels were evaluated in samples from 137 African-American male farmers (30-88 years of age; median, 64 years). Participants were recruited through black churches in four rural counties in eastern North Carolina. Data collection included a telephone interview pertaining to farming practices and health history, and one blood sample was collected from each participant. Linear and logistic regression, adjusting for age, cholesterol, triglycerides, smoking status, and years of any kind of pesticide use, was used to assess the association between immunologic parameters and plasma levels of p,p'-DDE. The median plasma p,p'-DDE concentration was 7.7 microg/L (range, 0.6-77.4 microg/L). There was no association between p,p'-DDE and IgA in any of the models. IgG levels decreased with increasing p,p'-DDE levels, with a statistically significant decrease of approximately 50% in the highest two categories of exposure (greater than or equal to 6.0 microg/L) compared with values of or = 12.0 microg/L compared with < 3.0 microg/L p,p'-DDE), but this difference was not statistically significant. These analyses provide evidence that p,p'-DDE modulates immune responses in humans. JF - Environmental health perspectives AU - Cooper, Glinda S AU - Martin, Stephen A AU - Longnecker, Matthew P AU - Sandler, Dale P AU - Germolec, Dori R AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1080 EP - 1084 VL - 112 IS - 10 SN - 0091-6765, 0091-6765 KW - Immunoglobulin A KW - 0 KW - Immunoglobulin G KW - Insecticides KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Index Medicus KW - Agriculture KW - Aged, 80 and over KW - Humans KW - North Carolina KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Occupational Exposure KW - Insecticides -- poisoning KW - Immunoglobulin G -- analysis KW - Dichlorodiphenyl Dichloroethylene -- poisoning KW - Immunoglobulin A -- analysis KW - African Americans KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Antibody Formation -- drug effects KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66676891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Associations+between+plasma+DDE+levels+and+immunologic+measures+in+African-American+farmers+in+North+Carolina.&rft.au=Cooper%2C+Glinda+S%3BMartin%2C+Stephen+A%3BLongnecker%2C+Matthew+P%3BSandler%2C+Dale+P%3BGermolec%2C+Dori+R&rft.aulast=Cooper&rft.aufirst=Glinda&rft.date=2004-07-01&rft.volume=112&rft.issue=10&rft.spage=1080&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 - 2004-09-21 N1 - Date created - 2004-07-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunol Res. 1999;20(1):67-78 [10467984] Am J Epidemiol. 2001 Jan 1;153(1):53-63 [11159147] Lancet. 2001 Jul 14;358(9276):110-4 [11463412] Toxicology. 2002 Jun 5;174(3):201-10 [12007859] Epidemiology. 2002 Jul;13(4):454-8 [12094101] Ann Clin Biochem. 2002 Jul;39(Pt 4):374-7 [12117441] Environ Health Perspect. 2002 Jul;110(7):617-24 [12117636] Environ Health Perspect. 2003 Aug;111(10):1273-7 [12896845] Pediatrics. 1966 May;37(5):715-27 [4956666] N Engl J Med. 1970 Sep 17;283(12):631-4 [4194865] Arch Environ Health. 1975 Feb;30(2):81-4 [234722] Infect Immun. 1978 Apr;20(1):30-5 [97225] Int Arch Occup Environ Health. 1982;50(4):329-40 [7174118] Clin Immunol Immunopathol. 1984 Oct;33(1):13-22 [6478653] Am J Public Health. 1987 Oct;77(10):1294-7 [3115123] Bull Environ Contam Toxicol. 1987 Nov;39(5):822-6 [3318960] Bull Environ Contam Toxicol. 1987 Nov;39(5):827-34 [3690008] Arch Environ Health. 1991 Jul-Aug;46(4):249-53 [2069434] Arch Environ Health. 1992 Jul-Aug;47(4):295-301 [1497384] Arch Environ Health. 1993 Mar-Apr;48(2):81-8 [8476309] Arch Environ Health. 1993 Mar-Apr;48(2):89-93 [7682805] Toxicol Appl Pharmacol. 1993 Oct;122(2):233-43 [8212005] Am J Public Health. 1995 Apr;85(4):504-8 [7702113] Nature. 1995 Jun 15;375(6532):581-5 [7791873] J AOAC Int. 1995 Nov-Dec;78(6):1353-63 [8664570] Environ Health Perspect. 1996 Apr;104(4):362-9 [8732939] Int J Lepr Other Mycobact Dis. 1997 Mar;65(1):97-9 [9207760] Clin Invest Med. 1998 Feb;21(1):4-11 [9512879] Arthritis Rheum. 1998 Oct;41(10):1714-24 [9778212] Arch Environ Contam Toxicol. 1999 May;36(4):504 [10227872] J Toxicol Environ Health A. 1999 Jun 25;57(4):225-36 [10406347] Environ Health Perspect. 1999 Oct;107 Suppl 5:783-92 [10502545] Bull Environ Contam Toxicol. 1992 Apr;48(4):535-40 [1504498] Environ Health Perspect. 2000 Mar;108(3):205-11 [10706525] Environ Health Perspect. 2001 Jan;109(1):27-33 [11171521] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparing questionnaire-based methods to assess occupational silica exposure. AN - 66674669; 15232404 AB - Epidemiologic assessment of occupational exposure to silica is typically limited to long-term work in the dusty trades, primarily in jobs held by men. We compared alternative questionnaire-based methods to assess silica exposure in a recent case-control study of 265 patients with systemic lupus erythematosus (mostly women) and 355 controls randomly selected from state driver's license registries and frequency-matched by age and sex. In-person interviews included a job history (all jobs held at least 12 months) and checklist of silica-related jobs and tasks (work of at least 2 weeks). Three industrial hygienists reviewed job descriptions without knowing case-control status. Potential high- or moderate-intensity exposures were confirmed or revised based on follow-up telephone interviews. In the full assessment including all work of at least 2 weeks, 9% of cases and 4% of controls were classified as medium or high silica exposure (odds ratio of disease = 2.9; 95% confidence interval = 1.3-6.4). In contrast, only 4% of cases and 9% of controls were identified by the standardized code groups index as having worked in silica-related industries or occupations for at least 12 months, providing a much lower risk estimate for disease (0.4; 0.2-0.9). Specific task-based questions must be included to assess the full potential of occupational silica exposure. These findings highlight the limitations of using standardized code groups to define exposure or to select jobs for industrial hygienist review. Copyright 2004 Lippincott Williams and Wilkins JF - Epidemiology (Cambridge, Mass.) AU - Parks, Christine G AU - Cooper, Glinda S AU - Nylander-French, Leena A AU - Hoppin, Jane A AU - Sanderson, Wayne T AU - Dement, John M AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Cqp8@cdc.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 433 EP - 441 VL - 15 IS - 4 SN - 1044-3983, 1044-3983 KW - Air Pollutants, Occupational KW - 0 KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Registries KW - Humans KW - Adult KW - Case-Control Studies KW - Task Performance and Analysis KW - Interviews as Topic KW - Middle Aged KW - North Carolina -- epidemiology KW - Male KW - Female KW - South Carolina -- epidemiology KW - Silicon Dioxide -- analysis KW - Air Pollutants, Occupational -- analysis KW - Surveys and Questionnaires KW - Silicon Dioxide -- toxicity KW - Occupational Exposure -- adverse effects KW - Lupus Erythematosus, Systemic -- chemically induced KW - Air Pollutants, Occupational -- toxicity KW - Risk Assessment -- methods KW - Occupations -- classification KW - Lupus Erythematosus, Systemic -- epidemiology KW - Occupational Exposure -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66674669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparing+questionnaire-based+methods+to+assess+occupational+silica+exposure.&rft.au=Parks%2C+Christine+G%3BCooper%2C+Glinda+S%3BNylander-French%2C+Leena+A%3BHoppin%2C+Jane+A%3BSanderson%2C+Wayne+T%3BDement%2C+John+M&rft.aulast=Parks&rft.aufirst=Christine&rft.date=2004-07-01&rft.volume=15&rft.issue=4&rft.spage=433&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 - 2004-09-09 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-throughput retroviral tagging for identification of genes involved in initiation and progression of mouse splenic marginal zone lymphomas. AN - 66674028; 15231650 AB - Human B-cell lymphomas are frequently associated with specific genetic changes caused by chromosomal translocations that activate proto-oncogenes. For lymphomas of mice expressing murine leukemia virus, mutagenic proviral insertions are thought to play a similar role. Here we report studies designed to determine whether specific retroviral integration sites might be associated with a specific subset of mouse B-cell lymphomas and if the genes associated with these sites are regularly altered in expression. We studied splenic marginal zone lymphomas (MZL) of NFS.V(+) mice that are unusual in exhibiting frequent progression from low to high grade, potentially allowing assignment of cancer genes to processes of initiation and progression. We used inverse PCR to clone and analyze 212 retroviral integration sites from 43 MZL at different stages of progression. Sixty-two marked common integration sites and included 31 that had been marked previously. Among the new common integration sites, seven were unique to MZL. Using microarrays and real-time quantitative PCR analysis, we defined differential patterns of gene expression in association with disease progression for Gfi1, Sox4, Brca2, Snf1lk, Nfkb1, Pou2af1, Prdm1, Stat6, and Blnk. Heightened expression of Gfi1 distinguishes MZL from other lymphoma types. The combined use of proviral tagging and analyses of gene expression thus provides a powerful approach to understanding of genes that collaborate in tumorigenesis. JF - Cancer research AU - Shin, Min Sun AU - Fredrickson, Torgny N AU - Hartley, Janet W AU - Suzuki, Takeshi AU - Akagi, Keiko AU - Agaki, Keiko AU - Morse, Herbert C AD - Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 4419 EP - 4427 VL - 64 IS - 13 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Hematologic Neoplasms -- pathology KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Polymerase Chain Reaction -- methods KW - Hematologic Neoplasms -- genetics KW - Mice, Inbred C57BL KW - Gene Expression KW - Disease Progression KW - Mice, Nude KW - Mice KW - Virus Integration -- genetics KW - Splenic Neoplasms -- genetics KW - Splenic Neoplasms -- pathology KW - Lymphoma, B-Cell -- pathology KW - Lymphoma, B-Cell -- genetics KW - Retroviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66674028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-throughput+retroviral+tagging+for+identification+of+genes+involved+in+initiation+and+progression+of+mouse+splenic+marginal+zone+lymphomas.&rft.au=Shin%2C+Min+Sun%3BFredrickson%2C+Torgny+N%3BHartley%2C+Janet+W%3BSuzuki%2C+Takeshi%3BAkagi%2C+Keiko%3BAgaki%2C+Keiko%3BMorse%2C+Herbert+C&rft.aulast=Shin&rft.aufirst=Min&rft.date=2004-07-01&rft.volume=64&rft.issue=13&rft.spage=4419&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 - 2004-08-26 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Res. 2006 Mar 15;66(6):3345 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fish intake during pregnancy and early cognitive development of offspring. AN - 66672651; 15232398 AB - Fish is a source of many nutrients that can be beneficial during pregnancy, as well as a source of neurotoxicant contaminants such as methylmercury. Previous investigations of fish intake in relation to neurodevelopment have focused on possible damage from contaminants, whereas potential benefits of fish consumption have been relatively unexplored We evaluated the association between maternal fish intake during pregnancy and offspring's early development of language and communication skills in a cohort of 7421 British children born in 1991-1992. Fish intake by the mother and child was measured by questionnaire. The child's cognitive development was assessed using adaptations of the MacArthur Communicative Development Inventory at 15 months of age and the Denver Developmental Screening Test at 18 months of age. Mercury was measured in umbilical cord tissue for a subset of 1054 children Total mercury concentrations were low and were not associated with neurodevelopment. Fish intake by the mother during pregnancy, and by the infant postnatally, was associated with higher mean developmental scores. For example, the adjusted mean MacArthur comprehension score for children whose mothers consumed fish 4 or more times per week was 72 (95% confidence interval = 71-74), compared with 68 (66-71) among those whose mothers did not consume fish. When fish is not contaminated, moderate fish intake during pregnancy and infancy may benefit development. Copyright 2004 Lippincott Williams and Wilkins JF - Epidemiology (Cambridge, Mass.) AU - Daniels, Julie L AU - Longnecker, Matthew P AU - Rowland, Andrew S AU - Golding, Jean AU - ALSPAC Study Team. University of Bristol Institute of Child Health AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. juliedanielsunc.edu ; ALSPAC Study Team. University of Bristol Institute of Child Health Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 394 EP - 402 VL - 15 IS - 4 SN - 1044-3983, 1044-3983 KW - Mercury KW - FXS1BY2PGL KW - Index Medicus KW - Fetal Blood -- chemistry KW - Mercury -- blood KW - Breast Feeding KW - Humans KW - Linear Models KW - Feeding Behavior KW - Longitudinal Studies KW - Pregnancy KW - Maternal-Fetal Exchange -- physiology KW - Infant KW - United Kingdom -- epidemiology KW - Risk Factors KW - Adult KW - Surveys and Questionnaires KW - Female KW - Male KW - Prenatal Exposure Delayed Effects KW - Cognition -- drug effects KW - Infant Nutritional Physiological Phenomena KW - Seafood -- adverse effects KW - Nervous System -- drug effects KW - Child Development -- drug effects KW - Child Development -- physiology KW - Maternal Nutritional Physiological Phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66672651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fish+intake+during+pregnancy+and+early+cognitive+development+of+offspring.&rft.au=Daniels%2C+Julie+L%3BLongnecker%2C+Matthew+P%3BRowland%2C+Andrew+S%3BGolding%2C+Jean%3BALSPAC+Study+Team.+University+of+Bristol+Institute+of+Child+Health&rft.aulast=Daniels&rft.aufirst=Julie&rft.date=2004-07-01&rft.volume=15&rft.issue=4&rft.spage=394&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 - 2004-09-09 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Epidemiology. 2004 Jul;15(4):383-4 [15232396] Epidemiology. 2005 Jan;16(1):133 [15613962] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The insertional history of an active family of L1 retrotransposons in humans. AN - 66671220; 15197167 AB - As humans contain a currently active L1 (LINE-1) non-LTR retrotransposon family (Ta-1), the human genome database likely provides only a partial picture of Ta-1-generated diversity. We used a non-biased method to clone Ta-1 retrotransposon-containing loci from representatives of four ethnic populations. We obtained 277 distinct Ta-1 loci and identified an additional 67 loci in the human genome database. This collection represents approximately 90% of the Ta-1 population in the individuals examined and is thus more representative of the insertional history of Ta-1 than the human genome database, which lacked approximately 40% of our cloned Ta-1 elements. As both polymorphic and fixed Ta-1 elements are as abundant in the GC-poor genomic regions as in ancestral L1 elements, the enrichment of L1 elements in GC-poor areas is likely due to insertional bias rather than selection. Although the chromosomal distribution of Ta-1 inserts is generally a function of chromosomal length and gene density, chromosome 4 significantly deviates from this pattern and has been much more hospitable to Ta-1 insertions than any other chromosome. Also, the intra-chromosomal distribution of Ta-1 elements is not uniform. Ta-1 elements tend to cluster, and the maximal gaps between Ta-1 inserts are larger than would be expected from a model of uniform random insertion. Copyright 2004 Cold Spring Harbor Laboratory Press ISSN JF - Genome research AU - Boissinot, Stéphane AU - Entezam, Ali AU - Young, Lynn AU - Munson, Peter J AU - Furano, Anthony V AD - Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1221 EP - 1231 VL - 14 IS - 7 SN - 1088-9051, 1088-9051 KW - Retroelements KW - 0 KW - Index Medicus KW - Genome, Human KW - Consensus Sequence -- genetics KW - Polymorphism, Genetic -- genetics KW - Humans KW - GC Rich Sequence -- genetics KW - Genetic Variation -- genetics KW - Chromosome Mapping -- statistics & numerical data KW - Databases, Genetic KW - Sequence Alignment -- methods KW - Male KW - Ethnic Groups -- genetics KW - Chromosomes, Human -- genetics KW - Statistical Distributions KW - Retroelements -- genetics KW - Mutagenesis, Insertional -- genetics KW - Evolution, Molecular KW - Long Interspersed Nucleotide Elements -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66671220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+research&rft.atitle=The+insertional+history+of+an+active+family+of+L1+retrotransposons+in+humans.&rft.au=Boissinot%2C+St%C3%A9phane%3BEntezam%2C+Ali%3BYoung%2C+Lynn%3BMunson%2C+Peter+J%3BFurano%2C+Anthony+V&rft.aulast=Boissinot&rft.aufirst=St%C3%A9phane&rft.date=2004-07-01&rft.volume=14&rft.issue=7&rft.spage=1221&rft.isbn=&rft.btitle=&rft.title=Genome+research&rft.issn=10889051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-03 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Biol Evol. 2000 Jun;17(6):915-28 [10833198] Nat Genet. 2000 Apr;24(4):363-7 [10742098] Mol Cell Biol. 2001 Feb;21(4):1429-39 [11158327] Nature. 2001 Feb 15;409(6822):860-921 [11237011] Mol Biol Evol. 2001 Jun;18(6):926-35 [11371580] Annu Rev Genet. 2001;35:501-38 [11700292] Mol Biol Evol. 2001 Dec;18(12):2186-94 [11719568] Genome Res. 2001 Dec;11(12):2050-8 [11731495] RNA. 2002 Mar;8(3):345-56 [12003494] Nat Genet. 2002 Jul;31(3):241-7 [12053178] Am J Hum Genet. 2002 Aug;71(2):312-26 [12070800] Genomics. 2002 Oct;80(4):402-6 [12376094] Nat Genet. 2002 Dec;32(4):655-60 [12415270] Nature. 2002 Dec 5;420(6915):520-62 [12466850] Am J Hum Genet. 2003 Apr;72(4):823-38 [12632328] Hum Genet. 2003 May;112(5-6):527-33 [12601470] Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5280-5 [12682288] Nucleic Acids Res. 2003 Aug 1;31(15):4385-90 [12888497] Nat Genet. 2003 Sep;35(1):41-8 [12897783] Proc Natl Acad Sci U S A. 1990 Apr;87(7):2531-5 [2157203] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] J Mol Biol. 1995 Feb 24;246(3):401-417 [7877164] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1872-7 [9050872] J Mol Evol. 1998 Sep;47(3):292-301 [9732456] Biochemistry. 1998 Dec 22;37(51):18081-93 [9922177] Hum Mol Genet. 1999 Aug;8(8):1557-60 [10401005] Nat Genet. 2003 Nov;35(3):221-8 [14517553] Nat Genet. 2003 Dec;35(4):363-6 [14625551] J Mol Biol. 1986 Jan 20;187(2):291-304 [3009828] Mol Cell Biol. 1988 Apr;8(4):1385-97 [2454389] Nucleic Acids Res. 1989 Jan 11;17(1):452 [2911481] Prog Nucleic Acid Res Mol Biol. 2000;64:255-94 [10697412] Genome Res. 2000 Oct;10(10):1496-508 [11042149] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endotoxin-induced uveitis in cyclooxygenase-2-deficient mice. AN - 66669784; 15223810 AB - Endotoxin-induced uveitis (EIU) is a model that mimics human acute anterior uveitis. Cyclooxygenase (COX)-2 is an enzyme that initiates the conversion of arachidonic acid (AA) into prostaglandins (PGs), whereas 5-lipoxygenase (5-LO) generates leukotrienes (LT). The purpose of this study was to delineate the role of COX-2 in acute ocular inflammation. EIU was induced in wild-type (WT), heterozygotic (COX-2(+/-)) and COX-2 null (COX-2(-/-)) mice by injection of lipopolysaccharide (LPS). Other mice were coinjected with LPS and IFN gamma. Ocular histology, serum cytokines, and AA products determined by ELISA, and relevant ocular messengers determined by RT-PCR were compared among the different groups. Histology showed that the EIU score was significantly enhanced in COX-2(-/-) mice in comparison to WT and COX-2(+/-). PGE(2) was increased in WT and COX-2(+/-) EIU but not in COX-2(-/-) EIU. LTB(4) in serum and ocular 5-LO transcripts were increased in COX-2(-/-) EIU mice in comparison with WT and COX-2(+/-) EIU mice. IL-6 increased, whereas IFN gamma decreased both in serum and ocular transcripts in COX-2(-/-) EIU mice in comparison with WT and COX-2(+/-). Furthermore, EIU was suppressed in mice treated with recombinant IFN gamma, as shown by the decreased EIU scores, the presence of serum LTB(4) and IL-6 and ocular 5-LO and IL-6 mRNA, and the increases in serum IFN gamma and ocular IFN gamma, particularly in COX-2(-/-) mice. These data suggest that disturbance of the AA pathway exacerbates EIU in COX-2-deficient mice. IFN gamma moderately reverses this exacerbation and protects against EIU. JF - Investigative ophthalmology & visual science AU - Tuo, Jingsheng AU - Tuaillon, Nadine AU - Shen, DeFen AU - Chan, Chi-Chao AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 2306 EP - 2313 VL - 45 IS - 7 SN - 0146-0404, 0146-0404 KW - Interleukin-6 KW - 0 KW - Isoenzymes KW - Lipopolysaccharides KW - Recombinant Proteins KW - Leukotriene B4 KW - 1HGW4DR56D KW - Arachidonic Acid KW - 27YG812J1I KW - Interferon-gamma KW - 82115-62-6 KW - Arachidonate 5-Lipoxygenase KW - EC 1.13.11.34 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Animals KW - Interferon-gamma -- genetics KW - Leukotriene B4 -- blood KW - Dinoprostone -- metabolism KW - Interleukin-6 -- metabolism KW - Interleukin-6 -- genetics KW - Interferon-gamma -- metabolism KW - Interferon-gamma -- pharmacology KW - Enzyme-Linked Immunosorbent Assay KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Arachidonate 5-Lipoxygenase -- genetics KW - Arachidonic Acid -- metabolism KW - Mice, Knockout KW - Uveitis, Anterior -- enzymology KW - Prostaglandin-Endoperoxide Synthases -- deficiency KW - Uveitis, Anterior -- prevention & control KW - Uveitis, Anterior -- chemically induced KW - Isoenzymes -- deficiency KW - Uveitis, Anterior -- pathology KW - Lipopolysaccharides -- toxicity KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Salmonella typhimurium KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66669784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endotoxin-induced+uveitis+in+cyclooxygenase-2-deficient+mice.&rft.au=Tuo%2C+Jingsheng%3BTuaillon%2C+Nadine%3BShen%2C+DeFen%3BChan%2C+Chi-Chao&rft.aulast=Tuo&rft.aufirst=Jingsheng&rft.date=2004-07-01&rft.volume=45&rft.issue=7&rft.spage=2306&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 - 2004-07-27 N1 - Date created - 2004-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad-binding defective mutant of transforming growth factor beta type I receptor enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. AN - 66669058; 15231662 AB - The role of transforming growth factor beta (TGF-beta) in carcinogenesis is complex, with tumor suppressor and pro-oncogenic activities depending on the particular tumor cell and its stage in malignant progression. We previously have demonstrated in breast cancer cell lines that Smad2/3 signaling played a dominant role in mediating tumor suppressor effects on well-differentiated breast cancer cell lines grown as xenografts and prometastatic effects on a more invasive, metastatic cell line. Our present data based on selective interference with activation of endogenous Smad2 and Smad3 by stable expression of a mutant form of the TGF-beta type I receptor (RImL45) unable to bind Smad2/3 but with a functional kinase again show that reduction in Smad2/3 signaling by expression of RImL45 enhanced the malignancy of xenografted tumors of the well-differentiated MCF10A-derived tumor cell line MCF10CA1h, resulting in formation of larger tumors with a higher proliferative index and more malignant histologic features. In contrast, expression of RImL45 in the more aggressive MCF10CA1a cell line strongly suppressed formation of lung metastases following tail vein injection. These results suggest a causal, dominant role for the endogenous Smad2/3 signaling pathway in the tumor suppressor and prometastatic activities of TGF-beta in these cells. Using an in vitro assay, we further show that non-Smad signaling pathways, including p38 and c-Jun NH(2)-terminal kinase, cooperate with TGF-beta/Smads in enhancing migration of metastatic MCF10CA1a cells, but that, although necessary for migration, these other pathways are not sufficient for metastasis. JF - Cancer research AU - Tian, Fang AU - Byfield, Stacey DaCosta AU - Parks, W Tony AU - Stuelten, Christina H AU - Nemani, Deepa AU - Zhang, Ying E AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 4523 EP - 4530 VL - 64 IS - 13 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - Receptors, Transforming Growth Factor beta KW - SMAD2 protein, human KW - SMAD3 protein, human KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - 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 - Animals KW - Humans KW - Cell Line, Tumor KW - Mice KW - Mice, Nude KW - Transcriptional Activation KW - Transforming Growth Factor beta -- antagonists & inhibitors KW - Transforming Growth Factor beta -- physiology KW - Phosphorylation KW - Neoplasm Metastasis KW - Mutation KW - Breast Neoplasms -- genetics KW - Trans-Activators -- metabolism KW - Receptors, Transforming Growth Factor beta -- genetics KW - Breast Neoplasms -- pathology KW - Trans-Activators -- genetics KW - Receptors, Transforming Growth Factor beta -- metabolism KW - DNA-Binding Proteins -- genetics KW - Breast Neoplasms -- metabolism KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66669058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Smad-binding+defective+mutant+of+transforming+growth+factor+beta+type+I+receptor+enhances+tumorigenesis+but+suppresses+metastasis+of+breast+cancer+cell+lines.&rft.au=Tian%2C+Fang%3BByfield%2C+Stacey+DaCosta%3BParks%2C+W+Tony%3BStuelten%2C+Christina+H%3BNemani%2C+Deepa%3BZhang%2C+Ying+E%3BRoberts%2C+Anita+B&rft.aulast=Tian&rft.aufirst=Fang&rft.date=2004-07-01&rft.volume=64&rft.issue=13&rft.spage=4523&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 - 2004-08-26 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: dose-dependent effects on ERG and retinal histology. AN - 66666351; 15223826 AB - ERG and histologic changes were investigated in normal rabbits after intravitreal implantation of encapsulated cell technology (ECT) devices releasing ciliary neurotrophic factor (CNTF). Fifteen adult New Zealand White albino rabbits had ECT devices secreting CNTF at 22, 5, or 0 ng/d implanted in the superior temporal quadrant of the left eye. The low dose has been shown to produce substantial rescue of photoreceptors in the rcd1 canine model of retinal degeneration. Right eyes were untreated. Ganzfeld dark- and light-adapted ERGs and clinical observations were performed at 5, 15, and 25 days after implantation. Rod a-waves and rod and cone b-waves and outer nuclear layer (ONL) morphology were evaluated at 25 days. Clinical examination showed minimal changes in a few CNTF-treated eyes, including vitreous membranes and engorgement of iris vessels at day 25. Retinas appeared normal. CNTF did not significantly affect the rod a- or b-waves, although the b-wave amplitude tended to be larger in CNTF-treated retinas at low flash intensities. The cone b-wave amplitude was significantly reduced in high-dose eyes at some flash intensities. The ONL area in high-dose eyes was significantly greater because of increased thickness than in fellow retinas. ONL cell size was significantly increased, and staining density decreased in CNTF-treated retinas. CNTF, given by intravitreal ECT device at doses that protect photoreceptors in a canine model of retinal degeneration (5 ng/d), did not adversely affect either rod or cone ERG function of normal rabbit retina. The cone ERG was more sensitive to suppression being reduced, at low flash intensities, by 22 ng/d. Dose-related changes in the ONL and photoreceptor cell nuclei did not represent a toxic effect, because they were not associated with deficits in the rod ERG over a broad range of intensities. JF - Investigative ophthalmology & visual science AU - Bush, Ronald A AU - Lei, Bo AU - Tao, Weng AU - Raz, Dorit AU - Chan, Chi-Chao AU - Cox, Terry A AU - Santos-Muffley, Maria AU - Sieving, Paul A AD - Department of Ophthalmology and Visual Science, Kellogg Eye Center, University of Michigan, Ann Arbor, USA. bushr@nidcd.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 2420 EP - 2430 VL - 45 IS - 7 SN - 0146-0404, 0146-0404 KW - Ciliary Neurotrophic Factor KW - 0 KW - Drug Implants KW - Index Medicus KW - Vitreous Body KW - Animals KW - Photic Stimulation KW - Dark Adaptation KW - Dose-Response Relationship, Drug KW - Rabbits KW - Drug Delivery Systems KW - Ciliary Neurotrophic Factor -- administration & dosage KW - Retina -- physiology KW - Retina -- drug effects KW - Retina -- pathology KW - Electroretinography -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66666351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Encapsulated+cell-based+intraocular+delivery+of+ciliary+neurotrophic+factor+in+normal+rabbit%3A+dose-dependent+effects+on+ERG+and+retinal+histology.&rft.au=Bush%2C+Ronald+A%3BLei%2C+Bo%3BTao%2C+Weng%3BRaz%2C+Dorit%3BChan%2C+Chi-Chao%3BCox%2C+Terry+A%3BSantos-Muffley%2C+Maria%3BSieving%2C+Paul+A&rft.aulast=Bush&rft.aufirst=Ronald&rft.date=2004-07-01&rft.volume=45&rft.issue=7&rft.spage=2420&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 - 2004-07-27 N1 - Date created - 2004-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell-autonomous and cell non-autonomous signaling through endothelin receptor B during melanocyte development. AN - 66663775; 15201217 AB - The endothelin receptor B gene (Ednrb) encodes a G-protein-coupled receptor that is expressed in a variety of cell types and is specifically required for the development of neural crest-derived melanocytes and enteric ganglia. In humans, mutations in this gene are associated with Waardenburg-Shah syndrome, a disorder characterized by pigmentation defects, deafness and megacolon. To address the question of whether melanocyte development depends entirely on a cell-autonomous action of Ednrb, we performed a series of tissue recombination experiments in vitro, using neural crest cell cultures from mouse embryos carrying a novel Ednrb-null allele characterized by the insertion of a lacZ marker gene. The results show that Ednrb is not required for the generation of early neural crest-derived melanoblasts but is required for the expression of the differentiation marker tyrosinase. Tyrosinase expression can be rescued, however, by the addition of Ednrb wild-type neural tubes. These Ednrb wild-type neural tubes need not be capable of generating melanocytes themselves, but must be capable of providing KIT ligand, the cognate ligand for the tyrosine kinase receptor KIT. In fact, soluble KIT ligand is sufficient to induce tyrosinase expression in Ednrb-deficient cultures. Nevertheless, these tyrosinase-expressing, Ednrb-deficient cells do not develop to terminally differentiated, pigmented melanocytes. Pigmentation can be induced, however, by treatment with tetradecanoyl phorbol acetate, which mimics EDNRB signaling, but not by treatment with endothelin 1, which stimulates the paralogous receptor EDNRA. The results suggest that Ednrb plays a significant role during melanocyte differentiation and effects melanocyte development by both cell non-autonomous and cell-autonomous signaling mechanisms. JF - Development (Cambridge, England) AU - Hou, Ling AU - Pavan, William J AU - Shin, Myung K AU - Arnheiter, Heinz AD - Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA. lhou@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 3239 EP - 3247 VL - 131 IS - 14 SN - 0950-1991, 0950-1991 KW - DNA-Binding Proteins KW - 0 KW - Genetic Markers KW - Microphthalmia-Associated Transcription Factor KW - Mitf protein, mouse KW - Phorbol Esters KW - Receptor, Endothelin B KW - Receptors, G-Protein-Coupled KW - Stem Cell Factor KW - Transcription Factors KW - Monophenol Monooxygenase KW - EC 1.14.18.1 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Pigmentation KW - Monophenol Monooxygenase -- metabolism KW - Animals KW - Stem Cell Factor -- metabolism KW - Phorbol Esters -- metabolism KW - Cell Lineage KW - Transcription Factors -- metabolism KW - Cell Differentiation KW - Mice KW - Models, Biological KW - Genotype KW - Alleles KW - beta-Galactosidase -- metabolism KW - Receptors, G-Protein-Coupled -- metabolism KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Time Factors KW - Mutation KW - Lac Operon KW - Neural Crest -- cytology KW - Cell Division KW - DNA-Binding Proteins -- metabolism KW - Melanocytes -- metabolism KW - Melanocytes -- cytology KW - Receptor, Endothelin B -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66663775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Cell-autonomous+and+cell+non-autonomous+signaling+through+endothelin+receptor+B+during+melanocyte+development.&rft.au=Hou%2C+Ling%3BPavan%2C+William+J%3BShin%2C+Myung+K%3BArnheiter%2C+Heinz&rft.aulast=Hou&rft.aufirst=Ling&rft.date=2004-07-01&rft.volume=131&rft.issue=14&rft.spage=3239&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-30 N1 - Date created - 2004-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exploration of low-dose estrogen effects: identification of No Observed Transcriptional Effect Level (NOTEL). AN - 66663208; 15223774 AB - Identifying a minimal dose capable of eliciting a biological response is a fundamental issue in a number of scientific fields, including: drug development, signal transduction research, and environmental toxicology. Frequently, proliferation, viability, and other assays based on the cellular response to a treatment are used to assess the threshold dose for minimal activity. Here we propose a novel approach for identifying the effects of low dose treatments and pinpointing the threshold dose. Using microarrays, we examined the transcriptional response of a hormone responsive breast cancer cell line (MCF-7) stimulated with various concentrations of estrogen. Previous studies have focused on transcriptional responses to physiologically relevant concentrations of estrogen. However, relatively few studies have examined the transcriptional effects of concentrations below normal physiologic levels. These doses may not stimulate the expression of any genes or, alternatively, may regulate a different subset of genes that had not been previously characterized as estrogen responsive. We used gene expression profiling, coupled with a detailed analysis of replicates, to measure estrogen effects on many transcriptional targets and found that only physiologically relevant doses of estrogen (1 x 10(-10) M and higher) were capable of inducing a transcriptional response. This study demonstrates the utility of gene expression profiling as a means to identify concentrations that do not elicit a change in gene expression, or simply a No Observed Transcriptional Effect Level (NOTEL). The identification of a NOTEL for a given compound may be beneficial in several different scientific disciplines. For example, in the development of therapeutic drugs, a NOTEL could be used to identify doses of pharmaceutical compounds that are no longer effective at modulating the expression of biomarkers of efficacy. JF - Toxicologic pathology AU - Lobenhofer, Edward K AU - Cui, Xiangqin AU - Bennett, Lee AU - Cable, P LouAnn AU - Merrick, B Alex AU - Churchill, Gary A AU - Afshari, Cynthia A AD - National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. elobenhofer@paragen.com PY - 2004 SP - 482 EP - 492 VL - 32 IS - 4 SN - 0192-6233, 0192-6233 KW - Estrogens KW - 0 KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Breast Neoplasms -- genetics KW - Analysis of Variance KW - No-Observed-Adverse-Effect Level KW - Oligonucleotide Array Sequence Analysis KW - Breast Neoplasms -- pathology KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line, Tumor KW - Reverse Transcriptase Polymerase Chain Reaction KW - Female KW - Gene Expression Regulation, Neoplastic KW - Estrogens -- genetics KW - Transcription, Genetic -- drug effects KW - Epithelial Cells -- drug effects KW - Estrogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66663208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Exploration+of+low-dose+estrogen+effects%3A+identification+of+No+Observed+Transcriptional+Effect+Level+%28NOTEL%29.&rft.au=Lobenhofer%2C+Edward+K%3BCui%2C+Xiangqin%3BBennett%2C+Lee%3BCable%2C+P+LouAnn%3BMerrick%2C+B+Alex%3BChurchill%2C+Gary+A%3BAfshari%2C+Cynthia+A&rft.aulast=Lobenhofer&rft.aufirst=Edward&rft.date=2004-07-01&rft.volume=32&rft.issue=4&rft.spage=482&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 - 2005-02-15 N1 - Date created - 2004-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for the involvement of SDF-1 and CXCR4 in the disruption of endothelial cell-branching morphogenesis and angiogenesis by TNF-alpha and IFN-gamma. AN - 66663052; 15075355 AB - Vigorous inflammatory responses are associated with tissue damage, particularly when toxic levels of inflammatory cytokines are produced. Despite proangiogenic factors being present early at sites of inflammation, vascular repair occurs toward the end of the inflammatory response, suggesting modulation of the proangiogenic response. Endogenous inhibitors of angiogenesis induced during acute inflammation are poorly characterized. Here, we looked for endothelial cell-derived modulators of angiogenesis that may account for delayed neovascularization during inflammation. Gene profiling of endothelial cells showed that the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) selectively promote expression of the antiangiogenic molecules, IFN-inducible protein-10, monokine induced by IFN-gamma, tryptophanyl-tRNA synthetase, and tissue inhibitor of metalmetalloproteinase-1, and inhibit expression of the proangiogenic molecules, platelet-endothelial cell adhesion molecule-1, vascular endothelial growth factor receptor-2, stromal cell-derived factor-1 (SDF-1), collagen type IV, endothelial cell growth factor-1, and carcinoembryonic antigen-related cell adhesion molecule-1. Reduced endothelial cell expression of SDF-1 protein by TNF-alpha and IFN-gamma disrupts extracellular matrix-dependent endothelial cell tube formation, an in vitro morphogenic process that recapitulates critical steps in angiogenesis. Replacement of SDF-1 onto the endothelial cell surface reconstitutes this morphogenic process. In vivo, TNF-alpha and IFN-gamma inhibit growth factor-induced angiogenesis and SDF-1 expression in endothelial cells. These results demonstrate that SDF-1/CXC chemokine receptor-4 constitutes a TNF-alpha- and IFN-gamma-regulated signaling system that plays a critical role in mediating angiogenesis inhibition by these inflammatory cytokines. JF - Journal of leukocyte biology AU - Salvucci, Ombretta AU - Basik, Mark AU - Yao, Lei AU - Bianchi, Rossella AU - Tosato, Giovanna AD - Center for Cancer Research, National Cancer Institute, Building 10, Room 12N226, MSC 1907, Bethesda, MD 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 217 EP - 226 VL - 76 IS - 1 SN - 0741-5400, 0741-5400 KW - CXCL12 protein, human KW - 0 KW - Chemokine CXCL12 KW - Chemokines, CXC KW - Receptors, CXCR4 KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Signal Transduction -- physiology KW - Gene Expression Profiling KW - Blotting, Western KW - Oligonucleotide Array Sequence Analysis KW - Cells, Cultured KW - Humans KW - Signal Transduction -- drug effects KW - Neovascularization, Pathologic -- metabolism KW - Up-Regulation KW - Reverse Transcriptase Polymerase Chain Reaction KW - Immunohistochemistry KW - Image Processing, Computer-Assisted KW - Endothelial Cells -- drug effects KW - Endothelial Cells -- physiology KW - Receptors, CXCR4 -- biosynthesis KW - Chemokines, CXC -- biosynthesis KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Receptors, CXCR4 -- drug effects KW - Interferon-gamma -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66663052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+for+the+involvement+of+SDF-1+and+CXCR4+in+the+disruption+of+endothelial+cell-branching+morphogenesis+and+angiogenesis+by+TNF-alpha+and+IFN-gamma.&rft.au=Salvucci%2C+Ombretta%3BBasik%2C+Mark%3BYao%2C+Lei%3BBianchi%2C+Rossella%3BTosato%2C+Giovanna&rft.aulast=Salvucci&rft.aufirst=Ombretta&rft.date=2004-07-01&rft.volume=76&rft.issue=1&rft.spage=217&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 - 2004-08-03 N1 - Date created - 2004-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted disruption of the IA-2beta gene causes glucose intolerance and impairs insulin secretion but does not prevent the development of diabetes in NOD mice. AN - 66661580; 15220191 AB - Insulinoma-associated protein (IA)-2beta, also known as phogrin, is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase family and is located in dense-core secretory vesicles. In patients with type 1 diabetes, autoantibodies to IA-2beta appear years before the development of clinical disease. The genomic structure and function of IA-2beta, however, is not known. In the present study, we determined the genomic structure of IA-2beta and found that both human and mouse IA-2beta consist of 23 exons and span approximately 1,000 and 800 kb, respectively. With this information, we prepared a targeting construct and inactivated the mouse IA-2beta gene as demonstrated by lack of IA-2beta mRNA and protein expression. The IA-2beta(-/-) mice, in contrast to wild-type controls, showed mild glucose intolerance and impaired glucose-stimulated insulin secretion. Knockout of the IA-2beta gene in NOD mice, the most widely studied animal model for human type 1 diabetes, failed to prevent the development of cyclophosphamide-induced diabetes. We conclude that IA-2beta is involved in insulin secretion, but despite its importance as a major autoantigen in human type 1 diabetes, it is not required for the development of diabetes in NOD mice. JF - Diabetes AU - Kubosaki, Atsutaka AU - Gross, Steffen AU - Miura, Junnosuke AU - Saeki, Keiichi AU - Zhu, Min AU - Nakamura, Shinichiro AU - Hendriks, Wiljan AU - Notkins, Abner Louis AD - Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4322, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1684 EP - 1691 VL - 53 IS - 7 SN - 0012-1797, 0012-1797 KW - Autoantigens KW - 0 KW - Immunosuppressive Agents KW - Insulin KW - Membrane Proteins KW - Cyclophosphamide KW - 8N3DW7272P KW - PTPRN2 protein, human KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 1 KW - Protein Tyrosine Phosphatases KW - Receptor-Like Protein Tyrosine Phosphatases, Class 8 KW - Glucose KW - IY9XDZ35W2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Genome, Human KW - Exons KW - Mice, Inbred NOD KW - Diabetes Mellitus -- chemically induced KW - Humans KW - Autoantigens -- genetics KW - Diabetes Mellitus -- genetics KW - Mice KW - Genome KW - Mice, Knockout KW - Glucose -- pharmacology KW - Molecular Sequence Data KW - Male KW - Female KW - Protein Tyrosine Phosphatases -- genetics KW - Glucose Intolerance -- genetics KW - Diabetes Mellitus, Type 1 -- genetics KW - Insulin -- secretion KW - Membrane Proteins -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66661580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Targeted+disruption+of+the+IA-2beta+gene+causes+glucose+intolerance+and+impairs+insulin+secretion+but+does+not+prevent+the+development+of+diabetes+in+NOD+mice.&rft.au=Kubosaki%2C+Atsutaka%3BGross%2C+Steffen%3BMiura%2C+Junnosuke%3BSaeki%2C+Keiichi%3BZhu%2C+Min%3BNakamura%2C+Shinichiro%3BHendriks%2C+Wiljan%3BNotkins%2C+Abner+Louis&rft.aulast=Kubosaki&rft.aufirst=Atsutaka&rft.date=2004-07-01&rft.volume=53&rft.issue=7&rft.spage=1684&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AJ583055; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. AN - 66661578; 15226321 AB - Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC. Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m(2) intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P =.32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group. In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Dahut, William L AU - Gulley, James L AU - Arlen, Philip M AU - Liu, Yinong AU - Fedenko, Katherine M AU - Steinberg, Seth M AU - Wright, John J AU - Parnes, Howard AU - Chen, Clara C AU - Jones, Elizabeth AU - Parker, Catherine E AU - Linehan, W Marston AU - Figg, William D AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 2532 EP - 2539 VL - 22 IS - 13 SN - 0732-183X, 0732-183X KW - Taxoids KW - 0 KW - docetaxel KW - 15H5577CQD KW - Thalidomide KW - 4Z8R6ORS6L KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Prostate-Specific Antigen -- analysis KW - Administration, Oral KW - Disease-Free Survival KW - Infusions, Intravenous KW - Aged, 80 and over KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Thalidomide -- administration & dosage KW - Middle Aged KW - Male KW - Taxoids -- administration & dosage KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66661578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+phase+II+trial+of+docetaxel+plus+thalidomide+in+androgen-independent+prostate+cancer.&rft.au=Dahut%2C+William+L%3BGulley%2C+James+L%3BArlen%2C+Philip+M%3BLiu%2C+Yinong%3BFedenko%2C+Katherine+M%3BSteinberg%2C+Seth+M%3BWright%2C+John+J%3BParnes%2C+Howard%3BChen%2C+Clara+C%3BJones%2C+Elizabeth%3BParker%2C+Catherine+E%3BLinehan%2C+W+Marston%3BFigg%2C+William+D&rft.aulast=Dahut&rft.aufirst=William&rft.date=2004-07-01&rft.volume=22&rft.issue=13&rft.spage=2532&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 - 2004-09-03 N1 - Date created - 2004-06-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2005 Mar 20;23(9):2113; author reply 2113-4 [15774812] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Whole-body biodistribution and radiation dosimetry estimates for the PET dopamine transporter probe 18F-FECNT in non-human primates. AN - 66659851; 15208503 AB - 2 beta-Carbomethoxy-3-(4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane (18F-FECNT) is a selective radioligand for the in vivo quantification of dopamine transporters by using positron emission tomography. The aim of the current study was to quantify the distribution of radioactivity in three rhesus monkeys after the injection of approximately 185 MBq (5 mCi) of 18F-FECNT. Whole-body images were acquired at 23-30 time points for a total of 220 min following injection of the radioligand. Source organs were identified at each time point from planar images. The peak activities in planar images in the six identified source organs (expressed as per cent injected dose (%ID)) were lungs (16.5%ID at 2 min), kidneys (12.5%ID at 3 min), brain (9.5%ID at 6 min), liver (7.5%ID at 3 min), red bone marrow (3.5%ID at 12 min), and urinary bladder (2%ID at 98 min). Radiation absorbed doses were calculated using the gastrointestinal tract model in two ways: (1) assuming no urine voiding, and (2) using a dynamic bladder model with voiding intervals of 2.4 and 4.8 h. Using the gastrointestinal tract model and dynamic bladder model with a voiding interval 4.8 h, the three organs with highest exposure (in mu Gy.MBq(-1) (mrad.mCi(-1)) were kidneys 75.68 (280), lungs 44.86 (166) and urinary bladder 58.38 (216). Effective doses estimated with and without urine voiding were in the range 21.35-22.70 mu Gy.MBq(-1) (79-84 mrad.mCi(-1)). The estimated radiation burden of 18F-FECNT is relatively modest and would allow multiple scans per research subject per year. JF - Nuclear medicine communications AU - Tipre, Dnyanesh N AU - Fujita, Masahiro AU - Chin, Frederick T AU - Seneca, Nicholas AU - Vines, Douglas AU - Liow, Jeih-San AU - Pike, Victor W AU - Innis, Robert B AD - Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bldg 1 Rm. B3-10, 1 Center Drive, Bethesda, MD 20892-0135, USA. TipreD@intra.nimh.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 737 EP - 742 VL - 25 IS - 7 SN - 0143-3636, 0143-3636 KW - 2-carbomethoxy-3-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Nortropanes KW - Radiopharmaceuticals KW - Index Medicus KW - Radiopharmaceuticals -- pharmacokinetics KW - Radiation Dosage KW - Animals KW - Relative Biological Effectiveness KW - Positron-Emission Tomography -- methods KW - Humans KW - Body Burden KW - Metabolic Clearance Rate KW - Organ Specificity KW - Macaca mulatta KW - Tissue Distribution KW - Drug Evaluation, Preclinical KW - Male KW - Whole-Body Counting -- methods KW - Nortropanes -- pharmacokinetics KW - Nerve Tissue Proteins -- metabolism KW - Brain -- metabolism KW - Radiometry -- methods KW - Membrane Transport Proteins -- metabolism KW - Brain -- diagnostic imaging KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66659851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nuclear+medicine+communications&rft.atitle=Whole-body+biodistribution+and+radiation+dosimetry+estimates+for+the+PET+dopamine+transporter+probe+18F-FECNT+in+non-human+primates.&rft.au=Tipre%2C+Dnyanesh+N%3BFujita%2C+Masahiro%3BChin%2C+Frederick+T%3BSeneca%2C+Nicholas%3BVines%2C+Douglas%3BLiow%2C+Jeih-San%3BPike%2C+Victor+W%3BInnis%2C+Robert+B&rft.aulast=Tipre&rft.aufirst=Dnyanesh&rft.date=2004-07-01&rft.volume=25&rft.issue=7&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=Nuclear+medicine+communications&rft.issn=01433636&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-07 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bleeding patterns after vaginal misoprostol for treatment of early pregnancy failure. AN - 66657743; 15178656 AB - Dilatation and curettage (D&C) has been the usual treatment for early pregnancy failure (EPF). Medical management with misoprostol may be an effective alternative. Bleeding patterns during and after medical management of EPF are unknown. A prospective cohort study was conducted at University-based clinics and physician offices. Eighty women <11 weeks estimated gestational age with a diagnosis of missed abortion or fetal demise were enrolled. Treatment consisted of either 800 micro g of moistened (2 ml of saline) or dry vaginal misoprostol. Self-reported bleeding and sanitary product usage were recorded in a daily 2 week diary. Haemoglobin was assessed at enrollment and 2 weeks later. After misoprostol treatment, patients reported bleeding or spotting every day for the 14 days observed. Self-assessed heavy bleeding days were few (median 3) and usually occurred immediately after treatment. Sanitary pad use was highly variable (mean 30.5, range 2-125 pads over the 2 week period) and not related to changes in haemoglobin. The mean decrease in haemoglobin was 0.5 g/dl (SD 1.2). Complete expulsion without D&C occurred in 85% of subjects. Bleeding for at least 2 weeks after vaginal misoprostol for EPF is common. Heavy bleeding is usually limited to a few days after treatment. Clinically important changes in haemoglobin are rare. JF - Human reproduction (Oxford, England) AU - Davis, A R AU - Robilotto, C M AU - Westhoff, C L AU - Forman, S AU - Zhang, J AU - NICHD Management of Early Pregnancy Failure Trial group AD - Department of Obstetrics and Gynecology, Columbia University, New York, NY 10032, USA. ard4@columbia.edu ; NICHD Management of Early Pregnancy Failure Trial group Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1655 EP - 1658 VL - 19 IS - 7 SN - 0268-1161, 0268-1161 KW - Abortifacient Agents, Nonsteroidal KW - 0 KW - Hemoglobins KW - Misoprostol KW - 0E43V0BB57 KW - Index Medicus KW - Medical Records KW - Pregnancy Trimester, First KW - Hemoglobins -- metabolism KW - Humans KW - Adult KW - Administration, Intravaginal KW - Time Factors KW - Female KW - Pregnancy KW - Uterine Hemorrhage -- physiopathology KW - Uterine Hemorrhage -- blood KW - Misoprostol -- adverse effects KW - Abortifacient Agents, Nonsteroidal -- adverse effects KW - Pregnancy Complications -- drug therapy KW - Abortion, Incomplete -- drug therapy KW - Uterine Hemorrhage -- chemically induced KW - Misoprostol -- administration & dosage KW - Abortifacient Agents, Nonsteroidal -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66657743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reproduction+%28Oxford%2C+England%29&rft.atitle=Bleeding+patterns+after+vaginal+misoprostol+for+treatment+of+early+pregnancy+failure.&rft.au=Davis%2C+A+R%3BRobilotto%2C+C+M%3BWesthoff%2C+C+L%3BForman%2C+S%3BZhang%2C+J%3BNICHD+Management+of+Early+Pregnancy+Failure+Trial+group&rft.aulast=Davis&rft.aufirst=A&rft.date=2004-07-01&rft.volume=19&rft.issue=7&rft.spage=1655&rft.isbn=&rft.btitle=&rft.title=Human+reproduction+%28Oxford%2C+England%29&rft.issn=02681161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-13 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic carcinoma. AN - 66656590; 15221998 AB - Cyclooxygenase-2 (COX-2) is up-regulated frequently and may constitute a promising therapeutic target in patients with pancreatic ductal adenocarcinoma (PDAC). Patients with advanced PDAC who had progressive disease after gemcitabine-based chemotherapy were eligible for this pilot study. Treatment was comprised of oral celecoxib (400 mg twice daily) and protracted intravenous (i.v.) infusion 5-fluorouracil (5-FU) (200 mg/m(2) per day), both given continuously for a maximum of 9 treatment months, in the absence of disease progression or unacceptable toxicity. Patients were examined weekly for toxicity and were restaged every 6-8 weeks for tumor assessment. Seventeen patients entered the study. Asymptomatic transaminase elevation was the most common toxicity and reached NCI-CTC (version 3.0) Grade 3-4 in 4 of 133 treatment weeks. No other hematologic or nonhematologic toxicity > Grade 2 was observed. Four patients discontinued celecoxib due to upper gastrointestinal tract toxicity. Two confirmed partial responses (durations of 23 weeks and 68 weeks, respectively) and 2 patients with stable disease (durations of 10 weeks and 13 weeks, respectively) were observed for an overall response rate of 12% (95% confidence interval, 0-27%) in the intent-to-treat population. A significant decrease (> or = 50%) in serum CA 19.9 levels was observed in 3 of 9 evaluable patients. The median time to disease progression was 8 weeks, and the median overall survival was 15 weeks. The combination of oral celecoxib and 5-FU by protracted i.v. infusion was found to be feasible and well tolerated, and was capable of inducing durable objective responses, even in patients with far advanced, gemcitabine-resistant/refractory PDAC. Further exploration of COX-2 inhibitor/fluropyrimidine combinations is warranted. Copyright 2004 American Cancer Society. JF - Cancer AU - Milella, Michele AU - Gelibter, Alain AU - Di Cosimo, Serena AU - Bria, Emilio AU - Ruggeri, Enzo Maria AU - Carlini, Paolo AU - Malaguti, Paola AU - Pellicciotta, Mario AU - Terzoli, Edmondo AU - Cognetti, Francesco AD - Divisions of Medical Oncology "A" and "C", Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. milella@ifo.it Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 133 EP - 138 VL - 101 IS - 1 SN - 0008-543X, 0008-543X KW - Carcinoembryonic Antigen KW - 0 KW - Pyrazoles KW - Sulfonamides KW - Celecoxib KW - JCX84Q7J1L KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Disease Progression KW - Aged KW - Pilot Projects KW - Sulfonamides -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Sulfonamides -- adverse effects KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Carcinoembryonic Antigen -- blood KW - Carcinoembryonic Antigen -- drug effects KW - Female KW - Male KW - Pancreatic Neoplasms -- pathology KW - Pancreatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66656590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pilot+study+of+celecoxib+and+infusional+5-fluorouracil+as+second-line+treatment+for+advanced+pancreatic+carcinoma.&rft.au=Milella%2C+Michele%3BGelibter%2C+Alain%3BDi+Cosimo%2C+Serena%3BBria%2C+Emilio%3BRuggeri%2C+Enzo+Maria%3BCarlini%2C+Paolo%3BMalaguti%2C+Paola%3BPellicciotta%2C+Mario%3BTerzoli%2C+Edmondo%3BCognetti%2C+Francesco&rft.aulast=Milella&rft.aufirst=Michele&rft.date=2004-07-01&rft.volume=101&rft.issue=1&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-16 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A potential cholinergic mechanism of procaine's limbic activation. AN - 66654808; 14997171 AB - The local anesthetic procaine, when administered to humans intravenously (i.v.), yields brief intense emotional and sensory experiences, and concomitant increases in anterior paralimbic cerebral blood flow, as measured by positron emission tomography (PET). Procaine's high muscarinic affinity, together with the distribution of muscarinic receptors that overlaps with brain regions activated by procaine, suggests a muscarinic contribution to procaine's emotional and sensory effects. This study evaluates the effects of procaine on cerebral muscarinic cholinergic receptors in the anesthetized rhesus monkey. Whole brain and regional muscarinic receptor binding was measured before and after procaine administration on the same day in three anesthetized rhesus monkeys with PET and the radiotracer 3-(3-(3[18F]fluoropropylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([18F]FP-TZTP), a cholinergic ligand that has preferential binding to muscarinic (M(2)) receptors. On separate days each animal received six different doses of i.v. procaine in a randomized fashion. Procaine blocked up to approximately 90% of [18F]FP-TZTP specific binding globally in a dose-related manner. There were no regional differences in procaine's inhibitory concentration for 50% blockade (IC50) for [18F]FP-TZTP. Tracer delivery, which was highly correlated to cerebral blood flow in previous monkey studies, was significantly increased at all doses of procaine with the greatest increases occurring near procaine's IC50 for average cortex. Furthermore, anterior limbic regions showed greater increases in tracer delivery than nonlimbic regions. Procaine has high affinity to muscarinic M2 receptors in vivo in the rhesus monkey. This, as well as a preferential increase of tracer delivery to paralimbic regions, suggests that action at these receptors could contribute to i.v. procaine's emotional and sensory effects in man. These findings are consistent with other evidence of cholinergic modulation of mood and emotion. Copyright 2004 Nature Publishing Group JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Benson, Brenda E AU - Carson, Richard E AU - Kiesewetter, Dale O AU - Herscovitch, Peter AU - Eckelman, William C AU - Post, Robert M AU - Ketter, Terence A AD - Biological Psychiatry Branch, NIMH, NIH, Bethesda, MD 20892-1272, USA. bbenson@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1239 EP - 1250 VL - 29 IS - 7 SN - 0893-133X, 0893-133X KW - Anesthetics, Local KW - 0 KW - FP-TZTP KW - Fluorine Radioisotopes KW - Pyridines KW - Receptors, Muscarinic KW - Thiazoles KW - Procaine KW - 4Z8Y51M438 KW - Index Medicus KW - Animals KW - Fluorine Radioisotopes -- pharmacokinetics KW - Anesthetics, Local -- pharmacology KW - Dose-Response Relationship, Drug KW - Pyridines -- pharmacokinetics KW - Thiazoles -- pharmacokinetics KW - Anesthetics, Local -- administration & dosage KW - Brain Mapping KW - Macaca mulatta KW - Inhibitory Concentration 50 KW - Autoradiography -- methods KW - Radioligand Assay -- methods KW - Male KW - Tomography, Emission-Computed -- methods KW - Limbic System -- drug effects KW - Limbic System -- metabolism KW - Cerebrovascular Circulation -- drug effects KW - Procaine -- pharmacology KW - Procaine -- administration & dosage KW - Receptors, Muscarinic -- physiology KW - Limbic System -- blood supply UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66654808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+potential+cholinergic+mechanism+of+procaine%27s+limbic+activation.&rft.au=Benson%2C+Brenda+E%3BCarson%2C+Richard+E%3BKiesewetter%2C+Dale+O%3BHerscovitch%2C+Peter%3BEckelman%2C+William+C%3BPost%2C+Robert+M%3BKetter%2C+Terence+A&rft.aulast=Benson&rft.aufirst=Brenda&rft.date=2004-07-01&rft.volume=29&rft.issue=7&rft.spage=1239&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 - 2004-08-02 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The nitric oxide donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), protects against cadmium-induced hepatotoxicity in mice. AN - 66653956; 15010501 AB - The nitric oxide (NO) donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), is metabolized by P450 enzymes to release NO within the liver and is effective in protecting against hepatotoxicity of endotoxin and acetaminophen. This study examined the effects of V-PYRRO/NO on cadmium (Cd) hepatotoxicity in mice. Mice were given multiple injections of V-PYRRO/NO (10 mg/kg, s.c. at 2-h intervals) before and after a hepatotoxic dose of Cd (3.7 mg/kg Cd as CdCl2, i.p.). V-PYRRO/NO administration reduced Cd-induced hepatotoxicity as evidenced by reduced serum alanine aminotransferase activity, improved pathology, and reduced hepatic lipid peroxidation. The protection by V-PYRRO/NO was not mediated by altered Cd distribution to the liver or within hepatic subcellular fractions. Similar inductions of metallothionein, a metal-binding protein, were observed in mice receiving Cd alone or Cd plus V-PYRRO/NO. Real-time reverse transcription-polymerase chain reaction analysis revealed that V-PYRRO/NO administration suppressed the expression of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intracellular adhesion molecular-1, and interleukin-6. V-PYRRO/NO also suppressed the expression of acute phase protein genes and genes related to cell-death pathways, such as c-jun/AP-1, nuclear factor-kappaB, early response growth factor-1, heme oxygenase-1, caspase-3, growth arrest, and DNA-damaging protein-153. In summary, the liver-selective NO donor, V-PYRRO/NO, protects against Cd hepatotoxicity in mice. This protection is not mediated through altered distribution of Cd but may be related to reduced hepatic inflammation, reduced acute phase responses, and the suppression of cell-death-related components. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, Jie AU - Qu, Wei AU - Saavedra, Joseph E AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Instititue of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 18 EP - 24 VL - 310 IS - 1 SN - 0022-3565, 0022-3565 KW - Nitric Oxide Donors KW - 0 KW - O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate KW - Pyrrolidines KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Subcellular Fractions KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Metallothionein -- metabolism KW - Male KW - Chemical and Drug Induced Liver Injury -- prevention & control KW - Pyrrolidines -- therapeutic use KW - Nitric Oxide Donors -- therapeutic use KW - Chemical and Drug Induced Liver Injury -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66653956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+nitric+oxide+donor%2C+O2-vinyl+1-%28pyrrolidin-1-yl%29diazen-1-ium-1%2C2-diolate+%28V-PYRRO%2FNO%29%2C+protects+against+cadmium-induced+hepatotoxicity+in+mice.&rft.au=Liu%2C+Jie%3BQu%2C+Wei%3BSaavedra%2C+Joseph+E%3BWaalkes%2C+Michael+P&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2004-07-01&rft.volume=310&rft.issue=1&rft.spage=18&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 - 2004-09-07 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells. AN - 66653646; 15016654 AB - Cellular inactivation through killer immunoglobulin-like receptors (KIRs) may allow neoplastic cells to evade host natural killer (NK) cell-mediated immunity. Recently, alloreactive NK cells were shown to mediate antileukemic effects against acute myelogenous leukemia (AML) after mismatched transplantation, when KIR ligand incompatibility existed in the direction of graft-versus-host disease (GVHD). Therefore, we investigated whether solid tumor cells would have similar enhanced susceptibility to allogeneic KIR-incompatible NK cells compared with their KIR-matched autologous or allogeneic counterparts. NK populations enriched and cloned from the blood of cancer patients or healthy donors homozygous for HLA-C alleles in group 1 (C-G1) or group 2 (C-G2) were tested in vitro for cytotoxicity against Epstein-Barr virus-transformed lymphoblastic cell lines (EBV-LCLs), renal cell carcinoma (RCC), and melanoma (MEL) cells with or without a matching KIR-inhibitory HLA-C ligand. Allogeneic NK cells were more cytotoxic to tumor targets mismatched for KIR ligands than their KIR ligand-matched counterparts. Bulk NK populations (CD3(-)/CD2(+)/CD56(+)) expanded 10(4)-fold from patients homozygous for C-G1 or C-G2 had enhanced cytotoxicity against KIR ligand-mismatched tumor cells but only minimal cytotoxicity against KIR ligand-matched targets. Further, NK cell lines from C-G1 or C-G2 homozygous cancer patients or healthy donors expanded but failed to kill autologous or KIR-matched MEL and RCC cells yet had significant cytotoxicity (more than 50% lysis at 20:1 effector-target [E/T] ratio) against allogeneic KIR-mismatched tumor lines. These data suggest immunotherapeutic strategies that use KIR-incompatible allogeneic NK cells might have superior antineoplastic effects against solid tumors compared with approaches using autologous NK cells. JF - Blood AU - Igarashi, Takehito AU - Wynberg, Jason AU - Srinivasan, Ramprasad AU - Becknell, Brian AU - McCoy, J Phillip AU - Takahashi, Yoshiyuki AU - Suffredini, Dante A AU - Linehan, W Marston AU - Caligiuri, Michael A AU - Childs, Richard W AD - Hematology Branch, Flow Cytometry Core Facility, National Heart, Lund, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 170 EP - 177 VL - 104 IS - 1 SN - 0006-4971, 0006-4971 KW - Antigens, CD KW - 0 KW - Histocompatibility Antigens Class I KW - Ligands KW - Receptors, Immunologic KW - Receptors, KIR KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Gamma Rays -- adverse effects KW - Homozygote KW - Humans KW - Histocompatibility Antigens Class I -- immunology KW - B-Lymphocytes -- immunology KW - Cell Line, Tumor KW - Histocompatibility Antigens Class I -- genetics KW - Cytotoxicity, Immunologic -- immunology KW - Histocompatibility Testing KW - Antigens, CD -- metabolism KW - Cytotoxicity Tests, Immunologic KW - Herpesvirus 4, Human -- immunology KW - Antigens, CD -- immunology KW - Histocompatibility -- immunology KW - Receptors, Immunologic -- immunology KW - Killer Cells, Natural -- transplantation KW - Histocompatibility -- genetics KW - Immunotherapy, Adoptive -- methods KW - Melanoma -- immunology KW - Killer Cells, Natural -- radiation effects KW - Carcinoma, Renal Cell -- immunology KW - Killer Cells, Natural -- immunology KW - Kidney Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66653646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cytotoxicity+of+allogeneic+NK+cells+with+killer+immunoglobulin-like+receptor+ligand+incompatibility+against+melanoma+and+renal+cell+carcinoma+cells.&rft.au=Igarashi%2C+Takehito%3BWynberg%2C+Jason%3BSrinivasan%2C+Ramprasad%3BBecknell%2C+Brian%3BMcCoy%2C+J+Phillip%3BTakahashi%2C+Yoshiyuki%3BSuffredini%2C+Dante+A%3BLinehan%2C+W+Marston%3BCaligiuri%2C+Michael+A%3BChilds%2C+Richard+W&rft.aulast=Igarashi&rft.aufirst=Takehito&rft.date=2004-07-01&rft.volume=104&rft.issue=1&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-27 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Laulimalide and paclitaxel: a comparison of their effects on tubulin assembly and their synergistic action when present simultaneously. AN - 66649420; 15213302 AB - Previous work has shown that laulimalide, a sponge-derived natural product, resembles paclitaxel in enhancing tubulin assembly and in its effects on cellular microtubules. The two compounds, however, seem to have distinct binding sites on tubulin polymer. Nearly equimolar amounts of tubulin, laulimalide, and paclitaxel are recovered from microtubules formed with both drugs. In the present study, we searched for differences between laulimalide and paclitaxel in their interactions with tubulin polymer. Laulimalide was compared with paclitaxel and epothilone A, a natural product that competes with paclitaxel in binding to microtubules, for assembly properties at different temperatures and for effects of GTP and microtubule-associated proteins on assembly. Although minor differences were observed among the three drugs, their overall effects were highly similar, except that aberrant assembly products were observed more frequently with paclitaxel and that the polymers formed with laulimalide and epothilone A were more stable at 0 degrees C. The most dramatic difference observed between laulimalide and epothilone A was that only laulimalide was able to enhance assembly synergistically with paclitaxel, as would be predicted if the two drugs bound at different sites in polymer. Because stoichiometric amounts of laulimalide and paclitaxel can cause extensive tubulin assembly, maximum synergy was observed at lower temperatures under reaction conditions in which each drug alone is relatively inactive. Laulimalide-induced assembly, like paclitaxel-induced assembly, was inhibited by drugs that inhibit tubulin assembly by binding at either the colchicine- or vinblastine-binding site. When radiolabeled GTP is present in a reaction mixture with either laulimalide or paclitaxel, nucleotide hydrolysis occurs with incorporation of radiolabeled GDP into polymer. JF - Molecular pharmacology AU - Gapud, Eric J AU - Bai, Ruoli AU - Ghosh, Arun K AU - Hamel, Ernest AD - Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnostics, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 113 EP - 121 VL - 66 IS - 1 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Biopolymers KW - Macrolides KW - Microtubule-Associated Proteins KW - Taxoids KW - Tubulin KW - Tubulin Modulators KW - laulimalide KW - Guanosine Triphosphate KW - 86-01-1 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Cattle KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Drug Synergism KW - Hydrolysis KW - Guanosine Triphosphate -- metabolism KW - Microtubule-Associated Proteins -- metabolism KW - Microtubules -- metabolism KW - Tubulin -- metabolism KW - Paclitaxel -- pharmacology KW - Microtubules -- drug effects KW - Taxoids -- pharmacology KW - Taxoids -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66649420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Laulimalide+and+paclitaxel%3A+a+comparison+of+their+effects+on+tubulin+assembly+and+their+synergistic+action+when+present+simultaneously.&rft.au=Gapud%2C+Eric+J%3BBai%2C+Ruoli%3BGhosh%2C+Arun+K%3BHamel%2C+Ernest&rft.aulast=Gapud&rft.aufirst=Eric&rft.date=2004-07-01&rft.volume=66&rft.issue=1&rft.spage=113&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 - 2004-07-15 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor spectrum in the p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) bitransgenic mouse model. AN - 66648782; 15204965 AB - The use of a bitransgenic mouse model for cancer is an effective approach for studying the impact of specific carcinogens and the occurrence of tissue-specific lesions. We studied the novel p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) mouse model because these mice contain a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele, both of which occur frequently in human cancers. Our aim was to characterize the short-term control and chemically induced tumor spectrum in this novel model. Mice were placed on basal semipurified diet containing 20% soy protein for 2 weeks prior to random allocation to groups. Subsequently, 15 male and 15 female mice were administered corn oil vehicle alone or containing benzo(a)pyrene (20 mg/kg body weight) via oral gavage 2 times per week for 10 weeks with subsequent observation for 18 weeks. Mice exhibited lesions characteristic of FVB/N, p53 heterozygous and Tg.AC mouse models. However, an array of unique, novel lesions were observed including uterine leiomyosarcomas, mammary gland carcinomas, mammary squamous cell carcinomas, and parotid salivary gland carcinomas suggesting tissue-specific interactions of the 2 genotypes. Thus, this bitransgenic model may provide further insight into the mechanistic interaction of 2 genes commonly mutated in neoplasia. JF - Toxicologic pathology AU - Martin, Keith R AU - Jokinen, Michael P AU - Honeycutt, Hayden P AU - Quinn, Anita AU - Kari, Frank W AU - Barrett, J Carl AU - French, John E AD - Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS, Research Triangle Park, North Carolina, USA. krm12@psu.edu PY - 2004 SP - 418 EP - 425 VL - 32 IS - 4 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Drug Administration Schedule -- veterinary KW - Animals KW - Alleles KW - Carcinogens -- administration & dosage KW - Gene Silencing KW - Heterozygote KW - Carcinogens -- toxicity KW - Mice KW - Male KW - Female KW - Neoplasms -- veterinary KW - Genes, ras KW - Benzo(a)pyrene -- administration & dosage KW - Neoplasms -- pathology KW - Neoplasms -- classification KW - Genes, p53 KW - Neoplasms -- chemically induced KW - Globins -- genetics KW - Benzo(a)pyrene -- toxicity KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66648782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+spectrum+in+the+p53+heterozygous+zeta+globin-promoted+Tg.AC+%28v-Ha-ras%29+bitransgenic+mouse+model.&rft.au=Martin%2C+Keith+R%3BJokinen%2C+Michael+P%3BHoneycutt%2C+Hayden+P%3BQuinn%2C+Anita%3BKari%2C+Frank+W%3BBarrett%2C+J+Carl%3BFrench%2C+John+E&rft.aulast=Martin&rft.aufirst=Keith&rft.date=2004-07-01&rft.volume=32&rft.issue=4&rft.spage=418&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 - 2005-02-15 N1 - Date created - 2004-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The development of phosphatidylinositol ether lipid analogues as inhibitors of the serine/threonine kinase, Akt. AN - 66647618; 15212619 AB - The serine/threonine kinase Akt is a component of the phosphatidylinositol 3'-kinase/Akt signal transduction pathway that is activated by receptor tyrosine kinases, activated Ras and integrins. As Akt regulates many processes crucial to carcinogenesis, and Akt activation has been observed in human cancers, intense efforts are underway to develop Akt inhibitors as cancer therapeutics. Towards this aim, phosphatidylinositol ether lipid analogues (PIAs), which are structurally similar to the products of phosphatidylinositol 3'-kinase, have been synthesised. PIAs inhibit Akt translocation, phosphorylation and kinase activity. Furthermore, they selectively induce apoptosis in cancer cell lines that depend on Akt for survival. This review will trace the development of PIAs, cover the biological activities of PIAs and discuss future steps and challenges in their development. JF - Expert opinion on investigational drugs AU - Gills, Joell J AU - Dennis, Phillip A AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20889, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 787 EP - 797 VL - 13 IS - 7 KW - Enzyme Inhibitors KW - 0 KW - Phosphatidylinositols KW - Phospholipid Ethers KW - Proto-Oncogene Proteins KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Index Medicus KW - Animals KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - Phospholipid Ethers -- pharmacology KW - Proto-Oncogene Proteins -- antagonists & inhibitors KW - Phosphatidylinositols -- pharmacology KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66647618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=The+development+of+phosphatidylinositol+ether+lipid+analogues+as+inhibitors+of+the+serine%2Fthreonine+kinase%2C+Akt.&rft.au=Gills%2C+Joell+J%3BDennis%2C+Phillip+A&rft.aulast=Gills&rft.aufirst=Joell&rft.date=2004-07-01&rft.volume=13&rft.issue=7&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=1744-7658&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-21 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Susceptibility of rats to mammary gland carcinogenesis by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) varies with age and is associated with the induction of differential gene expression. AN - 66646997; 15215175 AB - 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, induces mammary gland cancer when administered to adolescent female rats (43-day-old). In contrast, mature virgin rats (150-day-old) were resistant to mammary carcinogenesis by PhIP. To explore the possible mechanisms for the age-related differences in susceptibility, PhIP-DNA adduct levels, mutations, and gene expression were examined in glands from 43-day and 150-day-old PhIP-treated rats. In rats of different ages, PhIP-DNA adduct levels detected by the (32)P-post-labeling assay and mutant frequency measured in the lacI reporter gene of Big Blue rats were not statistically different. PhIP-DNA adduct levels, adduct removal, and mutation burden did not appear to account for the variation in carcinogen susceptibility with age. However, cDNA microarray analysis indicated that PhIP treatment differentially altered the profile of gene expression in glands from 43-day-old and 150-day-old rats. In 150-day-old rats, PhIP enhanced the expression of genes associated with differentiation (eg, beta-casein, kappa-casein, whey acidic protein) and induced morphological differentiation. In contrast, in 43-day-old rats, PhIP inhibited the expression of differentiation genes and enhanced cellular proliferation. From 3 hours to 6 weeks after PhIP dosing, the number of clones showing altered expression declined more than 50% in 150-day-old rats but increased fourfold in 43-day-old rats (29 clones versus 194, respectively) suggesting that PhIP induced a cascade of gene expression alterations only in susceptible rats. Genes showing altered expression specifically in 43-day-old rats included the Ras superfamily genes and genes associated with protein synthesis/degradation (lysosomal proteins, heat shock proteins, and proteasomes). The microarray data support the notion that the mechanism of age-dependent susceptibility to mammary gland cancer is largely associated with differential responses in expression of genes involved in cellular differentiation, proliferation, and protein homeostasis. JF - The American journal of pathology AU - Shan, Liang AU - Yu, Minshu AU - Schut, Herman A J AU - Snyderwine, Elizabeth G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, Building 37, National Cancer Institute/NIH, Bethesda, MD 20892-4262, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 191 EP - 202 VL - 165 IS - 1 SN - 0002-9440, 0002-9440 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Disease Susceptibility KW - Oligonucleotide Array Sequence Analysis KW - Aging KW - Cell Division -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Rats KW - Gene Expression Profiling KW - Rats, Sprague-Dawley KW - DNA Adducts -- analysis KW - Cell Differentiation -- drug effects KW - Time Factors KW - Cluster Analysis KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Imidazoles -- toxicity KW - Food KW - Carcinogens -- toxicity KW - Mammary Neoplasms, Experimental -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Susceptibility+of+rats+to+mammary+gland+carcinogenesis+by+the+food-derived+carcinogen+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29+varies+with+age+and+is+associated+with+the+induction+of+differential+gene+expression.&rft.au=Shan%2C+Liang%3BYu%2C+Minshu%3BSchut%2C+Herman+A+J%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Shan&rft.aufirst=Liang&rft.date=2004-07-01&rft.volume=165&rft.issue=1&rft.spage=191&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 - 2004-09-03 N1 - Date created - 2004-06-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochim Biophys Acta. 1995 May 17;1262(1):64-8 [7772601] Int Rev Immunol. 1999;18(5-6):429-48 [10672495] J Natl Cancer Inst. 2000 Aug 16;92(16):1352-4 [10944558] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11391-6 [11005832] Carcinogenesis. 1995 Nov;16(11):2725-31 [7586192] J Cell Biol. 1996 Jul;134(1):25-35 [8698819] Br J Cancer. 1996 Sep;74(5):717-21 [8795573] Biochem Soc Symp. 1998;63:101-13 [9513715] Carcinogenesis. 1998 Jul;19(7):1209-15 [9683179] Carcinogenesis. 1998 Sep;19(9):1573-81 [9771927] Nutr Cancer. 1998;31(3):160-7 [9795967] Carcinogenesis. 1998 Dec;19(12):2181-5 [9886576] Carcinogenesis. 1999 Mar;20(3):353-68 [10190547] Cancer Res. 1999 Apr 1;59(7 Suppl):1765-1771s; discussion 1771s-1772s [10197594] J Cell Sci. 1999 May;112 ( Pt 10):1477-86 [10212142] Science. 1969 Aug 22;165(3895):810-1 [5796556] J Natl Cancer Inst. 1974 Feb;52(2):609-10 [4816015] Biochemistry. 1975 Jul;14(13):2895-903 [1148182] Br J Cancer. 1975 Feb;31(2):189-96 [809048] J Natl Cancer Inst. 1978 Jan;60(1):173-7 [415147] J Natl Cancer Inst. 1978 Dec;61(6):1439-49 [102856] J Natl Cancer Inst. 1978 Dec;61(6):1451-9 [102857] J Mammary Gland Biol Neoplasia. 2000 Apr;5(2):165-85 [11149571] Microsc Res Tech. 2001 Jan 15;52(2):204-23 [11169868] J Mammary Gland Biol Neoplasia. 2001 Jan;6(1):101-13 [11467446] Mol Endocrinol. 2001 Nov;15(11):1993-2009 [11682629] Cell Growth Differ. 2001 Dec;12(12):649-56 [11751460] Ann N Y Acad Sci. 2001 Dec;952:23-35 [11795441] Anal Biochem. 2002 Feb 15;301(2):314-24 [11814302] Eur J Biochem. 2002 Feb;269(4):1209-18 [11856354] Environ Mol Mutagen. 2002;39(2-3):165-70 [11921185] Mol Cell Biochem. 2002 Jan;229(1-2):35-44 [11936845] J Cell Mol Med. 2002 Jan-Mar;6(1):25-48 [12003667] Carcinogenesis. 2002 May;23(5):877-84 [12016163] Surg Oncol. 2002 May;10(4):183-92 [12020673] Bioinformatics. 2002 May;18(5):774-5 [12050079] Proteomics. 2002 Jul;2(7):850-6 [12124930] Cancer Res. 2002 Aug 15;62(16):4540-4 [12183401] Environ Med. 1999 Dec;43(2):79-87 [12296368] Mutat Res. 2002 Sep 30;506-507:145-52 [12351154] Cancer Lett. 2003 Jan 28;189(2):117-28 [12490304] Carcinogenesis. 2002 Dec;23(12):2123-8 [12507937] Endocr Relat Cancer. 2002 Dec;9(4):207-20 [12542399] Curr Med Chem. 2003 Mar;10(6):479-503 [12570694] Nat Rev Cancer. 2003 Mar;3(3):179-92 [12612653] Biochem Biophys Res Commun. 2003 May 9;304(3):505-12 [12729585] Eur J Surg Oncol. 2003 Jun;29(5):475-9 [12798754] Metabolism. 2003 Jul;52(7):810-4 [12870152] J Endocrinol. 1966 Aug;35(4):331-40 [5923706] Am J Pathol. 1979 Sep;96(3):721-36 [112872] Cancer Res. 1980 Aug;40(8 Pt 1):2677-87 [7388818] J Natl Cancer Inst. 1981 Jul;67(1):155-61 [6788991] Carcinogenesis. 1981;2(12):1327-33 [6799218] J Natl Cancer Inst. 1983 Jan;70(1):209-12 [6571916] Int J Cancer. 1983 Mar 15;31(3):321-7 [6402455] Carcinogenesis. 1983;4(6):733-8 [6407772] Chem Biol Interact. 1985 Oct;55(1-2):13-21 [3933840] Lab Invest. 1990 Mar;62(3):244-78 [2107367] Mol Cell Biol. 1991 Aug;11(8):3842-9 [1712897] Cancer Res. 1992 Mar 15;52(6):1477-80 [1540955] Carcinogenesis. 1992 Sep;13(9):1535-9 [1394836] J Natl Cancer Inst. 1993 Jan 6;85(1):25-31 [8416252] Cancer Lett. 1992 Dec 24;67(2-3):117-24 [1483260] Epidemiol Rev. 1993;15(1):7-16 [8405214] Carcinogenesis. 1994 Nov;15(11):2429-33 [7955086] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Candida glabrata erg1 mutant with increased sensitivity to azoles and to low oxygen tension. AN - 66642713; 15215098 AB - A Candida glabrata erg1 (Cgerg1) mutant, CgTn201S, was identified by transposon mutagenesis and by increased fluconazole susceptibility. CgERG1 encodes a 489-amino-acid protein which, on the basis of its homology with Saccharomyces cerevisiae ERG1, is a squalene epoxidase essential for ergosterol synthesis. Interruption following codon 475 of CgErg1p decreased the ergosterol content by 50%; caused accumulation of the squalene precursor; increased the levels of susceptibility to fluconazole, itraconazole, and terbinafine; increased the level of resistance to amphotericin B; increased the levels of rhodamine 6G and [(3)H]-fluconazole uptake; reduced the level of growth; and blocked growth under conditions of low oxygen tension. In addition, CgTn201S efficiently took up exogenous cholesterol from cholesterol-containing serum. Cholesterol constituted 34% of the extractable sterols in CgTn201S when it was grown aerobically on serum-containing medium. Under the same conditions, C. albicans contained only 0.1 to 1.2% cholesterol. Exogenous sterols also restored growth under conditions of low oxygen tension. Finally, complementation of the Cgerg1 mutation restored the levels of [(3)H]fluconazole uptake and drug susceptibility to wild-type levels. JF - Antimicrobial agents and chemotherapy AU - Tsai, Huei-Fung AU - Bard, Martin AU - Izumikawa, Koichi AU - Krol, Anna A AU - Sturm, Aaron M AU - Culbertson, Nicholas T AU - Pierson, Charles A AU - Bennett, John E AD - Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Clinical Center NIH, Bethesda, MD 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 2483 EP - 2489 VL - 48 IS - 7 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Azoles KW - DNA Transposable Elements KW - ERG1 Potassium Channel KW - Ether-A-Go-Go Potassium Channels KW - Fluorescent Dyes KW - Potassium Channels KW - Potassium Channels, Voltage-Gated KW - Rhodamines KW - Sterols KW - rhodamine 6G KW - 037VRW83CF KW - Squalene KW - 7QWM220FJH KW - Fluconazole KW - 8VZV102JFY KW - Cholesterol KW - 97C5T2UQ7J KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Squalene -- metabolism KW - Plasmids -- genetics KW - Fluconazole -- pharmacology KW - Fluconazole -- metabolism KW - Cloning, Molecular KW - Phenotype KW - Cholesterol -- metabolism KW - Sterols -- metabolism KW - Drug Resistance, Fungal KW - Genetic Complementation Test KW - DNA Transposable Elements -- genetics KW - Microbial Sensitivity Tests KW - Candida glabrata -- metabolism KW - Candida glabrata -- genetics KW - Antifungal Agents -- pharmacology KW - Azoles -- pharmacology KW - Antifungal Agents -- metabolism KW - Potassium Channels -- genetics KW - Oxygen -- pharmacology KW - Mutation -- genetics KW - Candida glabrata -- drug effects KW - Azoles -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66642713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Candida+glabrata+erg1+mutant+with+increased+sensitivity+to+azoles+and+to+low+oxygen+tension.&rft.au=Tsai%2C+Huei-Fung%3BBard%2C+Martin%3BIzumikawa%2C+Koichi%3BKrol%2C+Anna+A%3BSturm%2C+Aaron+M%3BCulbertson%2C+Nicholas+T%3BPierson%2C+Charles+A%3BBennett%2C+John+E&rft.aulast=Tsai&rft.aufirst=Huei-Fung&rft.date=2004-07-01&rft.volume=48&rft.issue=7&rft.spage=2483&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 - 2004-09-07 N1 - Date created - 2004-06-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Yeast. 2003 Feb;20(3):249-61 [12557277] Genetics. 1993 Jul;134(3):717-28 [8349105] Biochem Biophys Res Commun. 2003 Sep 26;309(3):666-71 [12963042] Antimicrob Agents Chemother. 2000 Sep;44(9):2411-8 [10952588] Antimicrob Agents Chemother. 2001 Nov;45(11):3037-45 [11600353] Antimicrob Agents Chemother. 2002 Jun;46(6):1723-7 [12019081] EMBO J. 2002 Aug 1;21(15):4114-24 [12145211] Antimicrob Agents Chemother. 2003 Dec;47(12):3890-900 [14638499] Antimicrob Agents Chemother. 2004 May;48(5):1773-7 [15105134] J Gen Microbiol. 1972 Sep;72(2):339-48 [4562308] Gene. 1979 Dec;8(1):17-24 [395030] Antimicrob Agents Chemother. 1995 Aug;39(8):1696-9 [7486903] Antimicrob Agents Chemother. 1995 Dec;39(12):2708-17 [8593007] Yeast. 1996 May;12(6):609-13 [8771716] Gene. 1996 Oct 10;175(1-2):105-8 [8917084] J Bacteriol. 1999 Mar;181(6):1868-74 [10074081] J Antimicrob Chemother. 1999 Jul;44(1):27-31 [10459807] Genome Res. 2003 May;13(5):905-15 [12695329] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of phagocyte apoptosis by bacterial pathogens AN - 20191161; 6024536 AB - Phagocytic leukocytes such as neutrophils and macrophages are essential for the innate immune response against invading bacteria. Binding and ingestion of bacteria by these host cells triggers potent anti-microbial activity, including production of reactive oxygen species. Although phagocytes are highly adept at destroying bacteria, modulation of leukocyte apoptosis or cell death by bacteria has emerged as a mechanism of pathogenesis. Whereas induction of macrophage apoptosis by pathogens may adversely affect the host immune response to infection, acceleration of neutrophil apoptosis following phagocytic interaction with bacteria appears essential for the resolution of infection. This idea is supported by the finding that some bacterial pathogens alter normal phagocytosis-induced neutrophil apoptosis to survive and cause disease. This review summarizes what is currently known about modulation of phagocyte apoptosis by bacteria and describes a paradigm whereby bacteria-induced neutrophil apoptosis plays a role in the resolution of infection. JF - Apoptosis AU - DeLeo AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., fdeleo@niaid.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 399 EP - 413 PB - Kluwer Academic Publishers VL - 9 IS - 4 SN - 1360-8185, 1360-8185 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Macrophages KW - Bacteria KW - Apoptosis KW - Reactive oxygen species KW - Phagocytes KW - Reviews KW - Leukocytes (neutrophilic) KW - Pathogens KW - Immune response KW - Infection KW - A 01490:Miscellaneous KW - F 06910:Microorganisms & Parasites KW - J 02340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20191161?accountid=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=Apoptosis&rft.atitle=Modulation+of+phagocyte+apoptosis+by+bacterial+pathogens&rft.au=DeLeo&rft.aulast=DeLeo&rft.aufirst=&rft.date=2004-07-01&rft.volume=9&rft.issue=4&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Apoptosis&rft.issn=13608185&rft_id=info:doi/10.1023%2FB%3AAPPT.0000031448.64969.fa LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-08-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Macrophages; Apoptosis; Reactive oxygen species; Phagocytes; Reviews; Leukocytes (neutrophilic); Immune response; Pathogens; Infection; Bacteria DO - http://dx.doi.org/10.1023/B:APPT.0000031448.64969.fa ER - TY - JOUR T1 - Hyaluronic Acid Facilitates the Recovery of Hematopoiesis following 5- Fluorouracil Administration AN - 19941986; 5965494 AB - The fate of hematopoietic stem cells (HSCs) is determined by microenvironmental niches, but the molecular structure of these local networks is not yet completely characterized. Our recent observation that glycosaminoglycan hyaluronic acid (HA), a major component of the bone marrow extracellular matrix, is required for in vitro hematopoiesis led us to suggest a role for HA in structuring the hematopoietic niche. Accordingly, HA deprivation induced by various treatments might lead to an imbalance of normal HSC homeostasis. Since 5-fluorouracil (5-FU) administration sharply decreases the amount of cell surface-associated HA in bone marrow, we examined whether the administration of exogenous HA enhances suppressed hematopoiesis in 5-FU-treated mice. HA administered to mice following 5-FU infusion facilitated the recovery of leukocytes and thrombocytes in the peripheral blood. Intravenously infused HA was found in the bone marrow, where it bound endothelial cells and resident macrophages and increased expression of the hematopoiesis-supportive cytokines interleukin-1 and interleukin-6. In agreement with these observations, enhanced hematopoietic activity was detected in the bone marrow, as measured by elevated counts of long-term culture-initiating cells (LTC-ICs), committed progenitors, and the total number of mature bone marrow cells. Overall, our results suggest that HA is required for regulation of the hematopoiesis-supportive function of bone marrow accessory cells and, therefore, participates in hematopoietic niche assembly. JF - Stem Cells AU - Matrosova, Vera Y AU - Orlovskaya, Irina A AU - Serobyan, Naira AU - Khaldoyanidi, Sophia K AD - National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland. Institute for Clinical Immunology, Novosibirsk, Russia Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 544 EP - 555 VL - 22 IS - 4 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts KW - Macrophages KW - Interleukin 6 KW - Hyaluronic acid KW - Accessory cells KW - Interleukin 1 KW - Leukocytes KW - Bone marrow KW - Peripheral blood KW - Homeostasis KW - Endothelial cells KW - Stem cells KW - 5-Fluorouracil KW - Glycosaminoglycans KW - Extracellular matrix KW - Platelets KW - Hemopoiesis KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19941986?accountid=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=Stem+Cells&rft.atitle=Hyaluronic+Acid+Facilitates+the+Recovery+of+Hematopoiesis+following+5-+Fluorouracil+Administration&rft.au=Matrosova%2C+Vera+Y%3BOrlovskaya%2C+Irina+A%3BSerobyan%2C+Naira%3BKhaldoyanidi%2C+Sophia+K&rft.aulast=Matrosova&rft.aufirst=Vera&rft.date=2004-07-01&rft.volume=22&rft.issue=4&rft.spage=544&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-07-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Interleukin 6; Macrophages; Hyaluronic acid; Leukocytes; Interleukin 1; Accessory cells; Bone marrow; Peripheral blood; Homeostasis; Endothelial cells; Stem cells; Glycosaminoglycans; 5-Fluorouracil; Extracellular matrix; Platelets; Hemopoiesis ER - TY - JOUR T1 - Characterizing polychlorinated dibenzo-p-dioxins and dibenzofurans in the surrounding environment and workplace of a secondary aluminum smelter AN - 19815352; 5929599 AB - This study aims to characterize polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in the surrounding environment and workplace of a secondary aluminum smelter (secondary ALS). The mean I-TEQ concentrations in the stack flue gases and PCDD/F emission factor of the secondary ALS is 9.02 ng I-TEQ N m super(-3) and 50.1 mu g I-TEQ ton-feedstock super(- 1), respectively. The PCDD/F concentrations of outdoor (site O1, O2 and O3) and workplace air (site W1) during operation period are 0.670, 0.284, 0.141 and 0.571 pg I-TEQ N m super(-3), which are 3.3-, 2.1-, 1.8- and 2.5-fold higher than that during no operation period. The highest PCDD/F air concentrations (2.26 pg I-TEQ N-m super(-3)) were measured at site W2 during furnace maintenance. The elevated PCDD/F air concentration (2.26 pg I-TEQ N m super(-3)) caused by the fugitive particle during furnace maintenance implies that the PCDD/F concentration of air in the furnace that worker breathe could be extremely high. It reveals that PCDD/F exposure of furnace maintenance workers may be serious and further research on occupational exposure needs to be conducted. JF - Atmospheric Environment AU - Chen, S-J AU - Lee, W-S AU - Chang-Chien, G-P AU - Wang, L-C AU - Lee, W-J AU - Kao, J-H AU - Hu, M-TM-T AD - Department of Environmental Engineering and Science, National Pingtung University of Science and Technology, Nei Pu 91207, Ping Tung, Taiwan, ROC, guoping@csu.edu.tw Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 3729 EP - 3732 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 38 IS - 22 SN - 1352-2310, 1352-2310 KW - Toxicology Abstracts; Meteorological & Geoastrophysical Abstracts; Pollution Abstracts; Health & Safety Science Abstracts KW - Dioxin KW - Secondary aluminum smelter KW - Workplace KW - Furnace maintenance KW - Polychlorinated dibenzofurans in atmosphere KW - Atmospheric pollution effects on health KW - Aluminum deposition KW - Flue gas KW - Polychlorinated dibenzofurans KW - Stack emissions KW - Smelters KW - Air pollution KW - Workers KW - Amyotrophic lateral sclerosis KW - Gases KW - Dibenzofuran KW - Aluminum KW - PCDF KW - Emission measurements KW - Dibenzo-p-dioxin KW - Polychlorinated dibenzo-p-dioxins in atmosphere KW - PCDD KW - Occupational exposure KW - H 3000:Environment and Ecology KW - M2 551.510.42:Air Pollution (551.510.42) KW - P 0000:AIR POLLUTION KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19815352?accountid=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=Atmospheric+Environment&rft.atitle=Characterizing+polychlorinated+dibenzo-p-dioxins+and+dibenzofurans+in+the+surrounding+environment+and+workplace+of+a+secondary+aluminum+smelter&rft.au=Chen%2C+S-J%3BLee%2C+W-S%3BChang-Chien%2C+G-P%3BWang%2C+L-C%3BLee%2C+W-J%3BKao%2C+J-H%3BHu%2C+M-TM-T&rft.aulast=Chen&rft.aufirst=S-J&rft.date=2004-07-01&rft.volume=38&rft.issue=22&rft.spage=3729&rft.isbn=&rft.btitle=&rft.title=Atmospheric+Environment&rft.issn=13522310&rft_id=info:doi/10.1016%2Fj.atmosenv.2004.02.051 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-08-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Workers; Gases; Amyotrophic lateral sclerosis; Dibenzofuran; Aluminum; Dibenzo-p-dioxin; Polychlorinated dibenzofurans; Smelters; Occupational exposure; Polychlorinated dibenzofurans in atmosphere; Atmospheric pollution effects on health; Aluminum deposition; Polychlorinated dibenzo-p-dioxins in atmosphere; Air pollution; Emission measurements; PCDF; Flue gas; Stack emissions; PCDD DO - http://dx.doi.org/10.1016/j.atmosenv.2004.02.051 ER - TY - JOUR T1 - Development of a Multispecies Oral Bacterial Community in a Saliva-Conditioned Flow Cell AN - 18050885; 5963425 AB - Microbial communities within the human oral cavity are dynamic associations of more than 500 bacterial species that form biofilms on the soft and hard tissues of the mouth. Understanding the development and spatial organization of oral biofilms has been facilitated by the use of in vitro models. We used a saliva-conditioned flow cell, with saliva as the sole nutritional source, as a model to examine the development of multispecies biofilm communities from an inoculum containing the coaggregation partners Streptococcus gordonii, Actinomyces naeslundii, Veillonella atypica, and Fusobacterium nucleatum. Biofilms inoculated with individual species in a sequential order were compared with biofilms inoculated with coaggregates of the four species. Our results indicated that flow cells inoculated sequentially produced biofilms with larger biovolumes compared to those biofilms inoculated with coaggregates. Individual- species biovolumes within the four-species communities also differed between the two modes of inoculation. Fluorescence in situ hybridization with genus- and species-specific probes revealed that the majority of cells in both sequentially and coaggregate-inoculated biofilms were S. gordonii, regardless of the inoculation order. However, the representation of A. naeslundii and V. atypica was significantly higher in biofilms inoculated with coaggregates compared to sequentially inoculated biofilms. Thus, these results indicate that the development of multispecies biofilm communities is influenced by coaggregations preformed in planktonic phase. Coaggregating bacteria such as certain streptococci are especially adapted to primary colonization of saliva- conditioned surfaces independent of the mode of inoculation and order of addition in the multispecies inoculum. Preformed coaggregations favor other bacterial strains and may facilitate symbiotic relationships. JF - Applied and Environmental Microbiology AU - Foster, Jamie S AU - Kolenbrander, Paul E AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 4340 EP - 4348 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 70 IS - 7 SN - 0099-2240, 0099-2240 KW - streptococci KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Ecology Abstracts KW - Colonization KW - Veillonella atypica KW - Community composition KW - Symbiosis KW - Streptococcus gordonii KW - Biofilms KW - Saliva KW - Actinomyces naeslundii KW - Fusobacterium nucleatum KW - Plankton KW - Oral cavity KW - A 01116:Bacteria KW - D 04620:Microorganisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18050885?accountid=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=Applied+and+Environmental+Microbiology&rft.atitle=Development+of+a+Multispecies+Oral+Bacterial+Community+in+a+Saliva-Conditioned+Flow+Cell&rft.au=Foster%2C+Jamie+S%3BKolenbrander%2C+Paul+E&rft.aulast=Foster&rft.aufirst=Jamie&rft.date=2004-07-01&rft.volume=70&rft.issue=7&rft.spage=4340&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Colonization; Community composition; Symbiosis; Saliva; Biofilms; Oral cavity; Plankton; Veillonella atypica; Streptococcus gordonii; Actinomyces naeslundii; Fusobacterium nucleatum ER - TY - JOUR T1 - Evaluation of the Safety, Immunogenicity, and Protective Efficacy of Whole Inactivated Simian Immunodeficiency Virus (SIV) Vaccines with Conformationally and Functionally Intact Envelope Glycoproteins AN - 18046694; 6016301 AB - A novel, general approach to chemical inactivation of retroviruses was used to produce inactivated simian immunodeficiency virus (SIV) particles with functional envelope glycoproteins. Inactivated virions of three different virus isolates (SIVmne E11S, SIVmac239, and SIVmac239 g4,5), prepared by treatment with 2,2'dithiodipyridine (aldrithol-2, AT-2), were not detectably infectious, in vitro or in vivo. Immunization of pigtailed macaques with inactivated SIVmne E11S particles, without adjuvant, induced both humoral and cellular immune responses. Four of six animals immunized with the inactivated particles did not show measurable SIV RNA in plasma (<100 copy Eq/ml) following intravenous challenge with pathogenic, homologous virus (SIVmne E11S), compared to peak values of greater than or equal to 10 super(6) copy Eq/ml in challenged SIV-naive control animals (p = 0.0001). Despite the absence of measurable viral RNA in plasma in these animals, culturable virus and viral DNA were initially detectable in blood and lymph node specimens; in contrast to control animals, SIV DNA could no longer be detected in PBMC by 10 weeks postchallenge in five of six SIV-immunized animals (p = 0.0001). However, vaccines did not resist a sequential rechallenge with the heterologous pathogenic virus SIVsm E660. AT-2-inactivated virus with functional envelope glycoproteins is a novel class of vaccine immunogen and was noninfectious, under conditions of rigorous in vivo challenge, and induced both binding and neutralizing antibody responses, along with cellular immune responses. Results suggest that immunization facilitated effective containment of pathogenic homologous challenge virus. With further optimization, AT-2-inactivated viral particles may be a useful class of immunogen in the development of a vaccine to prevent AIDS. JF - AIDS Research and Human Retroviruses AU - Lifson, J D AU - Rossio, J L AU - Piatak, M Jr AU - Bess, J Jr AU - Chertova, E AU - Schneider, D K AU - Coalter, V J AU - Poore, B AU - Kiser, R F AU - Imming, R J AU - Scarzello, A J AU - Henderson, LE AU - Alvord, W G AU - Hirsch, V M AD - AIDS Vaccine Program, SAIC Frederick, National Cancer Institute-Frederick, Building 535, Fifth Floor, Frederick, MD 21702, USA, lifson@ncifcrf.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 772 EP - 787 VL - 20 IS - 7 SN - 0889-2229, 0889-2229 KW - immunogenicity KW - aldrithol-2 KW - SIV KW - Pigtail Macaque KW - 2,2'dithiodipyridine KW - Health & Safety Science Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - Virions KW - Acquired immune deficiency syndrome KW - vaccines KW - Macaca nemestrina KW - Adjuvants KW - immunization KW - Envelopes KW - Glycoproteins KW - Immune response (humoral) KW - Plasma KW - Lymph nodes KW - Immunization KW - Antibodies KW - Immune response (cell-mediated) KW - Immunogenicity KW - Immune response KW - Vaccines KW - Side effects KW - Simian immunodeficiency virus KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - F 06856:Animal KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18046694?accountid=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=AIDS+Research+and+Human+Retroviruses&rft.atitle=Evaluation+of+the+Safety%2C+Immunogenicity%2C+and+Protective+Efficacy+of+Whole+Inactivated+Simian+Immunodeficiency+Virus+%28SIV%29+Vaccines+with+Conformationally+and+Functionally+Intact+Envelope+Glycoproteins&rft.au=Lifson%2C+J+D%3BRossio%2C+J+L%3BPiatak%2C+M+Jr%3BBess%2C+J+Jr%3BChertova%2C+E%3BSchneider%2C+D+K%3BCoalter%2C+V+J%3BPoore%2C+B%3BKiser%2C+R+F%3BImming%2C+R+J%3BScarzello%2C+A+J%3BHenderson%2C+LE%3BAlvord%2C+W+G%3BHirsch%2C+V+M&rft.aulast=Lifson&rft.aufirst=J&rft.date=2004-07-01&rft.volume=20&rft.issue=7&rft.spage=772&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 - Simian immunodeficiency virus; Macaca nemestrina; Side effects; vaccines; immunization; Acquired immune deficiency syndrome; Vaccines; Immune response (cell-mediated); Immune response (humoral); Glycoproteins; Envelopes; Immune response; Immunization; Plasma; Immunogenicity; Lymph nodes; Adjuvants; Antibodies; Virions ER - TY - JOUR T1 - Another Look at Heavy Episodic Drinking and Alcohol Use Disorders among College and Noncollege Youth AN - 18046249; 6020569 AB - To estimate rates of heavy episodic drinking, alcohol abuse and alcohol dependence among U.S. adults 18-29 years of age and determine the relationship of these rates to student status and residence. The analysis is based on data from a subsample of U.S. adults 18-29 years of age (N = 8,666; 4,849 female) who were interviewed as part of the 2001-02 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Data were collected in personal interviews from a representative sample of adults 18 and older, living in households and selected group quarters in the United States, including Alaska, Hawaii and the District of Columbia. Of all adults 18-29 years of age, 73.1% reported any drinking in the past year, 39.6% reported any heavy episodic drinking, 21.1% reported heavy drinking more than once a month and 11.0% reported heavy drinking more than once a week. Among past-year drinkers, these correspond to rates of 54.3% for any heavy episodic drinking, 28.9% for heavy drinking more than once a month and 15.0% for heavy drinking more than once a week. Although rates of heavy episodic drinking were slightly higher for college students than for noncollege students (p < .01), differences according to place of residence were greater than differences according to student status. Overall, 7.0% of adults ages 18-29 met the DSM-IV criteria for alcohol abuse in the past year, and 9.2% met the criteria for alcohol dependence. The prevalence of abuse was highest among students living off campus (p < .01), and rates of dependence were highest among students living on campus (p < .01). Heavy episodic drinking and alcohol use disorders are youth as well as college phenomena. Prevention campaigns targeted at all youth are needed to supplement interventions conducted at the campus level. JF - Journal of Studies on Alcohol AU - Dawson, DA AU - Grant, B F AU - Stinson, F S AU - Chou, P S AD - NIAAA/LEB, 5635 Fishers Lane, Room 3083, MSC 9304, Bethesda, MD 20892-9304, USA, ddawson@willco.niaaa.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 477 EP - 488 VL - 65 IS - 4 SN - 0096-882X, 0096-882X KW - Physical Education Index KW - Alcohol KW - College students KW - Interviews KW - Youth KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18046249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Studies+on+Alcohol&rft.atitle=Another+Look+at+Heavy+Episodic+Drinking+and+Alcohol+Use+Disorders+among+College+and+Noncollege+Youth&rft.au=Dawson%2C+DA%3BGrant%2C+B+F%3BStinson%2C+F+S%3BChou%2C+P+S&rft.aulast=Dawson&rft.aufirst=DA&rft.date=2004-07-01&rft.volume=65&rft.issue=4&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Journal+of+Studies+on+Alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Alcohol; Youth; College students; Interviews ER - TY - JOUR T1 - Irreversible Ototoxicity Associated with Difluoromethylornithine AN - 18020213; 5968840 AB - Difluoromethylornithine (DFMO) is a potent, irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the synthesis of polyamines that promote cellular proliferation. DFMO has been tested as a potential cancer therapeutic and chemopreventive agent in clinical trials. Reversible hearing loss is a recognized toxicity of DFMO that usually occurs at doses above 2 g/m super(2)/d, and generally when the cumulative dose exceeds 250 g/m super(2). In a recently completed Barrett's esophagus chemoprevention trial, a participant developed a 15-dB decrease in hearing at frequencies of 250, 2,000, and 3,000 Hz in the right ear and a =>20-dB decrease in hearing at 4,000 to 6,000 Hz in the left ear after taking 0.5 g/m super(2)/d DFMO for approximately 13 weeks (cumulative dose of 45 g/m super(2)). The threshold shifts persisted 7 months after DFMO was discontinued. There was no obvious impact on the participant's clinical hearing, but these findings were consistent with irreversible hearing loss. This is the first case reported of irreversible ototoxicity in a clinical trial participant receiving DFMO and, thus, trial participants should be made aware of this small but important risk. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Lao, Christopher D AU - Backoff, Patricia AU - Shotland, Lawrence I AU - Mccarty, Deborah AU - Eaton, Tracy AU - Ondrey, Frank G AU - Viner, Jaye L AU - Spechler, Stuart Jon AU - Hawk, Ernest T AU - Brenner, Dean E AD - Departments of Internal Medicine and Pharmacology, University of Michigan Medical Center, Ann Arbor, Michigan. Ann Arbor VA Medical Center, Ann Arbor, Michigan. James H. Quillen VA Medical Center, Mountain Home, Tennessee. Dallas VA Medical Center, Dallas, Texas. Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota. Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 1250 EP - 1252 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 13 IS - 7 SN - 1055-9965, 1055-9965 KW - Toxicology Abstracts KW - polyamines KW - Ototoxicity KW - Ornithine decarboxylase KW - Barrett's esophagus KW - chemopreventive agents KW - Ear KW - Hearing loss KW - biomarkers KW - Clinical trials KW - Cancer KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18020213?accountid=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+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Irreversible+Ototoxicity+Associated+with+Difluoromethylornithine&rft.au=Lao%2C+Christopher+D%3BBackoff%2C+Patricia%3BShotland%2C+Lawrence+I%3BMccarty%2C+Deborah%3BEaton%2C+Tracy%3BOndrey%2C+Frank+G%3BViner%2C+Jaye+L%3BSpechler%2C+Stuart+Jon%3BHawk%2C+Ernest+T%3BBrenner%2C+Dean+E&rft.aulast=Lao&rft.aufirst=Christopher&rft.date=2004-07-01&rft.volume=13&rft.issue=7&rft.spage=1250&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&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 - Clinical trials; Cancer; Ear; Ototoxicity; Hearing loss; chemopreventive agents; biomarkers; Barrett's esophagus; polyamines; Ornithine decarboxylase ER - TY - JOUR T1 - The role of Par proteins in the active segregation of the P1 plasmid AN - 18014511; 5966454 AB - The parS centromere-like site promotes active P1 plasmid segregation in the presence of P1 ParA and ParB proteins. At the modest growth rate used here, time-lapse and still photomicroscopy shows that the plasmid copies are clustered as a focus at the Escherichia coli cell centre. Just before cell division, the focus is actively divided and ejects bidirectionally into opposite halves of the dividing cell. In the absence of the wild-type parS binding protein ParB, a focus was formed, but generally did not go to the cell centre. The randomly placed focus did not divide and was inherited by one daughter cell only. In the absence of ParA, foci formed and frequently fixed to the cell centre. However, they failed to divide or eject and were left at the new cell pole of one cell at division. Thus, ParB appears to be required for recognition of the plasmid and its attachment to the cell centre, and ParA is required for focus division and energetic ejection from the cell centre. The ATPase active site mutation, parAK122E, blocked ejection. Mutant parAM314I ejected weakly, and the daughter foci took two generations to reach a new cell centre. This explains the novel alternation of segregation and missegregation in successive generations seen in time-lapse images of this mutant. JF - Molecular Microbiology AU - Li, Y AU - Dabrazhynetskaya, A AU - Youngren, B AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, CCR, NCI-Frederick, Frederick, MD 21702-1201, USA., austin@ncifcrf.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 93 EP - 102 PB - Blackwell Science Ltd VL - 53 IS - 1 SN - 0950-382X, 0950-382X KW - parS gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - DNA-binding protein KW - ParB protein KW - Plasmids KW - ParA protein KW - Cell division KW - Segregation KW - Escherichia coli KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18014511?accountid=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+role+of+Par+proteins+in+the+active+segregation+of+the+P1+plasmid&rft.au=Li%2C+Y%3BDabrazhynetskaya%2C+A%3BYoungren%2C+B%3BAustin%2C+S&rft.aulast=Li&rft.aufirst=Y&rft.date=2004-07-01&rft.volume=53&rft.issue=1&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04111.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Plasmids; Segregation; ParB protein; DNA-binding protein; Cell division; ParA protein DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04111.x ER - TY - JOUR T1 - Transcriptional and translational regulation of the marRAB multiple antibiotic resistance operon in Escherichia coli AN - 18013166; 5966432 AB - The marRAB multiple antibiotic resistance operon of Escherichia coli is autorepressed by MarR. MarR binds to two palindromic sequences in vitro: site I lies between and overlaps the -35 and -10 hexamers for RNA polymerase binding; site II lies between the transcription start site and the GTG initiation codon of marR. To assess the importance of these sites in vivo, the effects of mutant sites on transcription were analysed using fusions to lacZ in the presence and absence of wild-type MarR. When both sites were wild type, transcription in the derepressed marR-deleted strain was 19-fold that of the wild-type strain; when only site I or site II was wild type, this ratio was reduced to 4.3- and 2.6-fold, respectively, showing that full repression requires both sites, but some repression can occur at one site independently of the other. Translational fusions of the wild-type promoter to lacZ demonstrated that marR translation proceeds at only 4.5% of the transcription rate. Analysis of translational fusions with mutant leader sequences demonstrated that the principal reason for inefficient translation is a weak Shine-Dalgarno (SD) sequence, AGG(G). Although the SD sequence is located within the potential stem-loop structure of site II, no evidence for occlusion of the SD sequence was found in the wild-type strain. However, a single basepair mutation that strengthens the stem-loop structure drastically reduced the translational efficiency. Substitution of ATG for GTG as the initiation codon increased translational efficiency by 50%. Increasing the 5 bp spacing between the SD sequence and the GTG codon by one to four bases reduced the translational efficiency by 50-75%. Inefficient translation of marR may help to sensitize the cell to environmental signals. JF - Molecular Microbiology AU - Martin, R G AU - Rosner, J L AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 5, Rm 333, National Institutes of Health, Bethesda, MD 20892-0560, USA., rgmartin@helix.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 183 EP - 191 PB - Blackwell Science Ltd VL - 53 IS - 1 SN - 0950-382X, 0950-382X KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - MarR protein KW - Escherichia coli KW - Antibiotic resistance KW - lacZ gene KW - N 14400:General KW - N 14550:General KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18013166?accountid=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=Transcriptional+and+translational+regulation+of+the+marRAB+multiple+antibiotic+resistance+operon+in+Escherichia+coli&rft.au=Martin%2C+R+G%3BRosner%2C+J+L&rft.aulast=Martin&rft.aufirst=R&rft.date=2004-07-01&rft.volume=53&rft.issue=1&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04080.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Antibiotic resistance; MarR protein; lacZ gene DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04080.x ER - TY - JOUR T1 - Hepatic Effects in Workers Exposed to 2-Methoxy Ethanol AN - 18012169; 5983882 AB - The objective of this study was to investigate the effects of 2-ME on hepatic function in exposed workers. Fifty-three impregnation workers from two copper-clad laminate-manufacturing factories using 2-ME as a solvent were recruited as the exposed group. Another group of 121 lamination workers with indirect exposure to 2-ME was recruited as the comparison group. Environmental monitoring of air 2-ME concentrations and biological monitoring of urine 2-methoxy acetic acid concentrations were performed. Venous blood was collected for blood biochemistry analyses. Liver function examination results showed that the aspartate amino transferase, alanine amino transferase, and gamma -glutamyl transferase in the 2-ME-exposed workers were not significantly different from those in the comparison workers. After adjustment for hepatitis carrier status, gender, body mass index, and duration of employment, no difference were found between exposed and comparison groups. We conclude that 2-ME was not a hepatotoxin. JF - Journal of Occupational and Environmental Medicine AU - Loh, Ching-Hui AU - Shih, Tung-Sheng AU - Hsieh, An-Tsz AU - Chen, Yeong-Hwang AU - Liao, Guo-Dong AU - Liou, Saou-Hsing AD - Department of Public Health, National Defense Medical Center, P.O. Box 90048-509, Nei-Hu, Taipei, Taiwan, 114, Republic of China, shliou@ndmctsgh.edu.tw Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 707 EP - 713 VL - 46 IS - 7 SN - 1076-2752, 1076-2752 KW - 2-methoxy acetic acid KW - 2-methoxy ethanol KW - hepatotoxin KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Biochemistry KW - Solvents KW - Alanine transaminase KW - Blood levels KW - Hepatitis KW - gamma -Glutamyltransferase KW - Factories KW - Blood KW - Urine KW - Liver KW - Occupational exposure KW - X 24156:Environmental impact KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18012169?accountid=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+Occupational+and+Environmental+Medicine&rft.atitle=Hepatic+Effects+in+Workers+Exposed+to+2-Methoxy+Ethanol&rft.au=Loh%2C+Ching-Hui%3BShih%2C+Tung-Sheng%3BHsieh%2C+An-Tsz%3BChen%2C+Yeong-Hwang%3BLiao%2C+Guo-Dong%3BLiou%2C+Saou-Hsing&rft.aulast=Loh&rft.aufirst=Ching-Hui&rft.date=2004-07-01&rft.volume=46&rft.issue=7&rft.spage=707&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/10.1097%2F01.jom.0000131785.15184.c5 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - gamma -Glutamyltransferase; Hepatitis; Blood; Biochemistry; Liver; Alanine transaminase; Occupational exposure; Factories; Urine; Solvents; Blood levels DO - http://dx.doi.org/10.1097/01.jom.0000131785.15184.c5 ER - TY - JOUR T1 - Replication of a unit-copy plasmid F in the bacterial cell cycle: a replication rate function analysis AN - 18009530; 5960796 AB - For stability, the replication of unit-copy plasmids ought to occur by a highly controlled process. We have characterized the replication dynamics of a unit-copy plasmid F by a replication rate function defined as the probability per unit age interval of the cell cycle that a plasmid will initiate replication. Analysis of baby-machine data by stochastics that make no detailed reference to underlying mechanism revealed that this rate function increased monotonically over the cell cycle with rapid increase near cell division. This feature is highly suggestive of a replication control mechanism that is designed to force most plasmids to replicate before cells undergo division. The replication rate function is developed anew from a mechanistic model incorporating the hypotheses that initiators are limiting and that steric hindrance of origins by handcuffing control initiation of replication. The model is based on correctly folded initiator protein monomers arising from an inactive dimer pool via chaperones in limiting amounts, their random distribution to high affinity sites (iterons) at the origin (ori) and an outside locus (incC), the statistical mechanics of bound monomer participation in pairing the two loci (cis-handcuffing), and initiation probability as proportional to the number of non-handcuffed ori-saturated plasmids. Provided cis-handcuffing is present, this model closely accounts for the shape of the replication rate function derived from experiment, and reproduces the observation that replication occurs throughout the cell cycle. Present concepts of iteron-based molecular mechanisms thus appear capable of yielding a quantitative description of unit-copy-number plasmid replication dynamics. JF - Plasmid AU - Morrison, P F AU - Chattoraj, D K AD - Division of Bioengineering and Physical Science, ORS, National Institutes of Health, Bethesda, MD 20892-5766, USA, chattord@dc37a.nci.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 13 EP - 30 VL - 52 IS - 1 SN - 0147-619X, 0147-619X KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Replication KW - Cell cycle KW - Plasmids KW - Copy number control KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18009530?accountid=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=Plasmid&rft.atitle=Replication+of+a+unit-copy+plasmid+F+in+the+bacterial+cell+cycle%3A+a+replication+rate+function+analysis&rft.au=Morrison%2C+P+F%3BChattoraj%2C+D+K&rft.aulast=Morrison&rft.aufirst=P&rft.date=2004-07-01&rft.volume=52&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Plasmid&rft.issn=0147619X&rft_id=info:doi/10.1016%2Fj.plasmid.2004.04.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Plasmids; Replication; Copy number control; Cell cycle DO - http://dx.doi.org/10.1016/j.plasmid.2004.04.001 ER - TY - JOUR T1 - Small RNAs Shed Some Light AN - 18005869; 5978657 AB - Small regulatory RNAs can act by pairing with their target messages, targeting themselves and the mRNA for degradation; Lenz et al. (this issue of Cell) now report that multiple small RNAs are essential regulators of the quorum-sensing systems of Vibrio species, including the regulation of virulence in V. cholerae. JF - Cell AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 1 EP - 2 PB - Cell Press, 1100 Massachusetts Avenue Cambridge MA 02138 USA, [mailto:subs@cell.com], [URL:http://www.cellpress.com] VL - 118 IS - 1 SN - 0092-8674, 0092-8674 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Virulence KW - Vibrio cholerae KW - quorum sensing KW - mRNA KW - J 02726:RNA and ribosomes KW - N 14540:Structure, sequence & physical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18005869?accountid=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=Cell&rft.atitle=Small+RNAs+Shed+Some+Light&rft.au=Gottesman%2C+S&rft.aulast=Gottesman&rft.aufirst=S&rft.date=2004-07-01&rft.volume=118&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/10.1016%2Fj.cell.2004.06.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vibrio cholerae; mRNA; quorum sensing; Virulence DO - http://dx.doi.org/10.1016/j.cell.2004.06.024 ER - TY - JOUR T1 - Brain hyperthermia induced by MDMA ('ecstasy'): modulation by environmental conditions AN - 17995684; 5966543 AB - Drugs of abuse, such as 3,4-methylenedioxymethamphetamine (MDMA), often have more powerful effects during states of increased activation and under specific environmental conditions. Because hyperthermia is a major complication of MDMA use and a factor potentiating neurotoxicity, we examined the effects of this drug (9 mg/kg, sc; approximately one-fifth of the known LD sub(50) in rats) on brain [nucleus accumbens (Nacc) and hippocampus (Hippo)] and muscle (musculus temporalis) temperatures in male rats under conditions that either model human drug use (social interaction with female, warm temperature) or restrict heat dissipation from the brain (chronic occlusion of jugular veins). Under quiet resting conditions at 23 degree C, MDMA induced a moderate but prolonged hyperthermia. Both NAcc and Hippo showed more rapid and stronger temperature increases than muscle, suggesting metabolic neural activation as a primary cause of brain hyperthermia. During social interaction with a female, brain hyperthermia induced by MDMA was significantly potentiated (+89%). Brain hyperthermia induced by MDMA was also strongly potentiated (+188%) in animals with chronically occluded jugular veins, suggesting impaired cerebral outflow enhances intrabrain heat accumulation. At 29 degree C, MDMA pushed temperatures in the brain to its biological limits (>41 degree C; +268%), resulting in fatalities in most (83%) tested animals. Therefore, by inducing metabolic brain activation and restricting heat dissipation, MDMA use under 'party' conditions may be much more dangerous than under standard laboratory conditions. JF - European Journal of Neuroscience AU - Brown, P L AU - Kiyatkin, E A AD - Behavioural Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA, ekiyatki@intra.nida.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 51 EP - 58 PB - Blackwell Science Ltd VL - 20 IS - 1 SN - 0953-816X, 0953-816X KW - rats KW - Toxicology Abstracts KW - Temperature effects KW - Nucleus accumbens KW - Hyperthermia KW - Environments KW - Hippocampus KW - Neurotoxicity KW - Muscles KW - Brain KW - MDMA KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17995684?accountid=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=European+Journal+of+Neuroscience&rft.atitle=Brain+hyperthermia+induced+by+MDMA+%28%27ecstasy%27%29%3A+modulation+by+environmental+conditions&rft.au=Brown%2C+P+L%3BKiyatkin%2C+E+A&rft.aulast=Brown&rft.aufirst=P&rft.date=2004-07-01&rft.volume=20&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Neuroscience&rft.issn=0953816X&rft_id=info:doi/10.1111%2Fj.0953-816X.2004.03453.x LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Temperature effects; Nucleus accumbens; Hyperthermia; Environments; Hippocampus; Neurotoxicity; Brain; Muscles; MDMA DO - http://dx.doi.org/10.1111/j.0953-816X.2004.03453.x ER - TY - JOUR T1 - Conformational stability and domain coupling in D-glucose/D-galactose-binding protein from Escherichia coli AN - 17850753; 6091457 AB - The monomeric D-glucose/D-galactose-binding protein (GGBP) from Escherichia coli (M sub(r) 33000) is a periplasmic protein that serves as a high-affinity receptor for the active transport and chemotaxis towards both sugars. The effect of D-glucose binding on the thermal unfolding of the GGBP protein at pH 7.0 has been measured by differential scanning calorimetry (DSC), far-UV CD and intrinsic tryptophanyl residue fluorescence (Trp fluorescence). All three techniques reveal reversible, thermal transitions and a midpoint temperature (T sub(m)) increase from 50 to 63 degree C produced by 10 mM D-glucose. Both in the absence and presence of D-glucose a single asymmetric endotherm for GGBP is observed in DSC, although each endotherm consists of two transitions about 4 degree C apart in T sub(m) values. In the absence of D-glucose, the protein unfolding is best described by two non-ideal transitions, suggesting the presence of unfolding intermediates. In the presence of D-glucose protein, unfolding is more co-operative than in the absence of the ligand, and the experimental data are best fitted to a model that assumes two ideal (two-state) sequential transitions. Thus D-glucose binding changes the character of the GGBP protein folding/unfolding by linking the two domains such that protein unfolding becomes a cooperative, two two-state process. A K sub(A) value of 5.6x10 super(6) M super(-1) at 63 degree C for D-glucose binding is estimated from DSC results. The domain with the lower stability in DSC measurements has been identified as the C-terminal domain of GGBP from thermally induced Trp fluorescence changes. JF - Biochemical Journal AU - Piszczek, G AU - D'Auria, S AU - Staiano, M AU - Rossi, M AU - Ginsburg, A AD - Section on Protein Chemistry, Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012, USA, grzegorz_piszczek@nih.gov Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 97 EP - 103 VL - 381 IS - 1 SN - 0264-6021, 0264-6021 KW - Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Sugar KW - Fluorescence KW - Protein folding KW - Glucose KW - Escherichia coli KW - Active transport KW - Chemotaxis KW - Differential scanning calorimetry KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17850753?accountid=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=Biochemical+Journal&rft.atitle=Conformational+stability+and+domain+coupling+in+D-glucose%2FD-galactose-binding+protein+from+Escherichia+coli&rft.au=Piszczek%2C+G%3BD%27Auria%2C+S%3BStaiano%2C+M%3BRossi%2C+M%3BGinsburg%2C+A&rft.aulast=Piszczek&rft.aufirst=G&rft.date=2004-07-01&rft.volume=381&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Biochemical+Journal&rft.issn=02646021&rft_id=info:doi/10.1042%2FBJ20040232 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Glucose; Protein folding; Fluorescence; Differential scanning calorimetry; Active transport; Temperature effects; Chemotaxis; Sugar DO - http://dx.doi.org/10.1042/BJ20040232 ER - TY - JOUR T1 - Potential use of procalcitonin as a diagnostic criterion in febrile neutropenia: experience from a multicentre study AN - 17788197; 5966871 AB - In order to assess the diagnostic value of procalcitonin, 158 patients with febrile neutropenia from centres across Europe were studied. Patients with fever were diagnosed on the basis of either: (1) clinical, radiological and microbiological criteria; or (2) the procalcitonin value. In the latter case, concentrations of 0.5-1.0 ng/mL were considered diagnostic of localised infection, concentrations of 1.0-5.0 ng/mL of bacteraemia, and concentrations of > 5.0 ng/mL of severe sepsis. Procalcitonin and C-reactive protein were estimated daily in serum by immunochemiluminescence and nephelometry, respectively. Overall, the sensitivity (specificity) of procalcitonin for bacteraemia was 44.2% (64.3%) at concentrations of 1.0-5.0 ng/mL, and 83.3% (100%) for severe sepsis at concentrations of > 5.0 ng/mL. It was concluded that procalcitonin is a marker strongly suggestive of severe sepsis at concentrations of > 5.0 ng/mL. Estimated concentrations of < 0.5 ng /mL indicate that infection is unlikely, but it was observed that bacteraemia associated with coagulase-negative staphylococci may fail to elevate serum procalcitonin levels. JF - Clinical Microbiology and Infection AU - Giamarellou, H AU - Giamarellos-Bourboulis, E J AU - Repoussis, P AU - Galani, L AU - Anagnostopoulos, N AU - Grecka, P AU - Lubos, D AU - Aoun, M AU - Athanassiou, K AU - Bouza, E AU - Devigili, E AU - Krcmery, V AU - Menichetti, F AU - Panaretou, E AU - Papageorgiou, E AU - Plachouras, D AD - 4th Department of Internal Medicine, Athens Medical School, Department of Haematology, Pireas Metaxa Hospital, Department of Haematology, Athens General Hospital G. Gennimatas, Athens, Greece, Department of Internal Medicine, National Cancer Institute, Bratislava, Slovakia, Department of Infectious Diseases, Institut J. Bordet, Bruxelles, Belgium, Hospital 'Gregorio Maranon', Madrid, Spain, Ospedale Generale Regionale, Centro Trapianti Di Midollo Osseo, Bolzano, Azienda Ospedaliera Pisana, UO Malattie Cisanelo, Pisa, Italy and Department of Haematology, Athens Hospital Evangelismos, Athens, Greece, giamarel@internet.gr Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 628 EP - 633 PB - Blackwell Science Ltd VL - 10 IS - 7 SN - 1198-743X, 1198-743X KW - Microbiology Abstracts B: Bacteriology KW - Fever KW - Nephelometry KW - Neutropenia KW - Sepsis KW - Bacteremia KW - procalcitonin KW - Infection KW - C-reactive protein KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17788197?accountid=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=Clinical+Microbiology+and+Infection&rft.atitle=Potential+use+of+procalcitonin+as+a+diagnostic+criterion+in+febrile+neutropenia%3A+experience+from+a+multicentre+study&rft.au=Giamarellou%2C+H%3BGiamarellos-Bourboulis%2C+E+J%3BRepoussis%2C+P%3BGalani%2C+L%3BAnagnostopoulos%2C+N%3BGrecka%2C+P%3BLubos%2C+D%3BAoun%2C+M%3BAthanassiou%2C+K%3BBouza%2C+E%3BDevigili%2C+E%3BKrcmery%2C+V%3BMenichetti%2C+F%3BPanaretou%2C+E%3BPapageorgiou%2C+E%3BPlachouras%2C+D&rft.aulast=Giamarellou&rft.aufirst=H&rft.date=2004-07-01&rft.volume=10&rft.issue=7&rft.spage=628&rft.isbn=&rft.btitle=&rft.title=Clinical+Microbiology+and+Infection&rft.issn=1198743X&rft_id=info:doi/10.1111%2Fj.1469-0691.2004.00883.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - procalcitonin; Bacteremia; Sepsis; Infection; Neutropenia; Nephelometry; Fever; C-reactive protein DO - http://dx.doi.org/10.1111/j.1469-0691.2004.00883.x ER - TY - JOUR T1 - Comparison of methods to assess change in children's body composition AN - 17704277; 5956508 AB - Background: Little is known about how simpler and more available methods to measure change in body fatness compare with criterion methods such as dual-energy X-ray absorptiometry (DXA) in children. Objective: Our objective was to determine the ability of air-displacement plethysmography (ADP) and formulas based on triceps skinfold thickness (TSF) and bioelectrical impedance analysis (BIA) to estimate changes in body fat over time in children. Design: Eighty-six nonoverweight and overweight boys (n = 34) and girls (n = 52) with an average age of 11.0 plus or minus 2.4 y underwent ADP, TSF measurement, BIA, and DXA to estimate body fatness at baseline and 1 plus or minus 0.3 y later. Recent equations were used to estimate percentage body fat by TSF measurement (Dezenberg equation) and by BIA (Suprasongsin and Lewy equations). Percentage body fat estimates by ADP, TSF measurement, and BIA were compared with those by DXA. Results: All methods were highly correlated with DXA (P < 0.001). No mean bias for estimates of percentage body fat change was found for ADP (Siri equation) compared with DXA for all subjects examined together, and agreement between body fat estimation by ADP and DXA did not vary with race or sex. Magnitude bias was present for ADP relative to DXA (P < 0.01). Estimates of change in percentage body fat were systematically overestimated by BIA equations (1.37 plus or minus 6.98%; P < 0.001). TSF accounted for only 13% of the variance in percentage body fat change. Conclusion: Compared with DXA, there appears to be no noninvasive and simple method to measure changes in children's percentage body fat accurately and precisely, but ADP performed better than did TSF or BIA. ADP could prove useful for measuring changes in adiposity in children. JF - American Journal of Clinical Nutrition AU - Elberg, J AU - McDuffie, J R AU - Sebring, NG AU - Salaita, C AU - Keil, M AU - Robotham, D AU - Reynolds, J C AU - Yanovski, JA AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and the Nutrition Department and the Department of Nuclear Medicine, Warren Magnuson Clinical Center, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 64 EP - 69 VL - 80 IS - 1 SN - 0002-9165, 0002-9165 KW - Physical Education Index KW - Obesity KW - Scanning KW - Nutrition (effects) KW - Body composition KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17704277?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Clinical+Nutrition&rft.atitle=Comparison+of+methods+to+assess+change+in+children%27s+body+composition&rft.au=Elberg%2C+J%3BMcDuffie%2C+J+R%3BSebring%2C+NG%3BSalaita%2C+C%3BKeil%2C+M%3BRobotham%2C+D%3BReynolds%2C+J+C%3BYanovski%2C+JA&rft.aulast=Elberg&rft.aufirst=J&rft.date=2004-07-01&rft.volume=80&rft.issue=1&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Clinical+Nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nutrition (effects); Body composition; Scanning; Obesity ER - TY - JOUR T1 - Inhibition of Mycobacterium tuberculosis AhpD, an Element of the Peroxiredoxin Defense against Oxidative Stress AN - 17700637; 5949423 AB - The resistance of Mycobacterium tuberculosis to isoniazid (INH) is largely linked to suppression of a catalase-peroxidase enzyme (KatG) that activates INH. In the absence of KatG, antioxidant protection is provided by enhanced expression of the peroxiredoxin AhpC, which is itself reduced by AhpD, a protein with low alkylhydroperoxidase activity of its own. Inhibition of AhpD might therefore impair the antioxidant protection afforded by AhpC and make KatG- negative strains more sensitive to oxidative stress. We report here that the 3(E),17-dioxime of testosterone is a potent competitive AhpD inhibitor, with a K sub(i) of 50 +/- 2 nM. The inhibitor is stereospecific, in that the 3(E) but not 3(Z) isomer is active. Computational studies provide support for a proposed AhpD substrate binding site. However, the inhibitor does not completely suppress the in vitro activity of AhpC/AhpD, because a low titer of AhpD suffices to maintain AhpC activity. This finding, and the low solubility of the inhibitor, explains its inability to suppress the growth of INH-resistant M. tuberculosis in infected mouse lungs. JF - Antimicrobial Agents & Chemotherapy AU - Koshkin, Aleksey AU - Zhou, Xiao-Ti AU - Kraus, Carl N AU - Brenner, Jason M AU - Bandyopadhyay, Pradipta AU - Kuntz, Irwin D AU - Barry, Clifton E AU - Ortiz De Montellano, Paul R AD - Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, California 94143-2280. Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852 Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 2424 EP - 2430 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 48 IS - 7 SN - 0066-4804, 0066-4804 KW - Microbiology Abstracts B: Bacteriology KW - Testosterone KW - Antioxidants KW - Solubility KW - Oxidative stress KW - Lung KW - Peroxiredoxin KW - Tuberculosis KW - Computer applications KW - Mycobacterium tuberculosis KW - Isomers KW - Isoniazid KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17700637?accountid=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=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Inhibition+of+Mycobacterium+tuberculosis+AhpD%2C+an+Element+of+the+Peroxiredoxin+Defense+against+Oxidative+Stress&rft.au=Koshkin%2C+Aleksey%3BZhou%2C+Xiao-Ti%3BKraus%2C+Carl+N%3BBrenner%2C+Jason+M%3BBandyopadhyay%2C+Pradipta%3BKuntz%2C+Irwin+D%3BBarry%2C+Clifton+E%3BOrtiz+De+Montellano%2C+Paul+R&rft.aulast=Koshkin&rft.aufirst=Aleksey&rft.date=2004-07-01&rft.volume=48&rft.issue=7&rft.spage=2424&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 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Testosterone; Solubility; Antioxidants; Lung; Oxidative stress; Peroxiredoxin; Tuberculosis; Computer applications; Isoniazid; Isomers; Mycobacterium tuberculosis ER - TY - JOUR T1 - NMR Structural Studies of Domain 1 of Receptor-associated Protein AN - 17688636; 6024344 AB - The 39 kDa receptor-associated protein (RAP) is an endoplasmic reticulum resident protein that binds tightly to the low-density lipoprotein receptor-related protein (LRP) as well as to other members of the low-density lipoprotein receptor superfamily. The association of RAP with LRP prevents this receptor from interacting with ligands. RAP is a three-domain protein that contains two independent LRP binding sites; one located within domains 1 and 2, and one located within domain 3. As the first step toward defining the structure of the full-length protein and understanding the interaction between RAP and this family of receptors, we have determined the 3D structure of domain 1 using constraints derived from heteronuclear multi-dimensional NMR spectra, including NOEs, dihedral angles, J-couplings and chemical shifts, as well as two sets of non-correlated residual dipolar couplings measured from the protein solutions in anisotropic media of Pf1 and 6% polyacrylamide gel. The backbone C sub( alpha ) rmsd between the current structure and a homo-nuclear NOE-based structure is about 2 Aa. The large rmsd mainly reflects the significant differences in helical orientation and in the structural details of the long helix (helix 2) between the two structures. JF - Journal of Biomolecular NMR AU - Wu, Y AU - Migliorini, M AU - Walsh, J AU - Yu, P AU - Strickland, D K AU - Wang, Y AD - Protein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, U.S.A. Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 271 EP - 279 PB - Kluwer Academic Publishers VL - 29 IS - 3 SN - 0925-2738, 0925-2738 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17688636?accountid=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+Biomolecular+NMR&rft.atitle=NMR+Structural+Studies+of+Domain+1+of+Receptor-associated+Protein&rft.au=Wu%2C+Y%3BMigliorini%2C+M%3BWalsh%2C+J%3BYu%2C+P%3BStrickland%2C+D+K%3BWang%2C+Y&rft.aulast=Wu&rft.aufirst=Y&rft.date=2004-07-01&rft.volume=29&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+NMR&rft.issn=09252738&rft_id=info:doi/10.1023%2FB%3AJNMR.0000032507.96325.6d LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1023/B:JNMR.0000032507.96325.6d ER - TY - JOUR T1 - Measurement and automatic correction of high-order B sub(0) inhomogeneity in the rat brain at 11.7 Tesla AN - 17680198; 5970351 AB - In vivo B sub(0) inhomogeneity in the rat brain at 11.7 Tesla was measured and decomposed up to the fourth-order spherical harmonic terms using an automatic slice shimming routine derived from the FLATNESS method. In vivo shimming of horizontal slices showed that significant improvement in the T sub(2)-weighted echo-planar imaging was achieved after correction of all first-, second- and third-order in-slice shims. For localized proton spectroscopy, reproducible, high quality data were obtained after correcting all first- and second-order shims. The measured high-order in vivo B sub(0) inhomogeneity in terms of spherical harmonic terms should provide a useful guide for designing shims to meet in vivo requirements. JF - Magnetic Resonance Imaging AU - Chen, Z AU - Li, S S AU - Yang, J AU - Letizia, D AU - Shen, J AD - Molecular Imaging Branch, NIMH, National Institute of Health, Bethesda, MD 20892, USA, shenj@intra.nimh.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 835 EP - 842 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 22 IS - 6 SN - 0730-725X, 0730-725X KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; CSA Neurosciences Abstracts KW - N3 11021:Neuroimaging techniques KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17680198?accountid=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=Magnetic+Resonance+Imaging&rft.atitle=Measurement+and+automatic+correction+of+high-order+B+sub%280%29+inhomogeneity+in+the+rat+brain+at+11.7+Tesla&rft.au=Chen%2C+Z%3BLi%2C+S+S%3BYang%2C+J%3BLetizia%2C+D%3BShen%2C+J&rft.aulast=Chen&rft.aufirst=Z&rft.date=2004-07-01&rft.volume=22&rft.issue=6&rft.spage=835&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+Imaging&rft.issn=0730725X&rft_id=info:doi/10.1016%2Fj.mri.2004.01.062 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.mri.2004.01.062 ER - TY - JOUR T1 - Application of the GA/KNN method to SELDI proteomics data AN - 17601247; 5946090 AB - SUMMARY: Proteomics technology has shown promise in identifying biomarkers for disease, toxicant exposure and stress. We show by example that the genetic algorithm/k-nearest neighbors method, developed for mining high-dimensional microarray gene expression data, is also capable of mining surface enhanced laser desorption/ionization-time-of-flight proteomics data. AVAILABILITY: The source code of the program and documentation on how to use it are freely available to non-commercial users at http://dir.niehs.nih.gov/dirbb/lifiles/softlic.htm JF - Bioinformatics AU - Li, Leping AU - Umbach, David M AU - Terry, Paul AU - Taylor, Jack A AD - Biostatistics Branch, Epidemiology Branch and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 1638 EP - 1640 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 20 IS - 10 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Gene expression KW - Desorption KW - Data processing KW - Toxicants KW - Algorithms KW - Stress KW - Lasers KW - Bioinformatics KW - proteomics KW - biomarkers KW - DNA microarrays KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17601247?accountid=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=Bioinformatics&rft.atitle=Application+of+the+GA%2FKNN+method+to+SELDI+proteomics+data&rft.au=Li%2C+Leping%3BUmbach%2C+David+M%3BTerry%2C+Paul%3BTaylor%2C+Jack+A&rft.aulast=Li&rft.aufirst=Leping&rft.date=2004-07-01&rft.volume=20&rft.issue=10&rft.spage=1638&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&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 - Data processing; proteomics; DNA microarrays; Bioinformatics; biomarkers; Lasers; Toxicants; Gene expression; Algorithms; Desorption; Stress ER - TY - JOUR T1 - The basolateral complex of the amygdala mediates the modulation of intracranial self-stimulation threshold by drug-associated cues AN - 17592217; 5966535 AB - Learning and memory appear to be critical aspects of drug abuse; presumably playing an especially important role in craving and relapse. Thus, understanding the interaction of learning- and memory-related brain areas with the classical reward circuitry is of importance. Toward this goal, the effect of drug-associated contextual cues on intracranial self-stimulation (ICSS) behaviour was assessed in rats. We used a method that allows the establishment of baseline behaviour, the pairing of drug exposure with unique cues, and testing the effect of cue exposure within the same apparatus. ICSS thresholds were decreased by morphine (5 mg /kg, i.p.) or cocaine (10 mg/kg, i.p.) during five days of paired drug-cue training sessions. Subsequent presentation of the drug-associated cues decreased thresholds in the absence of drug. Cues associated with saline had no effect. These results suggest a Pavlovian conditioning phenomenon in which the functioning of brain reward circuitry is modulated by drug-associated cues. In a second experiment, we tested the hypothesis that the mechanism by which conditioning affects ICSS thresholds may include the basolateral complex of the amygdala (BLC) due to its known role in conditioning and anatomical linkage with classical reward circuitry. Lesions of the BLC abolished the ability of cocaine-associated cues to lower ICSS threshold. Lesions did not alter response capability or the unconditioned effect of cocaine. We conclude that the BLC is necessary for cues associated with previous drug exposure to modulate activity within or downstream from the classical reward circuitry of the medial forebrain bundle. JF - European Journal of Neuroscience AU - Hayes, R J AU - Gardner, EL AD - Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Dr, Baltimore, Maryland 21224, USA, rhayes@intra.nida.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 273 EP - 280 PB - Blackwell Science Ltd VL - 20 IS - 1 SN - 0953-816X, 0953-816X KW - CSA Neurosciences Abstracts; Toxicology Abstracts 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/17592217?accountid=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=European+Journal+of+Neuroscience&rft.atitle=The+basolateral+complex+of+the+amygdala+mediates+the+modulation+of+intracranial+self-stimulation+threshold+by+drug-associated+cues&rft.au=Hayes%2C+R+J%3BGardner%2C+EL&rft.aulast=Hayes&rft.aufirst=R&rft.date=2004-07-01&rft.volume=20&rft.issue=1&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Neuroscience&rft.issn=0953816X&rft_id=info:doi/10.1111%2Fj.1460-9568.2004.03463.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-08-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1111/j.1460-9568.2004.03463.x ER - TY - JOUR T1 - Physical Activity, Exercise, and Inflammatory Markers in Older Adults: Findings from The Health, Aging and Body Composition Study AN - 17591500; 5965568 AB - To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use. Cross-sectional study, using baseline data from the Health, Aging and Body Composition Study. Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. Black and white, well-functioning men and women (N=3,075), aged 70 to 79. Interviewer-administered questionnaires of previous-week household, walking, exercise, and occupational/volunteer physical activities. Analysis of covariance was used to examine the association between activity level and serum C-reactive protein (CRP), interleukin-6 (IL-6), and plasma tumor necrosis factor alpha (TNF alpha ) with covariate adjustment. Antioxidant supplement use (multivitamin, vitamins E or C, beta carotene) was evaluated as an effect modifier of the association. Higher levels of exercise were associated with lower levels of CRP (P180 min/wk). Adjustment for body fatness attenuated the associations somewhat. Use of antioxidant supplements modified the CRP (P sub(interaction)=.01) and IL-6 (P sub(interaction)=.08) associations such that concentrations were low in those taking supplements (e.g., CRP=1.79-1.84 across exercise levels) and higher in nonsupplement users who did no exercise (2.03) than in those who did the most (1.72). Among nonexercisers, higher levels of other physical activity were related to lower levels of CRP (P<.01) and IL-6 (P=.02) but not TNF alpha (P=.36), even after accounting for body fat. Inflammatory markers are lower in older adults with higher levels of exercise and nonexercise activity and in antioxidant supplement users regardless of exercise level. JF - Journal of the American Geriatrics Society AU - Colbert, L H AU - Visser, M AU - Simonsick, E M AU - Tracy, R P AU - Newman, AB AU - Kritchevsky, S B AU - Pahor, M AU - Taaffe AU - Brach, J AU - Rubin, S AU - Harris, T B AD - From the Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland; , lhcolbert@education.wisc.edu Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 1098 EP - 1104 PB - Blackwell Science Ltd VL - 52 IS - 7 SN - 0002-8614, 0002-8614 KW - Physical Education Index KW - Antioxidants KW - Blacks KW - Gerontology KW - Surveys KW - Walking KW - Health KW - Analysis KW - Vitamins KW - Dietary supplements KW - Proteins KW - Exercise (effects) KW - Body composition KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17591500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Geriatrics+Society&rft.atitle=Physical+Activity%2C+Exercise%2C+and+Inflammatory+Markers+in+Older+Adults%3A+Findings+from+The+Health%2C+Aging+and+Body+Composition+Study&rft.au=Colbert%2C+L+H%3BVisser%2C+M%3BSimonsick%2C+E+M%3BTracy%2C+R+P%3BNewman%2C+AB%3BKritchevsky%2C+S+B%3BPahor%2C+M%3BTaaffe%3BBrach%2C+J%3BRubin%2C+S%3BHarris%2C+T+B&rft.aulast=Colbert&rft.aufirst=L&rft.date=2004-07-01&rft.volume=52&rft.issue=7&rft.spage=1098&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Geriatrics+Society&rft.issn=00028614&rft_id=info:doi/10.1111%2Fj.1532-5415.2004.52307.x LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antioxidants; Dietary supplements; Exercise (effects); Health; Gerontology; Body composition; Vitamins; Walking; Blacks; Analysis; Surveys; Proteins DO - http://dx.doi.org/10.1111/j.1532-5415.2004.52307.x ER - TY - CONF T1 - The LIFE study: A randomized clinical trial of exercise to prevent disability in high-risk older persons AN - 17328250; 6249852 AB - Sarcopenia and frailty in the oldest old population can be self-perpetuating syndromes rapidly leading to the loss of independence, increased falls risk, hospitalization and, ultimately, death. In the past 3 years, results from several randomized controlled trials across the world have demonstrated the feasibility of regular exercise training for the frail older adults, and most of these studies offer convincing evidence that exercise training is effective in reducing the negative correlates of frailty. Despite this positive message, it is still not clear what the most appropriate exercise regime is for the frail older adult, if the beneficial effects of exercise depend on initial levels of frailty, or if an active lifestyle is effective in delaying or preventing the onset of frailty. Exercise studies usually don't address frailty per se, rather the assumption is made that improvements in such variables as strength, endurance and agility will transfer to improved performance of functional tasks associated with daily living. There is good evidence that this transfer does in fact occur, and that a reduction in the incidence of falls can also be expected. A key question though is what happens after a research intervention is over? From the limited literature on detraining effects in the older population, it appears that any gains in physical function attained through a progressive exercise program will be gradually lost if the participants stop exercising. Therefore, researchers and geriatric professionals now need to focus on such things as exercise compliance, and which factors might "motivate" frail older adults to continue to exercise regularly. Nursing homes will need guidance not only on the specifics of the exercise program they should be offering to their frail population, but also on motivational strategies to ensure that regular exercise becomes integrated into the daily lifestyle of the oldest segment of our population. JF - Journal of Aging and Physical Activity AU - Guralnik, J Y1 - 2004/07// PY - 2004 DA - Jul 2004 PB - Human Kinetics Publishers, P.O. Box 5076 Champaign IL 61825-5076 USA VL - 12 IS - 3 KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17328250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Aging+and+Physical+Activity&rft.atitle=The+LIFE+study%3A+A+randomized+clinical+trial+of+exercise+to+prevent+disability+in+high-risk+older+persons&rft.au=Guralnik%2C+J&rft.aulast=Guralnik&rft.aufirst=J&rft.date=2004-07-01&rft.volume=12&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+Aging+and+Physical+Activity&rft.issn=10638652&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-02-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Production of Hydroxyl Radicals from the Decomposition of Hydrogen Peroxide Catalyzed by Various Iron Oxides at pH 7 AN - 17282840; 5956021 AB - The hydroxyl radical, generated from the Fenton-like catalysis of hydrogen peroxide (H sub(2)O sub(2)), is the major reactant involved in the oxidation of toxic organic contaminants. This study evaluated the effects of H sub(2)O sub(2) doses and types of iron oxides on the yields and production rates of hydroxyl radicals at molar ratio of H sub(2)O sub(2)/total iron oxide = 0.2-9.7 and pH = 7. The results showed that for both ferrihydrite and goethite, the yields and production rates were in the order of 10 super(-12) mM and 1-5 X 10 super(-14) mM/S, respectively, and irrelevant to the initial H sub(2)O sub(2) dose. However, a higher H sub(2)O sub(2) dose was required in aquifer sand to produce the same level of radicals. JF - Practice Periodical of Hazardous, Toxic, and Radioactive Waste Management AU - Yeh, CK-J AU - Chen, W-S AU - Chen, W-Y AD - Dept. of Environmental Science and Engineering, National Pingtung Univ. of Science and Technology, 1 Hseuh Fu Rd., Nei Pu 91207, Pingtung, Taiwan, ROC, kjyeh@mail.npust.edu.tw Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 161 EP - 165 VL - 8 IS - 3 SN - 1090-025X, 1090-025X KW - Pollution Abstracts KW - Aquifers KW - Radioactive wastes KW - Hydrogen KW - Iron KW - Hazardous wastes KW - pH KW - Hydroxyl radicals KW - Waste management KW - Catalysis KW - P 4000:WASTE MANAGEMENT UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17282840?accountid=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=Practice+Periodical+of+Hazardous%2C+Toxic%2C+and+Radioactive+Waste+Management&rft.atitle=Production+of+Hydroxyl+Radicals+from+the+Decomposition+of+Hydrogen+Peroxide+Catalyzed+by+Various+Iron+Oxides+at+pH+7&rft.au=Yeh%2C+CK-J%3BChen%2C+W-S%3BChen%2C+W-Y&rft.aulast=Yeh&rft.aufirst=CK-J&rft.date=2004-07-01&rft.volume=8&rft.issue=3&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Practice+Periodical+of+Hazardous%2C+Toxic%2C+and+Radioactive+Waste+Management&rft.issn=1090025X&rft_id=info:doi/10.1061%2F%28ASCE%291090-025X%282004%298%3A3%28161%29 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Aquifers; Radioactive wastes; Hydrogen; Iron; pH; Hazardous wastes; Catalysis; Waste management; Hydroxyl radicals DO - http://dx.doi.org/10.1061/(ASCE)1090-025X(2004)8:3(161) ER - TY - JOUR T1 - Protein microarray detection strategies: focus on direct detection technologies AN - 17275743; 6045675 AB - Protein microarrays are being utilized for functional proteomic analysis, providing information not obtainable by gene arrays. Microarray technology is applicable for studying protein-protein, protein-ligand, kinase activity and posttranslational modifications of proteins. A precise and sensitive protein microarray, the direct detection or reverse-phase microarray, has been applied to ongoing clinical trials at the National Cancer Institute for studying phosphorylation events in EGF-receptor-mediated cell signaling pathways. The variety of microarray applications allows for multiple, creative microarray designs and detection strategies. Herein, we discuss detection strategies and challenges for protein microarray technology, focusing on direct detection of protein microarrays. JF - Journal of Immunological Methods AU - Espina, V AU - Woodhouse, E C AU - Wulfkuhle, J AU - Asmussen, H D AU - Petricoin, EF III AU - Liotta, LA AD - FDA-NCI Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Room B1B53, Bldg. 10, 9000 Rockville Pike, Bethesda, MD 20892, USA, espinav@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 121 EP - 133 VL - 290 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Phosphorylation KW - Protein arrays KW - Protein kinase KW - Epidermal growth factor receptors KW - F 06713:Physicochemical methods KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17275743?accountid=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=Protein+microarray+detection+strategies%3A+focus+on+direct+detection+technologies&rft.au=Espina%2C+V%3BWoodhouse%2C+E+C%3BWulfkuhle%2C+J%3BAsmussen%2C+H+D%3BPetricoin%2C+EF+III%3BLiotta%2C+LA&rft.aulast=Espina&rft.aufirst=V&rft.date=2004-07-01&rft.volume=290&rft.issue=1-2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2Fj.jim.2004.04.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Protein arrays; Protein kinase; Phosphorylation; Epidermal growth factor receptors DO - http://dx.doi.org/10.1016/j.jim.2004.04.013 ER - TY - JOUR T1 - Influenza and pneumococcal vaccination of the elderly in Taiwan AN - 1500774039; 19046149 AB - In 1998, Taiwan became the first country in Asia to provide free influenza vaccination to high-risk groups, mainly the elderly. The purpose of this study is to determine: (1) the annual mortality rate from influenza and pneumococcal-related illnesses such as pneumonia, chronic bronchitis, pulmonary emphysema and asthma and (2) the effectiveness of and adverse events associated with the influenza vaccination. In the elderly, influenza vaccination caused the annual death rate due chronic bronchitis, pulmonary emphysema, and asthma to decline steadily but had no effect on the annual pneumonia death rate. The only adverse effect of concern was vertigo (in approximately 2-3%). JF - Vaccine AU - Chen, Yeong-Hwang AU - Liou, Saou-Hsing AU - Chou, Chih-Chieh AU - Su, Wen-Lin AU - Loh, Ching-Hui AU - Lin, Shih-Ha AD - Department of Family Medicine, Tri-Service General Hospital, No. 325, Section 2, Chen-Kung Road, Nei-Hu, Taipei, Taiwan, ROC Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 2806 EP - 2811 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 22 IS - 21 SN - 0264-410X, 0264-410X KW - Risk Abstracts; Health & Safety Science Abstracts; Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Emphysema KW - Mortality KW - Taiwan KW - Elderly KW - Asthma KW - Respiratory diseases KW - Vaccination KW - vertigo KW - Influenza KW - Streptococcus pneumoniae KW - Lung KW - Geriatrics KW - Risk groups KW - Bronchitis KW - Vaccines KW - Asia KW - Pneumonia KW - Side effects KW - F 06925:Hypersensitivity KW - R2 23060:Medical and environmental health KW - J 02350:Immunology KW - H 4000:Food and Drugs KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1500774039?accountid=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=Vaccine&rft.atitle=Influenza+and+pneumococcal+vaccination+of+the+elderly+in+Taiwan&rft.au=Chen%2C+Yeong-Hwang%3BLiou%2C+Saou-Hsing%3BChou%2C+Chih-Chieh%3BSu%2C+Wen-Lin%3BLoh%2C+Ching-Hui%3BLin%2C+Shih-Ha&rft.aulast=Chen&rft.aufirst=Yeong-Hwang&rft.date=2004-07-01&rft.volume=22&rft.issue=21&rft.spage=2806&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2004.01.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-02-01 N1 - Last updated - 2014-08-21 N1 - SubjectsTermNotLitGenreText - Influenza; Mortality; Emphysema; Lung; Geriatrics; Risk groups; Asthma; Bronchitis; Vaccination; Side effects; Pneumonia; vertigo; Elderly; Vaccines; Respiratory diseases; Streptococcus pneumoniae; Taiwan; Asia DO - http://dx.doi.org/10.1016/j.vaccine.2004.01.003 ER - TY - JOUR T1 - Chlormethiazole potentiates the discriminative stimulus effects of methamphetamine in rats. AN - 66646661; 15212973 AB - Chlormethiazole is a positive modulator of gamma-aminobutyric acid (GABA)(A) receptors used in the treatment of alcohol withdrawal seizures. It recently has been reported to attenuate seizures engendered by acute and repeated exposure to cocaine in mice and neurotoxic effects of methamphetamine in rats. The aim of the present study was to determine whether chlormethiazole could also attenuate the discriminative stimulus effects of methamphetamine, a behavior predictive of the subjective effects of methamphetamine in humans. In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine [intraperitoneally (i.p.)] from saline under a fixed-ratio schedule of food delivery, the ability of chlormethiazole (i.p.) to (1) substitute for methamphetamine, (2) antagonize effects of methamphetamine and to (3) shift the methamphetamine dose-effect function was investigated. Chlormethiazole (18 and 30 mg/kg, i.p.) partially substituted for the discriminative stimulus effects of methamphetamine when administered alone (maximum group average, 60% responses on the methamphetamine-appropriate lever). Chlormethiazole did not attenuate effects of methamphetamine when coadministered with the training dose of methamphetamine. Instead, chlormethiazole potentiated the discriminative stimulus effects of methamphetamine as demonstrated by a significant (about 2.5-fold) leftward and upward shift in the methamphetamine dose-effect function in the presence of chlormethiazole (10 mg/kg). In conclusion, the present findings suggest that there is a behavioral interaction between methamphetamine and chlormethiazole. The profile of this interaction is qualitatively different from that of methamphetamine and classical GABAergic drugs (i.e., benzodiazepines and barbiturates), suggesting the involvement of non-GABAergic mechanisms in the effects produced by chlormethiazole. JF - European journal of pharmacology AU - Gasior, Maciej AU - Witkin, Jeffrey M AU - Goldberg, Steven R AU - Munzar, Patrik AD - Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC: 1408, Building 10, Room 5N250, Bethesda, MD 20892-1408, USA. gasiorm@ninds.nih.gov Y1 - 2004/06/28/ PY - 2004 DA - 2004 Jun 28 SP - 183 EP - 189 VL - 494 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Central Nervous System Stimulants KW - 0 KW - GABA Modulators KW - Chlormethiazole KW - 0C5DBZ19HV KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Seizures -- chemically induced KW - Rats KW - Generalization (Psychology) -- drug effects KW - Discrimination Learning -- drug effects KW - Conditioning, Operant -- drug effects KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Neurotoxicity Syndromes -- physiopathology KW - Drug Synergism KW - Male KW - Discrimination (Psychology) -- drug effects KW - Central Nervous System Stimulants -- pharmacology KW - Central Nervous System Stimulants -- toxicity KW - GABA Modulators -- pharmacology KW - Chlormethiazole -- pharmacology KW - Methamphetamine -- pharmacology KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chlormethiazole+potentiates+the+discriminative+stimulus+effects+of+methamphetamine+in+rats.&rft.au=Gasior%2C+Maciej%3BWitkin%2C+Jeffrey+M%3BGoldberg%2C+Steven+R%3BMunzar%2C+Patrik&rft.aulast=Gasior&rft.aufirst=Maciej&rft.date=2004-06-28&rft.volume=494&rft.issue=2-3&rft.spage=183&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 - 2005-02-14 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High urea and NaCl carbonylate proteins in renal cells in culture and in vivo, and high urea causes 8-oxoguanine lesions in their DNA. AN - 66643313; 15190183 AB - Urea and NaCl are elevated in the renal inner medulla. We now find that a high concentration of urea or NaCl increases reactive oxygen species (ROS) in mouse renal inner medullary (mIMCD3) cells in culture. Previously, high NaCl, but not high urea, was found to cause DNA double-strand breaks. We now tested whether high urea or NaCl causes oxidative damage to DNA or cellular proteins. We find that high urea increases mIMCD3 cell DNA single-strand breaks and 8-oxoguanine lesions. High NaCl does not cause detectable 8-oxoguanine lesions. High urea or NaCl also greatly increases carbonylation of proteins in mIMCD3 cells. Carbonylation occurs within 5 min and with as little as 5 mM urea, a normal plasma level. It increases as urea is raised over the range in uremia. A high raffinose level increases ROS and carbonylation. High sorbitol and glycerol levels do not increase ROS or carbonylation. Carbonyl content is high in mouse renal inner medullas where interstitial NaCl and urea concentrations are normally high. There, numerous proteins are carbonylated, and carbonylation occurs in both collecting ducts and thin limbs. (i) Oxidative stress, associated with high urea, causes 8-oxoguanine DNA lesions in mIMCD3 cell DNA. (ii) High urea or NaCl carbonylates proteins in mIMCD3 cells and in renal inner medullary cells in vivo. (iii) In mIMCD3 cells a normal plasma concentration of urea causes carbonylation, and carbonylation increases over the uremic range of urea concentration, indicating that urea can contribute directly to the carbonylation found in uremia. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zhang, Zheng AU - Dmitrieva, Natalia I AU - Park, Jong-Hwan AU - Levine, Rodney L AU - Burg, Maurice B AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA. zhangz@nhlbi.nih.gov Y1 - 2004/06/22/ PY - 2004 DA - 2004 Jun 22 SP - 9491 EP - 9496 VL - 101 IS - 25 SN - 0027-8424, 0027-8424 KW - Reactive Oxygen Species KW - 0 KW - Sodium Chloride KW - 451W47IQ8X KW - Sorbitol KW - 506T60A25R KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - Urea KW - 8W8T17847W KW - Glycerol KW - PDC6A3C0OX KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Comet Assay KW - Animals KW - Cells, Cultured KW - Sorbitol -- pharmacology KW - Mice KW - Glycerol -- pharmacology KW - Kidney -- metabolism KW - Kidney Medulla -- metabolism KW - Kidney Medulla -- drug effects KW - Kidney -- cytology KW - Guanine -- analysis KW - Kidney Medulla -- cytology KW - Guanine -- analogs & derivatives KW - Urea -- pharmacology KW - Sodium Chloride -- pharmacology KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66643313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High+urea+and+NaCl+carbonylate+proteins+in+renal+cells+in+culture+and+in+vivo%2C+and+high+urea+causes+8-oxoguanine+lesions+in+their+DNA.&rft.au=Zhang%2C+Zheng%3BDmitrieva%2C+Natalia+I%3BPark%2C+Jong-Hwan%3BLevine%2C+Rodney+L%3BBurg%2C+Maurice+B&rft.aulast=Zhang&rft.aufirst=Zheng&rft.date=2004-06-22&rft.volume=101&rft.issue=25&rft.spage=9491&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 - 2004-08-23 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Physiol. 1985 Apr;248(4 Pt 2):F522-6 [3985159] Science. 1982 Sep 24;217(4566):1214-22 [7112124] Arch Biochem Biophys. 1991 Sep;289(2):371-5 [1680314] Am J Physiol. 1993 Sep;265(3 Pt 2):F416-24 [8214101] Methods Enzymol. 1994;233:346-57 [8015469] J Biol Chem. 1994 Oct 14;269(41):25865-70 [7929290] Mutat Res. 1995 Feb;339(1):37-59 [7877644] J Clin Invest. 1996 Apr 15;97(8):1884-9 [8621772] Free Radic Res. 1996 Jan;24(1):1-7 [8747887] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11242-7 [8855340] J Histochem Cytochem. 1998 Jun;46(6):731-5 [9603784] J Biol Chem. 1998 Aug 28;273(35):22165-8 [9712826] Clin Exp Pharmacol Physiol. 1999 Jan;26(1):69-73 [10027073] Am J Physiol. 1999 May;276(5 Pt 2):F786-93 [10330061] Am J Physiol. 1990 Jan;258(1 Pt 2):F154-61 [2105661] Ann N Y Acad Sci. 2000;899:191-208 [10863540] Methods Mol Biol. 2000;99:15-24 [10909073] Nat Cell Biol. 2000 Sep;2(9):E163-5 [10980714] Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1005-28 [11076791] Kidney Int. 2000 Dec;58(6):2571-8 [11115093] Kidney Int Suppl. 2001 Feb;78:S102-7 [11168993] Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1999-2004 [11172065] Free Radic Biol Med. 2002 May 1;32(9):790-6 [11978480] Am J Physiol Renal Physiol. 2002 Oct;283(4):F792-8 [12217871] Pflugers Arch. 2002 Oct;445(1):67-73 [12397389] DNA Repair (Amst). 2003 Feb 3;2(2):211-29 [12531391] Trends Mol Med. 2003 Apr;9(4):169-76 [12727143] Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2317-22 [14983007] Comment In: Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9177-8 [15199186] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of histone H2B at DNA double-strand breaks. AN - 66640091; 15197225 AB - Posttranslational modifications of histone tails regulate numerous biological processes including transcription, DNA repair, and apoptosis. Although recent studies suggest that structural alterations in chromatin are critical for triggering the DNA damage response, very little is known about the nature of DNA damage-induced chromatin perturbations. Here we show that the serine 14 residue in the NH(2)-terminal tail of histone H2B is rapidly phosphorylated at sites of DNA double-strand breaks. At late time points after irradiation, the phosphorylated form of H2B, H2B-(Ser14P), accumulates into irradiation-induced foci. H2B-(Ser14P) foci formation is not associated with the apoptotic phosphorylation of H2B but is strictly dependent on the phosphorylated isoform of H2AX. Our results broaden the spectrum of histone modifications that constitute the DNA damage "histone code" and suggest a model for the underlying chromatin structure within damage-induced foci. JF - The Journal of experimental medicine AU - Fernandez-Capetillo, Oscar AU - Allis, C David AU - Nussenzweig, André AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/06/21/ PY - 2004 DA - 2004 Jun 21 SP - 1671 EP - 1677 VL - 199 IS - 12 SN - 0022-1007, 0022-1007 KW - Chromatin KW - 0 KW - Histones KW - Index Medicus KW - Animals KW - DNA Repair KW - Protein Processing, Post-Translational KW - Chromatin -- physiology KW - Mice KW - Fibroblasts -- cytology KW - Dose-Response Relationship, Radiation KW - Models, Biological KW - Mice, Knockout KW - Mutagenesis, Site-Directed KW - Fibroblasts -- immunology KW - Infrared Rays KW - Phosphorylation KW - Genes, Reporter KW - Fibroblasts -- radiation effects KW - Embryo, Mammalian KW - Immunohistochemistry KW - T-Lymphocytes -- immunology KW - Signal Transduction KW - Amino Acid Substitution KW - Histones -- deficiency KW - DNA Damage -- physiology KW - Histones -- metabolism KW - Histones -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66640091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+of+histone+H2B+at+DNA+double-strand+breaks.&rft.au=Fernandez-Capetillo%2C+Oscar%3BAllis%2C+C+David%3BNussenzweig%2C+Andr%C3%A9&rft.aulast=Fernandez-Capetillo&rft.aufirst=Oscar&rft.date=2004-06-21&rft.volume=199&rft.issue=12&rft.spage=1671&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 - 2004-09-03 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Curr Biol. 2000 Jul 27-Aug 10;10(15):886-95 [10959836] Cell. 1998 May 1;93(3):477-86 [9590181] Nat Genet. 2001 Mar;27(3):271-6 [11242108] Science. 2001 Aug 10;293(5532):1074-80 [11498575] EMBO J. 2001 Nov 15;20(22):6383-93 [11707409] Nature. 2001 Dec 6;414(6864):660-5 [11740565] Science. 2002 May 3;296(5569):922-7 [11934988] Proc Natl Acad Sci U S A. 2002 May 28;99(11):7420-5 [12032298] Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8173-8 [12034884] Nat Cell Biol. 2002 Dec;4(12):993-7 [12447390] Nature. 2003 Jan 30;421(6922):499-506 [12556884] J Biol Chem. 2000 Mar 31;275(13):9390-5 [10734083] Nat Rev Cancer. 2003 Mar;3(3):155-68 [12612651] J Cell Biol. 2003 Mar 31;160(7):1017-27 [12668657] Dev Cell. 2003 Apr;4(4):497-508 [12689589] Cell. 2003 May 16;113(4):507-17 [12757711] J Exp Med. 2003 Jun 16;197(12):1767-78 [12810694] Nat Cell Biol. 2003 Jul;5(7):675-9 [12792649] Biochem Cell Biol. 2003 Jun;81(3):123-9 [12897845] Cell. 2003 Aug 8;114(3):359-70 [12914700] Cell. 2003 Aug 8;114(3):371-83 [12914701] Cell. 2003 Nov 26;115(5):523-35 [14651845] Int J Radiat Biol. 1994 Feb;65(2):203-15 [7907118] Mol Cell Biol. 1997 Oct;17(10):6087-96 [9315668] J Biol Chem. 1998 Mar 6;273(10):5858-68 [9488723] Curr Biol. 1998 Mar 26;8(7):377-85 [9545195] Science. 2000 Dec 8;290(5498):1962-5 [11110662] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation-induced cytosine deaminase (AID) is actively exported out of the nucleus but retained by the induction of DNA breaks. AN - 72019691; 15087440 AB - Activation-induced cytosine deaminase (AID) is a cytosine deaminase that is critical to immunoglobulin hypermutation, class switch recombination, and gene conversion. In the context of hypermutating B cells, AID deaminates cytosine in the DNA of immunoglobulin genes, leading to the accumulation of mutations in the variable regions. However, when AID is expressed ectopically, it is a generalized mutator of G:C base pairs. Therefore, we asked whether AID may be partially regulated by an active system of nuclear export. We found that removal of a highly conserved nuclear export signal in the C terminus of AID causes accumulation of AID in the nucleus. However, a putative nuclear localization signal in the N terminus does not appear to be functional. Finally, we found that agents that induce DNA breaks caused retention of AID in the nucleus, suggesting that DNA breaks or the repair patches initiated as a result are a substrate for AID binding. JF - The Journal of biological chemistry AU - Brar, Sukhdev S AU - Watson, Mary AU - Diaz, Marilyn AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 2004/06/18/ PY - 2004 DA - 2004 Jun 18 SP - 26395 EP - 26401 VL - 279 IS - 25 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Immunoglobulins KW - Proteome KW - Bleomycin KW - 11056-06-7 KW - Hydrogen Peroxide KW - BBX060AN9V KW - AICDA (activation-induced cytidine deaminase) KW - EC 3.5.4.- KW - Cytosine Deaminase KW - EC 3.5.4.1 KW - Cytidine Deaminase KW - EC 3.5.4.5 KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - Immunoglobulins -- genetics KW - DNA Damage KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Models, Biological KW - Molecular Sequence Data KW - Flow Cytometry KW - Sequence Homology, Amino Acid KW - Bleomycin -- pharmacology KW - Comet Assay KW - Active Transport, Cell Nucleus KW - Plasmids -- metabolism KW - DNA Repair KW - Gamma Rays KW - Amino Acid Sequence KW - Mice KW - Protein Binding KW - Chickens KW - DNA, Complementary -- metabolism KW - Protein Structure, Tertiary KW - Mutation KW - Cell Line KW - Protein Transport KW - Cell Nucleus -- metabolism KW - Cytosine Deaminase -- chemistry KW - Cytosine Deaminase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72019691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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-induced+cytosine+deaminase+%28AID%29+is+actively+exported+out+of+the+nucleus+but+retained+by+the+induction+of+DNA+breaks.&rft.au=Brar%2C+Sukhdev+S%3BWatson%2C+Mary%3BDiaz%2C+Marilyn&rft.aulast=Brar&rft.aufirst=Sukhdev&rft.date=2004-06-18&rft.volume=279&rft.issue=25&rft.spage=26395&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 - 2004-07-23 N1 - Date created - 2004-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. AN - 72039225; 15181200 AB - Loss-of-function DJ-1 mutations can cause early-onset Parkinson's disease. The function of DJ-1 is unknown, but an acidic isoform accumulates after oxidative stress, leading to the suggestion that DJ-1 is protective under these conditions. We addressed whether this represents a posttranslational modification at cysteine residues by systematically mutating cysteine residues in human DJ-1. WT or C53A DJ-1 was readily oxidized in cultured cells, generating a pI 5.8 isoform, but an artificial C106A mutant was not. We observed a cysteine-sulfinic acid at C106 in crystalline DJ-1 but no modification of C53 or C46. Oxidation of DJ-1 was promoted by the crystallization procedure. In addition, oxidation-induced mitochondrial relocalization of DJ-1 and protection against cell death were abrogated in C106A but not C53A or C46A. We suggest that DJ-1 protects against neuronal death, and that this is signaled by acidification of the key cysteine residue, C106. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Canet-Avilés, Rosa M AU - Wilson, Mark A AU - Miller, David W AU - Ahmad, Rili AU - McLendon, Chris AU - Bandyopadhyay, Sourav AU - Baptista, Melisa J AU - Ringe, Dagmar AU - Petsko, Gregory A AU - Cookson, Mark R AD - Laboratory of Neurogenetics, National Institute on Aging, 9000 Rockville Pike, Bethesda, MD 20892-1589, USA. Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 9103 EP - 9108 VL - 101 IS - 24 SN - 0027-8424, 0027-8424 KW - Intracellular Signaling Peptides and Proteins KW - 0 KW - Neuroprotective Agents KW - Neurotransmitter Agents KW - Oncogene Proteins KW - Protein Isoforms KW - Recombinant Proteins KW - cysteine sulfinic acid KW - 2381-08-0 KW - PARK7 protein, human KW - EC 3.1.2.- KW - Protein Deglycase DJ-1 KW - Cysteine KW - K848JZ4886 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Index Medicus KW - 1-Methyl-4-phenylpyridinium -- toxicity KW - Models, Molecular KW - Humans KW - Cell Line, Tumor KW - Recombinant Proteins -- genetics KW - Static Electricity KW - Oxidation-Reduction KW - Transfection KW - Recombinant Proteins -- metabolism KW - Oxidative Stress KW - Recombinant Proteins -- chemistry KW - Intracellular Membranes -- metabolism KW - Amino Acid Substitution KW - Cysteine -- metabolism KW - Cysteine -- chemistry KW - Oncogene Proteins -- chemistry KW - Cysteine -- genetics KW - Neuroprotective Agents -- metabolism KW - Oncogene Proteins -- genetics KW - Mitochondria -- metabolism KW - Oncogene Proteins -- metabolism KW - Cysteine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72039225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Parkinson%27s+disease+protein+DJ-1+is+neuroprotective+due+to+cysteine-sulfinic+acid-driven+mitochondrial+localization.&rft.au=Canet-Avil%C3%A9s%2C+Rosa+M%3BWilson%2C+Mark+A%3BMiller%2C+David+W%3BAhmad%2C+Rili%3BMcLendon%2C+Chris%3BBandyopadhyay%2C+Sourav%3BBaptista%2C+Melisa+J%3BRinge%2C+Dagmar%3BPetsko%2C+Gregory+A%3BCookson%2C+Mark+R&rft.aulast=Canet-Avil%C3%A9s&rft.aufirst=Rosa&rft.date=2004-06-15&rft.volume=101&rft.issue=24&rft.spage=9103&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 - 2004-08-05 N1 - Date created - 2004-06-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1SOA; PDB N1 - SuppNotes - Cited By: Neurobiol Dis. 2000 Aug;7(4):240-50 [10964596] Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 [2025413] Free Radic Res. 2001 Dec;35(6):885-93 [11811539] Neuron. 2002 Dec 19;36(6):1007-19 [12495618] Science. 2003 Jan 10;299(5604):256-9 [12446870] Hum Mol Genet. 2003 Mar 1;12(5):517-26 [12588799] J Biol Chem. 2003 Feb 21;278(8):6371-83 [12475980] Science. 2003 Apr 25;300(5619):650-3 [12714747] Science. 2003 Apr 25;300(5619):653-6 [12714748] Biochem Biophys Res Commun. 2003 May 9;304(3):463-70 [12729580] Acta Crystallogr D Biol Crystallogr. 2003 Aug;59(Pt 8):1502-3 [12876366] Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9256-61 [12855764] J Biol Chem. 2003 Aug 15;278(33):31372-9 [12761214] J Biol Chem. 2003 Aug 15;278(33):31380-4 [12796482] FEBS Lett. 2003 Aug 14;549(1-3):171-5 [12914946] J Biol Chem. 2003 Sep 19;278(38):36588-95 [12851414] J Biol Chem. 2003 Sep 26;278(39):37146-53 [12853451] Nature. 2003 Oct 30;425(6961):980-4 [14586471] Science. 2003 Oct 31;302(5646):819-22 [14593166] J Biol Chem. 2003 Nov 7;278(45):44552-9 [12939276] Biochem Biophys Res Commun. 2003 Dec 26;312(4):1342-8 [14652021] Nat Cell Biol. 2003 Dec;5(12):1083-9 [14634665] Brain. 2004 Feb;127(Pt 2):420-30 [14662519] EMBO Rep. 2004 Feb;5(2):213-8 [14749723] Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1531-6 [14745011] J Biol Chem. 2004 Feb 20;279(8):6943-51 [14607841] J Biol Chem. 2004 Feb 27;279(9):8506-15 [14665635] Biochem Biophys Res Commun. 2004 May 7;317(3):722-8 [15081400] BMC Evol Biol. 2004 Feb 19;4:6 [15070401] Free Radic Res. 2001 Sep;35(3):301-10 [11697128] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Herbal remedies in the United States: potential adverse interactions with anticancer agents. AN - 72029281; 15197212 AB - Interest in the use of herbal products has grown dramatically in the Western world. Recent estimates suggest an overall prevalence for herbal preparation use of 13% to 63% among cancer patients. With the narrow therapeutic range associated with most anticancer drugs, there is an increasing need for understanding possible adverse drug interactions in medical oncology. In this article, a literature overview is provided of known or suspected interactions of the 15 best-selling herbs in the United States with conventional allopathic therapies for cancer. Herbs with the potential to significantly modulate the activity of drug-metabolizing enzymes (notably cytochrome p450 isozymes) and/or the drug transporter P-glycoprotein include garlic (Allium sativum), ginkgo (Ginkgo biloba), echinacea (Echinacea purpurea), ginseng (Panax ginseng), St John' s wort (Hypericum perforatum), and kava (Piper methysticum). All of these products participate in potential pharmacokinetic interactions with anticancer drugs. It is suggested that health care professionals and consumers should be aware of the potential for adverse interactions with these herbs, question their patients on their use of them, especially among patients whose disease is not responding to treatments as expected, and urge patients to avoid herbs that could confound their cancer care. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Sparreboom, Alex AU - Cox, Michael C AU - Acharya, Milin R AU - Figg, William D AD - Clinical Pharmacology Research Core, Medical Oncology Clinical Research Unit, National Cancer Institute, Bethesda, Maryland 20892, USA. sparreba@mail.nih.gov Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 2489 EP - 2503 VL - 22 IS - 12 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Plant Preparations KW - Index Medicus KW - United States KW - Humans KW - Plant Preparations -- adverse effects KW - Dietary Supplements -- adverse effects KW - Herb-Drug Interactions KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72029281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Herbal+remedies+in+the+United+States%3A+potential+adverse+interactions+with+anticancer+agents.&rft.au=Sparreboom%2C+Alex%3BCox%2C+Michael+C%3BAcharya%2C+Milin+R%3BFigg%2C+William+D&rft.aulast=Sparreboom&rft.aufirst=Alex&rft.date=2004-06-15&rft.volume=22&rft.issue=12&rft.spage=2489&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 - 2004-06-29 N1 - Date created - 2004-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality from solid cancers among workers in formaldehyde industries. AN - 72015088; 15191929 AB - In industrial workers, formaldehyde exposure has been associated with cancer of the nasal cavities, nasopharynx, prostate, lung, and pancreas; however, these associations are inconsistent and remain controversial. Animals exposed to formaldehyde show excesses of nasal cancer. In an extended follow-up of a large cohort of formaldehyde-exposed workers, the authors evaluated mortality from solid cancers (1,921 deaths) among 25,619 workers (865,708 person-years) employed in 10 US formaldehyde-producing or -using facilities through 1994. Exposure assessment included quantitative estimates of formaldehyde exposure. Standardized mortality ratios and relative risks were calculated. Compared with that for the US population, mortality from solid cancers was significantly lower than expected among subjects exposed and nonexposed to formaldehyde (standardized mortality ratios = 0.91 and 0.78, respectively). Relative risks for nasopharyngeal cancer (nine deaths) increased with average exposure intensity, cumulative exposure, highest peak exposure, and duration of exposure to formaldehyde (p-trend = 0.066, 0.025, <0.001, and 0.147, respectively). Formaldehyde exposure did not appear to be associated with lung (744 deaths), pancreas (93 deaths), or brain (62 deaths) cancer. Although relative risks for prostate cancer (145 deaths) were elevated for some measures of formaldehyde exposure, the trend was inconsistent. In this cohort of formaldehyde-industry workers, some evidence was found of an exposure-response relation with mortality from nasopharyngeal cancer (based on small numbers) but not for cancers of the pancreas, brain, lung, or prostate. JF - American journal of epidemiology AU - Hauptmann, Michael AU - Lubin, Jay H AU - Stewart, Patricia A AU - Hayes, Richard B AU - Blair, Aaron AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, MD 20892, USA. hauptmann@nih.gov Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 1117 EP - 1130 VL - 159 IS - 12 SN - 0002-9262, 0002-9262 KW - Disinfectants KW - 0 KW - Formaldehyde KW - 1HG84L3525 KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Middle Aged KW - Male KW - Female KW - Occupational Exposure KW - Disinfectants -- poisoning KW - Neoplasms -- mortality KW - Formaldehyde -- poisoning KW - Neoplasms -- etiology KW - Chemical Industry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72015088?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Mortality+from+solid+cancers+among+workers+in+formaldehyde+industries.&rft.au=Hauptmann%2C+Michael%3BLubin%2C+Jay+H%3BStewart%2C+Patricia+A%3BHayes%2C+Richard+B%3BBlair%2C+Aaron&rft.aulast=Hauptmann&rft.aufirst=Michael&rft.date=2004-06-15&rft.volume=159&rft.issue=12&rft.spage=1117&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 completed - 2004-07-13 N1 - Date created - 2004-06-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Epidemiol. 2005 Jun 1;161(11):1089-90; author reply 1090-1 [15901630] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial DNA sequence heterogeneity in circulating normal human CD34 cells and granulocytes. AN - 72001932; 15016645 AB - We have reported marked mitochondrial DNA (mtDNA) sequence heterogeneity among individual CD34 clones from adult bone marrow (BM) and the age-dependent accumulation of mtDNA mutations in this mitotically active tissue. Here, we show direct evidence of clonal expansion of cells containing mtDNA mutations and that the mtDNA sequence may be easily determined by using peripheral blood (PB) as a CD34 cell source. Analysis of 594 circulating CD34 clones showed that 150 (25%) had mtDNA sequences different from the same donor's corresponding aggregate sequence. Examination of single granulocytes indicated that 103 (29%) from the same 6 individuals showed mtDNA heterogeneity, with sequences distinct from the corresponding aggregate tissue sequence and from the sequences of other single granulocytes. Circulating and BM CD34 cells showed virtually identical patterns of mtDNA heterogeneity, and the same changes were seen in progeny granulocytes as in their progenitors, indicating that blood sampling could be used in studies to determine whether mtDNA reflects an individual's cumulative or recent exposure to mutagens; as a marker of individual hematopoietic progenitors, stem cells, and their expansion; and for the detection of minimal residual disease in hematologic malignancies of CD34 cell origin. JF - Blood AU - Shin, Myung Geun AU - Kajigaya, Sachiko AU - Tarnowka, Magdalena AU - McCoy, J Philip AU - Levin, Barbara C AU - Young, Neal S AD - Hematology Branch and Flow Cytometry Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bldg 10, Rm 7C103, 9000 Rockville Pike, Bethesda, MD 20892-1652, USA. Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 4466 EP - 4477 VL - 103 IS - 12 SN - 0006-4971, 0006-4971 KW - Antigens, CD KW - 0 KW - Antigens, CD34 KW - DNA, Mitochondrial KW - Cytochromes b KW - 9035-37-4 KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Electron Transport Complex IV -- genetics KW - Humans KW - Cytochromes b -- genetics KW - Cell Separation KW - Cloning, Molecular KW - Antigens, CD -- blood KW - Genotype KW - Polymerase Chain Reaction KW - Base Sequence KW - Adult KW - Middle Aged KW - Antigens, CD34 -- blood KW - Male KW - Female KW - Granulocytes -- physiology KW - Bone Marrow Cells -- cytology KW - Bone Marrow Cells -- physiology KW - Granulocytes -- cytology KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72001932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mitochondrial+DNA+sequence+heterogeneity+in+circulating+normal+human+CD34+cells+and+granulocytes.&rft.au=Shin%2C+Myung+Geun%3BKajigaya%2C+Sachiko%3BTarnowka%2C+Magdalena%3BMcCoy%2C+J+Philip%3BLevin%2C+Barbara+C%3BYoung%2C+Neal+S&rft.aulast=Shin&rft.aufirst=Myung&rft.date=2004-06-15&rft.volume=103&rft.issue=12&rft.spage=4466&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-29 N1 - Date created - 2004-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance. AN - 72001392; 14996704 AB - Depsipeptide (FK228) is a novel histone deacetylase inhibitor currently in clinical trials and the first to demonstrate clinical activity in patients. Responses have been observed in patients with T-cell lymphomas, despite prior treatment with multiple chemotherapeutic agents. To better understand the effects of histone deacetylase inhibitors on T-cell lymphoma, the human T-cell lymphoma cell line HUT78 was tested for sensitivity and molecular response to depsipeptide. Treatment with depsipeptide, as well as other histone deacetylase inhibitors, caused induction of histone acetylation, induction of p21 expression, and substantial apoptosis without significant cell cycle arrest. Treatment with the caspase inhibitor z-VAD-fmk significantly inhibited depsipeptide-induced apoptosis, enabling detection of cell cycle arrest. Treatment with depsipeptide increased expression of the interleukin-2 (IL-2) receptor, and combination with the IL-2 toxin conjugate denileukin diftitox resulted in more than additive toxicity. Cells selected for resistance to depsipeptide overexpressed the multidrug resistance pump, P-glycoprotein (Pgp). However, cells selected for resistance to depsipeptide in the presence of a Pgp inhibitor had a Pgp-independent mechanism of resistance. These studies confirm the activity of depsipeptide in a T-cell lymphoma model and suggest a general sensitivity of T-cell lymphoma to histone deacetylase inhibitors, an emerging new class of anticancer agents. JF - Blood AU - Piekarz, Richard L AU - Robey, Robert W AU - Zhan, Zhirong AU - Kayastha, Ganesh AU - Sayah, Anousheh AU - Abdeldaim, Amina H AU - Torrico, Sonia AU - Bates, Susan E AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute/NIH, MSC 1903, 10 Center Drive, Building 10/Room 12C103, Bethesda, MD 20892-1903, USA. rpiekarz@nih.gov Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 4636 EP - 4643 VL - 103 IS - 12 SN - 0006-4971, 0006-4971 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Histone Deacetylase Inhibitors KW - Oligopeptides KW - Abridged Index Medicus KW - Index Medicus KW - Cell Survival -- drug effects KW - Humans KW - Drug Resistance, Neoplasm KW - Cell Line, Tumor KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Lymphoma, T-Cell -- pathology KW - Enzyme Inhibitors -- toxicity KW - Antineoplastic Agents -- toxicity KW - Oligopeptides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72001392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=T-cell+lymphoma+as+a+model+for+the+use+of+histone+deacetylase+inhibitors+in+cancer+therapy%3A+impact+of+depsipeptide+on+molecular+markers%2C+therapeutic+targets%2C+and+mechanisms+of+resistance.&rft.au=Piekarz%2C+Richard+L%3BRobey%2C+Robert+W%3BZhan%2C+Zhirong%3BKayastha%2C+Ganesh%3BSayah%2C+Anousheh%3BAbdeldaim%2C+Amina+H%3BTorrico%2C+Sonia%3BBates%2C+Susan+E&rft.aulast=Piekarz&rft.aufirst=Richard&rft.date=2004-06-15&rft.volume=103&rft.issue=12&rft.spage=4636&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-29 N1 - Date created - 2004-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD28 disruption exacerbates inflammation in Tgf-beta1-/- mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-beta1. AN - 71999146; 15016653 AB - Tgf-beta1-/- mice develop a progressive, lethal, inflammatory syndrome, but mechanisms leading to the spontaneous activation of Tgf-beta1-/- T cells remain unclear. Here we show the disruption of CD28 gene expression accelerates disease in Tgf-beta1-/- mice, and we link this increase in severity to a reduction in the number of CD4+CD25+ regulatory T cells. CD4+CD25+ T cells develop normally in Tgf-beta1-/- mice and display characteristic expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), alpha(E)beta7 integrin, and Foxp3. Adoptive transfer of Tgf-beta1-/- splenocytes to Tgf-beta1+/+/Rag2-/- mice induced an autoimmune inflammatory disease with features similar to those of the Tgf-beta1-/- phenotype, and disease transfer was accelerated by the depletion of Tgf-beta1-/- CD4+CD25+ T cells from donor splenocytes. Cotransfer of Tgf- beta1-/- CD4+CD25+ T cells clearly attenuated disease in Rag2-/- recipients of CD25+-depleted Tgf-beta1-/- spleen and lymph node cells, but suppression was incomplete when compared with Tgf-beta1+/+ CD4+CD25+ T cells. These data demonstrate that CD4+CD25+ regulatory T cells develop in complete absence of endogenous transforming growth factor-beta1 (TGF-beta1) expression and that autocrine TGF-beta1 expression is not essential for these cells to suppress inflammation in vivo. JF - Blood AU - Mamura, Mizuko AU - Lee, WoonKyu AU - Sullivan, Timothy J AU - Felici, Angelina AU - Sowers, Anastasia L AU - Allison, James P AU - Letterio, John J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bldg 41, 41 Library Drive/MSC 5055, Bethesda, MD 20892-5055, USA. Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 4594 EP - 4601 VL - 103 IS - 12 SN - 0006-4971, 0006-4971 KW - Antigens, CD28 KW - 0 KW - Antigens, CD4 KW - Receptors, Interleukin-2 KW - Tgfb1 protein, mouse KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Abridged Index Medicus KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Antigens, CD4 -- genetics KW - Mice KW - Cell Separation KW - Receptors, Interleukin-2 -- genetics KW - Mice, Knockout KW - Inflammation KW - Immunosuppression KW - T-Lymphocyte Subsets -- cytology KW - Antigens, CD28 -- genetics KW - T-Lymphocyte Subsets -- immunology KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- immunology KW - Transforming Growth Factor beta -- deficiency KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71999146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=CD28+disruption+exacerbates+inflammation+in+Tgf-beta1-%2F-+mice%3A+in+vivo+suppression+by+CD4%2BCD25%2B+regulatory+T+cells+independent+of+autocrine+TGF-beta1.&rft.au=Mamura%2C+Mizuko%3BLee%2C+WoonKyu%3BSullivan%2C+Timothy+J%3BFelici%2C+Angelina%3BSowers%2C+Anastasia+L%3BAllison%2C+James+P%3BLetterio%2C+John+J&rft.aulast=Mamura&rft.aufirst=Mizuko&rft.date=2004-06-15&rft.volume=103&rft.issue=12&rft.spage=4594&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-29 N1 - Date created - 2004-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterogeneous gene methylation patterns among pre-invasive and cancerous lesions of the prostate: a histopathologic study of whole mount prostate specimens. AN - 71917140; 15129426 AB - Gene methylation may contribute to prostate carcinogenesis through the silencing of gene transcription. We report on the methylation status of several genes shown to be silenced at different stages of progression using whole mount prostate specimens and laser capture microdissection. This is the first study to evaluate gene methylation patterns across multiple pre-cancerous and invasive cancer foci from the same prostate gland. Real-time PCR was used to evaluate methylation of five genes (GSTP1, RASSF1A, RAR beta 2, CD44, and EDNRB) across normal epithelium, high-grade prostatic intraepithelial neoplasia (HGPIN), and multiple tumor foci from each of 11 prostate cancer patients. Gene methylation was not found in normal epithelium. To our knowledge, this is the first report of RASSF1A and RAR beta 2 methylation in HGPIN lesions (30% prevalence for each gene). In addition, RASSF1A, RAR beta 2, and GSTP1 methylation was highly prevalent in tumor foci (>75% for all three genes). Methylation of CD44 and EDNRB was observed in 41 and 38% of tumors but was not present in HGPIN. These data suggest that genes may be methylated at different points in the histopathologic progression of prostate cancer and these differences can be found in various histologic foci from the same gland. Copyright 2004 Wiley-Liss, Inc. JF - The Prostate AU - Woodson, Karen AU - Gillespie, John AU - Hanson, Jeffrey AU - Emmert-Buck, Mike AU - Phillips, John M AU - Linehan, W Marston AU - Tangrea, Joseph A AD - Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. kw114v@nih.gov Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 25 EP - 31 VL - 60 IS - 1 SN - 0270-4137, 0270-4137 KW - Index Medicus KW - Humans KW - Disease Progression KW - Transcription, Genetic KW - Male KW - Prostatic Neoplasms -- pathology KW - Neoplasm Invasiveness KW - Prostatic Intraepithelial Neoplasia -- genetics KW - DNA Methylation KW - Gene Silencing KW - Prostatic Neoplasms -- genetics KW - Prostatic Intraepithelial Neoplasia -- pathology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71917140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Prostate&rft.atitle=Heterogeneous+gene+methylation+patterns+among+pre-invasive+and+cancerous+lesions+of+the+prostate%3A+a+histopathologic+study+of+whole+mount+prostate+specimens.&rft.au=Woodson%2C+Karen%3BGillespie%2C+John%3BHanson%2C+Jeffrey%3BEmmert-Buck%2C+Mike%3BPhillips%2C+John+M%3BLinehan%2C+W+Marston%3BTangrea%2C+Joseph+A&rft.aulast=Woodson&rft.aufirst=Karen&rft.date=2004-06-15&rft.volume=60&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=The+Prostate&rft.issn=02704137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-15 N1 - Date created - 2004-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of radiation and ibuprofen on normoxic renal carcinoma cells overexpressing hypoxia-inducible factors by loss of von Hippel-Lindau tumor suppressor gene function. AN - 66656048; 15217953 AB - Tumor hypoxia is a major limiting factor for radiation therapy. Hypoxia-inducible factors (HIFs) are overexpressed in several human cancers and are considered prognostic markers and potential targets for cancer therapy. The purpose of the present study was to investigate the impact of HIFs on radiosensitivity. Renal clear cell carcinoma (RCC) cell lines overexpressing HIFs under normoxic conditions because of inactivation of von Hippel-Lindau tumor suppressor gene function (VHL-ve) and their matched pairs in which overexpression of HIFs was abolished by expression of functional VHL (VHL+ve) were irradiated. Radiosensitivity was determined by clonogenic assay. HIF and VHL protein levels were evaluated by Western blot analysis. RCC cells were also treated with ibuprofen, a radiosensitizer and HIF inhibitor in prostate cancer cells. The effect of ibuprofen on radiosensitization and HIF and VHL proteins was compared in RCC matched-pair cell lines. The data showed only small differences in the radiosensitivity between the cells overexpressing HIFs and cells with basal HIF levels. The dose-modifying factors for C2, 786-0, and A498 RCC cells were 1.14, 1.14 and 1.15, respectively. Radiation did not alter HIF or VHL protein levels. Ibuprofen inhibited HIFs in VHL+ve cells expressing basal levels of HIFs. In VHL-ve cells overexpressing HIFs, the inhibition was very modest. Ibuprofen radiosensitized C2 RCC cells to the same extent irrespective of their HIF status. Overexpression of HIFs in RCC cells harboring VHL mutations has only a modest effect on the radiosensitivity. Radiosensitization by ibuprofen appears to be independent of HIF status. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Palayoor, Sanjeewani T AU - Burgos, Melissa A AU - Shoaibi, Azadeh AU - Tofilon, Philip J AU - Coleman, C Norman AD - Radiation Oncology Branch, Center for Cancer Research and the Molecular Radiation Therapeutics Branch, Division of Cancer and Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland, USA. Palayoor@mail.nih.gov Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 4158 EP - 4164 VL - 10 IS - 12 Pt 1 SN - 1078-0432, 1078-0432 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Basic Helix-Loop-Helix Transcription Factors KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Trans-Activators KW - Transcription Factors KW - Tumor Suppressor Proteins KW - Vascular Endothelial Growth Factor A KW - endothelial PAS domain-containing protein 1 KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - VHL protein, human KW - EC 6.3.2.- KW - Oxygen KW - S88TT14065 KW - Ibuprofen KW - WK2XYI10QM KW - Index Medicus KW - Immunoblotting KW - Dose-Response Relationship, Drug KW - Oxygen -- metabolism KW - Humans KW - Prognosis KW - Radiation Tolerance KW - Dose-Response Relationship, Radiation KW - Cell Survival KW - Blotting, Western KW - Transfection KW - Enzyme-Linked Immunosorbent Assay KW - Up-Regulation KW - Time Factors KW - Mutation KW - Cell Line KW - Vascular Endothelial Growth Factor A -- metabolism KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Kidney Neoplasms -- drug therapy KW - Transcription Factors -- physiology KW - Carcinoma -- radiotherapy KW - Tumor Suppressor Proteins -- genetics KW - Ibuprofen -- pharmacology KW - Ubiquitin-Protein Ligases -- physiology KW - Transcription Factors -- genetics KW - Trans-Activators -- genetics KW - Tumor Suppressor Proteins -- physiology KW - Carcinoma -- drug therapy KW - Ubiquitin-Protein Ligases -- genetics KW - Kidney Neoplasms -- radiotherapy KW - Trans-Activators -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66656048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+radiation+and+ibuprofen+on+normoxic+renal+carcinoma+cells+overexpressing+hypoxia-inducible+factors+by+loss+of+von+Hippel-Lindau+tumor+suppressor+gene+function.&rft.au=Palayoor%2C+Sanjeewani+T%3BBurgos%2C+Melissa+A%3BShoaibi%2C+Azadeh%3BTofilon%2C+Philip+J%3BColeman%2C+C+Norman&rft.aulast=Palayoor&rft.aufirst=Sanjeewani&rft.date=2004-06-15&rft.volume=10&rft.issue=12+Pt+1&rft.spage=4158&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 - 2005-01-03 N1 - Date created - 2004-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antitumor effects of thalidomide analogs in human prostate cancer xenografts implanted in immunodeficient mice. AN - 66655649; 15217957 AB - Thalidomide has demonstrated clinical activity in various malignancies including androgen-independent prostate cancer. The development of novel thalidomide analogs with better activity/toxicity profiles is an ongoing research effort. Our laboratory previously reported the in vitro antiangiogenic activity of the N-substituted thalidomide analog CPS11 and the tetrafluorinated analogs CPS45 and CPS49. The current study evaluated the therapeutic potential of these analogs in the treatment of prostate cancer in vivo. Severely combined immunodeficient mice bearing s.c. human prostate cancer (PC3 or 22Rv1) xenografts were treated with the analogs at their maximum tolerated doses. Tumors were then excised and processed for ELISA and CD31 immunostaining to determine the levels of various angiogenic factors and microvessel density (MVD), respectively. CPS11, CPS45, and CPS49 induced prominent and modest growth inhibition in PC3 and 22Rv1 tumors, respectively. Thalidomide had no effect on tumor growth in either xenograft. Vascular endothelial growth factor and basic fibroblast growth factor levels were not significantly altered by any of the thalidomide analogs or thalidomide in both PC3 and 22Rv1 tumors. CPS45, CPS49, and thalidomide significantly reduced PC3 tumor platelet-derived growth factor (PDGF)-AA levels by 58-82% (P /=1.5-fold) of genes encoding PDGF and PDGF receptor isoforms as determined by DNA microarray analysis. Intratumoral MVD of 22Rv1 xenografts was significantly decreased by CPS45 and CPS49. CPS49 also reduced MVD in PC3 xenografts. Thalidomide analogs CPS11 and 49 are promising anti-cancer agents. PDGF signaling pathway may be a potential target for these thalidomide analogs. Detailed microarray and functional analyses are under way with the aim of elucidating the molecular mechanism(s) of action of these thalidomide analogs. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Ng, Sylvia S W AU - MacPherson, Gordon R AU - Gütschow, Michael AU - Eger, Kurt AU - Figg, William D AD - Molecular Pharmacology Section, Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA. Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 4192 EP - 4197 VL - 10 IS - 12 Pt 1 SN - 1078-0432, 1078-0432 KW - Antigens, CD31 KW - 0 KW - Antineoplastic Agents KW - CPS 11 KW - CPS 45 KW - CPS 49 KW - Platelet-Derived Growth Factor KW - Protein Isoforms KW - platelet-derived growth factor A KW - Thalidomide KW - 4Z8R6ORS6L KW - Receptors, Platelet-Derived Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Receptors, Platelet-Derived Growth Factor -- metabolism KW - Platelet-Derived Growth Factor -- metabolism KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Antigens, CD31 -- biosynthesis KW - Cell Line, Tumor KW - Mice KW - Neoplasm Transplantation KW - Neoplasm Metastasis KW - Enzyme-Linked Immunosorbent Assay KW - Neovascularization, Pathologic KW - Mice, SCID KW - Microcirculation KW - Time Factors KW - Immunohistochemistry KW - Signal Transduction KW - Male KW - Thalidomide -- therapeutic use KW - Prostatic Neoplasms -- drug therapy KW - Thalidomide -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Thalidomide -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66655649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antitumor+effects+of+thalidomide+analogs+in+human+prostate+cancer+xenografts+implanted+in+immunodeficient+mice.&rft.au=Ng%2C+Sylvia+S+W%3BMacPherson%2C+Gordon+R%3BG%C3%BCtschow%2C+Michael%3BEger%2C+Kurt%3BFigg%2C+William+D&rft.aulast=Ng&rft.aufirst=Sylvia+S&rft.date=2004-06-15&rft.volume=10&rft.issue=12+Pt+1&rft.spage=4192&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 - 2005-01-03 N1 - Date created - 2004-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mesothelin: a new target for immunotherapy. AN - 66654837; 15217923 AB - Mesothelin is a differentiation antigen present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The mesothelin gene encodes a precursor protein that is processed to yield the 40-kDa protein, mesothelin, attached to the cell membrane by a glycosylphosphatidyl inositol linkage and a 31-kDa shed fragment named megakaryocyte-potentiating factor. The biological function of mesothelin is not known. Mesothelin is a promising candidate for tumor-specific therapy, given its limited expression in normal tissues and high expression in several cancers. SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin that is undergoing clinical evaluation in patients with mesothelin-expressing tumors. There is evidence that mesothelin is an immunogenic protein and could be exploited as a therapeutic cancer vaccine. A soluble mesothelin variant has been identified and could be a useful tumor marker for malignant mesotheliomas. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Hassan, Raffit AU - Bera, Tapan AU - Pastan, Ira AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland, USA. hassanr@mail.nih.gov Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 3937 EP - 3942 VL - 10 IS - 12 Pt 1 SN - 1078-0432, 1078-0432 KW - Antigens, Neoplasm KW - 0 KW - Biomarkers, Tumor KW - GPI-Linked Proteins KW - Glycosylphosphatidylinositols KW - Immunotoxins KW - Membrane Glycoproteins KW - Recombinant Proteins KW - mesothelin KW - Index Medicus KW - Megakaryocytes -- chemistry KW - Animals KW - Humans KW - Clinical Trials as Topic KW - Glycosylphosphatidylinositols -- chemistry KW - Mice KW - Mice, Nude KW - Immunotoxins -- chemistry KW - Models, Chemical KW - Recombinant Proteins -- chemistry KW - Protein Structure, Tertiary KW - Immunohistochemistry KW - Neoplasms -- metabolism KW - Membrane Glycoproteins -- chemistry KW - Membrane Glycoproteins -- physiology KW - Membrane Glycoproteins -- genetics KW - Immunotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66654837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mesothelin%3A+a+new+target+for+immunotherapy.&rft.au=Hassan%2C+Raffit%3BBera%2C+Tapan%3BPastan%2C+Ira&rft.aulast=Hassan&rft.aufirst=Raffit&rft.date=2004-06-15&rft.volume=10&rft.issue=12+Pt+1&rft.spage=3937&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 - 2005-01-03 N1 - Date created - 2004-06-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Cancer Res. 2004 Dec 15;10(24):8751; author reply 8752 [15623661] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diesel Exhaust, Solvents, and Other Occupational Exposures as Risk Factors for Wheeze among Farmers AN - 17698000; 6108051 AB - Farmers engage in activities that result in exposure to diesel exhaust, solvents, welding fumes, and other respiratory irritants. Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina, we evaluated the odds of wheeze associated with nonpesticide occupational exposures. We used logistic regression models controlling for age, state, smoking, and history of asthma or atopy to evaluate odds of wheeze in the past year among the 20,898 farmers who provided complete information on all covariates. Driving diesel tractors was associated with elevated odds of wheeze (odds ratio = 1.31; 95% confidence interval = 1.13, 1.52); the odds ratio for driving gasoline tractors was 1.11 (95% confidence interval = 1.02, 1.21). A duration-response relationship was observed for driving diesel tractors but not for driving gasoline tractors. Activities involving solvent exposure, including painting and use of solvents for cleaning, were associated with an increased odds of wheeze in a duration-dependent fashion. The highest odds of wheeze for farm activities were for daily painting (odds ratio = 1.82; 95% confidence interval = 0.89, 3.73), an indication of daily solvent exposure. These results add to the growing body of evidence of adverse respiratory effects of diesel exposure on the lung and suggest exposure to solvents may contribute as well. JF - American Journal of Respiratory and Critical Care Medicine AU - Hoppin, JA AU - Umbach, D M AU - London, S J AU - Alavanja, MCR AU - Sandler, D P AD - NIEHS, Epidemiology Branch, MD A3-05, P.O. Box 12233, Research Triangle Park, NC 27709-2233, USA, hoppin1@niehs.nih.gov Y1 - 2004/06/15/ PY - 2004 DA - 2004 Jun 15 SP - 1308 EP - 1313 VL - 169 IS - 12 SN - 0003-0805, 0003-0805 KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Historical account KW - USA, North Carolina KW - Gasoline KW - Respiratory diseases KW - Exhaust emissions KW - Asthma KW - Agriculture KW - Welding KW - Occupational exposure KW - Fumes KW - Solvents KW - USA, Iowa KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17698000?accountid=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+Respiratory+and+Critical+Care+Medicine&rft.atitle=Diesel+Exhaust%2C+Solvents%2C+and+Other+Occupational+Exposures+as+Risk+Factors+for+Wheeze+among+Farmers&rft.au=Hoppin%2C+JA%3BUmbach%2C+D+M%3BLondon%2C+S+J%3BAlavanja%2C+MCR%3BSandler%2C+D+P&rft.aulast=Hoppin&rft.aufirst=JA&rft.date=2004-06-15&rft.volume=169&rft.issue=12&rft.spage=1308&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.issn=00030805&rft_id=info:doi/10.1164%2Frccm.200309-1228OC LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA, North Carolina; USA, Iowa; Solvents; Agriculture; Exhaust emissions; Gasoline; Occupational exposure; Fumes; Welding; Historical account; Asthma; Respiratory diseases DO - http://dx.doi.org/10.1164/rccm.200309-1228OC ER - TY - JOUR T1 - The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991-1992 and 2001-2002. AN - 72022607; 15194200 AB - Alcohol abuse and dependence can be disabling disorders, but accurate information is lacking on the prevalence of current DSM-IV alcohol abuse and dependence and how this has changed over the past decade. The purpose of this study was to present nationally representative data on the prevalence of 12-month DSM-IV alcohol abuse and dependence in 2001-2002 and, for the first time, to examine trends in alcohol abuse and dependence between 1991-1992 and 2001-2002. Prevalences and trends of alcohol abuse and dependence in the United States were derived from face-to-face interviews in the National Institute on Alcohol Abuse and Alcoholism's (NIAAA) 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC: n = 43, 093 ) and NIAAA's 1991-1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES: n= 42, 862 ). Prevalences of DSM-IV alcohol abuse and dependence in 2001-2002 were 4.65 and 3.81%. Abuse and dependence were more common among males and among younger respondents. The prevalence of abuse was greater among Whites than among Blacks, Asians, and Hispanics. The prevalence of dependence was higher in Whites, Native Americans, and Hispanics than Asians. Between 1991-1992 and 2001-2002, abuse increased while dependence declined. Increases in alcohol abuse were observed among males, females, and young Black and Hispanic minorities, while the rates of dependence rose among males, young Black females and Asian males. This study underscores the need to continue monitoring prevalence and trends and to design culturally sensitive prevention and intervention programs. JF - Drug and alcohol dependence AU - Grant, Bridget F AU - Dawson, Deborah A AU - Stinson, Frederick S AU - Chou, S Patricia AU - Dufour, Mary C AU - Pickering, Roger P AD - Division of Intramural Clinical and Biological Research, Department of Health and Human Services, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9304, USA. bgrant@willco.niaaa.nih.gov Y1 - 2004/06/11/ PY - 2004 DA - 2004 Jun 11 SP - 223 EP - 234 VL - 74 IS - 3 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Aged KW - Socioeconomic Factors KW - Adult KW - Interviews as Topic KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcoholism -- psychology KW - Diagnostic and Statistical Manual of Mental Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72022607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+12-month+prevalence+and+trends+in+DSM-IV+alcohol+abuse+and+dependence%3A+United+States%2C+1991-1992+and+2001-2002.&rft.au=Grant%2C+Bridget+F%3BDawson%2C+Deborah+A%3BStinson%2C+Frederick+S%3BChou%2C+S+Patricia%3BDufour%2C+Mary+C%3BPickering%2C+Roger+P&rft.aulast=Grant&rft.aufirst=Bridget&rft.date=2004-06-11&rft.volume=74&rft.issue=3&rft.spage=223&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 - 2004-10-07 N1 - Date created - 2004-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations of bacteriophage T4 59 helicase loader defective in binding fork DNA and in interactions with T4 32 single-stranded DNA-binding protein. AN - 72002701; 15084598 AB - Bacteriophage T4 gene 59 protein greatly stimulates the loading of the T4 gene 41 helicase in vitro and is required for recombination and recombination-dependent DNA replication in vivo. 59 protein binds preferentially to forked DNA and interacts directly with the T4 41 helicase and gene 32 single-stranded DNA-binding protein. The helicase loader is an almost completely alpha-helical, two-domain protein, whose N-terminal domain has strong structural similarity to the DNA-binding domains of high mobility group proteins. We have previously speculated that this high mobility group-like region may bind the duplex ahead of the fork, with the C-terminal domain providing separate binding sites for the fork arms and at least part of the docking area for the helicase and 32 protein. Here, we characterize several mutants of 59 protein in an initial effort to test this model. We find that the I87A mutation, at the position where the fork arms would separate in the model, is defective in binding fork DNA. As a consequence, it is defective in stimulating both unwinding by the helicase and replication by the T4 system. 59 protein with a deletion of the two C-terminal residues, Lys(216) and Tyr(217), binds fork DNA normally. In contrast to the wild type, the deletion protein fails to promote binding of 32 protein on short fork DNA. However, it binds 32 protein in the absence of DNA. The deletion is also somewhat defective in stimulating unwinding of fork DNA by the helicase and replication by the T4 system. We suggest that the absence of the two terminal residues may alter the configuration of the lagging strand fork arm on the surface of the C-terminal domain, so that it is a poorer docking site for the helicase and 32 protein. JF - The Journal of biological chemistry AU - Jones, Charles E AU - Green, Erin M AU - Stephens, Julia A AU - Mueser, Timothy C AU - Nossal, Nancy G AD - Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. Y1 - 2004/06/11/ PY - 2004 DA - 2004 Jun 11 SP - 25721 EP - 25728 VL - 279 IS - 24 SN - 0021-9258, 0021-9258 KW - DNA, Single-Stranded KW - 0 KW - DNA-Binding Proteins KW - Viral Proteins KW - gene 59 protein, Enterobacteria phage T4 KW - gp32 protein, Enterobacteria phage T4 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Mutation KW - Structure-Activity Relationship KW - Virus Replication KW - DNA, Single-Stranded -- metabolism KW - DNA-Binding Proteins -- chemistry KW - Viral Proteins -- chemistry KW - Viral Proteins -- metabolism KW - Bacteriophage T4 -- genetics KW - DNA Replication KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72002701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+of+bacteriophage+T4+59+helicase+loader+defective+in+binding+fork+DNA+and+in+interactions+with+T4+32+single-stranded+DNA-binding+protein.&rft.au=Jones%2C+Charles+E%3BGreen%2C+Erin+M%3BStephens%2C+Julia+A%3BMueser%2C+Timothy+C%3BNossal%2C+Nancy+G&rft.aulast=Jones&rft.aufirst=Charles&rft.date=2004-06-11&rft.volume=279&rft.issue=24&rft.spage=25721&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 - 2004-07-01 N1 - Date created - 2004-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcific neurocysticercosis and epileptogenesis. AN - 72002084; 15184592 AB - Neurocysticercosis is responsible for increased rates of seizures and epilepsy in endemic regions. The most common form of the disease, chronic calcific neurocysticercosis, is the end result of the host's inflammatory response to the larval cysticercus of Taenia solium. There is increasing evidence indicating that calcific cysticercosis is not clinically inactive but a cause of seizures or focal symptoms in this population. Perilesional edema is at times also present around implicated calcified foci. A better understanding of the natural history, frequency, epidemiology, and pathophysiology of calcific cysticercosis and associated disease manifestations is needed to define its importance, treatment, and prevention. JF - Neurology AU - Nash, T E AU - Del Brutto, O H AU - Butman, J A AU - Corona, T AU - Delgado-Escueta, A AU - Duron, R M AU - Evans, C A W AU - Gilman, R H AU - Gonzalez, A E AU - Loeb, J A AU - Medina, M T AU - Pietsch-Escueta, S AU - Pretell, E J AU - Takayanagui, O M AU - Theodore, W AU - Tsang, V C W AU - Garcia, H H AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. tnash@niaid.nih.gov Y1 - 2004/06/08/ PY - 2004 DA - 2004 Jun 08 SP - 1934 EP - 1938 VL - 62 IS - 11 KW - Abridged Index Medicus KW - Index Medicus KW - Cysticercus -- isolation & purification KW - Brain Edema -- etiology KW - Animals KW - Brain Edema -- parasitology KW - Taenia solium -- physiology KW - Latin America -- epidemiology KW - Cysticercus -- physiology KW - Humans KW - Calcinosis -- parasitology KW - Calcinosis -- complications KW - Food Parasitology KW - Neurocysticercosis -- parasitology KW - Epilepsies, Partial -- physiopathology KW - Neurocysticercosis -- complications KW - Neurocysticercosis -- epidemiology KW - Epilepsies, Partial -- etiology KW - Epilepsies, Partial -- parasitology KW - Neurocysticercosis -- transmission KW - Neurocysticercosis -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72002084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Calcific+neurocysticercosis+and+epileptogenesis.&rft.au=Nash%2C+T+E%3BDel+Brutto%2C+O+H%3BButman%2C+J+A%3BCorona%2C+T%3BDelgado-Escueta%2C+A%3BDuron%2C+R+M%3BEvans%2C+C+A+W%3BGilman%2C+R+H%3BGonzalez%2C+A+E%3BLoeb%2C+J+A%3BMedina%2C+M+T%3BPietsch-Escueta%2C+S%3BPretell%2C+E+J%3BTakayanagui%2C+O+M%3BTheodore%2C+W%3BTsang%2C+V+C+W%3BGarcia%2C+H+H&rft.aulast=Nash&rft.aufirst=T&rft.date=2004-06-08&rft.volume=62&rft.issue=11&rft.spage=1934&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=1526-632X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-20 N1 - Date created - 2004-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neurology. 1999 Sep 11;53(4):777-81 [10489040] Clin Infect Dis. 1994 Jun;18(6):879-85 [8086547] Ann Trop Med Parasitol. 1999 Apr;93(3):247-58 [10562826] Epilepsia. 2000 Jun;41(6):718-26 [10840405] Pediatr Infect Dis J. 2000 Jun;19(6):581-3 [10877183] Ann Neurol. 2000 Aug;48(2):181-7 [10939568] Neurology. 2000 Nov 28;55(10):1485-91 [11094102] Parasitol Int. 1999 Mar;48(1):81-9 [11269329] Ann Trop Med Parasitol. 2001 Mar;95(2):167-75 [11299123] Clin Infect Dis. 2001 Nov 15;33(10):1649-53 [11595994] Pediatr Neurol. 2001 Oct;25(4):309-11 [11704400] Arq Neuropsiquiatr. 2002 Jun;60(2-B):416-9 [12131943] Neurol India. 2002 Jun;50(2):141-4 [12134175] Epilepsia. 2002 Dec;43(12):1502-8 [12460252] Neuroepidemiology. 2003 Mar-Apr;22(2):139-45 [12629280] Lancet. 2003 Aug 16;362(9383):547-56 [12932389] Epilepsia. 1985 Jul-Aug;26(4):334-9 [4006892] J Neurosurg. 1987 Mar;66(3):359-63 [3819831] Pediatrics. 1988 Jul;82(1):76-82 [3288959] Arch Intern Med. 1990 Feb;150(2):325-7 [2302008] J Neurol. 1990 Apr;237(2):69-72 [2192018] Neuroradiology. 1991;33(2):126-35 [2046896] J Neurol Neurosurg Psychiatry. 1991 Aug;54(8):702-5 [1940942] Neurology. 1992 Feb;42(2):389-92 [1736171] Acta Neurol Scand. 1991 Dec;84(6):465-70 [1792850] Infection. 1992 Mar-Apr;20(2):61-5 [1582685] J Neurol Neurosurg Psychiatry. 1992 Apr;55(4):252-4 [1583508] Epilepsia. 1994 Jan-Feb;35(1):35-41 [8112255] Pediatr Neurosurg. 1994;21(1):23-30 [7947306] Prog Clin Parasitol. 1994;4:77-116 [7948938] Arq Neuropsiquiatr. 1994 Sep;52(3):289-94 [7893199] Arch Intern Med. 1995 Oct 9;155(18):1982-8 [7575052] Am J Trop Med Hyg. 1996 Sep;55(3):282-9 [8842116] Clin Infect Dis. 1997 Feb;24(2):101-13; quiz 114-5 [9114131] Acta Neurol Scand. 1997 Apr;95(4):197-200 [9150808] Acta Neurol Scand. 1997 Sep;96(3):127-32 [9300062] AJNR Am J Neuroradiol. 1998 Jan;19(1):79-82 [9432161] Seizure. 1998 Apr;7(2):153-7 [9627207] Epilepsia. 1998 Dec;39(12):1334-9 [9860070] Seizure. 1998 Dec;7(6):497-500 [9888495] Am J Trop Med Hyg. 1999 Apr;60(4):664-7 [10348245] J Trop Pediatr. 1999 Jun;45(3):161-5 [10401195] Lancet. 1999 Jul 3;354(9172):44-5 [10406368] Int J Epidemiol. 1999 Aug;28(4):799-803 [10480714] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recognition of anionic phospholipid membranes by an antihemostatic protein from a blood-feeding insect. AN - 71974744; 15170336 AB - The saliva of blood-feeding insects contains a variety of molecules having antihemostatic activity. Here, we describe nitrophorin 7 (NP7), a salivary protein that binds with high affinity to anionic phospholipid membranes. The protein is apparently targeted to the negatively charged surfaces of activated platelets and other cells, where it can serve as a vasodilator, antihistamine, platelet aggregation inhibitor, and anticoagulant. As with other members of the nitrophorin group, NP7 reversibly binds a molecule of NO and binds histamine with high affinity. The protein differs from other nitrophorins in that it binds to membranes containing phosphatidylserine. Sedimentation and surface plasmon resonance experiments, revealed two classes of phospholipid-binding sites having K(d) values of 4.8 and 755 nM. NP7 inhibits prothrombin activation by blocking phospholipid binding sites for the prothrombinase complex on the surfaces of vesicles and activated platelets. As a NO complex, NP7 inhibits collagen and ADP-induced platelet aggregation and induces disaggregation of ADP-stimulated platelets by an NO-mediated mechanism. Molecular modeling of NP7 revealed a putative, positively charged membrane interaction surface comprised mainly of a helix lying outside of the lipocalin beta-barrel structure. JF - Biochemistry AU - Andersen, John F AU - Gudderra, Nanda P AU - Francischetti, Ivo M B AU - Valenzuela, Jesus G AU - Ribeiro, José M C AD - Laboratory of Malaria and Vector Research, National Institutes of Health, NIAID, Rockville, Maryland 20852, USA. jandersen@niaid.nih.gov Y1 - 2004/06/08/ PY - 2004 DA - 2004 Jun 08 SP - 6987 EP - 6994 VL - 43 IS - 22 SN - 0006-2960, 0006-2960 KW - Hemeproteins KW - 0 KW - Phosphatidylserines KW - Salivary Proteins and Peptides KW - nitrophorin KW - Sodium Chloride KW - 451W47IQ8X KW - Prothrombin KW - 9001-26-7 KW - Thromboplastin KW - 9035-58-9 KW - Index Medicus KW - Animals KW - Thromboplastin -- pharmacology KW - Models, Molecular KW - Surface Plasmon Resonance KW - Amino Acid Sequence KW - Sodium Chloride -- chemistry KW - Platelet Aggregation -- drug effects KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Thromboplastin -- metabolism KW - Molecular Sequence Data KW - Sodium Chloride -- metabolism KW - Sequence Homology, Amino Acid KW - Phosphatidylserines -- chemistry KW - Blood Coagulation KW - Salivary Proteins and Peptides -- metabolism KW - Hemeproteins -- metabolism KW - Prothrombin -- antagonists & inhibitors KW - Salivary Glands -- chemistry KW - Phosphatidylserines -- metabolism KW - Hemeproteins -- pharmacology KW - Cell Membrane -- physiology KW - Salivary Proteins and Peptides -- pharmacology KW - Blood Platelets -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71974744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recognition+of+anionic+phospholipid+membranes+by+an+antihemostatic+protein+from+a+blood-feeding+insect.&rft.au=Andersen%2C+John+F%3BGudderra%2C+Nanda+P%3BFrancischetti%2C+Ivo+M+B%3BValenzuela%2C+Jesus+G%3BRibeiro%2C+Jos%C3%A9+M+C&rft.aulast=Andersen&rft.aufirst=John&rft.date=2004-06-08&rft.volume=43&rft.issue=22&rft.spage=6987&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-11 N1 - Date created - 2004-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1996 Dec 24;35(51):16886-97 [8988028] Chem Phys Lipids. 1996 Nov 1;84(1):35-45 [8952051] Biochemistry. 1997 Apr 15;36(15):4423-8 [9109649] Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11845-50 [9342325] Biophys J. 1998 Feb;74(2 Pt 1):731-44 [9533686] Nat Struct Biol. 1998 Apr;5(4):304-9 [9546222] Biochemistry. 1998 Jul 28;37(30):10681-90 [9692958] Biochim Biophys Acta. 1998 Nov 10;1376(3):433-53 [9805008] Cytometry. 1999 Aug 1;36(4):340-8 [10404150] J Clin Invest. 1999 Dec;104(12):1663-5 [10606617] J Biol Chem. 2000 Mar 3;275(9):6636-41 [10692472] J Biol Chem. 2000 Apr 28;275(17):12639-50 [10777556] Cell Death Differ. 2000 Jul;7(7):645-53 [10889509] Biochemistry. 2000 Aug 22;39(33):10118-31 [10956000] J Biol Chem. 2000 Sep 29;275(39):30496-503 [10884386] Biochim Biophys Acta. 2000 Oct 18;1482(1-2):9-24 [11058743] Int Arch Allergy Immunol. 2000 Nov;123(3):249-58 [11112862] Thromb Haemost. 2001 Jul;86(1):266-75 [11487015] Thromb Haemost. 2001 Jul;86(1):298-307 [11487018] Biochemistry. 2002 Mar 19;41(11):3810-8 [11888300] J Biol Chem. 2003 Jan 24;278(4):2437-43 [12401794] J Biol Chem. 2003 Feb 14;278(7):4611-7 [12464610] Protein Eng. 1997 Jan;10(1):1-6 [9051728] Biochem J. 1996 Aug 15;318 ( Pt 1):1-14 [8761444] Science. 1995 May 26;268(5214):1144-9 [7761829] Cell Death Differ. 2003 Oct;10(10):1156-64 [14502239] Insect Biochem Mol Biol. 2004 Jan;34(1):61-79 [14976983] Blood. 2003 Jul 15;102(2):449-61 [12649139] Blood. 2003 Apr 1;101(7):2628-36 [12517809] Science. 1993 Apr 23;260(5107):539-41 [8386393] Biochem Soc Trans. 1993 May;21(2):248-53 [8359475] J Exp Med. 1994 Dec 1;180(6):2251-7 [7964498] Biochem J. 1995 May 15;308 ( Pt 1):243-9 [7755571] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mediation of BMP7 neuroprotection by MAPK and PKC IN rat primary cortical cultures. AN - 71903951; 15126117 AB - We have previously demonstrated that pretreatment with bone morphogenetic protein 7 (BMP7), a trophic factor in the TGFbeta superfamily, reduces ischemia-induced brain infarction induced by middle cerebral artery ligation in rats. Since the mitogen-activated protein kinase (MAPK) pathway is involved in many TGFbeta-mediated responses, we examined the interaction of BMP7 and MAPK in primary cultures obtained from the cerebral cortex of E16-17 rat embryos. Lactate dehydrogenase (LDH) in the media was used as an index of cell death. BMP7 did not alter LDH levels at low concentration (1.25 nM), but exhibited increased cellular toxicity at higher concentration (>12.5 nM). BMP7 at the low concentration significantly attenuated H2O2-induced increases in LDH activity and decreases in neuronal density. Pharmacological interactions were used to examine if MAPK was involved in this response. BMP7-induced protection was antagonized by the p42,44 MAPK kinase inhibitors PD98059 and U0125. The p38 MAPK antagonist SB203580, and their inactive analog SB202474, also attenuated BMP7-induced protection, suggesting that the interaction with p38 MAPK is nonspecific. Previous studies have indicated that SB202474 has inhibitory effects on other protein kinases. We found that the protein kinase C inhibitor chelerythrine antagonized BMP7-induced protection against H2O2. Western blot analysis indicated that BMP7 increased phosphorylation of p42,44 MAPK and PKC. Taken together, our data suggest that BMP7 is neuroprotective at low concentrations in primary cortical cell culture. The protective effects of BMP7 may involve the activation of p42,44 MAPK and PKC. Copyright 2004 Elsevier B.V. JF - Brain research AU - Cox, Suyu AU - Harvey, Brandon K AU - Sanchez, Joseph F AU - Wang, Jia-Yi AU - Wang, Yun AD - Neural Protection and Regeneration, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2004/06/04/ PY - 2004 DA - 2004 Jun 04 SP - 55 EP - 61 VL - 1010 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Bmp7 protein, rat KW - 0 KW - Bone Morphogenetic Protein 7 KW - Bone Morphogenetic Proteins KW - Enzyme Inhibitors KW - Neuroprotective Agents KW - Oxidants KW - Plant Proteins KW - Transforming Growth Factor beta KW - Hydrogen Peroxide KW - BBX060AN9V KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Protein Kinase C KW - EC 2.7.11.13 KW - MMK4 protein, Medicago sativa KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 1 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - Index Medicus KW - Animals KW - Cell Death -- physiology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Dose-Response Relationship, Drug KW - L-Lactate Dehydrogenase -- drug effects KW - Hydrogen Peroxide -- antagonists & inhibitors KW - Cell Death -- drug effects KW - Phosphorylation -- drug effects KW - Rats KW - Hydrogen Peroxide -- toxicity KW - Rats, Sprague-Dawley KW - Mitogen-Activated Protein Kinases -- drug effects KW - Oxidants -- antagonists & inhibitors KW - Cells, Cultured KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Oxidants -- toxicity KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Mitogen-Activated Protein Kinase 1 -- drug effects KW - L-Lactate Dehydrogenase -- metabolism KW - Protein Kinase C -- metabolism KW - Transforming Growth Factor beta -- pharmacology KW - Protein Kinase C -- drug effects KW - MAP Kinase Signaling System -- drug effects KW - Cerebral Cortex -- cytology KW - MAP Kinase Signaling System -- physiology KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- enzymology KW - Bone Morphogenetic Proteins -- pharmacology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71903951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mediation+of+BMP7+neuroprotection+by+MAPK+and+PKC+IN+rat+primary+cortical+cultures.&rft.au=Cox%2C+Suyu%3BHarvey%2C+Brandon+K%3BSanchez%2C+Joseph+F%3BWang%2C+Jia-Yi%3BWang%2C+Yun&rft.aulast=Cox&rft.aufirst=Suyu&rft.date=2004-06-04&rft.volume=1010&rft.issue=1-2&rft.spage=55&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 - 2004-09-01 N1 - Date created - 2004-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of TDP1 from budding yeast in the repair of DNA damage. AN - 71913460; 15135727 AB - The TDP1 gene encodes a protein that can hydrolyze certain types of 3'-terminal phosphodiesters, but the relevance of these catalytic activities to gene function has not been previously tested. In this work we engineered a point mutation in TDP1 and present evidence that, as per design, it severely diminishes tyrosyl-DNA phosphodiesterase enzyme activity without affecting protein folding. The phenotypes of yeast strains that express this mutant show that the contribution of TDP1 to the repair of two kinds of damaged termini-induced, respectively, by camptothecin (CPT) and by bleomycin-strongly depends on enzyme activity. In routine assays of cell survival and growth the contribution of this activity is often overshadowed by other repair pathways. However, the value of TDP1 in the economy of the cell is highlighted by our discovery of several phenotypes that are evident even without deliberate inactivation of parallel pathways. These non-redundant mutant phenotypes include increased spontaneous mutation rate, transient accumulation of cells in a mid-anaphase checkpoint after exposure to camptothecin and, in cells that overexpress topoisomerase I (Top1), decreased survival of camptothecin-induced damage. The relationship between the role of TDP1 in Saccharomyces and its role in metazoans is discussed. JF - DNA repair AU - Liu, Chunyan AU - Pouliot, Jeffrey J AU - Nash, Howard A AD - Laboratory of Molecular Biology, National Institute of Mental Health, 9000 Rockville Pike, Bethesda, MD 20892-4034, USA. Y1 - 2004/06/03/ PY - 2004 DA - 2004 Jun 03 SP - 593 EP - 601 VL - 3 IS - 6 SN - 1568-7864, 1568-7864 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents, Phytogenic KW - DNA, Fungal KW - Bleomycin KW - 11056-06-7 KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - tyrosyl-DNA phosphodiesterase KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Phenotype KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Anaphase KW - Camptothecin -- adverse effects KW - DNA, Fungal -- metabolism KW - DNA Topoisomerases, Type I -- metabolism KW - Bleomycin -- adverse effects KW - Saccharomyces cerevisiae -- genetics KW - Phosphoric Diester Hydrolases -- genetics KW - Cell Survival -- drug effects KW - DNA Damage KW - Mutation -- genetics KW - Saccharomyces cerevisiae -- enzymology KW - Phosphoric Diester Hydrolases -- metabolism KW - Saccharomyces cerevisiae -- drug effects KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71913460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+repair&rft.atitle=The+role+of+TDP1+from+budding+yeast+in+the+repair+of+DNA+damage.&rft.au=Liu%2C+Chunyan%3BPouliot%2C+Jeffrey+J%3BNash%2C+Howard+A&rft.aulast=Liu&rft.aufirst=Chunyan&rft.date=2004-06-03&rft.volume=3&rft.issue=6&rft.spage=593&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-16 N1 - Date created - 2004-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Forecasting the cytokine storm following systemic interleukin (IL)-2 administration. AN - 1859457648; 15175100 AB - Extensive clinical experience has shown that systemic interleukin (IL)-2 administration can induce complete or partial regression of renal cell cancer (RCC) metastases in 15 to 20 % of patients. Since IL-2 has no direct anti-cancer effects, it is believed that cancer regression is mediated either by a direct modulation of immune cell effector functions or through the mediation of soluble factors released as a result of IL-2 administration.We previously observed that transcriptional and protein changes induced by systemic IL-2 administration affect predominantly mononuclear phagocytes with little effect, particularly within the tumor microenvironment, on T cell activation, localization and proliferation. It further appeared that mononuclear phagocyte activation could be best explained by the indirect mediation of a secondary release of cytokines by IL-2 responsive cells either in the circulation or in peripheral tissues.To better characterize the cytokine outburst that follows systemic IL-2 administration we followed the serum levels of 68 soluble factors in ten patients with RCC undergoing high dose (720,000 IU/kg intravenously every 8 hours) IL-2 therapy. Serum was collected before therapy, 3 hours after the 1st and 4th dose and assayed on a multiplexed protein array platform. This study demonstrated that 1) the serum concentration of more than half the soluble factors studied changed significantly during therapy; 2) changes became more dramatic with increasing doses; 3) subclasses of soluble factors displayed different kinetics and 4) cytokine patterns varied quantitatively among patients.This study shows that the cytokine storm that follows systemic IL-2 administration is complex and far-reaching inclusive of soluble factors with disparate, partly redundant and partly contrasting effects on immune function. Therefore comparing in parallel large number of soluble factors, it sets a comprehensive foundation for further elucidation of "cytokine storm" in larger patient pools. Based on this analysis, we propose a prospective collection of serum samples in a larger cohort of patients undergoing IL-2 administration with the purpose of discerning patterns predictive of clinical outcome and toxicity. JF - Journal of translational medicine AU - Panelli, Monica C AU - White, Richard AU - Foster, Mareva AU - Martin, Brian AU - Wang, Ena AU - Smith, Kina AU - Marincola, Francesco M AD - Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD USA. fmarincola@mail.cc.nih.gov Y1 - 2004/06/02/ PY - 2004 DA - 2004 Jun 02 SP - 17 VL - 2 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859457648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+translational+medicine&rft.atitle=Forecasting+the+cytokine+storm+following+systemic+interleukin+%28IL%29-2+administration.&rft.au=Panelli%2C+Monica+C%3BWhite%2C+Richard%3BFoster%2C+Mareva%3BMartin%2C+Brian%3BWang%2C+Ena%3BSmith%2C+Kina%3BMarincola%2C+Francesco+M&rft.aulast=Panelli&rft.aufirst=Monica&rft.date=2004-06-02&rft.volume=2&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Journal+of+translational+medicine&rft.issn=1479-5876&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2004-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent advances in laryngeal sensorimotor control for voice, speech and swallowing. AN - 85391449; pmid-15167023 AB - This article reviews advances in knowledge on laryngeal sensorimotor control affecting the assessment, understanding, and treatment of laryngeal motor control disorders in voice, speech, and swallowing. Three topics are covered: new knowledge on laryngeal innervation and central nervous system control from basic research studies, the role of laryngeal sensation in normal swallowing and dysphagia in patients, and new approaches to the restoration of laryngeal motor control after recurrent laryngeal nerve disorders.A significant advance this year was tracing the efferent pathways from the cortex to the brainstem in monkeys. This provided new information on subcortical and brainstem connections in the laryngeal efferent pathways. Laryngeal sensory feedback continued to receive attention, and the role of sensory feedback in the control of the pharyngeal phase of swallowing is now well established. Further developments in neuromotor monitoring of the recurrent laryngeal nerve during thyroidectomy were seen, and a large case series recommended that these techniques become standard practice for surgery for thyroid benign recurrence or malignancy. Finally, the first tissue engineering papers in the field of vocal fold tissue and nerve restoration were published this year, beginning an exciting new approach to restoration of laryngeal motor control.Considerable attention has been given to laryngeal muscle physiology, denervation, and sensation in neurolaryngology. Relatively limited understanding is available regarding the central nervous system integrative control of laryngeal function for speech, respiration, and swallowing. JF - Current opinion in otolaryngology & head and neck surgery AU - Ludlow, Christy L AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1416, USA. Ludlowc@ninds.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 160 EP - 165 VL - 12 IS - 3 SN - 1068-9508, 1068-9508 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Brain Mapping KW - Brain Stem: physiopathology KW - Cerebral Cortex: physiology KW - *Deglutition: physiology KW - Humans KW - *Laryngeal Muscles: innervation KW - Motor Cortex: physiology KW - *Motor Neurons: physiology KW - Nerve Net: physiopathology KW - Recurrent Laryngeal Nerve: physiopathology KW - Recurrent Laryngeal Nerve Injuries KW - *Sensory Receptor Cells: physiopathology KW - *Speech: physiology KW - Vocal Cord Paralysis: physiopathology KW - Vocal Cord Paralysis: rehabilitation KW - *Voice: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85391449?accountid=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=Current+opinion+in+otolaryngology+%26+head+and+neck+surgery&rft.atitle=Recent+advances+in+laryngeal+sensorimotor+control+for+voice%2C+speech+and+swallowing.&rft.au=Ludlow%2C+Christy+L&rft.aulast=Ludlow&rft.aufirst=Christy&rft.date=2004-06-01&rft.volume=12&rft.issue=3&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+otolaryngology+%26+head+and+neck+surgery&rft.issn=10689508&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Minocycline in Huntington's disease: a pilot study. AN - 85385626; pmid-15197710 AB - Minocycline is a caspase inhibitor, decreases inducible nitric oxide synthase (iNOS), and has been shown to delay disease progression in the mouse model R6/2 of Huntington's disease (HD). This safety and tolerability study included 30 patients with HD who were given minocycline over a 6-month period and underwent assessments every 2 months with laboratory studies, the Abnormal Involuntary Movements Scale, the Unified Huntington's Disease Rating Scale, and the Mini-Mental State Examination. Minocycline was well tolerated during this study period and no serious adverse events were noted.Copyright 2004 Movement Disorder Society JF - Movement disorders : official journal of the Movement Disorder Society AU - Thomas, Madhavi AU - Ashizawa, Tetsuo AU - Jankovic, Joseph AD - Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. thomasmad@ninds.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 692 EP - 695 VL - 19 IS - 6 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Aged KW - Caspases: antagonists & inhibitors KW - Cognition Disorders: diagnosis KW - Cognition Disorders: etiology KW - *Enzyme Inhibitors: therapeutic use KW - Female KW - Humans KW - Huntington Disease: complications KW - *Huntington Disease: drug therapy KW - Huntington Disease: enzymology KW - Male KW - Middle Aged KW - *Minocycline: therapeutic use KW - Neuropsychological Tests KW - Nitric Oxide Synthase: metabolism KW - Nitric Oxide Synthase Type II KW - Pilot Projects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85385626?accountid=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=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Minocycline+in+Huntington%27s+disease%3A+a+pilot+study.&rft.au=Thomas%2C+Madhavi%3BAshizawa%2C+Tetsuo%3BJankovic%2C+Joseph&rft.aulast=Thomas&rft.aufirst=Madhavi&rft.date=2004-06-01&rft.volume=19&rft.issue=6&rft.spage=692&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 (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - SuppNotes - Comment In: Mov Disord. 2005 Apr;20(4):510-1; author reply 511[15806589] N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - The roles of orbital frontal cortex in the modulation of antisocial behavior. AN - 85380009; pmid-15134853 AB - This article considers potential roles of orbital frontal cortex in the modulation of antisocial behavior. Two forms of aggression are distinguished: reactive aggression elicited in response to frustration/threat and goal directed, instrumental aggression. It is suggested that orbital frontal cortex is directly involved in the modulation of reactive aggression. It is argued that orbital frontal cortex does not "inhibit" reactive aggression but rather may both increase or decrease its probability as a function of social cues present in the environment. Early dysfunction in this function of orbital frontal cortex may be linked to the development of Borderline Personality Disorder. Instrumental aggression is linked to a fundamental failure in moral socialization. However, the available data suggest that the amygdala, but not orbital frontal cortex, is required for functions such as aversive conditioning and passive avoidance learning that are necessary for moral socialization. Psychopathic individuals who present with significant instrumental aggression, are impaired in aversive conditioning and passive avoidance learning and show evidence of amygdala dysfunction. Orbital frontal cortex and the amygdala are involved in response reversal where instrumental responses must be reversed following contingency change. Impairments in response reversal are also seen in psychopathic individuals. However, it remains unclear whether impairment in response reversal per se is associated with antisocial behavior. JF - Brain and cognition AU - Blair, R J R AD - Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, 15K North Drive, Room 206, MSC 2670, Bethesda, MD 20892-2670, USA. blairj@intra.nimh.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 198 EP - 208 VL - 55 IS - 1 SN - 0278-2626, 0278-2626 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - *Aggression KW - Amygdala: physiopathology KW - Animals KW - *Antisocial Personality Disorder: physiopathology KW - Child KW - *Frontal Lobe: physiopathology KW - Humans KW - Internal-External Control KW - Models, Neurological KW - Models, Psychological KW - Nerve Net: physiopathology KW - Orbit KW - *Prefrontal Cortex: physiopathology KW - Social Behavior Disorders: physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85380009?accountid=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+cognition&rft.atitle=The+roles+of+orbital+frontal+cortex+in+the+modulation+of+antisocial+behavior.&rft.au=Blair%2C+R+J+R&rft.aulast=Blair&rft.aufirst=R+J&rft.date=2004-06-01&rft.volume=55&rft.issue=1&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Brain+and+cognition&rft.issn=02782626&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Regulation of hTERT transcription: a target of cellular and viral mechanisms for immortalization and carcinogenesis. AN - 733872391; 19003240 AB - A hallmark of human cancer cells is immortal cell growth, which is associated with telomere maintenance by telomerase. The transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene is a major mechanism that negatively and positively controls telomerase activity in normal and cancer cells, respectively. A growing body of data suggests that various cellular and viral factors and pathways involved in cell senescence, immortalization and carcinogenesis act on the hTERT promoter. The activity of the hTERT promoter is regulated, either directly or through signaling pathways, by oncogene products (e.g., Myc and Ets families) and tumor suppressor proteins (e.g., BRCA1). Endogenous factors involved in the physiological repression of the hTERT gene have also been revealed by chromosome transfer experiments. The integration of viral genomes in the hTERT locus can lead to hTERT activation and telomerase induction. Here, we summarize these findings and pay special attention to recent findings with relevance to the endogenous regulatory mechanisms of hTERT transcription. JF - Cytotechnology AU - Horikawa, Izumi AU - Michishita, Eriko AU - Barrett, J Carl AD - Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5046, Bethesda, MD, 20892, USA, horikawi@mail.nih.gov. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 23 EP - 32 VL - 45 IS - 1-2 SN - 0920-9069, 0920-9069 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/733872391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+hTERT+transcription%3A+a+target+of+cellular+and+viral+mechanisms+for+immortalization+and+carcinogenesis.&rft.au=Horikawa%2C+Izumi%3BMichishita%2C+Eriko%3BBarrett%2C+J+Carl&rft.aulast=Horikawa&rft.aufirst=Izumi&rft.date=2004-06-01&rft.volume=45&rft.issue=1-2&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Cytotechnology&rft.issn=09209069&rft_id=info:doi/10.1007%2Fs10616-004-5122-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2011-07-14 N1 - Date created - 2008-11-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 2002 Aug 15;62(16):4736-45 [12183433] Nature. 2003 May 15;423(6937):255-60 [12714970] Surv Synth Pathol Res. 1984;3(4):342-9 [6095401] Oncogene. 1995 Mar 16;10(6):1229-34 [7700648] Science. 1997 Aug 15;277(5328):955-9 [9252327] Eur J Cancer. 1997 Apr;33(5):710-5 [9282109] Cell. 1997 Aug 22;90(4):785-95 [9288757] Nature. 1999 Jan 14;397(6715):164-8 [9923679] Nature. 2003 May 15;423(6937):302-5 [12714971] Oncogene. 2003 Jun 12;22(24):3813-20 [12802289] Carcinogenesis. 2003 Jul;24(7):1167-76 [12807729] Oncogene. 2003 Jun 19;22(25):3911-6 [12813464] Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8211-6 [12821782] Cell. 2003 Jun 27;113(7):881-9 [12837246] Oncogene. 2003 Aug 14;22(34):5238-51 [12917625] Oncogene. 2003 Oct 16;22(46):7123-9 [14562040] Mol Cell Biol. 2004 Jan;24(1):25-35 [14673140] Cancer Res. 2003 Dec 1;63(23):8338-44 [14678994] Cancer Res. 2004 Jan 15;64(2):463-7 [14744757] EMBO J. 2004 May 5;23(9):1949-56 [15071503] Anticancer Drugs. 2004 Jan;15(1):7-14 [15090737] Genes Dev. 2003 May 1;17(9):1115-29 [12695333] Clin Cancer Res. 2000 Apr;6(4):1239-47 [10778946] Cell Growth Differ. 2001 Feb;12(2):119-27 [11243466] J Virol. 2001 May;75(9):4467-72 [11287602] Curr Opin Genet Dev. 2002 Feb;12(1):80-5 [11790559] Exp Cell Res. 2002 Mar 10;274(1):25-34 [11855854] Methods. 2002 Jan;26(1):27-36 [12054902] Mol Cell Biol. 2002 Jul;22(14):5054-63 [12077335] Cancer Res. 2002 Jul 1;62(13):3876-82 [12097303] Mol Biol Cell. 2002 Aug;13(8):2585-97 [12181331] J Mol Med (Berl). 2002 Sep;80(9):562-75 [12226738] Oncogene. 2003 Jan 23;22(3):381-91 [12545159] Exp Cell Res. 2003 Oct 1;289(2):326-34 [14499633] Exp Mol Pathol. 2003 Dec;75(3):238-47 [14611815] Mol Cell Biol. 2003 Dec;23(23):8668-90 [14612409] Ann N Y Acad Sci. 2003 Dec;1002:56-62 [14751822] Oncogene. 2004 Apr 29;23(20):3708-15 [15048086] Cancer Res. 1999 Feb 1;59(3):551-7 [9973199] Nat Genet. 1999 Feb;21(2):220-4 [9988278] Oncogene. 1999 Feb 4;18(5):1219-26 [10022128] Cancer Res. 1999 Feb 15;59(4):826-30 [10029071] Curr Opin Cell Biol. 1999 Jun;11(3):318-24 [10395557] J Biol Chem. 1999 Dec 24;274(52):37473-8 [10601322] Cancer Res. 1999 Dec 15;59(24):6087-90 [10626795] Exp Gerontol. 2000 Feb;35(1):7-13 [10705034] Cancer Res. 2000 Apr 15;60(8):2116-21 [10786671] Oncogene. 2000 Oct 26;19(45):5123-33 [11064449] Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):992-9 [11158583] Oncogene. 2000 Dec 18;19(55):6503-13 [11175366] Hum Mol Genet. 2001 Apr;10(7):677-85 [11257099] Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3826-31 [11274400] Gene. 2001 May 16;269(1-2):1-12 [11376932] J Virol. 2001 Aug;75(15):7198-201 [11435602] J Natl Cancer Inst. 2001 Aug 1;93(15):1171-3 [11481390] Mol Endocrinol. 2001 Oct;15(10):1653-64 [11579199] Exp Gerontol. 2001 Nov;36(10):1619-37 [11672984] J Biol Chem. 2002 Jan 4;277(1):854-61 [11689553] Cell. 2002 Jan 25;108(2):171-82 [11832208] Oncogene. 2002 Jan 21;21(4):541-52 [11850779] Oncogene. 2002 Jan 24;21(5):769-77 [11850805] J Cell Sci. 2002 Mar 15;115(Pt 6):1305-12 [11884529] Nat Rev Cancer. 2001 Dec;1(3):203-13 [11902575] J Biol Chem. 2002 Jun 7;277(23):20965-73 [11916966] Oncogene. 2002 Jun 13;21(26):4071-9 [12037663] N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1007/s10616-004-5122-4 ER - TY - JOUR T1 - Association of pesticide exposure with neurologic dysfunction and disease. AN - 72026773; 15198914 AB - Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neurotoxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease. JF - Environmental health perspectives AU - Kamel, Freya AU - Hoppin, Jane A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. kamel@niehs.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 950 EP - 958 VL - 112 IS - 9 SN - 0091-6765, 0091-6765 KW - Pesticides KW - 0 KW - Index Medicus KW - Parkinson Disease -- etiology KW - Epidemiologic Studies KW - Dose-Response Relationship, Drug KW - Humans KW - Genetic Predisposition to Disease KW - Risk Assessment KW - Nervous System Diseases -- etiology KW - Pesticides -- poisoning KW - Environmental Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72026773?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+of+pesticide+exposure+with+neurologic+dysfunction+and+disease.&rft.au=Kamel%2C+Freya%3BHoppin%2C+Jane+A&rft.aulast=Kamel&rft.aufirst=Freya&rft.date=2004-06-01&rft.volume=112&rft.issue=9&rft.spage=950&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 - 2004-09-10 N1 - Date created - 2004-06-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Res. 2001 May;86(1):37-45 [11386739] Mov Disord. 2001 May;16(3):565-8 [11391760] Environ Res. 2001 Jun;86(2):122-7 [11437458] Am J Ind Med. 2001 Jul;40(1):42-54 [11439396] Neurobiol Dis. 2002 Jul;10(2):119-27 [12127150] Hum Exp Toxicol. 2002 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Neuroepidemiology. 1991;10(5-6):242-5 [1798425] Environ Res. 1992 Oct;59(1):217-28 [1425511] Environ Res. 1992 Oct;59(1):229-37 [1425512] Br J Ind Med. 1992 Nov;49(11):791-8 [1463680] Acta Neurol Scand. 1993 Jul;88(1):56-8 [7690513] J Neurol Neurosurg Psychiatry. 1993 Nov;56(11):1200-6 [8229031] J Occup Med. 1993 Dec;35(12):1196-202 [8113922] Am J Public Health. 1994 Mar;84(3):446-51 [8129063] Am J Ind Med. 1994 Mar;25(3):325-34 [8160653] Neurology. 1993 Jun;43(6):1150-8 [8170560] Am J Public Health. 1994 May;84(5):731-6 [8179040] Toxicol Ind Health. 1993 Sep-Oct;9(5):913-59 [8184449] Arch Environ Health. 1994 May-Jun;49(3):188-95 [8185390] Ann Neurol. 1994 Jul;36(1):100-3 [7517654] Neurology. 1994 Nov;44(11):2073-80 [7969962] Occup Med. 1997 Apr-Jun;12(2):221-37 [9220483] Occup Med. 1997 Apr-Jun;12(2):291-304 [9220487] Neurotoxicol Teratol. 1997 Jul-Aug;19(4):277-86 [9253006] Environ Res. 1997;73(1-2):18-41 [9311528] Environ Res. 1997;73(1-2):132-45 [9311539] Am J Ind Med. 1997 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[13042137] Can Med Assoc J. 1965 Mar 20;92:597-602 [14264969] J Toxicol Environ Health A. 2000 Feb 25;59(4):229-34 [10706031] Environ Health Perspect. 2000 Apr;108(4):293-300 [10753086] Neurology. 1992 Jul;42(7):1328-35 [1620342] Br J Ind Med. 1992 Sep;49(9):615-9 [1390266] Mov Disord. 1999 Nov;14(6):928-39 [10584666] J Clin Psychiatry. 1999 Nov;60(11):776-82 [10584768] Am J Med Genet. 1999 Dec 15;88(6):742-9 [10581500] Neurotoxicology. 1999 Oct;20(5):819-26 [10591517] Ann Occup Hyg. 1999 Nov;43(8):519-25 [10616325] Am Ind Hyg Assoc J. 1999 Nov-Dec;60(6):789-93 [10635545] Am J Ind Med. 2000 Jun;37(6):618-28 [10797505] Int J Epidemiol. 2000 Apr;29(2):323-9 [10817132] Occup Environ Med. 2000 Mar;57(3):195-200 [10810102] Lancet. 2000 Sep 9;356(9233):912-3 [11036900] Nat Neurosci. 2000 Dec;3(12):1301-6 [11100151] J Neurosci. 2000 Dec 15;20(24):9207-14 [11124998] Neurotoxicology. 2000 Oct;21(5):837-46 [11130289] Occup Environ Med. 2001 Jan;58(1):24-30 [11119631] Lancet. 2001 Mar 31;357(9261):1014-6 [11293598] Ann Occup Hyg. 2001 Apr;45(3):227-39 [11295146] Can J Neurol Sci. 2001 May;28(2):144-7 [11383940] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A cross-national study of violence-related behaviors in adolescents. AN - 72003872; 15184216 AB - Violent behavior among adolescents is a significant problem worldwide, and a cross-national comparison of adolescent violent behaviors can provide information about the development and pattern of physical violence in young adolescents. To determine and compare frequencies of adolescent violence-related behaviors in 5 countries and to examine associations between violence-related behaviors and potential explanatory characteristics. Cross-sectional, school-based nationally representative survey at ages 11.5, 13.5, and 15.5 years in 5 countries (Ireland, Israel, Portugal, Sweden, and the United States). Frequency of physical fighting, bullying, weapon carrying, and fighting injuries in relation to other risk behaviors and characteristics in home and school settings. Fighting frequency among US youth was similar to that of all 5 countries (nonfighters: US, 60.2%; mean frequency of 5 countries, 60.2%), as were the frequencies of weapon carrying (noncarriers: US, 89.6%; mean frequency of 5 countries, 89.6%) and fighting injury (noninjured: US, 84.5%; mean frequency of 5 countries, 84.6%). Bullying frequency varied widely cross-nationally (nonbullies: from 57.0% for Israel to 85.2% for Sweden). Fighting was most highly associated with smoking, drinking, feeling irritable or bad tempered, and having been bullied. Adolescents in 5 countries behaved similarly in their expression of violence-related behaviors. Occasional fighting and bullying were common, whereas frequent fighting, frequent bullying, any weapon carrying, or any fighting injury were infrequent behaviors. These findings were consistent across countries, with little cross-national variation except for bullying rates. Traditional risk-taking behaviors (smoking and drinking) and being bullied were highly associated with the expression of violence-related behavior. JF - Archives of pediatrics & adolescent medicine AU - Smith-Khuri, Eleanor AU - Iachan, Ronaldo AU - Scheidt, Peter C AU - Overpeck, Mary D AU - Gabhainn, Saoirse Nic AU - Pickett, William AU - Harel, Yossi AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 539 EP - 544 VL - 158 IS - 6 SN - 1072-4710, 1072-4710 KW - Abridged Index Medicus KW - Index Medicus KW - Wounds and Injuries -- epidemiology KW - Israel -- epidemiology KW - Odds Ratio KW - Humans KW - Child KW - Portugal -- epidemiology KW - Age Distribution KW - Cross-Sectional Studies KW - Family Relations KW - Health Surveys KW - Sweden -- epidemiology KW - Adolescent KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Ireland -- epidemiology KW - Male KW - Substance-Related Disorders -- epidemiology KW - Adolescent Behavior KW - Violence -- statistics & numerical data KW - Cross-Cultural Comparison UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72003872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+cross-national+study+of+violence-related+behaviors+in+adolescents.&rft.au=Smith-Khuri%2C+Eleanor%3BIachan%2C+Ronaldo%3BScheidt%2C+Peter+C%3BOverpeck%2C+Mary+D%3BGabhainn%2C+Saoirse+Nic%3BPickett%2C+William%3BHarel%2C+Yossi&rft.aulast=Smith-Khuri&rft.aufirst=Eleanor&rft.date=2004-06-01&rft.volume=158&rft.issue=6&rft.spage=539&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 - 2004-07-08 N1 - Date created - 2004-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Pediatr Adolesc Med. 2004 Jun;158(6):592-4 [15184225] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Emerging technologies in neurotoxicology: Session III summary and research needs. AN - 72003327; 15183003 JF - Neurotoxicology AU - Harry, G Jean Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 503 EP - 506 VL - 25 IS - 4 KW - Index Medicus KW - Proteomics -- methods KW - Oligonucleotide Array Sequence Analysis -- trends KW - Animals KW - Magnetic Resonance Spectroscopy -- methods KW - Proteomics -- trends KW - Humans KW - Computational Biology -- methods KW - Oligonucleotide Array Sequence Analysis -- methods KW - Computational Biology -- trends KW - Neurotoxicity Syndromes -- diagnosis KW - Neurotoxicity Syndromes -- metabolism KW - Neurotoxicity Syndromes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72003327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Neurotoxicology&rft.atitle=Emerging+technologies+in+neurotoxicology%3A+Session+III+summary+and+research+needs.&rft.au=Harry%2C+G+Jean&rft.aulast=Harry&rft.aufirst=G&rft.date=2004-06-01&rft.volume=25&rft.issue=4&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-15 N1 - Date created - 2004-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucosylceramide synthase activity and ceramide levels are modulated during cerebral ischemia after ischemic preconditioning. AN - 72000931; 15181369 AB - After 24-hour middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats, brain ceramide level increased from baseline reached 595% (ischemic core) and 460% (perifocal/penumbral areas); brain glucosylceramide synthase (GCS) activities in these areas simultaneously decreased by 70% and 50%, respectively. Ten-minute MCAO preconditioning significantly attenuated 24-hour MCAO-induced ceramide accumulation by 40% to 60% in ischemic core and perifocal areas, and GCS activities improved by 60% to 70% in both areas. Thus, potentially toxic levels of brain ceramide induced by MCAO were attenuated to intermediate levels in preconditioned animals; brain GCS activity was relatively preserved. In ischemic tolerance, GCS appears to modulate otherwise high levels of brain ceramide. JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism AU - Takahashi, Kenzo AU - Ginis, Irene AU - Nishioka, Ryoji AU - Klimanis, Dace AU - Barone, Frank C AU - White, Raymond F AU - Chen, Yong AU - Hallenbeck, John M AD - Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 623 EP - 627 VL - 24 IS - 6 SN - 0271-678X, 0271-678X KW - Ceramides KW - 0 KW - Glucosyltransferases KW - EC 2.4.1.- KW - ceramide glucosyltransferase KW - EC 2.4.1.80 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred SHR KW - Infarction, Middle Cerebral Artery KW - Male KW - Brain -- enzymology KW - Brain Ischemia -- pathology KW - Brain -- pathology KW - Glucosyltransferases -- metabolism KW - Ceramides -- metabolism KW - Brain Ischemia -- metabolism KW - Ischemic Preconditioning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72000931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cerebral+blood+flow+and+metabolism+%3A+official+journal+of+the+International+Society+of+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Glucosylceramide+synthase+activity+and+ceramide+levels+are+modulated+during+cerebral+ischemia+after+ischemic+preconditioning.&rft.au=Takahashi%2C+Kenzo%3BGinis%2C+Irene%3BNishioka%2C+Ryoji%3BKlimanis%2C+Dace%3BBarone%2C+Frank+C%3BWhite%2C+Raymond+F%3BChen%2C+Yong%3BHallenbeck%2C+John+M&rft.aulast=Takahashi&rft.aufirst=Kenzo&rft.date=2004-06-01&rft.volume=24&rft.issue=6&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Journal+of+cerebral+blood+flow+and+metabolism+%3A+official+journal+of+the+International+Society+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-29 N1 - Date created - 2004-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of specific haplotypes of D2 dopamine receptor gene with vulnerability to heroin dependence in 2 distinct populations. AN - 71997686; 15184239 AB - Dopamine receptor-mediated pathways play critical roles in the mechanism of addiction. However, associations of the D(2) dopamine receptor gene (DRD2) with substance abuse are controversial. To determine whether susceptibility sites resided at DRD2. Haplotype-based case-control analysis of 2 distinct populations using 10 single nucleotide polymorphisms (SNPs) with heroin dependence. Universities of Mainz and Bonn, Germany, and 3 local hospitals in southwestern China. Patients Cases and control subjects recruited from China (486 cases, 313 controls) and Germany (471 cases, 192 controls). Genotyping for 10 SNPs by 5'-exonuclease fluorescence assays. The D' value of linkage disequilibrium and haplotypes were generated by the expectation-maximization algorithm. Genotype, allele, and haplotype frequencies were compared between cases and controls by chi(2) tests constructed for each population. An additional 32 SNPs randomly distributed in the genome were genotyped for detecting population admixture in the 2 populations. A haplotype block of 25.8 kilobases (kb) was defined by 8 SNPs extending from SNP3 (TaqIB) at the 5' end to SNP10 site (TaqIA) located 10 kb distal to the 3' end of the gene. Within this block, specific haplotype cluster A (carrying TaqIB1 allele) was associated with a high risk of heroin dependence in Chinese patients (P = 1.425 x 10(-22); odds ratio, 52.80; 95% confidence interval, 7.290-382.5 for 8-SNP analysis). A putative recombination "hot spot" was found near SNP6 (intron 6 ins/del G), creating 2 new daughter haplotypes that were associated with a lower risk of heroin dependence in Germans (P = 1.94 x 10(-11) for 8-SNP analysis). There was no evidence of population stratification in either population. These results strongly support a role of DRD2 as a susceptibility gene with heroin dependence in Chinese patients and was associated with low risk of heroin dependence in Germans. JF - Archives of general psychiatry AU - Xu, Ke AU - Lichtermann, Dirk AU - Lipsky, Robert H AU - Franke, Petra AU - Liu, Xiehe AU - Hu, Ying AU - Cao, Liping AU - Schwab, Sibylle G AU - Wildenauer, Dieter B AU - Bau, Claiton H D AU - Ferro, Erica AU - Astor, Will AU - Finch, Thembi AU - Terry, Jeanietta AU - Taubman, Julie AU - Maier, Wolfgang AU - Goldman, David AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. ke@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 597 EP - 606 VL - 61 IS - 6 SN - 0003-990X, 0003-990X KW - Receptors, Dopamine D2 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Genotype KW - Gene Frequency KW - African Continental Ancestry Group -- genetics KW - Humans KW - Germany -- ethnology KW - Adult KW - Case-Control Studies KW - Linkage Disequilibrium -- genetics KW - African Americans -- genetics KW - Genetic Predisposition to Disease KW - Polymorphism, Single Nucleotide -- genetics KW - China -- ethnology KW - Haplotypes -- genetics KW - Receptors, Dopamine D2 -- genetics KW - Heroin Dependence -- genetics KW - European Continental Ancestry Group -- genetics KW - Asian Continental Ancestry Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71997686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+of+specific+haplotypes+of+D2+dopamine+receptor+gene+with+vulnerability+to+heroin+dependence+in+2+distinct+populations.&rft.au=Xu%2C+Ke%3BLichtermann%2C+Dirk%3BLipsky%2C+Robert+H%3BFranke%2C+Petra%3BLiu%2C+Xiehe%3BHu%2C+Ying%3BCao%2C+Liping%3BSchwab%2C+Sibylle+G%3BWildenauer%2C+Dieter+B%3BBau%2C+Claiton+H+D%3BFerro%2C+Erica%3BAstor%2C+Will%3BFinch%2C+Thembi%3BTerry%2C+Jeanietta%3BTaubman%2C+Julie%3BMaier%2C+Wolfgang%3BGoldman%2C+David&rft.aulast=Xu&rft.aufirst=Ke&rft.date=2004-06-01&rft.volume=61&rft.issue=6&rft.spage=597&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 - 2004-06-24 N1 - Date created - 2004-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Gen Psychiatry. 2006 Aug;63(8):939; author reply 939-40 [16894071] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reliability and validity of opiate use self-report in a population at high risk for esophageal cancer in Golestan, Iran. AN - 71997187; 15184266 AB - To assess the reliability and validity of self-reported opium use in a rural Iranian population at high risk for esophageal cancer in preparation for a large cohort study. 1,057 subjects ages 33 to 84 years were recruited from Gonbad city and three surrounding villages in Golestan province of Iran and completed a questionnaire and provided biological samples. The history and duration of using opium, smoking tobacco, chewing nass, and drinking alcohol were measured by questionnaire in the entire cohort. A subgroup of 130 people was reinterviewed after 2 months to assess reliability. Validity of the opium question was assessed by comparing the questionnaire responses with the presence of codeine and morphine in the urine of 150 selected subjects. Self-reported opiate use is reliable and valid in this population. The reliability of ever opium use and duration of opium use had kappa's of 0.96 and 0.74, respectively. The validity of self-reported opium use was also high. Using urine codeine or morphine as the gold standard for use of opium, self-report had a sensitivity of 0.93 and a specificity of 0.89. The self-reported use of opium can provide a reliable and valid measurement in this population and will be useful for studying associations between opium use and occurrence of esophageal cancer and other diseases. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Abnet, Christian C AU - Saadatian-Elahi, Mitra AU - Pourshams, Akram AU - Boffetta, Paolo AU - Feizzadeh, Ali AU - Brennan, Paul AU - Taylor, Philip R AU - Kamangar, Farin AU - Dawsey, Sanford M AU - Malekzadeh, Reza AD - Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. abnetc@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1068 EP - 1070 VL - 13 IS - 6 SN - 1055-9965, 1055-9965 KW - Analgesics, Opioid KW - 0 KW - Morphine KW - 76I7G6D29C KW - Opium KW - 8008-60-4 KW - Codeine KW - Q830PW7520 KW - Index Medicus KW - Esophageal Neoplasms -- chemically induced KW - Rural Health KW - Morphine -- toxicity KW - Morphine -- urine KW - Codeine -- toxicity KW - Codeine -- urine KW - Humans KW - Iran -- epidemiology KW - Alcohol Drinking -- adverse effects KW - Aged KW - Pilot Projects KW - Analgesics, Opioid -- toxicity KW - Esophageal Neoplasms -- epidemiology KW - Neoplasms, Squamous Cell -- epidemiology KW - Aged, 80 and over KW - Adult KW - Male KW - Opium -- urine KW - Smoking -- adverse effects KW - Analgesics, Opioid -- urine KW - Neoplasms, Squamous Cell -- chemically induced KW - Substance Abuse Detection KW - Risk Factors KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Opium -- toxicity KW - Self Disclosure KW - Opioid-Related Disorders -- epidemiology KW - Opioid-Related Disorders -- complications KW - Surveys and Questionnaires KW - Opioid-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71997187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reliability+and+validity+of+opiate+use+self-report+in+a+population+at+high+risk+for+esophageal+cancer+in+Golestan%2C+Iran.&rft.au=Abnet%2C+Christian+C%3BSaadatian-Elahi%2C+Mitra%3BPourshams%2C+Akram%3BBoffetta%2C+Paolo%3BFeizzadeh%2C+Ali%3BBrennan%2C+Paul%3BTaylor%2C+Philip+R%3BKamangar%2C+Farin%3BDawsey%2C+Sanford+M%3BMalekzadeh%2C+Reza&rft.aulast=Abnet&rft.aufirst=Christian&rft.date=2004-06-01&rft.volume=13&rft.issue=6&rft.spage=1068&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 - 2004-09-03 N1 - Date created - 2004-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increasing secretion of a bivalent anti-T-cell immunotoxin by Pichia pastoris. AN - 71990025; 15184133 AB - The bivalent anti-T-cell immunotoxin A-dmDT390-bisFv(G(4)S) was developed for treatment of T-cell leukemia and autoimmune diseases and for tolerance induction for transplantation. This immunotoxin was produced extracellularly in toxin-sensitive Pichia pastoris JW102 (Mut(+)) under control of the AOX1 promoter. There were two major barriers to efficient immunotoxin production, the toxicity of the immunotoxin for P. pastoris and the limited capacity of P. pastoris to secrete the immunotoxin. The immunotoxin toxicity resulted in a decrease in the methanol consumption rate, cessation of cell growth, and low immunotoxin productivity after the first 22 h of methanol induction. Continuous cell growth and continuous immunotoxin secretion after the first 22 h of methanol induction were obtained by adding glycerol to the methanol feed by using a 4:1 methanol-glycerol mixed feed as an energy source and by continuously adding a yeast extract solution during methanol induction. The secretory capacity was increased from 22.5 to 37 mg/liter by lowering the induction temperature. A low temperature reduced the methanol consumption rate and protease activity in the supernatant but not cell growth. The effects of adding glycerol and yeast extract to the methanol feed were synergistic. Adding yeast extract primarily enhanced methanol utilization and cell growth, while adding glycerol primarily enhanced immunotoxin production. The synergy was further enhanced by decreasing the induction temperature from 23 to 15 degrees C, which resulted in a robust process with a yield of 37 mg/liter, which was sevenfold greater than the yield previously reported for a toxin-resistant CHO cell expression system. This methodology should be applicable to other toxin-related recombinant proteins in toxin-sensitive P. pastoris. JF - Applied and environmental microbiology AU - Woo, Jung Hee AU - Liu, Yuan Yi AU - Stavrou, Scott AU - Neville, David M AD - Biophysical Chemistry Section, Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4034, USA. wooj@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 3370 EP - 3376 VL - 70 IS - 6 SN - 0099-2240, 0099-2240 KW - Culture Media KW - 0 KW - Immunotoxins KW - Glycerol KW - PDC6A3C0OX KW - Methanol KW - Y4S76JWI15 KW - Index Medicus KW - Methanol -- metabolism KW - Glycerol -- metabolism KW - Fermentation KW - Humans KW - Temperature KW - Gene Expression Regulation KW - Biotechnology -- methods KW - Immunotoxins -- toxicity KW - Pichia -- genetics KW - Bioreactors KW - Pichia -- metabolism KW - Pichia -- drug effects KW - Immunotoxins -- genetics KW - Immunotoxins -- metabolism KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71990025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+and+environmental+microbiology&rft.atitle=Increasing+secretion+of+a+bivalent+anti-T-cell+immunotoxin+by+Pichia+pastoris.&rft.au=Woo%2C+Jung+Hee%3BLiu%2C+Yuan+Yi%3BStavrou%2C+Scott%3BNeville%2C+David+M&rft.aulast=Woo&rft.aufirst=Jung&rft.date=2004-06-01&rft.volume=70&rft.issue=6&rft.spage=3370&rft.isbn=&rft.btitle=&rft.title=Applied+and+environmental+microbiology&rft.issn=00992240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-10 N1 - Date created - 2004-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Cancer Res. 2003 Feb;9(2):861-5 [12576460] Protein Sci. 1994 Sep;3(9):1464-75 [7833808] Mol Biol Cell. 1998 Dec;9(12):3455-73 [9843581] Biotechniques. 1999 Jan;26(1):36-8, 40, 42 [9894589] Biotechnol Bioeng. 2000 May 20;68(4):389-95 [10745207] Protein Expr Purif. 2000 Jul;19(2):304-11 [10873546] Genes Dev. 2000 Dec 1;14(23):2962-75 [11114886] Protein Expr Purif. 2001 Apr;21(3):438-45 [11281719] Protein Eng. 2001 Dec;14(12):1035-41 [11809934] Protein Expr Purif. 2002 Jul;25(2):270-82 [12135560] J Cell Biol. 2003 Mar 31;160(7):1139-50 [12668662] Appl Environ Microbiol. 2003 Apr;69(4):2065-72 [12676684] Free Radic Biol Med. 2003 May 15;34(10):1315-25 [12726919] J Ind Microbiol Biotechnol. 2003 Apr;30(4):210-5 [12687491] Biochemistry. 2003 Jun 17;42(23):7171-7 [12795613] Protein Expr Purif. 2003 Aug;30(2):262-74 [12880776] Semin Oncol. 2003 Aug;30(4):545-57 [12939723] Biotechniques. 2003 Aug;35(2):392-8 [12951782] Adv Microb Physiol. 1983;24:1-82 [6364725] Biochim Biophys Acta. 1987 Aug 7;902(1):24-30 [3607056] J Biol Chem. 1995 Nov 24;270(47):28037-41 [7499288] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ovarian cancer risk after the use of ovulation-stimulating drugs. AN - 71975017; 15172852 AB - To assess the long-term effects of ovulation-stimulating drugs on the risk of ovarian cancer. A retrospective cohort study of 12,193 eligible study subjects (median age 30 years) who were evaluated for infertility during the period of 1965-1988 at 5 clinical sites identified 45 subsequent ovarian cancers in follow-up through 1999. Standardized incidence ratios compared the risk of cancer among the infertile patients to the general population, whereas analyses within the cohort allowed the derivation of rate ratios for drug usage compared with no usage after adjustment for other ovarian cancer predictors. The infertility patients had a significantly elevated ovarian cancer risk compared with the general population (standardized incidence ratio 1.98, 95% confidence intervals [CI] 1.4, 2.6). When patient characteristics were taken into account and risks assessed within the infertile women, the rate ratios associated with ever usage were 0.82 (95% CI 0.4, 1.5) for clomiphene and 1.09 (95% CI 0.4, 2.8) for gonadotropins. There were higher, albeit nonsignificant, risks with follow-up time, with the rate ratios after 15 or more years being 1.48 (95% CI 0.7, 3.2) for exposure to clomiphene (5 exposed cancer patients) and 2.46 (95% CI 0.7, 8.3) for gonadotropins (3 exposed cancer patients). Although drug effects did not vary by causes of infertility, there was a slightly higher risk associated with clomiphene use among women who remained nulligravid, based on 6 exposed patients (rate ratio 1.75; 95% CI 0.5, 5.7). The results of this study generally were reassuring in not confirming a strong link between ovulation-stimulating drugs and ovarian cancer. Slight but nonsignificant elevations in risk associated with drug usage among certain subgroups of users, however, support the need for continued monitoring of long-term risks. II-2 JF - Obstetrics and gynecology AU - Brinton, Louise A AU - Lamb, Emmet J AU - Moghissi, Kamran S AU - Scoccia, Bert AU - Althuis, Michelle D AU - Mabie, Jerome E AU - Westhoff, Carolyn L AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 7068, Bethesda, MD 20852-7234, USA. brinton@nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1194 EP - 1203 VL - 103 IS - 6 SN - 0029-7844, 0029-7844 KW - Fertility Agents, Female KW - 0 KW - Gonadotropins KW - Clomiphene KW - 1HRS458QU2 KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Registries -- statistics & numerical data KW - Humans KW - Cohort Studies KW - Adult KW - Retrospective Studies KW - Incidence KW - Follow-Up Studies KW - Time Factors KW - Female KW - Ovulation Induction KW - Infertility, Female -- drug therapy KW - Gonadotropins -- adverse effects KW - Fertility Agents, Female -- therapeutic use KW - Clomiphene -- therapeutic use KW - Ovarian Neoplasms -- chemically induced KW - Fertility Agents, Female -- adverse effects KW - Clomiphene -- adverse effects KW - Gonadotropins -- therapeutic use KW - Ovarian Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71975017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ovarian+cancer+risk+after+the+use+of+ovulation-stimulating+drugs.&rft.au=Brinton%2C+Louise+A%3BLamb%2C+Emmet+J%3BMoghissi%2C+Kamran+S%3BScoccia%2C+Bert%3BAlthuis%2C+Michelle+D%3BMabie%2C+Jerome+E%3BWesthoff%2C+Carolyn+L&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2004-06-01&rft.volume=103&rft.issue=6&rft.spage=1194&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 - 2004-07-02 N1 - Date created - 2004-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ritonavir decreases the nonrenal clearance of digoxin in healthy volunteers with known MDR1 genotypes. AN - 71974196; 15167636 AB - Our objective was to examine the influence of ritonavir on P-glycoprotein (P-gp) activity in humans by characterizing the effect of ritonavir on the pharmacokinetics of the P-gp substrate digoxin in individuals with known MDR1 genotypes. Healthy volunteers received a single dose of digoxin 0.4 mg orally before and after 14 days of ritonavir 200 mg twice daily. After each digoxin dose blood and urine were collected over 72 hours and analyzed for digoxin. Digoxin pharmacokinetic parameter values were determined using noncompartmental methods. MDR1 genotypes at positions 3435 and 2677 in exons 26 and 21, respectively, were determined using PCR-RFLP analysis. Ritonavir increased the digoxin AUC(0-72) from 26.20 +/- 8.67 to 31.96 +/- 11.24 ng x h/mL (P = 0.03) and the AUC(0-8) from 6.25 +/- 1.8 to 8.04 +/- 2.22 ng x h/mL (P = 0.02) in 12 subjects. Digoxin oral clearance decreased from 149 +/- 101 mL/h x kg to 105 +/- 57 mL/h x kg (P = 0.04). Other digoxin pharmacokinetic parameter values, including renal clearance, were unaffected by ritonavir. Overall, 75% (9/12) of subjects had higher concentrations of digoxin after ritonavir administration. The majority of subjects were heterozygous at position 3435 (C/T) (6 subjects) and position 2677 (G/T,A) (7 subjects); although data are limited, the effect of ritonavir on digoxin pharmacokinetics appears to occur across all tested MDR1 genotypes. Concomitant low-dose ritonavir reduced the nonrenal clearance of digoxin, thereby increasing its systemic availability. The most likely mechanism for this interaction is ritonavir-associated inhibition of P-gp. Thus, ritonavir can alter the pharmacokinetics of coadministered medications that are P-gp substrates. JF - Therapeutic drug monitoring AU - Penzak, Scott R AU - Shen, Jean M AU - Alfaro, Raul M AU - Remaley, Alan T AU - Natarajan, Ven AU - Falloon, Judith AD - Warren G. Magnuson Clinical Center, Pharmacy Department, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 322 EP - 330 VL - 26 IS - 3 SN - 0163-4356, 0163-4356 KW - HIV Protease Inhibitors KW - 0 KW - P-Glycoprotein KW - Digoxin KW - 73K4184T59 KW - Ritonavir KW - O3J8G9O825 KW - Index Medicus KW - Drug Interactions KW - Area Under Curve KW - Humans KW - Metabolic Clearance Rate KW - Genes, MDR KW - P-Glycoprotein -- antagonists & inhibitors KW - Genotype KW - Polymerase Chain Reaction KW - Patient Compliance KW - P-Glycoprotein -- metabolism KW - Adult KW - Middle Aged KW - Female KW - Male KW - Digoxin -- urine KW - Digoxin -- pharmacokinetics KW - Ritonavir -- pharmacology KW - HIV Protease Inhibitors -- pharmacology KW - HIV Protease Inhibitors -- adverse effects KW - Digoxin -- blood KW - Ritonavir -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71974196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Therapeutic+drug+monitoring&rft.atitle=Ritonavir+decreases+the+nonrenal+clearance+of+digoxin+in+healthy+volunteers+with+known+MDR1+genotypes.&rft.au=Penzak%2C+Scott+R%3BShen%2C+Jean+M%3BAlfaro%2C+Raul+M%3BRemaley%2C+Alan+T%3BNatarajan%2C+Ven%3BFalloon%2C+Judith&rft.aulast=Penzak&rft.aufirst=Scott&rft.date=2004-06-01&rft.volume=26&rft.issue=3&rft.spage=322&rft.isbn=&rft.btitle=&rft.title=Therapeutic+drug+monitoring&rft.issn=01634356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-28 N1 - Date created - 2004-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exocrine pancreatic pathology in female Harlan Sprague-Dawley rats after chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds. AN - 71971970; 15175180 AB - We evaluated the effect of chronic exposure to dioxin and dioxin-like compounds on the pancreas in female Harlan Sprague-Dawley rats. This investigation represents part of an ongoing National Toxicology Program initiative to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. Animals were treated by gavage for up to 2 years with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3,4,4,5-pentachlorobiphenyl (PCB-126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a toxic-equivalency-factor (TEF) mixture of these agents; control animals received corn oil-acetone vehicle alone. A complete necropsy was performed on all animals, and a full complement of tissues was collected and examined microscopically. Administration of each of the four compounds was associated with increased incidences of several nonneoplastic changes in the exocrine pancreas, including cytoplasmic vacuolation, chronic active inflammation, atrophy, and arteritis. Low incidences, but higher than those in the historical database, of pancreatic acinar adenoma and carcinoma were seen in the TCDD, PeCDF, and TEF-mixture groups. These results indicate that the pancreatic acini are target tissues for dioxin and certain dioxin-like compounds. Key words: carcinogenesis, dioxin, furans, inflammation, pancreas, polychlorinated biphenyls. JF - Environmental health perspectives AU - Nyska, Abraham AU - Jokinen, Micheal P AU - Brix, Amy E AU - Sells, Donald M AU - Wyde, Michael E AU - Orzech, Denise AU - Haseman, Joseph K AU - Flake, Gordon AU - Walker, Nigel J AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, PO Box 12233, Research Triangle Park, NC 27709, USA. nyska@niehs.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 903 EP - 909 VL - 112 IS - 8 SN - 0091-6765, 0091-6765 KW - Dioxins KW - 0 KW - Environmental Pollutants KW - Furans KW - Polychlorinated Dibenzodioxins KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Sprague-Dawley KW - Female KW - Inflammation KW - Pancreas -- pathology KW - Furans -- administration & dosage KW - Environmental Pollutants -- toxicity KW - Polychlorinated Biphenyls -- toxicity KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Polychlorinated Dibenzodioxins -- toxicity KW - Furans -- toxicity KW - Dioxins -- administration & dosage KW - Pancreas -- drug effects KW - Dioxins -- toxicity KW - Polychlorinated Biphenyls -- administration & dosage KW - Environmental Pollutants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71971970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Exocrine+pancreatic+pathology+in+female+Harlan+Sprague-Dawley+rats+after+chronic+treatment+with+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+and+dioxin-like+compounds.&rft.au=Nyska%2C+Abraham%3BJokinen%2C+Micheal+P%3BBrix%2C+Amy+E%3BSells%2C+Donald+M%3BWyde%2C+Michael+E%3BOrzech%2C+Denise%3BHaseman%2C+Joseph+K%3BFlake%2C+Gordon%3BWalker%2C+Nigel+J&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2004-06-01&rft.volume=112&rft.issue=8&rft.spage=903&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 - 2004-08-24 N1 - Date created - 2004-06-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Eur J Gastroenterol Hepatol. 2002 Jun;14(6):671-7 [12072602] Crit Rev Toxicol. 2002 May;32(3):211-32 [12071573] Pancreatology. 2002;2(6):510-8 [12435863] J Natl Cancer Inst. 2003 Jul 2;95(13):948-60 [12837831] Arch Toxicol. 2003 Jul;77(7):371-83 [12851740] Cardiovasc Toxicol. 2003;3(4):299-310 [14734827] JAMA. 1981 Jan 9;245(2):147-52 [7452829] Cancer Res. 1983 Jul;43(7):3219-25 [6601985] J Occup Med. 1984 Nov;26(11):844-6 [6502289] J Natl Cancer Inst. 1985 Dec;75(6):1067-73 [3865010] Biometrics. 1988 Jun;44(2):417-31 [3390507] J Toxicol Environ Health. 1988;25(2):201-5 [3050142] Toxicol Pathol. 1988;16(3):313-20 [3057589] Carcinogenesis. 1989 Feb;10(2):311-6 [2643485] Carcinogenesis. 1989 Jun;10(6):1127-30 [2720905] Fundam Appl Toxicol. 1989 May;12(4):731-7 [2744275] Am J Surg Pathol. 1992 Sep;16(9):815-37 [1384374] Toxicol Pathol. 1992;20(2):212-25 [1475582] N Engl J Med. 1993 May 20;328(20):1433-7 [8479461] J Pathol. 1993 Apr;169(4):457-63 [8501544] J Biochem Toxicol. 1993 Jun;8(2):71-81 [8355262] Am J Pathol. 1993 Sep;143(3):685-98 [8362971] Mol Pharmacol. 1993 Nov;44(5):911-7 [8246913] Pancreas. 1994 Jan;9(1):62-6 [8108373] Chem Res Toxicol. 1993 Nov-Dec;6(6):754-63 [8117913] J Gastroenterol Hepatol. 1995 Mar-Apr;10(2):215-32 [7787172] Int J Pancreatol. 1995 Aug;18(1):59-66 [7594771] Cancer Causes Control. 1996 Jan;7(1):69-82 [8850436] Pancreas. 1997 Mar;14(2):109-12 [9057181] J Natl Cancer Inst. 1997 Mar 19;89(6):442-6 [9091646] Arzneimittelforschung. 1997 Jul;47(7):879-84 [9272249] Br J Pharmacol. 1998 Jun;124(3):435-40 [9647465] Environ Health Perspect. 1998 Dec;106(12):775-92 [9831538] Exp Toxicol Pathol. 1999 Jan;51(1):105-7 [10048722] J Natl Cancer Inst. 1999 May 5;91(9):779-86 [10328108] Int J Cancer. 1999 Jun 11;81(6):889-96 [10362135] Ann N Y Acad Sci. 1999 Jun 30;880:191-200 [10415864] Ann Oncol. 1999;10 Suppl 4:69-73 [10436789] Toxicol Appl Pharmacol. 1978 Nov;46(2):279-303 [734660] Ann Clin Lab Sci. 2000 Jan;30(1):3-21 [10678579] Toxicol Sci. 2000 Apr;54(2):330-7 [10774815] Toxicol Appl Pharmacol. 2000 Jun 15;165(3):184-94 [10860868] Endocrinology. 2000 Aug;141(8):2938-44 [10919282] Am J Hum Genet. 2001 Mar;68(3):700-10 [11179017] Am J Epidemiol. 2001 Jun 1;153(11):1031-44 [11390319] Toxicol Sci. 2001 Nov;64(1):28-40 [11606799] Dig Dis. 2002;20(1):32-7 [12145418] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 153Sm-EDTMP for bone pain palliation in skeletal metastases. AN - 71968800; 15127241 AB - 153Sm-ethylene diamine tetramethylene phosphonate (EDTMP) is a widely available and extensively tested radiopharmaceutical for systemic radionuclide therapy in patients with symptomatic multiple skeletal metastases. Its use is approved for any secondary bone lesion which has been shown to accumulate (99m)Tc-methylene diphosphonate, including breast carcinoma. The molecule is stable in vitro and upon injection more than 50% of the dose is avidly fixed by lesional and non-lesional bone, with the rest being rapidly eliminated unchanged via the urine. The short half-life (46.3 h), the relatively low-energy beta emissions (E(ave)=233 keV) and the gamma emission (103 keV) make (153)Sm a very attractive radionuclide, allowing therapeutic delivery of short-range electrons at relatively high dose rates with external imaging to corroborate biodistribution and possible dosimetric estimates. For a standard dose of 2,590 MBq/70 kg, the estimated radiation dose to metastases is 86.5 Gy. Critical organs are the bladder wall (2.5 Gy/2,590 MBq) and red marrow (4 Gy/2,590 MBq), with the latter being the critical factor in clinical practice as the dose-limiting factor is marrow radiotoxicity. The therapy has, however, proved safe provided that the platelet count exceeds 100 x 10(9)/l and the white blood cell count exceeds 3.5 x 10(9)/l. Clinical data obtained in fewer than 250 patients, within several studies, lead to the following conclusions: a dose of 37 MBq/kg has a better therapeutic ratio than a dose of 18.5 MBq/kg; the mean pain palliation rate after a single treatment in breast cancer is about 80%; toxicity is generally mild and transitory; and re-treatments are effective and safe provided that haematological values have fully recovered. JF - European journal of nuclear medicine and molecular imaging AU - Maini, Carlo L AU - Bergomi, Serenella AU - Romano, Luisa AU - Sciuto, Rosa AD - Nuclear Medicine Department, Regina Elena National Cancer Institute, Rome, Italy. maini@ifo.it Y1 - 2004/06// PY - 2004 DA - June 2004 SP - S171 EP - S178 VL - 31 Suppl 1 SN - 1619-7070, 1619-7070 KW - Organometallic Compounds KW - 0 KW - Organophosphorus Compounds KW - Radiopharmaceuticals KW - samarium Sm-153 lexidronam KW - 745X144DZY KW - Index Medicus KW - Humans KW - Radiation Injuries -- prevention & control KW - Clinical Trials as Topic KW - Dose-Response Relationship, Radiation KW - Radiopharmaceuticals -- adverse effects KW - Radiopharmaceuticals -- therapeutic use KW - Radioimmunotherapy -- adverse effects KW - Radiotherapy Dosage KW - Treatment Outcome KW - Maximum Tolerated Dose KW - Female KW - Radioimmunotherapy -- methods KW - Radiation Injuries -- etiology KW - Pain -- radiotherapy KW - Pain -- etiology KW - Organophosphorus Compounds -- therapeutic use KW - Bone Neoplasms -- radiotherapy KW - Organophosphorus Compounds -- adverse effects KW - Organometallic Compounds -- adverse effects KW - Organometallic Compounds -- therapeutic use KW - Breast Neoplasms -- radiotherapy KW - Breast Neoplasms -- complications KW - Palliative Care -- methods KW - Bone Neoplasms -- secondary KW - Bone Neoplasms -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71968800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+molecular+imaging&rft.atitle=153Sm-EDTMP+for+bone+pain+palliation+in+skeletal+metastases.&rft.au=Maini%2C+Carlo+L%3BBergomi%2C+Serenella%3BRomano%2C+Luisa%3BSciuto%2C+Rosa&rft.aulast=Maini&rft.aufirst=Carlo&rft.date=2004-06-01&rft.volume=31+Suppl+1&rft.issue=&rft.spage=S171&rft.isbn=&rft.btitle=&rft.title=European+journal+of+nuclear+medicine+and+molecular+imaging&rft.issn=16197070&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-03 N1 - Date created - 2004-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of human small bowel intraepithelial lymphocytes by annexin V-coated magnetic beads. AN - 71968347; 15154017 AB - Human intestinal intraepithelial lymphocytes (IEL) are important effector cells of the mucosal immune system and their study is hampered by the difficulty of their isolation. The molecular study of enriched samples of IEL is mandatory in the diagnosis of enteropathy-associated T-cell lymphoma and refractory celiac sprue. In order to isolate human small bowel IEL, we took advantage of the stress that intestinal epithelial cells (IEC) suffer during the conventional initial steps of IEL isolation, which induces their apoptosis but not that of IEL. After cell individualization by dithiothreitol and ethylenediamine tetraacetic acid, two-thirds of human IEC can be stained with Annexin-V due to their surface exposure of phosphatidyl serine, a sign of apoptosis. This percentage increases to 95% after performing a density gradient to enrich for IEL. This allows for the use of Annexin-V-coated magnetic beads, originally designed for the removal of dead cells from cell cultures, to obtain >95% pure, 99% viable and untouched IEL after two rounds of depletion. This simple procedure has proven useful for the isolation of human IEL for functional and molecular studies and can conceivably facilitate the diagnosis of intestinal lymphoid malignancies that rely upon the study of pure IEL preparations. JF - Laboratory investigation; a journal of technical methods and pathology AU - León, Francisco AU - Roy, Garbiñe AD - Department of Immunology, Hospital Ramón y Cajal, Madrid, Spain. fleon@niaid.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 804 EP - 809 VL - 84 IS - 6 SN - 0023-6837, 0023-6837 KW - Annexin A5 KW - 0 KW - Phosphatidylserines KW - Index Medicus KW - Humans KW - Phosphatidylserines -- metabolism KW - Ileum -- metabolism KW - Phenotype KW - Duodenum -- immunology KW - Duodenum -- metabolism KW - Duodenum -- cytology KW - Cytotoxicity Tests, Immunologic KW - Staining and Labeling KW - Ileum -- cytology KW - Cell Line KW - Ileum -- immunology KW - Intestinal Mucosa -- cytology KW - Immunomagnetic Separation -- methods KW - Lymphocytes -- immunology KW - Intestinal Mucosa -- immunology KW - Lymphocytes -- metabolism KW - Intestinal Mucosa -- metabolism KW - Lymphocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71968347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolation+of+human+small+bowel+intraepithelial+lymphocytes+by+annexin+V-coated+magnetic+beads.&rft.au=Le%C3%B3n%2C+Francisco%3BRoy%2C+Garbi%C3%B1e&rft.aulast=Le%C3%B3n&rft.aufirst=Francisco&rft.date=2004-06-01&rft.volume=84&rft.issue=6&rft.spage=804&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 - 2004-08-13 N1 - Date created - 2004-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leu-574 of human HIF-1alpha is a molecular determinant of prolyl hydroxylation. AN - 71967005; 15084514 AB - Hypoxia-inducible factor (HIF)-1alpha, a master regulator of oxygen homeostasis, regulates genes crucial for cell growth and survival. In normoxia, HIF-1alpha is constantly degraded via the ubiquitin-proteasome pathway. The von Hippel-Lindau (VHL) E3 ubiquitin ligase binds HIF-1alpha through specific recognition of hydroxylated Pro-402 or Pro-564, both of which are modified by the oxygen-dependent HIF prolyl hydroxylases (PHDs/HPHs). Despite the identification of a conserved Leu-X-X-Leu-Ala-Pro motif, the molecular requirement of HIF-1alpha for PHDs/HPHs binding remains elusive. Recently, we demonstrated that Leu-574 of human HIF-1alpha--10 residues downstream of Pro-564--is essential for VHL recognition. We show here that the role of Leu-574 is to recruit PHD2/HPH2 for Pro-564 hydroxylation. An antibody specific for hydroxylated Pro-564 has been used to determine the hydroxylation status; mutation or deletion of Leu-574 results in a significant decrease in the ratio of the hydroxylated HIF-1alpha to the total amount. The nine-residue spacing between Pro-564 and Leu-574 is not obligatory for prolyl hydroxylation. Furthermore, mutation of Leu-574 disrupts the binding of PHD2/HPH2, a key prolyl hydroxylase for oxygen-dependent proteolysis of HIF-1alpha. Hence, our findings indicate that Leu-574 is essential for recruiting PHD2/HPH2, thereby providing a molecular basis for modulating HIF-1alpha activity. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Kageyama, Yukio AU - Koshiji, Minori AU - To, Kenneth K W AU - Tian, Ya-Min AU - Ratcliffe, Peter J AU - Huang, L Eric AD - Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1028 EP - 1030 VL - 18 IS - 9 KW - Antibodies KW - 0 KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Transcription Factors KW - Proline KW - 9DLQ4CIU6V KW - Procollagen-Proline Dioxygenase KW - EC 1.14.11.2 KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Antibodies -- immunology KW - Thermodynamics KW - Humans KW - Protein Processing, Post-Translational KW - Transcription, Genetic -- genetics KW - Amino Acid Sequence KW - Cell Line, Tumor KW - Protein Binding KW - Hydroxylation KW - Molecular Sequence Data KW - Procollagen-Proline Dioxygenase -- metabolism KW - Mutation KW - Cell Line KW - Proline -- metabolism KW - Leucine -- immunology KW - Transcription Factors -- metabolism KW - Leucine -- metabolism KW - Leucine -- genetics KW - Transcription Factors -- chemistry KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71967005?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Leu-574+of+human+HIF-1alpha+is+a+molecular+determinant+of+prolyl+hydroxylation.&rft.au=Kageyama%2C+Yukio%3BKoshiji%2C+Minori%3BTo%2C+Kenneth+K+W%3BTian%2C+Ya-Min%3BRatcliffe%2C+Peter+J%3BHuang%2C+L+Eric&rft.aulast=Kageyama&rft.aufirst=Yukio&rft.date=2004-06-01&rft.volume=18&rft.issue=9&rft.spage=1028&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-02 N1 - Date created - 2004-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteasome-mediated destruction of the cyclin a/cyclin-dependent kinase 2 complex suppresses tumor cell growth in vitro and in vivo. AN - 71965093; 15173007 AB - Cyclin-dependent kinases (cdks) represent potentially promising molecular targets for cancer therapeutic strategies. To evaluate the antitumor activity of selective cyclin/cdk inhibition, we constructed a chimeric protein composed of a F-box protein (TrCP) fused to a peptide comprising the cyclin/cdk2 binding motif in p21-like cdk inhibitors (TrCP-LFG). We now demonstrate that endogenous cyclin A and its binding substrate, cdk2, can be tethered to beta-TrCP, ubiquitinated, and effectively degraded. Degradation of cdk2 and cyclin A together, but not cdk2 alone, results in massive tumor cell apoptosis in vitro and in vivo in a proteasome-dependent manner with no toxicity to normal tissue. These data demonstrate that cyclin A and/or the cyclin A/cdk2 complex is a promising anticancer target with a high therapeutic index. JF - Cancer research AU - Chen, Wei AU - Lee, Jeongwu AU - Cho, Steve Y AU - Fine, Howard A AD - Neuro-Oncology Branch, National Cancer Institute, National Institutes of Neurological Disorder and Stroke, NIH, Bethesda, Maryland 20892, USA. Y1 - 2004/06/01/ PY - 2004 DA - 2004 Jun 01 SP - 3949 EP - 3957 VL - 64 IS - 11 SN - 0008-5472, 0008-5472 KW - Apoptosis Regulatory Proteins KW - 0 KW - Carrier Proteins KW - Cyclin A KW - FAIM2 protein, human KW - Membrane Proteins KW - Multienzyme Complexes KW - Recombinant Fusion Proteins KW - beta-Transducin Repeat-Containing Proteins KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - Cdk2 protein, mouse KW - Cyclin-Dependent Kinase 2 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Animals KW - HeLa Cells KW - Humans KW - Transduction, Genetic KW - Cell Division -- drug effects KW - Cell Division -- physiology KW - Mice, Nude KW - Mice KW - Cell Line, Tumor KW - Recombinant Fusion Proteins -- metabolism KW - Apoptosis -- genetics KW - Glioma -- pathology KW - Protein Engineering KW - Glioma -- drug therapy KW - Recombinant Fusion Proteins -- genetics KW - Xenograft Model Antitumor Assays KW - Recombinant Fusion Proteins -- pharmacology KW - Female KW - Cyclin A -- metabolism KW - Multienzyme Complexes -- metabolism KW - CDC2-CDC28 Kinases -- antagonists & inhibitors KW - beta-Transducin Repeat-Containing Proteins -- metabolism KW - Cyclin A -- antagonists & inhibitors KW - Carrier Proteins -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - Carrier Proteins -- genetics KW - Carrier Proteins -- pharmacology KW - beta-Transducin Repeat-Containing Proteins -- genetics KW - beta-Transducin Repeat-Containing Proteins -- pharmacology KW - CDC2-CDC28 Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71965093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proteasome-mediated+destruction+of+the+cyclin+a%2Fcyclin-dependent+kinase+2+complex+suppresses+tumor+cell+growth+in+vitro+and+in+vivo.&rft.au=Chen%2C+Wei%3BLee%2C+Jeongwu%3BCho%2C+Steve+Y%3BFine%2C+Howard+A&rft.aulast=Chen&rft.aufirst=Wei&rft.date=2004-06-01&rft.volume=64&rft.issue=11&rft.spage=3949&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 - 2004-07-26 N1 - Date created - 2004-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. AN - 71964976; 15172993 AB - Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators. JF - Cancer research AU - Cheung, Connie AU - Akiyama, Taro E AU - Ward, Jerrold M AU - Nicol, Christopher J AU - Feigenbaum, Lionel AU - Vinson, Charles AU - Gonzalez, Frank J AD - Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/06/01/ PY - 2004 DA - 2004 Jun 01 SP - 3849 EP - 3854 VL - 64 IS - 11 SN - 0008-5472, 0008-5472 KW - Anticholesteremic Agents KW - 0 KW - Carcinogens KW - Fatty Acids KW - Peroxisome Proliferators KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - Index Medicus KW - Oxidation-Reduction KW - Carcinogens -- pharmacology KW - Animals KW - Humans KW - Pyrimidines -- pharmacology KW - Peroxisome Proliferators -- pharmacology KW - Mice KW - Anticholesteremic Agents -- pharmacology KW - Mice, Transgenic KW - Species Specificity KW - DNA Replication -- drug effects KW - Fatty Acids -- metabolism KW - Cell Division KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Hepatocytes -- drug effects KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Hepatocytes -- physiology KW - Hepatocytes -- cytology KW - Transcription Factors -- genetics KW - Hepatocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71964976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diminished+hepatocellular+proliferation+in+mice+humanized+for+the+nuclear+receptor+peroxisome+proliferator-activated+receptor+alpha.&rft.au=Cheung%2C+Connie%3BAkiyama%2C+Taro+E%3BWard%2C+Jerrold+M%3BNicol%2C+Christopher+J%3BFeigenbaum%2C+Lionel%3BVinson%2C+Charles%3BGonzalez%2C+Frank+J&rft.aulast=Cheung&rft.aufirst=Connie&rft.date=2004-06-01&rft.volume=64&rft.issue=11&rft.spage=3849&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 - 2004-07-26 N1 - Date created - 2004-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of beta-catenin provides proliferative and invasive advantages in c-myc/TGF-alpha hepatocarcinogenesis promoted by phenobarbital. AN - 71964561; 14742323 AB - Previously, we have found that phenobarbital (PB) enhanced cell survival and facilitated tumor growth in our c-myc/transforming growth factor (TGF)-alpha transgenic mouse model of liver cancer. Given that PB selectively promoted initiated cells harboring beta-catenin mutations during chemically induced hepatocarcinogenesis and that Wnt/beta-catenin signaling is involved in both anti-apoptotic and proliferative processes, we now have extended our analysis to investigate whether promotion by PB affects the occurrence of beta-catenin mutations in c-myc/TGF-alpha-driven tumors. The frequency of beta-catenin activation as judged by somatic mutations and/or nuclear localization was significantly increased in hepatocellular carcinomas (HCCs) from c-myc/TGF-alpha mice treated with PB (15/28; 53.6%) as compared with that in control HCCs (2/28; 7.1%). Furthermore, an intact beta-catenin locus was detected in all neoplasms following PB treatment, whereas 57.1% (16/28) of malignant tumors from c-myc/TGF-alpha untreated mice displayed loss of heterozygosity at the beta-catenin locus. Strikingly, in the majority of PB-treated HCCs beta-catenin nuclear localization was limited to small cells with high nuclear/cytoplasmic ratio forming an invasion front (NAinv). beta-Catenin NAinv cells showed cytoplasmic redistribution of E-cadherin associated with intense mucin 1 and matrilysin immunostaining, suggesting their invasive phenotype. All beta-catenin-positive HCCs displayed increased proliferation and tumor size, but no difference in the apoptotic rate when compared with beta-catenin negative tumors. These findings show that PB treatment positively selects for a cell population displaying activation of beta-catenin in c-myc/TGF-alpha HCCs. beta-Catenin activation confers additional growth and invasive advantages in a model of liver cancer already accelerated by synergistic activity of the c-myc and TGF-alpha transgenes. JF - Carcinogenesis AU - Calvisi, Diego F AU - Ladu, Sara AU - Factor, Valentina M AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4262, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 901 EP - 908 VL - 25 IS - 6 SN - 0143-3334, 0143-3334 KW - CTNNB1 protein, mouse KW - 0 KW - Cytoskeletal Proteins KW - DNA Primers KW - Proto-Oncogene Proteins c-myc KW - Trans-Activators KW - Transforming Growth Factor alpha KW - beta Catenin KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Neoplasm Invasiveness KW - Animals KW - Base Sequence KW - Loss of Heterozygosity KW - Apoptosis KW - Mice KW - Mice, Transgenic KW - Immunohistochemistry KW - Cell Division KW - Trans-Activators -- metabolism KW - Phenobarbital -- pharmacology KW - Liver Neoplasms, Experimental -- pathology KW - Transforming Growth Factor alpha -- physiology KW - Proto-Oncogene Proteins c-myc -- physiology KW - Cytoskeletal Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71964561?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+beta-catenin+provides+proliferative+and+invasive+advantages+in+c-myc%2FTGF-alpha+hepatocarcinogenesis+promoted+by+phenobarbital.&rft.au=Calvisi%2C+Diego+F%3BLadu%2C+Sara%3BFactor%2C+Valentina+M%3BThorgeirsson%2C+Snorri+S&rft.aulast=Calvisi&rft.aufirst=Diego&rft.date=2004-06-01&rft.volume=25&rft.issue=6&rft.spage=901&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-15 N1 - Date created - 2004-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monitoring caspase activity in living cells using fluorescent proteins and flow cytometry. AN - 71960867; 15161627 AB - A molecular probe was developed to monitor caspase activity in living cells by flow cytometry. It consists of CFP and YFP with a peptide linker containing two caspase-cleavage sites (LEVD). Its expression resulted in intense fluorescence resonance energy transfer (FRET), whereas cleavage of this linker by caspases eliminated FRET because of physical separation of the CFP and YFP moieties. Using flow cytometry, cells expressing this probe exhibited two patterns, strong FRET and diminished or absent FRET. The appearance of diminished FRET was inhibited by a pan-caspase inhibitor z-VAD or D->A mutations in the LEVD sequence and was markedly increased by apoptosis-inducing agents, etoposide and camptothecin, or overexpression of a caspase 8-red fluorescent protein fusion protein. Importantly, this probe's ability to monitor caspase activity was comparable with results obtained with fluorogenic substrates or fluorochrome-labeled inhibitors of caspases. Specific caspase inhibitors indicated the probe was highly sensitive to cleavage by caspase 6 and 8, less sensitive to caspase 4, and resistant to other caspases. Activation of caspase 8 by Fas engagement markedly increased the probe's cleavage, whereas treatment of caspase 8-deficient cells with anti-Fas did not increase cleavage. However, staurosporine induced cleavage of the probe in caspase 8-deficient cells by a mechanism that was inhibited by overexpression of bcl-x. Taken together, the data indicate that this caspase-sensitive probe can be used to monitor the basal and apoptosis-related activities of caspases, including an initiator caspase, caspase 8, and effector caspases, such as caspase 6. JF - The American journal of pathology AU - He, Liusheng AU - Wu, Xiaoli AU - Meylan, Francoise AU - Olson, Douglas P AU - Simone, James AU - Hewgill, Derek AU - Siegel, Richard AU - Lipsky, Peter E AD - Flow Cytometry Section, Office of Science and Technology, National Institute of Arthritis and Musculosketal and Skin Diseases, National Institute of Health, Bethesda, Maryland 20892, USA. Lihe@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1901 EP - 1913 VL - 164 IS - 6 SN - 0002-9440, 0002-9440 KW - Caspase Inhibitors KW - 0 KW - Cysteine Proteinase Inhibitors KW - Fluorescent Dyes KW - Luminescent Proteins KW - Oligodeoxyribonucleotides, Antisense KW - Caspases KW - EC 3.4.22.- KW - Abridged Index Medicus KW - Index Medicus KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Base Sequence KW - HeLa Cells KW - Humans KW - Jurkat Cells KW - Molecular Sequence Data KW - Plasmids KW - Luminescent Proteins -- genetics KW - Environmental Monitoring -- methods KW - Flow Cytometry -- methods KW - Apoptosis -- physiology KW - Caspases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71960867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Monitoring+caspase+activity+in+living+cells+using+fluorescent+proteins+and+flow+cytometry.&rft.au=He%2C+Liusheng%3BWu%2C+Xiaoli%3BMeylan%2C+Francoise%3BOlson%2C+Douglas+P%3BSimone%2C+James%3BHewgill%2C+Derek%3BSiegel%2C+Richard%3BLipsky%2C+Peter+E&rft.aulast=He&rft.aufirst=Liusheng&rft.date=2004-06-01&rft.volume=164&rft.issue=6&rft.spage=1901&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 - 2004-07-08 N1 - Date created - 2004-05-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2002 Jul 5;277(27):24506-14 [11964393] Biochem Soc Trans. 2001 Nov;29(Pt 6):696-702 [11709057] Biol Chem. 2002 Jul-Aug;383(7-8):1035-44 [12437086] J Biol Chem. 2002 Dec 27;277(52):50573-8 [12370172] Ann Med. 2002;34(6):480-8 [12523503] J Microsc. 2003 Jan;209(Pt 1):56-70 [12535185] J Cell Biol. 2003 Jan 20;160(2):235-43 [12527749] Anticancer Res. 2002 Nov-Dec;22(6C):4029-37 [12553028] Indian J Exp Biol. 2002 May;40(5):513-24 [12622195] Cytometry A. 2003 May;53(1):39-54 [12701131] Biochem Biophys Res Commun. 2003 May 2;304(2):217-22 [12711301] Biochem J. 2003 May 15;372(Pt 1):33-40 [12662152] J Biol Chem. 2003 Jun 6;278(23):21307-13 [12670932] Cytometry A. 2003 Oct;55(2):71-85 [14505312] Annu Rev Cell Biol. 1991;7:663-98 [1809356] J Biol Chem. 1997 Jul 18;272(29):17907-11 [9218414] Br Med Bull. 1997;53(3):478-90 [9374032] Nucleic Acids Res. 1998 Apr 15;26(8):2034-5 [9518501] Biochem Biophys Res Commun. 1998 Apr 28;245(3):797-803 [9588194] J Cell Biol. 1998 Jun 1;141(5):1243-53 [9606215] Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13884-8 [11717445] Trends Cell Biol. 2001 Dec;11(12):526-34 [11719060] Adv Exp Med Biol. 2001;500:407-20 [11764974] Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15003-8 [11752449] Sci STKE. 2000 Jun 27;2000(38):pl1 [11752595] Sci STKE. 2000 Aug 8;2000(44):pe1 [11752601] Radiother Oncol. 2002 Jan;62(1):61-7 [11830313] Mol Cell. 2002 Mar;9(3):459-70 [11931755] J Virol. 2002 May;76(10):5094-107 [11967325] Nat Biotechnol. 1996 Mar;14(3):297-301 [9630889] Nat Biotechnol. 1996 Oct;14(10):1246-51 [9631087] Curr Biol. 1998 Sep 10;8(18):1001-8 [9740801] Structure. 1998 Oct 15;6(10):1267-77 [9782051] Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4552-7 [10200300] Cytometry. 2000 Jun 1;40(2):151-60 [10805935] J Exp Med. 2000 Jun 5;191(11):1819-28 [10839799] Proteins. 2000 Dec 1;41(4):429-37 [11056031] J Biomol Screen. 2000 Oct;5(5):307-18 [11080689] Curr Biol. 2000 Nov 2;10(21):1395-8 [11084343] Nat Biotechnol. 2001 Feb;19(2):167-9 [11175733] Cytometry. 2001 May 1;44(1):73-82 [11309811] Cell Death Differ. 2001 Jan;8(1):38-43 [11313701] Biochem Biophys Res Commun. 2001 May 25;283(5):1054-60 [11355879] J Biol Chem. 2001 Mar 16;276(11):8087-93 [11098060] Cell Death Differ. 2001 Jul;8(7):696-705 [11464214] Biochem Soc Trans. 2001 Aug;29(Pt 4):480-4 [11498013] Cytometry. 2001 Aug 1;44(4):361-8 [11500853] BMC Cell Biol. 2001;2:8 [11401727] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protective peptides that are orally active and mechanistically nonchiral. AN - 71957990; 15007105 AB - Previous reports identified two peptides that mimic the action of neuroprotective proteins derived from astrocytes. These peptides, NAPVSIPQ and SALLRSIPA, prevent neuronal cell death produced by electrical blockade, N-methyl-d-aspartate, and beta-amyloid peptide (25-35). In the present study, all d-amino acid peptides of NAPVSIPQ and SALLRSIPA were synthesized and compared respectively to the corresponding all l-amino acid peptides. In rat cerebral cortical test cultures cotreated with 1 microM tetrodotoxin, the d-amino acid peptides produced similar potency and efficacy for neuroprotection as that observed for their respective l-amino acid peptides. Since all these peptides tested individually exhibited attenuation of efficacy at concentrations of >10 pM, combinations of these peptides were tested for possible synergies. Equimolar d-NAPVSIPQ and d-SALLRSIPA combination treatment produced potent neuroprotection (EC(50), 0.03 fM) that did not attenuate with increasing concentrations. Similarly, the combination of l-NAPVSIPQ and d-SALLRSIPA also had high potency (EC(50), 0.07 fM) without attenuation of efficacy. Combined administration of peptides was tested in a model of fetal alcohol syndrome and in a model of learning impairment: apolipoprotein E knockout mice. Intraperitoneal administration of d-NAPVSIPQ plus d-SALLRSIPA to pregnant mice (embryonic day 8) attenuated fetal demise after treatment with an acute high dose of alcohol. Furthermore, oral administration of d-NAPVSIPQ plus d-SALLRSIPA significantly increased fetal survival after maternal alcohol treatment. Apolipoprotein E knockout mice injected with d-NAPVSIPQ plus d-SALLRSIPA showed improved performance in the Morris water maze. These studies suggest therapeutic potential for the combined administration of neuroprotective peptides that can act through a mechanism independent of chiral recognition. JF - The Journal of pharmacology and experimental therapeutics AU - Brenneman, Douglas E AU - Spong, Catherine Y AU - Hauser, Janet M AU - Abebe, Daniel AU - Pinhasov, Albert AU - Golian, Tania AU - Gozes, Illana AD - Section of Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. dbrennem@prdus.jnj.com Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1190 EP - 1197 VL - 309 IS - 3 SN - 0022-3565, 0022-3565 KW - Neuroprotective Agents KW - 0 KW - Oligopeptides KW - Peptides KW - Ethanol KW - 3K9958V90M KW - davunetide KW - GF00K3IIWE KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Cells, Cultured KW - Neurons -- drug effects KW - Ethanol -- toxicity KW - Disease Models, Animal KW - Mice KW - Peptides -- therapeutic use KW - Female KW - Pregnancy KW - Mice, Knockout KW - Fetal Alcohol Spectrum Disorders -- prevention & control KW - Oligopeptides -- therapeutic use KW - Neuroprotective Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71957990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protective+peptides+that+are+orally+active+and+mechanistically+nonchiral.&rft.au=Brenneman%2C+Douglas+E%3BSpong%2C+Catherine+Y%3BHauser%2C+Janet+M%3BAbebe%2C+Daniel%3BPinhasov%2C+Albert%3BGolian%2C+Tania%3BGozes%2C+Illana&rft.aulast=Brenneman&rft.aufirst=Douglas&rft.date=2004-06-01&rft.volume=309&rft.issue=3&rft.spage=1190&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 - 2004-07-01 N1 - Date created - 2004-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Addressing the need for treatment paradigms for drug-abusing patients with multiple morbidities. AN - 71956554; 15156429 AB - Persons who use and abuse drugs are at risk for multiple morbidities that involve addiction, bloodborne infectious diseases, and sexually transmitted diseases, in addition to psychiatric illness and social instability. Infectious diseases acquired as a result of drug use can diffuse into non-drug using populations through other high-risk behaviors. Drug users also have substantial comorbidities from noncommunicable diseases and complications that can affect virtually every organ system in the body. Diagnosis of comorbidities and complications associated with drug abuse usually occurs late in the disease course, particularly for persons who are disenfranchised and have limited or no access to medical care. Medical management of these comorbid conditions constitutes a significant challenge. Directly observed therapy (DOT) can be useful but needs to conform to the needs of the targeted treatment population for full efficacy. DOT may have its greatest impact with drug users destabilized by cocaine or methamphetamine use but has yet to be fully investigated in this patient population. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Kresina, Thomas F AU - Normand, Jacques AU - Khalsa, Jag AU - Mitty, Jennifer AU - Flanigan, Timothy AU - Francis, Henry AD - Center for AIDS and Other Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892-9593, USA. Tk13v@nih.gov Y1 - 2004/06/01/ PY - 2004 DA - 2004 Jun 01 SP - S398 EP - S401 VL - 38 Suppl 5 KW - Index Medicus KW - Hepatitis C -- therapy KW - Sexually Transmitted Diseases -- therapy KW - HIV Infections -- transmission KW - Hepatitis C -- transmission KW - Sexually Transmitted Diseases -- complications KW - Hepatitis C -- complications KW - Humans KW - Hepatitis B -- therapy KW - Hepatitis B -- transmission KW - Morbidity KW - Hepatitis B -- complications KW - HIV Infections -- complications KW - HIV Infections -- therapy KW - Sexually Transmitted Diseases -- transmission KW - Male KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- mortality KW - Substance-Related Disorders -- complications KW - Directly Observed Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71956554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Addressing+the+need+for+treatment+paradigms+for+drug-abusing+patients+with+multiple+morbidities.&rft.au=Kresina%2C+Thomas+F%3BNormand%2C+Jacques%3BKhalsa%2C+Jag%3BMitty%2C+Jennifer%3BFlanigan%2C+Timothy%3BFrancis%2C+Henry&rft.aulast=Kresina&rft.aufirst=Thomas&rft.date=2004-06-01&rft.volume=38+Suppl+5&rft.issue=&rft.spage=S398&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-06 N1 - Date created - 2004-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. AN - 71954509; 15098002 AB - The involvement of dopamine in drug reinforcement is well recognized but its role in drug addiction is much less clear. Imaging studies have shown that the reinforcing effects of drugs of abuse in humans are contingent upon large and fast increases in dopamine that mimic but exceed in the intensity and duration those induced by dopamine cell firing to environmental events. In addition, imaging studies have also documented a role of dopamine in motivation, which appears to be encoded both by fast as well as smooth DA increases. Since dopamine cells fire in response to salient stimuli, the supraphysiological activation by drugs is likely to be experienced as highly salient (driving attention, arousal conditioned learning and motivation) and may also reset the thresholds required for environmental events to activate dopamine cells. Indeed, imaging studies have shown that in drug-addicted subjects, dopamine function is markedly disrupted (decreases in dopamine release and in dopamine D2 receptors in striatum) and this is associated with reduced activity of the orbitofrontal cortex (neuroanatomical region involved with salience attribution and motivation and implicated in compulsive behaviors) and the cingulate gyrus (neuroanatomical region involved with inhibitory control and attention and implicated in impulsivity). However, when addicted subjects are exposed to drug-related stimuli, these hypoactive regions become hyperactive in proportion to the expressed desire for the drug. We postulate that decreased dopamine function in addicted subjects results in decreased sensitivity to nondrug-related stimuli (including natural reinforcers) and disrupts frontal inhibition, both of which contribute to compulsive drug intake and impaired inhibitory control. These findings suggest new strategies for pharmacological and behavioral treatments, which focus on enhancing DA function and restoring brain circuits disrupted by chronic drug use to help motivate the addicted subject in activities that provide alternative sources of reinforcement, counteract conditioned responses, enhance their ability to control their drive to take drugs and interfere with their compulsive administration. JF - Molecular psychiatry AU - Volkow, N D AU - Fowler, J S AU - Wang, G-J AU - Swanson, J M AD - National Institute on Drug Abuse, Bethesda, MD 20892, USA. nvolkow@nida Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 557 EP - 569 VL - 9 IS - 6 SN - 1359-4184, 1359-4184 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Brain -- physiopathology KW - Neurons -- drug effects KW - Humans KW - Brain -- drug effects KW - Neurons -- physiology KW - Child KW - Attention Deficit Disorder with Hyperactivity -- drug therapy KW - Dopamine -- therapeutic use KW - Substance-Related Disorders -- drug therapy KW - Dopamine -- physiology KW - Dopamine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71954509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychiatry&rft.atitle=Dopamine+in+drug+abuse+and+addiction%3A+results+from+imaging+studies+and+treatment+implications.&rft.au=Volkow%2C+N+D%3BFowler%2C+J+S%3BWang%2C+G-J%3BSwanson%2C+J+M&rft.aulast=Volkow&rft.aufirst=N&rft.date=2004-06-01&rft.volume=9&rft.issue=6&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=13594184&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-31 N1 - Date created - 2004-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. AN - 71953774; 15153530 AB - Alzheimer's disease (AD) is characterized by overproduction of beta amyloid peptides in the brain with progressive loss of neuronal cells. The 42-aa form of the beta amyloid peptide (Abeta(42)) is implied as a major causative factor, because it is toxic to neurons and elicits inflammatory responses in the brain by activating microglial cells. Despite the overproduction of Abeta(42), AD brain tissue also generates protective factor(s) that may antagonize the neurodestructive effect of Abeta(42). Humanin is a gene cloned from an apparently normal region of an AD brain and encodes a 24-aa peptide. Both secreted and synthetic Humanin peptides protect neuronal cells from damage by Abeta(42), and the effect of Humanin may involve putative cellular receptor(s). To elucidate the molecular identity of such receptor(s), we examined the activity of synthetic Humanin on various cells and found that Humanin induced chemotaxis of mononuclear phagocytes by using a human G protein-coupled formylpeptide receptor-like-1 (FPRL1) and its murine counterpart FPR2. Coincidentally, FPRL1 and FPR2 are also functional receptors used by Abeta(42) to chemoattract and activate phagocytic cells. Humanin reduced the aggregation and fibrillary formation by suppressing the effect of Abeta(42) on mononuclear phagocytes. In neuroblast cells, Humanin and Abeta(42) both activated FPRL1; however, only Abeta(42) caused apoptotic death of the cells, and its cytopathic effect was blocked by Humanin. We conclude that Humanin shares human FPRL1 and mouse FPR2 with Abeta(42) and suggest that Humanin may exert its neuroprotective effects by competitively inhibiting the access of FPRL1 to Abeta(42). JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ying, Guoguang AU - Iribarren, Pablo AU - Zhou, Ye AU - Gong, Wanghua AU - Zhang, Ning AU - Yu, Zu-Xi AU - Le, Yingying AU - Cui, Youhong AU - Wang, Ji Ming AD - Laboratory of Molecular Immunoregulation and. Basic Research Program, SAIC-Frederick, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2004/06/01/ PY - 2004 DA - 2004 Jun 01 SP - 7078 EP - 7085 VL - 172 IS - 11 SN - 0022-1767, 0022-1767 KW - Amyloid beta-Peptides KW - 0 KW - FPR2 protein, human KW - Intracellular Signaling Peptides and Proteins KW - Neuroprotective Agents KW - Proteins KW - Receptors, Formyl Peptide KW - Receptors, Lipoxin KW - formyl peptide receptor 2, mouse KW - humanin KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Amyloid beta-Peptides -- metabolism KW - Neurons -- drug effects KW - Humans KW - Amyloid beta-Peptides -- toxicity KW - Mice KW - Alzheimer Disease -- prevention & control KW - Proteins -- pharmacology KW - Receptors, Formyl Peptide -- metabolism KW - Receptors, Lipoxin -- drug effects KW - Receptors, Formyl Peptide -- drug effects KW - Receptors, Lipoxin -- agonists KW - Receptors, Formyl Peptide -- agonists KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71953774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Humanin%2C+a+newly+identified+neuroprotective+factor%2C+uses+the+G+protein-coupled+formylpeptide+receptor-like-1+as+a+functional+receptor.&rft.au=Ying%2C+Guoguang%3BIribarren%2C+Pablo%3BZhou%2C+Ye%3BGong%2C+Wanghua%3BZhang%2C+Ning%3BYu%2C+Zu-Xi%3BLe%2C+Yingying%3BCui%2C+Youhong%3BWang%2C+Ji+Ming&rft.aulast=Ying&rft.aufirst=Guoguang&rft.date=2004-06-01&rft.volume=172&rft.issue=11&rft.spage=7078&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 - 2004-08-06 N1 - Date created - 2004-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The anxiogenic drug yohimbine reinstates methamphetamine seeking in a rat model of drug relapse. AN - 71951084; 15158427 AB - Brain noradrenaline is involved in footshock stress-induced reinstatement of drug seeking in a rat relapse model. We studied whether yohimbine, an alpha-2 adrenoceptor antagonist that increases noradrenaline release and induces anxiety-like responses in human and nonhuman subjects, would reinstate methamphetamine seeking in rats. In experiment 1, the effect of yohimbine (1.25-2.5 mg/kg) on reinstatement was compared with that of intermittent footshock (5 min;.2-.6 mA) in rats that were trained to lever press for intravenous methamphetamine (9-11 days) and subsequently underwent 7 days of extinction training. In experiment 2, the effect of yohimbine on reinstatement of drug seeking was determined during early (1 day) and late (21 or 51 days) withdrawal periods. On the test days, rats were first given 3-hour extinction sessions and were then tested for reinstatement induced by yohimbine. In experiment 1, both yohimbine and footshock stress reinstated methamphetamine seeking after extinction. In experiment 2, extinction responding was higher after 21 or 51 withdrawal days than after 1 withdrawal day. In contrast, no significant time-dependent changes in yohimbine-induced reinstatement were observed. Results indicate that yohimbine is a potent stimulus for reinstatement of methamphetamine seeking in a rat relapse model. JF - Biological psychiatry AU - Shepard, Jack D AU - Bossert, Jennifer M AU - Liu, Shirley Y AU - Shaham, Yavin AD - Cellular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224, USA. Y1 - 2004/06/01/ PY - 2004 DA - 2004 Jun 01 SP - 1082 EP - 1089 VL - 55 IS - 11 SN - 0006-3223, 0006-3223 KW - Adrenergic alpha-Antagonists KW - 0 KW - Yohimbine KW - 2Y49VWD90Q KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Rats KW - Models, Animal KW - Animals KW - Self Administration KW - Rats, Long-Evans KW - Dose-Response Relationship, Drug KW - Electroshock -- methods KW - Adrenergic alpha-Antagonists -- toxicity KW - Extinction, Psychological -- physiology KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Male KW - Behavior, Animal KW - Behavior, Addictive -- chemically induced KW - Yohimbine -- toxicity KW - Substance-Related Disorders -- etiology KW - Behavior, Addictive -- psychology KW - Behavior, Addictive -- metabolism KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71951084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+anxiogenic+drug+yohimbine+reinstates+methamphetamine+seeking+in+a+rat+model+of+drug+relapse.&rft.au=Shepard%2C+Jack+D%3BBossert%2C+Jennifer+M%3BLiu%2C+Shirley+Y%3BShaham%2C+Yavin&rft.aulast=Shepard&rft.aufirst=Jack&rft.date=2004-06-01&rft.volume=55&rft.issue=11&rft.spage=1082&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 - 2004-07-06 N1 - Date created - 2004-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Micromolar concentrations of sodium arsenite induce cyclooxygenase-2 expression and stimulate p42/44 mitogen-activated protein kinase phosphorylation in normal human epidermal keratinocytes. AN - 71947953; 15056798 AB - Based on evidence that arsenic modulates proinflammatory events that are involved in skin carcinogenecity, we hypothesized that in normal human epidermal keratinocytes (NHEK) arsenic increases expression of the procarcinogenic enzyme cyclooxygenase-2 (COX-2) and that this occurs via specific mitogen and stress signaling pathways. To test this hypothesis, NHEK were exposed to sodium arsenite, and COX-2 expression, prostaglandin E2 (PGE(2)) secretion, mitogen-activated protein kinase (MAPK) phosphorylation, and DNA synthesis were quantified. Inhibitors of p42/44 and p38 MAPKs were used to evaluate the contribution of mitogen and stress signaling to the modulation of COX-2. Our results demonstrate that arsenite (0.005-5 microM) elevates COX-2 expression, PGE(2) secretion (2.5-5 microM), and DNA synthesis (1-5 microM). Arsenite stimulated p42/44 but not p38 MAPK phosphorylation (2.5 microM), responses different than those produced by epidermal growth factor. Inhibition of mitogen-activated protein kinase kinase (MAPKK) and p38 MAPK using PD98059 (20 microM) and SB202190 (5 microM), respectively, attenuated the elevation of COX-2 protein induced by arsenite, whereas physiological concentrations of three COX-2 inhibitors (e.g., NS-398, piroxicam, and aspirin) reduced arsenite-stimulated DNA synthesis. These data indicate that arsenite elevates COX-2 in NHEK at the transcriptional and translational levels as well as increases PGE(2) secretion. Compounds that inhibit COX-2 expression and activity may be useful in the scientific study, prevention, and treatment of arsenic skin carcinogenesis and deserve further investigation. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Trouba, K J AU - Germolec, D R AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 248 EP - 257 VL - 79 IS - 2 SN - 1096-6080, 1096-6080 KW - Arsenites KW - 0 KW - Enzyme Inhibitors KW - Membrane Proteins KW - RNA, Messenger KW - Sodium Compounds KW - sodium arsenite KW - 48OVY2OC72 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Blotting, Western KW - Gene Expression Regulation, Enzymologic KW - Blotting, Northern KW - Phosphorylation KW - Cells, Cultured KW - Humans KW - Dinoprostone -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Mitogen-Activated Protein Kinase 3 -- metabolism KW - Keratinocytes -- enzymology KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Keratinocytes -- drug effects KW - Mitogen-Activated Protein Kinase 3 -- antagonists & inhibitors KW - Arsenites -- toxicity KW - Sodium Compounds -- toxicity KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Keratinocytes -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Mitogen-Activated Protein Kinase 1 -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71947953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Micromolar+concentrations+of+sodium+arsenite+induce+cyclooxygenase-2+expression+and+stimulate+p42%2F44+mitogen-activated+protein+kinase+phosphorylation+in+normal+human+epidermal+keratinocytes.&rft.au=Trouba%2C+K+J%3BGermolec%2C+D+R&rft.aulast=Trouba&rft.aufirst=K&rft.date=2004-06-01&rft.volume=79&rft.issue=2&rft.spage=248&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-05 N1 - Date created - 2004-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Familial eosinophilia: a benign disorder? AN - 71939318; 14988154 AB - Familial eosinophilia (FE) is an autosomal dominant disorder characterized by marked eosinophilia and progression to end organ damage in some, but not all, affected family members. To better define the pathogenesis of FE, 13 affected and 11 unaffected family members (NLs) underwent a detailed clinical evaluation at the National Institutes of Health (NIH). No clinical abnormalities were more frequent in the family members with FE compared with the NLs. There was, however, a decreased prevalence of asthma in family members with FE compared with unaffected family members. Eosinophil morphology as assessed by either light or transmission electron microscopy was normal in family members with and without FE. Although levels of eosinophil-derived neurotoxin (EDN) and major basic protein (MBP) were elevated in patients with FE compared with NL, levels of both granule proteins were lower than in nonfamilial hypereosinophilic syndrome (HES). Similarly, increased surface expression of the activation markers CD69, CD25, and HLA-DR was detected by flow cytometry on eosinophils from patients with FE compared with NL, albeit less than that seen in HES. These data suggest that, despite prolonged marked eosinophilia, FE can be distinguished from HES by a more benign clinical course that may be related to a relative lack of eosinophil activation. JF - Blood AU - Klion, Amy D AU - Law, Melissa A AU - Riemenschneider, William AU - McMaster, Mary Lou AU - Brown, Margaret R AU - Horne, McDonald AU - Karp, Barbara AU - Robinson, Michael AU - Sachdev, Vandana AU - Tucker, Eben AU - Turner, Maria AU - Nutman, Thomas B AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. aklion@niaid.nih.gov Y1 - 2004/06/01/ PY - 2004 DA - 2004 Jun 01 SP - 4050 EP - 4055 VL - 103 IS - 11 SN - 0006-4971, 0006-4971 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, T-Lymphocyte KW - CD69 antigen KW - HLA-DR Antigens KW - Lectins, C-Type KW - Myelin Basic Protein KW - Peptide Fragments KW - Receptors, IgE KW - Receptors, Interleukin-2 KW - myelin basic protein 1-20 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Abridged Index Medicus KW - Index Medicus KW - Antigens, CD -- analysis KW - HLA-DR Antigens -- analysis KW - Receptors, Interleukin-2 -- analysis KW - Receptors, IgE -- analysis KW - Humans KW - Aged KW - Child KW - Cell Survival KW - Infant KW - Eosinophils -- chemistry KW - Adult KW - Microscopy, Electron KW - Adolescent KW - Family Health KW - Male KW - Eosinophils -- ultrastructure KW - Severity of Illness Index KW - Cytoplasmic Granules -- ultrastructure KW - Ribonucleases -- blood KW - Myelin Basic Protein -- blood KW - Peptide Fragments -- blood KW - Child, Preschool KW - Antigens, Differentiation, T-Lymphocyte -- analysis KW - Middle Aged KW - Female KW - Eosinophilia -- physiopathology KW - Eosinophilia -- pathology KW - Eosinophilia -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71939318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Familial+eosinophilia%3A+a+benign+disorder%3F&rft.au=Klion%2C+Amy+D%3BLaw%2C+Melissa+A%3BRiemenschneider%2C+William%3BMcMaster%2C+Mary+Lou%3BBrown%2C+Margaret+R%3BHorne%2C+McDonald%3BKarp%2C+Barbara%3BRobinson%2C+Michael%3BSachdev%2C+Vandana%3BTucker%2C+Eben%3BTurner%2C+Maria%3BNutman%2C+Thomas+B&rft.aulast=Klion&rft.aufirst=Amy&rft.date=2004-06-01&rft.volume=103&rft.issue=11&rft.spage=4050&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-08 N1 - Date created - 2004-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural effects of radiation damage and its potential for phasing. AN - 71936402; 15159568 AB - A detailed analysis of radiation-damage-induced structural and intensity changes is presented on the model protein thaumatin. Changes in reflection intensities induced by irradiation display a parabolic character. The most pronounced structural changes observed were disulfide-bond breakage and associated main-chain and side-chain movements as well as decarboxylation of aspartate and glutamate residues. The structural changes induced on the sulfur atoms were successfully used to obtain high-quality phase estimates via an RIP procedure. Results obtained with ACORN suggest that the contribution originating from the partial structure may play an important role in phasing even at less than atomic resolution. Copyright 2004 International Union of Crystallography JF - Acta crystallographica. Section D, Biological crystallography AU - Banumathi, Sankaran AU - Zwart, Petrus H AU - Ramagopal, Udupi A AU - Dauter, Miroslawa AU - Dauter, Zbigniew AD - Synchotron Radiation Research Section, MCL, National Cancer Institute, Brookhaven National Laboratory, Upton, NY 11973, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1085 EP - 1093 VL - 60 SN - 0907-4449, 0907-4449 KW - Plant Proteins KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - Glutamic Acid KW - 3KX376GY7L KW - thaumatin protein, plant KW - 53850-34-3 KW - Sulfur KW - 70FD1KFU70 KW - Index Medicus KW - X-Ray Diffraction KW - Models, Molecular KW - Glutamic Acid -- chemistry KW - Models, Statistical KW - Sulfur -- chemistry KW - Aspartic Acid -- chemistry KW - Protein Conformation KW - Models, Theoretical KW - Plant Proteins -- chemistry KW - Radiation Effects KW - Crystallography, X-Ray -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71936402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+crystallographica.+Section+D%2C+Biological+crystallography&rft.atitle=Structural+effects+of+radiation+damage+and+its+potential+for+phasing.&rft.au=Banumathi%2C+Sankaran%3BZwart%2C+Petrus+H%3BRamagopal%2C+Udupi+A%3BDauter%2C+Miroslawa%3BDauter%2C+Zbigniew&rft.aulast=Banumathi&rft.aufirst=Sankaran&rft.date=2004-06-01&rft.volume=60&rft.issue=&rft.spage=1085&rft.isbn=&rft.btitle=&rft.title=Acta+crystallographica.+Section+D%2C+Biological+crystallography&rft.issn=09074449&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-31 N1 - Date created - 2004-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Split calvarial bone graft for chemical burn-associated nasal augmentation. AN - 71931109; 15145198 AB - The nose is the central part of the face, and constitutes the most prominent projection in facial geometry. This report presents five cases that sustained a chemical burn injury with associated facial mutilation resulting from contact with strong acids. The chemical burn affected the nasal architecture after inflicting a burn injury to the face. Applying bone deriving from a split skull procedure for the nasal projection restoration and the augmentation of the dorsal nose is a feasible undertaking, and the overall result appears satisfactory. A retrospective survey of cases admitted to our clinic from January 1999 to December 2001, inclusively was undertaken and is described below. Split calvarial bone graft procedure for the nasal tip projection reconstruction was performed for five patients, all of whom had sustained chemical burns following assault by strong acid. The disfiguration of the nasal anatomical structure was due to healing from deep burn wounds. The tip became blunt and less protruberant following the arising of cicatricial tightness of the surrounding tissue. Strength and resistance to scar contraction are the first considerations for such implantation when attempting to correct the nasal tip projection. The five female patients sustained a severe chemical burn which involved a surface area ranging from 25 to 60% of total body surface area. The facial mutilation was noted simultaneously with the determination of the extent of the burning injury. A severe burn scar is the typical sequel following a deep chemical burn. Nasal tip projection was restored and a nasal dorsum augmentation procedure with a split calvarial bone graft under an "open" method was used. This particular surgical procedure was able to be used in order to improve the nasal tip projection and resist surrounding scar contracture. The three-dimensional surface structure of the face became more prominent subsequent to the administration of this procedure. JF - Burns : journal of the International Society for Burn Injuries AU - Chou, Trong-Duo AU - Lee, Wen-Ting AU - Chen, Shao-Liang AU - Lee, Chiu-Heng AU - Chen, Shyi-Gen AU - Chen, Tim-Mo AU - Wang, Hsian-Jenn AD - Division of Plastic Surgery, Tri-Service General Hospital 325, Section 2, Cheng-Kung Road, Nei-Hu, Taipei 100, Taiwan, ROC. choupsdr@yahoo.com.tw Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 380 EP - 385 VL - 30 IS - 4 SN - 0305-4179, 0305-4179 KW - Index Medicus KW - Humans KW - Adult KW - Retrospective Studies KW - Cicatrix -- etiology KW - Cicatrix -- surgery KW - Middle Aged KW - Female KW - Bone Transplantation -- methods KW - Rhinoplasty -- methods KW - Nose Deformities, Acquired -- surgery KW - Burns, Chemical -- complications KW - Nose Deformities, Acquired -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71931109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Burns+%3A+journal+of+the+International+Society+for+Burn+Injuries&rft.atitle=Split+calvarial+bone+graft+for+chemical+burn-associated+nasal+augmentation.&rft.au=Chou%2C+Trong-Duo%3BLee%2C+Wen-Ting%3BChen%2C+Shao-Liang%3BLee%2C+Chiu-Heng%3BChen%2C+Shyi-Gen%3BChen%2C+Tim-Mo%3BWang%2C+Hsian-Jenn&rft.aulast=Chou&rft.aufirst=Trong-Duo&rft.date=2004-06-01&rft.volume=30&rft.issue=4&rft.spage=380&rft.isbn=&rft.btitle=&rft.title=Burns+%3A+journal+of+the+International+Society+for+Burn+Injuries&rft.issn=03054179&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-11 N1 - Date created - 2004-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pediatric phase I trial and pharmacokinetic study of the platelet-derived growth factor (PDGF) receptor pathway inhibitor SU101. AN - 71917338; 14999430 AB - To determine the maximum tolerated dose and the toxicity profile of the PDGF receptor pathway inhibitor SU101 in pediatric patients with refractory solid tumors, and to define the plasma pharmacokinetics of SU101 and its active metabolite SU0020 in children. Patients between 3 and 21 years of age with CNS malignancy, neuroblastoma, or sarcoma refractory to standard therapy were eligible. The starting dose of SU101 was 230 mg/m(2) per day administered as a 96-h continuous infusion every 21 days. Blood for pharmacokinetic analysis was obtained during the first cycle. Entered into the trial were 27 patients, and 24 were fully evaluable for toxicity. Dose-limiting central nervous system toxicity was observed in two patients at the 440 mg/m(2) per day dose level. Non-dose-limiting toxicities included nausea, vomiting, headache, fatigue, abdominal discomfort, diarrhea, pruritus, anorexia, constipation, and paresthesias. There were no complete or partial responses. One patient with rapidly progressive desmoplastic small round-cell tumor experienced symptomatic improvement and prolonged stable disease. Steady-state concentrations of SU101 were rapidly achieved and proportional to dose. The concentration of SU0020 was 100- to 1000-fold greater than that of SU101. The median clearance of SU0020 was 0.19 l/day per m(2) and its terminal elimination half-life was 14 days. SU101 administered on this schedule was generally well tolerated. The maximum tolerated dose of SU101 is 390 mg/m(2) per day for 4 days repeated every 3 weeks. The neurotoxicity observed at the 440 mg/m(2) per day dose level suggests that patients receiving repetitive cycles must be monitored closely, as SU0020 may accumulate over time. JF - Cancer chemotherapy and pharmacology AU - Adamson, P C AU - Blaney, S M AU - Widemann, B C AU - Kitchen, B AU - Murphy, R F AU - Hannah, A L AU - Cropp, G F AU - Patel, M AU - Gillespie, A F AU - Whitcomb, P G AU - Balis, F M AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, USA. adamsonp@mail.med.upenn.edu Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 482 EP - 488 VL - 53 IS - 6 SN - 0344-5704, 0344-5704 KW - Aniline Compounds KW - 0 KW - Antineoplastic Agents KW - Isoxazoles KW - Nitriles KW - SU 0020 KW - leflunomide KW - G162GK9U4W KW - Index Medicus KW - Magnetic Resonance Imaging KW - Dose-Response Relationship, Drug KW - Humans KW - Tomography, X-Ray Computed KW - Child KW - Aniline Compounds -- blood KW - Child, Preschool KW - Nitriles -- blood KW - Half-Life KW - Adult KW - Treatment Outcome KW - Adolescent KW - Female KW - Male KW - Central Nervous System Neoplasms -- metabolism KW - Antineoplastic Agents -- pharmacokinetics KW - Central Nervous System Neoplasms -- drug therapy KW - Isoxazoles -- pharmacokinetics KW - Antineoplastic Agents -- therapeutic use KW - Isoxazoles -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71917338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pediatric+phase+I+trial+and+pharmacokinetic+study+of+the+platelet-derived+growth+factor+%28PDGF%29+receptor+pathway+inhibitor+SU101.&rft.au=Adamson%2C+P+C%3BBlaney%2C+S+M%3BWidemann%2C+B+C%3BKitchen%2C+B%3BMurphy%2C+R+F%3BHannah%2C+A+L%3BCropp%2C+G+F%3BPatel%2C+M%3BGillespie%2C+A+F%3BWhitcomb%2C+P+G%3BBalis%2C+F+M&rft.aulast=Adamson&rft.aufirst=P&rft.date=2004-06-01&rft.volume=53&rft.issue=6&rft.spage=482&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 - 2004-06-28 N1 - Date created - 2004-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - History of marijuana use and tobacco smoking topography in tobacco-dependent adolescents. AN - 71908346; 15135551 AB - Adolescent tobacco smokers have higher rates of marijuana (MJ) use than nonsmokers. Because MJ smoking typically involves deeper inhalation and longer breathholding than tobacco smoking, we hypothesized greater puff volume, longer puff duration and puff interval, and higher puff velocity during tobacco smoking among (1) MJ-using teens; (2) teens whose onset of MJ smoking occurred before tobacco (MBT). One hundred and three tobacco-dependent adolescents presented for smoking cessation treatment (66.0% female, 71.0% European American, mean age 15.3+/-1.25 years) smoked one cigarette of their own brand in the laboratory prior to study entry. Topography and associated physiological measures among current recreational (/=5 days in a 14-day period) MJ users (n=22) and current non-MJ-smoking teens (n=56) were compared. There were no differences in tobacco smoking topography or physiological measures by recent MJ-smoking history or by order of substance initiation. Significantly more African American than European American adolescent smokers reported MJ use before tobacco. Our findings in adolescent smokers are consistent with results from adult studies in which history of MJ smoking was not associated with changes in tobacco smoking topography. JF - Addictive behaviors AU - Aung, A Thiri AU - Pickworth, Wallace B AU - Moolchan, Eric T AD - Clinical Pharmacology and Treatment Research Branch, National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 699 EP - 706 VL - 29 IS - 4 SN - 0306-4603, 0306-4603 KW - Index Medicus KW - Analysis of Variance KW - Humans KW - African Americans KW - Exhalation -- physiology KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Inhalation -- physiology KW - Smoking -- physiopathology KW - Marijuana Abuse -- ethnology KW - Smoking -- ethnology KW - Respiratory Mechanics -- physiology KW - Marijuana Abuse -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71908346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=History+of+marijuana+use+and+tobacco+smoking+topography+in+tobacco-dependent+adolescents.&rft.au=Aung%2C+A+Thiri%3BPickworth%2C+Wallace+B%3BMoolchan%2C+Eric+T&rft.aulast=Aung&rft.aufirst=A&rft.date=2004-06-01&rft.volume=29&rft.issue=4&rft.spage=699&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-30 N1 - Date created - 2004-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. AN - 71869541; 15111016 AB - Although the mechanism of action of topiramate is not fully understood, its anticonvulsant properties may result, at least in part, from an interaction with AMPA/kainate receptors. We have recently shown that topiramate selectively inhibits postsynaptic responses mediated by GluR5 kainate receptors. To determine if this action of topiramate is relevant to the anticonvulsant effects of the drug in vivo, we determined the protective activity of topiramate against seizures induced by intravenous infusion of various ionotropic glutamate receptor agonists in mice. Topiramate (25-100 mg/kg, i.p.) produced a dose-dependent elevation in the threshold for clonic seizures induced by infusion of ATPA, a selective agonist of GluR5 kainate receptors. Topiramate was less effective in protecting against clonic seizures induced by kainate, a mixed agonist of AMPA and kainate receptors. Topiramate did not affect clonic seizures induced by AMPA or NMDA. In contrast, the thresholds for tonic seizures induced by higher doses of these various glutamate receptor agonists were all elevated by topiramate. Unlike topiramate, carbamazepine elevated the threshold for AMPA- but not ATPA-induced clonic seizures. Our results are consistent with the possibility that the effects of topiramate on clonic seizure activity are due to functional blockade of GluR5 kainate receptors. Protection from tonic seizures may be mediated by other actions of the drug. Together with our in vitro cellular electrophysiological results, the present observations strongly support a unique mechanism of action of topiramate, which involves GluR5 kainate receptors. JF - Neuropharmacology AU - Kaminski, Rafal M AU - Banerjee, Madhumita AU - Rogawski, Michael A AD - Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1097 EP - 1104 VL - 46 IS - 8 SN - 0028-3908, 0028-3908 KW - Excitatory Amino Acid Agonists KW - 0 KW - Gluk1 kainate receptor KW - Receptors, Kainic Acid KW - topiramate KW - 0H73WJJ391 KW - Fructose KW - 30237-26-4 KW - N-Methylaspartate KW - 6384-92-5 KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Kainic Acid -- pharmacology KW - N-Methylaspartate -- pharmacology KW - Dose-Response Relationship, Drug KW - In Vitro Techniques KW - Mice KW - Male KW - Seizures -- chemically induced KW - Receptors, Kainic Acid -- agonists KW - Fructose -- analogs & derivatives KW - Excitatory Amino Acid Agonists -- pharmacology KW - Fructose -- therapeutic use KW - Seizures -- prevention & control KW - Receptors, Kainic Acid -- physiology KW - Excitatory Amino Acid Agonists -- toxicity KW - Fructose -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71869541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topiramate+selectively+protects+against+seizures+induced+by+ATPA%2C+a+GluR5+kainate+receptor+agonist.&rft.au=Kaminski%2C+Rafal+M%3BBanerjee%2C+Madhumita%3BRogawski%2C+Michael+A&rft.aulast=Kaminski&rft.aufirst=Rafal&rft.date=2004-06-01&rft.volume=46&rft.issue=8&rft.spage=1097&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-13 N1 - Date created - 2004-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Emission of heavy metals from animal carcass incinerators in Taiwan. AN - 71834084; 15081760 AB - The metal emissions from three incinerators burning different feedstock in Taiwan were characterized in this study. It was found that the Incinerators A and B, treating pig carcasses and animal (including pigs) carcasses, respectively, had much higher metal concentrations in stack flue gases than Incinerator C that combusted medical wastes. However, Incinerator A obtained relative lower metal contents in fly ash and bottom ash than the other two incinerators, mainly because the former used a much lower feedstock rate (although burning at a lower temperature) than the latter. For all the incinerators, (1) Fe, Ni, Pb, and Zn were dominant in both the fly ash and bottom ash while most of the Cd and Pb (more volatile) were present in the fly ash; (2) Fe emission factor was the highest and Zn/Pb/Ni/Cr emission factors were greater than those of Mn/Cd/Cu; (3) the Cu emission factors in bottom ash were relatively higher in comparison with those in fly ash; and (4) indicatory metals were the same (Fe, Zn, Pb, and Cu). The metal emission factors obtained from the livestock incinerators were much higher than those reported from MSW incinerators. Likewise, crematories that burn human cadavers must create similar pollution issues since metal supplements are part of human's normal diets. This causes an environmental concern and this work has important ramifications both in technical and regulatory decisions. Copyright 2004 Elsevier Ltd. JF - Chemosphere AU - Chen, Shui-Jen AU - Hung, Ming-Cheng AU - Huang, Kuo-Lin AU - Hwang, Wen-Ing AD - Department of Environmental Engineering and Science, National Pingtung University of Science and Technology, Nei Pu, Pingtung 91201, Taiwan. chensj@mail.npust.edu.tw Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1197 EP - 1205 VL - 55 IS - 9 SN - 0045-6535, 0045-6535 KW - Air Pollutants KW - 0 KW - Industrial Waste KW - Medical Waste KW - Metals, Heavy KW - Index Medicus KW - Animals KW - Taiwan KW - Sus scrofa KW - Medical Waste -- analysis KW - Temperature KW - Industrial Waste -- analysis KW - Incineration KW - Abattoirs KW - Air Pollutants -- analysis KW - Metals, Heavy -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71834084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemosphere&rft.atitle=Emission+of+heavy+metals+from+animal+carcass+incinerators+in+Taiwan.&rft.au=Chen%2C+Shui-Jen%3BHung%2C+Ming-Cheng%3BHuang%2C+Kuo-Lin%3BHwang%2C+Wen-Ing&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=2004-06-01&rft.volume=55&rft.issue=9&rft.spage=1197&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-29 N1 - Date created - 2004-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-6-deficient mice are susceptible to ethanol-induced hepatic steatosis: IL-6 protects against ethanol-induced oxidative stress and mitochondrial permeability transition in the liver. AN - 67299287; 16219169 AB - Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however, the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro, IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes via induction of metallothionein protein expression, which may account for the protective role of IL-6 in alcoholic liver disease. JF - Cellular & molecular immunology AU - El-Assal, Osama AU - Hong, Feng AU - Kim, Won-Ho AU - Radaeva, Svetlana AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 205 EP - 211 VL - 1 IS - 3 SN - 1672-7681, 1672-7681 KW - Interleukin-6 KW - 0 KW - Solvents KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Rats KW - Animals KW - Liver -- pathology KW - Humans KW - Liver -- metabolism KW - Mice KW - Hepatocytes -- pathology KW - Mice, Knockout KW - Hepatocytes -- metabolism KW - Hepatitis, Alcoholic -- drug therapy KW - Solvents -- toxicity KW - Hepatitis, Animal -- chemically induced KW - Mitochondria, Liver -- metabolism KW - Mitochondria, Liver -- pathology KW - Interleukin-6 -- deficiency KW - Hepatitis, Alcoholic -- pathology KW - Hepatitis, Animal -- drug therapy KW - Interleukin-6 -- administration & dosage KW - Hepatitis, Animal -- metabolism KW - Interleukin-6 -- genetics KW - Oxidative Stress -- drug effects KW - Ethanol -- toxicity KW - Hepatitis, Alcoholic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67299287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+molecular+immunology&rft.atitle=IL-6-deficient+mice+are+susceptible+to+ethanol-induced+hepatic+steatosis%3A+IL-6+protects+against+ethanol-induced+oxidative+stress+and+mitochondrial+permeability+transition+in+the+liver.&rft.au=El-Assal%2C+Osama%3BHong%2C+Feng%3BKim%2C+Won-Ho%3BRadaeva%2C+Svetlana%3BGao%2C+Bin&rft.aulast=El-Assal&rft.aufirst=Osama&rft.date=2004-06-01&rft.volume=1&rft.issue=3&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Cellular+%26+molecular+immunology&rft.issn=16727681&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-21 N1 - Date created - 2005-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Systemic and haemodynamic toxicity after isolated limb perfusion (ILP) with TNF-alpha. AN - 66858876; 15354406 AB - The aim of this study was to evaluate the systemic and haemodynamic postoperative effects of ILP with medium-low dose of TNF alpha in patients diagnosed with primary or recurrent limb melanoma or sarcoma, and to compare the resulting toxicity with Systemic Inflammatory Response Syndrome (SIRS). A prospective study on 17 consecutive patients with primary or recurrent limb tumor (melanoma or sarcoma) subjected to ILP with escalating doses of TNF alpha (0.5-2.0mg) was carried out. Seventeen patients with primary or recurrent limb melanoma or sarcoma were subjected to ILP with escalating doses of TNF alpha. ILP was carried out with the standard techniques, blood being warmed at 42 degrees C for an hour. Serial serum TNF alpha determinations were performed before, during and after limb perfusion in nine patients. Systemic and pulmonary haemodynamics, by a radial and pulmonary artery catheter inserted before the induction of anesthesia, were monitored at 5 different times: before the induction of anesthesia (T0), and 6, 12, 24 and 48 hours after treatment (T1-4). Complete isolation of the limb was not always achieved, therefore leakage of TNF alpha occurred frequently during the perfusion in all patients with maximum systemic TNF alpha concentrations ranging from 431 to 111000 pg/ml. After perfusion only two patients showed detectable TNF alpha levels in peripheral blood which returned to baseline values within nine hours. These two patients had serious systemic toxicity: shock and respiratory failure secondary to pulmonary edema. Acute pulmonary edema was also observed in another patient. All three cases required supportive therapy provided by means of mechanical ventilation. In the remaining 14 patients a sepsis-like syndrome was observed. The most significant haemodynamic changes were due to the CO, which rose by 35%, and the SVR, which remained consistently low throughout. A reduction in Hb was observed in all patients (with an average decrease of 4 g/dl), while DO2 and VO2 levels rose, though not to statistically significant levels. Hypoxia occurred in all 14 patients. In three of the remaining 14 cases bilateral pulmonary leaks were noted, however the use of mechanical ventilation was not required. No perioperative death occurred and the aforementioned side effects were all reversible resulting in a patient's mean postoperative ICU permanence of 4 days (range 3 to 7 days). In conclusion, ILP with TNF alpha induces cardiovascular, respiratory and hematological toxicity with haemodynamic parameters being similar to those noted in SIRS probably due to leakage of TNF alpha in the systemic circulation during the perfusion. Nevertheless, this systemic toxicity was short-lived resulting in an acute reaction following a single application. JF - Journal of experimental & clinical cancer research : CR AU - Laurenzi, L AU - Natoli, S AU - Di Filippo, F AU - Calamaro, A AU - Centulio, F AU - Anzà, M AU - Cavaliere, F AU - Marcelli, M E AU - Garinei, R AU - Arcuri, E AD - Intensive Care Unit, Regina Elena National Cancer Institute, Rome, Italy. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 225 EP - 231 VL - 23 IS - 2 SN - 0392-9078, 0392-9078 KW - Tumor Necrosis Factor-alpha KW - 0 KW - Index Medicus KW - Skin Neoplasms -- drug therapy KW - Extremities KW - Skin Neoplasms -- surgery KW - Prospective Studies KW - Postoperative Care KW - Neoplasm Recurrence, Local -- drug therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Neoplasm Recurrence, Local -- surgery KW - Male KW - Female KW - Hemodynamics -- drug effects KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Melanoma -- drug therapy KW - Respiratory Tract Diseases -- chemically induced KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Sarcoma -- surgery KW - Cardiovascular Diseases -- chemically induced KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Sarcoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66858876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+clinical+cancer+research+%3A+CR&rft.atitle=Systemic+and+haemodynamic+toxicity+after+isolated+limb+perfusion+%28ILP%29+with+TNF-alpha.&rft.au=Laurenzi%2C+L%3BNatoli%2C+S%3BDi+Filippo%2C+F%3BCalamaro%2C+A%3BCentulio%2C+F%3BAnz%C3%A0%2C+M%3BCavaliere%2C+F%3BMarcelli%2C+M+E%3BGarinei%2C+R%3BArcuri%2C+E&rft.aulast=Laurenzi&rft.aufirst=L&rft.date=2004-06-01&rft.volume=23&rft.issue=2&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-18 N1 - Date created - 2004-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative evaluation of cancer chemopreventive efficacy of alpha-tocopherol and quercetin in a murine model. AN - 66858160; 15354409 AB - Chemopreventive efficacy and the mode of action of alpha-tocopherol and quercetin, both known to possess anti-oxidant properties, were evaluated during carcinogenesis in uterine cervix of mice by chronic exposure to methylcholanthrene. Oral administration of alpha-tocopherol and quercetin could reduce the genotoxic effect of the carcinogen as revealed by the micronucleus frequency in vaginal epithelial cells. Both could restrict the progression of dysplastic changes in cervix uteri leading to carcinoma in-situ but the influence of the quercetin was more pronounced. A decrease in lipid peroxides following ingestion of these agents suggests that their chemopreventive action is due to their protective role on DNA damage by free radicals. Increased glutathione and glutathione-s-transferase also indicate their involvement in detoxification. While alpha-tocopherol activated the PBL response towards mitogenic stimulation, quercetin had no such effect. JF - Journal of experimental & clinical cancer research : CR AU - De, S AU - Chakraborty, R N AU - Ghosh, S AU - Sengupta, A AU - Das, S AD - Dept of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 251 EP - 258 VL - 23 IS - 2 SN - 0392-9078, 0392-9078 KW - Antioxidants KW - 0 KW - Free Radicals KW - Methylcholanthrene KW - 56-49-5 KW - Quercetin KW - 9IKM0I5T1E KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Glutathione KW - GAN16C9B8O KW - alpha-Tocopherol KW - H4N855PNZ1 KW - Index Medicus KW - Animals KW - Methylcholanthrene -- toxicity KW - DNA Damage KW - Glutathione -- metabolism KW - Glutathione Transferase -- metabolism KW - Lipid Peroxidation -- drug effects KW - Mitosis -- drug effects KW - Mice KW - Chemoprevention KW - Female KW - Micronuclei, Chromosome-Defective KW - Models, Animal KW - Uterine Cervical Neoplasms -- prevention & control KW - Carcinoma in Situ -- chemically induced KW - Quercetin -- therapeutic use KW - Antioxidants -- therapeutic use KW - Uterine Cervical Neoplasms -- diagnosis KW - Carcinoma in Situ -- diagnosis KW - Uterine Cervical Neoplasms -- chemically induced KW - Carcinoma in Situ -- prevention & control KW - alpha-Tocopherol -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66858160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+clinical+cancer+research+%3A+CR&rft.atitle=Comparative+evaluation+of+cancer+chemopreventive+efficacy+of+alpha-tocopherol+and+quercetin+in+a+murine+model.&rft.au=De%2C+S%3BChakraborty%2C+R+N%3BGhosh%2C+S%3BSengupta%2C+A%3BDas%2C+S&rft.aulast=De&rft.aufirst=S&rft.date=2004-06-01&rft.volume=23&rft.issue=2&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-18 N1 - Date created - 2004-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Small molecule-mediated anti-cancer therapy via hypoxia-inducible factor-1 blockade. AN - 66808106; 15197355 AB - Despite reservations regarding potential toxicities, small molecule-mediated blockade of the hypoxia-inducible factor-1 transcription factor has emerged as a viable anti-cancer strategy in vivo. Recent experiments by Welsh et al. revealed unprecedented anti-tumor responses of various aggressive solid tumors to the HIF-1-inhibitory small molecule drug PX-478. Compared with other anti-cancer drugs, PX-478 had markedly improved regression, growth delay and log10 cell kill profiles, particularly against large tumors that are normally refractory to small molecule drug therapy. Importantly, pharmacokinetic and toxicity profiles were within acceptable limits, providing rationale for the clinical development of HIF-1 inhibitors in general. Though the mechanism of action for PX-478 is not completely understood, inhibition of glycolysis rather than angiogenesis appeared to be the primary mode of anti-cancer activity. JF - Cancer biology & therapy AU - Macpherson, Gordon R AU - Figg, William D AD - Molecular Pharmacology Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 503 EP - 504 VL - 3 IS - 6 SN - 1538-4047, 1538-4047 KW - 2-amino-3-(4'-N,N-bis(2-chloroethyl)amino)phenylpropionic acid N-oxide KW - 0 KW - Antineoplastic Agents KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Mustard Compounds KW - Phenylpropionates KW - Transcription Factors KW - Index Medicus KW - Animals KW - Humans KW - Neoplasms -- drug therapy KW - Transcription Factors -- antagonists & inhibitors KW - Mustard Compounds -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Phenylpropionates -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66808106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+%26+therapy&rft.atitle=Small+molecule-mediated+anti-cancer+therapy+via+hypoxia-inducible+factor-1+blockade.&rft.au=Macpherson%2C+Gordon+R%3BFigg%2C+William+D&rft.aulast=Macpherson&rft.aufirst=Gordon&rft.date=2004-06-01&rft.volume=3&rft.issue=6&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Cancer+biology+%26+therapy&rft.issn=15384047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-19 N1 - Date created - 2004-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk standards for pediatric research: rethinking the Grimes ruling. AN - 66747629; 15281189 AB - In Grimes v. Kennedy Krieger Institute (KKI), the Maryland Court of Appeals, while noting that U.S. federal regulations include risk standards for pediatric research, endorses its own risk standards. The Grimes case has implications for the debate over whether the minimal risk standard should be interpreted based on the risks in the daily lives of most children (the objective interpretation) or the risks in the daily lives of the children who will be enrolled in a given study (the subjective interpretation). The court's use of the objective interpretation to block studies like the KKI study protects individual children who are worse off than the average child. Unfortunately, this approach also may block research intended to improve the lives of these same individuals. A similar dilemma arises in the context of multinational research, suggesting that a "modified objective standard," proposed to address this dilemma in the multinational setting, may offer a framework for addressing the dilemma in the context of pediatric research as well. JF - Kennedy Institute of Ethics journal AU - Wendler, David AD - Unit on Vulnerable Populations, Department of Clinical Bioethics, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 187 EP - 198 VL - 14 IS - 2 SN - 1054-6863, 1054-6863 KW - Lead KW - 2P299V784P KW - Bioethics KW - Biomedical and Behavioral Research KW - Analytical Approach KW - Legal Approach KW - United States KW - Lead Poisoning -- prevention & control KW - Government Regulation KW - Judicial Role KW - Humans KW - Clinical Trials as Topic -- ethics KW - Federal Government KW - Research Design KW - Public Housing KW - Baltimore KW - Lead -- adverse effects KW - Poverty KW - Developing Countries KW - Maryland KW - Ethics, Research KW - Lead -- analysis KW - Nontherapeutic Human Experimentation -- legislation & jurisprudence KW - Child KW - Risk Assessment -- standards KW - Nontherapeutic Human Experimentation -- ethics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66747629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kennedy+Institute+of+Ethics+journal&rft.atitle=Risk+standards+for+pediatric+research%3A+rethinking+the+Grimes+ruling.&rft.au=Wendler%2C+David&rft.aulast=Wendler&rft.aufirst=David&rft.date=2004-06-01&rft.volume=14&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Kennedy+Institute+of+Ethics+journal&rft.issn=10546863&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-11 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased serum inhibin B/FSH ratio as a marker of Sertoli cell function in male survivors after chemotherapy in childhood and adolescence. AN - 66732624; 15270406 AB - Inhibin B produced by Sertoli cells may be an important marker of seminiferous tubule function in patients treated with chemotherapy (CT). The aim of this study was to evaluate the inhibin B/FSH ratio to detect male gonadal dysfunction in cancer survivors treated in childhood and adolescence. Twenty-one male patients (group A) treated with 6-10 courses of CT for Hodgkin's disease during childhood and adolescence were examined 3-11 years after the conclusion of treatment. Twenty healthy young men (18-23 years old) were used as controls (group B). Serum samples for the determination of inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), sex hormone-binding globulin (SHBG) and semen for analysis were collected. The median testicular volume of patients of group A was lower than those of group B (p = 0.001) and a positive correlation was found between testicular size and sperm count (r = -0.5, p = 0.01). Semen analysis revealed azoospermia in 11 patients, severe oligospermia in four and normal sperm count in three. No significant difference was found in the median of T, LH, SHBG, inhibin B concentrations and T/LH ratio between the groups. Serum inhibin B was correlated with the serum FSH levels (r = -0.5, p = 0.02). Median FSH was significantly higher (p = 0.0001), and median inhibin B/FSH ratio was significantly lower in group A than in controls (p = 0.0002), but the inhibin B/FSH ratio was higher in the patients with normal sperm count than in those with oligospermia (p = 0.00004). These results show that the cytotoxic effects of CT cause severe damage to the germinal epithelium with subtle effects on Sertoli cells. To assess Sertoli cell function in men with primary testicular damage after treatment with CT in childhood and adolescence, the inhibin B level needs to be interpreted in the context of the circulating FSH, especially when normal FSH levels are observed. JF - Journal of pediatric endocrinology & metabolism : JPEM AU - Bordallo, Maria Alice Neves AU - Guimarães, Marília Martins AU - Pessoa, Cencita Hosanha C N AU - Carriço, Maria Kadma AU - Dimetz, Trude AU - Gazolla, Helena Mussi AU - Dobbin, Jane AU - Castilho, Ilda Akemi Muramoto Alves AD - Division of Endocrinology and Hematology, National Cancer Institute, State University of Rio de Janeiro, Hospital Pedro Ernesto, Brazil. maliceb@attglobal.net Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 879 EP - 887 VL - 17 IS - 6 SN - 0334-018X, 0334-018X KW - Biomarkers KW - 0 KW - inhibin B KW - Procarbazine KW - 35S93Y190K KW - Inhibins KW - 57285-09-3 KW - Vincristine KW - 5J49Q6B70F KW - Cyclophosphamide KW - 8N3DW7272P KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Sperm Count KW - Humans KW - Adult KW - Case-Control Studies KW - Child KW - Biomarkers -- blood KW - Oligospermia -- etiology KW - Male KW - Survival Analysis KW - Organ Size -- drug effects KW - Child, Preschool KW - Vincristine -- adverse effects KW - Hodgkin Disease -- pathology KW - Prednisone -- therapeutic use KW - Testis -- pathology KW - Hodgkin Disease -- blood KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Follicle Stimulating Hormone -- blood KW - Cyclophosphamide -- adverse effects KW - Sertoli Cells -- drug effects KW - Hodgkin Disease -- physiopathology KW - Testis -- physiopathology KW - Procarbazine -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Prednisone -- adverse effects KW - Vincristine -- therapeutic use KW - Inhibins -- blood KW - Hodgkin Disease -- drug therapy KW - Procarbazine -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66732624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatric+endocrinology+%26+metabolism+%3A+JPEM&rft.atitle=Decreased+serum+inhibin+B%2FFSH+ratio+as+a+marker+of+Sertoli+cell+function+in+male+survivors+after+chemotherapy+in+childhood+and+adolescence.&rft.au=Bordallo%2C+Maria+Alice+Neves%3BGuimar%C3%A3es%2C+Mar%C3%ADlia+Martins%3BPessoa%2C+Cencita+Hosanha+C+N%3BCarri%C3%A7o%2C+Maria+Kadma%3BDimetz%2C+Trude%3BGazolla%2C+Helena+Mussi%3BDobbin%2C+Jane%3BCastilho%2C+Ilda+Akemi+Muramoto+Alves&rft.aulast=Bordallo&rft.aufirst=Maria+Alice&rft.date=2004-06-01&rft.volume=17&rft.issue=6&rft.spage=879&rft.isbn=&rft.btitle=&rft.title=Journal+of+pediatric+endocrinology+%26+metabolism+%3A+JPEM&rft.issn=0334018X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-22 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physiological and pathological consequences of the interactions of the p53 tumor suppressor with the glucocorticoid, androgen, and estrogen receptors. AN - 66725897; 15265773 AB - The p53 tumor suppressor plays a key role in protection from the effects of different physiological stresses (DNA damage, hypoxia, transcriptional defects, etc.), and loss of its activity has dire consequences, such as cancer. Its activity is finely tuned through interactions with other important regulatory circuits in the cell. Recently, striking evidence has emerged for crosstalk with another class of important regulators, the steroid hormone receptors, and in particular the glucocorticoid (GR), androgen (AR), and estrogen (ER) receptors. These receptors are important in maintaining homeostasis in response to internal and external stresses (GR) and in the development, growth, and maintenance of the male and female reproductive systems (AR and ER, respectively). We review how p53 interacts closely with these receptors, to the extent that they share the same E3 ubiquitin ligase, the MDM2 oncoprotein. We discuss the different physiological contexts in which such interactions occur, and also how these interactions have been undermined in various pathological situations. We will describe future areas for research, with special emphasis on GR, and how certain common features, such as cytoplasmic anchoring of p53 by the receptors, may become targets for the development of therapeutic interventions. Given the importance of GR in inflammation, erythropoiesis, and autoimmune diseases, and the importance of AR and ER in prostate and breast cancer (respectively), the studies on p53 interactions with the steroid receptors will be an important domain in the near future. JF - Annals of the New York Academy of Sciences AU - Sengupta, Sagar AU - Wasylyk, Bohdan AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 54 EP - 71 VL - 1024 SN - 0077-8923, 0077-8923 KW - Receptors, Androgen KW - 0 KW - Receptors, Estrogen KW - Receptors, Glucocorticoid KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Apoptosis KW - Humans KW - Receptors, Androgen -- metabolism KW - Receptors, Estrogen -- metabolism KW - Receptors, Estrogen -- physiology KW - Receptors, Androgen -- physiology KW - Neoplasms -- etiology KW - Male KW - Immune System Diseases -- etiology KW - Female KW - Cell Division KW - Tumor Suppressor Protein p53 -- physiology KW - Tumor Suppressor Protein p53 -- metabolism KW - Receptors, Glucocorticoid -- physiology KW - Receptors, Glucocorticoid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66725897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Physiological+and+pathological+consequences+of+the+interactions+of+the+p53+tumor+suppressor+with+the+glucocorticoid%2C+androgen%2C+and+estrogen+receptors.&rft.au=Sengupta%2C+Sagar%3BWasylyk%2C+Bohdan&rft.aulast=Sengupta&rft.aufirst=Sagar&rft.date=2004-06-01&rft.volume=1024&rft.issue=&rft.spage=54&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 - 2004-08-13 N1 - Date created - 2004-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The importance of adolescence in the development of nicotine dependence: comments on part V. AN - 66702338; 15251889 JF - Annals of the New York Academy of Sciences AU - Merikangas, Kathleen Ries AD - National Institute of Mental Health, NIH, 15K North Drive, Bethesda, MD 20892-2670, USA. merikank@intra.nimh.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 198 EP - 201 VL - 1021 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Rats KW - Animals KW - Age Factors KW - Risk Factors KW - Humans KW - Research KW - Adolescent KW - Adolescent Behavior -- psychology KW - Psychology, Adolescent KW - Tobacco Use Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66702338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+importance+of+adolescence+in+the+development+of+nicotine+dependence%3A+comments+on+part+V.&rft.au=Merikangas%2C+Kathleen+Ries&rft.aulast=Merikangas&rft.aufirst=Kathleen&rft.date=2004-06-01&rft.volume=1021&rft.issue=&rft.spage=198&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 - 2004-08-23 N1 - Date created - 2004-07-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Ann N Y Acad Sci. 2004 Jun;1021:167-74 [15251887] Ann N Y Acad Sci. 2004 Jun;1021:175-97 [15251888] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of calorie restriction mimetics as a prolongevity strategy. AN - 66689219; 15247056 AB - By applying calorie restriction (CR) at 30-50% below ad libitum levels, studies in numerous species have reported increased life span, reduced incidence and delayed onset of age-related diseases, improved stress resistance, and decelerated functional decline. Whether this nutritional intervention is relevant to human aging remains to be determined; however, evidence emerging from CR studies in nonhuman primates suggests that response to CR in primates parallels that observed in rodents. To evaluate CR effects in humans, clinical trials have been initiated. Even if evidence could substantiate CR as an effective antiaging strategy for humans, application of this intervention would be problematic due to the degree and length of restriction required. To meet this challenge for potential application of CR, new research to create "caloric restriction mimetics" has emerged. This strategy focuses on identifying compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. Microarray studies show that gene expression profiles of key enzymes in glucose (energy) handling pathways are modified by CR. Drugs that inhibit glycolysis (2-deoxyglucose) or enhance insulin action (metformin) are being assessed as CR mimetics. Promising results have emerged from initial studies regarding physiological responses indicative of CR (reduced body temperature and plasma insulin) as well as protection against neurotoxicity, enhanced dopamine action, and upregulated brain-derived neurotrophic factor. Further life span analyses in addition to expanded toxicity studies must be completed to assess the potential of any CR mimetic, but this strategy now appears to offer a very promising and expanding research field. JF - Annals of the New York Academy of Sciences AU - Ingram, Donald K AU - Anson, R Michael AU - de Cabo, Rafael AU - Mamczarz, Jacek AU - Zhu, Min AU - Mattison, Julie AU - Lane, Mark A AU - Roth, George S AD - Laboratory of Experimental Gerontology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. ingramd@grc.nia.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 412 EP - 423 VL - 1019 SN - 0077-8923, 0077-8923 KW - Dopamine Agents KW - 0 KW - Insulin KW - Metformin KW - 9100L32L2N KW - Deoxyglucose KW - 9G2MP84A8W KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Dopamine Agents -- pharmacology KW - Dopamine -- metabolism KW - Insulin -- metabolism KW - Rats KW - Metformin -- metabolism KW - Body Temperature KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Up-Regulation KW - Time Factors KW - Glycolysis KW - Deoxyglucose -- metabolism KW - Caloric Restriction KW - Longevity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66689219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Development+of+calorie+restriction+mimetics+as+a+prolongevity+strategy.&rft.au=Ingram%2C+Donald+K%3BAnson%2C+R+Michael%3Bde+Cabo%2C+Rafael%3BMamczarz%2C+Jacek%3BZhu%2C+Min%3BMattison%2C+Julie%3BLane%2C+Mark+A%3BRoth%2C+George+S&rft.aulast=Ingram&rft.aufirst=Donald&rft.date=2004-06-01&rft.volume=1019&rft.issue=&rft.spage=412&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 - 2004-08-20 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generating mouse models for studying the function and fate of intrinsic cardiac adrenergic cells. AN - 66678897; 15240397 AB - Embryos lacking the ability to synthesize epinephrine and norepinephrine die (probably due to cardiac failure) without exogenous supplementation while mutant neonates can grow into fertile adults without supplementation. These experiments define a critical period during embryogenesis, when norepinephrine and/or epinephrine are essential for mouse development. The critical period is prior to sympathetic innervation of the heart and prior to synthesis of catecholamines by the adrenal medullae. Recent work indicates that the developing heart is likely to be a major source of catecholamines in the developing mammalian embryo. The spatial pattern of biosynthetic enzymes suggests an association of the intrinsic cardiac adrenergic cells with the developing pacemaker and cardiac conduction cells. To address the functional characteristics and the fate of these cardiac adrenergic cells, we have developed two mouse models that allow us to identify and to characterize the adrenergic cells and their descendants. JF - Annals of the New York Academy of Sciences AU - Pfeifer, Karl AU - Boe, Steve P AU - Rong, Qi AU - Ebert, Steven N AD - Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. pfeiferk@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 418 EP - 423 VL - 1018 SN - 0077-8923, 0077-8923 KW - Catecholamines KW - 0 KW - Receptors, Adrenergic KW - Dopamine beta-Hydroxylase KW - EC 1.14.17.1 KW - Phenylethanolamine N-Methyltransferase KW - EC 2.1.1.28 KW - Index Medicus KW - Dopamine beta-Hydroxylase -- genetics KW - Animals KW - Phenylethanolamine N-Methyltransferase -- genetics KW - Catecholamines -- biosynthesis KW - Mice KW - Mutagenesis KW - Models, Animal KW - Myocardium -- cytology KW - Myocardium -- enzymology KW - Heart -- physiology KW - Receptors, Adrenergic -- physiology KW - Myocardium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66678897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Generating+mouse+models+for+studying+the+function+and+fate+of+intrinsic+cardiac+adrenergic+cells.&rft.au=Pfeifer%2C+Karl%3BBoe%2C+Steve+P%3BRong%2C+Qi%3BEbert%2C+Steven+N&rft.aulast=Pfeifer&rft.aufirst=Karl&rft.date=2004-06-01&rft.volume=1018&rft.issue=&rft.spage=418&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 - 2004-08-18 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methylation and expression of the lactoferrin gene in human tissues and cancer cells. AN - 66662922; 15222484 AB - The lactoferrin gene promoter contains GC-rich regions that harbor consensus sequences for a variety of transcription factors. Previous work in our laboratory has demonstrated a link between methylation at the CpG sites of the mouse lactoferrin gene promoter and the level of its expression. The current work investigates the methylation profile in three regions of the human lactoferrin gene by bisulfite genomic sequencing. In addition, the methylation profiles of normal leukocyte DNA, and leukemia cell line and patient DNA were compared. The three regions are located at the -504/-190, which includes the estrogen response element, the -282/+271 which contains the lactoferrin promoter and the +1087/+1476, a region within the first intron that has the alternative delta lactoferrin promoter. Differential methylations were found within all the regions. Increased methylation at the CpG sites and the presence of non-CpG methylation of the lactoferrin promoters were found in the cancer samples. JF - Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine AU - Teng, Christina AU - Gladwell, Wesley AU - Raphiou, Ibrahim AU - Liu, Eric AD - Gene Regulation Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Teng@niehs.nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 317 EP - 323 VL - 17 IS - 3 SN - 0966-0844, 0966-0844 KW - Sulfites KW - 0 KW - Lactoferrin KW - EC 3.4.21.- KW - sodium bisulfite KW - TZX5469Z6I KW - Index Medicus KW - Animals KW - Promoter Regions, Genetic KW - Humans KW - CpG Islands KW - Sulfites -- metabolism KW - Tissue Distribution KW - Cell Line KW - Lactoferrin -- genetics KW - Tumor Cells, Cultured KW - DNA Methylation KW - Gene Expression Regulation KW - Lactoferrin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66662922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometals+%3A+an+international+journal+on+the+role+of+metal+ions+in+biology%2C+biochemistry%2C+and+medicine&rft.atitle=Methylation+and+expression+of+the+lactoferrin+gene+in+human+tissues+and+cancer+cells.&rft.au=Teng%2C+Christina%3BGladwell%2C+Wesley%3BRaphiou%2C+Ibrahim%3BLiu%2C+Eric&rft.aulast=Teng&rft.aufirst=Christina&rft.date=2004-06-01&rft.volume=17&rft.issue=3&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Biometals+%3A+an+international+journal+on+the+role+of+metal+ions+in+biology%2C+biochemistry%2C+and+medicine&rft.issn=09660844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-02 N1 - Date created - 2004-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aryl hydrocarbon receptor activation of an antitumor aminoflavone: basis of selective toxicity for MCF-7 breast tumor cells. AN - 66644396; 15210858 AB - Aminoflavone (4H-1-benzopyran-4-one, 5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methyl; NSC 686288) demonstrates differential antiproliferative activity in the National Cancer Institute's anticancer drug screen. We demonstrate here that MCF-7 human breast cancer cells are sensitive to aminoflavone both in vitro and when grown in vivo as xenografts in athymic mice. As previous work has indicated that aminoflavone requires metabolic activation by cytochrome P450 1A1 (CYP1A1), we investigated the effect of aminoflavone on CYP1A1 expression and on the aryl hydrocarbon receptor (AhR), a transcriptional regulator of CYP1A1. In aminoflavone-sensitive but not aminoflavone-resistant cells, the drug caused a 100-fold induction of CYP1A1 mRNA and a corresponding increase in ethoxyresorufin-O-deethylase activity. An AhR-deficient variant of the MCF-7 breast carcinoma, AH(R100), with diminished CYP1A1 inducibility, exhibits cellular resistance to aminoflavone and is refractory to CYP1A1 mRNA induction by the drug. The increase in CYP1A1 mRNA in the aminoflavone-sensitive MCF-7 breast tumor cell results from transcriptional activation of xenobiotic-responsive element (XRE)-controlled transcription. Aminoflavone treatment causes a translocation of the AhR from the cytoplasm to the nucleus with subsequent formation of AhR-XRE protein DNA complexes. In contrast to the aminoflavone-sensitive MCF-7 cells, the resistant cell lines (MDA-MB-435, PC-3, and AH(R100)) demonstrated constitutive nuclear localization of AhR. Additionally, aminoflavone failed to induce ethoxyresorufin-O-deethylase activity, CYP1A1 transcription, AhR-XRE complex formation, and apoptosis in aminoflavone-resistant cells. These results suggest that the cytotoxicity of aminoflavone in a sensitive breast tumor cell line is the result of the engagement of AhR-mediated signal transduction. JF - Molecular cancer therapeutics AU - Loaiza-Pérez, Andrea I AU - Kenney, Susan AU - Boswell, Jamie AU - Hollingshead, Melinda AU - Alley, Michael C AU - Hose, Curtis AU - Ciolino, Henry P AU - Yeh, Grace C AU - Trepel, Jane B AU - Vistica, David T AU - Sausville, Edward A AD - Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick, Building 322, Room 104, Frederick, MD 21702, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 715 EP - 725 VL - 3 IS - 6 SN - 1535-7163, 1535-7163 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Receptors, Aryl Hydrocarbon KW - aminoflavone KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cyp1b1 protein, mouse KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1B1 KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Animals KW - Cytochrome P-450 CYP1A1 -- genetics KW - Transcription, Genetic -- drug effects KW - Cell Nucleus -- metabolism KW - Protein Transport -- drug effects KW - Humans KW - Transcriptional Activation -- drug effects KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Mice, Nude KW - Cell Line, Tumor KW - Mice KW - Enzyme Induction -- drug effects KW - Apoptosis -- drug effects KW - Xenograft Model Antitumor Assays KW - Response Elements -- genetics KW - Promoter Regions, Genetic -- genetics KW - Aryl Hydrocarbon Hydroxylases -- genetics KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Antineoplastic Agents -- metabolism KW - Antineoplastic Agents -- toxicity KW - Breast Neoplasms -- metabolism KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Flavonoids -- pharmacology KW - Flavonoids -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Flavonoids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66644396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+therapeutics&rft.atitle=Aryl+hydrocarbon+receptor+activation+of+an+antitumor+aminoflavone%3A+basis+of+selective+toxicity+for+MCF-7+breast+tumor+cells.&rft.au=Loaiza-P%C3%A9rez%2C+Andrea+I%3BKenney%2C+Susan%3BBoswell%2C+Jamie%3BHollingshead%2C+Melinda%3BAlley%2C+Michael+C%3BHose%2C+Curtis%3BCiolino%2C+Henry+P%3BYeh%2C+Grace+C%3BTrepel%2C+Jane+B%3BVistica%2C+David+T%3BSausville%2C+Edward+A&rft.aulast=Loaiza-P%C3%A9rez&rft.aufirst=Andrea&rft.date=2004-06-01&rft.volume=3&rft.issue=6&rft.spage=715&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-18 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide prodrugs and metallochemotherapeutics: JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation. AN - 66643558; 15210857 AB - Development of chemotherapeutic resistance is a major cause of pharmacologic failure in cancer treatment. One mechanism of resistance in tumor cells is the overexpression of glutathione S-transferases (GSTs) that serve two distinct roles in the development of drug resistance via the formation of glutathione conjugates with drugs for their cellular efflux, and the inhibition of the mitogen-activated protein kinase pathway. To target GST-based resistance to chemotherapeutics, a series of nitric oxide (NO)-releasing diazeniumdiolates was synthesized and shown to release NO on reaction with GST and/or glutathione. Two diazeniumdiolates, JS-K [O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] and CB-3-100 [O(2)-(2,4-dinitrophenyl) 1-[4-(N,N-diethylcarboxamido)piperazin-1-yl]diazen-1-ium-1,2-diolate], were studied on their ability in reversing arsenic and cisplatin resistance in a rat liver cell line that is tumorigenic and shows acquired tolerance to arsenic and cisplatin, with overexpression of GSTs. The enhanced cytolethality produced by the NO donors was accompanied by increased accumulation of arsenic and platinum within cells and by enhanced activation of mitogen-activated protein kinase members c-jun-NH-kinase and extracellular signal-regulated kinase. Our data indicate that JS-K and CB-3-100 are promising lead compounds for the possible development of a novel class of adjuvant chemotherapeutic agents potentially capable of reversing arsenic and cisplatin resistance in certain tumor cells. JF - Molecular cancer therapeutics AU - Liu, Jie AU - Li, Chengxiu AU - Qu, Wei AU - Leslie, Elaine AU - Bonifant, Challice L AU - Buzard, Gregory S AU - Saavedra, Joseph E AU - Keefer, Larry K AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, mail drop F0-09, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 709 EP - 714 VL - 3 IS - 6 SN - 1535-7163, 1535-7163 KW - Azo Compounds KW - 0 KW - Nitric Oxide Donors KW - O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate KW - O(2)-(2,4-dinitrophenyl) 1-(4-(N,N-diethylcarboxamido)piperazin-1-yl)diazen-1-ium 1,2-diolate KW - Piperazines KW - Prodrugs KW - diazeniumdiolate KW - Platinum KW - 49DFR088MY KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 1 KW - Mitogen-Activated Protein Kinase 3 KW - MAP Kinase Kinase 4 KW - EC 2.7.12.2 KW - Mitogen-Activated Protein Kinase Kinases KW - Arsenic KW - N712M78A8G KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Rats KW - Mitogen-Activated Protein Kinase 3 -- metabolism KW - Platinum -- metabolism KW - MAP Kinase Signaling System -- drug effects KW - Animals KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Mitogen-Activated Protein Kinase Kinases -- metabolism KW - Cell Line KW - Phosphorylation -- drug effects KW - JNK Mitogen-Activated Protein Kinases -- metabolism KW - Nitric Oxide Donors -- pharmacology KW - Prodrugs -- toxicity KW - Arsenic -- toxicity KW - Arsenic -- metabolism KW - Prodrugs -- pharmacology KW - Cisplatin -- toxicity KW - Azo Compounds -- toxicity KW - Azo Compounds -- pharmacology KW - Nitric Oxide Donors -- toxicity KW - Piperazines -- pharmacology KW - Cisplatin -- metabolism KW - Piperazines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66643558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+therapeutics&rft.atitle=Nitric+oxide+prodrugs+and+metallochemotherapeutics%3A+JS-K+and+CB-3-100+enhance+arsenic+and+cisplatin+cytolethality+by+increasing+cellular+accumulation.&rft.au=Liu%2C+Jie%3BLi%2C+Chengxiu%3BQu%2C+Wei%3BLeslie%2C+Elaine%3BBonifant%2C+Challice+L%3BBuzard%2C+Gregory+S%3BSaavedra%2C+Joseph+E%3BKeefer%2C+Larry+K%3BWaalkes%2C+Michael+P&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2004-06-01&rft.volume=3&rft.issue=6&rft.spage=709&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-18 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Environmental Genome Project: phase I and beyond. AN - 66642750; 15210868 AB - Human illness is caused by many interrelated factors including aging, inherited genetic predispositions, and a variety of environmental exposures. There is increasing awareness of the role of genetics as a factor that can dramatically alter susceptibility to all disease, especially environmentally induced chronic disease, such as cancer, asthma, diabetes, cardiovascular disease, and neurodegenerative disorders. In some cases, a genetic factor influences disease susceptibility in a small fraction of the population because it occurs at a low frequency or involves a relatively low-incidence disease; however, in other cases, a genetic factor increases susceptibility in a large number of individuals and involves a disease that occurs at high incidence, creating a large public health burden. JF - Molecular interventions AU - Wilson, Samuel H AU - Olden, Kenneth AD - National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive Research Triangle Park, NC 27709-2233. Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 147 EP - 156 VL - 4 IS - 3 KW - Methylenetetrahydrofolate Reductase (NADPH2) KW - EC 1.5.1.20 KW - Aryldialkylphosphatase KW - EC 3.1.8.1 KW - PON1 protein, human KW - Index Medicus KW - United States KW - Polymorphism, Single Nucleotide KW - Aryldialkylphosphatase -- genetics KW - Humans KW - Environmental Exposure KW - Bioethics KW - Databases, Genetic KW - Methylenetetrahydrofolate Reductase (NADPH2) -- genetics KW - Leukemia -- genetics KW - Environment KW - Genome, Human KW - Genetic Predisposition to Disease -- genetics KW - Genetic Predisposition to Disease -- epidemiology KW - National Institute of Environmental Health Sciences (U.S.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66642750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+interventions&rft.atitle=The+Environmental+Genome+Project%3A+phase+I+and+beyond.&rft.au=Wilson%2C+Samuel+H%3BOlden%2C+Kenneth&rft.aulast=Wilson&rft.aufirst=Samuel&rft.date=2004-06-01&rft.volume=4&rft.issue=3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Molecular+interventions&rft.issn=1543-2548&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-03-24 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship of asthma medication use to perinatal outcomes. AN - 66639270; 15208581 AB - Maternal asthma has been reported to increase the risk of preeclampsia, preterm deliveries, and lower-birth-weight infants, but the mechanisms of this effect are not defined. We sought to evaluate the relationship between the use of contemporary asthma medications and adverse perinatal outcomes. Asthmatic patients were recruited from the 16 centers of the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network from December 1994 through February 2000. Gestational medication use was determined on the basis of patient history at enrollment and at monthly visits during pregnancy. Perinatal data were obtained at postpartum chart reviews. Perinatal outcome variables included gestational hypertension, preterm births, low-birth-weight infants, small-for-gestational-age infants, and major malformations. The final cohort included 2123 asthmatic participants. No significant relationships were found between the use of inhaled beta-agonists (n=1828), inhaled corticosteroids (n=722), or theophylline (n=273) and adverse perinatal outcomes. After adjusting for demographic and asthma severity covariates, oral corticosteroid use was significantly associated with both preterm birth at less than 37 weeks' gestation (odds ratio, 1.54; 95% CI, 1.02-2.33) and low birth weight of less than 2500 g (odds ratio, 1.80; 95% CI, 1.13-2.88). Use of inhaled beta-agonists, inhaled steroids, and theophylline do not appear to increase perinatal risks in pregnant asthmatic women. The mechanism of the association between maternal oral corticosteroid use and prematurity remains to be determined. JF - The Journal of allergy and clinical immunology AU - Schatz, Michael AU - Dombrowski, Mitchell P AU - Wise, Robert AU - Momirova, Valerija AU - Landon, Mark AU - Mabie, William AU - Newman, Roger B AU - Hauth, John C AU - Lindheimer, Marshall AU - Caritis, Steve N AU - Leveno, Kenneth J AU - Meis, Paul AU - Miodovnik, Menachem AU - Wapner, Ronald J AU - Paul, Richard H AU - Varner, Michael W AU - O'Sullivan, Mary Jo AU - Thurnau, Gary R AU - Conway, Deborah L AU - Maternal-Fetal Medicine Units Network, The National Institute of Child Health and Development AU - National Heart, Lung and Blood Institute AD - Allergy Department, Kaiser Permanente Medical Center, 7060 Clairemont Mesa Boulevard, San Diego, CA 92111, USA. michael.x.schatz@kp.org ; Maternal-Fetal Medicine Units Network, The National Institute of Child Health and Development ; National Heart, Lung and Blood Institute Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 1040 EP - 1045 VL - 113 IS - 6 SN - 0091-6749, 0091-6749 KW - Adrenal Cortex Hormones KW - 0 KW - Anti-Asthmatic Agents KW - Abridged Index Medicus KW - Index Medicus KW - Prospective Studies KW - Humans KW - Cohort Studies KW - Adult KW - Infant, Newborn KW - Birth Weight -- drug effects KW - Adolescent KW - Obstetric Labor, Premature -- chemically induced KW - Female KW - Pregnancy KW - Adrenal Cortex Hormones -- adverse effects KW - Fetus -- drug effects KW - Asthma -- drug therapy KW - Pregnancy Complications -- drug therapy KW - Anti-Asthmatic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66639270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+relationship+of+asthma+medication+use+to+perinatal+outcomes.&rft.au=Schatz%2C+Michael%3BDombrowski%2C+Mitchell+P%3BWise%2C+Robert%3BMomirova%2C+Valerija%3BLandon%2C+Mark%3BMabie%2C+William%3BNewman%2C+Roger+B%3BHauth%2C+John+C%3BLindheimer%2C+Marshall%3BCaritis%2C+Steve+N%3BLeveno%2C+Kenneth+J%3BMeis%2C+Paul%3BMiodovnik%2C+Menachem%3BWapner%2C+Ronald+J%3BPaul%2C+Richard+H%3BVarner%2C+Michael+W%3BO%27Sullivan%2C+Mary+Jo%3BThurnau%2C+Gary+R%3BConway%2C+Deborah+L%3BMaternal-Fetal+Medicine+Units+Network%2C+The+National+Institute+of+Child+Health+and+Development%3BNational+Heart%2C+Lung+and+Blood+Institute&rft.aulast=Schatz&rft.aufirst=Michael&rft.date=2004-06-01&rft.volume=113&rft.issue=6&rft.spage=1040&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 - 2004-07-14 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Institute on Alcohol Abuse and Alcoholism report on moderate drinking. AN - 66636701; 15201626 AB - In support of the 2005 update of the U.S. Department of Agriculture/U.S. Department of Health and Human Services Dietary Guidelines, the National Institute on Alcohol Abuse and Alcoholism was asked to assess the strength of the evidence related to health risks and potential benefits of moderate alcohol consumption, with particular focus on the areas of cardiovascular disease, breast cancer, obesity, birth defects, breastfeeding, and aging. The findings were reviewed by external researchers with extensive research backgrounds on the consequences and benefits of alcohol consumption. This report now serves as the National Institutes of Health's formal position paper on the health risks and potential benefits of moderate alcohol use. Copyright 2004 Research Society on Alcoholism JF - Alcoholism, clinical and experimental research AU - Gunzerath, Lorraine AU - Faden, Vivian AU - Zakhari, Samir AU - Warren, Kenneth AD - Strategic Research Planning Branch , Division of Metabolism & Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-9304, USA. Lg72x@nih.gov Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 829 EP - 847 VL - 28 IS - 6 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Risk Factors KW - Humans KW - National Institutes of Health (U.S.) KW - United States -- epidemiology KW - Temperance -- statistics & numerical data KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- epidemiology KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66636701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=National+Institute+on+Alcohol+Abuse+and+Alcoholism+report+on+moderate+drinking.&rft.au=Gunzerath%2C+Lorraine%3BFaden%2C+Vivian%3BZakhari%2C+Samir%3BWarren%2C+Kenneth&rft.aulast=Gunzerath&rft.aufirst=Lorraine&rft.date=2004-06-01&rft.volume=28&rft.issue=6&rft.spage=829&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 - 2004-10-01 N1 - Date created - 2004-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Food Insufficiency and Physical and Mental Health in a Longitudinal Survey of Welfare Recipients AN - 61325129; 200405378 AB - Food insufficiency is a significant problem in the US, & poor African American women with children are at especially high risk. An inadequate household food supply can potentially affect the well-being of household members, but it is difficult to distinguish the effects of food insufficiency from risk factors for poor health that are also common among the food insufficient, such as poverty. We examined food insufficiency & physical & mental health among African American & white women (n = 676) who were welfare recipients in 1997. Controlling for common risk factors, women who reported food insufficiency in both 1997 & 1998 were more likely to report fair or poor health at the later date. Food insufficiency in 1998 was significantly associated with meeting the diagnostic screening criteria for recent major depression. Food insufficiency at both times & in 1998 only was related to women's sense of mastery. These findings add to growing evidence that household food insufficiency is associated with poor physical & mental health. 6 Tables, 55 References. Adapted from the source document. JF - Journal of Health and Social Behavior AU - Siefert, Kristine AU - Heflin, Colleen M AU - Corcoran, Mary E AU - Williams, David R AD - NIMH Research Center Poverty/Risk/Mental Health, U Michigan, Ann Arbor ksiefert@umich.edu Y1 - 2004/06// PY - 2004 DA - June 2004 SP - 171 EP - 186 VL - 45 IS - 2 SN - 0022-1465, 0022-1465 KW - Hunger KW - Depression (Psychology) KW - Poverty KW - Welfare Recipients KW - Health KW - Mental Health KW - Females KW - article KW - 6141: poverty & homelessness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61325129?accountid=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=Journal+of+Health+and+Social+Behavior&rft.atitle=Food+Insufficiency+and+Physical+and+Mental+Health+in+a+Longitudinal+Survey+of+Welfare+Recipients&rft.au=Siefert%2C+Kristine%3BHeflin%2C+Colleen+M%3BCorcoran%2C+Mary+E%3BWilliams%2C+David+R&rft.aulast=Siefert&rft.aufirst=Kristine&rft.date=2004-06-01&rft.volume=45&rft.issue=2&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Journal+of+Health+and+Social+Behavior&rft.issn=00221465&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-10-30 N1 - Number of references - 55 N1 - Last updated - 2016-09-28 N1 - CODEN - JHSBA5 N1 - SubjectsTermNotLitGenreText - Mental Health; Health; Females; Hunger; Poverty; Depression (Psychology); Welfare Recipients ER - TY - JOUR T1 - Antibody-targeted radiation cancer therapy AN - 21374963; 11937957 AB - Several monoclonal antibodies are now approved for cancer therapy, such as rituximab, an anti-CD20 monoclonal antibody for the treatment of B-cell non-Hodgkin's lymphoma. Such 'naked' antibodies can recruit the body's immune effector mechanisms to kill cells expressing the target of the antibody. In recent years, the linking of radionuclides to antibodies to either augment inherent activity or to exploit the specific targeting properties of monoclonal antibodies has been a major area of development. Two radionuclide-bearing monoclonal antibody therapies have recently been approved by the US FDA, and several more are in clinical trials. Here, we discuss the development and use of radiolabelled monoclonal antibody therapies, with a focus on radiolabelled monoclonal antibodies that have been evaluated in clinical trials. JF - Nature Reviews: Drug Discovery AU - Milenic, Diane E AU - Brady, Erik D AU - Brechbiel, Martin W AD - Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1002, USA. Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 488 EP - 499 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 3 IS - 6 SN - 1474-1776, 1474-1776 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - Non-Hodgkin's lymphoma KW - Radiation KW - Monoclonal antibodies KW - Lymphocytes B KW - rituximab KW - Radioisotopes KW - Clinical trials KW - Cancer KW - F 06955:Immunomodulation & Immunopharmacology KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21374963?accountid=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+Reviews%3A+Drug+Discovery&rft.atitle=Antibody-targeted+radiation+cancer+therapy&rft.au=Milenic%2C+Diane+E%3BBrady%2C+Erik+D%3BBrechbiel%2C+Martin+W&rft.aulast=Milenic&rft.aufirst=Diane&rft.date=2004-06-01&rft.volume=3&rft.issue=6&rft.spage=488&rft.isbn=&rft.btitle=&rft.title=Nature+Reviews%3A+Drug+Discovery&rft.issn=14741776&rft_id=info:doi/10.1038%2Fnrd1413 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-03-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Non-Hodgkin's lymphoma; Radiation; rituximab; Lymphocytes B; Monoclonal antibodies; Radioisotopes; Clinical trials; Cancer DO - http://dx.doi.org/10.1038/nrd1413 ER - TY - JOUR T1 - Rapid analysis of inflammatory cytokines in cerebrospinal fluid using chip-based immunoaffinity electrophoresis AN - 20525990; 7762052 AB - A chip-based capillary electrophoresis system has been designed for rapidly measuring the concentrations of inflammatory cytokines in the cerebrospinal fluid of patients with head trauma. Isolation of the reactive cytokines was achieved by immunoaffinity capture using a panel of six immobilized antibodies, directly attached to the injection port of the chip. The captured cytokines were labeled in situ with a red light-emitting laser dye and electroeluted into the separation channel. Separation of the isolated cytokines was achieved by electrophoresis in under 2min with quantification of the resolved peaks being achieved by on-line laser-induced fluorescence and integration of each peak area. Comparison of the results to commercially available high-sensitivity immunoassays demonstrates that the chip-based assay provides a fast, accurate procedure for studying the concentrations of these analytes in complex biological materials. The degree of accuracy and precision achieved by the chip-based CE is comparable to conventional immunoassays, the system being able to analyze between 10-12 samples per hour. With the ever-expanding array of antibodies that are commercially available, this chip-based system can be applied to a wide variety of different analyses. JF - Electrophoresis AU - Phillips, Terry M AD - Ultramicro Analytical Immunochemistry Resource, Division of Bioengineering & Physical Science, Office of Research Services, National Institutes of Health, Bethesda, MS, USA, phillipt@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 1652 EP - 1659 PB - Wiley-VCH, Postfach 101161 Weinheim 69451 Germany, [mailto:info@wiley-vch.de], [URL:http://www.wiley-vch.de/publish/en/] VL - 25 IS - 10-11 SN - 0173-0835, 0173-0835 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Fluorescence KW - Head KW - Trauma KW - Inflammation KW - Integration KW - Cerebrospinal fluid KW - Antibodies KW - capillary electrophoresis KW - Cytokines KW - Lasers KW - Immunoassays KW - N3 11027:Neurology & neuropathology KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20525990?accountid=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=Electrophoresis&rft.atitle=Rapid+analysis+of+inflammatory+cytokines+in+cerebrospinal+fluid+using+chip-based+immunoaffinity+electrophoresis&rft.au=Phillips%2C+Terry+M&rft.aulast=Phillips&rft.aufirst=Terry&rft.date=2004-06-01&rft.volume=25&rft.issue=10-11&rft.spage=1652&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/10.1002%2Felps.200305873 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cytokines; Inflammation; Antibodies; Immunoassays; Cerebrospinal fluid; Head; Lasers; capillary electrophoresis; Fluorescence; Integration; Trauma DO - http://dx.doi.org/10.1002/elps.200305873 ER - TY - JOUR T1 - Functional Neuroimaging of Sympathetic Innervation of the Heart AN - 20225565; 5953360 AB - Many concepts about acute and chronic effects of stress depend on alterations in sympathetic nerves supplying the heart. Physiologic, pharmacologic, and neurochemical approaches have been used to evaluate cardiac sympathetic function. This article describes a fourth approach that is based on nuclear scanning to visualize cardiac sympathetic innervation and function and relationships between the neuroimaging findings and those from other approaches. Multiple-system atrophy with orthostatic hypotension (formerly the Shy-Drager syndrome) features normal cardiac sympathetic innervation and normal entry of norepinephrine into the coronary sinus (cardiac norepinephrine spillover), in contrast to Parkinson disease with orthostatic hypotension, which features neuroimaging and neurochemical evidence for loss of cardiac sympathetic nerves. This difference may have important implications not only for diagnosis but also for understanding the etiology of Parkinson disease. By analysis of curves relating myocardial radioactivity with time (time-activity curves) after injection of a sympathoneural imaging agent, it is possible to obtain information about cardiac sympathetic function. Abnormal time-activity curves are seen in common disorders such as heart failure and diabetic neuropathy and provide an independent, adverse prognostic index. Analogous abnormalities might help explain increased cardiovascular risk in psychiatric disorders such as melancholic depression. JF - Annals of the New York Academy of Sciences AU - Goldstein, David S AD - Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 231 EP - 243 PB - The New York Academy of Sciences VL - 1018 SN - 0077-8923, 0077-8923 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Hypotension KW - Heart KW - Innervation KW - Neuroimaging KW - Etiology KW - Depression KW - Parkinson's disease KW - Stress KW - Sinus KW - Methodology KW - Diabetes mellitus KW - Neurodegenerative diseases KW - Mental disorders KW - sympathetic nerves KW - Movement disorders KW - Scanning KW - Chronic effects KW - Norepinephrine KW - Atrophy KW - Cardiovascular diseases KW - Radioactivity KW - Neuropathy KW - Heart diseases KW - W 30910:Imaging KW - N3 11145:Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20225565?accountid=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=Functional+Neuroimaging+of+Sympathetic+Innervation+of+the+Heart&rft.au=Goldstein%2C+David+S&rft.aulast=Goldstein&rft.aufirst=David&rft.date=2004-06-01&rft.volume=1018&rft.issue=&rft.spage=231&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 revised - 2007-01-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Innervation; Heart; Hypotension; Etiology; Neuroimaging; Depression; Parkinson's disease; Stress; Sinus; Methodology; Diabetes mellitus; Neurodegenerative diseases; Mental disorders; Movement disorders; sympathetic nerves; Scanning; Chronic effects; Norepinephrine; Atrophy; Radioactivity; Cardiovascular diseases; Heart diseases; Neuropathy ER - TY - JOUR T1 - Pharmacokinetics and Safety of Intravenous Voriconazole in Children after Single- or Multiple-Dose Administration AN - 19947037; 5917792 AB - We conducted a multicenter study of the safety, tolerability, and plasma pharmacokinetics of the parenteral formulation of voriconazole in immunocompromised pediatric patients (2 to 11 years old). Single doses of 3 or 4 mg/kg of body weight were administered to six and five children, respectively. In the multiple-dose study, 28 patients received loading doses of 6 mg/kg every 12 h on day 1, followed by 3 mg/kg every 12 h on day 2 to day 4 and 4 mg/kg every 12 h on day 4 to day 8. Standard population pharmacokinetic approaches and generalized additive modeling were used to construct the structural pharmacokinetic and covariate models used in this analysis. In contrast to that in adult healthy volunteers, elimination of voriconazole was linear in children following doses of 3 and 4 mg/kg every 12 h. Body weight was more influential than age in accounting for the observed variability in voriconazole pharmacokinetics. Elimination capacity correlated with the CYP2C19 genotype. Exposures were similar at 4 mg/kg every 12 h in children (median area under the concentration-time curve (AUC), 14,227 ng super(.) h/ml) and 3 mg/kg in adults (median AUC, 13,855 ng super(.) h/ml). Visual disturbances occurred in 5 (12.8%) of the 39 patients and were the only drug-related adverse events that occurred more than once. No withdrawals from the study were related to voriconazole. We conclude that pediatric patients have a higher capacity for elimination of voriconazole per kilogram of body weight than do adult healthy volunteers and that dosages of 4 mg/kg may be required in children to achieve exposures consistent with those in adults following dosages of 3 mg/kg. JF - Antimicrobial Agents & Chemotherapy AU - Walsh, T J AU - Karlsson, MO AU - Driscoll, T AU - Arguedas, A G AU - Adamson, P AU - Saez-Llorens, X AU - Vora, A J AU - Arrieta, A C AU - Blumer, J AU - Lutsar, I AU - Milligan, P AU - Wood, N AD - Pediatric Oncology Branch, National Cancer Institute, Bldg. 10, Rm. 13N240, Bethesda, MD 20892, walsht@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 2166 EP - 2172 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 48 IS - 6 SN - 0066-4804, 0066-4804 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Intravenous administration KW - Age KW - Body weight KW - Pediatrics KW - Voriconazole KW - Genotypes KW - Children KW - Pharmacokinetics KW - Models KW - A 01340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19947037?accountid=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=Pharmacokinetics+and+Safety+of+Intravenous+Voriconazole+in+Children+after+Single-+or+Multiple-Dose+Administration&rft.au=Walsh%2C+T+J%3BKarlsson%2C+MO%3BDriscoll%2C+T%3BArguedas%2C+A+G%3BAdamson%2C+P%3BSaez-Llorens%2C+X%3BVora%2C+A+J%3BArrieta%2C+A+C%3BBlumer%2C+J%3BLutsar%2C+I%3BMilligan%2C+P%3BWood%2C+N&rft.aulast=Walsh&rft.aufirst=T&rft.date=2004-06-01&rft.volume=48&rft.issue=6&rft.spage=2166&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/10.1128%2FAAC.48.6.2166-2172.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-06-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Age; Intravenous administration; Body weight; Pediatrics; Voriconazole; Genotypes; Children; Pharmacokinetics; Models DO - http://dx.doi.org/10.1128/AAC.48.6.2166-2172.2004 ER - TY - JOUR T1 - Novel Repression of the Glucocorticoid Receptor by Anthrax Lethal Toxin AN - 19401723; 5964272 AB - Death from anthrax has been reported to occur from systemic shock. The lethal toxin (LeTx) is the major effector of anthrax mortality. Although the mechanism of entry of this toxin into cells is well understood, its actions once inside the cell are not as well understood. LeTx is known to cleave and inactivate MAPKKs. We have recently shown that LeTx represses the glucocorticoid receptor (GR) both in vitro and in vivo. This repression is partial and specific, repressing the glucocorticoid, progesterone, and estrogen receptor alpha , but not the mineralocorticoid or estrogen receptor beta . This toxin does not affect GR ligand or DNA binding, and we have suggested that it may function by removing/inactivating one or more of the many cofactors involved in nuclear hormone receptor signaling. Although the precise involvement of this nuclear hormone receptor repression in LeTx toxicity is unknown, examples of blunted HPA axis and glucocorticoid signaling in numerous autoimmune/inflammatory diseases suggest that such repression of critically important receptors could have deleterious effects on health. JF - Annals of the New York Academy of Sciences AU - Webster, Jeanette I AU - Moayeri, Mahtab AU - Sternberg, Esther M AD - Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, and National Institute of Autoimmune and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 9 EP - 23 PB - The New York Academy of Sciences VL - 1024 SN - 0077-8923, 0077-8923 KW - Toxicology Abstracts; Immunology Abstracts KW - Mortality KW - Anthrax lethal toxin KW - Progesterone KW - Nuclear receptors KW - Toxicity KW - Hypothalamic-pituitary-adrenal axis KW - Glucocorticoids KW - Corticoids KW - Cofactors KW - Shock KW - Inflammatory diseases KW - Glucocorticoid receptors KW - DNA KW - Anthrax KW - Estrogen receptors KW - Signal transduction KW - X 24370:Natural Toxins KW - F 06935:Development, Aging & Organ Systems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19401723?accountid=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=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Novel+Repression+of+the+Glucocorticoid+Receptor+by+Anthrax+Lethal+Toxin&rft.au=Webster%2C+Jeanette+I%3BMoayeri%2C+Mahtab%3BSternberg%2C+Esther+M&rft.aulast=Webster&rft.aufirst=Jeanette&rft.date=2004-06-01&rft.volume=1024&rft.issue=&rft.spage=9&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 revised - 2007-04-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Anthrax lethal toxin; Mortality; Progesterone; Nuclear receptors; Toxicity; Hypothalamic-pituitary-adrenal axis; Glucocorticoids; Corticoids; Cofactors; Glucocorticoid receptors; Inflammatory diseases; Shock; DNA; Anthrax; Estrogen receptors; Signal transduction ER - TY - JOUR T1 - An apoptosis differentiation programme in human polymorphonuciear leucocytes AN - 19383692; 7151553 AB - Human PMNs (polymorphonuciear leucocytes or neutrophils) are essential to the innate immune response against bacterial pathogens and are a key part of the acute inflammatory response. Although progress has been made, the molecular basis for termination of inflammation during bacterial infection in humans is largely undefined. To that end, we used genomics strategies to gain new insight into processes that facilitate resolution of neutrophil-mediated inflammation and bacterial infection. On the basis of a series of recent studies, we propose that global changes in PMN gene expression after phagocytosis comprise an apoptosis differentiation programme, which represents the final stage of transcription-regulated PMN maturation. Our studies indicate that the apoptosis differentiation programme regulates multiple post-phagocytic processes in human neutrophils, such as cell fate and proinflammatory activity, and is modulated by PMN-derived reactive oxygen species. Collectively, these studies establish a global model of host cell-pathogen interaction, which provides fundamental insight into the resolution of infection in humans. JF - Biochemical Society Transactions AU - Kobayashi, S D AU - DeLeo AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, fdeleo@niaid.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 474 EP - 476 VL - 32 IS - 3 SN - 0300-5127, 0300-5127 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Apoptosis KW - Leukocytes (neutrophilic) KW - Transcription KW - pmn gene KW - Pathogens KW - Infection KW - Inflammation KW - Differentiation KW - Reactive oxygen species KW - Immune response KW - Cell fate KW - genomics KW - Phagocytosis KW - J 02350:Immunology KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19383692?accountid=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=Biochemical+Society+Transactions&rft.atitle=An+apoptosis+differentiation+programme+in+human+polymorphonuciear+leucocytes&rft.au=Kobayashi%2C+S+D%3BDeLeo&rft.aulast=Kobayashi&rft.aufirst=S&rft.date=2004-06-01&rft.volume=32&rft.issue=3&rft.spage=474&rft.isbn=&rft.btitle=&rft.title=Biochemical+Society+Transactions&rft.issn=03005127&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Apoptosis; Leukocytes (neutrophilic); Transcription; pmn gene; Pathogens; Infection; Inflammation; Differentiation; Reactive oxygen species; genomics; Cell fate; Immune response; Phagocytosis ER - TY - JOUR T1 - Job strain and plasminogen activator inhibitor-1: results from the Swedish WOLF study AN - 18043064; 6018531 AB - Objectives. To investigate the association between job strain and elevated levels of plasminogen activator inhibitor-1. Methods. A cross-sectional study was carried out, comprising 1,954 actively working men and women between the ages of 19-64 years. Data were collected by questionnaire, clinical examination and blood samples. Results. Elevated plasminogen activator inhibitor-1 levels were more commonly noted in women exposed to job strain than in unexposed women (odds ratio 1.33; 95% confidence interval 1.06-1.65). This association remained after we had adjusted for factors related to behaviour and general health, but became close to 1 after we had adjusted for factors related to the metabolic syndrome. For men, no association between job strain and elevated levels of plasminogen activator inhibitor-1 was observed (odds ratio 0.94; 95% confidence interval 0.71-1.26). Conclusions. Women exposed to job strain were more inclined to respond with increased plasminogen activator inhibitor-1 than men. In this first study on the association between job strain and plasminogen activator inhibitor-1 in both men and women, we observed such a relationship among women but not among men. The data support the notion that job strain might affect the risk of coronary heart disease by influencing an important cardiovascular system: the metabolic syndrome. JF - International Archives of Occupational and Environmental Health AU - Brostedt, E M AU - de Faire, U AU - Westerholm, P AU - Knutsson, A AU - Alfredsson, L AD - Section on Developmental Genetic Epidemiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, 15 K North Drive, MSC 2670, MD 20892-2670, Bethesda, Maryland, USA, ericabrostedt@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 341 EP - 344 PB - Springer-Verlag VL - 77 IS - 5 SN - 0340-0131, 0340-0131 KW - Health & Safety Science Abstracts KW - Bioindicators KW - Stress KW - Gender KW - Cardiovascular diseases KW - Metabolism KW - Occupational health KW - Sweden KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18043064?accountid=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=International+Archives+of+Occupational+and+Environmental+Health&rft.atitle=Job+strain+and+plasminogen+activator+inhibitor-1%3A+results+from+the+Swedish+WOLF+study&rft.au=Brostedt%2C+E+M%3Bde+Faire%2C+U%3BWesterholm%2C+P%3BKnutsson%2C+A%3BAlfredsson%2C+L&rft.aulast=Brostedt&rft.aufirst=E&rft.date=2004-06-01&rft.volume=77&rft.issue=5&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=International+Archives+of+Occupational+and+Environmental+Health&rft.issn=03400131&rft_id=info:doi/10.1007%2Fs00420-004-0514-5 L2 - http://link.springer.de/link/service/journals/00420/bibs/4077005/40770341.htm LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sweden; Occupational health; Stress; Cardiovascular diseases; Gender; Metabolism; Bioindicators DO - http://dx.doi.org/10.1007/s00420-004-0514-5 ER - TY - JOUR T1 - Cytotoxic Activity of the Recombinant Anti-mesothelin Immunotoxin, SS1(dsFv)PE38, Towards Tumor Cell Lines Established from Ascites of Patients with Peritoneal Mesotheliomas AN - 18023345; 5981201 AB - Mesothelin, a cell surface glycoprotein, is an attractive candidate for targeted therapy given its overexpression, as detected by immunohistochemistry, in mesotheliomas. The goal of this study was to evaluate mesothelin expression in fresh tumor cells obtained from ascites of patients with peritoneal mesothelioma, as well as to determine the sensitivity of these cells to an immunotoxin targeting mesothelin. Tumor cells were evaluated for mesothelin expression by flow cytometry using the murine anti-mesothelin monoclonal antibody K1. The sensitivity of these tumor cells to SS1(dsFv)PE38, an immunotoxin consisting of the anti-mesothelin Fv linked to a mutated Pseudomonas exotoxin, was evaluated using a cell proliferation assay. Of the 7 tumor cell lines established from ascites of 12 patients with peritoneal mesothelioma, 6 expressed mesothelin while one cell line did not. Cell lines that expressed mesothelin were very sensitive to SS1(dsFv)PE38 with IC sub(50)s ranging between 0.08-3.9 ng/ml, while the cell line that was mesothelin-negative was resistant to SS1(dsFv)PE38. High expression of mesothelin is seen on tumor cells of patients with peritoneal mesothelioma and correlates with sensitivity to SS1(dsFv)PE38. JF - Anticancer Research AU - Li, Q AU - Verschraegen, C F AU - Mendoza, J AU - Hassan, R AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Rm. 5116, Bethesda, MD 20892-4264, USA, hassanr@mail.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 1327 EP - 1336 VL - 24 IS - 3A SN - 0250-7005, 0250-7005 KW - mesothelin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Flow cytometry KW - Monoclonal antibodies KW - mesothelioma KW - Immunotoxins KW - Pharmacogenetics KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18023345?accountid=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=Anticancer+Research&rft.atitle=Cytotoxic+Activity+of+the+Recombinant+Anti-mesothelin+Immunotoxin%2C+SS1%28dsFv%29PE38%2C+Towards+Tumor+Cell+Lines+Established+from+Ascites+of+Patients+with+Peritoneal+Mesotheliomas&rft.au=Li%2C+Q%3BVerschraegen%2C+C+F%3BMendoza%2C+J%3BHassan%2C+R&rft.aulast=Li&rft.aufirst=Q&rft.date=2004-06-01&rft.volume=24&rft.issue=3A&rft.spage=1327&rft.isbn=&rft.btitle=&rft.title=Anticancer+Research&rft.issn=02507005&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 - Pharmacogenetics; Immunotoxins; mesothelioma; Flow cytometry; Monoclonal antibodies ER - TY - JOUR T1 - Exploration of Moraxella catarrhalis outer membrane proteins, CD and UspA, as new carriers for lipooligosaccharide-based conjugates AN - 18014212; 5957541 AB - Moraxella catarrhalis outer membrane proteins, CD and ubiquitous surface protein A (UspA), were used as carriers for M. catarrhalis detoxified lipooligosaccharide (dLOS)-based conjugates. Our study was designed to investigate the feasibility of CD and UspA as protein carriers for dLOS-based conjugates and their possible synergic effects on protection from both anti-LOS and anti-CD or anti-UspA antibody responses. Female Balb/c mice were immunized subcutaneously three times with dLOS-CD or dLOS-UspA conjugate in Ribi adjuvant. Antisera elicited by the conjugates showed high titers of specific anti-LOS antibodies with complement-dependent bactericidal activity towards M. catarrhalis strain 25238. In a mouse aerosol challenge model, mice immunized with both conjugates showed a significant enhancement of the clearance of strain 25238 from lungs as compared with the control mice. Although both conjugates elicited reduced (relative to unconjugated CD or UspA) but significant levels of anti-CD or UspA antibodies, they did not show synergetic effects with anti-LOS antibodies on the bactericidal activity or the pulmonary bacterial clearance. Nevertheless, CD and UspA are safe and effective new carriers for dLOS-based or other potential carbohydrate-based conjugate vaccines to help thymus-independent carbohydrate antigens for production of anti-carbohydrate antibodies against target pathogens. JF - FEMS Immunology and Medical Microbiology AU - Hu, W AU - Berry, J AU - Chen, J AU - Gu, X AD - Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 109 EP - 115 PB - Federation of European Microbiological Societies VL - 41 IS - 2 SN - 0928-8244, 0928-8244 KW - UspA protein KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Outer membranes KW - Moraxella catarrhalis KW - Vaccines KW - Antibody response KW - Lipooligosaccharides KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18014212?accountid=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=FEMS+Immunology+and+Medical+Microbiology&rft.atitle=Exploration+of+Moraxella+catarrhalis+outer+membrane+proteins%2C+CD+and+UspA%2C+as+new+carriers+for+lipooligosaccharide-based+conjugates&rft.au=Hu%2C+W%3BBerry%2C+J%3BChen%2C+J%3BGu%2C+X&rft.aulast=Hu&rft.aufirst=W&rft.date=2004-06-01&rft.volume=41&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=FEMS+Immunology+and+Medical+Microbiology&rft.issn=09288244&rft_id=info:doi/10.1016%2Fj.femsim.2004.02.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Moraxella catarrhalis; Outer membranes; Lipooligosaccharides; Antibody response; Vaccines DO - http://dx.doi.org/10.1016/j.femsim.2004.02.001 ER - TY - JOUR T1 - Variation in lipid A structure in the pathogenic yersiniae AN - 17999510; 5947319 AB - Important pathogens in the genus Yersinia include the plague bacillus Yersinia pestis and two enteropathogenic species, Yersinia pseudotuberculosis and Yersinia enterocolitica. A shift in growth temperature induced changes in the number and type of acyl groups on the lipid A of all three species. After growth at 37 degree C, Y. pestis lipopolysaccharide (LPS) contained the tetra-acylated lipid IV sub(A) and smaller amounts of lipid IV sub(A) modified with C10 or C12 acyl groups, Y. pseudotuberculosis contained the same forms as part of a more heterogeneous population in which lipid IV sub(A) modified with C16:0 predominated, and Y. enterocolitica produced a unique tetra-acylated lipid A. When grown at 21 degree C, however, the three yersiniae synthesized LPS containing predominantly hexa-acylated lipid A. This more complex lipid A stimulated human monocytes to secrete tumour necrosis factor- alpha , whereas the lipid A synthesized by the three species at 37 degree C did not. The Y. pestis phoP gene was required for aminoarabinose modification of lipid A, but not for the temperature-dependent acylation changes. The results suggest that the production of a less immunostimulatory form of LPS upon entry into the mammalian host is a conserved pathogenesis mechanism in the genus Yersinia, and that species-specific lipid A forms may be important for life cycle and pathogenicity differences. JF - Molecular Microbiology AU - Rebeil, R AU - Ernst, R K AU - Gowen, B B AU - Miller, SI AU - Hinnebusch, B J AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA., jhinnebusch@niaid.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 1363 EP - 1373 PB - Blackwell Science Ltd VL - 52 IS - 5 SN - 0950-382X, 0950-382X KW - man KW - phoP gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Pathogenicity KW - Yersinia enterocolitica KW - Yersinia pestis KW - Yersinia pseudotuberculosis KW - Lipopolysaccharides KW - Life cycle KW - Lipid A KW - Tumor necrosis factor- alpha KW - Monocytes KW - J 02731:Lipids KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17999510?accountid=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=Variation+in+lipid+A+structure+in+the+pathogenic+yersiniae&rft.au=Rebeil%2C+R%3BErnst%2C+R+K%3BGowen%2C+B+B%3BMiller%2C+SI%3BHinnebusch%2C+B+J&rft.aulast=Rebeil&rft.aufirst=R&rft.date=2004-06-01&rft.volume=52&rft.issue=5&rft.spage=1363&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04059.x LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Temperature effects; Pathogenicity; Life cycle; Lipopolysaccharides; phoP gene; Lipid A; Monocytes; Tumor necrosis factor- alpha; Yersinia pseudotuberculosis; Yersinia pestis; Yersinia enterocolitica DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04059.x ER - TY - JOUR T1 - Characterization of the Human Ig Heavy Chain Antigen Binding Complementarity Determining Region 3 Using a Newly Developed Software Algorithm, JOINSOLVER AN - 17991312; 5925732 AB - We analyzed 77 nonproductive and 574 productive human V sub(H)DJ sub(H) rearrangements with a newly developed program, JOINSOLVER. In the productive repertoire, the H chain complementarity determining region 3 (CDR3 sub(H)) was significantly shorter (46.7 plus or minus 0.5 nucleotides) than in the nonproductive repertoire (53.8 plus or minus 1.9 nucleotides) because of the tendency to select rearrangements with less TdT activity and shorter D segments. Using criteria established by Monte Carlo simulations, D segments could be identified in 71.4% of nonproductive and 64.4% of productive rearrangements, with a mean of 17.6 plus or minus 0.7 and 14.6 plus or minus 0.2 retained germline nucleotides, respectively. Eight of 27 D segments were used more frequently than expected in the nonproductive repertoire, whereas 3 D segments were positively selected and 3 were negatively selected, indicating that both molecular mechanisms and selection biased the D segment usage. There was no bias for D segment reading frame (RF) use in the nonproductive repertoire, whereas negative selection of the RFs encoding stop codons and positive selection of RF2 that frequently encodes hydrophilic amino acids were noted in the productive repertoire. Except for serine, there was no consistent selection or expression of hydrophilic amino acids. A bias toward the pairing of 5' D segments with 3' J sub(H) segments was observed in the nonproductive but not the productive repertoire, whereas V sub(H) usage was random. Rearrangements using inverted D segments, DIR family segments, chromosome 15 D segments and multiple D segments were found infrequently. Analysis of the human CDR3 sub(H) with JOINSOLVER has provided comprehensive information on the influences that shape this important Ag binding region of V sub(H) chains. JF - Journal of Immunology AU - Souto-Carneiro, MMargarida AU - Longo, Nancy S AU - Russ, Daniel E AU - Sun, Hong-wei AU - Lipsky, Peter E AD - Repertoire Analysis Group, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Division of Computational Bioscience, Center for Information Technology, and Biodata Mining and Discovery Section, Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 Y1 - 2004/06/01/ PY - 2004 DA - 2004 Jun 01 SP - 6790 EP - 6802 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 172 IS - 11 SN - 0022-1767, 0022-1767 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Immunology Abstracts KW - complementarity-determining region 3 KW - V(D)J recombination KW - Algorithms KW - Antigen-antibody interactions KW - DNA nucleotidylexotransferase KW - F 06074:Antigen-antibody interactions KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17991312?accountid=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=Characterization+of+the+Human+Ig+Heavy+Chain+Antigen+Binding+Complementarity+Determining+Region+3+Using+a+Newly+Developed+Software+Algorithm%2C+JOINSOLVER&rft.au=Souto-Carneiro%2C+MMargarida%3BLongo%2C+Nancy+S%3BRuss%2C+Daniel+E%3BSun%2C+Hong-wei%3BLipsky%2C+Peter+E&rft.aulast=Souto-Carneiro&rft.aufirst=MMargarida&rft.date=2004-06-01&rft.volume=172&rft.issue=11&rft.spage=6790&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - V(D)J recombination; Algorithms; DNA nucleotidylexotransferase; complementarity-determining region 3; Antigen-antibody interactions ER - TY - JOUR T1 - An ELISA for putative neutralizing antibodies to hepatitis E virus detects antibodies to genotypes 1, 2, 3, and 4 AN - 17982263; 5929139 AB - Two monoclonal antibodies that neutralize hepatitis E virus (HEV) were used to identify a subregion of ORF2 capsid protein spanning amino acids 459-607 as the shortest peptide to form the corresponding neutralization epitopes. An enzyme-linked immunosorbent assay (ELISA) based on a purified recombinant protein covering amino acids 458-607 in ORF2 of the Sar-55 strain (genotype 1) efficiently detected anti-HEV in non-human primates which had been experimentally infected with the four known mammalian genotypes of HEV, respectively. However, anti-HEV in these animals did not react with a shorter ORF2 peptide spanning amino acids 475-607. The ELISA was highly specific and sensitive when human or non-human primate sera were tested in parallel with a previously established ELISA based on amino acids 112-607 in ORF2. The antibody titer to peptides 458-607 in two ORF2-vaccinated rhesus monkeys which had different HEV challenge outcomes differed at the time of challenge. Since the ELISA appeared to be specific for neutralizing antibodies against HEV, it should be especially useful for quantifying the humoral immune response in hepatitis E vaccine trials. JF - Vaccine AU - Zhou, Y-H AU - Purcell, R H AU - Emerson, SU AD - Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive MSC-8009, Bethesda, MD 20892, USA, semerson@niaid.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 2578 EP - 2585 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 22 IS - 20 SN - 0264-410X, 0264-410X KW - Rhesus monkey KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Genotypes KW - Macaca mulatta KW - Immune response (humoral) KW - Enzyme-linked immunosorbent assay KW - Monoclonal antibodies KW - Hepatitis E virus KW - Hepatitis KW - Antibodies KW - Capsid protein KW - W3 33240:Immunology KW - F 06720:ELISA KW - V 22091:Immunological techniques & reagents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17982263?accountid=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=Vaccine&rft.atitle=An+ELISA+for+putative+neutralizing+antibodies+to+hepatitis+E+virus+detects+antibodies+to+genotypes+1%2C+2%2C+3%2C+and+4&rft.au=Zhou%2C+Y-H%3BPurcell%2C+R+H%3BEmerson%2C+SU&rft.aulast=Zhou&rft.aufirst=Y-H&rft.date=2004-06-01&rft.volume=22&rft.issue=20&rft.spage=2578&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2003.12.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hepatitis E virus; Macaca mulatta; Enzyme-linked immunosorbent assay; Genotypes; Hepatitis; Monoclonal antibodies; Antibodies; Capsid protein; Immune response (humoral) DO - http://dx.doi.org/10.1016/j.vaccine.2003.12.017 ER - TY - JOUR T1 - The Essential Nature of the Ubiquitous 26-Kilobase Circular Replicon of Borrelia burgdorferi AN - 17979369; 5917760 AB - The genome of the type strain (B31) of Borrelia burgdorferi, the causative agent of Lyme disease, is composed of 12 linear and 9 circular plasmids and a linear chromosome. Plasmid content can vary among strains, but one 26-kb circular plasmid (cp26) is always present. The ubiquitous nature of cp26 suggests that it provides functions required for bacterial viability. We tested this hypothesis by attempting to selectively displace cp26 with an incompatible but replication-proficient vector, pBSV26. While pBSV26 transformants contained this incompatible vector, the vector coexisted with cp26, which is consistent with the hypothesis that cp26 carries essential genes. Several cp26 genes with ascribed or predicted functions may be essential. These include the Jr29 gene, which has sequence homology to a gene encoding a glucose-specific phosphotransferase system component, and the resT gene, which encodes a telomere resolvase involved in resolution of the replicated telomeres of the linear chromosome and plasmids. The Jr29 gene was successfully inactivated by allelic exchange, but attempted inactivation of resT resulted in merodiploid transformants, suggesting that resT is required for B. burgdorferi growth. To determine if resT is the only cp26 gene essential for growth, we introduced resT into B. burgdorferi on pBSV26. This did not result in displacement of cp26, suggesting that additional cp26 genes encode vital functions. We concluded that B. burgdorferi plasmid cp26 encodes functions critical for survival and thus shares some features with the chromosome. JF - Journal of Bacteriology AU - Byram, R AU - Stewart, P E AU - Rosa, P AD - 903 S. 4th St., Hamilton, MT 59840, prosa@niaid.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 3561 EP - 3569 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 11 SN - 0021-9193, 0021-9193 KW - Jr29 gene KW - cp26 gene KW - phosphotransferase system KW - resT gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Genomes KW - Telomeres KW - Chromosomes KW - Replicons KW - CP26 protein KW - Borrelia burgdorferi KW - Glucose KW - Cloning vectors KW - Vectors KW - Plasmids KW - Lyme disease KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17979369?accountid=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=The+Essential+Nature+of+the+Ubiquitous+26-Kilobase+Circular+Replicon+of+Borrelia+burgdorferi&rft.au=Byram%2C+R%3BStewart%2C+P+E%3BRosa%2C+P&rft.aulast=Byram&rft.aufirst=R&rft.date=2004-06-01&rft.volume=186&rft.issue=11&rft.spage=3561&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.186.11.3561-3569.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Genomes; Telomeres; Chromosomes; CP26 protein; Replicons; Cloning vectors; Glucose; Vectors; Plasmids; Lyme disease; Borrelia burgdorferi DO - http://dx.doi.org/10.1128/JB.186.11.3561-3569.2004 ER - TY - JOUR T1 - Bacterial signal transduction network in a genomic perspective AN - 17974140; 5920799 AB - Bacterial signalling network includes an array of numerous interacting components that monitor environmental and intracellular parameters and effect cellular response to changes in these parameters. The complexity of bacterial signalling systems makes comparative genome analysis a particularly valuable tool for their studies. Comparative studies revealed certain general trends in the organization of diverse signalling systems. These include (i) modular structure of signalling proteins; (ii) common organization of signalling components with the flow of information from N-terminal sensory domains to the C-terminal transmitter or signal output domains (N-to-C flow); (iii) use of common conserved sensory domains by different membrane receptors; (iv) ability of some organisms to respond to one environmental signal by activating several regulatory circuits; (v) abundance of intracellular signalling proteins, typically consisting of a PAS or GAF sensor domains and various output domains; (vi) importance of secondary messengers, cAMP and cyclic diguanylate; and (vii) crosstalk between components of different signalling pathways. Experimental characterization of the novel domains and domain combinations would be needed for achieving a better understanding of the mechanisms of signalling response and the intracellular hierarchy of different signalling pathways. JF - Environmental Microbiology AU - Galperin, MY AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA., galperin@ncbi.nlm.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 552 EP - 567 PB - Blackwell Science Ltd VL - 6 IS - 6 SN - 1462-2912, 1462-2912 KW - secondary messengers KW - Microbiology Abstracts B: Bacteriology KW - Membranes KW - Intracellular KW - Genetic analysis KW - Receptors KW - Pathway KW - Domains KW - Signal transduction KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17974140?accountid=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=Environmental+Microbiology&rft.atitle=Bacterial+signal+transduction+network+in+a+genomic+perspective&rft.au=Galperin%2C+MY&rft.aulast=Galperin&rft.aufirst=MY&rft.date=2004-06-01&rft.volume=6&rft.issue=6&rft.spage=552&rft.isbn=&rft.btitle=&rft.title=Environmental+Microbiology&rft.issn=14622912&rft_id=info:doi/10.1111%2Fj.1462-2920.2004.00633.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Membranes; Intracellular; Genetic analysis; Receptors; Pathway; Domains; Signal transduction DO - http://dx.doi.org/10.1111/j.1462-2920.2004.00633.x ER - TY - JOUR T1 - Predominant Outer Membrane Antigens of Bartonella henselae AN - 17972087; 5917628 AB - A hallmark of Bartonella henselae is persistent bacteremia in cats despite the presence of a vigorous host immune response. To understand better the long-term survival of B. henselae in cats, we examined the feline humoral immune response to B. henselae outer membrane (OM) proteins in naturally and experimentally infected cats. Initially, a panel of sera (n = 42) collected throughout North America from naturally infected cats was used to probe B. henselae total membranes to detect commonly recognized antigens. Twelve antigens reacted with sera from at least 85% of cats, and five were recognized by sera from all cats. To localize these antigens further, OMs were purified on discontinuous sucrose density step gradients. Each membrane fraction (OM, hybrid or inner membrane (IM)) contained less than 1% of the total malate dehydrogenase activity (soluble marker), indicating very little contamination by cytoplasmic proteins. FtsI, an integral IM cell division protein, was used to identify the low-density fraction ( rho = 1.13 g/cm) as putative IM (<5% of the total FtsI localized to the high-density fraction) while lipopolysaccharide (LPS) and Pap31, a homolog of the Bartonella quintana heme-binding protein A (HbpA), defined the high-density fraction ( rho = 1.20 g/cm) as putative OM. Additionally, little evidence of cross-contamination between the IM and OM was evident by two-dimensional gel electrophoresis. When purified OMs were probed with feline sera, antigenic proteins profiles were very similar to those observed with total membranes, indicating that many, but not all, of the immunoreactive proteins detected in the initial immunoblots were OM components. Interestingly, two-dimensional immunoblots indicated that B. henselae LPS and members of the Hbp family of proteins did not appear to stimulate an humoral response in any infected cats. Seven proteins were recognized by at least 70% of sera tested, but only three were recognized by all sera. Nanospray-tandem mass spectrometry was used to identify OM components, including the immunodominant OM proteins. Recognition of the nonimmunogenic nature of the major OM components, such as LPS, and identification of the predominant immunogens should elucidate the mechanisms by which B. henselae establishes persistent bacteremic infections within cats. Additionally, the common antigens may serve as potential feline vaccine candidates to eliminate the pathogen from its animal reservoir. JF - Infection and Immunity AU - Chenoweth, M R AU - Greene, CE AU - Krause, D C AU - Gherardini, F C AD - Rocky Mountain Laboratories, 903 S. 4th St., Hamilton, MT 59840, FGHERARDINI@NIAID.NIH.GOV Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 3097 EP - 3105 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 6 SN - 0019-9567, 0019-9567 KW - cats KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - North America KW - Outer membranes KW - Bartonella henselae KW - Vaccines KW - Membrane proteins KW - Antibody response KW - Immune response (humoral) KW - J 02832:Antigenic properties and virulence KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17972087?accountid=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=Predominant+Outer+Membrane+Antigens+of+Bartonella+henselae&rft.au=Chenoweth%2C+M+R%3BGreene%2C+CE%3BKrause%2C+D+C%3BGherardini%2C+F+C&rft.aulast=Chenoweth&rft.aufirst=M&rft.date=2004-06-01&rft.volume=72&rft.issue=6&rft.spage=3097&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.72.6.3097-3105.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Outer membranes; Antibody response; Membrane proteins; Vaccines; Immune response (humoral); Bartonella henselae; North America DO - http://dx.doi.org/10.1128/IAI.72.6.3097-3105.2004 ER - TY - JOUR T1 - Inhalation toxicology and carcinogenesis studies of propylene glycol mono- t-butyl ether in rats and mice AN - 17947973; 5903758 AB - Propylene glycol mono-t-butyl ether (PGMBE) is used as a solvent in a variety of commercial applications. Male and female F344/N rats and B6C3F sub(1) mice were exposed to PGMBE by whole-body inhalation for 2 or 14 weeks (0, 75, 150, 300, 600, or 1200 ppm) or 2 years (0, 75, 300, or 1200 ppm); male NBR rats were exposed for 2 weeks. The kidney and the liver were targets of PGMBE toxicity in rats. Renal lesions suggestive of alpha sub(2u)-globulin nephropathy were observed in male F344/N, in the 2 and 14-week studies, no kidney lesions were seen in NBR rats. In the 2-year study, male rats displayed exposure-related nonneoplastic lesions in the kidney, and may have shown marginal increases in tubular neoplasms. In the liver, the incidences of hepatocellular adenomas occurred with a positive trend in male rats, and may have been related to PGMBE exposure. In mice of both sexes, the major target of PGMBE toxicity was the liver. In the 2-week study, liver weights and in the 14-week study, liver weights and the incidences of centrilobular hypertrophy were increased. In the 2-year study, the incidences of exposure-related hepatocellular adenoma, adenoma or carcinoma combined, and hepatoblastoma occurred with a positive trend, and were significantly increased in 1200 ppm groups. In summary, exposure to PGMBE resulted in nonneoplastic lesions of the kidney characteristic of alpha sub(2u)- globulin nephropathy, and may have increased renal tubular neoplasms in male rats. Exposure to PGMBE also produced increases in hepatic tumors in male and female mice. JF - Toxicology AU - Doi, A M AU - Roycroft, J H AU - Herbert, R A AU - Haseman, J K AU - Hailey, J R AU - Chou, B J AU - Dill, JA AU - Grumbein, S L AU - Miller, R A AU - Renne, R A AU - Bucher, J R AD - National Institute of Environmental Health Sciences, 79 Alexander Dr. Mail Drop EC-34, Research Triangle Park, NC 27709, USA, doi@niehs.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 1 EP - 22 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 199 IS - 1 SN - 0300-483X, 0300-483X KW - propylene glycol mono-butyl ether KW - rats KW - mice KW - Toxicology Abstracts KW - Inhalation KW - Propylene glycol KW - Carcinogenesis KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17947973?accountid=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&rft.atitle=Inhalation+toxicology+and+carcinogenesis+studies+of+propylene+glycol+mono-+t-butyl+ether+in+rats+and+mice&rft.au=Doi%2C+A+M%3BRoycroft%2C+J+H%3BHerbert%2C+R+A%3BHaseman%2C+J+K%3BHailey%2C+J+R%3BChou%2C+B+J%3BDill%2C+JA%3BGrumbein%2C+S+L%3BMiller%2C+R+A%3BRenne%2C+R+A%3BBucher%2C+J+R&rft.aulast=Doi&rft.aufirst=A&rft.date=2004-06-01&rft.volume=199&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2003.12.020 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenesis; Inhalation; Propylene glycol DO - http://dx.doi.org/10.1016/j.tox.2003.12.020 ER - TY - JOUR T1 - A novel cell-free protein synthesis system AN - 17715382; 5918624 AB - An efficient cell-free protein synthesis system has been developed using a novel energy-regenerating source. Using the new energy source, 3- phosphoglycerate (3-PGA), protein synthesis continues beyond 2 h. In contrast, the reaction rate slowed down considerably within 30-45 min using a conventional energy source, phosphoenol pyruvate (PEP) under identical reaction conditions. This improvement results in the production of twice the amount of protein obtained with PEP as an energy source. We have also shown that Gam protein of phage lambda, an inhibitor of RecBCD (ExoV), protects linear PCR DNA templates from degradation in vitro. Furthermore, addition of purified Gam protein in extracts of Escherichia coli BL21 improves protein synthesis from PCR templates to a level comparable to plasmid DNA template. Therefore, combination of these improvements should be amenable to rapid expression of proteins in a high-throughput manner for proteomics and structural genomics applications. JF - Journal of Biotechnology AU - Sitaraman, K AU - Esposito, D AU - Klarmann, G AU - Le Grice, SF AU - Hartley, J L AU - Chatterjee, D K AD - SAIC-National Cancer Institute at Frederick, 1050 Boyles Street, Building 327, Frederick, MD 21702-1201, USA, chatterjee@ncifcrf.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 257 EP - 263 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 110 IS - 3 SN - 0168-1656, 0168-1656 KW - 3-phosphoglycerate KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - Protein biosynthesis KW - Polymerase chain reaction KW - proteomics KW - genomics KW - phosphoenolpyruvic acid KW - W2 32340:Other peptides, proteins, amino acids KW - W 30965:Miscellaneous, Reviews KW - W4 320:Cell Culture & Batch Fermentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17715382?accountid=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=A+novel+cell-free+protein+synthesis+system&rft.au=Sitaraman%2C+K%3BEsposito%2C+D%3BKlarmann%2C+G%3BLe+Grice%2C+SF%3BHartley%2C+J+L%3BChatterjee%2C+D+K&rft.aulast=Sitaraman&rft.aufirst=K&rft.date=2004-06-01&rft.volume=110&rft.issue=3&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biotechnology&rft.issn=01681656&rft_id=info:doi/10.1016%2Fj.jbiotec.2004.02.014 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Protein biosynthesis; Polymerase chain reaction; genomics; proteomics; phosphoenolpyruvic acid DO - http://dx.doi.org/10.1016/j.jbiotec.2004.02.014 ER - TY - JOUR T1 - beta -Endorphin elevations in the ventral tegmental area regulate the discriminative effects of Delta -9-tetrahydrocannabinol AN - 17591368; 5966492 AB - beta -Endorphin is an endogenous opioid that produces behavioral effects similar to heroin and morphine and is released in the nucleus accumbens by cocaine, amphetamine and ethanol, suggesting a general involvement in the reinforcing effects of abused drugs. Here we show that, in rats, Delta -9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, produces large increases in extracellular levels of beta -endorphin in the ventral tegmental area and lesser increases in the shell of the nucleus accumbens. We then used a two-lever choice THC-discrimination procedure to investigate whether THC-induced changes in endogenous levels of beta -endorphin regulate the discriminative effects of THC. In rats that had learned to discriminate injections of THC from injections of vehicle, the opioid agonist morphine did not produce THC-like discriminative effects but markedly potentiated discrimination of THC. Conversely, the opioid antagonist naloxone reduced the discriminative effects of THC. Bilateral microinjections of beta -endorphin directly into the ventral tegmental area, but not into the shell of the nucleus accumbens, markedly potentiated the discriminative effects of ineffective threshold doses of THC but had no effect when given alone. This potentiation was blocked by naloxone. Together these results indicate that certain psychotropic effects of THC related to drug abuse liability are regulated by THC-induced elevations in extracellular beta -endorphin levels in brain areas involved in opiate reward and reinforcement processes. JF - European Journal of Neuroscience AU - Solinas, M AU - Zangen, A AU - Thiriet, N AU - Goldberg AD - Preclinical Pharmacology Section, Department of Health and Human Services, NIH, NIDA, IRP, Baltimore, MD, 21224, USA, sgoldber@intra.nida.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 3183 EP - 3192 PB - Blackwell Science Ltd VL - 19 IS - 12 SN - 0953-816X, 0953-816X KW - CSA Neurosciences Abstracts; Toxicology Abstracts 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/17591368?accountid=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=European+Journal+of+Neuroscience&rft.atitle=beta+-Endorphin+elevations+in+the+ventral+tegmental+area+regulate+the+discriminative+effects+of+Delta+-9-tetrahydrocannabinol&rft.au=Solinas%2C+M%3BZangen%2C+A%3BThiriet%2C+N%3BGoldberg&rft.aulast=Solinas&rft.aufirst=M&rft.date=2004-06-01&rft.volume=19&rft.issue=12&rft.spage=3183&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Neuroscience&rft.issn=0953816X&rft_id=info:doi/10.1111%2Fj.0953-816X.2004.03420.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-08-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1111/j.0953-816X.2004.03420.x ER - TY - JOUR T1 - Individual thyroid dose estimation for a case-control study of Chernobyl-related thyroid cancer among children of Belarus--part I: super(131)I, short-lived radioiodines ( super(132)I, super(133)I, super(135)I), and short-lived radiotelluriums ( super(131M)Te and super(132)Te) AN - 16175121; 5934781 AB - Large amounts of radioiodines were released into the atmosphere during the accident at the Chernobyl nuclear power plant on 26 April 1986. In order to investigate whether the thyroid cancers observed among children in Belarus could have been caused by radiation exposures from the Chernobyl accident, a team of Belarusian, Russian, and American scientists conducted a case-control study to compare cases and controls according to estimated thyroid dose. The primary purpose of this paper is to present detailed information on the estimated thyroid doses, due to intakes of super(131)I, that were used in the case-control study. The range of the super(131)I thyroid doses among the 107 cases and the 214 controls was found to extend from 0.00002 to 4.3 Gy, with medians of approximately 0.2 Gy for the cases and 0.07 Gy for the controls. In addition, the thyroid doses resulting from the intakes of short-lived radioiodines ( super(132)I, super(133)I, and super(135)I) and radiotelluriums ( super(131m)Te and super(132)Te) were estimated and compared to the doses from super(131)I. The ratios of the estimated thyroid doses from the short-lived radionuclides and from super(131)I for the cases and the controls range from 0.003 to 0.1, with median values of approximately 0.02 for both cases and controls. JF - Health Physics AU - Gavrilin, Y AU - Khrouch, V AU - Shinkarev, S AU - Drozdovitch, V AU - Minenko, V AU - Shemiakina, E AU - Ulanovsky, A AU - Bouville, A AU - Anspaugh, L AU - Voilleque, P AU - Luckyanov, N AD - National Cancer Institute, Radiation Epidemiology Branch, 6120 Executive Blvd, EPS 7094, Bethesda, MD 20822-7391, USA, bouvilla@epndce.nci.nih.gov Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 565 EP - 585 VL - 86 IS - 6 SN - 0017-9078, 0017-9078 KW - dose estimation KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Belarus KW - Ukraine, Chernobyl KW - tellurium KW - Thyroid KW - Children KW - Cancer KW - Nuclear power plants KW - Accidents KW - Radioactive fallout KW - Dose-response effects KW - Radioisotopes KW - Iodine KW - H 8000:Radiation Safety/Electrical Safety KW - X 24210:Radiation & radioactive materials KW - P 8000:RADIATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16175121?accountid=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=Health+Physics&rft.atitle=Individual+thyroid+dose+estimation+for+a+case-control+study+of+Chernobyl-related+thyroid+cancer+among+children+of+Belarus--part+I%3A+super%28131%29I%2C+short-lived+radioiodines+%28+super%28132%29I%2C+super%28133%29I%2C+super%28135%29I%29%2C+and+short-lived+radiotelluriums+%28+super%28131M%29Te+and+super%28132%29Te%29&rft.au=Gavrilin%2C+Y%3BKhrouch%2C+V%3BShinkarev%2C+S%3BDrozdovitch%2C+V%3BMinenko%2C+V%3BShemiakina%2C+E%3BUlanovsky%2C+A%3BBouville%2C+A%3BAnspaugh%2C+L%3BVoilleque%2C+P%3BLuckyanov%2C+N&rft.aulast=Gavrilin&rft.aufirst=Y&rft.date=2004-06-01&rft.volume=86&rft.issue=6&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-07-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - tellurium; Thyroid; Radioisotopes; Iodine; Children; Cancer; Nuclear power plants; Accidents; Radioactive fallout; Dose-response effects; Belarus; Ukraine, Chernobyl ER - TY - JOUR T1 - Requirement for the Rac GTPase in Chlamydia trachomatis Invasion of Non-phagocytic Cells AN - 1285087043; 16613018 AB - Chlamydiae are gram-negative obligate intracellular pathogens to which access to an intracellular environment is paramount to their survival and replication. To this end, chlamydiae have evolved extremely efficient means of invading nonphagocytic cells. To elucidate the host cell machinery utilized by Chlamydia trachomatis in invasion, we examined the roles of the Rho GTPase family members in the internalization of chlamydial elementary bodies. Upon binding of elementary bodies on the cell surface, actin is rapidly recruited to the sites of internalization. Members of the Rho GTPase family are frequently involved in localized recruitment of actin. Clostridial Toxin B, which is a known enzymatic inhibitor of Rac, Cdc42 and Rho GTPases, significantly reduced chlamydial invasion of HeLa cells. Expression of dominant negative constructs in HeLa cells revealed that chlamydial uptake was dependent on Rac, but not on Cdc42 or RhoA. Rac but not Cdc42 was found to be activated by chlamydial attachment. The effect of dominant negative Rac expression on chlamydial uptake is manifested through the inhibition of actin recruitment to the sites of chlamydial entry. Studies utilizing Green Fluorescent Protein fusion constructs of Rac, Cdc42 and RhoA, showed Rac to be the sole member of the Rho GTPase family recruited to the site of chlamydial entry. JF - Traffic AU - Carabeo, Rey A AU - Grieshaber, Scott S AU - Hasenkrug, Aaron AU - Dooley, Cheryl AU - Hackstadt, Ted AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, NIAID, NIH, Rocky Mountain Laboratories, Hamilton, MT 59840, USA Y1 - 2004/06// PY - 2004 DA - Jun 2004 SP - 418 EP - 425 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 5 IS - 6 SN - 1398-9219, 1398-9219 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Actin KW - Chlamydia trachomatis KW - Guanosinetriphosphatase KW - J 02310:Genetics & Taxonomy KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1285087043?accountid=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=Traffic&rft.atitle=Requirement+for+the+Rac+GTPase+in+Chlamydia+trachomatis+Invasion+of+Non-phagocytic+Cells&rft.au=Carabeo%2C+Rey+A%3BGrieshaber%2C+Scott+S%3BHasenkrug%2C+Aaron%3BDooley%2C+Cheryl%3BHackstadt%2C+Ted&rft.aulast=Carabeo&rft.aufirst=Rey&rft.date=2004-06-01&rft.volume=5&rft.issue=6&rft.spage=418&rft.isbn=&rft.btitle=&rft.title=Traffic&rft.issn=13989219&rft_id=info:doi/10.1111%2Fj.1398-9219.2004.00184.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-02-01 N1 - Document feature - figure 5 N1 - Last updated - 2014-03-20 N1 - SubjectsTermNotLitGenreText - Guanosinetriphosphatase; Chlamydia trachomatis DO - http://dx.doi.org/10.1111/j.1398-9219.2004.00184.x ER - TY - JOUR T1 - Protective effect of soybean against hepatocarcinogenesis induced by DL-ethionine. AN - 66953514; 15469721 AB - There has been increasing interest in the value of using soybean to delay or reduce the tumor incidence. This study was undertaken to investigate the possible protective effects of soybean against hepatocarcinogenesis induced by DL-ethionine. Accordingly, we measured biochemical changes occurring in serum and liver of rats treated with DL-ethionine in the presence or absence of soybean. Male albino rats were fed a control diet containing the hepatocarcinogen, DL-ethionine, or the control diet plus soybean 30%, or the control diet plus soybean plus DL-ethionine 0.25% for three months and then returned to a control diet for up to nine months. Rats fed a control diet plus DL-ethionine showed a gradual decrease in liver DNA, RNA, total protein, and liver weight and enzyme activities of liver transaminases (GOT and GPT) and alkaline phosphatase over the 7-month study period. This was followed by a large increase in the liver parameters at the end of the 9(th) month, except for 5'-nucleotidase and glucose-6-phosphatase that showed a large decrease. On the other hand, a gradual increase in the serum enzyme activities of GOT, GPT, 5-nucleotidase, alkaline phosphatase, and in the albumin/globulin (A/G) ratio is observed in the group of rats fed a control diet plus DL-ethionine compared to the control group over 8 months, and this was followed by a large increase in all serum parameters studied at nine-months. The administration of 30% soybean to the rat diet in addition to DL-ethionine maintained all parameters studied at near control values until the end of the 9(th) month. This study suggests that soybean has a protective effect against the hepatocarcinogenesis induced by DL-ethionine. JF - Journal of biochemistry and molecular biology AU - Aiad, Fatma AU - El-Gamal, Basiouny AU - Al-Meer, Jehan AU - El-Kerdasy, Zinab AU - Zakhary, Nadia AU - El-Aaser, Abdelbaset AD - Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt. Y1 - 2004/05/31/ PY - 2004 DA - 2004 May 31 SP - 370 EP - 375 VL - 37 IS - 3 SN - 1225-8687, 1225-8687 KW - Antimetabolites KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Carcinogens KW - Plant Extracts KW - Protective Agents KW - Ethionine KW - WX1BN24WZT KW - Index Medicus KW - Protective Agents -- administration & dosage KW - Animals KW - Liver -- pathology KW - Carcinogens -- administration & dosage KW - Random Allocation KW - Carcinogens -- toxicity KW - Liver -- physiology KW - Rats KW - Antimetabolites -- toxicity KW - Protective Agents -- therapeutic use KW - Antimetabolites -- administration & dosage KW - Diet KW - Male KW - Ethionine -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Plant Extracts -- therapeutic use KW - Ethionine -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Liver Neoplasms, Experimental -- prevention & control KW - Soybeans KW - Liver Neoplasms, Experimental -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66953514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biochemistry+and+molecular+biology&rft.atitle=Protective+effect+of+soybean+against+hepatocarcinogenesis+induced+by+DL-ethionine.&rft.au=Aiad%2C+Fatma%3BEl-Gamal%2C+Basiouny%3BAl-Meer%2C+Jehan%3BEl-Kerdasy%2C+Zinab%3BZakhary%2C+Nadia%3BEl-Aaser%2C+Abdelbaset&rft.aulast=Aiad&rft.aufirst=Fatma&rft.date=2004-05-31&rft.volume=37&rft.issue=3&rft.spage=370&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemistry+and+molecular+biology&rft.issn=12258687&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-15 N1 - Date created - 2004-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thalidomide. AN - 71969810; 15172781 AB - Despite its history as a human teratogen, thalidomide is emerging as a treatment for cancer and inflammatory diseases. Although the evolution of its clinical application could not have been predicted from the tragedy associated with its misuse in the past, its history serves as a lesson in drug development that underscores the need to understand the molecular pharmacology of a compound's activity, including associated toxicities. Here, we summarise the applications for thalidomide with an emphasis on clinical trials published over the past 10 years, and consider our knowledge of the molecular pharmacology of the drug in the context of clinical trial data, attempting to provide a mechanism-guided understanding of its activity. JF - Lancet (London, England) AU - Franks, Michael E AU - Macpherson, Gordon R AU - Figg, William D AD - Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20030, USA. Y1 - 2004/05/29/ PY - 2004 DA - 2004 May 29 SP - 1802 EP - 1811 VL - 363 IS - 9423 KW - Thalidomide KW - 4Z8R6ORS6L KW - Abridged Index Medicus KW - Index Medicus KW - Skin Diseases -- drug therapy KW - Neoplasms -- drug therapy KW - Gastrointestinal Diseases -- drug therapy KW - HIV Infections -- complications KW - Humans KW - Clinical Trials as Topic KW - Rheumatic Diseases -- drug therapy KW - Thalidomide -- adverse effects KW - Thalidomide -- therapeutic use KW - Thalidomide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71969810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thalidomide.&rft.au=Franks%2C+Michael+E%3BMacpherson%2C+Gordon+R%3BFigg%2C+William+D&rft.aulast=Franks&rft.aufirst=Michael&rft.date=2004-05-29&rft.volume=363&rft.issue=9423&rft.spage=1802&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=1474-547X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-15 N1 - Date created - 2004-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of high affinity camptothecin-bombesin conjugates that have targeted cytotoxicity for bombesin receptor-containing tumor cells. AN - 71960936; 15016826 AB - Mammalian bombesin (BN) receptors are among those most frequently overexpressed by a number of common tumors including prostate, breast, lung, and colon cancers. The aim of this study was to develop a camptothecin-bombesin (CPT-BN) conjugate that interacts with all classes of BN receptors and possibly functions as a prodrug via a labile linker with site-specific cytotoxicity for cancer cells bearing these receptors. CPT was coupled to analogs of [D-Tyr6,beta-Ala11,Phe13,Nle14]BN-(6-14) (BA0) using carbamate linkers (L1 and L2) with built-in nucleophile-assisted releasing groups for intracellular cleavage of free cytotoxic agents. One conjugate, CPT-L2-BA3, bound to all three BN receptor classes with high affinity and functioned as a full agonist at each. 125I-CPT-L2-BA3 was rapidly internalized by cells expressing each BN receptor class and, using fluorescent imaging, was found to co-localize with BN receptors initially and later to be internalized in cytoplasmic compartments. HPLC analysis of internalized ligand showed that 40% was intact, 25% was metabolized by releasing free CPT, and 35% was metabolized to other breakdown products. CPT-L2-BA3 inhibited the growth of NCI-H1299 non-small cell lung cancer cells in 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyl-2H-tetrazolium bromide (MTT) and clonal growth assays. CPT-L2-BA3 was cytotoxic in an MTT assay for cells transfected with each class of BN receptor; however, it had significantly less effect in cells lacking BN receptors. These results indicate that CTP-L2-BA3 is a potent agonist that is cytotoxic for cells overexpressing any of the three BN receptor classes and functions as a prodrug for receptor-mediated cytoxicity. It therefore should be a useful prototype to explore the effectiveness of tumor-specific cytotoxicity delivery using a receptor-mediated mechanism. JF - The Journal of biological chemistry AU - Moody, Terry W AU - Mantey, Samuel A AU - Pradhan, Tapas K AU - Schumann, Michael AU - Nakagawa, Tomoo AU - Martinez, Alfredo AU - Fuselier, Joseph AU - Coy, David H AU - Jensen, Robert T AD - Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/05/28/ PY - 2004 DA - 2004 May 28 SP - 23580 EP - 23589 VL - 279 IS - 22 SN - 0021-9258, 0021-9258 KW - Antineoplastic Agents KW - 0 KW - Receptors, Bombesin KW - Bombesin KW - PX9AZU7QPK KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Drug Delivery Systems KW - Animals KW - Mice KW - Cell Death -- drug effects KW - Protein Binding KW - Drug Design KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Camptothecin -- metabolism KW - Camptothecin -- toxicity KW - Antineoplastic Agents -- metabolism KW - Antineoplastic Agents -- toxicity KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- antagonists & inhibitors KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71960936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Development+of+high+affinity+camptothecin-bombesin+conjugates+that+have+targeted+cytotoxicity+for+bombesin+receptor-containing+tumor+cells.&rft.au=Moody%2C+Terry+W%3BMantey%2C+Samuel+A%3BPradhan%2C+Tapas+K%3BSchumann%2C+Michael%3BNakagawa%2C+Tomoo%3BMartinez%2C+Alfredo%3BFuselier%2C+Joseph%3BCoy%2C+David+H%3BJensen%2C+Robert+T&rft.aulast=Moody&rft.aufirst=Terry&rft.date=2004-05-28&rft.volume=279&rft.issue=22&rft.spage=23580&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 - 2004-07-29 N1 - Date created - 2004-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A TM2 residue in the beta1 subunit determines spontaneous opening of homomeric and heteromeric gamma-aminobutyric acid-gated ion channels. AN - 71958799; 15014066 AB - Gamma-aminobutyric acid type A (GABAA) receptors are major inhibitory neurotransmitter-gated ion channels in the central nervous system. GABAA receptors consist of multiple subunits and exhibit distinct pharmacological and channel properties. Of all GABAA receptor subunits, the beta subunit is thought to be a key component for the functionality of the receptors. Certain types of GABAA receptors have been found to be constitutively active. However, the molecular basis for spontaneous opening of channels of these receptors is not totally understood. In this study, we showed that channels that contain the beta1 but not beta3 subunits opened spontaneously when these subunits were expressed homomerically or co-expressed with other types of GABAA receptor subunits in Xenopus oocytes. Using subunit chimeras and site-directed mutagenesis, we localized a key amino acid residue, a serine at position 265, that is critical in conferring an open state of the beta1 subunit-containing GABAA receptors in the absence of agonist. Moreover, some point mutations of Ser-265 also produced constitutively active channels. The magnitude of spontaneous activity of these receptors was correlated with the molecular volume of the residue at 265 for both homomeric and heteromeric GABAA receptors, suggesting that the spontaneous activity of the beta1 subunit-containing GABAA receptors may be mediated through a similar molecular mechanism that is dependent on the molecular volume of the residue at 265. JF - The Journal of biological chemistry AU - Miko, Angela AU - Werby, Elena AU - Sun, Hui AU - Healey, Julia AU - Zhang, Li AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8115, USA. Y1 - 2004/05/28/ PY - 2004 DA - 2004 May 28 SP - 22833 EP - 22840 VL - 279 IS - 22 SN - 0021-9258, 0021-9258 KW - Protein Subunits KW - 0 KW - Receptors, GABA-A KW - Recombinant Fusion Proteins KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Recombinant Fusion Proteins -- genetics KW - Point Mutation KW - Xenopus KW - Ion Channel Gating -- genetics KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- chemistry KW - Receptors, GABA-A -- genetics KW - Receptors, GABA-A -- metabolism KW - Receptors, GABA-A -- chemistry KW - Receptors, GABA-A -- analysis KW - Protein Subunits -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71958799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+TM2+residue+in+the+beta1+subunit+determines+spontaneous+opening+of+homomeric+and+heteromeric+gamma-aminobutyric+acid-gated+ion+channels.&rft.au=Miko%2C+Angela%3BWerby%2C+Elena%3BSun%2C+Hui%3BHealey%2C+Julia%3BZhang%2C+Li&rft.aulast=Miko&rft.aufirst=Angela&rft.date=2004-05-28&rft.volume=279&rft.issue=22&rft.spage=22833&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 - 2004-07-29 N1 - Date created - 2004-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulatory influence of garlic and tomato on cyclooxygenase-2 activity, cell proliferation and apoptosis during azoxymethane induced colon carcinogenesis in rat. AN - 71920895; 15142670 AB - Preventive intervention of colorectal cancer has become essential as a major portion of the population may develop the disease at some points during their lives. Diet and nutrition play an important role during this multistep colon carcinogenic process. Inhibitory activity of aqueous suspensions of garlic and tomato, individually and in combination, were tested on azoxymethane induced colon carcinogenesis in Sprague-Dawley rats. The effect was observed on aberrant crypt foci (ACF), the preneoplastic lesion. To investigate the mechanism of action of the agents used, cell proliferation and the level of apoptosis were determined and the expression of cyclooxygenase-2 (COX-2) protein was analyzed in the colon. Following treatment, significant inhibition of the level of cell proliferation (P<0.01 in garlic; P<0.001 in tomato and P<0.001 in combination treatment group with respect to the carcinogen control group), significant induction of apoptosis (P<0.01 in garlic treated; P<0.01 in tomato treated and P<0.001 in combination treatment group with respect to the carcinogen control group) and suppression of COX-2 expression among the treated groups resulted in significant reduction in the incidences of ACF (by 45.27% in garlic, 68.24% in tomato and 71.62% in combination treatment group). The preventive effect was better when the combination of garlic and tomato was administered in comparison to the individual treatment groups, suggesting the synergistic action of garlic and tomato. JF - Cancer letters AU - Sengupta, Archana AU - Ghosh, Samit AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India. archanadi1@rediffmail.com Y1 - 2004/05/28/ PY - 2004 DA - 2004 May 28 SP - 127 EP - 136 VL - 208 IS - 2 SN - 0304-3835, 0304-3835 KW - Isoenzymes KW - 0 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Azoxymethane KW - MO0N1J0SEN KW - Index Medicus KW - Rats KW - Lycopersicon esculentum KW - Animals KW - Rats, Sprague-Dawley KW - Male KW - Cell Division KW - Apoptosis KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Precancerous Conditions -- prevention & control KW - Garlic KW - Colonic Neoplasms -- prevention & control KW - Colonic Neoplasms -- pathology KW - Isoenzymes -- metabolism KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71920895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modulatory+influence+of+garlic+and+tomato+on+cyclooxygenase-2+activity%2C+cell+proliferation+and+apoptosis+during+azoxymethane+induced+colon+carcinogenesis+in+rat.&rft.au=Sengupta%2C+Archana%3BGhosh%2C+Samit%3BDas%2C+Sukta&rft.aulast=Sengupta&rft.aufirst=Archana&rft.date=2004-05-28&rft.volume=208&rft.issue=2&rft.spage=127&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 - 2004-06-24 N1 - Date created - 2004-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dominant-negative c-Jun (TAM67) target genes: HMGA1 is required for tumor promoter-induced transformation. AN - 71983838; 15064752 AB - Activation of the transcription factor AP-1 (activator protein-1) is required for tumor promotion and maintenance of malignant phenotype. A number of AP-1-regulated genes that play a role in tumor progression have been identified. However, AP-1-regulated genes driving tumor induction are yet to be defined. Previous studies have established that expression of a dominant-negative c-Jun (TAM67) inhibits phorbol 12-tetradecanoyl-13-acetate (TPA)-induced AP-1 transactivation as well as transformation in mouse epidermal JB6/P+ cells and tumor promotion in mouse skin carcinogenesis. In this study, we utilized the tumor promotion-sensitive JB6/P+ cells to identify AP-1-regulated TAM67 target genes and to establish causal significance in transformation for one target gene. A 2700 cDNA microarray was queried with RNA from TPA-treated P+ cells with or without TAM67 expression. Under conditions in which TAM expression inhibited TPA-induced transformation, microarray analysis identified a subset of six genes induced by TPA and suppressed by TAM67. One of the identified genes, the high-mobility group protein A1 (Hmga1) is induced by TPA in P+, but not in transformation-resistant P cells. We show that TPA induction of the architectural transcription factor HMGA1 is inhibited by TAM67, is extracellular-signal-regulated kinase (ERK)-activation dependent, and is mediated by AP-1. HMGA1 antisense construct transfected into P+ cells blocked HMGA1 protein expression and inhibited TPA-induced transformation indicating that HMGA1 is required for transformation. HMGA1 is not however sufficient as HMGA1a or HMGA1b overexpression did not confer transformation sensitivity on P- cells. Although HMGA1 expression is ERK dependent, it is not the only ERK-dependent event required for transformation because it does not suffice to rescue ERK-deficient P- cells. Our study shows (a) TAM 67 when it inhibits AP-1 and transformation, targets a relatively small number of genes; (b) HMGA1, a TAM67 target gene, is causally related to transformation and therefore a potentially important target for cancer prevention. JF - Oncogene AU - Dhar, Arindam AU - Hu, Jing AU - Reeves, Raymond AU - Resar, Linda M S AU - Colburn, Nancy H AD - Gene Regulation Section, Laboratory of Cancer Prevention, NCI at Frederick, Frederick, MD 21702-1201, USA. adhar@ncifcrf.gov Y1 - 2004/05/27/ PY - 2004 DA - 2004 May 27 SP - 4466 EP - 4476 VL - 23 IS - 25 SN - 0950-9232, 0950-9232 KW - Butadienes KW - 0 KW - DNA, Complementary KW - Nitriles KW - Oligonucleotides, Antisense KW - Proto-Oncogene Proteins c-jun KW - Sialoglycoproteins KW - Spp1 protein, mouse KW - Transcription Factor AP-1 KW - U 0126 KW - Osteopontin KW - 106441-73-0 KW - HMGA1b Protein KW - 124543-08-4 KW - HMGA1a Protein KW - 124544-67-8 KW - Cyclin D1 KW - 136601-57-5 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - MAP Kinase Kinase Kinase 1 KW - EC 2.7.11.25 KW - MAP Kinase Kinase Kinases KW - Map3k1 protein, mouse KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Cell Line -- drug effects KW - Cyclin D1 -- genetics KW - Cyclin D1 -- biosynthesis KW - Mice, Transgenic KW - Mitogen-Activated Protein Kinases -- physiology KW - Transcription Factor AP-1 -- physiology KW - Mitogen-Activated Protein Kinase 1 -- physiology KW - Clone Cells -- metabolism KW - Clone Cells -- drug effects KW - Tetradecanoylphorbol Acetate -- toxicity KW - DNA, Complementary -- genetics KW - Nitriles -- pharmacology KW - Disease Susceptibility KW - Cell Line -- metabolism KW - Sialoglycoproteins -- genetics KW - Mice KW - Oligonucleotides, Antisense -- pharmacology KW - MAP Kinase Kinase Kinases -- antagonists & inhibitors KW - Gene Expression Profiling KW - MAP Kinase Signaling System KW - Butadienes -- pharmacology KW - Sialoglycoproteins -- biosynthesis KW - HMGA1b Protein -- physiology KW - HMGA1a Protein -- physiology KW - Transcription, Genetic -- drug effects KW - Epidermis -- cytology KW - Epidermis -- metabolism KW - Transcription, Genetic -- genetics KW - Cell Transformation, Neoplastic -- drug effects KW - Epidermis -- drug effects KW - Proto-Oncogene Proteins c-jun -- physiology KW - Proto-Oncogene Proteins c-jun -- deficiency KW - Cell Transformation, Neoplastic -- genetics KW - Genes, jun -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71983838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dominant-negative+c-Jun+%28TAM67%29+target+genes%3A+HMGA1+is+required+for+tumor+promoter-induced+transformation.&rft.au=Dhar%2C+Arindam%3BHu%2C+Jing%3BReeves%2C+Raymond%3BResar%2C+Linda+M+S%3BColburn%2C+Nancy+H&rft.aulast=Dhar&rft.aufirst=Arindam&rft.date=2004-05-27&rft.volume=23&rft.issue=25&rft.spage=4466&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-01 N1 - Date created - 2004-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs AN - 20125555; 5918108 AB - A remarkable diversity of bioactive lipophilic alkaloids is present in the skin of poison frogs and toads worldwide. Originally discovered in neotropical dendrobatid frogs, these alkaloids are now known from mantellid frogs of Madagascar, certain myobatrachid frogs of Australia, and certain bufonid toads of South America. Presumably serving as a passive chemical defense, these alkaloids appear to be sequestered from a variety of alkaloid-containing arthropods. The pumiliotoxins represent a major, widespread, group of alkaloids that are found in virtually all anurans that are chemically defended by the presence of lipophilic alkaloids. Identifying an arthropod source for these alkaloids has been a considerable challenge for chemical ecologists. However, an extensive collection of neotropical forest arthropods has now revealed a putative arthropod source of the pumiliotoxins. Here we report on the presence of pumiliotoxins in formicine ants of the genera Brachymyrmex and Paratrechina, as well as the presence of these ants in the stomach contents of the microsympatric pumiliotoxin-containing dendrobatid frog, Dendrobates pumilio. These pumiliotoxins are major alkaloids in D. pumilio, and Brachymyrmex and Paratrechina ants now represent the only known dietary sources of these toxic alkaloids. These findings further support the significance of ant-specialization and alkaloid sequestration in the evolution of bright warning coloration in poison frogs and toads. JF - Proceedings of the National Academy of Sciences, USA AU - Saporito, R A AU - Garraffo, H M AU - Donnelly, MA AU - Edwards, AL AU - Longino, J T AU - Daly, J W AD - Department of Biological Sciences, Florida International University, Miami, FL 33199, jdaly@nih.gov Y1 - 2004/05/25/ PY - 2004 DA - 2004 May 25 SP - 8045 EP - 8050 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 21 SN - 0027-8424, 0027-8424 KW - Ants KW - Hymenoptera KW - pumiliotoxin KW - Ecology Abstracts; ASFA 1: Biological Sciences & Living Resources; Entomology Abstracts KW - ECOLOGY / CHEMISTRY KW - Neotropical Region KW - Skin KW - Amphibiotic species KW - Anura KW - Formicidae KW - Paratrechina KW - Forests KW - Dendrobates pumilio KW - Lipophilic KW - Amphibia KW - Stomach content KW - South America KW - Alkaloids KW - Arthropoda KW - Coloration KW - ISW, Indian Ocean, Madagascar KW - Species diversity KW - Australia KW - Brachymyrmex KW - Defense mechanisms KW - Evolution KW - Stomach KW - D 04040:Ecosystem and Ecology Studies KW - Z 05183:Toxicology & resistance KW - Q1 08425:Nutrition and feeding habits UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20125555?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Formicine+ants%3A+An+arthropod+source+for+the+pumiliotoxin+alkaloids+of+dendrobatid+poison+frogs&rft.au=Saporito%2C+R+A%3BGarraffo%2C+H+M%3BDonnelly%2C+MA%3BEdwards%2C+AL%3BLongino%2C+J+T%3BDaly%2C+J+W&rft.aulast=Saporito&rft.aufirst=R&rft.date=2004-05-25&rft.volume=101&rft.issue=21&rft.spage=8045&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0402365101 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-02-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Stomach content; Alkaloids; Amphibiotic species; Species diversity; Skin; Coloration; Forests; Defense mechanisms; Stomach; Lipophilic; Evolution; Amphibia; Arthropoda; Formicidae; Anura; Paratrechina; Brachymyrmex; Dendrobates pumilio; South America; Neotropical Region; ISW, Indian Ocean, Madagascar; Australia DO - http://dx.doi.org/10.1073/pnas.0402365101 ER - TY - CPAPER T1 - High throughput peptide synthesis on a biomek FX liquidhandler AN - 39857073; 3849363 AU - Rasmussen, L AU - Saxinger, C AU - Frankenberger, C AU - Munroe, D AU - Goldstein, M Y1 - 2004/05/20/ PY - 2004 DA - 2004 May 20 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39857073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=High+throughput+peptide+synthesis+on+a+biomek+FX+liquidhandler&rft.au=Rasmussen%2C+L%3BSaxinger%2C+C%3BFrankenberger%2C+C%3BMunroe%2C+D%3BGoldstein%2C+M&rft.aulast=Rasmussen&rft.aufirst=L&rft.date=2004-05-20&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: LabAutomation2004, 3N866 Ferson Creek Road, St. Charles, IL 60174, USA; phone: 866-263-4928; fax: 312-803-1927; URL: labautomation.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Role of genomics in toxicology AN - 39856614; 3853813 AU - Heinloth, A Y1 - 2004/05/20/ PY - 2004 DA - 2004 May 20 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39856614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Role+of+genomics+in+toxicology&rft.au=Heinloth%2C+A&rft.aulast=Heinloth&rft.aufirst=A&rft.date=2004-05-20&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: LabAutomation2004, 3N866 Ferson Creek Road, St. Charles, IL 60174, USA; phone: 866-263-4928; fax: 312-803-1927; URL: labautomation.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - RNass H inhibitor assay by capillary electrophoresis with laser-induced fluorescence detection AN - 39852404; 3863220 AU - Chan, K C AU - Beutler, JA AU - Budihas AU - Le Grice, S AU - Veenstra, T D AU - Issaq, HJ Y1 - 2004/05/20/ PY - 2004 DA - 2004 May 20 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39852404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=RNass+H+inhibitor+assay+by+capillary+electrophoresis+with+laser-induced+fluorescence+detection&rft.au=Chan%2C+K+C%3BBeutler%2C+JA%3BBudihas%3BLe+Grice%2C+S%3BVeenstra%2C+T+D%3BIssaq%2C+HJ&rft.aulast=Chan&rft.aufirst=K&rft.date=2004-05-20&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Pittsburgh Conference, 300 Penn Center Blvd., Suite 332, Pittsburgh, PA 15235, USA; phone: 412-825-3220; fax: 412-825-3224; email: pittconinfo@pittcon.org; URL: www.pittcon.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Automated process of Q-PCR/gene expression AN - 39819669; 3845560 AU - Stewart, C AU - Cherry, J M AU - Martin, K T AU - Bhat, N K AU - Munroe, D Y1 - 2004/05/20/ PY - 2004 DA - 2004 May 20 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39819669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Automated+process+of+Q-PCR%2Fgene+expression&rft.au=Stewart%2C+C%3BCherry%2C+J+M%3BMartin%2C+K+T%3BBhat%2C+N+K%3BMunroe%2C+D&rft.aulast=Stewart&rft.aufirst=C&rft.date=2004-05-20&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: LabAutomation2004, 3N866 Ferson Creek Road, St. Charles, IL 60174, USA; phone: 866-263-4928; fax: 312-803-1927; URL: labautomation.org N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Integration of clinical and gene expression endpoints to explore furan-mediated hepatotoxicity. AN - 71894418; 15120969 AB - Molecular techniques, such as cDNA microarrays, are being used to aid in the elucidation of the mechanisms of toxicity of a variety of compounds. In this study, we evaluate the molecular effects of furan in the rat liver. Sprague-Dawley rats were exposed to 4 or 40 mg/kg furan for up to 14 days. Furan induced an initial degenerative and necrotic phenotype that was followed by inflammation and fibrosis, consistent with previous observations for this compound. RNA was harvested from each lobe of the liver at several time points to observe whether lobe-specific gene expression effects occurred. Similar gene expression changes were observed in all lobes, however the magnitude of gene expression change was more pronounced in the right lobe. Finally, to help determine the correlation between gene expression changes and liver pathology, we applied traditional microarray visualization tools to the assessment of clinical chemistry and pathology parameters. JF - Mutation research AU - Hamadeh, Hisham K AU - Jayadev, Supriya AU - Gaillard, Elias T AU - Huang, Qihong AU - Stoll, Raymond AU - Blanchard, Kerry AU - Chou, Jeff AU - Tucker, Charles J AU - Collins, Jennifer AU - Maronpot, Robert AU - Bushel, Pierre AU - Afshari, Cynthia A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. hhamadeh@amgen.com Y1 - 2004/05/18/ PY - 2004 DA - 2004 May 18 SP - 169 EP - 183 VL - 549 IS - 1-2 SN - 0027-5107, 0027-5107 KW - DNA, Complementary KW - 0 KW - Furans KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Oligonucleotide Array Sequence Analysis KW - Male KW - Gene Expression Profiling KW - Liver -- drug effects KW - Furans -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71894418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Integration+of+clinical+and+gene+expression+endpoints+to+explore+furan-mediated+hepatotoxicity.&rft.au=Hamadeh%2C+Hisham+K%3BJayadev%2C+Supriya%3BGaillard%2C+Elias+T%3BHuang%2C+Qihong%3BStoll%2C+Raymond%3BBlanchard%2C+Kerry%3BChou%2C+Jeff%3BTucker%2C+Charles+J%3BCollins%2C+Jennifer%3BMaronpot%2C+Robert%3BBushel%2C+Pierre%3BAfshari%2C+Cynthia+A&rft.aulast=Hamadeh&rft.aufirst=Hisham&rft.date=2004-05-18&rft.volume=549&rft.issue=1-2&rft.spage=169&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 - 2004-07-13 N1 - Date created - 2004-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microarray analysis of epigenetic silencing of gene expression in the KAS-6/1 multiple myeloma cell line. AN - 71936614; 15150099 AB - The epigenetic control of gene transcription in cancer has been the theme of many recent studies and therapeutic approaches. Carcinogenesis is frequently associated with hypermethylation and consequent down-regulation of genes that prevent cancer, e.g., those that control cell proliferation and apoptosis. We used the demethylating drug zebularine to induce changes in DNA methylation, then examined patterns of gene expression using cDNA array analysis and Restriction Landmark Genomic Scanning followed by RNase protection assay and reverse transcription-PCR to confirm the results. Microarray studies revealed that many genes were epigenetically regulated by methylation. We concluded that methylation decreased the expression of, or silenced, several genes, contributing to the growth and survival of multiple myeloma cells. For example, a number of genes (BAD, BAK, BIK, and BAX) involved in apoptosis were found to be suppressed by methylation. Sequenced methylation-regulated DNA fragments identified by Restriction Landmark Genomic Scanning were found to contain CpG islands, and some corresponded to promoters of genes that were regulated by methylation. We also observed that after the removal of the demethylating drug, the addition of interleukin 6 restored CpG methylation and re-established previously silenced gene patterns, thus implicating a novel role of interleukin 6 in processes regulating epigenetic gene repression and carcinogenesis. JF - Cancer research AU - Pompeia, Celine AU - Hodge, David R AU - Plass, Christoph AU - Wu, Yue-Zhong AU - Marquez, Victor E AU - Kelley, James A AU - Farrar, William L AD - Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 2004/05/15/ PY - 2004 DA - 2004 May 15 SP - 3465 EP - 3473 VL - 64 IS - 10 SN - 0008-5472, 0008-5472 KW - Pyrimidine Nucleosides KW - 0 KW - Cytidine KW - 5CSZ8459RP KW - pyrimidin-2-one beta-ribofuranoside KW - 7A9Y5SX0GY KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Genome, Human KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - DNA Methylation -- drug effects KW - Pyrimidine Nucleosides -- pharmacology KW - Cell Line, Tumor KW - Reverse Transcriptase Polymerase Chain Reaction KW - Ribonucleases -- metabolism KW - Cytidine -- analogs & derivatives KW - Gene Expression Regulation, Neoplastic KW - Multiple Myeloma -- genetics KW - Gene Silencing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71936614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Microarray+analysis+of+epigenetic+silencing+of+gene+expression+in+the+KAS-6%2F1+multiple+myeloma+cell+line.&rft.au=Pompeia%2C+Celine%3BHodge%2C+David+R%3BPlass%2C+Christoph%3BWu%2C+Yue-Zhong%3BMarquez%2C+Victor+E%3BKelley%2C+James+A%3BFarrar%2C+William+L&rft.aulast=Pompeia&rft.aufirst=Celine&rft.date=2004-05-15&rft.volume=64&rft.issue=10&rft.spage=3465&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 - 2004-08-02 N1 - Date created - 2004-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Viral FLIP impairs survival of activated T cells and generation of CD8+ T cell memory. AN - 71904622; 15128821 AB - Viral FLIPs (vFLIPs) interfere with apoptosis signaling by death-domain-containing receptors in the TNFR superfamily (death receptors). In this study, we show that T cell-specific transgenic expression of MC159-vFLIP from the human Molluscum contagiosum virus blocks CD95-induced apoptosis in thymocytes and peripheral T cells, but also impairs postactivation survival of in vitro activated primary T cells despite normal early activation parameters. MC159 vFLIP impairs T cell development to a lesser extent than does Fas-associated death domain protein deficiency or another viral FLIP, E8. In the periphery, vFLIP expression leads to a specific deficit of functional memory CD8(+) T cells. After immunization with a protein Ag, Ag-specific CD8(+) T cells initially proliferate, but quickly disappear and fail to produce Ag-specific memory CD8(+) T cells. Viral FLIP transgenic mice exhibit impaired CD8(+) T cell responses to lymphocytic choriomeningitis virus and Trypanosoma cruzi infections, and a specific defect in CD8(+) T cell recall responses to influenza virus was seen. These results suggest that vFLIP expression in T cells blocks signals necessary for the sustained survival of CD8(+) T cells and the generation of CD8(+) T cell memory. Through this mechanism, vFLIP proteins expressed by T cell tropic viruses may impair the CD8(+) T cell immune responses directed against them. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wu, Zhengqi AU - Roberts, Margaret AU - Porter, Melissa AU - Walker, Fabianne AU - Wherry, E John AU - Kelly, John AU - Gadina, Massimo AU - Silva, Elisabeth M AU - DosReis, George A AU - Lopes, Marcela F AU - O'Shea, John AU - Leonard, Warren J AU - Ahmed, Rafi AU - Siegel, Richard M AD - Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/05/15/ PY - 2004 DA - 2004 May 15 SP - 6313 EP - 6323 VL - 172 IS - 10 SN - 0022-1767, 0022-1767 KW - Antigens, CD95 KW - 0 KW - DNA-Binding Proteins KW - Epitopes, T-Lymphocyte KW - Milk Proteins KW - Receptors, Tumor Necrosis Factor KW - STAT5 Transcription Factor KW - Trans-Activators KW - Viral Proteins KW - viral FLIP protein, Human herpesvirus 8 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Molluscum contagiosum virus -- immunology KW - Epitopes, T-Lymphocyte -- immunology KW - Mice, Transgenic KW - Apoptosis -- genetics KW - Cell Division -- immunology KW - Signal Transduction -- immunology KW - Trypanosoma cruzi -- immunology KW - Male KW - Antigens, CD95 -- genetics KW - Chagas Disease -- immunology KW - Chagas Disease -- genetics KW - Cell Survival -- genetics KW - Apoptosis -- immunology KW - Mice KW - Cell Survival -- immunology KW - Lymphopenia -- genetics KW - Epitopes, T-Lymphocyte -- administration & dosage KW - Receptors, Tumor Necrosis Factor -- physiology KW - Mice, Inbred C57BL KW - Signal Transduction -- genetics KW - DNA-Binding Proteins -- physiology KW - Lymphopenia -- immunology KW - Trans-Activators -- physiology KW - Immunophenotyping KW - Cell Division -- genetics KW - Viral Proteins -- genetics KW - CD8-Positive T-Lymphocytes -- metabolism KW - Viral Proteins -- biosynthesis KW - Viral Proteins -- toxicity KW - CD8-Positive T-Lymphocytes -- transplantation KW - T-Lymphocyte Subsets -- metabolism KW - CD8-Positive T-Lymphocytes -- pathology KW - Immunologic Memory -- genetics KW - Lymphocyte Activation -- genetics KW - CD8-Positive T-Lymphocytes -- immunology KW - Lymphocyte Activation -- immunology KW - T-Lymphocyte Subsets -- immunology KW - T-Lymphocyte Subsets -- virology KW - T-Lymphocyte Subsets -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71904622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Viral+FLIP+impairs+survival+of+activated+T+cells+and+generation+of+CD8%2B+T+cell+memory.&rft.au=Wu%2C+Zhengqi%3BRoberts%2C+Margaret%3BPorter%2C+Melissa%3BWalker%2C+Fabianne%3BWherry%2C+E+John%3BKelly%2C+John%3BGadina%2C+Massimo%3BSilva%2C+Elisabeth+M%3BDosReis%2C+George+A%3BLopes%2C+Marcela+F%3BO%27Shea%2C+John%3BLeonard%2C+Warren+J%3BAhmed%2C+Rafi%3BSiegel%2C+Richard+M&rft.aulast=Wu&rft.aufirst=Zhengqi&rft.date=2004-05-15&rft.volume=172&rft.issue=10&rft.spage=6313&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 - 2004-09-02 N1 - Date created - 2004-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Midlife Dietary Intake of Antioxidants and Risk of Late-Life Incident Dementia: The Honolulu-Asia Aging Study AN - 18002889; 5968185 AB - Antioxidants have been hypothesized to protect against Alzheimer's disease, but studies conducted in late life have been inconsistent. Risk factors measured in midlife may better predict dementia in late life because they are less affected by the disease process. The authors examined the association of midlife dietary intake of antioxidants to late-life dementia and its subtypes. Data were obtained from the Honolulu-Asia Aging Study, a prospective community-based study of Japanese-American men who were aged 45-68 years in 1965-1968, when a 24-hour dietary recall was administered. The analysis included 2,459 men with complete dietary data who were dementia-free at the first assessment in 1991-1993 and were examined up to two times for dementia between 1991 and 1999. The sample included 235 incident cases of dementia (102 cases of Alzheimer's disease, 38 cases of Alzheimer's disease with contributing cerebrovascular disease, and 44 cases of vascular dementia). Relative risks by quartile of intake were calculated using Cox proportional hazards models with age as the time scale, after adjustment for sociodemographic and lifestyle factors, cardiovascular risk factors, other dietary constituents, and apolipoprotein E e4. Intakes of beta-carotene, flavonoids, and vitamins E and C were not associated with the risk of dementia or its subtypes. This analysis suggests that midlife dietary intake of antioxidants does not modify the risk of late-life dementia or its most prevalent subtypes. JF - American Journal of Epidemiology AU - Laurin, D AU - Masaki, KH AU - Foley, D J AU - White, L R AU - Launer, L J AD - Neuroepidemiology Section, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA Y1 - 2004/05/15/ PY - 2004 DA - 2004 May 15 SP - 959 EP - 967 VL - 159 IS - 10 SN - 0002-9262, 0002-9262 KW - dementia KW - Risk Abstracts KW - Diets KW - Antioxidants KW - Alzheimer's disease KW - mental disorders KW - Nutrition KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18002889?accountid=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=Midlife+Dietary+Intake+of+Antioxidants+and+Risk+of+Late-Life+Incident+Dementia%3A+The+Honolulu-Asia+Aging+Study&rft.au=Laurin%2C+D%3BMasaki%2C+KH%3BFoley%2C+D+J%3BWhite%2C+L+R%3BLauner%2C+L+J&rft.aulast=Laurin&rft.aufirst=D&rft.date=2004-05-15&rft.volume=159&rft.issue=10&rft.spage=959&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 - Nutrition; Diets; Antioxidants; mental disorders; Alzheimer's disease ER - TY - JOUR T1 - Combination of a Poxvirus-Based Vaccine with a Cyclooxygenase-2 Inhibitor (Celecoxib) Elicits Antitumor Immunity and Long-Term Survival in CEA.Tg/MIN Mice AN - 17996214; 5937055 AB - The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with lowered plasma prostaglandin E sub(2) levels and reduced COX-2 mRNA expression levels in their splenic T cells. Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN- gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib. When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc super( Delta 850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning at 30 days of age, the administration of a diversified prime/boost recombinant CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet reduced the number of intestinal neoplasms by 54% and 65%, respectively. Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced tumor burden by 95% and significantly improved overall long-term survival. Both tumor reduction and improved overall survival were achieved without any evidence of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is prescribed for the treatment of familial adenomatous polyposis in humans, and the CEA-based vaccines have been well tolerated and capable of eliciting anti-CEA host immune responses in early clinical studies. The results suggest that the administration of a recombinant poxvirus-based vaccine is compatible with celecoxib, and this combined chemoimmuno-based approach might lead to an additive therapeutic antitumor benefit not only in patients diagnosed with familial adenomatous polyposis but, perhaps, in other preventive settings in which COX-2 overexpression is associated with progression from premalignancy to neoplasia. JF - Cancer Research AU - Zeytin, HE AU - Patel, A C AU - Rogers, C J AU - Canter, D AU - Hursting, S D AU - Schlom, J AU - Greiner, J W AD - Laboratories of Tumor Immunology and Biology, and Biosystems and Cancer, Center for Cancer Research, and Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland, USA Y1 - 2004/05/15/ PY - 2004 DA - 2004 May 15 SP - 3668 EP - 3678 VL - 64 IS - 10 SN - 0008-5472, 0008-5472 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cyclooxygenase-2 KW - Celecoxib KW - Polyposis coli KW - Poxvirus KW - Carcinoembryonic antigen KW - Vaccines KW - Cancer KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17996214?accountid=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=Combination+of+a+Poxvirus-Based+Vaccine+with+a+Cyclooxygenase-2+Inhibitor+%28Celecoxib%29+Elicits+Antitumor+Immunity+and+Long-Term+Survival+in+CEA.Tg%2FMIN+Mice&rft.au=Zeytin%2C+HE%3BPatel%2C+A+C%3BRogers%2C+C+J%3BCanter%2C+D%3BHursting%2C+S+D%3BSchlom%2C+J%3BGreiner%2C+J+W&rft.aulast=Zeytin&rft.aufirst=HE&rft.date=2004-05-15&rft.volume=64&rft.issue=10&rft.spage=3668&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 - Poxvirus; Vaccines; Celecoxib; Cyclooxygenase-2; Polyposis coli; Cancer; Carcinoembryonic antigen ER - TY - JOUR T1 - Crystallographic and biochemical investigations of kumamolisin-As, a serine-carboxyl peptidase with collagenase activity. AN - 71918066; 15014068 AB - Kumamolisin-As (previously called ScpA) is the first known example of a collagenase from the sedolisin family (MEROPS S53). This enzyme is active at low pH and in elevated temperatures. In this study that used x-ray crystallographic and biochemical methods, we investigated the structural basis of the preference of this enzyme for collagen and the importance of a glutamate residue in the unique catalytic triad (Ser(278)-Glu(78)-Asp(82)) for enzymatic activity. Crystal structures of the uninhibited enzyme and its complex with a covalently bound inhibitor, N-acetyl-isoleucyl-prolyl-phenylalaninal, showed the occurrence of a narrow S2 pocket and a groove that encompasses the active site and is rich in negative charges. Limited endoproteolysis studies of bovine type-I collagen as well as kinetic studies using peptide libraries randomized at P1 and P1', showed very strong preference for arginine at the P1 position, which correlated very well with the presence of a negatively charged residue in the S1 pocket of the enzyme. All of these features, together with those predicted through comparisons with fiddler crab collagenase, a serine peptidase, rationalize the enzyme's preference for collagen. A comparison of the Arrhenius plots of the activities of kumamolisin-As with either collagen or peptides as substrates suggests that collagen should be relaxed before proteolysis can occur. The E78H mutant, in which the catalytic triad was engineered to resemble that of subtilisin, showed only 0.01% activity of the wild-type enzyme, and its structure revealed that Ser(278), His(78), and Asp(82) do not interact with each other; thus, the canonical catalytic triad is disrupted. JF - The Journal of biological chemistry AU - Wlodawer, Alexander AU - Li, Mi AU - Gustchina, Alla AU - Tsuruoka, Naoki AU - Ashida, Masako AU - Minakata, Hiroyuki AU - Oyama, Hiroshi AU - Oda, Kohei AU - Nishino, Tokuzo AU - Nakayama, Toru AD - Protein Structure Section, Macromolecular Crystallography Laboratory, NCI-Frederick, National Institutes of Health, Frederick, MD 21702, USA. wlodawer@ncifcrf.gov Y1 - 2004/05/14/ PY - 2004 DA - 2004 May 14 SP - 21500 EP - 21510 VL - 279 IS - 20 SN - 0021-9258, 0021-9258 KW - Carboxypeptidases KW - EC 3.4.- KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - kumamolysin KW - Collagenases KW - EC 3.4.24.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Structure, Secondary KW - Thermodynamics KW - Models, Molecular KW - Kinetics KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Substrate Specificity KW - Amino Acid Substitution KW - Cloning, Molecular KW - Binding Sites KW - Carboxypeptidases -- metabolism KW - Carboxypeptidases -- chemistry KW - Aspartic Acid Endopeptidases -- metabolism KW - Aspartic Acid Endopeptidases -- chemistry KW - Collagenases -- chemistry KW - Collagenases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71918066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Crystallographic+and+biochemical+investigations+of+kumamolisin-As%2C+a+serine-carboxyl+peptidase+with+collagenase+activity.&rft.au=Wlodawer%2C+Alexander%3BLi%2C+Mi%3BGustchina%2C+Alla%3BTsuruoka%2C+Naoki%3BAshida%2C+Masako%3BMinakata%2C+Hiroyuki%3BOyama%2C+Hiroshi%3BOda%2C+Kohei%3BNishino%2C+Tokuzo%3BNakayama%2C+Toru&rft.aulast=Wlodawer&rft.aufirst=Alexander&rft.date=2004-05-14&rft.volume=279&rft.issue=20&rft.spage=21500&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 - 2004-07-21 N1 - Date created - 2004-05-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1SIU; PDB; 1SIO; 1SN7 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Role of MmpL8 in Sulfatide Biogenesis and Virulence of Mycobacterium tuberculosis AN - 17817846; 5919142 AB - To study the role of MmpL8-mediated lipid transport in sulfatide biogenesis, we insertionally inactivated the mmpL8 gene in Mycobacterium tuberculosis. Characterization of this strain showed that the synthesis of mature sulfolipid SL-1 was interrupted and that a more polar sulfated molecule, termed SL-N, accumulated within the cell. Purification of SL-N and structural analysis identified this molecule as a family of 2,3-diacyl- alpha , alpha '-D-trehalose- 2'-sulfates. This structure suggests that transport and biogenesis of SL-1 are coupled and that the final step in sulfatide biosynthesis may be the extra- cellular esterification of two trehalose 6-positions with hydroxyphthioceranic acids. To assess the effect of the loss of this anionic surface lipid on virulence, we infected mice via aerosol with the MmpL8 mutant and found that, although initial replication rates and containment levels were identical, compared with the wild type, a significant attenuation of the MmpL8 mutant strain in time-to-death was observed. Early in infection, differential expression of cytokines and cytokine receptors revealed that the mutant strain less efficiently suppresses key indicators of a Th1-type immune response, suggesting an immunomodulatory role for sulfatides in the pathogenesis of tuberculosis. JF - Journal of Biological Chemistry AU - Domenech, P AU - Reed, M B AU - Dowd, C S AU - Manca, C AU - Kaplan, G AU - Barry, CE III AD - Tuberculosis Research Section, NIAID, National Institutes of Health, Rockville, Maryland 20852, cbarry@niaid.nih.gov Y1 - 2004/05/14/ PY - 2004 DA - 2004 May 14 SP - 21257 EP - 21265 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 20 SN - 0021-9258, 0021-9258 KW - mice KW - Microbiology Abstracts B: Bacteriology KW - Aerosols KW - Replication KW - Lipids KW - Trehalose KW - Virulence KW - sulfatide KW - Esterification KW - Acids KW - Cytokine receptors KW - Tuberculosis KW - Immune response KW - Mycobacterium tuberculosis KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17817846?accountid=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=The+Role+of+MmpL8+in+Sulfatide+Biogenesis+and+Virulence+of+Mycobacterium+tuberculosis&rft.au=Domenech%2C+P%3BReed%2C+M+B%3BDowd%2C+C+S%3BManca%2C+C%3BKaplan%2C+G%3BBarry%2C+CE+III&rft.aulast=Domenech&rft.aufirst=P&rft.date=2004-05-14&rft.volume=279&rft.issue=20&rft.spage=21257&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M400324200 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Virulence; Aerosols; sulfatide; Esterification; Replication; Acids; Lipids; Cytokine receptors; Tuberculosis; Trehalose; Immune response; Mycobacterium tuberculosis DO - http://dx.doi.org/10.1074/jbc.M400324200 ER - TY - JOUR T1 - Chlamydial histone-DNA interactions are disrupted by a metabolite in the methylerythritol phosphate pathway of isoprenoid biosynthesis AN - 17975887; 5918005 AB - The chlamydial developmental cycle is characterized by an intracellular replicative form, termed the reticulate body, and an extracellular form called the elementary body. Elementary bodies are characterized by a condensed chromatin, which is maintained by a histone H1-like protein, Hc1. Differentiation of elementary bodies to reticulate bodies is accompanied by dispersal of the chromatin as chlamydiae become transcriptionally active, although the mechanisms of Hc1 release from DNA have remained unknown. Dissociation of the nucleoid requires chlamydial transcription and translation with negligible loss of Hc1. A genetic screen was therefore designed to identify chlamydial genes rescuing Escherichia coli from the lethal effects of Hc1 overexpression. CT804, a gene homologous to ispE, which encodes an intermediate enzyme of the non-mevalonate methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, was selected. E. coli coexpressing CT804 and Hc1 grew normally, although they expressed Hc1 to a level equivalent to that which condensed the chromatin of parent Hc1-expressing controls. Inhibition of the MEP pathway with fosmidomycin abolished IspE rescue of Hc1-expressing E. coli. Deproteinated extract from IspE-expressing bacteria caused dispersal of purified chlamydial nucleoids, suggesting that chlamydial histone-DNA interactions are disrupted by a small metabolite within the MEP pathway rather than by direct action of IspE. By partial reconstruction of the MEP pathway, we determined that 2-C-methylerythritol 2,4-cyclodiphosphate dissociated Hc1 from chlamydial chromatin. These results suggest that chlamydial histone-DNA interactions are disrupted upon germination by a small metabolite in the MEP pathway of isoprenoid biosynthesis. JF - Proceedings of the National Academy of Sciences, USA AU - Grieshaber, NA AU - Fischer, E R AU - Mead, D J AU - Dooley, CA AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, ted_hackstadt@nih.gov Y1 - 2004/05/11/ PY - 2004 DA - 2004 May 11 SP - 7451 EP - 7456 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 19 SN - 0027-8424, 0027-8424 KW - Hc1 protein KW - elementary body KW - methylerythritol phosphate KW - reticulate body KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Microbiology KW - Histones KW - Overexpression KW - Escherichia coli KW - Development KW - Isoprenoids KW - Elementary bodies KW - Chlamydia KW - J 02725:DNA KW - N 14920:Chromatin & chromosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17975887?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Chlamydial+histone-DNA+interactions+are+disrupted+by+a+metabolite+in+the+methylerythritol+phosphate+pathway+of+isoprenoid+biosynthesis&rft.au=Grieshaber%2C+NA%3BFischer%2C+E+R%3BMead%2C+D+J%3BDooley%2C+CA%3BHackstadt%2C+T&rft.aulast=Grieshaber&rft.aufirst=NA&rft.date=2004-05-11&rft.volume=101&rft.issue=19&rft.spage=7451&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0400754101 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Histones; Overexpression; Development; Elementary bodies; Isoprenoids; Escherichia coli; Chlamydia DO - http://dx.doi.org/10.1073/pnas.0400754101 ER - TY - JOUR T1 - The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase. AN - 71911502; 15064730 AB - The human MSH2/6 complex is essential for mismatch recognition during the repair of replication errors. Although mismatch repair components have been implicated in DNA homologous recombination repair, the exact function of hMSH2/6 in this pathway is unclear. Here, we show that the recombinant hMSH2/6 protein complex stimulated the ability of the Bloom's syndrome gene product, BLM, to process Holliday junctions in vitro, an activity that could also be regulated by p53. Consistent with these observations, hMSH6 colocalized with BLM and phospho-ser15-p53 in hydroxyurea-induced RAD51 nuclear foci that may correspond to the sites of presumed stalled DNA replication forks and more likely the resultant DNA double-stranded breaks. In addition, we show that hMSH2 and hMSH6 coimmunoprecipitated with BLM, p53, and RAD51. Both the number of RAD51 foci and the amount of the BLM-p53-RAD51 complex are increased in hMSH2- or hMSH6-deficient cells. These data suggest that hMSH2/6 formed a complex with BLM-p53-RAD51 in response to the damaged DNA forks during double-stranded break repair. JF - Oncogene AU - Yang, Qin AU - Zhang, Ran AU - Wang, Xin W AU - Linke, Steven P AU - Sengupta, Sagar AU - Hickson, Ian D AU - Pedrazzi, Graziella AU - Perrera, Claudia AU - Stagljar, Igor AU - Littman, Susan J AU - Modrich, Paul AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bldg 37, Rm 3068, 37 Convent Drive, Bethesda, MD 20892-4255, USA. Y1 - 2004/05/06/ PY - 2004 DA - 2004 May 06 SP - 3749 EP - 3756 VL - 23 IS - 21 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - G-T mismatch-binding protein KW - Proto-Oncogene Proteins KW - Tumor Suppressor Protein p53 KW - RAD51 protein, human KW - EC 2.7.7.- KW - Rad51 Recombinase KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Bloom syndrome protein KW - MSH2 protein, human KW - EC 3.6.1.3 KW - MutS Homolog 2 Protein KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - Index Medicus KW - Tumor Suppressor Protein p53 -- analysis KW - Humans KW - Dimerization KW - Base Pair Mismatch KW - Cell Line, Tumor KW - Female KW - DNA-Binding Proteins -- analysis KW - DNA Repair KW - DNA-Binding Proteins -- chemistry KW - DNA Helicases -- metabolism KW - Proto-Oncogene Proteins -- analysis KW - Proto-Oncogene Proteins -- chemistry KW - Adenosine Triphosphatases -- metabolism KW - Adenosine Triphosphatases -- analysis KW - DNA-Binding Proteins -- physiology KW - DNA Helicases -- analysis KW - Proto-Oncogene Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71911502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+mismatch+DNA+repair+heterodimer%2C+hMSH2%2F6%2C+regulates+BLM+helicase.&rft.au=Yang%2C+Qin%3BZhang%2C+Ran%3BWang%2C+Xin+W%3BLinke%2C+Steven+P%3BSengupta%2C+Sagar%3BHickson%2C+Ian+D%3BPedrazzi%2C+Graziella%3BPerrera%2C+Claudia%3BStagljar%2C+Igor%3BLittman%2C+Susan+J%3BModrich%2C+Paul%3BHarris%2C+Curtis+C&rft.aulast=Yang&rft.aufirst=Qin&rft.date=2004-05-06&rft.volume=23&rft.issue=21&rft.spage=3749&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-20 N1 - Date created - 2004-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent Extracellular Signal-regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated protein 1b distribution in neurons. AN - 71907304; 15128856 AB - Cyclin-dependent kinase 5 (Cdk5) is a proline-directed kinase the activity of which is dependent on association with its neuron-specific activators, p35 and p39. Cdk5 activity is critical for the proper formation of cortical structures and lamination during development. In the adult nervous system, Cdk5 function is implicated in cellular adhesion, dopamine signaling, neurotransmitter release, and synaptic activity. In addition, Cdk5 is also involved in "cross-talk" with other signal transduction pathways. To further examine its involvement in cross-talk with other pathways, we identified proteins that interacted with p35 using the yeast two-hybrid system. We report here that p35 associates with Ras guanine nucleotide releasing factor 2 (RasGRF2) in coimmunoprecipitation and colocalization studies using transfected cell lines as well as primary cortical neurons. Additionally, Cdk5 phosphorylates RasGRF2 both in vitro and in vivo, leading to a decrease in Rac-guanidine exchange factor activity and a subsequent reduction in extracellular signal-regulated kinase 1/2 activity. We show that p35/Cdk5 phosphorylates RasGRF2 on serine737, which leads to an accumulation of RasGRF2 in the neuronal cell bodies coinciding with an accumulation of microtubule-associated protein 1b. The membrane association of p35 and subsequent localization of Cdk5 activity toward RasGRF2 and Rac provide insights into important cellular signaling processes that occur at the membrane, resulting in downstream effects on signal transduction cascades. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Kesavapany, Sashi AU - Amin, Niranjana AU - Zheng, Ya-Li AU - Nijhara, Ruchika AU - Jaffe, Howard AU - Sihag, Ram AU - Gutkind, J Silvio AU - Takahashi, Satoru AU - Kulkarni, Ashok AU - Grant, Philip AU - Pant, Harish C AD - Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/05/05/ PY - 2004 DA - 2004 May 05 SP - 4421 EP - 4431 VL - 24 IS - 18 KW - Microtubule-Associated Proteins KW - 0 KW - Nerve Tissue Proteins KW - RASGRF2 protein, human KW - Rasgrf2 protein, mouse KW - Rasgrf2 protein, rat KW - microtubule-associated protein 1B KW - neuronal Cdk5 activator (p25-p35) KW - ras Guanine Nucleotide Exchange Factors KW - Cyclin-Dependent Kinase 5 KW - EC 2.7.11.1 KW - CDK5 protein, human KW - EC 2.7.11.22 KW - Cdk5 protein, mouse KW - Cdk5 protein, rat KW - Cyclin-Dependent Kinases KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - rac GTP-Binding Proteins KW - EC 3.6.5.2 KW - ras Proteins KW - Index Medicus KW - rac GTP-Binding Proteins -- metabolism KW - Animals KW - Humans KW - Two-Hybrid System Techniques KW - Mice KW - Binding Sites -- physiology KW - Mice, Knockout KW - Rats KW - Mutagenesis, Site-Directed KW - Signal Transduction -- physiology KW - Phosphorylation KW - Transfection KW - Cells, Cultured KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - COS Cells -- metabolism KW - Cercopithecus aethiops KW - ras Proteins -- metabolism KW - Binding Sites -- genetics KW - Cricetinae KW - Cyclin-Dependent Kinases -- metabolism KW - Microtubule-Associated Proteins -- metabolism KW - Neurons -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Neurons -- cytology KW - ras Guanine Nucleotide Exchange Factors -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - ras Guanine Nucleotide Exchange Factors -- genetics KW - Nerve Tissue Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71907304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p35%2Fcyclin-dependent+kinase+5+phosphorylation+of+ras+guanine+nucleotide+releasing+factor+2+%28RasGRF2%29+mediates+Rac-dependent+Extracellular+Signal-regulated+kinase+1%2F2+activity%2C+altering+RasGRF2+and+microtubule-associated+protein+1b+distribution+in+neurons.&rft.au=Kesavapany%2C+Sashi%3BAmin%2C+Niranjana%3BZheng%2C+Ya-Li%3BNijhara%2C+Ruchika%3BJaffe%2C+Howard%3BSihag%2C+Ram%3BGutkind%2C+J+Silvio%3BTakahashi%2C+Satoru%3BKulkarni%2C+Ashok%3BGrant%2C+Philip%3BPant%2C+Harish+C&rft.aulast=Kesavapany&rft.aufirst=Sashi&rft.date=2004-05-05&rft.volume=24&rft.issue=18&rft.spage=4421&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-03 N1 - Date created - 2004-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of marijuana use disorders in the United States: 1991-1992 and 2001-2002. AN - 71901893; 15126440 AB - Among illicit substance use disorders, marijuana use disorders are the most prevalent in the population. Yet, information about the prevalence of current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) marijuana use disorders and how prevalence has changed is lacking. To examine changes in the prevalence of marijuana use, abuse, and dependence in the United States between 1991-1992 and 2001-2002. Face-to-face interviews were conducted in 2 large national surveys conducted 10 years apart: the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey ([NLAES] n = 42,862) and the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions ([NESARC] n = 43,093). Rates of past year marijuana use, abuse, and dependence. Among the adult US population, the prevalence of marijuana use remained stable at about 4.0% over the past decade. In contrast, the prevalence of DSM-IV marijuana abuse or dependence significantly (P =.01) increased between 1991-1992 (1.2%) and 2001-2002 (1.5%), with the greatest increases observed among young black men and women (P<.001) and young Hispanic men (P =.006). Further, marijuana use disorders among marijuana users significantly increased (P =.002) in the absence of increased frequency and quantity of marijuana use, suggesting that the concomitant increase in potency of delta-9-tetrahydrocannabinol (Delta9-THC) may have contributed to the rising rates. Despite the stability in the overall prevalence of marijuana use, more adults in the United States had a marijuana use disorder in 2001-2002 than in 1991-1992. Increases in the prevalence of marijuana use disorders were most notable among young black men and women and young Hispanic men. Although rates of marijuana abuse and dependence did not increase among young white men and women, their rates have remained high. The results of this study underscore the need to develop and implement new prevention and intervention programs targeted at youth, particularly minority youth. JF - JAMA AU - Compton, Wilson M AU - Grant, Bridget F AU - Colliver, James D AU - Glantz, Meyer D AU - Stinson, Frederick S AD - Division of Epidemiology, Services and Prevention Research, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Md 20892-9589, USA. wcompton@nida.nih.gov Y1 - 2004/05/05/ PY - 2004 DA - 2004 May 05 SP - 2114 EP - 2121 VL - 291 IS - 17 KW - Abridged Index Medicus KW - Index Medicus KW - Hispanic Americans KW - Humans KW - European Continental Ancestry Group KW - Health Surveys KW - Adult KW - African Americans KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Marijuana Abuse -- ethnology KW - Marijuana Abuse -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71901893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prevalence+of+marijuana+use+disorders+in+the+United+States%3A+1991-1992+and+2001-2002.&rft.au=Compton%2C+Wilson+M%3BGrant%2C+Bridget+F%3BColliver%2C+James+D%3BGlantz%2C+Meyer+D%3BStinson%2C+Frederick+S&rft.aulast=Compton&rft.aufirst=Wilson&rft.date=2004-05-05&rft.volume=291&rft.issue=17&rft.spage=2114&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=1538-3598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-07 N1 - Date created - 2004-05-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2004 Aug 18;292(7):802; author reply 802-3 [15315991] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. AN - 71901416; 15071503 AB - Hypoxia induces angiogenesis and glycolysis for cell growth and survival, and also leads to growth arrest and apoptosis. HIF-1alpha, a basic helix-loop-helix PAS transcription factor, acts as a master regulator of oxygen homeostasis by upregulating various genes under low oxygen tension. Although genetic studies have indicated the requirement of HIF-1alpha for hypoxia-induced growth arrest and activation of p21(cip1), a key cyclin-dependent kinase inhibitor controlling cell cycle checkpoint, the mechanism underlying p21(cip1) activation has been elusive. Here we demonstrate that HIF-1alpha, even in the absence of hypoxic signal, induces cell cycle arrest by functionally counteracting Myc, thereby derepressing p21(cip1). The HIF-1alpha antagonism is mediated by displacing Myc binding from p21(cip1) promoter. Neither HIF-1alpha transcriptional activity nor its DNA binding is essential for cell cycle arrest, indicating a divergent role for HIF-1alpha. In keeping with its antagonism of Myc, HIF-1alpha also downregulates Myc-activated genes such as hTERT and BRCA1. Hence, we propose that Myc is an integral part of a novel HIF-1alpha pathway, which regulates a distinct group of Myc target genes in response to hypoxia. JF - The EMBO journal AU - Koshiji, Minori AU - Kageyama, Yukio AU - Pete, Erin A AU - Horikawa, Izumi AU - Barrett, J Carl AU - Huang, L Eric AD - Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/05/05/ PY - 2004 DA - 2004 May 05 SP - 1949 EP - 1956 VL - 23 IS - 9 SN - 0261-4189, 0261-4189 KW - BRCA1 Protein KW - 0 KW - CDKN1A protein, human KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p21 KW - DNA Primers KW - DNA-Binding Proteins KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - MYC protein, human KW - Nuclear Proteins KW - Proto-Oncogene Proteins c-myc KW - Transcription Factors KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Microscopy, Confocal KW - Adenoviridae KW - Animals KW - COS Cells KW - Humans KW - Immunoprecipitation KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cell Cycle Proteins -- metabolism KW - Binding, Competitive -- genetics KW - Blotting, Western KW - Cell Cycle Proteins -- genetics KW - Transfection KW - Cercopithecus aethiops KW - BRCA1 Protein -- metabolism KW - Chromatin Immunoprecipitation KW - Enzyme-Linked Immunosorbent Assay KW - Promoter Regions, Genetic -- genetics KW - Genetic Vectors -- genetics KW - RNA Interference KW - Telomerase -- metabolism KW - Fluorescent Antibody Technique KW - Signal Transduction -- physiology KW - Proto-Oncogene Proteins c-myc -- antagonists & inhibitors KW - Transcription Factors -- metabolism KW - Cell Cycle -- physiology KW - Hypoxia -- metabolism KW - Gene Expression Regulation KW - Nuclear Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71901416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=HIF-1alpha+induces+cell+cycle+arrest+by+functionally+counteracting+Myc.&rft.au=Koshiji%2C+Minori%3BKageyama%2C+Yukio%3BPete%2C+Erin+A%3BHorikawa%2C+Izumi%3BBarrett%2C+J+Carl%3BHuang%2C+L+Eric&rft.aulast=Koshiji&rft.aufirst=Minori&rft.date=2004-05-05&rft.volume=23&rft.issue=9&rft.spage=1949&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Impact of antibody framework residue VH-71 on the stability of a humanised anti-MUC1 scFv and derived immunoenzyme. AN - 66653098; 15150594 AB - Anti-MUC1 single-chain Fv (scFv) fragments generated from the humanised antibody huHMFG1 had adequate antigen-binding properties but very poor stability irrespective of the applied linker or domain orientation. Mutagenesis of heavy-chain framework residue V(H)-71, previously described as a key residue for maintaining the CDR-H2 main-chain conformation and thus important for antigen binding, markedly stabilised the scFv while having only a minor effect on the binding affinity of the molecule. Because of its improved stability, the engineered fragment exhibited immunoreactivity with tumour cells even after 7 days of incubation in human serum at 37 degrees C. It also showed, in contrast to the wild-type scFv, a concentration-dependent binding to the target antigen when displayed on phage. When fusing the scFv to the recombinant ribonuclease rapLRI, only the fusion protein generated with the stable mutant scFv was able to kill MUC1(+) tumour cells with an IC(50) of 80 nM. We expect this novel immunoenzyme to become a promising tool for the treatment of MUC1(+) malignancies. JF - British journal of cancer AU - Krauss, J AU - Arndt, M A E AU - Zhu, Z AU - Newton, D L AU - Vu, B K AU - Choudhry, V AU - Darbha, R AU - Ji, X AU - Courtenay-Luck, N S AU - Deonarain, M P AU - Richards, J AU - Rybak, S M AD - SAIC, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Y1 - 2004/05/04/ PY - 2004 DA - 2004 May 04 SP - 1863 EP - 1870 VL - 90 IS - 9 SN - 0007-0920, 0007-0920 KW - Antibodies, Monoclonal KW - 0 KW - Immunoglobulin Fragments KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Variable Region KW - Membrane Proteins KW - Recombinant Proteins KW - pemtumomab KW - Index Medicus KW - Immunoglobulin Variable Region -- genetics KW - Animals KW - Immunoglobulin Heavy Chains -- immunology KW - Computer Simulation KW - Humans KW - Immunoglobulin Fragments -- genetics KW - Immunoglobulin Variable Region -- immunology KW - Amino Acid Sequence KW - Immunoglobulin Heavy Chains -- genetics KW - Immunoglobulin Fragments -- chemistry KW - Tumor Cells, Cultured KW - Models, Immunological KW - Enzyme Stability KW - Recombinant Proteins -- immunology KW - Recombinant Proteins -- chemistry KW - Protein Structure, Tertiary KW - Mutation KW - Protein Engineering KW - Membrane Proteins -- immunology KW - Antibody Affinity KW - Antibodies, Monoclonal -- chemistry KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66653098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Impact+of+antibody+framework+residue+VH-71+on+the+stability+of+a+humanised+anti-MUC1+scFv+and+derived+immunoenzyme.&rft.au=Krauss%2C+J%3BArndt%2C+M+A+E%3BZhu%2C+Z%3BNewton%2C+D+L%3BVu%2C+B+K%3BChoudhry%2C+V%3BDarbha%2C+R%3BJi%2C+X%3BCourtenay-Luck%2C+N+S%3BDeonarain%2C+M+P%3BRichards%2C+J%3BRybak%2C+S+M&rft.aulast=Krauss&rft.aufirst=J&rft.date=2004-05-04&rft.volume=90&rft.issue=9&rft.spage=1863&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 - 2004-07-15 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1991 Dec 1;51(23 Pt 1):6363-71 [1933899] Mol Immunol. 1990 Aug;27(8):795-802 [1698259] J Mol Biol. 1992 Mar 20;224(2):487-99 [1560463] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4285-9 [1350088] Cancer Res. 1992 Jun 15;52(12):3402-8 [1596900] Biotechnology (N Y). 1992 Jul;10(7):779-83 [1368267] Immunology. 1993 Mar;78(3):364-70 [7682986] Protein Eng. 1994 Jun;7(6):815-22 [7937713] J Mol Biol. 1995 Oct 27;253(3):385-90 [7473721] Biochemistry. 1996 Jan 16;35(2):545-53 [8555226] J Immunol Methods. 1996 Sep 13;196(1):51-62 [8841443] J Mol Biol. 1996 Nov 15;263(5):800-15 [8947577] J Immunol Methods. 1997 Feb 28;201(2):223-31 [9050944] Hum Antibodies. 1997;8(1):3-16 [9265500] Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9637-42 [9275175] J Mol Graph Model. 1997 Apr;15(2):132-4, 112-3 [9385560] Cancer Res. 1998 Feb 1;58(3):485-90 [9458094] J Mol Biol. 1998 May 1;278(2):457-79 [9571064] Proc Natl Acad Sci U S A. 1998 May 26;95(11):5929-34 [9600894] Clin Cancer Res. 1998 Nov;4(11):2605-14 [9829723] Biochim Biophys Acta. 1999 Oct 8;1455(2-3):301-13 [10571020] Cancer Res. 1999 Nov 15;59(22):5758-67 [10582696] Nucleic Acids Res. 2000 Jan 1;28(1):235-42 [10592235] Glycobiology. 2000 May;10(5):439-49 [10764832] Nucleic Acids Res. 2000 Jun 15;28(12):2375-82 [10871370] Proteins. 2000 Sep 1;40(4):572-8 [10899782] Cancer Res. 2000 Nov 15;60(22):6434-40 [11103810] J Immunol. 2001 Jul 1;167(1):296-301 [11418663] Cancer Res. 2001 Sep 15;61(18):6846-50 [11559560] J Clin Oncol. 2002 Jan 1;20(1):274-81 [11773179] Br J Cancer. 2002 Mar 18;86(6):870-8 [11953817] Am J Pathol. 2002 May;160(5):1597-608 [12000712] Histopathology. 2002 May;40(5):440-9 [12010364] Leuk Lymphoma. 2002 May;43(5):953-9 [12148905] Int J Cancer. 2003 Dec 10;107(5):822-9 [14566834] Int J Cancer. 1981 Jul 15;28(1):17-21 [7309278] J Mol Biol. 1985 Dec 5;186(3):651-63 [4093982] Cancer Res. 1988 Jun 1;48(11):3188-96 [3365702] Proteins. 1986 Sep;1(1):74-80 [3449853] J Biol Chem. 1988 Sep 15;263(26):12820-3 [3417635] Gene. 1989 Apr 15;77(1):51-9 [2744487] Nature. 1989 Dec 21-28;342(6252):877-83 [2687698] J Mol Biol. 1990 Sep 5;215(1):175-82 [2118959] J Mol Biol. 1991 Dec 5;222(3):581-97 [1748994] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain network interactions in auditory, visual and linguistic processing. AN - 85385065; pmid-15068921 AB - In the paper, we discuss the importance of network interactions between brain regions in mediating performance of sensorimotor and cognitive tasks, including those associated with language processing. Functional neuroimaging, especially PET and fMRI, provide data that are obtained essentially simultaneously from much of the brain, and thus are ideal for enabling one to assess interregional functional interactions. Two ways to use these types of data to assess network interactions are presented. First, using PET, we demonstrate that anterior and posterior perisylvian language areas have stronger functional connectivity during spontaneous narrative production than during other less linguistically demanding production tasks. Second, we show how one can use large-scale neural network modeling to relate neural activity to the hemodynamically-based data generated by fMRI and PET. We review two versions of a model of object processing - one for visual and one for auditory objects. The regions comprising the models include primary and secondary sensory cortex, association cortex in the temporal lobe, and prefrontal cortex. Each model incorporates specific assumptions about how neurons in each of these areas function, and how neurons in the different areas are interconnected with each other. Each model is able to perform a delayed match-to-sample task for simple objects (simple shapes for the visual model; tonal contours for the auditory model). We find that the simulated electrical activities in each region are similar to those observed in nonhuman primates performing analogous tasks, and the absolute values of the simulated integrated synaptic activity in each brain region match human fMRI/PET data. Thus, this type of modeling provides a way to understand the neural bases for the sensorimotor and cognitive tasks of interest. JF - Brain and language AU - Horwitz, Barry AU - Braun, Allen R AD - Voice, Speech, Language Branch, National Institute on Deafness and Other Communications Disorders, National Institutes of Health, 9000 Rockville Pike, Bldg. 10, Rm. 6C420, MSC 1591, Bethesda, MD 20892, USA. horwitz@helix.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 377 EP - 384 VL - 89 IS - 2 SN - 0093-934X, 0093-934X KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Attention: physiology KW - *Auditory Perception: physiology KW - *Brain: physiology KW - Cerebral Cortex: physiology KW - *Discrimination Learning: physiology KW - Electroencephalography KW - Evoked Potentials: physiology KW - Geniculate Bodies: physiology KW - Gyrus Cinguli: physiology KW - Haplorhini KW - Humans KW - Image Processing, Computer-Assisted KW - Magnetic Resonance Imaging KW - Models, Neurological KW - *Nerve Net: physiology KW - Neural Networks (Computer) KW - *Pattern Recognition, Visual: physiology KW - Psychomotor Performance: physiology KW - Species Specificity KW - *Speech: physiology KW - Tomography, Emission-Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85385065?accountid=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+language&rft.atitle=Brain+network+interactions+in+auditory%2C+visual+and+linguistic+processing.&rft.au=Horwitz%2C+Barry%3BBraun%2C+Allen+R&rft.aulast=Horwitz&rft.aufirst=Barry&rft.date=2004-05-01&rft.volume=89&rft.issue=2&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Brain+and+language&rft.issn=0093934X&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Context-specific memory and apolipoprotein E (ApoE) epsilon 4: cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease. AN - 85377691; pmid-15147594 AB - The aim of the study was to determine whether the epsilon 4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the epsilon 4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale-Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of epsilon 4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an epsilon 4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative epsilon 4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies. JF - Journal of the International Neuropsychological Society : JINS AU - Levy, James A AU - Bergeson, Judy AU - Putnam, Karen AU - Rosen, Virginia AU - Cohen, Robert AU - Lalonde, Francois AU - Mirza, Nadeem AU - Linker, Gary AU - Sunderland, Trey AD - Geriatric Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. jameslevy@mail.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 362 EP - 370 VL - 10 IS - 3 SN - 1355-6177, 1355-6177 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Aged KW - Aged, 80 and over KW - Alleles KW - *Alzheimer Disease: genetics KW - *Alzheimer Disease: physiopathology KW - Apolipoprotein E4 KW - *Apolipoproteins E: genetics KW - Female KW - Gene Frequency KW - Genotype KW - Humans KW - Linear Models KW - Male KW - *Memory: physiology KW - Mental Status Schedule KW - Middle Aged KW - National Institute of Mental Health (U.S.) KW - Neuropsychological Tests KW - Prospective Studies KW - Risk KW - United States KW - Verbal Learning: physiology KW - Wechsler Scales UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85377691?accountid=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+%3A+JINS&rft.atitle=Context-specific+memory+and+apolipoprotein+E+%28ApoE%29+epsilon+4%3A+cognitive+evidence+from+the+NIMH+prospective+study+of+risk+for+Alzheimer%27s+disease.&rft.au=Levy%2C+James+A%3BBergeson%2C+Judy%3BPutnam%2C+Karen%3BRosen%2C+Virginia%3BCohen%2C+Robert%3BLalonde%2C+Francois%3BMirza%2C+Nadeem%3BLinker%2C+Gary%3BSunderland%2C+Trey&rft.aulast=Levy&rft.aufirst=James&rft.date=2004-05-01&rft.volume=10&rft.issue=3&rft.spage=362&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+International+Neuropsychological+Society+%3A+JINS&rft.issn=13556177&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Post-surgical scleritis associated with the ganciclovir implant. AN - 71999702; 15185797 AB - Although the ganciclovir implant is an effective and well-tolerated treatment for cytomegalovirus retinitis in patients with human immunodeficiency virus infection, complications that may occur include retinal detachment, implant extrusion, and endophthalmitis. A 22-year-old woman with human immunodeficiency virus infection presented with a painful left eye with scleritis overlying previous ganciclovir implant sclerotomy sites. The inflammation progressed 360 degrees around the pars plana with progressive thinning at the implant sites. Post-surgical necrotizing scleritis is another complication that can occur in patients with ganciclovir implants. JF - Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye AU - Srivastava, Sunil AU - Taylor, Perdita AU - Wood, Lauren V AU - Lee, Susan S AU - Robinson, Michael R AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1863, USA. PY - 2004 SP - 254 EP - 255 VL - 35 IS - 3 SN - 1542-8877, 1542-8877 KW - Antiviral Agents KW - 0 KW - Drug Implants KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - Cytomegalovirus Retinitis -- drug therapy KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Humans KW - Adult KW - Female KW - Drug Implants -- adverse effects KW - Antiviral Agents -- administration & dosage KW - Postoperative Complications KW - Ganciclovir -- administration & dosage KW - Scleritis -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71999702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ophthalmic+surgery%2C+lasers+%26+imaging+%3A+the+official+journal+of+the+International+Society+for+Imaging+in+the+Eye&rft.atitle=Post-surgical+scleritis+associated+with+the+ganciclovir+implant.&rft.au=Srivastava%2C+Sunil%3BTaylor%2C+Perdita%3BWood%2C+Lauren+V%3BLee%2C+Susan+S%3BRobinson%2C+Michael+R&rft.aulast=Srivastava&rft.aufirst=Sunil&rft.date=2004-05-01&rft.volume=35&rft.issue=3&rft.spage=254&rft.isbn=&rft.btitle=&rft.title=Ophthalmic+surgery%2C+lasers+%26+imaging+%3A+the+official+journal+of+the+International+Society+for+Imaging+in+the+Eye&rft.issn=15428877&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-06 N1 - Date created - 2004-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predictors of falling cholesterol levels in older adults: the Cardiovascular Health Study. AN - 71997443; 15177271 AB - To estimate 4-year change in serum total cholesterol levels in a population-based sample of older adults and identify independent predictors of cholesterol decline. Prospective study of 2837 adults aged 65 years and older with serum cholesterol measured in 1992-1993 and 1996-1997. Mean serum cholesterol levels declined 6.3 mg/dl between the two examinations. Declines were greater in white (-7.3 mg/dl) than black (-1.4 mg/dl) participants and in those in good/excellent health (-0.9 mg/dl) vs. fair/poor health (-3.1 mg/dl; both p < 0.01). Factors associated with greater decline on multivariate analysis included age, male gender, and higher white cell count, albumin, and baseline cholesterol. Cholesterol levels declined 2.0 mg/dl per 6 year increment in baseline age and 6.8 mg/dl more in men than women after adjustment for other factors. C-reactive protein levels were unrelated to cholesterol change. Declining cholesterol levels were associated with male gender, advanced age, weight loss, and white blood cell count but not with C-reactive protein levels. The role of declining cholesterol synthesis, due to as yet undefined age-related changes or to cytokine-mediated reductions related to illness, should be examined to help clarify the mechanisms of the sometimes marked declines in cholesterol levels observed at advanced ages. JF - Annals of epidemiology AU - Manolio, Teri A AU - Cushman, Mary AU - Gottdiener, John S AU - Dobs, Adrian AU - Kuller, Lewis H AU - Kronmal, Richard A AU - CHS Collaborative Research Group AD - Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, MD 20892-7934, USA. manolio@nih.gov ; CHS Collaborative Research Group Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 325 EP - 331 VL - 14 IS - 5 SN - 1047-2797, 1047-2797 KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - African Americans -- statistics & numerical data KW - Health Status KW - Medicare KW - Aged KW - European Continental Ancestry Group -- statistics & numerical data KW - Prospective Studies KW - Risk Factors KW - Forecasting KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Cholesterol -- blood KW - Cardiovascular Diseases -- epidemiology KW - Cholesterol -- adverse effects KW - Cardiovascular Diseases -- physiopathology KW - Cardiovascular Diseases -- ethnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71997443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Predictors+of+falling+cholesterol+levels+in+older+adults%3A+the+Cardiovascular+Health+Study.&rft.au=Manolio%2C+Teri+A%3BCushman%2C+Mary%3BGottdiener%2C+John+S%3BDobs%2C+Adrian%3BKuller%2C+Lewis+H%3BKronmal%2C+Richard+A%3BCHS+Collaborative+Research+Group&rft.aulast=Manolio&rft.aufirst=Teri&rft.date=2004-05-01&rft.volume=14&rft.issue=5&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Annals+of+epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-21 N1 - Date created - 2004-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of the anticarcinogenic activity of Swertia chirata Buch.Ham, an Indian medicinal plant, on DMBA-induced mouse skin carcinogenesis model. AN - 71977523; 15173996 AB - Considerable attention has been focused on plants which are sources of natural anti-oxidant compounds, because most of them have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process. Such compounds are likely to afford protection from cytotoxic, genotoxic and metabolic actions of environmental toxicant thereby reducing the risk for cancer. The present study reports the anticarcinogenic activity of Swertia chirata Buch.Ham, an Indian medicinal plant. All the four detoxification enzymes studied viz, GST, GPx, SOD and CAT were found to be activated in different degrees following treatment with infusion of Swertia chirata, its crude extract and a purified 'Amarogentin' rich extract. The activation of the enzymes was accompanied by significant reduction in lipid peroxidation and inhibition of incidence as well as multiplicity of Dimethylbenz(a)anthracene (DMBA) induced papillomas. The effect of S.chirata on apoptosis and cell proliferation was also studied in mice skin exposed to DMBA. Both the crude and purified extracts significantly inhibited cell proliferation and induced apoptosis. This is the fi rst report of its kind and the observation suggests the chemopreventive potential of Swertia chirata. Copyright 2004 John Wiley & Sons, Ltd. JF - Phytotherapy research : PTR AU - Saha, Prosenjit AU - Mandal, Suvra AU - Das, Ashes AU - Das, Prabhas C AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 373 EP - 378 VL - 18 IS - 5 SN - 0951-418X, 0951-418X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Plant Extracts KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Animals KW - Apoptosis KW - Mice KW - Male KW - Medicine, Traditional KW - India KW - Cell Division KW - Phytotherapy KW - Papilloma -- pathology KW - Papilloma -- prevention & control KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- prevention & control KW - Plant Extracts -- pharmacology KW - Swertia KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Skin Neoplasms -- chemically induced KW - Plant Extracts -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Papilloma -- chemically induced KW - Plant Extracts -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71977523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Phytotherapy+research+%3A+PTR&rft.atitle=Evaluation+of+the+anticarcinogenic+activity+of+Swertia+chirata+Buch.Ham%2C+an+Indian+medicinal+plant%2C+on+DMBA-induced+mouse+skin+carcinogenesis+model.&rft.au=Saha%2C+Prosenjit%3BMandal%2C+Suvra%3BDas%2C+Ashes%3BDas%2C+Prabhas+C%3BDas%2C+Sukta&rft.aulast=Saha&rft.aufirst=Prosenjit&rft.date=2004-05-01&rft.volume=18&rft.issue=5&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Phytotherapy+research+%3A+PTR&rft.issn=0951418X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-13 N1 - Date created - 2004-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chinese strains (Type 7) of JC virus are afro-asiatic in origin but are phylogenetically distinct from the Mongolian and Indian strains (Type 2D) and the Korean and Japanese strains (Type 2A). AN - 71970494; 15170260 AB - We have further characterized the Asian genotypes (Types 2 and 7) and subtypes of JC virus (JCV). Urine samples from 224 individuals with Han and Mongolian populations were collected in five regions in eastern China: Kunming, Chengdu, Shenyang, Chifeng, and Manzhouli. Also, 99 urine samples were collected from coastal and hill groups in Kerala, southern India, and 23 urine samples from Seoul, Korea. PCR products of four typing fragments were sequenced, including two in the VP1 gene, as well as one each in the VT intergenic region and regulatory region. It was possible to clone and sequence a total of 42 JCV whole genomes (approximately 5120 bp). Five genotypes of JCV (Types 7A, 7B, 7C, 2D, and 4) were found in China, four genotypes (Types 2D, 7C, 4, and 1B) in southern India, and three genotypes (Types 7B, 2A, and 1A) in Korea. Type 7A was most prevalent in South China (59-64%) and Type 7B was predominant in northeast China and Inner Mongolia (67-77%). Type 7C strains were spread throughout North and South China (3-14%), while Type 2D strains were found only in the two Mongolian groups (9-10%). In southern India, Type 2D was predominant in the coastal group (95%), and two major types, Type 7C (50%) and Type 2D (35%), were prevalent in the tribal hill groups. In Korea two major genotypes were found: Type 7B (50%) and Type 2A (43%). Phylogenetic reconstruction places the Chinese genotypes in the Afro-Asiatic supercluster, but distinct from the Mongolian and Indian strains (Type 2D), as well as the Korean and Japanese genotype (Type 2A) that predominates in the Americas. JF - Journal of molecular evolution AU - Cui, Xiaohong AU - Wang, Jian C AU - Deckhut, Alison AU - Joseph, Bindu C AU - Eberwein, Philipp AU - Cubitt, Christopher L AU - Ryschkewitsch, Caroline F AU - Agostini, Hansjurgen T AU - Stoner, Gerald L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, MSC-4126, 36 Convent Drive, Bethesda, MD 20892-4126, USA. cuixh@aug.ukl.uni-freiburg.de Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 568 EP - 583 VL - 58 IS - 5 SN - 0022-2844, 0022-2844 KW - DNA, Viral KW - 0 KW - Index Medicus KW - Mongolia KW - Humans KW - Continental Population Groups KW - Sequence Analysis, DNA KW - Korea KW - India KW - Genotype KW - Base Sequence KW - Molecular Sequence Data KW - Africa KW - DNA, Viral -- urine KW - Asia KW - China KW - Japan KW - Phylogeny KW - JC Virus -- genetics KW - JC Virus -- classification KW - Genome, Viral KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71970494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chinese+strains+%28Type+7%29+of+JC+virus+are+afro-asiatic+in+origin+but+are+phylogenetically+distinct+from+the+Mongolian+and+Indian+strains+%28Type+2D%29+and+the+Korean+and+Japanese+strains+%28Type+2A%29.&rft.au=Cui%2C+Xiaohong%3BWang%2C+Jian+C%3BDeckhut%2C+Alison%3BJoseph%2C+Bindu+C%3BEberwein%2C+Philipp%3BCubitt%2C+Christopher+L%3BRyschkewitsch%2C+Caroline+F%3BAgostini%2C+Hansjurgen+T%3BStoner%2C+Gerald+L&rft.aulast=Cui&rft.aufirst=Xiaohong&rft.date=2004-05-01&rft.volume=58&rft.issue=5&rft.spage=568&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 - 2004-12-08 N1 - Date created - 2004-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Toxicogenomics through the eyes of informatics: conference overview and recommendations. AN - 71950875; 15159210 AB - Virginia Bioinformatics Institute, in conjunction with National Institutes of Environmental Health Sciences, hosted a conference, "Toxicogenomics through the Eyes of Informatics," in Bethesda, Maryland, USA, on 12-13 May 2003. Researchers around the world met to discuss how the application of bioinformatics tools, methodologies, and technologies will enhance our understanding of how cells and organisms respond to toxins. Conference topics included statistical methods, quantitative molecular data sets, computational algorithms for data analysis, computational modeling and simulation, challenges and opportunities in computational biology, and information technology infrastructure for data and tool management. This meeting report is a summary of conference presentations, survey results, current toxicogenomics concerns, and future directions of the toxicogenomics community. In conclusion this report discusses toxicogenomics as related to environmental agents, cell-chemical reactions, and gene-environment interactions. JF - Environmental health perspectives AU - Olden, Kenneth AU - Call, Neysa AU - Sobral, Bruno AU - Oakes, Robin Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 805 EP - 807 VL - 112 IS - 7 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Animals KW - Cell Physiological Phenomena KW - International Cooperation KW - Environmental Health KW - Humans KW - Environmental Pollutants -- toxicity KW - Algorithms KW - Information Science -- trends KW - Toxicogenetics -- trends KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71950875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Toxicogenomics+through+the+eyes+of+informatics%3A+conference+overview+and+recommendations.&rft.au=Olden%2C+Kenneth%3BCall%2C+Neysa%3BSobral%2C+Bruno%3BOakes%2C+Robin&rft.aulast=Olden&rft.aufirst=Kenneth&rft.date=2004-05-01&rft.volume=112&rft.issue=7&rft.spage=805&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 - 2004-08-18 N1 - Date created - 2004-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco carcinogen-induced cellular transformation increases Akt activation in vitro and in vivo. AN - 71918541; 15136436 JF - Chest AU - West, Kip A AU - Linnoila, Ilona R AU - Brognard, John AU - Belinsky, Steven AU - Harris, Curtis AU - Dennis, Phillip A AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20889-5105, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 101S EP - 2S VL - 125 IS - 5 Suppl SN - 0012-3692, 0012-3692 KW - Carcinogens KW - 0 KW - Nitrosamines KW - Proto-Oncogene Proteins KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Abridged Index Medicus KW - Index Medicus KW - Mice, Inbred A KW - Animals KW - Receptor, Epidermal Growth Factor -- metabolism KW - Apoptosis KW - Phosphorylation KW - Enzyme Activation KW - Cells, Cultured KW - Humans KW - Mice KW - Lung Neoplasms -- enzymology KW - Proto-Oncogene Proteins -- antagonists & inhibitors KW - Lung Neoplasms -- prevention & control KW - Protein-Serine-Threonine Kinases -- metabolism KW - Cell Transformation, Neoplastic -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71918541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tobacco+carcinogen-induced+cellular+transformation+increases+Akt+activation+in+vitro+and+in+vivo.&rft.au=West%2C+Kip+A%3BLinnoila%2C+Ilona+R%3BBrognard%2C+John%3BBelinsky%2C+Steven%3BHarris%2C+Curtis%3BDennis%2C+Phillip+A&rft.aulast=West&rft.aufirst=Kip&rft.date=2004-05-01&rft.volume=125&rft.issue=5+Suppl&rft.spage=101S&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-29 N1 - Date created - 2004-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of beta-catenin pathway or genomic instability define two distinct categories of liver cancer in transgenic mice. AN - 71915953; 15131798 AB - Human liver cancer can be divided into 2 categories that are characterized by activation of beta-catenin and genomic instability. Here we investigate whether similar categories exist among 5 transgenic models of liver cancer, including c-myc, transforming growth factor-alpha, E2F-1, c-myc/transforming growth factor-alpha, and c-myc/E2F-1 mice. The random amplified polymorphic DNA method was used to assess the overall genomic instability, and chromosomal loci affected by genomic alterations were determined by microsatellite analysis. beta-Catenin mutations and deletions were analyzed by polymerase chain reaction and sequencing screening. Cellular localization of beta-catenin and expression of alpha-fetoprotein, a prognostic marker of hepatocellular carcinoma, were investigated by immunohistochemistry. Liver tumors from the transgenic mice could be divided into 2 broad categories characterized by extensive genomic instability (exemplified by the c-myc/transforming growth factor-alpha mouse) and activation of beta-catenin (exemplified by the c-myc/E2F-1 mouse). The c-myc/transforming growth factor-alpha tumors displayed extensive genomic instability with recurrent loss of heterozygosity at chromosomes 1, 2, 4, 6, 7, 9, 12, 14, and X and a low rate of beta-catenin activation. The genomic instability was evident from the early dysplastic stage and occurred concomitantly with increased expression of alpha-fetoprotein. The c-myc/E2F-1 tumors were characterized by a high frequency of beta-catenin activation in the presence of a relatively stable genome and low alpha-fetoprotein levels. We have identified 2 prototype experimental models, i.e., c-myc/transforming growth factor-alpha and c-myc/E2F-1 mice, for the 2 categories of human hepatocellular carcinoma characterized by genomic instability and beta-catenin activation, respectively. These mouse models will assist in the elucidation of the molecular basis of human hepatocellular carcinoma. JF - Gastroenterology AU - Calvisi, Diego F AU - Factor, Valentina M AU - Ladu, Sara AU - Conner, Elizabeth A AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute/NIH, Building 37, 37 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1374 EP - 1386 VL - 126 IS - 5 SN - 0016-5085, 0016-5085 KW - CTNNB1 protein, mouse KW - 0 KW - Cell Cycle Proteins KW - Cytoskeletal Proteins KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - E2F1 Transcription Factor KW - E2f1 protein, mouse KW - Quinoxalines KW - Trans-Activators KW - Transcription Factors KW - Transforming Growth Factor alpha KW - alpha-Fetoproteins KW - beta Catenin KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Gene Frequency KW - Genes, myc KW - DNA-Binding Proteins -- genetics KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Transcription Factors -- genetics KW - Phenotype KW - Loss of Heterozygosity KW - Transforming Growth Factor alpha -- genetics KW - Quinoxalines -- pharmacology KW - alpha-Fetoproteins -- metabolism KW - Trans-Activators -- metabolism KW - Liver Neoplasms -- metabolism KW - Genomic Instability KW - Trans-Activators -- genetics KW - Cytoskeletal Proteins -- metabolism KW - Mutation KW - Liver Neoplasms -- genetics KW - Gene Deletion KW - Cytoskeletal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71915953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=Disruption+of+beta-catenin+pathway+or+genomic+instability+define+two+distinct+categories+of+liver+cancer+in+transgenic+mice.&rft.au=Calvisi%2C+Diego+F%3BFactor%2C+Valentina+M%3BLadu%2C+Sara%3BConner%2C+Elizabeth+A%3BThorgeirsson%2C+Snorri+S&rft.aulast=Calvisi&rft.aufirst=Diego&rft.date=2004-05-01&rft.volume=126&rft.issue=5&rft.spage=1374&rft.isbn=&rft.btitle=&rft.title=Gastroenterology&rft.issn=00165085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-23 N1 - Date created - 2004-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products. AN - 71915678; 15128270 AB - The hypothalamic-pituitary-adrenal (HPA) axis is activated during many bacterial and viral infections, resulting in an increase in circulating glucocorticoid levels. This HPA axis activation and glucocorticoid response are critical for the survival of the host, as demonstrated by the fact that removal of the HPA axis (by adrenalectomy or hypophysectomy) or glucocorticoid receptor (GR) blockade enhances the severity of the infection and in some cases enhances the mortality rate. Replacement with a synthetic glucocorticoid reverses these effects by reducing the severity of the infection and provides protection against lethal effects. In addition, some bacteria and viral infections have been shown to affect the GR directly. These have been described and the implications of such an effect discussed. JF - The Journal of endocrinology AU - Webster, Jeanette I AU - Sternberg, Esther M AD - Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 207 EP - 221 VL - 181 IS - 2 SN - 0022-0795, 0022-0795 KW - Bacterial Proteins KW - 0 KW - Cytokines KW - Glucocorticoids KW - Receptors, Glucocorticoid KW - Viral Proteins KW - Index Medicus KW - Animals KW - Humans KW - Cytokines -- immunology KW - Bacterial Proteins -- metabolism KW - Viral Proteins -- metabolism KW - Shock, Septic -- physiopathology KW - Shock, Septic -- metabolism KW - Hypothalamo-Hypophyseal System -- physiology KW - Glucocorticoids -- metabolism KW - Virus Diseases -- immunology KW - Bacterial Infections -- physiopathology KW - Virus Diseases -- physiopathology KW - Bacterial Infections -- immunology KW - Receptors, Glucocorticoid -- metabolism KW - Pituitary-Adrenal System -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71915678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+endocrinology&rft.atitle=Role+of+the+hypothalamic-pituitary-adrenal+axis%2C+glucocorticoids+and+glucocorticoid+receptors+in+toxic+sequelae+of+exposure+to+bacterial+and+viral+products.&rft.au=Webster%2C+Jeanette+I%3BSternberg%2C+Esther+M&rft.aulast=Webster&rft.aufirst=Jeanette&rft.date=2004-05-01&rft.volume=181&rft.issue=2&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+endocrinology&rft.issn=00220795&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-16 N1 - Date created - 2004-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ESR investigation of the oxidative damage in lungs caused by asbestos and air pollution particles. AN - 71915406; 15134737 AB - Exposure to asbestos and air pollution particles can be associated with increased human morbidity and mortality. However, the molecular mechanism of lung injuries remains unknown. It has been postulated that the in vivo toxicity results from the catalysis of free radical generation. Using electron spin resonance (ESR) in conjunction with the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) we previously investigated in vivo free radical production by rats treated with intratracheal instillation of asbestos (crocidolite fibers) and an emission source air pollution particle (oil fly ash). In this report we compare the effect of two different exposures on the type of free radicals they induce in in vivo animal model. Twenty-four hours after the exposure, ESR spectroscopy of the chloroform extract from lungs of animals exposed to either asbestos or oil fly ash gave a spectrum consistent with a carbon-centered radical adduct (aN = 15.01 G and aH = 2.46 G). To test whether free radical formation occurred in vivo and not in vitro, a number of control experiments were performed. Combinations (both individually and together) of asbestos or oil fly ash and 4-POBN were added to lung homogenate of unexposed rats prior to chloroform extraction. No detectable ESR signal resulted. To exclude the possibility of ex vivo free radical generation, asbestos or oil fly ash was added to lung homogenate of an animal treated with 4-POBN. Also, 4-POBN was added to lung homogenate from rats instilled with asbestos or oil fly ash. Neither system produced radical adducts, indicating that the ESR signal detected in the lung extracts of the treated animals must be produced in vivo and not ex vivo or in vitro. In conclusion, ESR analysis of lung tissue demonstrated that both exposures produce lipid-derived radical metabolites despite their different composition and structure. Analogously, both exposures provide evidence of in vivo enhanced lipid peroxidation. Furthermore, it is concluded that without the presence of a spin-trapping agent, no free radical metabolites could be detected directly by ESR in either exposure. JF - Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy AU - Kadiiska, M B AU - Ghio, A J AU - Mason, R P AD - National Institutes of Environmental Health Sciences, National Institutes of Health, MD F0-02, P.O. Box 12233, Research Triangle Park, NC 27709, USA. kadiiska@niehs.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1371 EP - 1377 VL - 60 IS - 6 SN - 1386-1425, 1386-1425 KW - Air Pollutants KW - 0 KW - Carcinogens KW - Coal Ash KW - Free Radicals KW - Particulate Matter KW - Asbestos, Crocidolite KW - 12001-28-4 KW - Carbon KW - 7440-44-0 KW - Index Medicus KW - Animals KW - Lung Diseases -- etiology KW - Particle Size KW - Carbon -- metabolism KW - Free Radicals -- metabolism KW - Lipid Peroxidation KW - Carbon -- administration & dosage KW - Rats KW - Oxidation-Reduction KW - Rats, Sprague-Dawley KW - Spin Trapping KW - Instillation, Drug KW - Male KW - Electron Spin Resonance Spectroscopy KW - Asbestos, Crocidolite -- administration & dosage KW - Lung -- drug effects KW - Carcinogens -- toxicity KW - Lung -- pathology KW - Lung -- metabolism KW - Air Pollutants -- toxicity KW - Asbestos, Crocidolite -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71915406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Spectrochimica+acta.+Part+A%2C+Molecular+and+biomolecular+spectroscopy&rft.atitle=ESR+investigation+of+the+oxidative+damage+in+lungs+caused+by+asbestos+and+air+pollution+particles.&rft.au=Kadiiska%2C+M+B%3BGhio%2C+A+J%3BMason%2C+R+P&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=2004-05-01&rft.volume=60&rft.issue=6&rft.spage=1371&rft.isbn=&rft.btitle=&rft.title=Spectrochimica+acta.+Part+A%2C+Molecular+and+biomolecular+spectroscopy&rft.issn=13861425&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-07 N1 - Date created - 2004-05-11 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 - 71913260; 15136428 JF - Chest AU - Hofseth, Lorne J AU - Robles, Ana I AU - Yang, Qin AU - Wang, Xin W AU - Hussain, S Perwez AU - Harris, Curtis AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 83S EP - 5S VL - 125 IS - 5 Suppl SN - 0012-3692, 0012-3692 KW - Abridged Index Medicus KW - Index Medicus KW - Molecular Epidemiology KW - Risk Factors KW - Humans KW - Smoking -- adverse effects KW - Mutation KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Genes, p53 -- genetics KW - Lung Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71913260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53%3A+at+the+crossroads+of+molecular+carcinogenesis+and+molecular+epidemiology.&rft.au=Hofseth%2C+Lorne+J%3BRobles%2C+Ana+I%3BYang%2C+Qin%3BWang%2C+Xin+W%3BHussain%2C+S+Perwez%3BHarris%2C+Curtis&rft.aulast=Hofseth&rft.aufirst=Lorne&rft.date=2004-05-01&rft.volume=125&rft.issue=5+Suppl&rft.spage=83S&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-29 N1 - Date created - 2004-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allogeneic hematopoietic stem cell transplantation for metastatic breast cancer. AN - 71912694; 15136224 AB - The prognosis is poor and the options are limited for patients with metastatic breast cancer (MBC), especially for those patients who have previously received taxanes and anthracyclines; treatment strategies are primarily palliative. Murine models have demonstrated that allogeneic T cells are capable of eliciting graft-versus-tumor (GVT) effects against breast cancer, inhibiting growth of breast cancer cell lines in vivo, providing the rationale to pursue allogeneic adoptive cellular therapy as a strategy to treat MBC. However, the clinical application of allogeneic hematopoietic stem cell transplantation (alloHSCT) was limited by concerns over toxicity and unproven efficacy. The development of non-myeloablative (a.k.a. reduced-intensity) conditioning regimens, which have less treatment-related mortality but preserve the T-cell mediated GVT effects, led to increased investigation of alloHSCT in MBC. Early reports of non-myeloablative alloHSCT indicate that a clinical GVT effect against breast cancer does exist. The responses, observed in 20-40% of patients, appear to be associated with the development of complete donor lymphoid chimerism and may be delayed. In its current form, alloHSCT by itself is unlikely to result in complete eradication of MBC; however, it may serve as a therapeutic platform to complement and enhance the effects of existing cytotoxic therapies and immunotherapies (e.g. trastuzumab), as well as therapies under development (e.g. vaccines). Current data on alloHSCT for MBC should be interpreted cautiously and carefully used for the design of future studies to fully determine the clinical efficacy of this form of adoptive cellular therapy in MBC. JF - Haematologica AU - Bishop, Michael R AD - Experimental Transplantation and Immunology Branch, National Cancer Institute, Building 10, Room 12N226 Bethesda, MD 20892, USA. mbishop@mail.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 599 EP - 605 VL - 89 IS - 5 KW - Index Medicus KW - Models, Animal KW - Animals KW - Graft vs Tumor Effect KW - Transplantation Conditioning KW - Combined Modality Therapy KW - Humans KW - Neoplasm Metastasis KW - Immunotherapy, Adoptive KW - T-Lymphocytes -- physiology KW - Transplantation, Homologous KW - Female KW - Breast Neoplasms -- immunology KW - Breast Neoplasms -- pathology KW - Hematopoietic Stem Cell Transplantation KW - Breast Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71912694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Haematologica&rft.atitle=Allogeneic+hematopoietic+stem+cell+transplantation+for+metastatic+breast+cancer.&rft.au=Bishop%2C+Michael+R&rft.aulast=Triggle&rft.aufirst=Nick&rft.date=2015-01-01&rft.volume=21&rft.issue=9&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Nursing+Management+%282014%2B%29&rft.issn=13545760&rft_id=info:doi/10.7748%2Fnm.21.9.6.s2 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-04-25 N1 - Date created - 2004-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the interaction of ingenol 3-angelate with protein kinase C. AN - 71905156; 15126366 AB - Ingenol 3-angelate (I3A) is one of the active ingredients in Euphorbia peplus, which has been used in traditional medicine. Here, we report the initial characterization of I3A as a protein kinase C (PKC) ligand. I3A bound to PKC-alpha in the presence of phosphatidylserine with high affinity; however, under these assay conditions, little PKC isoform selectivity was observed. PKC isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate (PMA) in WEHI-231, HOP-92, and Colo-205 cells. In all of the three cell types, I3A inhibited cell proliferation with somewhat lower potency than did PMA. In intact CHO-K1 cells, I3A was able to translocate different green fluorescent protein-tagged PKC isoforms, visualized by confocal microscopy, with equal or higher potency than PMA. PKC-delta in particular showed a different pattern of translocation in response to I3A and PMA. I3A induced a higher level of secretion of the inflammatory cytokine interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction. I3A was unable to cause the same extent of association of the C1b domain of PKC-delta with lipids, compared with PMA or the physiological regulator diacylglycerol, and was able to partially block the association induced by these agents, measured by surface plasmon resonance. The in vitro kinase activity of PKC-alpha induced by I3A was lower than that induced by PMA. The novel pattern of behavior of I3A makes it of great interest for further evaluation. JF - Cancer research AU - Kedei, Noemi AU - Lundberg, Daniel J AU - Toth, Attila AU - Welburn, Peter AU - Garfield, Susan H AU - Blumberg, Peter M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 2004/05/01/ PY - 2004 DA - 2004 May 01 SP - 3243 EP - 3255 VL - 64 IS - 9 SN - 0008-5472, 0008-5472 KW - Diterpenes KW - 0 KW - Interleukin-6 KW - Isoenzymes KW - Ligands KW - Liposomes KW - ingenol KW - 30220-46-3 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Down-Regulation KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - CHO Cells KW - Liposomes -- chemistry KW - Interleukin-6 -- biosynthesis KW - Isoenzymes -- metabolism KW - Euphorbia -- chemistry KW - Cricetinae KW - Protein Kinase C -- metabolism KW - Diterpenes -- pharmacology KW - Diterpenes -- metabolism KW - Diterpenes -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71905156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+interaction+of+ingenol+3-angelate+with+protein+kinase+C.&rft.au=Kedei%2C+Noemi%3BLundberg%2C+Daniel+J%3BToth%2C+Attila%3BWelburn%2C+Peter%3BGarfield%2C+Susan+H%3BBlumberg%2C+Peter+M&rft.aulast=Kedei&rft.aufirst=Noemi&rft.date=2004-05-01&rft.volume=64&rft.issue=9&rft.spage=3243&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 - 2004-06-23 N1 - Date created - 2004-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Weight and body composition changes during and after adjuvant chemotherapy in women with breast cancer. AN - 71902821; 15126549 AB - Uncontrolled trials have reported significant weight gain in women with breast cancer during treatment with adjuvant chemotherapy. We prospectively evaluated body composition before (visit 1), immediately after (visit 2), and 6 months after (visit 3) chemotherapy in 20 women with stages I-IIIA breast cancer [body mass index (BMI): 24.1 +/- 3.9 kg/m(2)]. We compared their weight change to 51 age- and BMI-matched healthy controls (BMI: 25.5 +/- 3.8 kg/m(2)). In women with breast cancer, there was no weight change from visit 1-2, or from visit 1-3, but weight increased from visit 2-3 (+1.09 +/- 2.46 kg; P = 0.05). Weight change was not different from controls during either interval. In the breast cancer group, the percentage of body fat assessed by air displacement plethysmography increased, and fat-free mass decreased from visit 1-2 (+2.3 +/- 4% and -2.2 +/- 4%; P = 0.02) and from visit 1-3 (+4.0 +/- 6% and -3.8 +/- 6%; P = 0.01). By dual energy x-ray absorptiometry, the percentage of body fat increased from visit 2-3 (+0.9 +/- 1.6%; P = 0.02). Bone mineral content decreased from visit 2-3 (-0.02 +/- 0.04 kg; P = 0.02) and from visit 1-3 (-0.04 +/- 0.06 kg; P = 0.005). By computed tomography, the visceral adipose to sc adipose tissue ratio decreased from visit 1-3 (-0.02 +/- 0.05 ml; P = 0.02). We conclude that, compared with controls, women with breast cancer receiving modern adjuvant chemotherapy regimens show no significant changes in weight during the first year of their treatment. They do, however, appear to undergo unfavorable changes in body composition. JF - The Journal of clinical endocrinology and metabolism AU - Freedman, R J AU - Aziz, N AU - Albanes, D AU - Hartman, T AU - Danforth, D AU - Hill, S AU - Sebring, N AU - Reynolds, J C AU - Yanovski, J A AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20892, USA. freedmanr@mail.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 2248 EP - 2253 VL - 89 IS - 5 SN - 0021-972X, 0021-972X KW - Antineoplastic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Bone Density -- drug effects KW - Neoplasm Staging KW - Humans KW - Adult KW - Case-Control Studies KW - Absorptiometry, Photon KW - Middle Aged KW - Body Mass Index KW - Plethysmography KW - Chemotherapy, Adjuvant -- adverse effects KW - Menopause KW - Female KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- diagnostic imaging KW - Breast Neoplasms -- pathology KW - Body Weight -- drug effects KW - Breast Neoplasms -- metabolism KW - Body Composition -- drug effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71902821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Weight+and+body+composition+changes+during+and+after+adjuvant+chemotherapy+in+women+with+breast+cancer.&rft.au=Freedman%2C+R+J%3BAziz%2C+N%3BAlbanes%2C+D%3BHartman%2C+T%3BDanforth%2C+D%3BHill%2C+S%3BSebring%2C+N%3BReynolds%2C+J+C%3BYanovski%2C+J+A&rft.aulast=Freedman&rft.aufirst=R&rft.date=2004-05-01&rft.volume=89&rft.issue=5&rft.spage=2248&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 - 2004-07-14 N1 - Date created - 2004-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control. AN - 71901821; 15124026 AB - Control of cancer, neuropathic, and postoperative pain is frequently inadequate or compromised by debilitating side effects. Inhibition or removal of certain nociceptive neurons, while retaining all other sensory modalities and motor function, would represent a new therapeutic approach to control severe pain. The enriched expression of transient receptor potential cation channel, subfamily V, member 1 (TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trigeminal ganglia allowed us to test this concept. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya induces calcium cytotoxicity by opening the TRPV1 ion channel and selectively ablates nociceptive neurons. This treatment blocks experimental inflammatory hyperalgesia and neurogenic inflammation in rats and naturally occurring cancer and debilitating arthritic pain in dogs. Sensations of touch, proprioception, and high-threshold mechanosensitive nociception, as well as locomotor function, remained intact in both species. In separate experiments directed at postoperative pain control, subcutaneous administration of RTX transiently disrupted nociceptive nerve endings, yielding reversible analgesia. In human dorsal root ganglion cultures, RTX induced a prolonged increase in intracellular calcium in vanilloid-sensitive neurons, while leaving other, adjacent neurons unaffected. The results suggest that nociceptive neuronal or nerve terminal deletion will be effective and broadly applicable as strategies for pain management. JF - The Journal of clinical investigation AU - Karai, Laszlo AU - Brown, Dorothy C AU - Mannes, Andrew J AU - Connelly, Stephen T AU - Brown, Jacob AU - Gandal, Michael AU - Wellisch, Ofer M AU - Neubert, John K AU - Olah, Zoltan AU - Iadarola, Michael J AD - National Institute of Dental and Craniofacial Research, Bethesda, Maryland 20892, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1344 EP - 1352 VL - 113 IS - 9 SN - 0021-9738, 0021-9738 KW - Diterpenes KW - 0 KW - Receptors, Drug KW - resiniferatoxin KW - A5O6P1UL4I KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Microinjections KW - Extravasation of Diagnostic and Therapeutic Materials -- prevention & control KW - Analgesia -- methods KW - Rats KW - Neurons, Afferent -- metabolism KW - Ganglia, Spinal -- cytology KW - Rats, Sprague-Dawley KW - Calcium -- toxicity KW - Trigeminal Ganglion -- drug effects KW - Cells, Cultured KW - Ganglia, Spinal -- metabolism KW - Adult KW - Nociceptors -- metabolism KW - Dogs KW - Neurons, Afferent -- drug effects KW - Time Factors KW - Male KW - Stereotaxic Techniques KW - Receptors, Drug -- metabolism KW - Pain Management KW - Pain Measurement -- methods KW - Diterpenes -- administration & dosage KW - Pain Measurement -- drug effects KW - Diterpenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71901821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deletion+of+vanilloid+receptor+1-expressing+primary+afferent+neurons+for+pain+control.&rft.au=Karai%2C+Laszlo%3BBrown%2C+Dorothy+C%3BMannes%2C+Andrew+J%3BConnelly%2C+Stephen+T%3BBrown%2C+Jacob%3BGandal%2C+Michael%3BWellisch%2C+Ofer+M%3BNeubert%2C+John+K%3BOlah%2C+Zoltan%3BIadarola%2C+Michael+J&rft.aulast=Karai&rft.aufirst=Laszlo&rft.date=2004-05-01&rft.volume=113&rft.issue=9&rft.spage=1344&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 - 2004-05-21 N1 - Date created - 2004-05-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Regul Pept. 1992 Jun 11;39(2-3):123-35 [1279751] N Engl J Med. 1994 Mar 3;330(9):592-6 [7508092] Neurosurgery. 1996 May;38(5):865-71 [8727810] Life Sci. 1997;60(10):681-96 [9064473] Nature. 1997 Oct 23;389(6653):816-24 [9349813] Gen Pharmacol. 1998 Jan;30(1):5-11 [9457475] Brain. 1998 May;121 ( Pt 5):931-47 [9619195] JAMA. 1998 Jun 17;279(23):1877-82 [9634258] Neuroreport. 1998 Jun 22;9(9):2045-8 [9674591] Neuron. 1998 Sep;21(3):531-43 [9768840] Clin Pharmacol Ther. 1998 Nov;64(5):562-8 [9834049] Brain Res. 1998 Nov 2;809(2):246-52 [9853117] Neurosci Biobehav Rev. 1998;23(1):111-29 [9861616] Pain. 1999 Feb;79(2-3):243-53 [10068170] Pain. 1999 May;81(1-2):135-45 [10353501] J Neurosci. 1999 Jul 1;19(13):5420-8 [10377351] Nature. 2000 May 11;405(6783):183-7 [10821274] J Biol Chem. 2001 Apr 6;276(14):11021-30 [11124944] Eur J Pharmacol. 2001 Apr 6;417(1-2):51-8 [11301059] J Urol. 2001 Jun;165(6 Pt 1):1849-57; discussion 157-8 [11371866] Br J Anaesth. 2001 Jul;87(1):88-98 [11460816] Support Care Cancer. 2001 Sep;9(6):403-7 [11585266] N Engl J Med. 2000 Feb 3;342(5):326-33 [10655532] Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3655-60 [10725386] Science. 2000 Apr 14;288(5464):306-13 [10764638] Eur J Pharmacol. 2001 Oct 19;429(1-3):23-37 [11698024] Brain Res Mol Brain Res. 2002 Jan 31;98(1-2):51-7 [11834295] Curr Oncol Rep. 2002 May;4(3):242-9 [11937015] Eur J Neurosci. 2002 Jul;16(2):175-85 [12169100] J Pharmacol Exp Ther. 2002 Sep;302(3):839-45 [12183638] Neuron. 2002 Aug 15;35(4):721-31 [12194871] J Physiol. 2002 Sep 1;543(Pt 2):531-40 [12205187] J Clin Oncol. 2002 Oct 1;20(19):4040-9 [12351602] Nat Neurosci. 2002 Nov;5 Suppl:1062-7 [12403987] Neuroscience. 2003;116(3):621-7 [12573705] Expert Opin Investig Drugs. 2003 Apr;12(4):545-59 [12665411] J Neurosci. 2003 Apr 1;23(7):2911-9 [12684478] Neuroscience. 2003;120(1):155-62 [12849749] Pain. 2003 Jul;104(1-2):219-28 [12855332] Neurotoxicology. 2003 Dec;24(6):895-908 [14637384] Br J Pharmacol Chemother. 1967 Sep;31(1):138-51 [6055248] Science. 1973 Aug 3;181(4098):407-14 [4123997] Science. 1979 Oct 26;206(4417):481-3 [228392] Brain Res. 1981 Apr 6;210(1-2):83-9 [7225825] Brain Res. 1981 May 4;211(2):497-502 [6165438] Neurosurgery. 1984 Dec;15(6):928-32 [6514166] Pain. 1988 Jan;32(1):77-88 [3340425] Brain Res. 1988 Jul 12;455(2):205-12 [2900057] Neuroscience. 1989;30(2):515-20 [2747924] Peptides. 1989 Sep-Oct;10(5):979-83 [2608558] Brain Res. 1990 Jun 18;520(1-2):131-40 [2169951] Pharmacol Rev. 1991 Jun;43(2):143-201 [1852779] Nature. 1992 Jan 2;355(6355):75-8 [1370574] Neuroscience. 1990;37(2):531-9 [1723514] J Physiol. 1992 Mar;448:749-64 [1593488] Neurosci Lett. 1992 Jul 20;141(2):259-61 [1436645] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reducing the toxicity associated with the use of radiotherapy in men with localized prostate cancer. AN - 71898825; 15123413 AB - The risk for serious complications associated with modern radiotherapy is relatively low. Compared with conventional radiotherapy, 3DCRT and IMRT allow higher doses to be given more safely. The use of IMRT increases the time and effort required by physicians and physicists. Although there is a clear move toward IMRT, 3DCRT is considered standard. The quality assurance procedures for and fundamental questions regarding IMRT are evolving, including the radiobiologic consequences of altered time-dose fractionation and the greater dose heterogeneity in the target. Defining an accurate target volume and routinely correcting for set-up error and organ movement before each treatment promise to reduce the complications associated with EBRT in the next 5 years. Complications following prostate brachytherapy are better understood now than 10 years ago. Dosimetric or patient selection factors that correlate with a higher risk for complications, such as acute retention, strictures, severe prolonged urinary symptoms, fistulas, proctitis, and impotence, often can be accounted for or avoided. Finally, the role of radiation protectors is beginning to be addressed. It is hoped that these advances will eliminate toxicity associated with radiotherapy and increase cure rates. JF - The Urologic clinics of North America AU - Roach, Mack AD - Department of Radiation Oncology, University of California, San Francisco, UCSF/Mt Zion NCI-Designated Comprehensive Cancer, 1600 Divisadero Street, San Francisco, CA 94143-1708, USA. roach@radonc17.ucsf.edu Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 353 EP - 366 VL - 31 IS - 2 SN - 0094-0143, 0094-0143 KW - Abridged Index Medicus KW - Index Medicus KW - Radiotherapy Planning, Computer-Assisted -- methods KW - Radiotherapy Dosage KW - Humans KW - Brachytherapy -- adverse effects KW - Prognosis KW - Brachytherapy -- methods KW - Incidence KW - Aged KW - Middle Aged KW - Dose-Response Relationship, Radiation KW - Male KW - Risk Assessment KW - Prostatic Neoplasms -- pathology KW - Radiotherapy, Conformal -- methods KW - Radiation Injuries -- prevention & control KW - Radiation Injuries -- epidemiology KW - Primary Prevention -- methods KW - Prostatic Neoplasms -- radiotherapy KW - Radiotherapy, Conformal -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71898825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Urologic+clinics+of+North+America&rft.atitle=Reducing+the+toxicity+associated+with+the+use+of+radiotherapy+in+men+with+localized+prostate+cancer.&rft.au=Roach%2C+Mack&rft.aulast=Roach&rft.aufirst=Mack&rft.date=2004-05-01&rft.volume=31&rft.issue=2&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=The+Urologic+clinics+of+North+America&rft.issn=00940143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-22 N1 - Date created - 2004-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health and environmental consequences of the world trade center disaster. AN - 71892715; 15121517 AB - The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperreactivity. Evaluation of 10,116 firefighters showed exposure-related increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on 11 September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster. JF - Environmental health perspectives AU - Landrigan, Philip J AU - Lioy, Paul J AU - Thurston, George AU - Berkowitz, Gertrud AU - Chen, L C AU - Chillrud, Steven N AU - Gavett, Stephen H AU - Georgopoulos, Panos G AU - Geyh, Alison S AU - Levin, Stephen AU - Perera, Frederica AU - Rappaport, Stephen M AU - Small, Christopher AU - NIEHS World Trade Center Working Group AD - Mount Sinai School of Medicine, New York, New York 10029, USA. phil.landrigan@mssm.edu ; NIEHS World Trade Center Working Group Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 731 EP - 739 VL - 112 IS - 6 SN - 0091-6765, 0091-6765 KW - Polycyclic Aromatic Hydrocarbons KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Hydrogen-Ion Concentration KW - Infant, Newborn KW - Mice KW - Lung -- pathology KW - Risk Assessment KW - Pregnancy KW - Lung -- immunology KW - New York City KW - Adult KW - Polycyclic Aromatic Hydrocarbons -- analysis KW - Incidence KW - Middle Aged KW - Polycyclic Aromatic Hydrocarbons -- poisoning KW - Female KW - Infant, Small for Gestational Age KW - Male KW - Prevalence KW - Occupational Exposure KW - Terrorism KW - Aircraft KW - Respiratory Tract Diseases -- etiology KW - Respiratory Tract Diseases -- epidemiology KW - Environmental Exposure KW - Construction Materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71892715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Health+and+environmental+consequences+of+the+world+trade+center+disaster.&rft.au=Landrigan%2C+Philip+J%3BLioy%2C+Paul+J%3BThurston%2C+George%3BBerkowitz%2C+Gertrud%3BChen%2C+L+C%3BChillrud%2C+Steven+N%3BGavett%2C+Stephen+H%3BGeorgopoulos%2C+Panos+G%3BGeyh%2C+Alison+S%3BLevin%2C+Stephen%3BPerera%2C+Frederica%3BRappaport%2C+Stephen+M%3BSmall%2C+Christopher%3BNIEHS+World+Trade+Center+Working+Group&rft.aulast=Landrigan&rft.aufirst=Philip&rft.date=2004-05-01&rft.volume=112&rft.issue=6&rft.spage=731&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 - 2004-06-10 N1 - Date created - 2004-05-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 2002 Jul;110(7):703-14 [12117648] Environ Health Perspect. 2003 Jun;111(7):972-80 [12782501] J Urban Health. 2002 Sep;79(3):340-53 [12200503] N Engl J Med. 2002 Sep 12;347(11):806-15 [12226151] N Engl J Med. 2002 Sep 12;347(11):840-2 [12226157] Am J Respir Crit Care Med. 2002 Sep 15;166(6):785-6 [12231482] Am J Respir Crit Care Med. 2002 Sep 15;166(6):797-800 [12231487] Int J Emerg Ment Health. 2002 Summer;4(3):143-55 [12387188] Am J Ind Med. 2002 Dec;42(6):532-8 [12439878] Am J Ind Med. 2002 Dec;42(6):539-42 [12439879] Am J Ind Med. 2002 Dec;42(6):543-4 [12439880] Am J Ind Med. 2002 Dec;42(6):545-7 [12439881] Am J Ind Med. 2002 Dec;42(6):548-9 [12439882] Environ Health Perspect. 2003 Jun;111(7):981-91 [12782502] JAMA. 2003 Aug 6;290(5):595-6 [12902358] Ambul Pediatr. 2003 Nov-Dec;3(6):304-11 [14616045] Environ Health Perspect. 2003 Dec;111(16):1906-11 [14644665] Am Ind Hyg Assoc J. 1972 Mar;33(3):178-91 [5074675] Am J Obstet Gynecol. 1976 Nov 1;126(5):555-64 [984126] Ann N Y Acad Sci. 1991 Dec 31;643:53-60 [1809166] Child Dev. 1992 Jun;63(3):711-24 [1600831] Lancet. 2002 Dec;360 Suppl:s37-8 [12504497] Ann N Y Acad Sci. 2002 Dec;982:160-76 [12562635] Environ Sci Technol. 2003 Feb 1;37(3):502-8 [12630465] Epidemiology. 2000 Sep;11(5):502-11 [10955401] J Expo Anal Environ Epidemiol. 2000 Nov-Dec;10(6 Pt 1):566-78 [11140440] Epidemiology. 2001 May;12(3):358-9 [11338317] Hum Reprod Update. 2001 May-Jun;7(3):331-9 [11392380] Environ Health Perspect. 2001 Sep;109(9):915-9 [11673120] Environ Health Perspect. 2001 Nov;109(11):A514-5 [11713006] N Engl J Med. 2002 Mar 28;346(13):982-7 [11919308] J Urban Health. 2002 Mar;79(1):2-5 [11937606] Am J Epidemiol. 2002 Jun 1;155(11):988-96 [12034577] Psychiatr Serv. 2002 Jul;53(7):815-22 [12096163] Am J Epidemiol. 1998 Feb 1;147(3):309-14 [9482506] N Engl J Med. 1998 May 28;338(22):1565-71 [9603793] Environ Health Perspect. 1999 Jun;107(6):475-80 [10339448] JAMA. 2002 Aug 7;288(5):581-8 [12150669] Comment In: Environ Health Perspect. 2004 Aug;112(11):A606-7; author reply A607 [15289176] Environ Health Perspect. 2004 Sep;112(13):A728 [15345360] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. AN - 71888223; 15122762 AB - The central role of T cell activation in hepatocellular injury has been well documented. In this article, we provide evidence suggesting that T cells may also play a protective role in liver disease by releasing interleukin-22 (IL-22), a recently identified T cell-derived cytokine whose biological significance is unclear. IL-22 messenger RNA and protein expression are significantly elevated in T cell-mediated hepatitis induced by concanavalin A (ConA) but are less extensively elevated in the carbon tetrachloride-induced liver injury model. Activated CD3(+) T cells are likely responsible for the production of IL-22 in the liver after injection of ConA. The IL-22 receptor is normally expressed at high levels by hepatocytes and further induced after ConA injection. IL-22 blockade with a neutralizing antibody reduces signal transducer and activator of transcription factor 3 (STAT3) activation and worsens liver injury in T cell-mediated hepatitis, whereas injection of recombinant IL-22 attenuates such injury. In vitro treatment with recombinant IL-22 or overexpression of IL-22 promotes cell growth and survival in human hepatocellular carcinoma HepG2 cells. Stable overexpression of IL-22 in HepG2 cells constitutively activates STAT3 and induces expression of a variety of antiapoptotic (e.g., Bcl-2, Bcl-xL, Mcl-1) and mitogenic (e.g., c-myc, cyclin D1, Rb2, CDK4) proteins. Blocking STAT3 activation abolishes the antiapoptotic and mitogenic actions of IL-22 in hepatic cells. In conclusion, the T cell-derived cytokine IL-22 is a survival factor for hepatocytes; this suggests that T cell activation may also prevent and repair liver injury by releasing hepatoprotective cytokine IL-22 in addition to its previously documented central role in hepatocellular injury. JF - Hepatology (Baltimore, Md.) AU - Radaeva, Svetlana AU - Sun, Rui AU - Pan, Hong-Na AU - Hong, Feng AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1332 EP - 1342 VL - 39 IS - 5 SN - 0270-9139, 0270-9139 KW - DNA-Binding Proteins KW - 0 KW - Interleukins KW - Receptors, Interleukin KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - Stat3 protein, mouse KW - Trans-Activators KW - interleukin-22 KW - interleukin-22 receptor KW - Concanavalin A KW - 11028-71-0 KW - Agar KW - 9002-18-0 KW - Index Medicus KW - Animals KW - Receptors, Interleukin -- metabolism KW - Humans KW - Receptors, Interleukin -- genetics KW - Cell Division -- physiology KW - Chemical and Drug Induced Liver Injury -- physiopathology KW - Mice, Nude KW - Mice KW - Cell Line, Tumor KW - Cell Survival -- immunology KW - Chemical and Drug Induced Liver Injury -- immunology KW - Neoplasm Transplantation KW - Hepatocytes -- immunology KW - Hepatocytes -- cytology KW - Hepatocytes -- metabolism KW - Trans-Activators -- metabolism KW - Liver Neoplasms -- pathology KW - Hepatitis -- immunology KW - Interleukins -- metabolism KW - Carcinoma, Hepatocellular -- pathology KW - Interleukins -- immunology KW - Hepatitis -- physiopathology KW - T-Lymphocytes -- immunology KW - Interleukins -- genetics KW - Carcinoma, Hepatocellular -- immunology KW - Liver Neoplasms -- immunology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71888223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interleukin+22+%28IL-22%29+plays+a+protective+role+in+T+cell-mediated+murine+hepatitis%3A+IL-22+is+a+survival+factor+for+hepatocytes+via+STAT3+activation.&rft.au=Radaeva%2C+Svetlana%3BSun%2C+Rui%3BPan%2C+Hong-Na%3BHong%2C+Feng%3BGao%2C+Bin&rft.aulast=Radaeva&rft.aufirst=Svetlana&rft.date=2004-05-01&rft.volume=39&rft.issue=5&rft.spage=1332&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 - 2004-05-24 N1 - Date created - 2004-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent dual initiation in human immunodeficiency virus-based vectors containing two primer-binding sites: a quantitative in vivo assay for function of initiation complexes. AN - 71882333; 15113919 AB - We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-binding sites (PBSs) have the capacity to initiate reverse transcription more than once (Y. A. Voronin and V. K. Pathak, Virology 312:281-294, 2003). To determine whether human immunodeficiency virus (HIV)-based vectors also have the capacity to initiate reverse transcription twice, we constructed an HIV type 1 (HIV-1)-based vector containing the HIV-1 PBS, a green fluorescent protein reporter gene (GFP), and a second PBS derived from HIV-2 3' of GFP. Simultaneous initiation of reverse transcription at both the 5' HIV-1 PBS and 3' HIV-2 PBS was predicted to result in deletion of GFP. As in the MLV-based vectors, GFP was deleted in approximately 25% of all proviruses, indicating frequent dual initiation in HIV-based vectors containing two PBSs. Quantitative real-time PCR analysis of early reverse transcription products indicated that HIV-1 reverse transcriptase efficiently used the HIV-2 PBS. To investigate tRNA primer-RNA template interactions in vivo, we introduced several mutations in the HIV-2 U5 region. The effects of these mutations on the efficiency of reverse transcription initiation were measured by quantitative real-time PCR analysis of early reverse transcription products, with initiation at the HIV-1 PBS used as an internal control. Disruption of the lower and upper parts of the U5-inverted repeat stem reduced the efficiency of initiation 20- and 6-fold, respectively. In addition, disruption of the proposed interactions between viral RNA and tRNA(Lys3) thymidine-pseudouridine-cytidine and anticodon loops decreased the efficiency of initiation seven- and sixfold, respectively. These results demonstrate the relative influence of various RNA-RNA interactions on the efficiency of initiation in vivo. Furthermore, the two-PBS vector system provides a sensitive and quantitative in vivo assay for analysis of RNA-RNA and protein-RNA interactions that can influence the efficiency of reverse transcription initiation. JF - Journal of virology AU - Voronin, Yegor A AU - Pathak, Vinay K AD - HIV Drug Resistance Program, National Cancer Institute at Frederick, Building 535, Frederick, MD 21702, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 5402 EP - 5413 VL - 78 IS - 10 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - DNA, Viral KW - Luminescent Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - Polymerase Chain Reaction KW - DNA, Viral -- biosynthesis KW - Base Sequence KW - Molecular Sequence Data KW - Luminescent Proteins -- metabolism KW - Mutagenesis KW - Binding Sites KW - Transcription, Genetic KW - Genetic Vectors -- genetics KW - HIV -- genetics KW - DNA Primers -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71882333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Frequent+dual+initiation+in+human+immunodeficiency+virus-based+vectors+containing+two+primer-binding+sites%3A+a+quantitative+in+vivo+assay+for+function+of+initiation+complexes.&rft.au=Voronin%2C+Yegor+A%3BPathak%2C+Vinay+K&rft.aulast=Voronin&rft.aufirst=Yegor&rft.date=2004-05-01&rft.volume=78&rft.issue=10&rft.spage=5402&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 - 2004-05-27 N1 - Date created - 2004-04-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1988 Aug;62(8):2636-43 [2839690] J Virol. 1988 Oct;62(10):3622-30 [2458484] J Virol. 1989 Jan;63(1):319-27 [2908924] J Acquir Immune Defic Syndr. 1988;1(4):317-23 [3265154] Science. 1990 Nov 30;250(4985):1227-33 [1700865] J Virol. 1991 Jul;65(7):3864-72 [1710292] J Virol. 1991 Sep;65(9):4555-64 [1714513] J Virol. 1992 Apr;66(4):2464-72 [1548772] 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] Genomics. 1993 Jan;15(1):21-9 [7916736] J Virol. 2002 Apr;76(8):3739-47 [11907213] J Virol. 2002 Jun;76(11):5803-6 [11992009] J Virol. 1995 Oct;69(10):6021-9 [7545240] J Virol. 1996 Feb;70(2):966-75 [8551637] Arch Biochem Biophys. 1996 Jan 15;325(2):209-16 [8561499] Science. 1996 Apr 12;272(5259):263-7 [8602510] Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11382-8 [8876144] J Gen Virol. 1997 Apr;78 ( Pt 4):837-40 [9129656] J Virol. 1997 Jun;71(6):4254-63 [9151812] J Virol. 1997 Aug;71(8):6218-24 [9223521] Nucleic Acids Res. 1993 Mar 11;21(5):1171-8 [8464701] J Virol. 1993 Jun;67(6):3246-53 [8497049] J Virol. 1994 Jan;68(1):207-16 [8254730] J Virol. 1994 Feb;68(2):611-8 [7507181] J Virol. 1994 Mar;68(3):1605-14 [7508999] J Virol. 1994 Apr;68(4):2065-72 [7511167] J Virol. 1994 Sep;68(9):5863-70 [8057466] Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9564-8 [7937806] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9823-7 [7937898] J Virol. 1994 Dec;68(12):7676-83 [7966556] Nucleic Acids Res. 1995 Apr 25;23(8):1319-26 [7538660] FEBS Lett. 1998 Jul 3;430(3):165-70 [9688531] Trends Biochem Sci. 1998 Aug;23(8):297-301 [9757830] Virology. 1999 Apr 25;257(1):95-105 [10208924] J Virol. 1999 Aug;73(8):7050-5 [10400808] Eur J Biochem. 2000 May;267(9):2803-11 [10785403] J Biol Chem. 2000 May 19;275(20):15474-81 [10809779] Nat Genet. 2000 Jun;25(2):217-22 [10835641] Nucleic Acids Res. 2000 Nov 1;28(21):4130-7 [11058109] Blood. 2000 Dec 15;96(13):4103-10 [11110680] Nat Med. 2001 May;7(5):631-4 [11329067] Nucleic Acids Res. 2001 Jul 1;29(13):2757-65 [11433020] J Biol Chem. 2001 Aug 17;276(33):31247-56 [11384976] J Virol. 2002 Mar;76(5):2329-39 [11836411] RNA. 2002 Jan;8(1):8-15 [11873759] J Virol. 1997 Sep;71(9):6940-6 [9261422] J Virol. 1998 Feb;72(2):1186-94 [9445017] Nucleic Acids Res. 1998 Mar 1;26(5):1198-204 [9469827] J Virol. 2002 Aug;76(15):7473-84 [12097560] J Virol. 2002 Dec;76(24):13111-5 [12438642] Virology. 2003 Aug 1;312(2):281-94 [12919734] Nucleic Acids Res. 2003 Oct 1;31(19):5764-75 [14500840] Nature. 1970 Jun 27;226(5252):1209-11 [4316300] Nature. 1970 Jun 27;226(5252):1211-3 [4316301] Proc Natl Acad Sci U S A. 1974 Oct;71(10):4254-8 [4372615] Proc Natl Acad Sci U S A. 1974 Sep;71(9):3560-4 [4372625] J Biol Chem. 1975 May 10;250(9):3487-97 [164470] Cold Spring Harb Symp Quant Biol. 1975;39 Pt 2:827-34 [169036] Cell. 1976 Apr;7(4):595-607 [182376] J Virol. 1977 Mar;21(3):1031-41 [66325] Prog Nucleic Acid Res Mol Biol. 1977;20:131-60 [71747] J Virol. 1978 Jan;25(1):104-4 [202729] Virology. 1978 Aug;89(1):95-101 [80059] J Virol. 1979 Jan;29(1):328-35 [219227] Mol Gen Genet. 1979;177(1):65-72 [231729] J Virol. 1980 Mar;33(3):1046-57 [6154153] Cell. 1980 Nov;22(2 Pt 2):379-86 [6256079] J Virol. 1980 Dec;36(3):692-700 [6162035] Proc Natl Acad Sci U S A. 1981 Jan;78(1):124-8 [6264426] J Virol. 1981 Oct;40(1):164-72 [6457158] Gene. 1983 Nov;25(2-3):179-88 [6319235] Nature. 1985 Jan 24-30;313(6000):277-84 [2578615] Science. 1985 Jul 5;229(4708):69-73 [2990040] J Virol. 1986 Jan;57(1):379-84 [3001360] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epigenetic and gene expression changes related to transgenerational carcinogenesis. AN - 71867675; 15108325 AB - Transgenerational carcinogenesis refers to transmission of cancer risk to the untreated progeny of parents exposed to carcinogens before mating. Accumulated evidence suggests that the mechanism of this process is epigenetic, and might involve hormonal and gene expression changes in offspring. To begin to test this hypothesis, we utilized a mouse model (NIH Swiss) in which exposure of fathers to Cr(III) chloride 2 wk before mating can alter incidence of neoplastic and nonneoplastic changes in offspring tissues. Utilizing a MS-RDA approach, we found that the sperm of these fathers had a significantly higher percentage of undermethylated copies of the 45S ribosomal RNA gene (rRNA); this finding was confirmed by bisulfite sequencing. Because gene methylation is a known mechanism of expression control in germ cells, and ribosomal RNA levels have been linked to cancer, these findings are consistent with the hypothesis. Secondly, we observed that offspring of Cr(III)-treated fathers were significantly heavier than controls, and had higher levels of serum T3. Possible effects of T3 levels on gene expression in the offspring were examined by microarray analysis of cDNAs from liver. A total of 58 genes, including 25 named genes, had expression ratios that correlated significantly with serum T3 ratios at P or = 35 years old during four 8.5-year time intervals. To assess the effect of access to RRT on IHD death rates, trends were reexamined after subjects receiving RRT were classified as if they had died of DN. During a median follow-up of 11.1 years (range 0.01-34), 818 subjects died. The age- and sex-adjusted DN death rate decreased over the 34-year study (P = 0.05), whereas the IHD death rate increased from 3.3 deaths/1,000 person-years (95% CI 1.4-5.2) to 6.3 deaths/1,000 person-years (95% CI 4.5-8.0; P = 0.03). After 151 subjects on RRT were reclassified as if they had died of DN, the death rate for DN increased from 4.8 deaths/1,000 person-years (95% CI 2.6-7) to 11.3 deaths/1,000 person-years (95% CI 9-13.6; P = 0.0007), whereas the increase in the IHD death rate disappeared (P = 0.57). The incidence rate of renal failure attributable to diabetes has increased rapidly over the past 34 years in Pima Indians. IHD has emerged as the leading cause of death due largely to the availability of RRT and to changes in the pattern of death among those with DN. JF - Diabetes care AU - Pavkov, Meda E AU - Sievers, Maurice L AU - Knowler, William C AU - Bennett, Peter H AU - Nelson, Robert G AD - Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85011-4972, USA. mpavkov@phx.niddk.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1132 EP - 1136 VL - 27 IS - 5 SN - 0149-5992, 0149-5992 KW - Index Medicus KW - Sex Characteristics KW - Neoplasms -- mortality KW - Humans KW - Diabetic Angiopathies -- mortality KW - Infection -- mortality KW - Cause of Death KW - Age Distribution KW - Smoking KW - Ethnic Groups KW - Risk Factors KW - Arizona KW - Incidence KW - Liver Diseases, Alcoholic -- mortality KW - Female KW - Male KW - Indians, North American KW - Heart Diseases -- mortality KW - Diabetes Mellitus, Type 2 -- mortality KW - Renal Replacement Therapy KW - Diabetic Nephropathies -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71864881?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+explanation+for+the+increase+in+heart+disease+mortality+rates+in+diabetic+Pima+Indians%3A+effect+of+renal+replacement+therapy.&rft.au=Pavkov%2C+Meda+E%3BSievers%2C+Maurice+L%3BKnowler%2C+William+C%3BBennett%2C+Peter+H%3BNelson%2C+Robert+G&rft.aulast=Pavkov&rft.aufirst=Meda&rft.date=2004-05-01&rft.volume=27&rft.issue=5&rft.spage=1132&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 - 2004-11-16 N1 - Date created - 2004-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analytical and statistical methods to evaluate microsatellite allelic imbalance in small amounts of DNA. AN - 71864551; 15048133 AB - Microsatellite analysis is a powerful tool for the assessment of genetic instability and loss of heterozygosity in cancer cells. However, most human tumors harbor significant numbers of normal cells, which may contribute to false-negative results. Recent techniques based on fluorescently labeled primers and semiautomated capillary electrophoresis of polymerase chain reaction (PCR) products allow a reliable quantitative assessment of (PCR) products while requiring very small numbers of cells. We report a highly sensitive protocol for the semiautomated analysis of allelic imbalance based on time-release PCR and capillary electrophoresis. With this protocol, as few as 100 cells can be used to reliably assess allelic imbalance (AI) in DNA samples. Using a panel of seven microsatellite markers, we determined allelic variation in a large set of heterozygous lymphocyte DNA samples and examined the use of different statistical analysis techniques. Using these statistical approaches, we describe a calibration method to evaluate AI from microsatellite results. Using a simple formula, cutoff points at preset confidence levels are used to decide whether allelic imbalance exists in a given sample at the loci under investigation. Our method allows the reliable detection of AI with very small amounts of DNA, and is sufficiently quantitative to assess allelic ratios in nonclonal tissue specimens. JF - Laboratory investigation; a journal of technical methods and pathology AU - Slebos, Robbert J C AU - Umbach, David M AU - Sommer, Courtney A AU - Horner, Geoffrey A AU - Choi, Jane Y AU - Taylor, Jack A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 649 EP - 657 VL - 84 IS - 5 SN - 0023-6837, 0023-6837 KW - DNA, Neoplasm KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Sensitivity and Specificity KW - Lymphocytes -- chemistry KW - Lung Neoplasms -- diagnosis KW - Loss of Heterozygosity KW - Aneuploidy KW - Polymerase Chain Reaction -- statistics & numerical data KW - Humans KW - Polymerase Chain Reaction -- methods KW - Lung Neoplasms -- genetics KW - DNA, Neoplasm -- genetics KW - DNA, Neoplasm -- analysis KW - Electrophoresis, Capillary -- methods KW - Microsatellite Repeats KW - Allelic Imbalance KW - DNA -- genetics KW - DNA -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71864551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analytical+and+statistical+methods+to+evaluate+microsatellite+allelic+imbalance+in+small+amounts+of+DNA.&rft.au=Slebos%2C+Robbert+J+C%3BUmbach%2C+David+M%3BSommer%2C+Courtney+A%3BHorner%2C+Geoffrey+A%3BChoi%2C+Jane+Y%3BTaylor%2C+Jack+A&rft.aulast=Slebos&rft.aufirst=Robbert+J&rft.date=2004-05-01&rft.volume=84&rft.issue=5&rft.spage=649&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 - 2004-06-17 N1 - Date created - 2004-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of N-substituted analogs of benztropine: diminished cocaine-like effects in dopamine transporter ligands. AN - 71859918; 14755006 AB - Previous studies demonstrated that analogs of benztropine (BZT) possess high affinity for the dopamine transporter, inhibit dopamine uptake, but generally have behavioral effects different from those of cocaine. One hypothesis is that muscarinic-M(1) receptor actions interfere with cocaine-like effects. Several tropane-nitrogen substitutions of 4',4"-diF-BZT have reduced M(1) affinity compared with the CH(3)-analog (AHN 1-055; 3alpha-[bis-(4-fluorophenyl)methoxy]tropane). All of the compounds displaced [(3)H]WIN 35,428 (2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) binding with affinities ranging from 11 to 108 nM. Affinities at norepinephrine ([(3)H]nisoxetine) and serotonin ([(3)H]citalopram) transporters ranged from 457 to 4810 and 376 to 3260 nM, respectively, and at muscarinic M(1) receptors ([(3)H]pirenzepine) from 11.6 (AHN 1-055) to higher values, reaching 1030 nM for the other BZT-analogs. Cocaine and AHN 1-055 produced dose-related increases in locomotor activity in mice, with AHN 1-055 less effective than cocaine. The other compounds were ineffective in stimulating activity. In rats discriminating cocaine (29 micromol/kg i.p.) from saline, WIN 35,428 fully substituted for cocaine, whereas AHN 1-055 produced a maximal substitution of 79%. None of the other analogs fully substituted for cocaine. WIN 35,428 produced dose-related leftward shifts in the cocaine dose-effect curve, whereas selected BZT analogs produced minimal changes in the effects of cocaine. The results suggest that reducing M(1) affinity of 4',4"-diF-BZT with N-substitutions reduces effectiveness in potentiating the effects of cocaine. Furthermore, although the BZT-analogs bind with high affinity at the dopamine transporter, their behavioral effects differ from those of cocaine. These compounds have reduced efficacy compared with cocaine, a long duration of action, and may serve as leads for the development of medications to treat cocaine abuse. JF - The Journal of pharmacology and experimental therapeutics AU - Katz, Jonathan L AU - Kopajtic, Theresa A AU - Agoston, Gregory E AU - Newman, Amy Hauck AD - Psychobiology, Medications Discovery Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. jkatz@intra.nida.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 650 EP - 660 VL - 309 IS - 2 SN - 0022-3565, 0022-3565 KW - Antiparkinson Agents KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Benztropine KW - 1NHL2J4X8K KW - (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester KW - 50370-56-4 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Mice KW - Radioligand Assay KW - Antiparkinson Agents -- pharmacology KW - Male KW - Discrimination Learning -- drug effects KW - Cocaine -- analogs & derivatives KW - Benztropine -- analogs & derivatives KW - Nerve Tissue Proteins -- metabolism KW - Motor Activity -- drug effects KW - Benztropine -- pharmacology KW - Cocaine -- pharmacology KW - Membrane Transport Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71859918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+N-substituted+analogs+of+benztropine%3A+diminished+cocaine-like+effects+in+dopamine+transporter+ligands.&rft.au=Katz%2C+Jonathan+L%3BKopajtic%2C+Theresa+A%3BAgoston%2C+Gregory+E%3BNewman%2C+Amy+Hauck&rft.aulast=Katz&rft.aufirst=Jonathan&rft.date=2004-05-01&rft.volume=309&rft.issue=2&rft.spage=650&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 - 2004-06-21 N1 - Date created - 2004-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-6 prevents T cell-mediated hepatitis via inhibition of NKT cells in CD4+ T cell- and STAT3-dependent manners. AN - 71855034; 15100309 AB - The hepatoprotective effect of IL-6 on various forms of liver injury including T cell-mediated hepatitis has been well documented, and it is believed that induction of antiapoptotic proteins is an important mechanism. In this study, we provide evidence suggesting an additional mechanism involved in the protective role of IL-6 in T cell-mediated hepatitis. In NKT cell-depleted mice, Con A-induced liver injury is diminished; this can be restored by the adoptive transfer of liver mononuclear cells or NKT cells from wild-type mice, but not from IL-6-treated mice. In vitro IL-6 treatment inhibits the ability of mononuclear cells to restore Con A-induced liver injury in NKT-depleted mice, whereas the same treatment does not inhibit purified NKT cells from restoring the injury. The addition of CD3(+) T cells or CD4(+) T cells can restore the inhibitory effect of IL-6 on purified NKT cells, whereas the addition of CD3(+) T cells from CD4-deficient mice fails to restore this inhibitory effect. The expression of IL-6R was detected in 52.6% of hepatic CD3(+) T cells and 32.7% of hepatic CD4(+) T cells, but only in 3.9% of hepatic NK and 1.5% of hepatic NKT cells. Finally, treatment with IL-6 induces STAT3 activation in hepatic lymphocytes and hepatic T cells, and blocking such activation abolishes the inhibitory effect of IL-6 on hepatic lymphocytes to restore liver injury. Taken together, these findings suggest that in addition to its antiapoptotic abilities, as previously well documented, IL-6/STAT3 inhibits NKT cells via targeting CD4(+) T cells and consequently prevents T cell-mediated hepatitis. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Sun, Rui AU - Tian, Zhigang AU - Kulkarni, Shalini AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/05/01/ PY - 2004 DA - 2004 May 01 SP - 5648 EP - 5655 VL - 172 IS - 9 SN - 0022-1767, 0022-1767 KW - Antibodies, Monoclonal KW - 0 KW - Antigens KW - Antigens, Surface KW - DNA-Binding Proteins KW - Immunosuppressive Agents KW - Interleukin-6 KW - KLRB1 protein, human KW - Lectins, C-Type KW - NK Cell Lectin-Like Receptor Subfamily B KW - Proteins KW - Receptors, Interleukin-6 KW - Recombinant Proteins KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - Stat3 protein, mouse KW - Trans-Activators KW - Concanavalin A KW - 11028-71-0 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Receptors, Interleukin-6 -- biosynthesis KW - Mice, Inbred BALB C KW - Cell Death -- immunology KW - Mice, Knockout KW - Leukocytes, Mononuclear -- transplantation KW - Hepatocytes -- immunology KW - Signal Transduction -- immunology KW - Antigens -- immunology KW - Recombinant Proteins -- therapeutic use KW - Recombinant Proteins -- administration & dosage KW - Male KW - Concanavalin A -- toxicity KW - Injections, Intravenous KW - Leukocytes, Mononuclear -- immunology KW - Mice KW - Hepatocytes -- pathology KW - Antibodies, Monoclonal -- administration & dosage KW - Proteins -- immunology KW - Adoptive Transfer KW - Leukocytes, Mononuclear -- metabolism KW - Lymphocyte Depletion KW - Mice, Inbred C57BL KW - Cytotoxicity Tests, Immunologic KW - Concanavalin A -- antagonists & inhibitors KW - Hepatitis, Animal -- pathology KW - Interleukin-6 -- therapeutic use KW - Hepatitis, Animal -- immunology KW - Interleukin-6 -- metabolism KW - CD4-Positive T-Lymphocytes -- immunology KW - Interleukin-6 -- administration & dosage KW - T-Lymphocyte Subsets -- metabolism KW - CD4-Positive T-Lymphocytes -- metabolism KW - Hepatitis, Animal -- prevention & control KW - Lymphocyte Activation -- immunology KW - T-Lymphocyte Subsets -- immunology KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Killer Cells, Natural -- immunology KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71855034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=IL-6+prevents+T+cell-mediated+hepatitis+via+inhibition+of+NKT+cells+in+CD4%2B+T+cell-+and+STAT3-dependent+manners.&rft.au=Sun%2C+Rui%3BTian%2C+Zhigang%3BKulkarni%2C+Shalini%3BGao%2C+Bin&rft.aulast=Sun&rft.aufirst=Rui&rft.date=2004-05-01&rft.volume=172&rft.issue=9&rft.spage=5648&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 - 2004-08-17 N1 - Date created - 2004-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Down-regulation and altered localization of gamma-catenin in cisplatin-resistant adenocarcinoma cells. AN - 71850071; 15102950 AB - Resistance to cisplatin, one of the most widely used anticancer chemotherapeutic agents, is a major clinical problem. There is no effective way to predict development of cisplatin resistance in cancers. As determined by reverse transcription-polymerase chain reaction and Western blotting, the expression of gamma-catenin, an adherens junction protein, was decreased in KB-CP20 and 7404-CP20 cells compared with parental-sensitive cells. Short-term treatment with cisplatin of the parental cells resulted in proteolysis of gamma-catenin as evaluated in membrane pellet preparations, and the extent of cleavage increased as cisplatin concentration was raised from 1 to 5 microg/ml during 1 h of treatment. Uncleaved cytoplasmic gamma-catenin increased under the same conditions. These biochemical results were supported by confocal microscopy, which showed a loss of gamma-catenin from adherens plaques after cisplatin treatment. Cleavage of gamma-catenin was specific to cisplatin treatment in that cleavage did not occur after treatment with doxorubicin and cytosine arabinoside. Pretreatment of KB and 7404 cells with cisplatin for 1 h resulted in reduced uptake of [(14)C]carboplatin, suggesting that the biochemical changes induced by cisplatin treatment, including cleavage of gamma-catenin, could affect the ability of cells to internalize platinum compounds. Cells transfected with the gamma-catenin gene are sensitive to cisplatin compared with cells transfected with a control vector. Our data suggest that proteolysis and altered localization of gamma-catenin are early markers for the response of cells to cisplatin, and reduced levels of gamma-catenin in resistant cells may indicate an important role for gamma-catenin in mediating or modulating the toxicity of cisplatin in cancer cells. JF - Molecular pharmacology AU - Liang, Xing-Jie AU - Shen, Ding-Wu AU - Gottesman, Michael M AD - Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 1A09, Bethesda, MD 20892-4254, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1217 EP - 1224 VL - 65 IS - 5 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents KW - 0 KW - Carbon Radioisotopes KW - Cytoskeletal Proteins KW - Desmoplakins KW - JUP protein, human KW - gamma Catenin KW - Tritium KW - 10028-17-8 KW - Carboplatin KW - BG3F62OND5 KW - Cisplatin KW - Q20Q21Q62J KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - KB Cells KW - Antineoplastic Agents -- pharmacokinetics KW - Humans KW - Methotrexate -- pharmacokinetics KW - Tumor Cells, Cultured KW - Down-Regulation KW - Transfection KW - Cisplatin -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Carboplatin -- pharmacokinetics KW - Male KW - Adenocarcinoma -- metabolism KW - Drug Resistance, Neoplasm -- physiology KW - Cytoskeletal Proteins -- metabolism KW - Cytoskeletal Proteins -- genetics KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71850071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Down-regulation+and+altered+localization+of+gamma-catenin+in+cisplatin-resistant+adenocarcinoma+cells.&rft.au=Liang%2C+Xing-Jie%3BShen%2C+Ding-Wu%3BGottesman%2C+Michael+M&rft.aulast=Liang&rft.aufirst=Xing-Jie&rft.date=2004-05-01&rft.volume=65&rft.issue=5&rft.spage=1217&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 - 2004-05-28 N1 - Date created - 2004-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fas-mediated signaling pathway in ethanol-induced liver apoptosis: inhibition by zinc. AN - 71843714; 15096646 JF - Experimental biology and medicine (Maywood, N.J.) AU - Liu, Jie AD - Inorganic Carcinogenesis, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Research Triangle Park, North Carolina 27709, USA. Liu6@niehs.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 365 EP - 366 VL - 229 IS - 5 SN - 1535-3702, 1535-3702 KW - Antigens, CD95 KW - 0 KW - Ethanol KW - 3K9958V90M KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Animals KW - Drug Antagonism KW - Zinc -- pharmacology KW - Liver -- cytology KW - Liver -- drug effects KW - Ethanol -- pharmacology KW - Antigens, CD95 -- physiology KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71843714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.atitle=Fas-mediated+signaling+pathway+in+ethanol-induced+liver+apoptosis%3A+inhibition+by+zinc.&rft.au=Liu%2C+Jie&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2004-05-01&rft.volume=229&rft.issue=5&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=Experimental+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.issn=15353702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-11 N1 - Date created - 2004-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Exp Biol Med (Maywood). 2003 Apr;228(4):406-12 [12671185] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-(4-hydroxyphenyl) retinamide (4HPR) enhances TRAIL-mediated apoptosis through enhancement of a mitochondrial-dependent amplification loop in ovarian cancer cell lines. AN - 71842858; 14765134 AB - The majority of ovarian cancer cells are resistant to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Subtoxic concentrations of the semisynthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) enhanced TRAIL-mediated apoptosis in ovarian cancer cell lines but not in immortalized nontumorigenic ovarian epithelial cells. The enhancement of TRAIL-mediated apoptosis by 4HPR was not due to changes in the levels of proteins known to modulate TRAIL sensitivity. The combination of 4HPR and TRAIL enhanced cleavage of multiple caspases in the death receptor pathway (including the two initiator caspases, caspase-8 and caspase-9). The 4HPR and TRAIL combination leads to mitochondrial permeability transition, significant increase in cytochrome c release, and increased caspase-9 activation. Caspase-9 may further activate caspase-8, generating an amplification loop. Stable overexpression of Bcl-xL abrogates the interaction between 4HPR and TRAIL at the mitochondrial level by blocking cytochrome c release. As a consequence, a decrease in activation of caspase-9, caspase-8, and TRAIL-mediated apoptosis occurs. These results indicate that the enhancement in TRAIL-mediated apoptosis induced by 4HPR is due to the increase in activation of multiple caspases involving an amplification loop via the mitochondrial-death pathway. These findings offer a promising and novel strategy for the treatment of ovarian cancer. 2004 JF - Cell death and differentiation AU - Cuello, M AU - Coats, A O AU - Darko, I AU - Ettenberg, S A AU - Gardner, G J AU - Nau, M M AU - Liu, J R AU - Birrer, M J AU - Lipkowitz, S AD - Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 527 EP - 541 VL - 11 IS - 5 SN - 1350-9047, 1350-9047 KW - Apoptosis Regulatory Proteins KW - 0 KW - Membrane Glycoproteins KW - Retinoid X Receptors KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFSF10 protein, human KW - Tumor Necrosis Factor-alpha KW - Fenretinide KW - 187EJ7QEXL KW - Cytochromes c KW - 9007-43-6 KW - Caspases KW - EC 3.4.22.- KW - Index Medicus KW - Ovary -- metabolism KW - Cytochromes c -- metabolism KW - Tumor Cells, Cultured KW - Humans KW - DNA Fragmentation -- drug effects KW - Female KW - Caspases -- metabolism KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Mitochondria -- metabolism KW - Fenretinide -- toxicity KW - Tumor Necrosis Factor-alpha -- metabolism KW - Retinoid X Receptors -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71842858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+death+and+differentiation&rft.atitle=N-%284-hydroxyphenyl%29+retinamide+%284HPR%29+enhances+TRAIL-mediated+apoptosis+through+enhancement+of+a+mitochondrial-dependent+amplification+loop+in+ovarian+cancer+cell+lines.&rft.au=Cuello%2C+M%3BCoats%2C+A+O%3BDarko%2C+I%3BEttenberg%2C+S+A%3BGardner%2C+G+J%3BNau%2C+M+M%3BLiu%2C+J+R%3BBirrer%2C+M+J%3BLipkowitz%2C+S&rft.aulast=Cuello&rft.aufirst=M&rft.date=2004-05-01&rft.volume=11&rft.issue=5&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Cell+death+and+differentiation&rft.issn=13509047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-17 N1 - Date created - 2004-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel function of the MA-3 domains in transformation and translation suppressor Pdcd4 is essential for its binding to eukaryotic translation initiation factor 4A. AN - 71840254; 15082783 AB - An alpha-helical MA-3 domain appears in several translation initiation factors, including human eukaryotic translation initiation factor 4G (eIF4G) and DAP-5/NAT1/p97, as well as in the tumor suppressor Pdcd4. The function of the MA-3 domain is, however, unknown. C-terminal eIF4G (eIG4Gc) contains an MA-3 domain that is located within the eIF4A-binding region, suggesting a role for eIF4A binding. Interestingly, C-terminal DAP-5/NAT1/p97 contains an MA-3 domain, but it does not bind to eIF4A. Mutation of amino acid residues conserved between Pdcd4 and eIF4Gc but not in DAP-5/NAT1/p97 to the amino acid residues found in the DAP-5/NAT1/p97 indicates that some of these amino acid residues within the MA-3 domain are critical for eIF4A-binding activity. Six Pdcd4 mutants (Pdcd4(E249K), Pdcd4(D253A), Pdcd4(D414K), Pdcd4(D418A), Pdcd4(E249K,D414K), and Pdcd4(D253A,D418A)) lost >90% eIF4A-binding activity. Mutation of the corresponding amino acid residues in the eIF4Gc also produced similar results, as seen for Pdcd4. These results demonstrate that the MA-3 domain is important for eIF4A binding and explain the ability of Pdcd4 or eIF4Gc but not DAP-5/NAT1/p97 to bind to eIF4A. Competition experiments indicate that Pdcd4 prevents ca. 60 to 70% of eIF4A binding to eIF4Gc at a Pdcd4/eIF4A ratio of 1:1, but mutants Pdcd4(D253A) and Pdcd4(D253A,D418A) do not. Translation of stem-loop structured mRNA is susceptible to inhibition by wild-type Pdcd4 but not by Pdcd4(D253A), Pdcd4(D418A), or Pdcd4(D235A,D418A). Together, these results indicate that not only binding to eIF4A but also prevention of eIF4A binding to the MA-3 domain of eIF4Gc contributes to the mechanism by which Pdcd4 inhibits translation. JF - Molecular and cellular biology AU - Yang, Hsin-Sheng AU - Cho, Myung-Haing AU - Zakowicz, Halina AU - Hegamyer, Glenn AU - Sonenberg, Nahum AU - Colburn, Nancy H AD - Gene Regulation Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA. hyang@ncifcrf.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 3894 EP - 3906 VL - 24 IS - 9 SN - 0270-7306, 0270-7306 KW - 5' Untranslated Regions KW - 0 KW - Apoptosis Regulatory Proteins KW - PDCD4 protein, human KW - RNA, Messenger KW - RNA-Binding Proteins KW - Eukaryotic Initiation Factor-4A KW - EC 2.7.7.- KW - Index Medicus KW - Animals KW - Humans KW - Two-Hybrid System Techniques KW - RNA, Messenger -- chemistry KW - Amino Acid Sequence KW - RNA, Messenger -- genetics KW - Nucleic Acid Conformation KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - RNA, Messenger -- metabolism KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Cell Line KW - Protein Biosynthesis KW - Eukaryotic Initiation Factor-4A -- metabolism KW - RNA-Binding Proteins -- metabolism KW - RNA-Binding Proteins -- genetics KW - Eukaryotic Initiation Factor-4A -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71840254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+novel+function+of+the+MA-3+domains+in+transformation+and+translation+suppressor+Pdcd4+is+essential+for+its+binding+to+eukaryotic+translation+initiation+factor+4A.&rft.au=Yang%2C+Hsin-Sheng%3BCho%2C+Myung-Haing%3BZakowicz%2C+Halina%3BHegamyer%2C+Glenn%3BSonenberg%2C+Nahum%3BColburn%2C+Nancy+H&rft.aulast=Yang&rft.aufirst=Hsin-Sheng&rft.date=2004-05-01&rft.volume=24&rft.issue=9&rft.spage=3894&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 - 2004-06-10 N1 - Date created - 2004-04-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 2003 Jun 12;22(24):3712-20 [12802278] Mol Cell Biol. 2003 Jan;23(1):26-37 [12482958] J Pathol. 2003 Aug;200(5):640-6 [12898601] Cell. 1978 Dec;15(4):1109-23 [215319] J Biol Chem. 1987 Mar 15;262(8):3826-32 [2950099] EMBO J. 1988 Jul;7(7):2097-105 [3046931] Nucleic Acids Res. 1988 Nov 11;16(21):10359 [3057442] Mol Cell Biol. 1989 Nov;9(11):5134-42 [2601712] Mol Cell Biol. 1990 Mar;10(3):1134-44 [2304461] Gene Expr. 1991 May;1(2):117-25 [1820209] EMBO J. 1992 Jul;11(7):2643-54 [1378397] Mol Cell Biol. 1993 Nov;13(11):6789-98 [8413273] EMBO J. 1994 Mar 1;13(5):1205-15 [8131750] Nature. 1994 Oct 27;371(6500):747-8 [7935831] Mol Biol Rep. 1994 May;19(3):195-200 [7969107] Carcinogenesis. 1995 Apr;16(4):749-56 [7728951] Gene. 1995 Dec 12;166(2):297-301 [8543179] Cell. 1996 Aug 23;86(4):517-20 [8752206] Biochem Biophys Res Commun. 1996 Nov 1;228(1):7-13 [8912629] Mol Cell Biol. 1996 Dec;16(12):6859-69 [8943341] EMBO J. 1997 Feb 17;16(4):817-25 [9049310] Mol Cell Biol. 1997 Dec;17(12):6940-7 [9372926] J Biol Chem. 1998 Mar 27;273(13):7579-87 [9516461] RNA. 1998 Jul;4(7):828-36 [9671055] J Immunol. 1998 Oct 1;161(7):3493-500 [9759869] Int J Biochem Cell Biol. 1999 Jan;31(1):59-72 [10216944] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14037-42 [10570194] FEBS Lett. 1999 Nov 26;462(1-2):79-84 [10580096] Mol Cell Biol. 2000 Jan;20(2):468-77 [10611225] Mol Cell Biol. 2000 Aug;20(16):6019-29 [10913184] Free Radic Biol Med. 2000 May 1;28(9):1338-48 [10924853] Genome Res. 2000 Aug;10(8):1172-84 [10958635] Trends Biochem Sci. 2000 Sep;25(9):423-6 [10973054] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13080-5 [11087862] Oncogene. 2001 Feb 8;20(6):669-76 [11314000] RNA. 2001 Mar;7(3):382-94 [11333019] Int J Biochem Cell Biol. 2001 Sep;33(9):902-13 [11461832] J Biol Chem. 2001 Aug 17;276(33):30914-22 [11418588] Oncogene. 2002 Feb 21;21(9):1346-58 [11857078] Br J Cancer. 2002 Apr 8;86(7):1023-7 [11953842] Prog Nucleic Acid Res Mol Biol. 2002;72:307-31 [12206455] Biochem Biophys Res Commun. 2002 Sep 13;297(1):78-82 [12220511] Genes Dev. 2002 Nov 15;16(22):2906-22 [12435632] Oncogene. 2003 Jul 31;22(31):4905-10 [12894233] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NTP-CERHR expert panel report on the reproductive and developmental toxicity of methanol. AN - 71828424; 15082073 AB - The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of the Center is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction, including development, caused by agents to which humans may be exposed. Methanol was selected for evaluation by the CERHR based on high production volume, extent of human exposure, and published evidence of reproductive or developmental toxicity. Methanol is used in chemical syntheses and as an industrial solvent. It is a natural component of the human diet and is found in consumer products such as paints, antifreeze, cleaning solutions, and adhesives. It is used in race car fuels and there is potential for expanded use as an automobile fuel. This evaluation is the result of a 10-month effort by a 12-member panel of government and non-government scientists that culminated in a public Expert Panel meeting. This report has been reviewed by CERHR staff scientists, and by members of the Methanol Expert Panel. Copies have been provided to the CERHR Core Committee, which is made up of representatives of NTP-participating agencies. This report is a product of the Expert Panel and is intended to (1). interpret the strength of scientific evidence that a given exposure or exposure circumstance may pose a hazard to reproduction and the health and welfare of children; (2). provide objective and scientifically thorough assessments of the scientific evidence that adverse reproductive/development health effects are associated with exposure to specific chemicals or classes of chemicals, including descriptions of any uncertainties that would diminish confidence in assessment of risks; and (3). identify knowledge gaps to help establish research and testing priorities. The expert panel report becomes a central part of the subsequent NTP-CERHR Monograph. Each monograph includes the NTP Brief on the chemical under evaluation, the expert panel report, and all public comments on the expert panel report. The NTP Brief contains the NTP's conclusions on the potential for exposure to result in adverse effects on human development and reproduction. It is based on the expert panel report, public comments on the report, and relevant data published after the expert panel report was completed. NTP-CERHR Monographs are publicly available and are transmitted to appropriate health and regulatory agencies. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Shelby, Michael AU - Portier, Christopher AU - Goldman, Lynn AU - Moore, John AU - Iannucci, Annette AU - Jahnke, Gloria AU - Donkin, Steve AU - NTP-CERHR Expert Panel AD - NIEHS, Research Triangle Park, NC 27709, USA. shelby@niehs.nih.gov ; NTP-CERHR Expert Panel Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 303 EP - 390 VL - 18 IS - 3 SN - 0890-6238, 0890-6238 KW - Carcinogens KW - 0 KW - Mutagens KW - Solvents KW - Teratogens KW - Methanol KW - Y4S76JWI15 KW - Index Medicus KW - Occupational Exposure KW - Animals KW - Humans KW - Carcinogens -- toxicity KW - Infant, Newborn KW - Mutagens -- toxicity KW - Mice KW - Haplorhini KW - Risk Assessment KW - Pregnancy KW - Rats KW - Adult KW - Environmental Exposure KW - Species Specificity KW - Female KW - Growth -- drug effects KW - Male KW - Developmental Disabilities -- chemically induced KW - Teratogens -- pharmacokinetics KW - Methanol -- toxicity KW - Infertility -- chemically induced KW - Teratogens -- toxicity KW - Teratogens -- chemistry KW - Methanol -- pharmacokinetics KW - Methanol -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71828424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=NTP-CERHR+expert+panel+report+on+the+reproductive+and+developmental+toxicity+of+methanol.&rft.au=Shelby%2C+Michael%3BPortier%2C+Christopher%3BGoldman%2C+Lynn%3BMoore%2C+John%3BIannucci%2C+Annette%3BJahnke%2C+Gloria%3BDonkin%2C+Steve%3BNTP-CERHR+Expert+Panel&rft.aulast=Shelby&rft.aufirst=Michael&rft.date=2004-05-01&rft.volume=18&rft.issue=3&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-06 N1 - Date created - 2004-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incorporation of mammalian metabolism into mutagenicity testing. AN - 71824687; 15082236 AB - In the 1950's and 1960's it became obvious that many chemicals in daily use were mutagenic or carcinogenic, but there seemed to be little relation between the two activities. As scientists were debating the cause of this discrepancy, it was hypothesized that mammalian metabolism could form highly reactive intermediates from rather innocuous chemicals and that these intermediates could react with DNA and were mutagenic. This commentary presents the historical development of metabolic activation in mutagenicity tests, beginning with Udenfriend's hydroxylation system, which mimics aspects of mammalian metabolism in a purely chemical mixture, and extending through procedures that moved closer and closer to incorporating actual mammalian metabolism into the test systems. The stages include microsomal activation systems, host-mediated assays, incorporation of human P450 genes into the target cells or organisms, and detecting mutations in single cells in vivo. A recent development in this progression is the insertion of recoverable vectors containing mutational targets into the mammalian genome. Since the target genes of transgenic assays are in the genome, they are not only exposed to active metabolites, but they also undergo the same repair processes as endogenous genes of the mammalian genome. JF - Mutation research AU - Malling, Heinrich V AD - Mammalian Mutagenesis Group, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709-2233, USA. malling@niehs.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 183 EP - 189 VL - 566 IS - 3 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Mutagenicity Tests -- methods KW - Biotransformation KW - Humans KW - Carcinogens -- metabolism KW - DNA Damage KW - Mutagens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71824687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Incorporation+of+mammalian+metabolism+into+mutagenicity+testing.&rft.au=Malling%2C+Heinrich+V&rft.aulast=Malling&rft.aufirst=Heinrich&rft.date=2004-05-01&rft.volume=566&rft.issue=3&rft.spage=183&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 - 2004-06-02 N1 - Date created - 2004-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of tyrosine 24 in the VPg protein is lethal for feline calicivirus. AN - 71814243; 15078978 AB - The genome of feline calicivirus (FCV) is an approximately 7.7-kb single-stranded positive-sense RNA molecule that is polyadenylated at its 3' end and covalently linked to a VPg protein (calculated mass, 12.6 kDa) at its 5' end. We performed a mutational analysis of the VPg protein in order to identify amino acids potentially involved in linkage to the genome and replication. The tyrosine residues at positions 12, 24, 76, and 104 were changed to alanines by mutagenesis of an infectious FCV cDNA clone. Viruses were recovered when Tyr-12, Tyr-76, or Tyr-104 of the VPg protein was changed to alanine, but virus was not recovered when Tyr-24 was changed to alanine. Growth properties of the recovered viruses were similar to those of the parental virus. We examined whether the amino acids serine, threonine, and phenylalanine could substitute for the tyrosine at position 24, but these mutations were lethal as well. A tyrosine at this relative position is conserved among all calicivirus VPg proteins examined thus far, suggesting that the VPg protein of caliciviruses, like those of picornaviruses and potyviruses, utilizes tyrosine in the formation of a covalent bond with RNA. JF - Journal of virology AU - Mitra, Tanaji AU - Sosnovtsev, Stanislav V AU - Green, Kim Y AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 4931 EP - 4935 VL - 78 IS - 9 SN - 0022-538X, 0022-538X KW - Viral Proteins KW - 0 KW - Tyrosine KW - 42HK56048U KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Viral Plaque Assay KW - Reticulocytes -- virology KW - Cats KW - Molecular Sequence Data KW - Rabbits KW - Amino Acid Sequence KW - Cell Line KW - Virus Replication KW - Viral Proteins -- genetics KW - Calicivirus, Feline -- physiology KW - Calicivirus, Feline -- pathogenicity KW - Calicivirus, Feline -- genetics KW - Viral Proteins -- chemistry KW - Point Mutation KW - Viral Proteins -- metabolism KW - Tyrosine -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71814243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutagenesis+of+tyrosine+24+in+the+VPg+protein+is+lethal+for+feline+calicivirus.&rft.au=Mitra%2C+Tanaji%3BSosnovtsev%2C+Stanislav+V%3BGreen%2C+Kim+Y&rft.aulast=Mitra&rft.aufirst=Tanaji&rft.date=2004-05-01&rft.volume=78&rft.issue=9&rft.spage=4931&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 - 2004-06-01 N1 - Date created - 2004-04-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 2000 Nov 10;277(1):193-203 [11062050] J Virol. 1999 Aug;73(8):6626-33 [10400760] Virology. 2001 Nov 10;290(1):21-9 [11883002] J Virol. 2002 Jun;76(12):6398-407 [12021375] J Virol. 2002 Jul;76(14):7060-72 [12072506] Curr Biol. 2002 Jun 25;12(12):1046-51 [12123581] J Virol. 2002 Sep;76(17):8582-95 [12163578] EMBO J. 2003 Jun 2;22(11):2852-9 [12773399] Vet Clin North Am. 1976 Aug;6(3):399-413 [183336] J Gen Virol. 1978 Jun;39(3):537-40 [660166] J Biol Chem. 1978 Aug 10;253(15):5263-6 [209034] J Gen Virol. 1978 Nov;41(2):443-6 [569187] J Virol. 1988 Nov;62(11):4207-15 [2845132] J Virol. 1990 Jun;64(6):2967-75 [2159557] J Virol. 1991 Jan;65(1):511-3 [1702164] Arch Virol. 1992;122(3-4):223-35 [1731695] Virology. 1992 Sep;190(1):443-8 [1529544] Crit Rev Biochem Mol Biol. 1993;28(5):375-430 [8269709] Annu Rev Genet. 1993;27:353-436 [8122908] Virology. 1995 Jul 10;210(2):383-90 [7618275] J Virol. 1995 Nov;69(11):7159-68 [7474137] J Gen Virol. 1996 Jan;77 ( Pt 1):123-7 [8558120] Virology. 1996 Jun 15;220(2):535-8 [8661407] J Gen Virol. 1997 May;78 ( Pt 5):1033-40 [9152420] J Virol. 1997 Nov;71(11):8624-31 [9343220] J Virol. 1998 Apr;72(4):3051-9 [9525628] Nature. 1998 May 21;393(6682):280-4 [9607767] J Gen Virol. 1998 Aug;79 ( Pt 8):2043-9 [9714256] Arch Virol. 1998;143(12):2421-30 [9930197] J Gen Virol. 1999 Feb;80 ( Pt 2):291-6 [10073687] J Biol Chem. 2001 Jul 27;276(30):27787-92 [11369764] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combined unilateral lesions of the amygdala and orbital prefrontal cortex impair affective processing in rhesus monkeys. AN - 71809867; 14711973 AB - The amygdala and orbital prefrontal cortex (PFo) interact as part of a system for affective processing. To assess whether there is a hemispheric functional specialization for the processing of emotion or reward or both in nonhuman primates, rhesus monkeys (Macaca mulatta) with combined lesions of the amygdala and PFo in one hemisphere, either left or right, were compared with unoperated controls on a battery of tasks that tax affective processing, including two tasks that tax reward processing and two that assess emotional reactions. Although the two operated groups did not differ from each other, monkeys with unilateral lesions, left and right, showed altered reward-processing abilities as evidenced by attenuated reinforcer devaluation effects and an impairment in object reversal learning relative to controls. In addition, both operated groups showed blunted emotional reactions to a rubber snake. By contrast, monkeys with unilateral lesions did not differ from controls in their responses to an unfamiliar human (human "intruder"). Although the results provide no support for a hemispheric specialization of function, they yield the novel finding that unilateral lesions of the amygdala-orbitofrontal cortical circuit in monkeys are sufficient to significantly disrupt affective processing. JF - Journal of neurophysiology AU - Izquierdo, Alicia AU - Murray, Elisabeth A AD - Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. alicia@ln.nimh.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 2023 EP - 2039 VL - 91 IS - 5 SN - 0022-3077, 0022-3077 KW - Excitatory Amino Acid Agonists KW - 0 KW - Ibotenic Acid KW - 2552-55-8 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Eating -- physiology KW - Discrimination Learning -- physiology KW - Reinforcement (Psychology) KW - Reversal Learning -- physiology KW - Excitatory Amino Acid Agonists -- toxicity KW - Satiation -- physiology KW - Psychomotor Performance -- physiology KW - Visual Perception -- physiology KW - Facial Expression KW - Emotions -- physiology KW - Movement -- physiology KW - Food Preferences -- physiology KW - Macaca mulatta KW - Fear -- physiology KW - Ibotenic Acid -- toxicity KW - Male KW - Functional Laterality -- physiology KW - Affect -- physiology KW - Prefrontal Cortex -- physiology KW - Amygdala -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71809867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurophysiology&rft.atitle=Combined+unilateral+lesions+of+the+amygdala+and+orbital+prefrontal+cortex+impair+affective+processing+in+rhesus+monkeys.&rft.au=Izquierdo%2C+Alicia%3BMurray%2C+Elisabeth+A&rft.aulast=Izquierdo&rft.aufirst=Alicia&rft.date=2004-05-01&rft.volume=91&rft.issue=5&rft.spage=2023&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-25 N1 - Date created - 2004-04-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Neurophysiol. 2004 May;91(5):1938-9 [15069091] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Remarkable response to rituximab in a patient with atypical CD20(++) mantle cell lymphoma of the bone marrow leading to severe pancytopenia. AN - 71795542; 15064861 AB - Rituximab, a chimeric monoclonal antibody which binds to the CD20 antigen, has been reported in several studies to induce remissions in low- and high-grade non-Hodgkin's lymphoma without causing myelosuppression. We report here a case of a 68-year-old female patient with an atypical mantle cell lymphoma infiltrating only the bone marrow without leukemic involvement or any other nodal or extranodal manifestations. Progressive severe pancytopenia due to the diffuse bone marrow infiltration led to life-threatening infections following oral chlorambucil treatment. No response to chlorambucil was noted. The patient attained a complete remission after salvage therapy with four weekly infusions of single-agent rituximab at a standard dose of 375 mg/m(2). Thus, anti-CD20 antibody may be the treatment of choice for patients with CD20(+) B-non-Hodgkin's lymphoma who cannot tolerate chemotherapy due to high risk of infectious complications as a result of severe pancytopenia. JF - Annals of hematology AU - Seggewiss, R AU - Ho, A D AU - Kraemer, A AD - Department of Internal Medicine V, University of Heidelberg, Hospitalstr. 3, 69115, Heidelberg, Germany. seggewir@nhlbi.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 316 EP - 318 VL - 83 IS - 5 SN - 0939-5555, 0939-5555 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Antigens, CD20 KW - Antineoplastic Agents KW - Antineoplastic Agents, Alkylating KW - Chlorambucil KW - 18D0SL7309 KW - Rituximab KW - 4F4X42SYQ6 KW - Index Medicus KW - Bone Marrow -- pathology KW - Treatment Failure KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Humans KW - Salvage Therapy KW - Aged KW - Chlorambucil -- therapeutic use KW - Pancytopenia -- etiology KW - Female KW - Antigens, CD20 -- analysis KW - Lymphoma, Mantle-Cell -- complications KW - Bone Neoplasms -- immunology KW - Lymphoma, Mantle-Cell -- drug therapy KW - Bone Neoplasms -- drug therapy KW - Lymphoma, Mantle-Cell -- pathology KW - Bone Neoplasms -- pathology KW - Lymphoma, Mantle-Cell -- immunology KW - Antineoplastic Agents -- therapeutic use KW - Bone Neoplasms -- complications KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71795542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Remarkable+response+to+rituximab+in+a+patient+with+atypical+CD20%28%2B%2B%29+mantle+cell+lymphoma+of+the+bone+marrow+leading+to+severe+pancytopenia.&rft.au=Seggewiss%2C+R%3BHo%2C+A+D%3BKraemer%2C+A&rft.aulast=Seggewiss&rft.aufirst=R&rft.date=2004-05-01&rft.volume=83&rft.issue=5&rft.spage=316&rft.isbn=&rft.btitle=&rft.title=Annals+of+hematology&rft.issn=09395555&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-25 N1 - Date created - 2004-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of organophosphate insecticide-induced airway hyperreactivity. AN - 71794665; 14704222 AB - It has been suggested that pesticide exposure may be a contributing factor underlying the increased incidence of asthma in the United States and other industrialized nations. To test this hypothesis, airway hyperreactivity was measured in guinea pigs exposed to chlorpyrifos, a widely used organophosphate pesticide. Electrical stimulation of the vagus nerves caused frequency-dependent bronchoconstriction that was significantly potentiated in animals 24 h or 7 days after a single subcutaneous injection of either 390 mg/kg or 70 mg/kg of chlorpyrifos, respectively. Mechanisms by which chlorpyrifos may cause airway hyperreactivity include inhibition of acetylcholinesterase (AChE) or dysfunction of M3 muscarinic receptors on airway smooth muscle or of autoinhibitory M2 muscarinic receptors on parasympathetic nerves in the lung. AChE activity in the lung was significantly inhibited 24 h after treatment with 390 mg/kg of chlorpyrifos, but not 7 days after injection of 70 mg/kg of chlorpyrifos. Acute exposure to eserine (250 microg/ml) also significantly inhibited lung AChE but did not potentiate vagally induced bronchoconstriction. Neuronal M2 receptor function was tested using the M2 agonist pilocarpine, which inhibits vagally induced bronchoconstriction in control animals. In chlorpyrifos-treated animals, pilocarpine dose-response curves were shifted significantly to the right, demonstrating decreased responsiveness of neuronal M2 receptors. In contrast, chlorpyrifos treatment did not alter methacholine-induced bronchoconstriction, suggesting that chlorpyrifos does not alter M3 muscarinic receptor function on airway smooth muscle. These data demonstrate that organophosphate insecticides can cause airway hyperreactivity in the absence of AChE inhibition by decreasing neuronal M2 receptor function. JF - American journal of physiology. Lung cellular and molecular physiology AU - Fryer, Allison D AU - Lein, Pamela J AU - Howard, Angela S AU - Yost, Bethany L AU - Beckles, Rondell A AU - Jett, David A AD - National Institutes of Health National Institute of Neurological Disorders and Stroke, 6001 Executive Blvd. NSC, Suite 2149, MSC 9535, Bethesda, MD 20892-9835, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - L963 EP - L969 VL - 286 IS - 5 SN - 1040-0605, 1040-0605 KW - Cholinesterase Inhibitors KW - 0 KW - Insecticides KW - Receptor, Muscarinic M3 KW - Pilocarpine KW - 01MI4Q9DI3 KW - Physostigmine KW - 9U1VM840SP KW - Chlorpyrifos KW - JCS58I644W KW - Index Medicus KW - Cholinesterase Inhibitors -- pharmacology KW - Animals KW - Vagus Nerve -- physiology KW - Guinea Pigs KW - Neurons -- drug effects KW - Kinetics KW - Neurons -- physiology KW - Pilocarpine -- pharmacology KW - Vagus Nerve -- drug effects KW - Receptor, Muscarinic M3 -- drug effects KW - Male KW - Receptor, Muscarinic M3 -- physiology KW - Insecticides -- toxicity KW - Bronchial Hyperreactivity -- chemically induced KW - Chlorpyrifos -- toxicity KW - Bronchial Hyperreactivity -- physiopathology KW - Physostigmine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71794665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Lung+cellular+and+molecular+physiology&rft.atitle=Mechanisms+of+organophosphate+insecticide-induced+airway+hyperreactivity.&rft.au=Fryer%2C+Allison+D%3BLein%2C+Pamela+J%3BHoward%2C+Angela+S%3BYost%2C+Bethany+L%3BBeckles%2C+Rondell+A%3BJett%2C+David+A&rft.aulast=Fryer&rft.aufirst=Allison&rft.date=2004-05-01&rft.volume=286&rft.issue=5&rft.spage=L963&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Lung+cellular+and+molecular+physiology&rft.issn=10400605&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-17 N1 - Date created - 2004-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PCR-probe capture hybridization assay and statistical model for SEN virus prevalence estimation. AN - 71769217; 15042659 AB - SEN viruses (SENV) are newly discovered blood-borne single-stranded circular DNA viruses that may play a role in liver disease. To date, no serologic assays are available for the detection of SENV antigens or antibodies. We report on a rapid and sensitive molecular assay for the detection of four SENV strains (SENV-A, -C, -D, -H). This method uses PCR with universal primers and microwell capture hybridization with type-specific probes. Cut-off points to define "infected" based on chemiluminescence readings were determined from a statistical mixture model applied to samples from 300 injection drug users (IDUs) in San Francisco. Based on the estimated cut-off points, we examined the prevalence of SENV infection among 232 healthy US blood donors and assessed sensitivity and specificity of the assay in a small validation sample of infected individuals with partial sequence information. Copyright 2004 Wiley-Liss, Inc. JF - Journal of medical virology AU - Tanaka, Yasuhito AU - Pfeiffer, Ruth AU - Yeo, Anthony E T AU - Mizokami, Masashi AU - Edlin, Brian R AU - Castle, Philip AU - O'Brien, Thomas R AU - Alter, Harvey J AU - Shih, J Wai-Kuo AD - Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, The National Institutes of Health, DHHS, Bethesda, Maryland, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 123 EP - 130 VL - 73 IS - 1 SN - 0146-6615, 0146-6615 KW - DNA, Viral KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Polymerase Chain Reaction -- statistics & numerical data KW - Sequence Homology, Nucleic Acid KW - Humans KW - Models, Statistical KW - Models, Biological KW - Base Sequence KW - Polymerase Chain Reaction -- methods KW - Molecular Sequence Data KW - DNA, Viral -- isolation & purification KW - San Francisco -- epidemiology KW - Substance Abuse, Intravenous -- complications KW - United States -- epidemiology KW - DNA, Viral -- genetics KW - Circoviridae Infections -- epidemiology KW - Circoviridae -- genetics KW - Circoviridae Infections -- virology KW - Circoviridae Infections -- complications KW - Circoviridae -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71769217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+virology&rft.atitle=PCR-probe+capture+hybridization+assay+and+statistical+model+for+SEN+virus+prevalence+estimation.&rft.au=Tanaka%2C+Yasuhito%3BPfeiffer%2C+Ruth%3BYeo%2C+Anthony+E+T%3BMizokami%2C+Masashi%3BEdlin%2C+Brian+R%3BCastle%2C+Philip%3BO%27Brien%2C+Thomas+R%3BAlter%2C+Harvey+J%3BShih%2C+J+Wai-Kuo&rft.aulast=Tanaka&rft.aufirst=Yasuhito&rft.date=2004-05-01&rft.volume=73&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Journal+of+medical+virology&rft.issn=01466615&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-02 N1 - Date created - 2004-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 humanised mice. AN - 67164350; 15588489 AB - Humans are exposed to countless foreign compounds, typically referred to as xenobiotics. These can include clinically used drugs, environmental pollutants, food additives, pesticides, herbicides and even natural plant compounds. Xenobiotics are metabolised primarily in the liver, but also in the gut and other organs, to derivatives that are more easily eliminated from the body. In some cases, however, a compound is converted to an electrophile that can cause cell toxicity and transformation leading to cancer. Among the most important xenobiotic-metabolising enzymes are the cytochromes P450 (P450s). These enzymes represent a superfamily of multiple forms that exhibit marked species differences in their expression and catalytic activities. To predict how humans will metabolise xenobiotics, including drugs, human liver extracts and recombinant P450s have been used. New humanised mouse models are being developed which will be of great value in the study of drug metabolism, pharmacokinetics and pharmacodynamics in vivo, and in carrying out human risk assessment of xenobiotics. Humanised mice expressing CYP2D6 and CYP3A4, two major drug-metabolising P450s, have revealed the feasibility of this approach. JF - Human genomics AU - Gonzalez, Frank J AD - Laboratory of Metabolism, National Cancer Institute, Building 37, Room 3106B, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 300 EP - 306 VL - 1 IS - 4 SN - 1473-9542, 1473-9542 KW - Xenobiotics KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - CYP3A4 protein, human KW - EC 1.14.13.67 KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP2D6 KW - Cytochrome P-450 CYP3A KW - Index Medicus KW - Animals KW - Xenobiotics -- metabolism KW - Humans KW - Mice KW - Mice, Transgenic KW - Cytochrome P-450 CYP2D6 -- genetics KW - Cytochrome P-450 CYP2D6 -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67164350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genomics&rft.atitle=Cytochrome+P450+humanised+mice.&rft.au=Gonzalez%2C+Frank+J&rft.aulast=Gonzalez&rft.aufirst=Frank&rft.date=2004-05-01&rft.volume=1&rft.issue=4&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Human+genomics&rft.issn=14739542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-29 N1 - Date created - 2004-12-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Biochem Biophys. 1996 May 15;329(2):235-240 [8638957] Annu Rev Pharmacol Toxicol. 1995;35:369-90 [7598499] J Pharmacol Exp Ther. 1997 Sep;282(3):1435-41 [9316857] Mutat Res. 1998 May 25;400(1-2):201-13 [9685642] Pharmacol Ther. 1999 Nov;84(2):121-31 [10596902] Annu Rev Pharmacol Toxicol. 2000;40:159-76 [10836131] Chem Biol Interact. 2000 Dec 1;129(1-2):41-59 [11154734] Chem Biol Interact. 2000 Dec 1;129(1-2):77-97 [11154736] Curr Oncol Rep. 2000 May;2(3):251-6 [11122850] Mol Cell Biol. 2001 Feb;21(4):1393-403 [11158324] Curr Drug Metab. 2000 Sep;1(2):143-61 [11465080] Mutat Res. 2001 Oct 1;482(1-2):21-6 [11535245] Mol Pharmacol. 2001 Dec;60(6):1260-7 [11723233] Nat Genet. 2002 Jan;30(1):66-72 [11740496] Methods Mol Biol. 2002;180:175-204 [11873650] Drug Metab Rev. 2002 Feb-May;34(1-2):83-448 [11996015] Drug Metab Rev. 2002 Aug;34(3):503-11 [12214662] Mutat Res. 2002 Sep 30;506-507:65-77 [12351146] Adv Drug Deliv Rev. 2002 Nov 18;54(10):1271-94 [12406645] Curr Drug Metab. 2003 Feb;4(1):45-58 [12570745] Pharmacogenetics. 2003 Mar;13(3):173-81 [12618595] Drug Metab Dispos. 2003 May;31(5):548-58 [12695342] Pharmacogenomics. 2003 Jul;4(4):387-95 [12831319] Pharmacogenetics. 2004 Jan;14(1):1-18 [15128046] Lancet. 1977 Sep 17;2(8038):584-6 [71400] Am J Hum Genet. 1989 Dec;45(6):889-904 [2574001] Trends Genet. 1990 Jun;6(6):182-6 [2196721] J Pharmacol Exp Ther. 1994 Oct;271(1):549-56 [7965755] Toxicol Pathol. 1996 Jan-Feb;24(1):48-57 [8839280] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [A series of cases of sinonasal cancer among shoemakers and tannery workers]. TT - Analisi di una serie di casi di neoplasie maligne delle fosse nasali e dei seni accessori nel settore conciario e delle calzature. AN - 67060248; 15532874 AB - A series of cases of sinunasal cancer has been observed among shoe-makers (11 cases) and tannery workers (8 cases) in the leather production area in Tuscany in the period 1990-2002. We stress the possible etiologic role of tannins both in leather and in wood industry. JF - Epidemiologia e prevenzione AU - Iaia, Tonina Enza AU - Farina, Giuseppe AU - Ferraro, Maria Teresa AU - Miceli, Giovanni Battista AU - Mugnaini, Elisabetta AU - Papaleo, Bruno AU - Battista, Giuseppe AD - UO igiene e salute nei luoghi di lavoro, USL 11, S. Romano, PI. PY - 2004 SP - 169 EP - 173 VL - 28 IS - 3 SN - 1120-9763, 1120-9763 KW - Tannins KW - 0 KW - Index Medicus KW - Humans KW - Adult KW - Aged KW - Shoes KW - Middle Aged KW - Male KW - Female KW - Paranasal Sinus Neoplasms -- chemically induced KW - Tanning KW - Tannins -- adverse effects KW - Occupational Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67060248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiologia+e+prevenzione&rft.atitle=%5BA+series+of+cases+of+sinonasal+cancer+among+shoemakers+and+tannery+workers%5D.&rft.au=Iaia%2C+Tonina+Enza%3BFarina%2C+Giuseppe%3BFerraro%2C+Maria+Teresa%3BMiceli%2C+Giovanni+Battista%3BMugnaini%2C+Elisabetta%3BPapaleo%2C+Bruno%3BBattista%2C+Giuseppe&rft.aulast=Iaia&rft.aufirst=Tonina&rft.date=2004-05-01&rft.volume=28&rft.issue=3&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Epidemiologia+e+prevenzione&rft.issn=11209763&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-19 N1 - Date created - 2004-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of alpha2u-globulin nephropathy and adrenal medullary pheochromocytomas in male rats following exposure to Stoddard solvent IIC. AN - 66883140; 15371178 AB - Stoddard solvent IIC is widely used as a solvent in paints and varnishes, and for dry cleaning and other grease removal applications. Because concern exists regarding the long-term effects of occupational exposure in industrial settings, the toxicity and carcinogenicity of Stoddard solvent IIC were evaluated in male and female F344/N rats and B6C3F1 mice. Rats and mice were exposed to 0, 138, 275, 550, 1100, or 2200 mg/m3 Stoddard solvent IIC by whole-body inhalation for 3 mo, and to 0, 138 (male rats), 550, 1100, or 2200 (female rats and male and female mice) mg/m3 for 2 yr. The kidney, liver, and adrenal medulla were targets of Stoddard solvent IIC toxicity in rats. After 3 mo of exposure, male rats developed lesions characteristic of alpha2u-globulin nephropathy. Male and female rats displayed increased liver weights and/or clinical pathology changes suggestive of hepatic injury, although no accompanying histopathologic changes were observed. After 2 yr, increased incidences of adrenal medullary pheochromocytomas provided some evidence of carcinogenicity in male rats. Renal tubule adenomas were slightly increased in male rats after 2 yr, and may have been related to exposure. In mice, there was no chemical-related toxicity after 3 mo, with the exception of increased liver weights in male mice exposed to 2200 mg/m3. After 2 yr, the incidences of hepatocellular adenomas were increased in female mice exposed to 2200 mg/m3; however, these increases were marginal and associated with increases in body weight. There was no evidence of Stoddard solvent IIC carcinogenicity in female rats or male mice. In summary, inhalation exposures of Stoddard solvent IIC resulted in renal toxicity and adrenal medullary pheochromocytomas in male rats. The liver also appeared to be a site of toxicity in male and female rats and mice. Copyright Taylor & Francis Inc. JF - Inhalation toxicology AU - Doi, Adriana AU - Peckham, John AU - Chou, Billy AU - Dill, Jeffrey AU - Renne, Roger AU - Grumbein, Sondra AU - Chhabra, Rajendra AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. doi@niehs.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 247 EP - 257 VL - 16 IS - 5 SN - 0895-8378, 0895-8378 KW - Alpha-Globulins KW - 0 KW - Carcinogens KW - Hydrocarbons KW - alpha 2u globulin KW - Stoddard solvent KW - 8052-41-3 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Kidney Tubules, Proximal -- pathology KW - Mice KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Kidney Tubules, Proximal -- metabolism KW - Inhalation Exposure KW - Carcinogenicity Tests KW - Environmental Exposure KW - Kidney Tubules, Proximal -- drug effects KW - Administration, Inhalation KW - Female KW - Male KW - Kidney Neoplasms -- pathology KW - Carcinogens -- administration & dosage KW - Pheochromocytoma -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Pheochromocytoma -- pathology KW - Alpha-Globulins -- metabolism KW - Pheochromocytoma -- metabolism KW - Adenoma -- metabolism KW - Adrenal Gland Neoplasms -- metabolism KW - Hydrocarbons -- administration & dosage KW - Kidney Neoplasms -- metabolism KW - Adenoma -- chemically induced KW - Adrenal Gland Neoplasms -- chemically induced KW - Adrenal Gland Neoplasms -- pathology KW - Hydrocarbons -- toxicity KW - Adenoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66883140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inhalation+toxicology&rft.atitle=Development+of+alpha2u-globulin+nephropathy+and+adrenal+medullary+pheochromocytomas+in+male+rats+following+exposure+to+Stoddard+solvent+IIC.&rft.au=Doi%2C+Adriana%3BPeckham%2C+John%3BChou%2C+Billy%3BDill%2C+Jeffrey%3BRenne%2C+Roger%3BGrumbein%2C+Sondra%3BChhabra%2C+Rajendra&rft.aulast=Doi&rft.aufirst=Adriana&rft.date=2004-05-01&rft.volume=16&rft.issue=5&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Inhalation+toxicology&rft.issn=08958378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-05 N1 - Date created - 2004-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pupillometry in the detection of concomitant drug use in opioid-maintained patients. AN - 66801791; 15319805 AB - Pupillometry and ocular response measures are sensitive to a variety of acutely administered drugs and as such are useful for drug detection and fitness-for-duty applications. The utility of pupillometry to complement urine testing in methadone clinics, where there is considerable non-therapeutic drug use, has not been tested. A video-based pupillometer (FIT 2000) was evaluated in 37 opioid-maintained patients. Three times a week they provided urine samples and pupillometry measures of: initial diameter (ID) in mm; constriction amplitude (CA) in mm; constriction latency (CL) in msec; and saccadic velocity (SV) in mm/sec. Analysis of the success rates indicated that 92.9% of subjects obtained an acceptable reading, 59% on the first attempt. Low variability in pupillary parameters on drug-free days are necessary for effective identification of concomitant drug use. The variability (standard deviation) of ID (0.51 vs. 0.68), CA (0.12 vs. 0.27) and SV (7.2 vs. 11.1) increased on days when the urine was positive for abused drugs compared with drug-free urine days in subjects (n = 6). Subjects who were always drug-free (n = 4) had lower variability than those who always had urine positive for additional drugs (n = 20). These preliminary results suggest that pupillometry may be useful to verify concomitant drug use in a methadone-maintained population. Successful implementation of the methodology could reduce costly and intrusive urine testing. JF - Methods and findings in experimental and clinical pharmacology AU - Murillo, R AU - Crucilla, C AU - Schmittner, J AU - Hotchkiss, E AU - Pickworth, W B AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 271 EP - 275 VL - 26 IS - 4 SN - 0379-0355, 0379-0355 KW - Street Drugs KW - 0 KW - Buprenorphine KW - 40D3SCR4GZ KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Drug Interactions KW - Buprenorphine -- therapeutic use KW - Methadone -- therapeutic use KW - Biometry -- methods KW - Buprenorphine -- pharmacology KW - Humans KW - Street Drugs -- blood KW - Miosis -- chemically induced KW - Methadone -- pharmacology KW - Miosis -- physiopathology KW - Diagnostic Techniques, Ophthalmological -- instrumentation KW - Street Drugs -- adverse effects KW - Adult KW - Female KW - Male KW - Opioid-Related Disorders -- diagnosis KW - Reflex, Pupillary -- drug effects KW - Reflex, Pupillary -- physiology KW - Pupil -- physiology KW - Opioid-Related Disorders -- drug therapy KW - Opioid-Related Disorders -- blood KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66801791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+findings+in+experimental+and+clinical+pharmacology&rft.atitle=Pupillometry+in+the+detection+of+concomitant+drug+use+in+opioid-maintained+patients.&rft.au=Murillo%2C+R%3BCrucilla%2C+C%3BSchmittner%2C+J%3BHotchkiss%2C+E%3BPickworth%2C+W+B&rft.aulast=Murillo&rft.aufirst=R&rft.date=2004-05-01&rft.volume=26&rft.issue=4&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Methods+and+findings+in+experimental+and+clinical+pharmacology&rft.issn=03790355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-25 N1 - Date created - 2004-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epirubicin plus docetaxel in metastatic breast cancer: escalating dose does not improve efficacy. A phase II study. AN - 66743155; 15274385 AB - The combination of anthracyclines and docetaxel have demonstrated a significant activity in metastatic breast cancer (MBC) as first-line chemotherapy. In a previous multicenter phase I study, we recommended two schedules of epirubicin-docetaxel combination for MBC: 1) epirubicin 75 mg/m2, docetaxel 80 mg/m2 every 3 weeks without G-CSF; 2) epirubicin 90 mg/m2 plus docetaxel 90 mg/m2 every 3 weeks, with G-CSF support. Twenty-five advanced breast cancer patients were treated with epirubicin 90 mg/m2 plus docetaxel 90 mg/m2 every 3 weeks, with prophylactic G-CSF. The main toxicity was grade 3-4 neutropenia (41% of cycles) despite the use of G-CSF; febrile neutropenia was observed in 14% of cycles necessitating a dose reduction of both drugs in 30% of patients. Response was observed in 79% of patients: 21% complete responses and 58% partial responses. The median response duration was 10 months (range: 3-16). The median time to progression was 11 months. The overall 3-year survival was 49.7%. The antitumor activity observed in this series was comparable with that seen in other studies of taxane/anthracycline combinations. The degree of myelosuppression was severe, even though G-CSF was administered as a prophylactic. We recommend a lower dose of both drugs as reported by other authors. JF - Anticancer research AU - Fabi, Alessandra AU - Papaldo, Paola AU - Pino, Maria Simona AU - Ferretti, Gianluigi AU - Carlini, Paolo AU - Pacetti, Umberto AU - Di Cosimo, Serena AU - Nardoni, Chiara AU - Giannarelli, Diana AU - Sacchi, Italo AU - Cognetti, Francesco AD - Division of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. alessandra.fabi@virgilio.it PY - 2004 SP - 1963 EP - 1967 VL - 24 IS - 3b SN - 0250-7005, 0250-7005 KW - Taxoids KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - docetaxel KW - 15H5577CQD KW - Epirubicin KW - 3Z8479ZZ5X KW - Index Medicus KW - Drug Administration Schedule KW - Humans KW - Adult KW - Taxoids -- adverse effects KW - Neoplasm Metastasis KW - Aged KW - Middle Aged KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Epirubicin -- adverse effects KW - Epirubicin -- administration & dosage KW - Female KW - Taxoids -- administration & dosage KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology 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/66743155?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Epirubicin+plus+docetaxel+in+metastatic+breast+cancer%3A+escalating+dose+does+not+improve+efficacy.+A+phase+II+study.&rft.au=Fabi%2C+Alessandra%3BPapaldo%2C+Paola%3BPino%2C+Maria+Simona%3BFerretti%2C+Gianluigi%3BCarlini%2C+Paolo%3BPacetti%2C+Umberto%3BDi+Cosimo%2C+Serena%3BNardoni%2C+Chiara%3BGiannarelli%2C+Diana%3BSacchi%2C+Italo%3BCognetti%2C+Francesco&rft.aulast=Fabi&rft.aufirst=Alessandra&rft.date=2004-05-01&rft.volume=24&rft.issue=3b&rft.spage=1963&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 - 2004-09-09 N1 - Date created - 2004-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electron microscopy of wet tissues: a case study in renal pathology. AN - 66649281; 15204979 AB - In this report we introduce wet-tissue scanning electron microscopy, a novel technique for direct imaging of wet tissue samples using backscattered electrons. Samples placed in sealed capsules are imaged through a resilient, electron-transparent membrane. The contrast of the imaged samples may be enhanced by chemical staining. The samples several millimeters thick and imaged without sectioning, makes this technique suitable for rapid analysis of tissue specimens. We applied this technique to D-limonene-induced nephropathy where accumulation of hyaline protein droplets is induced in proximal and distal convoluted tubules of the kidney. Images obtained by scanning electron microscopy of hydrated kidney specimens exhibited superior resolution, contrast, and magnification compared with those obtained by conventional light microscopy of paraffin sections. The electron micrographs can be obtained within an hour of tissue removal, whereas preparation for light microscopy requires at least 1 day. These advantages of the wet scanning electron microscopy technique indicate its potential utility in a wide range of applications in histopathology and toxicology. JF - Toxicologic pathology AU - Nyska, Abraham AU - Cummings, Connie A AU - Vainshtein, Anya AU - Nadler, Jonathan AU - Ezov, Nathan AU - Grunfeld, Yona AU - Gileadi, Opher AU - Behar, Vered AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. nyska@niehs.nih.gov PY - 2004 SP - 357 EP - 363 VL - 32 IS - 3 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Cyclohexenes KW - Terpenes KW - limonene KW - 9MC3I34447 KW - Index Medicus KW - Terpenes -- toxicity KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Paraffin Embedding KW - Carcinogens -- toxicity KW - Time Factors KW - Male KW - Kidney Diseases -- pathology KW - Kidney -- pathology KW - Kidney -- ultrastructure KW - Histological Techniques -- methods KW - Microscopy, Electron, Scanning -- instrumentation KW - Microscopy, Electron, Scanning -- methods KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66649281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Electron+microscopy+of+wet+tissues%3A+a+case+study+in+renal+pathology.&rft.au=Nyska%2C+Abraham%3BCummings%2C+Connie+A%3BVainshtein%2C+Anya%3BNadler%2C+Jonathan%3BEzov%2C+Nathan%3BGrunfeld%2C+Yona%3BGileadi%2C+Opher%3BBehar%2C+Vered&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2004-05-01&rft.volume=32&rft.issue=3&rft.spage=357&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 - 2005-01-31 N1 - Date created - 2004-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiac damage in rodents after exposure to bis(2-chloroethoxy)methane. AN - 66648853; 15204972 AB - We report that an environmental agent, bis(2-chloroethoxy)methane (CEM), caused cardiac toxicity in male and female F344 rats and B6C3F1 mice exposed to the chemical by dermal administration at doses of 0, 50, 100, 200, 400 or 600 mg/kg 5 days a week for up to 14 weeks. Treatment-related deaths occurred in 10/10 male and 10/10 female rats at 600 mg/kg, in 2/10 female rats at 400 mg/kg, and in 3/10 female mice at 600 mg/kg. The heart lesions were more severe in rats than mice, and more severe in females than males. In rats, the no-observed-adverse-effect level (NOAEL) for the heart lesions was 200 mg/kg for males and 100 mg/kg for females; in mice, it was more than 600 mg/kg for males and 200 mg/kg for females. Multifocal, widespread vacuolization of the myocytes comprised the main morphological feature of the lesions, and only in rats was it accompanied by mononuclear cell infiltration, myocytic necrosis and atrial thrombosis. Hearts from male rats were immunohistochemically stained for troponin T (cTnT) protein. Loss of cytoplasmic cTnT correlated with histopathological damage only in the 600 mg/kg animals. CEM is metabolized to thiodiglycolic acid, a chemical that causes mitochondrial dysfunction. It is hypothesized that mitochondrial damage leads to the heart toxicity from bis(2-chloroethoxy)methane. JF - Toxicologic pathology AU - Dunnick, June K AU - Lieuallen, Warren AU - Moyer, Carolyn AU - Orzech, Denise AU - Nyska, Abraham AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. dunnickj@niehs.nih.gov PY - 2004 SP - 309 EP - 317 VL - 32 IS - 3 SN - 0192-6233, 0192-6233 KW - Ethyl Ethers KW - 0 KW - Solvents KW - Troponin T KW - bis(2-chloroethoxy)methane KW - Index Medicus KW - Animals KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Inflammation -- chemically induced KW - Mitochondria -- pathology KW - Mice KW - Troponin T -- drug effects KW - Rats KW - Mitochondria -- drug effects KW - Species Specificity KW - Immunohistochemistry KW - Female KW - Male KW - Inflammation -- pathology KW - Solvents -- toxicity KW - Myocardium -- pathology KW - Ethyl Ethers -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66648853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cardiac+damage+in+rodents+after+exposure+to+bis%282-chloroethoxy%29methane.&rft.au=Dunnick%2C+June+K%3BLieuallen%2C+Warren%3BMoyer%2C+Carolyn%3BOrzech%2C+Denise%3BNyska%2C+Abraham&rft.aulast=Dunnick&rft.aufirst=June&rft.date=2004-05-01&rft.volume=32&rft.issue=3&rft.spage=309&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 - 2005-01-31 N1 - Date created - 2004-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NTP technical report on the toxicology and carcinogenesis studies of Elmiron (Cas No. 37319-17-8) in F344/N rats and B6C3F1 mice (Gavage Studies). AN - 66641291; 15213766 AB - [structure--see text] Elmiron, a white powder, is the sodium salt of pentosan polysulfate, a semisynthetic sulfated polyanion composed of beta-D-xylopyranose residues with biological properties similar to heparin. Elmiron is used in the United States for the relief of urinary bladder pain associated with interstitial cystitis. Because of its stimulating effect on fibrinolysis, Elmiron has been used clinically in the treatment and prevention of thrombotic disorders. The United States Food and Drug Administration nominated Elmiron for toxicology and carcinogenicity testing by the National Toxicology Program because of its orphan drug status. Male and female F344/N rats and B6C3F1 mice received Elmiron, which met product specifications provided by the manufacturer, in deionized water by gavage for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were administered 0, 33, 111, 333, 1,000, or 3,000 mg Elmiron/kg body weight in deionized water by gavage, 5 days per week, for 16 days. Elmiron administration had no effect on survival or body weight gain. Activated partial thromboplastin time was significantly increased in 3,000 mg/kg rats. Liver weights of 3,000 mg/kg rats were significantly greater than those of the vehicle controls. Hepatocellular cytoplasmic vacuolization occurred in all 3,000 mg/kg females. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were administered Elmiron in deionized water by gavage at doses of 0, 33, 111, 333, 1,000, or 3,000 mg/kg, 5 days per week, for 16 days. All mice survived to the end of the study. Mean body weight gains of male mice administered 333 mg/kg or greater were significantly greater than that of the vehicle control group. Liver weights of 1,000 and 3,000 mg/kg males were significantly increased. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered Elmiron in deionized water by gavage at doses of 0, 63, 125, 250, 500, or 1,000 mg/kg, 5 days per week, for 14 weeks. No deaths were attributed to administration of Elmiron. Mean body weights of 125 mg/kg males were less than those of vehicle controls and the mean body weights of all dosed groups of females were greater. Hematology results indicated that Elmiron, at the doses selected, induced a minimal erythron decrease and leukocyte and platelet count increases that may have been secondarily related to the inflammatory lesions observed in various tissues of rats. Liver and spleen weights of males administered 250 mg/kg or greater were significantly increased. Liver weights of all dosed groups of females, and kidney, lung, and spleen weights of 1,000 mg/kg females were significantly increased. Histiocytic cellular infiltration, chronic active inflammation, and ulcers of the rectum occurred in most 500 and 1,000 mg/kg rats. Administration of Elmiron was associated with the presence of vacuolated histiocytes in the mandibular and mesenteric lymph nodes, lung, kidney, and liver of male and female rats. Histochemical investigations of the vacuolated histiocytes indicated the presence of neutral and acidic mucins and lipid material within the vacuoles. Transmission electron microscopy identified these vacuoles as lysosomal structures that exhibited a variety of contents. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were administered Elmiron in deionized water by gavage at doses of 0, 63, 125, 250, 500, or 1,000 mg/kg, 5 days per week, for 14 weeks. One 250 mg/kg female mouse was sacrificed moribund on day 84; all other mice survived to the end of the study. Mean body weights of dosed groups were similar to those of the vehicle control groups. Hematology results indicated that Elmiron, at the doses selected, induced a minimal erythron decrease and leukocyte and platelet count increases that may have been secondarily related to the inflammatory lesions observed in various tissues of mice. in various tissues of mice. Liver weights of 500 mg/kg males and 1,000 mg/kg males and females, and spleen weights of 1,000 mg/kg males were significantly increased. Histiocytic cellular infiltration and chronic active inflammation of the rectum occurred in most 1,000 mg/kg mice. Administration of Elmiron was associated with the presence of vacuolated histiocytes in the mandibular and mesenteric lymph nodes, liver, and spleen of males and females. Histochemical investigations of the vacuolated histiocytes indicated the presence of neutral and acidic mucins within the vacuoles. Transmission electron microscopy identified these vacuoles as lysosomal structures that exhibited a variety of contents. 2-YEAR STUDY IN RATS: Groups of 50 males and 50 females were administered Elmiron in deionized water by gavage at doses of 0, 14, 42, or 126 mg/kg to males and 0, 28, 84, or 252 mg/kg to females, 5 days per week, for 104 or 105 weeks. Survival of all dosed groups of rats was similar to that of the vehicle control groups. Mean body weights of all dosed groups were similar to those of the vehicle controls throughout the 2-year study. Microscopically, myxomatous changes were present in the rectum of 56% of 126 mg/kg males and 83% of 252 mg/kg females. The incidences of chronic active focal alveolar inflammation of the lung were increased in all dosed groups. The incidences of histiocytic cellular infiltration of the mesenteric lymph nodes were increased in 42 and 126 mg/kg males and in 84 and 252 mg/kg females, and lymphohistiocytic hyperplasia was present in the spleen of 126 mg/kg males and 252 mg/kg females. 2-YEAR STUDY IN MICE: Groups of 50 males and 50 females were administered Elmiron in deionized water by gavage at doses of 0, 56, 168, or 504 mg/kg, 5 days per week, for 104 or 105 weeks. Survival of all dosed groups of mice was similar to that of the vehicle control groups. Mean body weights of males were similar to those of vehicle controls. Mean body weights of 504 mg/kg females were progressively less than those of the vehicle controls during the second year of the study. Increased incidences of hemangiosarcomas of the liver and hepatocellular neoplasms were observed in male and female mice. The incidences of hemangiosarcomas in the 504 mg/kg groups exceeded the historical control ranges for males and females; both the trend and the incidence in the 504 mg/kg groups were significant for males. Hemangiosarcomas in males and females were attributed to Elmiron administration. The incidence of hepatocellular adenoma in 504 mg/kg females was significantly increased and exceeded the historical control range; the trends for hepatocellular adenoma and for hepatocellular adenoma or carcinoma (combined) were also significant in females and were attributed to Elmiron administration. There was also a marginal increase in the incidences of hepatocellular neoplasms in male mice, which may have been associated with Elmiron administration. Malignant lymphomas occurred with a positive trend in female mice; the incidence in the 504 mg/kg group was also significantly increased and matched the upper limit of the historical control range. These malignant lymphomas may have been associated with Elmiron administration. Nonneoplastic lesions related to the administration of Elmiron occurred in the liver, rectum, mesenteric lymph node, and spleen of 504 mg/kg mice and to a lesser extent in 168 mg/kg mice. These lesions were similar to those observed in the 3-month study. Elmiron was not mutagenic in S. typhimurium strains TA97, TA98, TA100, or TA1535 with or without induced hamster or rat liver S9 enzymes. No increases in the frequency of micronucleated polychromatic erythrocytes were seen in bone marrow cells of rats or mice administered Elmiron by gavage three times at 24-hour intervals. No significant alterations in the frequency of micronucleated normochromatic erythrocytes were seen in peripheral blood samples from male or female mice administered Elmiron for 3 months by gavage. Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of Elmiron in male F344/N rats administered 14, 42, or 126 mg/kg or in female F344/N rats administered 28, 84, or 252 mg/kg. There was some evidence of carcinogenic activity of Elmiron in male B6C3F1 mice based on increased incidences of liver hemangiosarcoma. The increased incidences of hepatocellular neoplasms in male mice may have been related to Elmiron administration. There was some evidence of carcinogenic activity of Elmiron in female B6C3F1 mice based on the increased incidences of liver hemangiosarcoma and hepatocellular neoplasms. The increased incidences of malignant lymphomas in female mice may have been related to Elmiron administration. Elmiron administration caused increased incidences of nonneoplastic lesions (presence of vacuolated histiocytes) of the rectum, lung, mesenteric lymph node, and spleen (males) in rats and of the liver, rectum, mesenteric lymph node, and spleen in mice. JF - National Toxicology Program technical report series AU - National Toxicology Program, Public Health Services, National Institutes of Health, US Department of Health and Human Services, AD - National Toxicology Program, Public Health Services, National Institutes of Health, US Department of Health and Human Services, Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 7 EP - 289 IS - 512 SN - 0888-8051, 0888-8051 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Carcinogens KW - Pentosan Sulfuric Polyester KW - 37300-21-3 KW - Index Medicus KW - Administration, Oral KW - Animals KW - Dose-Response Relationship, Drug KW - Liver Neoplasms -- chemically induced KW - Mice KW - Hemangiosarcoma -- chemically induced KW - Adenoma, Liver Cell -- chemically induced KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - Liver Neoplasms -- pathology KW - Body Weight -- drug effects KW - Hemangiosarcoma -- pathology KW - Toxicity Tests, Chronic KW - Carcinogenicity Tests KW - Carcinoma, Hepatocellular -- pathology KW - Adenoma, Liver Cell -- pathology KW - Male KW - Carcinoma, Hepatocellular -- chemically induced KW - Female KW - Carcinogens -- administration & dosage KW - Pentosan Sulfuric Polyester -- administration & dosage KW - Neoplasms, Experimental -- chemically induced KW - Carcinogens -- toxicity KW - Pentosan Sulfuric Polyester -- toxicity KW - Anti-Inflammatory Agents, Non-Steroidal -- administration & dosage KW - Neoplasms, Experimental -- pathology KW - Anti-Inflammatory Agents, Non-Steroidal -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66641291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=National+Toxicology+Program+technical+report+series&rft.atitle=NTP+technical+report+on+the+toxicology+and+carcinogenesis+studies+of+Elmiron+%28Cas+No.+37319-17-8%29+in+F344%2FN+rats+and+B6C3F1+mice+%28Gavage+Studies%29.&rft.au=National+Toxicology+Program%2C+Public+Health+Services%2C+National+Institutes+of+Health%2C+US+Department+of+Health+and+Human+Services&rft.aulast=National+Toxicology+Program&rft.aufirst=Public+Health&rft.date=2004-05-01&rft.volume=&rft.issue=512&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=National+Toxicology+Program+technical+report+series&rft.issn=08888051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-03 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NTP toxicology and carcinogenesis studies of triethanolamine (Cas No. 102-71-6) in B6C3F1 mice (dermal studies). AN - 66640813; 15213765 AB - [structure--see text] Triethanolamine is widely used in the manufacturing of household detergents and polishes, textiles, agricultural herbicides, mineral and vegetable oils, paraffin and waxes, pharmaceutical ointments, petroleum demulsifiers, synthetic resins, plasticizers, adhesives, and sealants. It is used as a chemical intermediate for anionic and nonionic surfactants, a vulcanization accelerator, a humectant and softening agent and in many other industrial applications. The National Cancer Institute nominated triethanolamine for study because of its widespread use in cosmetics and other consumer products, its high potential for worker exposure due to its many industrial uses, and its potential for conversion to the carcinogen N-nitrosodiethanolamine. Previous 3-month and 2-year studies of triethanolamine were conducted by the National Toxicology Program in F344/N rats and B6C3F1 mice; results from the 2-year rat study indicated equivocal evidence of carcinogenic activity based on a marginal increase in the incidence of renal tubule adenoma (NTP, 1991). Interpretation of the results from the 2-year study in mice was complicated by Helicobacter hepaticus infection, prompting a repeat 2-year study in mice. Male and female B6C3F1 mice received triethanolamine (greater than 99% pure) by dermal application for 2 years; a study of absorption, distribution, metabolism, and excretion was performed in additional mice. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, Drosophila melanogaster, and mouse peripheral blood erythrocytes. 2-YEAR STUDY: Groups of 50 male and 50 female mice received dermal applications of 0, 200, 630, or 2,000 mg/kg (males) and 0, 100, 300, or 1,000 mg/kg (females) triethanolamine in acetone, 5 days per week, for 104 (males) or 104 to 105 (females) weeks. Survival of all dosed groups was similar to that of the vehicle control groups. Body weights of 2,000 mg/kg males were less than those of the vehicle controls from weeks 17 to 37 and at the end of the study; body weights of dosed groups of females were similar to those of the vehicle controls throughout the study. Treatment-related clinical findings included skin irritation at the site of application, which increased with increasing dose and was more severe in males than in females. Gross lesions observed at necropsy included nodules and masses of the liver in dosed females. The incidences of hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined) were significantly increased in all dosed groups of females. The incidence of hemangiosarcoma of the liver in 630 mg/kg males was marginally increased. The incidences of eosinophilic focus in all dosed groups of mice were greater than those in the vehicle controls. Gross lesions observed at necropsy included visible crusts at the site of application in all dosed groups of mice. Treatment-related epidermal hyperplasia, suppurative inflammation, ulceration, and dermal chronic inflammation occurred at the site of application in most dosed groups of mice, and the incidences and severities of these lesions generally increased with increasing dose. Triethanolamine was not mutagenic in any of the in vitro or in vivo tests. It did not induce mutations in Salmonella typhimurium, and no induction of sister chromatid exchanges or chromosomal aberrations was noted in cultured Chinese hamster ovary cells exposed to triethanolamine. These in vitro tests were all conducted with and without S9 metabolic activation. Triethanolamine did not induce sex-linked recessive lethal mutations in germ cells of adult male Drosophila melanogaster exposed by feeding or injection. No increase in the frequency of micronucleated erythrocytes was observed in peripheral blood samples of male or female mice that received dermal applications of triethanolamine for 13 weeks. Under the conditions of this 2-year dermal study, there was equivocal evidence of carcinogenic activity of triethanolamine in male B6C3F1 mice based on the occurrence of liver hemangiosarcoma. There was some evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular adenoma. Exposure to triethanolamine by dermal application resulted in increased incidences of eosinophilic focus of the liver in males and females. Dosed mice developed treatment-related nonneoplastic lesions at the site of application. JF - National Toxicology Program technical report series AU - National Toxicology Program, Public Health Service, National Institutes of Health, US Department of Health and Human Services AD - National Toxicology Program, Public Health Service, National Institutes of Health, US Department of Health and Human Services Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 5 EP - 163 IS - 518 SN - 0888-8051, 0888-8051 KW - Carcinogens KW - 0 KW - Environmental Pollutants KW - Ethanolamines KW - triethanolamine KW - 9O3K93S3TK KW - Index Medicus KW - Animals KW - Administration, Cutaneous KW - Dose-Response Relationship, Drug KW - Hemangiosarcoma -- chemically induced KW - Mice KW - Adenoma, Liver Cell -- chemically induced KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - Body Weight -- drug effects KW - Hemangiosarcoma -- pathology KW - Toxicity Tests, Chronic KW - Carcinogenicity Tests KW - Adenoma, Liver Cell -- pathology KW - Female KW - Male KW - Liver Neoplasms -- pathology KW - Environmental Pollutants -- toxicity KW - Carcinogens -- administration & dosage KW - Neoplasms, Experimental -- chemically induced KW - Ethanolamines -- administration & dosage KW - Liver Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Ethanolamines -- toxicity KW - Neoplasms, Experimental -- pathology KW - Environmental Pollutants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66640813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=National+Toxicology+Program+technical+report+series&rft.atitle=NTP+toxicology+and+carcinogenesis+studies+of+triethanolamine+%28Cas+No.+102-71-6%29+in+B6C3F1+mice+%28dermal+studies%29.&rft.au=National+Toxicology+Program%2C+Public+Health+Service%2C+National+Institutes+of+Health%2C+US+Department+of+Health+and+Human+Services&rft.aulast=National+Toxicology+Program&rft.aufirst=Public+Health&rft.date=2004-05-01&rft.volume=&rft.issue=518&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=National+Toxicology+Program+technical+report+series&rft.issn=08888051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-03 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Women's Situational Coping with Acquaintance Sexual Assault: Applying an Appraisal-Based Model AN - 61532587; 200404399 AB - Drawing on theories of appraisal-based coping, the present study applied structural modeling to examine relationships among personal goal orientations, primary & secondary appraisals of acquaintance sexual assault, & women's emotional & behavioral responses to it. Based on 415 college women's reports of a sexual assault experience, the model shows both direct & indirect effects. Assertive, diplomatic, & immobilized responding were each predicted by a unique profile of appraisals & orientations; personal goal orientations & primary appraisals were completely mediated by secondary appraisals. Ways that these findings can facilitate self-protective coping in an acquaintance sexual assault situation, leading to the development of effective, well-tailored self-defense & resistance programs, are discussed. 3 Tables, 1 Figure, 67 References. [Reprinted by permission of Sage Publications Inc., copyright 2004.] JF - Violence Against Women AU - Nurius, Paula S AU - Norris, Jeanette AU - Macy, Rebecca J AU - Huang, Bu AD - NIMH Predoctoral Prevention Research Training Program, School Social Work, U Washington Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 450 EP - 478 VL - 10 IS - 5 SN - 1077-8012, 1077-8012 KW - Rape KW - College Students KW - Females KW - Coping KW - article KW - 6146: crime & corrections UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61532587?accountid=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=Violence+Against+Women&rft.atitle=Women%27s+Situational+Coping+with+Acquaintance+Sexual+Assault%3A+Applying+an+Appraisal-Based+Model&rft.au=Nurius%2C+Paula+S%3BNorris%2C+Jeanette%3BMacy%2C+Rebecca+J%3BHuang%2C+Bu&rft.aulast=Nurius&rft.aufirst=Paula&rft.date=2004-05-01&rft.volume=10&rft.issue=5&rft.spage=450&rft.isbn=&rft.btitle=&rft.title=Violence+Against+Women&rft.issn=10778012&rft_id=info:doi/10.1177%2F1077801204264367 LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Number of references - 67 N1 - Last updated - 2016-09-28 N1 - CODEN - VAWOFG N1 - SubjectsTermNotLitGenreText - Rape; Females; Coping; College Students DO - http://dx.doi.org/10.1177/1077801204264367 ER - TY - JOUR T1 - Limits to growth: why neuroscience needs large-scale science AN - 250189010; 15114352 JF - Nature Neuroscience AU - Insel, Thomas R AU - Volkow, Nora D AU - Landis, Story C AU - Ting-Kai, Li AU - Battey, James F AU - Sieving, Paul Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 426 EP - 7 CY - New York PB - Nature Publishing Group VL - 7 IS - 5 SN - 10976256 KW - Medical Sciences--Psychiatry And Neurology KW - Weights & Measures KW - Molecular Biology KW - Biomedical Research KW - Humans KW - Database Management Systems KW - Neurosciences -- trends KW - Research Support as Topic -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/250189010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Neuroscience&rft.atitle=Limits+to+growth%3A+why+neuroscience+needs+large-scale+science&rft.au=Insel%2C+Thomas+R%3BVolkow%2C+Nora+D%3BLandis%2C+Story+C%3BTing-Kai%2C+Li%3BBattey%2C+James+F%3BSieving%2C+Paul&rft.aulast=Insel&rft.aufirst=Thomas&rft.date=2004-05-01&rft.volume=7&rft.issue=5&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Nature+Neuroscience&rft.issn=10976256&rft_id=info:doi/10.1038%2Fnn0504-426 LA - English DB - ProQuest Central N1 - Copyright - Copyright Nature Publishing Group May 2004 N1 - Last updated - 2014-04-21 N1 - CODEN - NANEFN DO - http://dx.doi.org/10.1038/nn0504-426 ER - TY - JOUR T1 - Organization of designed nanofibrils assembled from alpha -helical peptides as determined by electron microscopy AN - 21141868; 11338216 AB - Self-assembling peptides present attractive platforms for engineering materials with controlled nanostructures. Recently, an -helical fibril forming peptide (FFP) was designed that self-assembles into nanofibrils at acid pH. Circular dichroism spectroscopy, electron-microscopy and x-ray fibre diffraction data showed that the most likely structure of FFP fibrils is a five-stranded coiled coil rope. In the present study, scanning transmission electron microscopy (STEM) was used to improve our understanding of the FFP fibril structure. The measurements of fibril mass per length suggest that there are ten -helices in transverse sections of the fibrils. Based on the known data, it is proposed that a predominant fibrillar structure of FFP is a dimer of -helical five-stranded protofilaments wrapped around a common axis. It is shown that these structures have an axial dimension of 58 - 16 nm and a width of 4 - 1 nm. A small number of thin fibrils is also observed in the negative stained preparation and STEM images. The thin fibrils may correspond to the single protofilament. JF - Journal of Peptide Science AU - Kajava, Dr Andrey V AU - Potekhin, Sergey A AU - Corradin, Giampietro AU - Leapman, Richard D AD - Center for Molecular Modeling, CIT, National Institutes of Health, Bethesda, MD 20892, USA, kajava@cnrs-mop.fr Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 291 EP - 297 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 10 IS - 5 SN - 1075-2617, 1075-2617 KW - Biotechnology and Bioengineering Abstracts KW - Data processing KW - Ionizing radiation KW - Transmission electron microscopy KW - C.D. KW - Diffraction KW - Spectroscopy KW - pH effects KW - Fibrils KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21141868?accountid=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+Peptide+Science&rft.atitle=Organization+of+designed+nanofibrils+assembled+from+alpha+-helical+peptides+as+determined+by+electron+microscopy&rft.au=Kajava%2C+Dr+Andrey+V%3BPotekhin%2C+Sergey+A%3BCorradin%2C+Giampietro%3BLeapman%2C+Richard+D&rft.aulast=Kajava&rft.aufirst=Dr+Andrey&rft.date=2004-05-01&rft.volume=10&rft.issue=5&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Journal+of+Peptide+Science&rft.issn=10752617&rft_id=info:doi/10.1002%2Fpsc.520 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Fibrils; Data processing; C.D.; Transmission electron microscopy; Ionizing radiation; pH effects; Diffraction; Spectroscopy DO - http://dx.doi.org/10.1002/psc.520 ER - TY - JOUR T1 - Proteomic analysis of detergent-resistant membrane rafts AN - 20397297; 7762010 AB - A combined, detergent- and organic solvent-based proteomic method for the analysis of detergent-resistant membrane rafts (DRMR) is described. These specialized domains of the plasma membrane contain a distinctive and dynamic protein and/or lipid complement, which can be isolated from most mammalian cells. Lipid rafts are predominantly involved in signal transduction and adapted to mediate and produce different cellular responses. To facilitate a better understanding of their biology and role, DRMR were isolated from Vero cells as a Triton X-100 insoluble fraction. After detergent removal, sonication in 60% buffered methanol was used to extract, solubilize and tryptically digest the resulting protein complement. The peptide digestate was analyzed by microcapillary reversed-phase liquid chromatography-tandem mass spectrometry. Gas-phase fractionation in the mass-to-charge range was employed to broaden the selection of precursor ions and increase the number of identifications in an effort to detect less abundant proteins. A total of 380 proteins were identified including all known lipid raft markers. A total of 91 (24%) proteins were classified as integral -helical membrane proteins, of which 51 (56%) were predicted to have multiple transmembrane domains. JF - Electrophoresis AU - Blonder, Josip AU - Hale, Martha L AU - Lucas, David A AU - Schaefer, Carl F AU - Yu, Li-Rong AU - Conrads, Thomas P AU - Issaq, Haleem J AU - Stiles, Bradley G AU - Veenstra, Timothy D AD - Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, National Cancer Institute, veenstra@ncifcrf.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1307 EP - 1318 PB - Wiley-VCH, Postfach 101161 Weinheim 69451 Germany, [mailto:info@wiley-vch.de], [URL:http://www.wiley-vch.de/publish/en/] VL - 25 IS - 9 SN - 0173-0835, 0173-0835 KW - Biotechnology and Bioengineering Abstracts KW - Ions KW - Vero cells KW - Detergents KW - Methanol KW - Membrane proteins KW - Transmembrane domains KW - Mass spectroscopy KW - Sonication KW - Lipid rafts KW - Plasma membranes KW - Mammalian cells KW - proteomics KW - Signal transduction KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20397297?accountid=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=Electrophoresis&rft.atitle=Proteomic+analysis+of+detergent-resistant+membrane+rafts&rft.au=Blonder%2C+Josip%3BHale%2C+Martha+L%3BLucas%2C+David+A%3BSchaefer%2C+Carl+F%3BYu%2C+Li-Rong%3BConrads%2C+Thomas+P%3BIssaq%2C+Haleem+J%3BStiles%2C+Bradley+G%3BVeenstra%2C+Timothy+D&rft.aulast=Blonder&rft.aufirst=Josip&rft.date=2004-05-01&rft.volume=25&rft.issue=9&rft.spage=1307&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/10.1002%2Felps.200405891 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lipid rafts; proteomics; Mass spectroscopy; Vero cells; Transmembrane domains; Signal transduction; Sonication; Membrane proteins; Mammalian cells; Methanol; Ions; Detergents; Plasma membranes DO - http://dx.doi.org/10.1002/elps.200405891 ER - TY - JOUR T1 - An investigation into the human serum interactome AN - 20393657; 7762008 AB - The protein content of human serum is composed of a millieu of proteins from almost every type of cell and tissue within the body. The serum proteome has been shown tocontain information that directly reflects pathophysiological states and represents an invaluable source of diagnostic information for a variety of different diseases. Unfortunately, the dynamic range of protein abundance, ranging from mg/mL level to pg/mL level, renders complete characterization of this proteome nearly impossible with current analytical methods. To study low-abundance proteins, which have potential value for clinical diagnosis, the high-abundant species, such as immunoglobulins andalbumin, are generally eliminated as the first step in many analytical protocols. This step, however, is hypothesized to concomitantly remove proteins/peptides associated with the high-abundant proteins targeted for depletion. In this study, immunoprecipitation was combined with microcapillary reversed-phase liquid chromatography (RPLC) coupled on-line with tandem mass spectrometry (MS/MS) to investigate the low-molecular-weight proteins/peptides that associate with the most abundant species in serum. By this targeted isolation of select highly abundant serum proteins, the associated proteins/peptides can be enriched and effectively identified by RPLC-MS/MS. Among the 210 proteins identified, 73% and 67% were not found in previous studies of the low-molecular-weight or whole-serum proteome, respectively. JF - Electrophoresis AU - Zhou, Ming AU - Lucas, David A AU - Chan, King C AU - Issaq, Haleem J AU - Petricoin III, Emanuel F AU - Liotta, Lance A AU - Veenstra, Timothy D AU - Conrads, Thomas P AD - Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD, USA, Conrads@ncifcrf.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1289 EP - 1298 PB - Wiley-VCH, Postfach 101161 Weinheim 69451 Germany, [mailto:info@wiley-vch.de], [URL:http://www.wiley-vch.de/publish/en/] VL - 25 IS - 9 SN - 0173-0835, 0173-0835 KW - Biotechnology and Bioengineering Abstracts KW - Liquid chromatography KW - Immunoprecipitation KW - Mass spectroscopy KW - Immunoglobulins KW - Serum proteins KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20393657?accountid=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=Electrophoresis&rft.atitle=An+investigation+into+the+human+serum+interactome&rft.au=Zhou%2C+Ming%3BLucas%2C+David+A%3BChan%2C+King+C%3BIssaq%2C+Haleem+J%3BPetricoin+III%2C+Emanuel+F%3BLiotta%2C+Lance+A%3BVeenstra%2C+Timothy+D%3BConrads%2C+Thomas+P&rft.aulast=Zhou&rft.aufirst=Ming&rft.date=2004-05-01&rft.volume=25&rft.issue=9&rft.spage=1289&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/10.1002%2Felps.200405866 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Serum proteins; Immunoprecipitation; Mass spectroscopy; Immunoglobulins; Liquid chromatography DO - http://dx.doi.org/10.1002/elps.200405866 ER - TY - JOUR T1 - Differences between human and mouse embryonic stem cells AN - 19764176; 5891835 AB - We compared gene expression profiles of mouse and human ES cells by immunocytochemistry, RT-PCR, and membrane-based focused cDNA array analysis. Several markers that in concert could distinguish undifferentiated ES cells from their differentiated progeny were identified. These included known markers such as SSEA antigens, OCT3/4, SOX-2, REX-1 and TERT, as well as additional markers such as UTF-1, TRF1, TRF2, connexin43, and connexin45, FGFR-4, ABCG-2, and Glut- 1. A set of negative markers that confirm the absence of differentiation was also developed. These include genes characteristic of trophoectoderm, markers of germ layers, and of more specialized progenitor cells. While the expression of many of the markers was similar in mouse and human cells, significant differences were found in the expression of vimentin, beta -III tubulin, alpha- fetoprotein, eomesodermin, HEB, ARNT, and FoxD3 as well as in the expression of the LIF receptor complex LIFR/IL6ST (gp130). Profound differences in cell cycle regulation, control of apoptosis, and cytokine expression were uncovered using focused microarrays. The profile of gene expression observed in H1 cells was similar to that of two other human ES cell lines tested (line I-6 and clonal line-H9.2) and to feeder-free subclones of H1, H7, and H9, indicating that the observed differences between human and mouse ES cells were species-specific rather than arising from differences in culture conditions. JF - Developmental Biology AU - Ginis, I AU - Luo, Y AU - Miura, T AU - Thies, S AU - Brandenberger, R AU - Gerecht-Nir, S AU - Amit, M AU - Hoke, A AU - Carpenter, M K AU - Itskovitz-Eldor, J AU - Rao AD - Stem Cell Section, Laboratory of Neurosciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA, raomah@grc.nia.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 360 EP - 380 PB - Academic Press, Inc., 525 B St. Ste. 1900 San Diego CA 92101-4495 USA, [mailto:apsubs@acad.com] VL - 269 IS - 2 SN - 0012-1606, 0012-1606 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Embryonic stem cells KW - Human KW - Mouse KW - Markers KW - RT-PCR KW - cDNA microarray KW - Leukemia inhibitory factor KW - Apoptosis KW - Cell cycle KW - Cytokines KW - Interleukin 6 KW - Immunocytochemistry KW - TRF2 protein KW - Connexins KW - Cell culture KW - DNA microarrays KW - Vimentin KW - Connexin 43 KW - Gene expression KW - Differentiation KW - Glycoprotein gp130 KW - Stem cells KW - Embryo cells KW - Polymerase chain reaction KW - Telomere-binding protein KW - Progeny KW - Tubulin KW - Oct-4 protein KW - G 07730:Development & Cell Cycle KW - W 30945:Fermentation & Cell Culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19764176?accountid=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=Developmental+Biology&rft.atitle=Differences+between+human+and+mouse+embryonic+stem+cells&rft.au=Ginis%2C+I%3BLuo%2C+Y%3BMiura%2C+T%3BThies%2C+S%3BBrandenberger%2C+R%3BGerecht-Nir%2C+S%3BAmit%2C+M%3BHoke%2C+A%3BCarpenter%2C+M+K%3BItskovitz-Eldor%2C+J%3BRao&rft.aulast=Ginis&rft.aufirst=I&rft.date=2004-05-01&rft.volume=269&rft.issue=2&rft.spage=360&rft.isbn=&rft.btitle=&rft.title=Developmental+Biology&rft.issn=00121606&rft_id=info:doi/10.1016%2Fj.ydbio.2003.12.034 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Interleukin 6; Immunocytochemistry; Apoptosis; TRF2 protein; Connexins; Cell cycle; Cell culture; DNA microarrays; Vimentin; Connexin 43; Gene expression; Differentiation; Stem cells; Glycoprotein gp130; Embryo cells; Polymerase chain reaction; Progeny; Telomere-binding protein; Oct-4 protein; Tubulin DO - http://dx.doi.org/10.1016/j.ydbio.2003.12.034 ER - TY - JOUR T1 - Detecting the vanishing populations of the highly endangered Darwin's fox, Pseudalopex fulvipes AN - 18065868; 6020515 AB - Darwin's fox (Pseudalopex fulvipes) is known to survive only on Chiloe Island off the coast of southern Chile and in Nahuelbuta National Park, 600 km to the north in mainland Chile. The Valdivian coastal forest, in which the Darwin's fox lives, historically spanned from Nahuelbuta National Park southward past Chiloe Island on the mainland. Furthermore, the forest on Chiloe Island was connected to the mainland forest by a land bridge for much of the Pleistocene. Thus, the distribution of Valdivian forest suggests that the historic range of Darwin's fox may have been much larger. We searched the remnant pockets of coastal forest on mainland Chile using live traps, noninvasive techniques and interviews to look for new populations of the critically endangered Darwin's fox. Although no Darwin's fox was captured, evidence of a new population near Punta Chanchan was found. JF - Animal Conservation AU - Vila, C AU - Leonard, JA AU - Iriarte, A AU - O'Brien, S J AU - Johnson, W E AU - Wayne, R K AD - Laboratory of Genomic Diversity, National Cancer Institute-FCRDC, Frederick, MD 21702-1201, USA, johnsonw@ncifcrf.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 147 EP - 153 VL - 7 IS - 2 SN - 1367-9430, 1367-9430 KW - Ecology Abstracts KW - Surveys KW - Forests KW - Endangered species KW - Pseudalopex fulvipes KW - Chile, Chiloe I. KW - D 04705:Conservation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18065868?accountid=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=Animal+Conservation&rft.atitle=Detecting+the+vanishing+populations+of+the+highly+endangered+Darwin%27s+fox%2C+Pseudalopex+fulvipes&rft.au=Vila%2C+C%3BLeonard%2C+JA%3BIriarte%2C+A%3BO%27Brien%2C+S+J%3BJohnson%2C+W+E%3BWayne%2C+R+K&rft.aulast=Vila&rft.aufirst=C&rft.date=2004-05-01&rft.volume=7&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Animal+Conservation&rft.issn=13679430&rft_id=info:doi/10.1017%2FS1367943004001271 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pseudalopex fulvipes; Chile, Chiloe I.; Endangered species; Forests; Surveys DO - http://dx.doi.org/10.1017/S1367943004001271 ER - TY - JOUR T1 - Targeting hypoxia-A2A adenosine receptor-mediated mechanisms of tissue protection AN - 18005615; 5944732 AB - Despite inflammation having beneficial effects, the action of toxic proinflammatory molecules can result in excessive tissue damage that subsequently contributes to the pathogenesis of many major diseases. The development of novel drugs and therapeutic strategies for the treatment of inflammation requires an improved understanding of the molecular mechanisms that terminate inflammation. The physiological hypothesis proposes that excessive levels of inflammatory tissue damage result in local hypoxia and accumulation of extracellular adenosine. The A2A adenosine receptor and hypoxia-inducible factor play important roles in the attenuation of proinflammatory processes in a delayed, negative-feedback manner and thus protect organs from excessive damage. Targeting individual stages of the hypoxia-A2A receptor signaling pathway represents an attractive strategy for the modulation of inflammation. JF - Drug Discovery Today AU - Lukashev, D AU - Ohta, A AU - Sitkovsky, M AD - Biochemistry and Immunopharmacology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA Y1 - 2004/05/01/ PY - 2004 DA - 2004 May 01 SP - 403 EP - 409 PB - Elsevier Ltd VL - 9 IS - 9 SN - 1359-6446, 1359-6446 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Drug discovery KW - Reviews KW - Adenosine A2A receptors KW - Hypoxia-inducible factors KW - Inflammation KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18005615?accountid=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=Drug+Discovery+Today&rft.atitle=Targeting+hypoxia-A2A+adenosine+receptor-mediated+mechanisms+of+tissue+protection&rft.au=Lukashev%2C+D%3BOhta%2C+A%3BSitkovsky%2C+M&rft.aulast=Lukashev&rft.aufirst=D&rft.date=2004-05-01&rft.volume=9&rft.issue=9&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Drug+Discovery+Today&rft.issn=13596446&rft_id=info:doi/10.1016%2FS1359-6446%2804%2903044-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Drug discovery; Inflammation; Adenosine A2A receptors; Reviews; Hypoxia-inducible factors DO - http://dx.doi.org/10.1016/S1359-6446(04)03044-2 ER - TY - JOUR T1 - Inhibition of Ape1 Nuclease Activity by Lead, Iron, and Cadmium AN - 18000526; 5955285 AB - Many environmental metals are co-carcinogens, eliciting their effects via inhibition of DNA repair. Apurinic/apyrimidinic (AP) endonuclease 1 (Ape1) is the major mammalian abasic endonuclease and initiates repair of this cytotoxic/mutagenic lesion by incising the DNA backbone via a Mg super(2+)-dependent reaction. In this study we examined the effects of arsenite [As(III)], cadmium [Cd(II)], cobalt [Co(II)], iron [Fe(II)], nickel [Ni(II)], and lead [Pb(II)] at concentrations ranging from 0.3 to 100 mu M on the incision activity of Ape1 in the presence of 1 mM MgCl sub(2). Pb(II) and Fe(II) inhibited Ape1 activity at each of the concentrations tested, with an IC sub(50) (half-maximal inhibitory concentration) of 0.61 and 1.0 mu M, respectively. Cd(II) also inhibited Ape1 activity but only at concentrations > 10 mu M. No inhibition was seen with As(III), Co(II), or Ni(II). A similar inhibition pattern was observed with the homologous Escherichia coli protein, exonuclease III, but no inhibition was seen with the structurally distinct AP endonuclease E. coli endonuclease IV, indicating a targeted effect of Pb(II), Fe(II), and Cd(II) on the Ape1-like repair enzymes. Excess nonspecific DNA did not abrogate the metal inactivation, suggesting a protein-specific effect. Notably, Cd(II), Fe(II), and Pb(II) [but not As(III), Co(II), or Ni(II)] inhibited AP endonuclease activity in whole-cell extracts but had no significant effect on single nucleotide gap filling, 5'-flap endonuclease, and nick ligation activities, supporting the idea of selective inactivation of Ape1 in cells. Our results are the first to identify a potential DNA repair enzyme target for lead and suggest a means by which these prevalent environmental metals may elicit their deleterious effects. JF - Environmental Health Perspectives AU - McNeill AU - Narayana, A AU - Wong, Heng-Kuan AU - Wilson, DM III AD - Laboratory of Molecular Gerontology, GRC, National Institute on Aging, IRP, NIH, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825, USA, wilsonda@grc.nia.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 799 EP - 804 VL - 112 IS - 7 SN - 0091-6765, 0091-6765 KW - Toxicology Abstracts KW - Heavy metals KW - Ape1 protein KW - Nuclease KW - Cadmium KW - Inhibition KW - Iron KW - Lead KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18000526?accountid=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=Inhibition+of+Ape1+Nuclease+Activity+by+Lead%2C+Iron%2C+and+Cadmium&rft.au=McNeill%3BNarayana%2C+A%3BWong%2C+Heng-Kuan%3BWilson%2C+DM+III&rft.aulast=McNeill&rft.aufirst=&rft.date=2004-05-01&rft.volume=112&rft.issue=7&rft.spage=799&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Ftxg.7038 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Ape1 protein; Heavy metals; Nuclease; Cadmium; Inhibition; Iron; Lead DO - http://dx.doi.org/10.1289/txg.7038 ER - TY - JOUR T1 - Plasmid partitioning and the spreading of P1 partition protein ParB AN - 17968301; 5920354 AB - Bacterial plasmids of low copy number, P1 prophage among them, are actively partitioned to nascent daughter cells. The process is typically mediated by a pair of plasmid-encoded proteins and a cis-acting DNA site or cluster of sites, referred to as the plasmid centromere. P1 ParB protein, which binds to the P1 centromere (parS), can spread for several kilobases along flanking DNA. We argue that studies of mutant ParB that demonstrated a strong correlation between spreading capacity and the ability to engage in partitioning may be misleading, and describe here a critical test of the dependence of partitioning on the spreading of the wild-type protein. Physical constraints imposed on the spreading of P1 ParB were found to have only a minor, but reproducible, effect on partitioning. We conclude that, whereas extensive ParB spreading is not required for partitioning, spreading may have an auxiliary role in the process. JF - Molecular Microbiology AU - Rodionov, O AU - Yarmolinsky, M AD - Laboratory of Biochemistry, National Cancer Institute, NIH, Bldg 37, Room 6044C, 37 Convent Drive, Bethesda, MD 20892-4255, USA., myarmo@helix.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 1215 EP - 1223 PB - Blackwell Science Ltd VL - 52 IS - 4 SN - 0950-382X, 0950-382X KW - partitioning KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - ParB protein KW - Plasmids KW - Centromeres KW - copy number KW - J 02760:Plasmids KW - N 14681:Mutagenesis techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17968301?accountid=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=Plasmid+partitioning+and+the+spreading+of+P1+partition+protein+ParB&rft.au=Rodionov%2C+O%3BYarmolinsky%2C+M&rft.aulast=Rodionov&rft.aufirst=O&rft.date=2004-05-01&rft.volume=52&rft.issue=4&rft.spage=1215&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04055.x LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - ParB protein; Plasmids; copy number; Centromeres DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04055.x ER - TY - JOUR T1 - A suf operon requirement for Fe-S cluster assembly during iron starvation in Escherichia coli AN - 17963339; 5920334 AB - The suf and isc operons of Escherichia coli have been implicated in Fe-S cluster assembly. However, it has been unclear why E. coli has two systems for Fe-S cluster biosynthesis. We have examined the regulatory characteristics and mutant phenotypes of both operons to discern if the two operons have redundant functions or if their cellular roles are divergent. Both operons are similarly induced by hydrogen peroxide and the iron chelator 2,2'-dipyridyl, although by different mechanisms. Regulation of the isc operon is mediated by IscR, whereas the suf operon requires OxyR and IHF for the response to oxidative stress and Fur for induction by iron starvation. Simultaneous deletion of iscS and most suf genes is synthetically lethal. However, although the suf and isc operons have overlapping functions, they act as distinct complexes because the SufS desulphurase alone cannot substitute for the IscS enzyme. In addition, suf deletion mutants are more sensitive to iron starvation than isc mutants, and the activity of the Fe-S enzyme gluconate dehydratase is diminished in the suf mutant during iron starvation. These findings are consistent with the model that the isc operon encodes the housekeeping Fe-S cluster assembly system in E. coli, whereas the suf operon is specifically adapted to synthesize Fe-S clusters when iron or sulphur metabolism is disrupted by iron starvation or oxidative stress. JF - Molecular Microbiology AU - Outten, F W AU - Djaman, O AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA., storz@helix.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 861 EP - 872 PB - Blackwell Science Ltd VL - 52 IS - 3 SN - 0950-382X, 0950-382X KW - OxyR protein KW - SufS protein KW - isc gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Sulfur KW - oxyR gene KW - Fur protein KW - sufS gene KW - IHF protein KW - Hydrogen peroxide KW - Oxidative stress KW - Gene regulation KW - Gluconate dehydratase KW - Escherichia coli KW - Iron KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17963339?accountid=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=A+suf+operon+requirement+for+Fe-S+cluster+assembly+during+iron+starvation+in+Escherichia+coli&rft.au=Outten%2C+F+W%3BDjaman%2C+O%3BStorz%2C+G&rft.aulast=Outten&rft.aufirst=F&rft.date=2004-05-01&rft.volume=52&rft.issue=3&rft.spage=861&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04025.x LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - oxyR gene; Sulfur; sufS gene; Fur protein; IHF protein; Oxidative stress; Hydrogen peroxide; Gene regulation; Gluconate dehydratase; Iron; Escherichia coli DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04025.x ER - TY - JOUR T1 - Simultaneous Analysis of Multiple Staphylococcal Enterotoxin Genes by an Oligonucleotide Microarray Assay AN - 17960550; 5896925 AB - Staphylococcal enterotoxins (SEs) are a family of 17 major serological types of heat-stable enterotoxins that are one of the leading causes of gastroenteritis resulting from consumption of contaminated food. SEs are considered potential bioweapons. Many Staphylococcus aureus isolates contain multiple SEs. Because of the large number of SEs, serological typing and PCR typing are laborious and time-consuming. Furthermore, serological typing may not always be practical because of antigenic similarities among enterotoxins. We report on a microarray-based one-tube assay for the simultaneous detection and identification (genetic typing) of multiple enterotoxin (ent) genes. The proposed typing method is based on PCR amplification of the target region of the ent genes with degenerate primers, followed by characterization of the PCR products by microchip hybridization with oligonucleotide probes specific for each ent gene. We verified the performance of this method by using several other techniques, including PCR amplification with gene-specific primers, followed by gel electrophoresis or microarray hybridization, and sequencing of the enterotoxin genes. The assay was evaluated by analysis of previously characterized staphylococcal isolates containing 16 ent genes. The microarray assay revealed that some of these isolates contained additional previously undetected ent genes. The use of degenerate primers allows the simultaneous amplification and identification of as many as nine different ent genes in one S. aureus strain. The results of this study demonstrate the usefulness of the oligonucleotide microarray assay for the analysis of multitoxigenic strains, which are common among S. aureus strains, and for the analysis of microbial pathogens in general. JF - Journal of Clinical Microbiology AU - Sergeev, N AU - Volokhov, D AU - Chizhikov, V AU - Rasooly, A AD - NIH/NCI, 6130 Executive Blvd. EPN, Room 6035A, Rockville, MD 20852, rasoolya@mail.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 2134 EP - 2143 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 42 IS - 5 SN - 0095-1137, 0095-1137 KW - ent gene KW - Microbiology Abstracts B: Bacteriology KW - Polymerase chain reaction KW - Enterotoxins KW - Primers KW - Staphylococcus aureus KW - Gastroenteritis KW - Oligonucleotides KW - DNA microarrays KW - Food-borne diseases KW - Hybridization analysis KW - Gel electrophoresis KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17960550?accountid=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+Clinical+Microbiology&rft.atitle=Simultaneous+Analysis+of+Multiple+Staphylococcal+Enterotoxin+Genes+by+an+Oligonucleotide+Microarray+Assay&rft.au=Sergeev%2C+N%3BVolokhov%2C+D%3BChizhikov%2C+V%3BRasooly%2C+A&rft.aulast=Sergeev&rft.aufirst=N&rft.date=2004-05-01&rft.volume=42&rft.issue=5&rft.spage=2134&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.42.5.2134-2143.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Polymerase chain reaction; Primers; Enterotoxins; Gastroenteritis; DNA microarrays; Oligonucleotides; Gel electrophoresis; Hybridization analysis; Food-borne diseases; Staphylococcus aureus DO - http://dx.doi.org/10.1128/JCM.42.5.2134-2143.2004 ER - TY - JOUR T1 - Genomics in environmental health research--opportunities and challenges AN - 17957716; 5903755 AB - Environmental health research impacts both environmental health regulatory policy and the practice of medicine. However, this area of medical research has not garnered public support and attention of medical researchers because of its emphasis on prevention and public health. Also, the pervasiveness of a scientific culture wedded to old problems and outdated technologies and models systems has not been helpful in generating enthusiasm for the field. While the emphasis on prevention is both laudable and appropriate, the adoption of cutting-edge technologies to exploit the new scientific opportunities, made possible by the nation's investment in genomics, is essential if the discipline expects to be competitive with other highly deserving programs. The new 'omics' era of environmental health research, ushered in over the past decade, characterized by the linkage of genomics, proteomics and metabolomics to conventional toxicology and pathology databases, holds great promise for elucidating mechanisms of gene-environment interaction in human health and disease. These combined approaches will allow one to monitor multiple molecular events, pathways and interactive networks simultaneously--a requirement for elucidating toxic mechanisms. But, before embracing the 'omics' technologies as the 'be all-end all; ' they need to be validated for their predictive capacities in large-scale multi-institutional studies, such as those described in this article. JF - Toxicology AU - Olden, K AD - Department of Health and Human Services, National Institute of Environmental Health Sciences and The National Toxicology Program, National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709, USA, olden@niehs.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 19 EP - 24 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 198 IS - 1-3 SN - 0300-483X, 0300-483X KW - environmental health KW - research KW - Toxicology Abstracts KW - Databases KW - Regulation KW - proteomics KW - genomics KW - Public health KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17957716?accountid=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&rft.atitle=Genomics+in+environmental+health+research--opportunities+and+challenges&rft.au=Olden%2C+K&rft.aulast=Olden&rft.aufirst=K&rft.date=2004-05-01&rft.volume=198&rft.issue=1-3&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2004.01.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - genomics; Databases; proteomics; Regulation; Public health DO - http://dx.doi.org/10.1016/j.tox.2004.01.015 ER - TY - JOUR T1 - The U.S. National Library of Medicine's Toxicology and Environmental Health Information Program AN - 17947968; 5903778 AB - For nearly 40 years, the National Library of Medicine's (NLM) Toxicology and Environmental Health Information Program (TEHIP) has been a significant leader in organizing and providing public access to an extensive storehouse of toxicological information through its online databases. With the advent of the Internet, TEHIP has expanded its role to also serve as a pre-eminent portal to toxicological information worldwide. Its primary databases reside within the web-based TOXNET system, and include the scientifically peer-reviewed Hazardous Substances Data Bank (HSDB), the U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) and Toxics Release Inventory, the National Cancer Institute's Chemical Carcinogenesis Research Information System (CCRIS) and the TOXLINE file of over 3 million bibliographic references. TEHIP's ChemIDplus is an extensive chemical dictionary that extends beyond simple nomenclature to offer displays of molecular structures and links from particular chemicals to other databases containing more information. Specialty files in occupational safety and health, and household products have recently been added to TEHIP's suite of resources. Additional databases in risk assessment, drugs, toxicology education, and global resources, are under development. 'Special Topics' pages lead users to structured summaries and links in areas such as arsenic, chemical warfare agents, biological warfare, and West Nile Virus. A database on alternatives to the use of live animals, a three-module toxicology tutor, and a glossary of terms in toxicology are among TEHIP's other information aids, as well an increasing commitment to serving consumers, as witnessed by the animated ToxTown program. Outside the sphere of TEHIP, NLM offers additional databases, such as PubMed, of significant value to toxicology researchers. JF - Toxicology AU - Wexler, P AD - National Library of Medicine, 2 Democracy Plaza, Suite 510, Bethesda, MD 20892-5467, USA, wexlerp@mail.nlm.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 161 EP - 168 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 198 IS - 1-3 SN - 0300-483X, 0300-483X KW - Toxicology Abstracts KW - Information KW - Databases KW - Computerized access KW - World Wide Web KW - TOXNET KW - National Library of Medicine KW - USA KW - Reviews KW - Information systems KW - X 24230:Legislation & recommended standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17947968?accountid=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&rft.atitle=The+U.S.+National+Library+of+Medicine%27s+Toxicology+and+Environmental+Health+Information+Program&rft.au=Wexler%2C+P&rft.aulast=Wexler&rft.aufirst=P&rft.date=2004-05-01&rft.volume=198&rft.issue=1-3&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2004.01.037 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Databases; Reviews; Information systems; USA DO - http://dx.doi.org/10.1016/j.tox.2004.01.037 ER - TY - JOUR T1 - Mechanisms underlying arsenic carcinogenesis: hypersensitivity of mice exposed to inorganic arsenic during gestation AN - 17945531; 5903760 AB - Inorganic arsenic is an important human carcinogen of unknown etiology. Defining carcinogenic mechanisms is critical to assessing the human health hazard of arsenic exposure but requires appropriate model systems. It has proven difficult to induced tumors in animals with inorganic arsenic alone. Several groups have studied the carcinogenic potential of inorganic arsenic in rodents, finding it to act as co-promoter or co-carcinogen, but not as a complete carcinogen. As gestation is a time of high sensitivity to chemical carcinogenesis, we performed two in utero exposure studies with inorganic arsenic. In the first study, pregnant mice received drinking water containing sodium arsenite at 0 (control), 42.5 and 85 ppm arsenic from gestation day 8 to 18, and the offspring were observed for up to 90 weeks. As adults, male offspring developed hepatocellular carcinoma (HCC) and adrenal tumors after in utero arsenite exposure. Although liver tumors were not induced by arsenic in female offspring, they did develop lung carcinoma, ovarian tumors, and uterine and oviduct preneoplasia. In a second study, the same doses of arsenic were used and the skin tumor promoting phorbol ester, TPA, was applied to the skin after birth in an effort to promote skin tumors potentially initiated by arsenic in utero. TPA did not promote dermal tumors after in utero arsenite exposure. Otherwise, results from the second chronic study largely duplicated the first and, irrespective of additional TPA exposure, arsenic exposure in utero induced HCC and adrenal tumors in males and ovarian tumors in females. In addition, combined arsenic and TPA induced a significant increase in hepatocellular tumors in female offspring, although arsenic alone was not effective. Thus, in utero inorganic arsenic exposure can act as a complete carcinogen in mice, with brief exposures consistently inducing tumors at several sites. In addition, it appears gestational arsenic can act as a tumor initiator in the female mouse liver, inducing liver lesions that can be promoted by TPA. JF - Toxicology AU - Waalkes, M P AU - Liu, J AU - Ward, J M AU - Diwan, BA AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233, MD F0-09, Research Triangle Park, NC 27709, USA, waalkes@niehs.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 31 EP - 38 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 198 IS - 1-3 SN - 0300-483X, 0300-483X KW - mice KW - Toxicology Abstracts KW - Arsenic KW - Prenatal experience KW - Carcinogenesis KW - Offspring KW - Pregnancy KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17945531?accountid=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&rft.atitle=Mechanisms+underlying+arsenic+carcinogenesis%3A+hypersensitivity+of+mice+exposed+to+inorganic+arsenic+during+gestation&rft.au=Waalkes%2C+M+P%3BLiu%2C+J%3BWard%2C+J+M%3BDiwan%2C+BA&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2004-05-01&rft.volume=198&rft.issue=1-3&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2004.01.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arsenic; Offspring; Prenatal experience; Pregnancy; Carcinogenesis DO - http://dx.doi.org/10.1016/j.tox.2004.01.017 ER - TY - JOUR T1 - Impairment of Tetanus-Specific Cellular and Humoral Responses following Tetanus Vaccination in Human Lymphatic Filariasis AN - 17944275; 5887628 AB - To investigate the consequences of the impaired parasite-specific immune response in lymphatic filariasis, the effect of concurrent Wuchereria bancrofti infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied in 20 asymptomatic microfilaremic (MF) patients, 20 patients with chronic lymphatic obstruction/elephantiasis (chronic pathology (CP)), and 10 endemic normal (EN) control individuals at baseline and at 3 and 6 months after TT vaccination. Peripheral blood mononuclear cell (PBMC) proliferative responses to TT before vaccination were not significantly different between the EN control and CP groups, but the MF group showed significantly lower baseline proliferative responses to TT compared with either the EN or CP group. Six months following vaccination, the change in proliferative response to TT was significantly greater in the EN and CP groups than in the MF group. This difference in proliferative response was reiterated in the gamma interferon (IFN- gamma ) response in the EN group, in that they increased IFN- gamma production by 400% at 6 months, in contrast to that seen in the filaria-infected groups. In contrast to the IFN- gamma responses, PBMCs from the MF group produced significantly increased levels of TT-specific IL-10 compared with PBMCs from the EN group. Although there was significantly greater TT-specific immunoglobulin G (IgG) production at baseline between the EN and MF groups, postvaccination IgG (and IgG1 isotype) responses did not differ among the groups, whereas TT-specific IgG2, IgG3, and IgG4 were all increased in the EN group compared with the filaria-infected groups. These studies indicate that concurrent infection with W. bancrofti can diminish the immune response to an unrelated antigen by a mechanism that is likely to involve IL-10. JF - Infection and Immunity AU - Nookala, S AU - Srinivasan, S AU - Kaliraj, P AU - Narayanan, R B AU - Nutman, T B AD - Laboratory of Parasitic Diseases, 4 Center Dr., Room 4/B1-03, National Institutes of Health, Bethesda, MD 20892-0425, tnutman@niaid.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 2598 EP - 2604 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 5 SN - 0019-9567, 0019-9567 KW - man KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Filariasis KW - Antibody response KW - Vaccination KW - Interleukin 10 KW - Immune response (cell-mediated) KW - Wuchereria bancrofti KW - Immunoglobulin G KW - tetanus toxin KW - Immune response (humoral) KW - F 06807:Active immunization KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17944275?accountid=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=Impairment+of+Tetanus-Specific+Cellular+and+Humoral+Responses+following+Tetanus+Vaccination+in+Human+Lymphatic+Filariasis&rft.au=Nookala%2C+S%3BSrinivasan%2C+S%3BKaliraj%2C+P%3BNarayanan%2C+R+B%3BNutman%2C+T+B&rft.aulast=Nookala&rft.aufirst=S&rft.date=2004-05-01&rft.volume=72&rft.issue=5&rft.spage=2598&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.72.5.2598-2604.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Wuchereria bancrofti; tetanus toxin; Immunoglobulin G; Antibody response; Vaccination; Filariasis; Immune response (cell-mediated); Immune response (humoral); Interleukin 10 DO - http://dx.doi.org/10.1128/IAI.72.5.2598-2604.2004 ER - TY - JOUR T1 - The theta Subunit of Escherichia coli DNA Polymerase III: a Role in Stabilizing the epsilon Proofreading Subunit AN - 17941323; 5880984 AB - The function of the theta subunit of Escherichia coli DNA polymerase III holoenzyme is not well established. theta is a tightly bound component of the DNA polymerase III core, which contains the alpha subunit (polymerase), the epsilon subunit (3'-> 5' exonuclease), and the theta subunit, in the linear order alpha - epsilon - theta . Previous studies have shown that the theta subunit is not essential, as strains carrying a deletion of the holE gene (which encodes theta ) proved fully viable. No significant phenotypic effects of the holE deletion could be detected, as the strain displayed normal cell health, morphology, and mutation rates. On the other hand, in vitro experiments have indicated the efficiency of the 3'-exonuclease activity of epsilon to be modestly enhanced by the presence of theta . Here, we report a series of genetic experiments that suggest that theta has a stabilizing role for the epsilon proofreading subunit. The observations include (i) defined [Delta] holE mutator effects in mismatch-repair- defective mutL backgrounds, (ii) strong [Delta] holE mutator effects in certain proofreading-impaired dnaQ strains, and (iii) yeast two- and three- hybrid experiments demonstrating enhancement of alpha - epsilon interactions by the presence of theta . theta appears conserved among gram- negative organisms which have an exonuclease subunit that exists as a separate protein (i.e., not part of the polymerase polypeptide), and the presence of theta might be uniquely beneficial in those instances where the proofreading 3'-exonuclease is not part of the polymerase polypeptide. JF - Journal of Bacteriology AU - Taft-Benz, SA AU - Schaaper, R M AD - NIEHS, Laboratory of Molecular Genetics, MD E3-01, P.O. Box 12233, 111 T. W. Alexander Dr., Research Triangle Park, NC 27709, schaaper@niehs.nih.gov Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 2774 EP - 2780 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 9 SN - 0021-9193, 0021-9193 KW - e subunit KW - epsilon subunit KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - mismatch repair KW - Structure-function relationships KW - DNA-directed DNA polymerase KW - Escherichia coli KW - Subunits KW - Proofreading KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17941323?accountid=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=The+theta+Subunit+of+Escherichia+coli+DNA+Polymerase+III%3A+a+Role+in+Stabilizing+the+epsilon+Proofreading+Subunit&rft.au=Taft-Benz%2C+SA%3BSchaaper%2C+R+M&rft.aulast=Taft-Benz&rft.aufirst=SA&rft.date=2004-05-01&rft.volume=186&rft.issue=9&rft.spage=2774&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.186.9.2774-2780.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; mismatch repair; Proofreading; DNA-directed DNA polymerase; Subunits; Structure-function relationships DO - http://dx.doi.org/10.1128/JB.186.9.2774-2780.2004 ER - TY - JOUR T1 - Identification of Chimpanzee Fab Fragments by Repertoire Cloning and Production of a Full-Length Humanized Immunoglobulin G1 Antibody That Is Highly Efficient for Neutralization of Dengue Type 4 Virus AN - 17937001; 5874274 AB - A safe and effective dengue vaccine is still not available. Passive immunization with monoclonal antibodies from humans or nonhuman primates represents an attractive alternative for the prevention of dengue virus infection. Fab monoclonal antibodies to dengue type 4 virus (DENV-4) were recovered by repertoire cloning of bone marrow mRNAs from an immune chimpanzee and analyzed for antigen binding specificity, V sub(H) and V sub(L) sequences, and neutralizing activity against DENV-4 in vitro. Fabs 5A7, 3C1, 3E4, and 7G4 were isolated from a library constructed from a chimpanzee following intrahepatic transfection with infectious DENV-4 RNA. Fabs 5H2 and 5D9, which had nearly identical V sub(H) sequences but varied in their V sub(L) sequences, were recovered from a library constructed from the same chimpanzee after superinfection with a mixture of DENV-1, DENV-2, and DENV-3. In radioimmunoprecipitation, Fab 5A7 precipitated only DENV-4 prM, and Fabs 3E4, 7G4, 5D9, and 5H2 precipitated DENV- 4 E but little or no prM. Fab 3E4 and Fab 7G4 competed with each other for binding to DENV-4 in an enzyme-linked immunosorbent assay, as did Fab 3C1 and Fab 5A7. Fab 5H2 recognized an epitope on DENV-4 that was separate from the epitope(s) recognized by other Fabs. Both Fab 5H2 and Fab 5D9 neutralized DENV-4 efficiently with a titer of 0.24 to 0.58 mu g/ml by plaque reduction neutralization test (PRNT), whereas DENV-4-neutralizing activity of other Fabs was low or not detected. Fab 5H2 was converted to full-length immunoglobulin G1 (IgG1) by combining it with human sequences. The humanized chimpanzee antibody IgG1 5H2 produced in CHO cells neutralized DENV-4 strains from different geographical origins at a similar 50% plaque reduction (PRNT sub(50)) titer of 0.03 to 0.05 mu g/ml. The DENV-4 binding affinities were 0.42 nM for Fab 5H2 and 0.24 nM for full-length IgG1 5H2. Monoclonal antibody IgG1 5H2 may prove valuable for passive immunoprophylaxis against dengue virus in humans. JF - Journal of Virology AU - Men, R AU - Yamashiro, T AU - Goncalvez AU - Wernly, C AU - Schofield, D J AU - Emerson, SU AU - Purcell, R H AU - Lai, C-J AD - Molecular Viral Biology Section, Laboratory of Infectious Diseases, NIAID, NIH, 50 South Dr., MSC 8009, Bethesda, MD 20892-8009 Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 4665 EP - 4674 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 78 IS - 9 SN - 0022-538X, 0022-538X KW - Primates KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Monoclonal antibodies KW - Immunoprecipitation KW - Dengue KW - Vaccines KW - Dengue virus type 4 KW - W3 33375:Antibodies KW - F 06807:Active immunization KW - V 22098:Immunization: Vaccines & vaccination: Animal KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17937001?accountid=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=Identification+of+Chimpanzee+Fab+Fragments+by+Repertoire+Cloning+and+Production+of+a+Full-Length+Humanized+Immunoglobulin+G1+Antibody+That+Is+Highly+Efficient+for+Neutralization+of+Dengue+Type+4+Virus&rft.au=Men%2C+R%3BYamashiro%2C+T%3BGoncalvez%3BWernly%2C+C%3BSchofield%2C+D+J%3BEmerson%2C+SU%3BPurcell%2C+R+H%3BLai%2C+C-J&rft.aulast=Men&rft.aufirst=R&rft.date=2004-05-01&rft.volume=78&rft.issue=9&rft.spage=4665&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.78.9.4665-4674.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dengue virus type 4; Vaccines; Monoclonal antibodies; Immunoprecipitation; Dengue DO - http://dx.doi.org/10.1128/JVI.78.9.4665-4674.2004 ER - TY - JOUR T1 - John Henryism and Self-Reported Physical Health Among High-Socioeconomic Status African American Men AN - 17709939; 5967986 AB - We performed a cross-sectional survey of high-socioeconomic status (SES) African American men and their health to examine the relationship between John Henryism (the strong behavioral predisposition to directly confront barriers to upward social mobility) and selfreported physical health status. We found a positive association between John Henryism and better physical health among high-SES African American men. The study of social and behavioral implications of health of men of differing SES is required to develop strategies to improve the health of African American men. JF - American Journal of Public Health AU - Bonham, V L AU - Sellers, S L AU - Neighbors, H W AD - National Human Genome Research Institute, National Institutes of Health, 31 Center Drive Bldg. 31, Room 4B09, Bethesda, MD 20892, USA, bonhamv@mail.nih.gov Y1 - 2004/05/01/ PY - 2004 DA - 2004 May 01 SP - 737 EP - 738 VL - 94 IS - 5 SN - 0090-0036, 0090-0036 KW - Physical Education Index KW - Socioeconomic factors KW - Self evaluation KW - Health (status) KW - Men KW - Ethnic groups KW - Public health KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17709939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Public+Health&rft.atitle=John+Henryism+and+Self-Reported+Physical+Health+Among+High-Socioeconomic+Status+African+American+Men&rft.au=Bonham%2C+V+L%3BSellers%2C+S+L%3BNeighbors%2C+H+W&rft.aulast=Bonham&rft.aufirst=V&rft.date=2004-05-01&rft.volume=94&rft.issue=5&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Public+Health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Men; Ethnic groups; Self evaluation; Socioeconomic factors; Health (status); Public health ER - TY - JOUR T1 - Basal and exercise-induced sympathetic nervous activity and lipolysis in adipose tissue of patients with anorexia nervosa AN - 17578089; 5946566 AB - The sympathetic nervous system plays an important role in the regulation of adipose tissue (AT) lipolysis, which is a key step in the metabolic processes leading to the decrease of fat mass. The present study was designed to determine in vivo basal and exercise-stimulated lipolysis and concentrations of catecholamines, the major hormones controlling lipolysis, in subcutaneous abdominal AT in patients with anorexia nervosa (AN), characterized by self-induced starvation and excessive exercises resulting in severe malnutrition and fat store loss. The results of local catecholamines and glycerol levels were compared with those in plasma in both experimental groups. An in vivo microdialysis technique was used for the assessment of norepinephrine, dihydroxyphenylalanine, dihydroxyphenylacetic acid and glycerol concentrations in subcutaneous AT of 10 women with AN (body mass index: 15.57 plus or minus 0.55 kg m super(-2)) and 10 age-matched controls (body mass index: 21.56 plus or minus 0.41 kg m super(-2)). Both the AN patients and the control subjects underwent a 1.5 W kg super(-1) exercise test. Basal AT norepinephrine concentrations were increased in the AN patients in comparison with the controls. Basal AT glycerol concentrations were similar in both groups. During exercise, a local increase in the AT norepinephrine and glycerol concentrations was observed in the AN patients only. In contrast to the controls, the basal AT dihydroxyphenylalanine and dihydroxyphenylacetic acid levels in the AN patients were high and remained unchanged during exercise. Basal and exercise-stimulated plasma norepinephrine, dihydroxyphenylalanine, dihydroxyphenylacetic acid and glycerol levels were not different in the AN patients and healthy controls. Our study provides evidence of elevated baseline and exercise-induced sympathetic nervous activity and exercise-induced lipolysis in abdominal AT of AN patients. JF - European Journal of Clinical Investigation AU - Bartak, V AU - Vybiral, S AU - Papezova, H AU - Dostalova, I AU - Pacak, K AU - Nedvidkova, J AD - Institute of Endocrinology, and Charles University, Prague, Czech Republic, Pediatric and Reproductive Endocrinology Branch, NICHD, NIH, Bethesda, MD, jara.nedvidkova@tiscali.cz Y1 - 2004/05// PY - 2004 DA - May 2004 SP - 371 EP - 377 PB - Blackwell Science Ltd VL - 34 IS - 5 SN - 0014-2972, 0014-2972 KW - Physical Education Index KW - Lipids KW - Body mass KW - Nutrition (effects) KW - Women KW - Techniques KW - Patients KW - Exercise KW - Hormones KW - Evaluation KW - Nervous system KW - Fats KW - Metabolism KW - Anorexia nervosa KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17578089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Clinical+Investigation&rft.atitle=Basal+and+exercise-induced+sympathetic+nervous+activity+and+lipolysis+in+adipose+tissue+of+patients+with+anorexia+nervosa&rft.au=Bartak%2C+V%3BVybiral%2C+S%3BPapezova%2C+H%3BDostalova%2C+I%3BPacak%2C+K%3BNedvidkova%2C+J&rft.aulast=Bartak&rft.aufirst=V&rft.date=2004-05-01&rft.volume=34&rft.issue=5&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Clinical+Investigation&rft.issn=00142972&rft_id=info:doi/10.1111%2Fj.1365-2362.2004.01344.x LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Patients; Metabolism; Exercise; Hormones; Fats; Anorexia nervosa; Body mass; Nervous system; Women; Evaluation; Techniques; Lipids; Nutrition (effects) DO - http://dx.doi.org/10.1111/j.1365-2362.2004.01344.x ER - TY - JOUR T1 - Medicine. Modulation of radiation injury. AN - 71880776; 15118152 JF - Science (New York, N.Y.) AU - Coleman, C Norman AU - Stone, Helen B AU - Moulder, John E AU - Pellmar, Terry C AD - Radiation Research Program, Division of Cancer Treatment & Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004/04/30/ PY - 2004 DA - 2004 Apr 30 SP - 693 EP - 694 VL - 304 IS - 5671 KW - Cytokines KW - 0 KW - Free Radical Scavengers KW - Isoflavones KW - Radiation-Protective Agents KW - Index Medicus KW - Animals KW - Free Radical Scavengers -- therapeutic use KW - Cytokines -- therapeutic use KW - Humans KW - Whole-Body Irradiation -- adverse effects KW - Disease Models, Animal KW - Radiation Injuries, Experimental -- drug therapy KW - Isoflavones -- therapeutic use KW - Radiotherapy -- adverse effects KW - Radiation Injuries -- drug therapy KW - Radiation-Protective Agents -- therapeutic use KW - Radiation-Protective Agents -- administration & dosage KW - Radiation Injuries -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71880776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Medicine.+Modulation+of+radiation+injury.&rft.au=Coleman%2C+C+Norman%3BStone%2C+Helen+B%3BMoulder%2C+John+E%3BPellmar%2C+Terry+C&rft.aulast=Coleman&rft.aufirst=C&rft.date=2004-04-30&rft.volume=304&rft.issue=5671&rft.spage=693&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=1095-9203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-20 N1 - Date created - 2004-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyoma enhancer activator 3, an ets transcription factor, mediates the induction of cyclooxygenase-2 by nitric oxide in colorectal cancer cells. AN - 71868690; 14976201 AB - Abundant evidence supports the role of cyclooxygenase-2 (COX-2) in colorectal cancer. Nitric oxide (NO), a pro-inflammatory signaling factor, may regulate COX-2 expression and activity thereby linking hyper-inflammatory states to cancer susceptibility. Previously we showed that NO induced COX-2 expression. Although NO also activated the beta-catenin.T-cell factor/lymphocyte enhancing factor transcriptional pathway, a direct causal link between this pathway and COX-2 expression was not demonstrated. In this current study, we focused on NO-induced transcriptional activity and elucidated its role in COX-2 expression. NO donors stimulated the expression of peroxisome proliferator-activated receptor-delta and c-myc, both downstream genes of beta-catenin. They also induced the expression of polyoma enhancer activator 3 (PEA3) and increased its DNA-binding activity. To establish a role for PEA3 to beta-catenin-induced COX-2, we transfected RKO cells with beta-catenin and found that beta-catenin increased PEA3 expression. Also, there was higher PEA3 in immortal mouse colon epithelium cells (Apc(Min/)(+)) compared with young adult mouse colon cells (Apc(+/+)). Luciferase reporter assays revealed that, although several transcription factors/coactivator, acting alone or in synergistic combination, induced COX-2 promoter activity, PEA3 was one of the most potent. Interestingly, NO from NO donors or generated endogenously from transfected inducible nitric-oxide synthase, increased PEA3/p300-induced COX-2 promoter activity. We also found that an ETS site (-75/-72) and the NF-IL6 site were responsible for COX-2 activity induced by PEA3, PEA3/p300, and NO. Taken together, our results demonstrated that NO through beta-catenin signaling stimulated PEA3 to increase COX-2 activity. In addition, NO augmented the synergistic interaction between PEA3 and CBP/p300. JF - The Journal of biological chemistry AU - Liu, Yongmin AU - Borchert, Gregory L AU - Phang, James M AD - Metabolism & Cancer Susceptibility Section, Laboratory of Comparative Carcinogenesis, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2004/04/30/ PY - 2004 DA - 2004 Apr 30 SP - 18694 EP - 18700 VL - 279 IS - 18 SN - 0021-9258, 0021-9258 KW - CTNNB1 protein, human KW - 0 KW - CTNNB1 protein, mouse KW - Cytoskeletal Proteins KW - Isoenzymes KW - Membrane Proteins KW - Nitric Oxide Donors KW - Nuclear Proteins KW - Trans-Activators KW - Transcription Factors KW - beta Catenin KW - transcription factor PEA3 KW - Nitric Oxide KW - 31C4KY9ESH KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - CREB-Binding Protein KW - EC 2.3.1.48 KW - CREBBP protein, human KW - Crebbp protein, mouse KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Humans KW - Cell Line, Tumor KW - Mice KW - Protein Binding KW - Nitric Oxide Donors -- pharmacology KW - Gene Expression Regulation KW - Trans-Activators -- physiology KW - Cytoskeletal Proteins -- metabolism KW - Nuclear Proteins -- metabolism KW - Nuclear Proteins -- physiology KW - Transcription Factors -- physiology KW - Transcription Factors -- metabolism KW - Colorectal Neoplasms -- pathology KW - Isoenzymes -- biosynthesis KW - Nitric Oxide -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Colorectal Neoplasms -- enzymology KW - Isoenzymes -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71868690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polyoma+enhancer+activator+3%2C+an+ets+transcription+factor%2C+mediates+the+induction+of+cyclooxygenase-2+by+nitric+oxide+in+colorectal+cancer+cells.&rft.au=Liu%2C+Yongmin%3BBorchert%2C+Gregory+L%3BPhang%2C+James+M&rft.aulast=Liu&rft.aufirst=Yongmin&rft.date=2004-04-30&rft.volume=279&rft.issue=18&rft.spage=18694&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 - 2004-06-10 N1 - Date created - 2004-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of syntaphilin by cAMP-dependent protein kinase modulates its interaction with syntaxin-1 and annuls its inhibitory effect on vesicle exocytosis. AN - 71866428; 14985338 AB - cAMP-dependent protein kinase (PKA) can modulate synaptic transmission by acting directly on the neurotransmitter secretory machinery. Here, we identify one possible target: syntaphilin, which was identified as a molecular clamp that controls free syntaxin-1 and dynamin-1 availability and thereby regulates synaptic vesicle exocytosis and endocytosis. Deletion mutation and site-directed mutagenesis experiments pinpoint dominant PKA phosphorylation sites to serines 43 and 56. PKA phosphorylation of syntaphilin significantly decreases its binding to syntaxin-1A in vitro. A syntaphilin mutation of serine 43 to aspartic acid (S43D) shows similar effects on binding. To characterize in vivo phosphorylation events, we generated antisera against a peptide of syntaphilin containing a phosphorylated serine 43. Treatment of rat brain synaptosomes or syntaphilin-transfected HEK 293 cells with the cAMP analogue BIMPS induces in vivo phosphorylation of syntaphilin and inhibits its interaction with syntaxin-1 in neurons. To determine whether PKA phosphorylation of syntaphilin is involved in the regulation of Ca(2+)-dependent exocytosis, we investigated the effect of overexpression of syntaphilin and its S43D mutant on the regulated secretion of human growth hormone from PC12 cells. Although expression of wild type syntaphilin in PC12 cells exhibits significant reduction in high K(+)-induced human growth hormone release, the S43D mutant fails to inhibit exocytosis. Our data predict that syntaphilin could be a highly regulated molecule and that PKA phosphorylation could act as an "off" switch for syntaphilin, thus blocking its inhibitory function via the cAMP-dependent signal transduction pathway. JF - The Journal of biological chemistry AU - Boczan, Judit AU - Leenders, A G Miriam AU - Sheng, Zu-Hang AD - Synaptic Function Unit, National Institute of Neurological Dideases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4154, USA. Y1 - 2004/04/30/ PY - 2004 DA - 2004 Apr 30 SP - 18911 EP - 18919 VL - 279 IS - 18 SN - 0021-9258, 0021-9258 KW - Antigens, Surface KW - 0 KW - Carrier Proteins KW - Nerve Tissue Proteins KW - SNPH protein, human KW - STX1A protein, human KW - Stx1a protein, rat KW - Syntaxin 1 KW - Vesicular Transport Proteins KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Rats KW - Animals KW - Phosphorylation KW - Brain KW - Binding Sites -- genetics KW - Protein Binding KW - Synaptosomes -- metabolism KW - Synaptosomes -- chemistry KW - Signal Transduction KW - Amino Acid Substitution KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Carrier Proteins -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - Exocytosis KW - Nerve Tissue Proteins -- metabolism KW - Antigens, Surface -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71866428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+of+syntaphilin+by+cAMP-dependent+protein+kinase+modulates+its+interaction+with+syntaxin-1+and+annuls+its+inhibitory+effect+on+vesicle+exocytosis.&rft.au=Boczan%2C+Judit%3BLeenders%2C+A+G+Miriam%3BSheng%2C+Zu-Hang&rft.aulast=Boczan&rft.aufirst=Judit&rft.date=2004-04-30&rft.volume=279&rft.issue=18&rft.spage=18911&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 - 2004-06-10 N1 - Date created - 2004-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to Combivir. AN - 71839373; 15096804 AB - Although most uninfected infants born to women infected with HIV-1 show no clinical evidence of mitochondrial compromise, mitochondrial dysfunction has been reported in children born to women receiving zidovudine and/or lamivudine during pregnancy. In this pilot study we examined mitochondrial integrity in HIV-1-uninfected infants born to HIV-1-infected women receiving Combivir during pregnancy. : Samples of umbilical cord and cord blood were obtained from HIV-1-uninfected infants born to either HIV-1-infected women receiving Combivir therapy during pregnancy (n = 10) or HIV-1-uninfected women (n = 9). Mitochondrial morphological integrity was examined in umbilical cords (n = 16) by electron microscopy and mtDNA quantity was determined in DNA from cord blood (n = 18) and umbilical cord (n = 18) by PCR-chemiluminescence immunoassay detection. In umbilical cords from six of nine infants born to HIV-1-infected mothers taking Combivir moderate to severe mitochondrial morphological damage was observed (P = 0.011), while none of seven unexposed infants showed similar damage. Compared to unexposed infants, statistically significant mtDNA depletion was observed in umbilical cord (P = 0.006) and cord blood (P = 0.003) from drug-exposed infants. A cohort of HIV-1-uninfected Combivir-exposed infants with no clinical symptoms showed morphological and molecular evidence of mitochondrial damage. JF - AIDS (London, England) AU - Divi, Rao L AU - Walker, Vernon E AU - Wade, Nancy A AU - Nagashima, Kunio AU - Seilkop, Steven K AU - Adams, Mary Ellen AU - Nesel, Carol J AU - O'Neill, J Patrick AU - Abrams, Elaine J AU - Poirier, Miriam C AD - CDI Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2004/04/30/ PY - 2004 DA - 2004 Apr 30 SP - 1013 EP - 1021 VL - 18 IS - 7 SN - 0269-9370, 0269-9370 KW - Anti-HIV Agents KW - 0 KW - DNA, Mitochondrial KW - Drug Combinations KW - lamivudine, zidovudine drug combination KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Umbilical Cord -- ultrastructure KW - HIV-1 -- isolation & purification KW - Humans KW - Infant, Newborn KW - Umbilical Cord -- metabolism KW - Pilot Projects KW - CD4 Lymphocyte Count KW - Pregnancy Complications, Infectious -- drug therapy KW - Pregnancy KW - Fetal Blood -- metabolism KW - HIV Infections -- drug therapy KW - Microscopy, Electron KW - Female KW - Prenatal Exposure Delayed Effects KW - Maternal-Fetal Exchange KW - DNA, Mitochondrial -- drug effects KW - Zidovudine -- adverse effects KW - Mitochondria -- ultrastructure KW - Mitochondria -- drug effects KW - Lamivudine -- adverse effects KW - DNA, Mitochondrial -- analysis KW - Anti-HIV Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71839373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mitochondrial+damage+and+DNA+depletion+in+cord+blood+and+umbilical+cord+from+infants+exposed+in+utero+to+Combivir.&rft.au=Divi%2C+Rao+L%3BWalker%2C+Vernon+E%3BWade%2C+Nancy+A%3BNagashima%2C+Kunio%3BSeilkop%2C+Steven+K%3BAdams%2C+Mary+Ellen%3BNesel%2C+Carol+J%3BO%27Neill%2C+J+Patrick%3BAbrams%2C+Elaine+J%3BPoirier%2C+Miriam+C&rft.aulast=Divi&rft.aufirst=Rao&rft.date=2004-04-30&rft.volume=18&rft.issue=7&rft.spage=1013&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 - 2004-08-03 N1 - Date created - 2004-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor. AN - 71827709; 15083177 AB - The aims of this study were to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics of irinotecan given with oral R115777 (tipifarnib), a farnesyl protein transferase inhibitor. Patients were treated with escalating doses of irinotecan with interval-modulated dosing of R115777 (continuously or on days 1-14, and repeated every 21 days). In total, 35 patients were entered onto the trial for a median duration of treatment of 43 days (range, 5-224 days). Neutropenia and thrombocytopenia were the dose-limiting toxicities; other side effects were mostly mild. The MTD was established at R115777 300 mg b.i.d. for 14 consecutive days with irinotecan 350 mg x m(-2) given every 3 weeks starting on day 1. Three patients had a partial response and 14 had stable disease. In the continuous schedule, the area under the curves of irinotecan and its active metabolite SN-38 were 20.0% (P=0.004) and 38.0% (P<0.001) increased by R115777, respectively. Intermittent dosing of R115777 at a dose of 300 mg b.i.d. for 14 days every 3 weeks is the recommended dose of R115777 in combination with the recommended single-agent irinotecan dose of 350 mg x m(-2). JF - British journal of cancer AU - Sparreboom, A AU - Kehrer, D F S AU - Mathijssen, R H J AU - Xie, R AU - de Jonge, M J A AU - de Bruijn, P AU - Planting, A S T AU - Eskens, F A L M AU - Verheij, C AU - de Heus, G AU - Klaren, A AU - Zhang, S AU - Verhaeghe, T AU - Palmer, P A AU - Verweij, J AD - Department of Medical Oncology, Erasmus MC - Daniel den Hoed Cancer Center, 3075 EA, Rotterdam, the Netherlands. Sparreb@mail.nih.gov Y1 - 2004/04/19/ PY - 2004 DA - 2004 Apr 19 SP - 1508 EP - 1515 VL - 90 IS - 8 SN - 0007-0920, 0007-0920 KW - Quinolones KW - 0 KW - irinotecan KW - 0H43101T0J KW - tipifarnib KW - MAT637500A KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Administration, Oral KW - Quinolones -- adverse effects KW - Infusions, Intravenous KW - Quinolones -- pharmacokinetics KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Maximum Tolerated Dose KW - Quinolones -- administration & dosage KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Camptothecin -- pharmacokinetics KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Camptothecin -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Camptothecin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71827709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+I+and+pharmacokinetic+study+of+irinotecan+in+combination+with+R115777%2C+a+farnesyl+protein+transferase+inhibitor.&rft.au=Sparreboom%2C+A%3BKehrer%2C+D+F+S%3BMathijssen%2C+R+H+J%3BXie%2C+R%3Bde+Jonge%2C+M+J+A%3Bde+Bruijn%2C+P%3BPlanting%2C+A+S+T%3BEskens%2C+F+A+L+M%3BVerheij%2C+C%3Bde+Heus%2C+G%3BKlaren%2C+A%3BZhang%2C+S%3BVerhaeghe%2C+T%3BPalmer%2C+P+A%3BVerweij%2C+J&rft.aulast=Sparreboom&rft.aufirst=A&rft.date=2004-04-19&rft.volume=90&rft.issue=8&rft.spage=1508&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 - 2004-05-26 N1 - Date created - 2004-04-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1369-74 [9465021] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6403-7 [1631135] Invest New Drugs. 2005 Oct;23(5):485-7 [16133800] J Clin Oncol. 1999 Nov;17(11):3631-52 [10550163] J Clin Oncol. 2000 Feb;18(4):927-41 [10673536] Cancer Res. 2001 Jan 1;61(1):131-7 [11196150] Anticancer Drugs. 2001 Mar;12(3):193-7 [11290865] Blood. 2001 Jun 1;97(11):3361-9 [11369625] J Natl Cancer Inst. 2001 Jul 18;93(14):1062-74 [11459867] Clin Cancer Res. 2001 Aug;7(8):2182-94 [11489791] Curr Med Chem. 2001 Oct;8(12):1419-36 [11562275] Xenobiotica. 2001 Oct;31(10):687-99 [11695848] Clin Cancer Res. 2001 Nov;7(11):3544-50 [11705875] Lancet Oncol. 2001 Jan;2(1):18-26 [11905614] J Clin Oncol. 2002 Jun 1;20(11):2726-35 [12039935] Clin Cancer Res. 2002 Jun;8(6):2002-9 [12060646] Drug Metab Dispos. 2002 Jul;30(7):823-30 [12065441] Oncology (Williston Park). 2002 May;16(5 Suppl 4):7-13 [12102580] Expert Rev Anticancer Ther. 2002 Feb;2(1):113-9 [12113060] J Clin Oncol. 2002 Jul 15;20(14):3122-9 [12118026] J Clin Oncol. 2002 Aug 1;20(15):3293-301 [12149304] Eur J Cancer. 2002 Sep;38(13):1685-700 [12175684] Mol Pharmacol. 2002 Sep;62(3):608-17 [12181437] Blood. 2003 Mar 1;101(5):1692-7 [12411300] J Clin Oncol. 2003 Apr 1;21(7):1301-6 [12663718] J Clin Oncol. 2003 May 1;21(9):1760-6 [12721252] Curr Top Med Chem. 2003;3(10):1095-102 [12769710] J Chromatogr B Biomed Sci Appl. 1998 Aug 7;712(1-2):225-35 [9698245] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selenium deficiency abrogates inflammation-dependent plasma cell tumors in mice. AN - 71834717; 15087411 AB - The role of the micronutrient, selenium, in human cancers associated with chronic inflammations and persistent infections is poorly understood. Peritoneal plasmacytomas (PCTs) in strain BALB/c (C), the premier experimental model of inflammation-dependent plasma cell transformation in mice, may afford an opportunity to gain additional insights into the significance of selenium in neoplastic development. Here, we report that selenium-depleted C mice (n = 32) maintained on a torula-based low-selenium diet (5-8 micro g of selenium/kg) were totally refractory to pristane induction of PCT. In contrast, 11 of 26 (42.3%) control mice maintained on a selenium adequate torula diet (300 micro g of selenium/kg) and 15 of 40 (37.5%) control mice fed standard Purina chow (440 micro g of selenium/kg) developed PCT by 275 days postpristane. Abrogation of PCT was caused in part by the striking inhibition of the formation of the inflammatory tissue in which PCT develop (pristane granuloma). This was associated with the reduced responsiveness of selenium-deficient inflammatory cells (monocytes and neutrophils) to chemoattractants, such as thioredoxin and chemokines. Selenium-deficient C mice exhibited little evidence of disturbed redox homeostasis and increased mutant frequency of a transgenic lacZ reporter gene in vivo. These findings implicate selenium, via the selenoproteins, in the promotion of inflammation-induced PCT and suggest that small drug inhibitors of selenoproteins might be useful for preventing human cancers linked with chronic inflammations and persistent infections. JF - Cancer research AU - Felix, Klaus AU - Gerstmeier, Simone AU - Kyriakopoulos, Antonios AU - Howard, O M Zack AU - Dong, Hui-Fang AU - Eckhaus, Michael AU - Behne, Dietrich AU - Bornkamm, Georg W AU - Janz, Siegfried AD - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute and Veterinary Resources Program, NIH, Bethesda, Maryland, USA. Y1 - 2004/04/15/ PY - 2004 DA - 2004 Apr 15 SP - 2910 EP - 2917 VL - 64 IS - 8 SN - 0008-5472, 0008-5472 KW - Terpenes KW - 0 KW - pristane KW - 26HZV48DT1 KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Animals KW - Chemotaxis -- physiology KW - Mice KW - Tissue Distribution KW - Mice, Inbred BALB C KW - Mice, Transgenic KW - Oxidation-Reduction KW - Mice, Inbred C57BL KW - Chemotaxis -- drug effects KW - Inflammation -- metabolism KW - Terpenes -- pharmacology KW - Diet KW - Mutation KW - Male KW - Selenium -- deficiency KW - Selenium -- metabolism KW - Plasmacytoma -- genetics KW - Plasmacytoma -- metabolism KW - Selenium -- pharmacokinetics KW - Plasmacytoma -- pathology KW - Peritoneal Neoplasms -- pathology KW - Peritoneal Neoplasms -- genetics KW - Selenium -- administration & dosage KW - Peritoneal Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71834717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Selenium+deficiency+abrogates+inflammation-dependent+plasma+cell+tumors+in+mice.&rft.au=Felix%2C+Klaus%3BGerstmeier%2C+Simone%3BKyriakopoulos%2C+Antonios%3BHoward%2C+O+M+Zack%3BDong%2C+Hui-Fang%3BEckhaus%2C+Michael%3BBehne%2C+Dietrich%3BBornkamm%2C+Georg+W%3BJanz%2C+Siegfried&rft.aulast=Felix&rft.aufirst=Klaus&rft.date=2004-04-15&rft.volume=64&rft.issue=8&rft.spage=2910&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 - 2004-06-10 N1 - Date created - 2004-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of nickel and iron co-exposure on human lung cells. AN - 71827173; 15081272 AB - Exposure to ambient air particulate matter (PM) is associated with increased mortality and morbidity in susceptible populations. The epidemiological data also suggest a relationship between PM air pollution and impairment of cardiopulmonary function. The mechanisms that may be responsible for these effects are not fully understood and are likely related to perturbations of cellular and molecular functions. One type of PM, residual oil fly ash (ROFA), is of particular interest. ROFA does not contain much organic material, but does contain relatively high quantities of transition metals, predominantly nickel, vanadium, and iron, as well as black carbon and sulfates. In this study, we investigated the effect of two metals (iron and nickel) on the induction of "hypoxia-like" stress and the production of interleukins (ILs) in minimally transformed human airway epithelial cells (1HAEo(-)). We found that exposure to soluble nickel sulfate results in the induction of hypoxia-inducible genes and IL-8 production by the 1HAEo(-) cells. The simultaneous addition of iron in either ferric or ferrous form and nickel completely inhibited IL-8 production and had no effect on "hypoxia-like" stress caused by nickel, suggesting the existence of two different pathways for the induction "hypoxia-like" stress and IL-8 production. The effect of nickel was not related to the blocking of iron entry into cells since the level of intracellular iron was not affected by co-exposure with nickel. The obtained data indicate that nickel can induce different signaling pathways with or without interference with iron metabolism. Our observations suggest that in some cases the excess of iron in PM can cancel the effects of nickel. JF - Toxicology and applied pharmacology AU - Salnikow, Konstantin AU - Li, Xiaomei AU - Lippmann, Morton AD - Nelson Institute of Environmental Medicine, EPA PM Health Effects Research Center and NIEHS Environmental Health Sciences Center, New York University School of Medicine, New York, NY 10016, USA. salnikow@ncifcrf.gov Y1 - 2004/04/15/ PY - 2004 DA - 2004 Apr 15 SP - 258 EP - 265 VL - 196 IS - 2 SN - 0041-008X, 0041-008X KW - Air Pollutants KW - 0 KW - Cell Cycle Proteins KW - Chlorides KW - Coal Ash KW - Ferric Compounds KW - Interleukin-8 KW - Intracellular Signaling Peptides and Proteins KW - Iron Chelating Agents KW - N-myc downstream-regulated gene 1 protein KW - Particulate Matter KW - nickel sulfate KW - 4FLT4T3WUN KW - Carbon KW - 7440-44-0 KW - Nickel KW - 7OV03QG267 KW - Deferoxamine KW - J06Y7MXW4D KW - ferric chloride KW - U38V3ZVV3V KW - Index Medicus KW - Interleukin-8 -- secretion KW - Hypoxia -- pathology KW - Interleukin-8 -- antagonists & inhibitors KW - Cell Cycle Proteins -- biosynthesis KW - Humans KW - Iron Chelating Agents -- pharmacology KW - Epithelial Cells -- metabolism KW - Blotting, Western KW - Deferoxamine -- pharmacology KW - Epithelial Cells -- drug effects KW - Interleukin-8 -- biosynthesis KW - Hypoxia -- chemically induced KW - Lung -- secretion KW - Ferric Compounds -- pharmacokinetics KW - Ferric Compounds -- toxicity KW - Lung -- drug effects KW - Nickel -- toxicity KW - Lung -- metabolism KW - Air Pollutants -- toxicity KW - Carbon -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71827173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+nickel+and+iron+co-exposure+on+human+lung+cells.&rft.au=Salnikow%2C+Konstantin%3BLi%2C+Xiaomei%3BLippmann%2C+Morton&rft.aulast=Salnikow&rft.aufirst=Konstantin&rft.date=2004-04-15&rft.volume=196&rft.issue=2&rft.spage=258&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 - 2004-05-19 N1 - Date created - 2004-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mycophenolate mofetil for remission maintenance in the treatment of Wegener's granulomatosis. AN - 71813046; 15077273 AB - To examine the safety of mycophenolate mofetil (MMF) for remission maintenance in patients with Wegener's granulomatosis (WG) who had been treated with daily cyclophosphamide (CYC) and glucocorticoids to induce remission. Fourteen patients were treated for active WG using a standardized regimen of CYC and glucocorticoids for induction of remission and MMF for remission maintenance. Outcome was assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. Remission occurred in all 14 patients (100%) at a median time of 3 months. The median time to discontinuation of glucocorticoids was 8 months. No patients died during protocol treatment and 6 patients (43%) relapsed at a median of 10 months after achieving remission. MMF was well tolerated and no patients had to be withdrawn as a result of medication toxicity. The use of CYC and glucocorticoids for induction of remission and MMF for remission maintenance was well tolerated, but disease relapses were observed. JF - Arthritis and rheumatism AU - Langford, Carol A AU - Talar-Williams, Cheryl AU - Sneller, Michael C AD - National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA. clangford@niaid.nih.gov Y1 - 2004/04/15/ PY - 2004 DA - 2004 Apr 15 SP - 278 EP - 283 VL - 51 IS - 2 SN - 0004-3591, 0004-3591 KW - Immunosuppressive Agents KW - 0 KW - Mycophenolic Acid KW - HU9DX48N0T KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Recurrence KW - Male KW - Female KW - Remission Induction KW - Mycophenolic Acid -- analogs & derivatives KW - Mycophenolic Acid -- adverse effects KW - Granulomatosis with Polyangiitis -- drug therapy KW - Mycophenolic Acid -- administration & dosage KW - Immunosuppressive Agents -- adverse effects KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71813046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Mycophenolate+mofetil+for+remission+maintenance+in+the+treatment+of+Wegener%27s+granulomatosis.&rft.au=Langford%2C+Carol+A%3BTalar-Williams%2C+Cheryl%3BSneller%2C+Michael+C&rft.aulast=Langford&rft.aufirst=Carol&rft.date=2004-04-15&rft.volume=51&rft.issue=2&rft.spage=278&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-11 N1 - Date created - 2004-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Translocation of protein kinase C-betaII in astrocytes requires organized actin cytoskeleton and is not accompanied by synchronous RACK1 relocation. AN - 71755587; 15042584 AB - Protein kinase C (PKC)-betaII is the most abundant PKC isoform in astrocytes. Upon activation, this isoform of PKC translocates from the cytosol to the plasma membrane (PM). In this study, we investigated in astrocytes the modality of PKC-betaII translocation as far as the participation of the receptor for activated C kinase-1 (RACK1) and the requirement for intact cytoskeleton in the process. In astrocytes, Western blots and immunocytochemistry coupled to confocal microscopic quantitative analysis showed that after 5 min of phorbol-12-myristate-13-acetate (PMA) exposure, native PKC-betaII, but not PKC-betaI, is relocated efficiently from the cytosol to the PM. Translocation of PKC-betaII was not associated with synchronous RACK1 relocation. Furthermore, the quantity of PM-associated PKC-betaII that co-immunoprecipitated with PM-bound RACK1 increased following PMA exposure, indicating a post activation binding of the two proteins in the PM. Because RACK1 and PKC-betaII relocation seemed not to be synchronous, we hypothesized that an intermediate interaction with the cytoskeleton was taking place. In fact, we were able to show that pharmacological disruption of actin-based cytoskeleton greatly deranged PKC-betaII translocation to the PM. The requirement for intact actin cytoskeleton was specific, because depolymerization of tubulin had no effect on the ability of the kinase to translocate to the PM. These results indicate that in astrocytes, RACK1 and PKC-betaII synchronous relocation is not essential for relocation of PKC-betaII to the PM. In addition, we show for the first time that the integrity of the actin cytoskeleton plays a specific role in PKC-betaII movements in these cells. We hypothesize that in glial cells, rapidly occurring changes of actin cytoskeleton arrangement may be involved in the fast reprogramming of PKC targeting to specific PM location to phosphorylate substrates in different cellular locations. Published 2003 Wiley-Liss, Inc. JF - Glia AU - Pascale, Alessia AU - Alkon, Daniel L AU - Grimaldi, Maurizio AD - Laboratory of Adaptive Systems, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/04/15/ PY - 2004 DA - 2004 Apr 15 SP - 169 EP - 182 VL - 46 IS - 2 SN - 0894-1491, 0894-1491 KW - Actins KW - 0 KW - Carcinogens KW - Membrane Proteins KW - Receptors, Cell Surface KW - receptors for activated C kinase KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C beta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Protein Binding -- physiology KW - Cerebral Cortex -- cytology KW - Carcinogens -- pharmacology KW - Animals KW - Cells, Cultured KW - Protein Binding -- drug effects KW - Membrane Proteins -- metabolism KW - Microtubules -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Substrate Specificity KW - Receptors, Cell Surface -- metabolism KW - Protein Kinase C -- metabolism KW - Astrocytes -- cytology KW - Actin Cytoskeleton -- metabolism KW - Actins -- metabolism KW - Astrocytes -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71755587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Translocation+of+protein+kinase+C-betaII+in+astrocytes+requires+organized+actin+cytoskeleton+and+is+not+accompanied+by+synchronous+RACK1+relocation.&rft.au=Pascale%2C+Alessia%3BAlkon%2C+Daniel+L%3BGrimaldi%2C+Maurizio&rft.aulast=Pascale&rft.aufirst=Alessia&rft.date=2004-04-15&rft.volume=46&rft.issue=2&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Glia&rft.issn=08941491&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-28 N1 - Date created - 2004-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current Issues Pertaining to the Nocardia species AN - 17968819; 5909889 AB - Because the number of recognized Nocardia species is continuing to increase, members of the genus Nocardia are becoming increasingly difficult to identify using phenotypic criteria. Molecular techniques, such as restriction endonuclease analysis and 16S rRNA gene sequencing, have become increasingly useful methodologies for the definitive identification of clinical isolates in this genus. While molecular methods have been useful for rapid and accurate identification, their use has complicated nocardial taxonomy by revealing new, clinically relevant species that are genetically distinct from known species but which may have few distinguishing phenotypic characteristics. We present here an overview of some taxonomic issues concerning Nocardia species and describe molecular techniques that are useful in the identification of the majority of clinically relevant species. JF - Clinical Microbiology Newsletter AU - Conville, P S AU - Witebsky, F G AD - Building 10, 2C-385, 10 Center Dr., MSC 1508, Bethesda, MD 20892-1508, USA, pconville@nih.gov Y1 - 2004/04/15/ PY - 2004 DA - 2004 Apr 15 SP - 57 EP - 62 VL - 26 IS - 8 SN - 0196-4399, 0196-4399 KW - Microbiology Abstracts B: Bacteriology KW - Reviews KW - Nucleotide sequence KW - Restriction endonuclease mapping KW - Taxonomy KW - rRNA 16S KW - Nocardia KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17968819?accountid=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=Clinical+Microbiology+Newsletter&rft.atitle=Current+Issues+Pertaining+to+the+Nocardia+species&rft.au=Conville%2C+P+S%3BWitebsky%2C+F+G&rft.aulast=Conville&rft.aufirst=P&rft.date=2004-04-15&rft.volume=26&rft.issue=8&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Clinical+Microbiology+Newsletter&rft.issn=01964399&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 - Nocardia; rRNA 16S; Nucleotide sequence; Restriction endonuclease mapping; Reviews; Taxonomy ER - TY - JOUR T1 - The role of the theta isoform of protein kinase C (PKC) in activity-dependent synapse elimination: evidence from the PKC theta knock-out mouse in vivo and in vitro. AN - 71837097; 15084656 AB - PKC plays a critical role in competitive activity-dependent synapse modification at the neuromuscular synapse in vitro and in vivo. This action involves a reduction of the strength of inactive inputs to muscle cells that are activated by other inputs. A decrease of postsynaptic responsiveness and a loss of postsynaptic acetyl choline receptors account for the heterosynaptic loss in vitro. The loss is not seen in preparations in which PKC has been blocked pharmacologically. Here, we show that the loss does not occur in in vitro preparations made from animals genetically modified to lack the theta isoform of PKC. Synapse elimination in the newborn period in vivo is delayed but is eventually expressed in knock-out animals. PKC-dependent synapse reduction is suppressed in heterologous cultures combining normal nerve and PKC theta-deficient muscle, as might be expected from the postsynaptic locus of the changes that underlie the activity-dependent plasticity. Preparations in which PKC theta-deficient neurons innervated normal muscle also exhibited a marked deficit in PKC-deficient synapse reduction. The presynaptic action of PKC theta implied by this observation is blocked by TTX, and we propose that activity-related synapse strengthening is decreased by presynaptic PKC theta. Thus, PKC theta in both presynaptic and postsynaptic elements plays a critical role in activity-dependent synapse modulation and loss. We provide a model for activity-dependent synapse loss incorporating these findings. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Li, Min-Xu AU - Jia, Min AU - Yang, Li-Xia AU - Jiang, Hao AU - Lanuza, Maria A AU - Gonzalez, Carmen M AU - Nelson, Phillip G AD - Section on Neurobiology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutesof Health, Bethesda, Maryland 20892, USA. liminxu@mail.nih.gov Y1 - 2004/04/14/ PY - 2004 DA - 2004 Apr 14 SP - 3762 EP - 3769 VL - 24 IS - 15 KW - Isoenzymes KW - 0 KW - Phorbol Esters KW - Prkcq protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Phorbol Esters -- pharmacology KW - Animals, Newborn KW - Animals KW - Blotting, Western KW - Diffusion Chambers, Culture KW - Muscles -- innervation KW - Mice, Inbred C57BL KW - Mice KW - Time Factors KW - Muscles -- physiology KW - Microelectrodes KW - Mice, Knockout KW - Neuromuscular Junction -- drug effects KW - Isoenzymes -- deficiency KW - Isoenzymes -- physiology KW - Protein Kinase C -- genetics KW - Protein Kinase C -- deficiency KW - Neuromuscular Junction -- physiology KW - Synaptic Transmission -- physiology KW - Protein Kinase C -- physiology KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71837097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+role+of+the+theta+isoform+of+protein+kinase+C+%28PKC%29+in+activity-dependent+synapse+elimination%3A+evidence+from+the+PKC+theta+knock-out+mouse+in+vivo+and+in+vitro.&rft.au=Li%2C+Min-Xu%3BJia%2C+Min%3BYang%2C+Li-Xia%3BJiang%2C+Hao%3BLanuza%2C+Maria+A%3BGonzalez%2C+Carmen+M%3BNelson%2C+Phillip+G&rft.aulast=Li&rft.aufirst=Min-Xu&rft.date=2004-04-14&rft.volume=24&rft.issue=15&rft.spage=3762&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-21 N1 - Date created - 2004-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevated presence of retrotransposons at sites of DNA double strand break repair in mouse models of metabolic oxidative stress and MYC-induced lymphoma. AN - 71796664; 15063142 AB - The chromosomally integrated shuttle vector pUR288 contains a lacZ reporter gene to study mutagenesis in vivo. We used pUR288 to compare patterns of genomic instability in two mouse models, lymphoma resulting from deregulated c-MYC expression (lambda-MYC), and endogenous oxidative stress caused by partial glucose 6-phosphate dehydrogenase (G6PD) deficiency. We found previously that spontaneous mutations in both models were predominantly genomic rearrangements of lacZ with mouse sequences, while most mutations in controls were point mutations. Here, we characterized the fine structure of 68 lacZ/mouse rearrangements from lambda-MYC lymphomas and G6PD deficient mice by sequencing breakpoint junctions and determining the origin of recombining mouse sequences. Fifty-eight of 68 (85%) recombination partners were identified. The structure of rearrangements from both lambda-MYC and G6PD deficient mice were remarkably alike. Intra-chromosomal deletions and inversions were common, occurring in 41% (24/58) of rearrangements, while 59% (34/58) were random translocations between lacZ and other chromosomes. Signatures of double strand break repair by nonhomologous end joining were observed at breakpoint junctions; 37% (25/68) contained 1-4 bp microhomologies, while the remaining breakpoints had no sequence homology. Long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons, which constitute approximately 10% of the mouse genome, were present at 25% (17/68) of breakpoints, suggesting their participation in rearrangements. The similarity in the structure of rearrangements is consistent with the hypothesis that genetic rearrangements in lambda-MYC lymphomas and G6PD deficient mice result from the same mechanism, mutagenic repair of DNA double strand breaks arising from oxidative damage. JF - Mutation research AU - Rockwood, Lynne D AU - Felix, Klaus AU - Janz, Siegfried AD - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institute of Health, Building 37, Room 3140A, Bethesda, MD 20892-4256, USA. Y1 - 2004/04/14/ PY - 2004 DA - 2004 Apr 14 SP - 117 EP - 125 VL - 548 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Retroelements KW - 0 KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Index Medicus KW - Animals KW - Genomic Instability KW - Lac Operon -- physiology KW - Recombination, Genetic KW - Mice, Inbred C57BL KW - Mice KW - Glucosephosphate Dehydrogenase -- physiology KW - Mice, Transgenic KW - Mutation KW - Genes, myc -- physiology KW - Male KW - Glucosephosphate Dehydrogenase -- genetics KW - DNA Repair -- genetics KW - Lymphoma -- etiology KW - Lymphoma -- genetics KW - Oxidative Stress KW - Chromosome Aberrations KW - Disease Models, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71796664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Elevated+presence+of+retrotransposons+at+sites+of+DNA+double+strand+break+repair+in+mouse+models+of+metabolic+oxidative+stress+and+MYC-induced+lymphoma.&rft.au=Rockwood%2C+Lynne+D%3BFelix%2C+Klaus%3BJanz%2C+Siegfried&rft.aulast=Rockwood&rft.aufirst=Lynne&rft.date=2004-04-14&rft.volume=548&rft.issue=1-2&rft.spage=117&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 - 2004-05-20 N1 - Date created - 2004-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single amino acid substitution in human APOBEC3G antiretroviral enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion. AN - 71832602; 15054139 AB - HIV-1 and other retroviruses occasionally undergo hypermutation, characterized by a high rate of G-to-A substitution. Recently, the human apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G), first identified as CEM15, was shown to be packaged into retroviral virions and to deaminate deoxycytidine to deoxyuridine in newly synthesized viral minus-strand DNA, thereby inducing G-to-A hypermutation. This innate mechanism of resistance to retroviral infection is counteracted by the HIV-1 viral infectivity factor (Vif), which protects the virus by preventing the incorporation of APOBEC3G into virions by rapidly inducing its ubiquitination and proteasomal degradation. To gain insights into the mechanism by which Vif protects HIV-1 from APOBEC3G, we substituted several amino acids in human APOBEC3G with equivalent residues in simian APOBEC3Gs that are resistant to HIV-1 Vif and determined the effects of the mutations on HIV-1 replication in the presence and absence of Vif. We found that a single amino acid substitution mutant of human APOBEC3G (D128K) can interact with HIV-1 Vif but is not depleted from cells; thus, it inhibits HIV-1 replication in an HIV-1 Vif-resistant manner. Interestingly, rhesus macaque simian immunodeficiency virus 239 or HIV-2 Vif coexpression depleted the intracellular steady state levels of the D128K mutant and abrogated its antiviral activity, indicating that it can be a substrate for the proteasomal pathway. The HIV-1 Vif-resistant mutant APOBEC3G could provide a gene therapy approach to combat HIV-1 infection. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Xu, Hongzhan AU - Svarovskaia, Evguenia S AU - Barr, Rebekah AU - Zhang, Yijun AU - Khan, Mohammad A AU - Strebel, Klaus AU - Pathak, Vinay K AD - HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. Y1 - 2004/04/13/ PY - 2004 DA - 2004 Apr 13 SP - 5652 EP - 5657 VL - 101 IS - 15 SN - 0027-8424, 0027-8424 KW - Gene Products, vif KW - 0 KW - Proteins KW - Recombinant Proteins KW - Repressor Proteins KW - vif Gene Products, Human Immunodeficiency Virus KW - Nucleoside Deaminases KW - EC 3.5.4.- KW - APOBEC-3G Deaminase KW - EC 3.5.4.5 KW - APOBEC3G protein, human KW - Cytidine Deaminase KW - Index Medicus KW - DNA Mutational Analysis KW - Humans KW - Amino Acid Sequence KW - Virus Replication -- physiology KW - Recombinant Proteins -- genetics KW - Mutagenesis, Site-Directed KW - Phenotype KW - Transfection KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Flow Cytometry KW - Amino Acid Substitution KW - Cell Line KW - HIV-1 -- pathogenicity KW - Gene Products, vif -- metabolism KW - HIV-1 -- physiology KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71832602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+single+amino+acid+substitution+in+human+APOBEC3G+antiretroviral+enzyme+confers+resistance+to+HIV-1+virion+infectivity+factor-induced+depletion.&rft.au=Xu%2C+Hongzhan%3BSvarovskaia%2C+Evguenia+S%3BBarr%2C+Rebekah%3BZhang%2C+Yijun%3BKhan%2C+Mohammad+A%3BStrebel%2C+Klaus%3BPathak%2C+Vinay+K&rft.aulast=Xu&rft.aufirst=Hongzhan&rft.date=2004-04-13&rft.volume=101&rft.issue=15&rft.spage=5652&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 - 2004-05-19 N1 - Date created - 2004-04-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Cell Dev Biol. 1999;15:435-67 [10611969] Cell. 1997 Feb 21;88(4):427-30 [9038332] Nature. 2002 Aug 8;418(6898):646-50 [12167863] J Virol. 2003 May;77(10):5810-20 [12719574] Science. 2003 May 16;300(5622):1112 [12750511] Cell. 2003 Jun 13;113(6):803-9 [12809610] Nature. 2003 Jul 3;424(6944):94-8 [12808465] Nature. 2003 Jul 3;424(6944):99-103 [12808466] Cell. 2003 Jul 11;114(1):21-31 [12859895] Mol Cell. 2003 Sep;12(3):591-601 [14527406] J Virol. 2003 Nov;77(21):11398-407 [14557625] Nat Med. 2003 Nov;9(11):1404-7 [14528300] Nat Med. 2003 Nov;9(11):1398-403 [14528301] Science. 2003 Nov 7;302(5647):1056-60 [14564014] Curr Biol. 2003 Nov 11;13(22):2009-13 [14614829] Nature. 1987 Aug 20-26;328(6132):728-30 [2441266] Science. 1987 Aug 21;237(4817):888-93 [3497453] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6019-23 [2201018] J Virol. 1991 Apr;65(4):1779-88 [2002543] AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221-31 [2078405] J Virol. 1992 Nov;66(11):6489-95 [1357189] Virology. 1997 Aug 18;235(1):104-8 [9300041] J Virol. 1998 Nov;72(11):8873-83 [9765432] J Exp Med. 1999 Jun 7;189(11):1735-46 [10359577] J Biol Chem. 2004 Feb 27;279(9):7792-8 [14672928] Nature. 1987 Apr 16-22;326(6114):662-9 [3031510] J Virol. 1993 Mar;67(3):1663-6 [8437236] J Virol. 1993 Aug;67(8):4945-55 [8331734] EMBO J. 1994 Jun 15;13(12):2935-47 [8026477] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11787-91 [7527543] Methods Cell Biol. 1994;43 Pt A:99-112 [7823872] Annu Rev Biochem. 2001;70:503-33 [11395416] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro processing of HIV-1 nucleocapsid protein by the viral proteinase: effects of amino acid substitutions at the scissile bond in the proximal zinc finger sequence. AN - 71801789; 15065874 AB - The human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein flanked by Gag sequences (r-preNC) was expressed in Escherichia coli and purified. HIV-1 proteinase cleaved r-preNC to the "mature" NCp7 form, which is comprised of 55 residues. Further incubation resulted in cleavages of NCp7 itself between Phe16 and Asn17 of the proximal zinc finger domain and between Cys49 and Thr50 in the C-terminal part. Kinetic parameters determined for the cleavage of oligopeptides corresponding to the cleavage sites in r-preNC correlated well with the sequential processing of r-preNC. Mutations of Asn17 were introduced to alter the susceptibility of NC protein to HIV-1 proteinase. While mutating Asn17 to Ala resulted in a protein which was processed in a manner similar to that of the wild type, mutating it to Phe or Leu resulted in proteins which were processed at a substantially higher rate at this site than the wild type. Mutation of Asn17 to Lys or Gly resulted in proteins which were very poorly cleaved at this site. Oligopeptides containing the same amino acid substitutions at the cleavage site of the proximal zinc finger domain were also tested as substrates of the proteinase, and the kinetic parameters agreed well with the semiquantitative results obtained with the protein substrates. JF - Biochemistry AU - Tözsér, József AU - Shulenin, Sergey AU - Louis, John M AU - Copeland, Terry D AU - Oroszlan, Stephen AD - National Cancer Institute, Frederick, Maryland 21701, USA. Y1 - 2004/04/13/ PY - 2004 DA - 2004 Apr 13 SP - 4304 EP - 4312 VL - 43 IS - 14 SN - 0006-2960, 0006-2960 KW - Capsid Proteins KW - 0 KW - Gene Products, gag KW - NCP7 protein, Human immunodeficiency virus 1 KW - Oligopeptides KW - Protein Precursors KW - Recombinant Proteins KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - Protein Precursors -- metabolism KW - Recombinant Proteins -- biosynthesis KW - DNA Mutational Analysis KW - Humans KW - Oligopeptides -- genetics KW - Amino Acid Sequence KW - Hydrolysis KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Protein Precursors -- biosynthesis KW - Molecular Sequence Data KW - Oligopeptides -- metabolism KW - Protein Precursors -- isolation & purification KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - Gene Products, gag -- genetics KW - Capsid Proteins -- metabolism KW - Protein Processing, Post-Translational -- genetics KW - Amino Acid Substitution -- genetics KW - HIV-1 -- enzymology KW - HIV Protease -- metabolism KW - Gene Products, gag -- metabolism KW - Capsid Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71801789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+processing+of+HIV-1+nucleocapsid+protein+by+the+viral+proteinase%3A+effects+of+amino+acid+substitutions+at+the+scissile+bond+in+the+proximal+zinc+finger+sequence.&rft.au=T%C3%B6zs%C3%A9r%2C+J%C3%B3zsef%3BShulenin%2C+Sergey%3BLouis%2C+John+M%3BCopeland%2C+Terry+D%3BOroszlan%2C+Stephen&rft.aulast=T%C3%B6zs%C3%A9r&rft.aufirst=J%C3%B3zsef&rft.date=2004-04-13&rft.volume=43&rft.issue=14&rft.spage=4304&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-06 N1 - Date created - 2004-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of alcohol use disorders in general hospital admissions in the United States. AN - 71816721; 15078644 AB - Previous studies in which research-based assessment for alcohol problems at admission was compared with physician diagnoses indicated that many alcohol diagnoses in hospitalized patients were missed. We estimated the extent to which hospital records documented detection of alcohol abuse or dependence and other alcohol-related problems in a national sample of hospital admissions having a research-based diagnosis of alcohol use disorder ("interview-positive admissions"). We also estimated rates of inpatient alcohol intervention and referral for treatment. A complex, multistage, probability sample was designed to represent nonmaternity, acute-care admissions to nonfederal, short-stay, general hospitals in the contiguous United States. The study included 2040 admissions, 1613 male and 427 female. Research-based diagnoses of current (ie, past 12 months) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol use disorder were derived from a structured, computer-assisted, personal interview containing the Alcohol Use Disorders and Associated Disabilities Interview Schedule. Information on detection, inpatient intervention, and treatment referral were obtained via retrospective analysis of closed hospital records covering the index visit. Record-documented diagnoses of alcohol-related problems were found in 40% to 42% of interview-positive admissions. Inpatient intervention rate was estimated at 21% for interview-positive admissions, and treatment referral rate, 24%. For detected interview-positive admissions, estimated rates of intervention and referral were 50% and 53%, respectively. Estimated rates of detection, inpatient intervention, and treatment referral of alcohol use disorders in hospital admissions were low. Current-drinking hospital admissions should be screened for alcohol problems as part of the admission routine, with further professional evaluation, intervention, and treatment referral as indicated. JF - Archives of internal medicine AU - Smothers, Barbara A AU - Yahr, Harold T AU - Ruhl, Constance E AD - Division of Epidemiology and Prevention Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. bs86h@nih.gov Y1 - 2004/04/12/ PY - 2004 DA - 2004 Apr 12 SP - 749 EP - 756 VL - 164 IS - 7 SN - 0003-9926, 0003-9926 KW - Abridged Index Medicus KW - Index Medicus KW - Length of Stay KW - Humans KW - Adult KW - Referral and Consultation KW - Middle Aged KW - Hospitals, General KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Alcohol-Related Disorders -- diagnosis KW - Patient Admission KW - Alcohol-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71816721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+internal+medicine&rft.atitle=Detection+of+alcohol+use+disorders+in+general+hospital+admissions+in+the+United+States.&rft.au=Smothers%2C+Barbara+A%3BYahr%2C+Harold+T%3BRuhl%2C+Constance+E&rft.aulast=Smothers&rft.aufirst=Barbara&rft.date=2004-04-12&rft.volume=164&rft.issue=7&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=Archives+of+internal+medicine&rft.issn=00039926&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-27 N1 - Date created - 2004-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mini-and microsatellite mutations in children from Chernobyl accident cleanup workers. AN - 71806222; 15066582 AB - Knowledge about possible genotoxic effects of low-dose radiation on the human germline is limited and relies primarily on extrapolations from high-dose exposures. To test whether ionizing radiation can cause paternal genetic mutations that are transmitted to offspring, we enrolled families of 88 Chernobyl cleanup workers exposed to ionizing radiation. We analyzed DNA isolated from lymphocytes for mutations via DNA blotting with the multi-locus minisatellite probes 33.6 and 33.15 and via PCR in a panel of six tetranucleotide repeats. Children conceived before and children conceived after their father's exposure showed no statistically significant differences in mutation frequencies. We saw an increase in germline microsatellite mutations after radiation exposure that was not statistically significant. We found no dependence of mutation rate on increasing exposure. A novel finding was that the tetranucleotide marker D7S1482 demonstrated germline hypermutability. In conclusion, our results do not support an increased level of germline minisatellite mutations but suggest a modest increase in germline mutations in tetranucleotide repeats. Small sample size, however, limited statistical power. JF - Mutation research AU - Slebos, Robbert J C AU - Little, Ruth E AU - Umbach, David M AU - Antipkin, Yurij AU - Zadaorozhnaja, Tamara D AU - Mendel, Nikola A AU - Sommer, Courtney A AU - Conway, Kathleen AU - Parrish, Eloise AU - Gulino, Sara AU - Taylor, Jack A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. Y1 - 2004/04/11/ PY - 2004 DA - 2004 Apr 11 SP - 143 EP - 151 VL - 559 IS - 1-2 SN - 0027-5107, 0027-5107 KW - DNA Probes KW - 0 KW - Index Medicus KW - Ukraine -- epidemiology KW - Humans KW - Adult KW - Child KW - Lymphocytes KW - Dose-Response Relationship, Radiation KW - Male KW - Female KW - Occupational Exposure KW - Microsatellite Repeats -- genetics KW - Paternal Exposure KW - Radioactive Hazard Release KW - Mutation -- genetics KW - Minisatellite Repeats -- genetics KW - Mutation -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71806222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mini-and+microsatellite+mutations+in+children+from+Chernobyl+accident+cleanup+workers.&rft.au=Slebos%2C+Robbert+J+C%3BLittle%2C+Ruth+E%3BUmbach%2C+David+M%3BAntipkin%2C+Yurij%3BZadaorozhnaja%2C+Tamara+D%3BMendel%2C+Nikola+A%3BSommer%2C+Courtney+A%3BConway%2C+Kathleen%3BParrish%2C+Eloise%3BGulino%2C+Sara%3BTaylor%2C+Jack+A&rft.aulast=Slebos&rft.aufirst=Robbert+J&rft.date=2004-04-11&rft.volume=559&rft.issue=1-2&rft.spage=143&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 - 2004-06-21 N1 - Date created - 2004-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antidepressant medications in children. AN - 71804348; 15071123 JF - The New England journal of medicine AU - Vitiello, Benedetto AU - Swedo, Susan AD - National Institute of Mental Health, Bethesda, Md, USA. Y1 - 2004/04/08/ PY - 2004 DA - 2004 Apr 08 SP - 1489 EP - 1491 VL - 350 IS - 15 KW - Antidepressive Agents, Second-Generation KW - 0 KW - Serotonin Uptake Inhibitors KW - Fluoxetine KW - 01K63SUP8D KW - Paroxetine KW - 41VRH5220H KW - Abridged Index Medicus KW - Index Medicus KW - Causality KW - Humans KW - Obsessive-Compulsive Disorder -- drug therapy KW - Fluoxetine -- therapeutic use KW - Child KW - Paroxetine -- adverse effects KW - Adolescent KW - Risk Assessment KW - Antidepressive Agents, Second-Generation -- adverse effects KW - Depressive Disorder -- psychology KW - Suicide KW - Depressive Disorder -- drug therapy KW - Serotonin Uptake Inhibitors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71804348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antidepressant+medications+in+children.&rft.au=Vitiello%2C+Benedetto%3BSwedo%2C+Susan&rft.aulast=Vitiello&rft.aufirst=Benedetto&rft.date=2004-04-08&rft.volume=350&rft.issue=15&rft.spage=1489&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-23 N1 - Date created - 2004-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin C pharmacokinetics: implications for oral and intravenous use. AN - 71810112; 15068981 AB - Vitamin C at high concentrations is toxic to cancer cells in vitro. Early clinical studies of vitamin C in patients with terminal cancer suggested clinical benefit, but 2 double-blind, placebo-controlled trials showed none. However, these studies used different routes of administration. To determine whether plasma vitamin C concentrations vary substantially with the route of administration. Dose concentration studies and pharmacokinetic modeling. Academic medical center. 17 healthy hospitalized volunteers. Vitamin C plasma and urine concentrations were measured after administration of oral and intravenous doses at a dose range of 0.015 to 1.25 g, and plasma concentrations were calculated for a dose range of 1 to 100 g. Peak plasma vitamin C concentrations were higher after administration of intravenous doses than after administration of oral doses (P < 0.001), and the difference increased according to dose. Vitamin C at a dose of 1.25 g administered orally produced mean (+/-sd) peak plasma concentrations of 134.8 +/- 20.6 micromol/L compared with 885 +/- 201.2 micromol/L for intravenous administration. For the maximum tolerated oral dose of 3 g every 4 hours, pharmacokinetic modeling predicted peak plasma vitamin C concentrations of 220 micromol/L and 13 400 micromol/L for a 50-g intravenous dose. Peak predicted urine concentrations of vitamin C from intravenous administration were 140-fold higher than those from maximum oral doses. Patient data are not available to confirm pharmacokinetic modeling at high doses and in patients with cancer. Oral vitamin C produces plasma concentrations that are tightly controlled. Only intravenous administration of vitamin C produces high plasma and urine concentrations that might have antitumor activity. Because efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated. JF - Annals of internal medicine AU - Padayatty, Sebastian J AU - Sun, He AU - Wang, Yaohui AU - Riordan, Hugh D AU - Hewitt, Stephen M AU - Katz, Arie AU - Wesley, Robert A AU - Levine, Mark AD - National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institut, and the Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1372, USA. Y1 - 2004/04/06/ PY - 2004 DA - 2004 Apr 06 SP - 533 EP - 537 VL - 140 IS - 7 KW - Antineoplastic Agents KW - 0 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Reference Values KW - Injections, Intravenous KW - Humans KW - Adult KW - Antineoplastic Agents -- therapeutic use KW - Male KW - Female KW - Ascorbic Acid -- therapeutic use KW - Ascorbic Acid -- administration & dosage KW - Ascorbic Acid -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71810112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vitamin+C+pharmacokinetics%3A+implications+for+oral+and+intravenous+use.&rft.au=Padayatty%2C+Sebastian+J%3BSun%2C+He%3BWang%2C+Yaohui%3BRiordan%2C+Hugh+D%3BHewitt%2C+Stephen+M%3BKatz%2C+Arie%3BWesley%2C+Robert+A%3BLevine%2C+Mark&rft.aulast=Padayatty&rft.aufirst=Sebastian&rft.date=2004-04-06&rft.volume=140&rft.issue=7&rft.spage=533&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=1539-3704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-20 N1 - Date created - 2004-04-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 2004 Apr 6;140(7):I61 [15069006] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response [corrected]. AN - 71798737; 15066282 AB - Enzymes of the Rel/Spo family enable bacteria to survive prolonged periods of nutrient limitation by producing an intracellular signaling alarmone, (p)ppGpp, which triggers the so-called stringent response. Both the synthesis of (p)ppGpp from ATP and GDP(GTP), and its hydrolysis to GDP(GTP) and pyrophosphate, are catalyzed by Rel/Spo proteins. The 2.1 A crystal structure of the bifunctional catalytic fragment of the Rel/Spo homolog from Streptococcus dysgalactiae subsp. equisimilis, Rel(Seq), reveals two conformations of the enzyme corresponding to known reciprocal activity states: (p)ppGpp-hydrolase-OFF/(p)ppGpp-synthetase-ON and hydrolase-ON/synthetase-OFF. The hydrolase and synthetase domains bear remarkable similarities to the catalytic domains of the cyclic phosphodiesterase and nucleotidyltransferase superfamilies, respectively. The active sites, separated by more than 30 A, contain bound nucleotides including an unusual (p)ppGpp derivative, GDP-2':3'-cyclic monophosphate. Reciprocal regulation of the antagonistic catalytic activities, suggested by the structure, is supported by mutagenesis experiments and appears to involve ligand-induced signal transmission between the two active sites. JF - Cell AU - Hogg, Tanis AU - Mechold, Undine AU - Malke, Horst AU - Cashel, Mike AU - Hilgenfeld, Rolf AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/04/02/ PY - 2004 DA - 2004 Apr 02 SP - 57 EP - 68 VL - 117 IS - 1 SN - 0092-8674, 0092-8674 KW - Nucleotides KW - 0 KW - Guanosine Pentaphosphate KW - 38918-96-6 KW - GTP Pyrophosphokinase KW - EC 2.7.6.5 KW - Ligases KW - EC 6.- KW - guanosine 3',5'-polyphosphate synthetases KW - Index Medicus KW - Nucleotides -- metabolism KW - Models, Molecular KW - Energy Metabolism -- physiology KW - Amino Acid Sequence KW - Binding Sites -- physiology KW - Structure-Activity Relationship KW - Signal Transduction -- physiology KW - Starvation -- metabolism KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Protein Structure, Tertiary KW - Sequence Homology, Amino Acid KW - Catalytic Domain -- physiology KW - Protein Conformation KW - Ligases -- genetics KW - Bacteria -- genetics KW - GTP Pyrophosphokinase -- metabolism KW - Bacteria -- enzymology KW - Ligases -- metabolism KW - GTP Pyrophosphokinase -- genetics KW - Guanosine Pentaphosphate -- metabolism KW - Ligases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71798737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conformational+antagonism+between+opposing+active+sites+in+a+bifunctional+RelA%2FSpoT+homolog+modulates+%28p%29ppGpp+metabolism+during+the+stringent+response+%5Bcorrected%5D.&rft.au=Hogg%2C+Tanis%3BMechold%2C+Undine%3BMalke%2C+Horst%3BCashel%2C+Mike%3BHilgenfeld%2C+Rolf&rft.aulast=Hogg&rft.aufirst=Tanis&rft.date=2004-04-02&rft.volume=117&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-06 N1 - Date created - 2004-04-06 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1VJ7; PDB N1 - SuppNotes - Erratum In: Cell. 2004 Apr 30;117(3):415 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel testis- and embryo-specific isoforms of the phosphofructokinase-1 muscle type gene. AN - 71747623; 15020257 AB - We have identified novel transcriptional isoforms of the human and mouse genes encoding muscle type phosphofructokinase-1 (PFK-M). These isoforms are expressed specifically in the testis and in the mid-gestation embryo, and have been termed TE-PFK-M (testis- and embryo-specific PFK-M). The 5'UTR of TE-PFK-M is composed of three newly identified exons that lie much farther upstream of the PFK-M coding region than the previously characterized 5'UTR. In addition, this upstream region encodes a series of small polyadenylated transcripts, some of which share the same exons found in the 5'UTR of TE-PFK-M, and which may play some role in regulating TE-PFK-M expression. These findings indicate an even more complex level of control of PFK-M expression than previously thought. JF - Biochemical and biophysical research communications AU - Yamada, Satoru AU - Nakajima, Hiromu AU - Kuehn, Michael R AD - Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, NCI-Frederick, Frederick, MD 21702, USA. Y1 - 2004/04/02/ PY - 2004 DA - 2004 Apr 02 SP - 580 EP - 587 VL - 316 IS - 2 SN - 0006-291X, 0006-291X KW - DNA, Complementary KW - 0 KW - Isoenzymes KW - RNA, Messenger KW - Phosphofructokinase-1, Muscle Type KW - EC 2.7.1.- KW - Index Medicus KW - Transcription Initiation Site KW - Animals KW - RNA, Messenger -- metabolism KW - Isoenzymes -- biosynthesis KW - Humans KW - Proviruses -- genetics KW - DNA, Complementary -- isolation & purification KW - Mice KW - Tissue Distribution KW - Isoenzymes -- genetics KW - Mutagenesis, Insertional KW - Male KW - Phosphofructokinase-1, Muscle Type -- biosynthesis KW - Embryo, Mammalian -- enzymology KW - Testis -- enzymology KW - Phosphofructokinase-1, Muscle Type -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71747623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Novel+testis-+and+embryo-specific+isoforms+of+the+phosphofructokinase-1+muscle+type+gene.&rft.au=Yamada%2C+Satoru%3BNakajima%2C+Hiromu%3BKuehn%2C+Michael+R&rft.aulast=Yamada&rft.aufirst=Satoru&rft.date=2004-04-02&rft.volume=316&rft.issue=2&rft.spage=580&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 - 2004-04-27 N1 - Date created - 2004-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type XI collagen genotype. AN - 85378586; pmid-15141750 AB - Mutations in the fibrillar collagen genes COL11A1 and COL11A2 can cause sensorineural hearing loss associated with Stickler syndrome. There is a correlation of hearing loss severity, onset, progression and affected frequencies with the underlying mutated collagen gene. We sought to determine whether differences in spatial or temporal expression of these genes underlie this correlation, and to identify the cochlear cell populations expressing these genes and the structures likely to be affected by mutations.We used in situ hybridization analysis of C57BL/6J mouse temporal bones.Similar, diffuse expression of Col11a1 and Col11a2 mRNA was first observed in the cochlear duct at embryonic Day 15.5, with increasingly focal hybridization being noted at postnatal Days 1 and 5 in the greater epithelial ridge and lateral wall of the cochlea. The greater epithelial ridge appeared to be the main, if not only, source of mRNA encoding Col11a1 and Col11a2 in the tectorial membrane. At postnatal Day 13, Col11a1 and Col11a2 expression became more focal and co-localized in the inner sulcus, Claudius' cells and cells of Boettcher.We did not observe spatial or temporal differences in mRNA expression that could account for the auditory phenotype genotype correlation. The expression patterns suggest essential roles for Col11a1 and Col11a2 in the basilar or tectorial membranes. JF - Acta oto-laryngologica AU - Shpargel, Karl B AU - Makishima, Tomoko AU - Griffith, Andrew J AD - Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, USA. Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 242 EP - 248 VL - 124 IS - 3 SN - 0001-6489, 0001-6489 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Basilar Membrane: embryology KW - Basilar Membrane: physiology KW - Cochlea: embryology KW - *Cochlea: physiology KW - *Collagen Type XI: genetics KW - Collagen Type XI: metabolism KW - Extracellular Matrix: physiology KW - *Gene Expression Regulation, Developmental KW - Genotype KW - *Hearing Loss, Sensorineural: genetics KW - In Situ Hybridization KW - Mice KW - Mice, Inbred C57BL KW - Mutation KW - Phenotype KW - *RNA, Messenger: biosynthesis KW - Regression Analysis KW - Tectorial Membrane: embryology KW - Tectorial Membrane: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85378586?accountid=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=Acta+oto-laryngologica&rft.atitle=Col11a1+and+Col11a2+mRNA+expression+in+the+developing+mouse+cochlea%3A+implications+for+the+correlation+of+hearing+loss+phenotype+with+mutant+type+XI+collagen+genotype.&rft.au=Shpargel%2C+Karl+B%3BMakishima%2C+Tomoko%3BGriffith%2C+Andrew+J&rft.aulast=Shpargel&rft.aufirst=Karl&rft.date=2004-04-01&rft.volume=124&rft.issue=3&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Acta+oto-laryngologica&rft.issn=00016489&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Distinct mechanisms lead to HPRT gene mutations in leukemic cells. AN - 80174107; 14978792 AB - Leukemias are considered malignant clonal disorders arising from the accumulation of mutations in hematopoietic cells; the majority of these mutations are thought to be acquired somatically. Measurement of mutation frequency (Mf) at the hypoxanthine phosphoribosyltransferase (HPRT) locus has been developed as a method for estimating genomic instability. We investigated the Mf in 16 leukemic cell lines to determine whether these cell lines showed evidence of genomic instability. Although some leukemic cell lines had markedly elevated Mfs, the Mfs at the HPRT locus in leukemic cell lines were not always higher than those of B-lymphoblastoid cell lines and T lymphocytes from normal individuals. We were able to identify the HPRT mutation for 159 of 160 individual HPRT mutants. The HPRT mutations were characterized at a molecular level and classified as either gross chromosomal rearrangements (GCRs) or point mutations, such as single-nucleotide substitutions, insertions, or deletions. With rare exceptions, individual leukemic cell lines showed either point mutations or GCR, but not both. Of note, all the cell lines that primarily showed point mutations are known to be defective in mismatch repair machinery. Copyright 2004 Wiley-Liss, Inc. JF - Genes, chromosomes & cancer AU - Lin, Ying-Wei AU - Perkins, Jonathan J AU - Zhang, Zhenhua AU - Aplan, Peter D AD - Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20889-510, USA. aplanp@mail.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 311 EP - 323 VL - 39 IS - 4 SN - 1045-2257, 1045-2257 KW - Genetic Markers KW - 0 KW - RNA, Messenger KW - RNA, Neoplasm KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Jurkat Cells -- chemistry KW - B-Lymphocytes -- pathology KW - K562 Cells -- chemistry KW - Jurkat Cells -- metabolism KW - Humans KW - Aged KW - Child KW - Pilot Projects KW - B-Lymphocytes -- metabolism KW - Recombination, Genetic -- genetics KW - Adult KW - K562 Cells -- metabolism KW - Adolescent KW - Male KW - B-Lymphocytes -- chemistry KW - DNA Mutational Analysis -- methods KW - HL-60 Cells -- chemistry KW - Genomic Instability -- genetics KW - Cell Line, Tumor KW - RNA, Neoplasm -- genetics KW - Mutagenesis -- genetics KW - U937 Cells -- chemistry KW - Child, Preschool KW - RNA Splicing -- genetics KW - Genetic Markers -- genetics KW - HL-60 Cells -- metabolism KW - RNA, Messenger -- metabolism KW - Female KW - U937 Cells -- metabolism KW - Leukemia -- pathology KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Mutation -- genetics KW - Leukemia -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80174107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Distinct+mechanisms+lead+to+HPRT+gene+mutations+in+leukemic+cells.&rft.au=Lin%2C+Ying-Wei%3BPerkins%2C+Jonathan+J%3BZhang%2C+Zhenhua%3BAplan%2C+Peter+D&rft.aulast=Lin&rft.aufirst=Ying-Wei&rft.date=2004-04-01&rft.volume=39&rft.issue=4&rft.spage=311&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 - 2004-05-04 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitivity of the neuronal network biosensor to environmental threats. AN - 72016920; 15192870 AB - It is widely acknowledged that there is a critical need for broad-spectrum environmental threat detection. While cells/tissue-based biosensors have been discussed for many years as a means of meeting this critical need, these kinds of systems have met with logistic concerns, in particular with regard to stability. Our group has been working with cultured neuronal networks, which have the capacity to respond to a wide range of neuroactive compounds and are sufficiently robust to be shipped to end users. The basis of operation involves extracellular recording using thin-film microelectrode arrays where spontaneous bioelectrical activity, that is, spike firing, can be monitored in a noninvasive manner conducive for potentially long-term measurements. This work describes the current status of our efforts for the fabrication of a portable biosensor that incorporates cultured neuronal networks grown over standardized microelectrode arrays. Based on our protocol for aqueous phase sample introduction under constant flow conditions, minimal variation in mean spike rate is observed, consistent with temporal stability, such that changes of > 10% are readily distinguished. To demonstrate the capability of this system, changes are reported in mean spike rate and network synchronization resulting from exposure to different model environmental threats, cadmium and strychnine. The sensitivity of this assay approach and implications of the experimental findings for environmental threat detection are discussed. JF - Journal of toxicology and environmental health. Part A AU - Pancrazio, Joseph J AU - Kulagina, Nadezhda V AU - Shaffer, Kara M AU - Gray, Samuel A AU - O'Shaughnessy, Thomas J AD - Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington, DC, USA. pancrazj@ninds.nih.gov PY - 2004 SP - 809 EP - 818 VL - 67 IS - 8-10 SN - 1528-7394, 1528-7394 KW - Neurotoxins KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Strychnine KW - H9Y79VD43J KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Electrophysiology -- methods KW - Cells, Cultured KW - Electrophysiology -- instrumentation KW - Predictive Value of Tests KW - Strychnine -- toxicity KW - Cadmium -- analysis KW - Environmental Exposure KW - Cadmium -- toxicity KW - Neurotoxins -- analysis KW - Strychnine -- analysis KW - Biosensing Techniques -- methods KW - Biosensing Techniques -- instrumentation KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72016920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Part+A&rft.atitle=Sensitivity+of+the+neuronal+network+biosensor+to+environmental+threats.&rft.au=Pancrazio%2C+Joseph+J%3BKulagina%2C+Nadezhda+V%3BShaffer%2C+Kara+M%3BGray%2C+Samuel+A%3BO%27Shaughnessy%2C+Thomas+J&rft.aulast=Pancrazio&rft.aufirst=Joseph&rft.date=2004-04-01&rft.volume=67&rft.issue=8-10&rft.spage=809&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-24 N1 - Date created - 2004-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of peptides that bind to cyanovirin-N, a potent human immunodeficiency virus-inactivating protein. AN - 71965444; 15165709 AB - Cyanovirin-N (CV-N) exerts a potent human immunodeficiency virus (HIV)-inactivating activity against diverse strains of HIV by binding to the viral surface envelope glycoprotein gp120 and blocking its essential interactions with cellular receptors. Based on previous thermodynamic analyses, it has been speculated that discrete protein-protein interactions might play an important ancillary role in the CV-N/gp120 binding event, in addition to the interactions of CV-N with specific oligosaccharides present on gp120. Here, we report the identification and characterization of CV-N-binding peptides, which were isolated by screening of M13 phage-displayed peptide libraries. After performing three rounds of biopanning of the libraries against biotinylated CV-N, a CV-N-binding motif, X3CX6(W/F)(Y/F)CX2(Y/F), was evident. A vector was designed to express CV-N-binding peptides as a fusion with thioredoxin (Trx) containing a penta-His affinity tag. The CV-N-binding peptides fused with His-tagged Trx inhibited binding of the corresponding peptide-bearing phages to CV-N, confirming that the peptides possessed CV-N-binding activity. Optical biosensor binding studies showed that the one of the CV-N-binding peptide, TN10-1, bound to CV-N with a KD value of 1.9 microM. The results of alanine scanning mutagenesis of the peptide showed that aromatic residues at positions 11, 12, and 16, as well as the conformational structure of the peptide secured by a disulfide bond, were important for the binding interactions. A series of competitive binding assays confirmed that gp120 inhibited CV-N binding of the corresponding peptide-bearing phages, and suggested that TN10-1 peptides were mimicking the protein component of gp120 rather than mimicking specific oligosaccharides present on gp120. Copyright 2004 Elsevier Inc. JF - Peptides AU - Han, Zhaozhong AU - Simpson, John T AU - Fivash, Matthew J AU - Fisher, Robert AU - Mori, Toshiyuki AD - Molecular Targets Development Program, Center for Cancer Research, National Cancer Institute, NCI-Frederick, Frederick, MD 21702-1201, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 551 EP - 561 VL - 25 IS - 4 SN - 0196-9781, 0196-9781 KW - Amino Acids, Aromatic KW - 0 KW - Bacterial Proteins KW - Carrier Proteins KW - HIV Envelope Protein gp120 KW - Oligosaccharides KW - Peptide Library KW - Peptides KW - Recombinant Fusion Proteins KW - cyanovirin N KW - 184539-38-6 KW - Index Medicus KW - Amino Acid Motifs -- genetics KW - Surface Plasmon Resonance KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Amino Acid Substitution -- genetics KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- genetics KW - Amino Acids, Aromatic -- genetics KW - Protein Binding -- genetics KW - Binding Sites -- genetics KW - Oligosaccharides -- chemistry KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Bacterial Proteins -- chemistry KW - HIV Envelope Protein gp120 -- chemistry KW - Bacterial Proteins -- metabolism KW - Peptides -- metabolism KW - Peptides -- chemistry KW - Peptides -- genetics KW - HIV -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71965444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Identification+and+characterization+of+peptides+that+bind+to+cyanovirin-N%2C+a+potent+human+immunodeficiency+virus-inactivating+protein.&rft.au=Han%2C+Zhaozhong%3BSimpson%2C+John+T%3BFivash%2C+Matthew+J%3BFisher%2C+Robert%3BMori%2C+Toshiyuki&rft.aulast=Han&rft.aufirst=Zhaozhong&rft.date=2004-04-01&rft.volume=25&rft.issue=4&rft.spage=551&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-18 N1 - Date created - 2004-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad3 as a mediator of the fibrotic response. AN - 71962548; 15154911 AB - Transforming growth factor-beta (TGF-beta) plays a central role in fibrosis, contributing to the influx and activation of inflammatory cells, the epithelial to mesenchymal transdifferentiation (EMT) of cells and the influx of fibroblasts and their subsequent elaboration of extracellular matrix. TGF-beta signals through transmembrane receptor serine/threonine kinases to activate novel signalling intermediates called Smad proteins, which modulate the transcription of target genes. The use of mice with a targeted deletion of Smad3, one of the two homologous proteins which signals from TGF-beta/activin, shows that most of the pro-fibrotic activities of TGF-beta are mediated by Smad3. Smad3 null inflammatory cells and fibroblasts do not respond to the chemotactic effects of TGF-beta and do not autoinduce TGF-beta. The loss of Smad3 also interferes with TGF-beta-mediated induction of EMT and genes for collagens, plasminogen activator inhibitor-1 and the tissue inhibitor of metalloprotease-1. Smad3 null mice are resistant to radiation-induced cutaneous fibrosis, bleomycin-induced pulmonary fibrosis, carbon tetrachloride-induced hepatic fibrosis as well as glomerular fibrosis induced by induction of type 1 diabetes with streptozotocin. In fibrotic conditions that are induced by EMT, such as proliferative vitreoretinopathy, ocular capsule injury and glomerulosclerosis resulting from unilateral ureteral obstruction, Smad3 null mice also show an abrogated fibrotic response. Animal models of scleroderma, cystic fibrosis and cirrhosis implicate involvement of Smad3 in the observed fibrosis. Additionally, inhibition of Smad3 by overexpression of the inhibitory Smad7 protein or by treatment with the small molecule, halofuginone, dramatically reduces responses in animal models of kidney, lung, liver and radiation-induced fibrosis. Small moleucule inhibitors of Smad3 may have tremendous clinical potential in the treatment of pathological fibrotic diseases. JF - International journal of experimental pathology AU - Flanders, Kathleen C AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-5055, USA. flanderk@dce41.nci.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 47 EP - 64 VL - 85 IS - 2 SN - 0959-9673, 0959-9673 KW - Cytokines KW - 0 KW - DNA-Binding Proteins KW - SMAD2 protein, human KW - SMAD3 protein, human KW - SMAD7 protein, human KW - Smad2 Protein KW - Smad3 Protein KW - Smad7 Protein KW - Trans-Activators KW - Transforming Growth Factor beta KW - Cholecalciferol KW - 1C6V77QF41 KW - Index Medicus KW - Animals KW - Extracellular Matrix -- metabolism KW - Humans KW - Cytokines -- immunology KW - Cholecalciferol -- therapeutic use KW - Extracellular Matrix -- pathology KW - Gene Expression Regulation KW - Fibrosis -- drug therapy KW - Transforming Growth Factor beta -- metabolism KW - Fibrosis -- immunology KW - Trans-Activators -- metabolism KW - Signal Transduction -- physiology KW - Signal Transduction -- drug effects KW - DNA-Binding Proteins -- antagonists & inhibitors KW - Trans-Activators -- antagonists & inhibitors KW - Wound Healing -- physiology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71962548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+experimental+pathology&rft.atitle=Smad3+as+a+mediator+of+the+fibrotic+response.&rft.au=Flanders%2C+Kathleen+C&rft.aulast=Flanders&rft.aufirst=Kathleen&rft.date=2004-04-01&rft.volume=85&rft.issue=2&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=International+journal+of+experimental+pathology&rft.issn=09599673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-13 N1 - Date created - 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Cell. 2003 Jun 13;113(6):685-700 [12809600] Nat Med. 2003 Jul;9(7):964-8 [12808448] J Invest Dermatol. 2003 Jul;121(1):41-50 [12839562] Gastroenterology. 2003 Jul;125(1):178-91 [12851882] Biol Blood Marrow Transplant. 2003 Jul;9(7):417-25 [12869955] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins for treating cancer. AN - 71930891; 15149034 AB - Recombinant immunotoxins are antibody-toxin chimeric molecules that kill cancer cells via binding to a surface antigen, internalization and delivery of the toxin moiety to the cell cytosol. In the cytosol, toxins catalytically inhibit a critical cell function and cause cell death. The antibody portion of the chimera targets antigens that are expressed preferentially on the surface of cancer cells. Truncated versions of either diphtheria toxin (DT) or Pseudomonas exotoxin (PE) can be used to construct fusions with cDNAs encoding antibody fragments or cell-binding ligands. Recombinant immunotoxins are routinely produced in E. coli and purified using standard chromatographic methods. Before they can be evaluated for anticancer activity in humans, recombinant immunotoxins undergo extensive preclinical testing. Immunotoxins must demonstrate cell-killing activity in tissue culture, antitumor activity in an animal model and have favorable pharmacokinetic and toxicity profiles. Candidate molecules with favorable characteristics are then evaluated in clinical trials. Here we report on the initial evaluation of BL22, a recombinant immunotoxin targeted to CD22 expressed on the surface of B-cell malignancies. JF - International journal of medical microbiology : IJMM AU - FitzGerald, David J AU - Kreitman, Robert AU - Wilson, Wyndham AU - Squires, David AU - Pastan, Ira AD - Laboratory of Molecular Biology, CCR, National Cancer Institute, Bethesda, MD 20892, USA. djpf@helix.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 577 EP - 582 VL - 293 IS - 7-8 SN - 1438-4221, 1438-4221 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cell Adhesion Molecules KW - Diphtheria Toxin KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Lectins KW - Recombinant Fusion Proteins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Index Medicus KW - Diphtheria Toxin -- immunology KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Immunoglobulin Variable Region -- immunology KW - Clinical Trials as Topic KW - Exotoxins -- immunology KW - Immunoglobulin Variable Region -- therapeutic use KW - Immunoglobulin Fragments -- therapeutic use KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Diphtheria Toxin -- therapeutic use KW - Exotoxins -- therapeutic use KW - Immunoglobulin Fragments -- immunology KW - Recombinant Fusion Proteins -- therapeutic use KW - Lectins -- immunology KW - Antigens, CD -- immunology KW - Lymphoma, B-Cell -- therapy KW - Lymphoma, B-Cell -- immunology KW - Immunotoxins -- immunology KW - Leukemia, B-Cell -- therapy KW - Immunotoxins -- therapeutic use KW - Leukemia, B-Cell -- immunology KW - Immunotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71930891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medical+microbiology+%3A+IJMM&rft.atitle=Recombinant+immunotoxins+for+treating+cancer.&rft.au=FitzGerald%2C+David+J%3BKreitman%2C+Robert%3BWilson%2C+Wyndham%3BSquires%2C+David%3BPastan%2C+Ira&rft.aulast=FitzGerald&rft.aufirst=David&rft.date=2004-04-01&rft.volume=293&rft.issue=7-8&rft.spage=577&rft.isbn=&rft.btitle=&rft.title=International+journal+of+medical+microbiology+%3A+IJMM&rft.issn=14384221&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-30 N1 - Date created - 2004-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Micronutrients and cancer therapy. AN - 71929403; 15141429 AB - The effect of micronutrient supplementation on the effectiveness of cancer chemotherapeutic agents is reviewed, and the efficacy of antioxidants, folic acid, and other vitamins and minerals is discussed. Although some micronutrients show promise in enhancing the cytotoxicity of anticancer agents in vitro, caution should be exercised in recommending micronutrient supplementation for cancer patients receiving chemotherapeutic drugs. To date, few well-controlled clinical trials have been conducted to evaluate the efficacy of micronutrients in promoting the sensitivity of tumors to chemotherapeutic agents. JF - Nutrition reviews AU - Whiteside, Martin A AU - Heimburger, Douglas C AU - Johanning, Gary L AD - Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 142 EP - 147 VL - 62 IS - 4 SN - 0029-6643, 0029-6643 KW - Antineoplastic Agents KW - 0 KW - Antioxidants KW - Micronutrients KW - Folic Acid KW - 935E97BOY8 KW - Index Medicus KW - Animals KW - Combined Modality Therapy KW - Humans KW - Antioxidants -- therapeutic use KW - Treatment Outcome KW - Folic Acid -- therapeutic use KW - Drug Synergism KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Neoplasms -- drug therapy KW - Micronutrients -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71929403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Micronutrients+and+cancer+therapy.&rft.au=Whiteside%2C+Martin+A%3BHeimburger%2C+Douglas+C%3BJohanning%2C+Gary+L&rft.aulast=Whiteside&rft.aufirst=Martin&rft.date=2004-04-01&rft.volume=62&rft.issue=4&rft.spage=142&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 - 2004-06-01 N1 - Date created - 2004-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NTP technical report on the toxicity studies of 2- and 4-Methylimidazole (CAS No. 693-98-1 and 822-36-6) administered in feed to F344/N rats and B6C3F1 mice. AN - 71923473; 15146214 AB - [Structure-see text] 2-Methylimidazole and 4-methylimidazole are intermediate/starting materials or components in the manufacture of pharmaceuticals, photographic and photothermographic chemicals, dyes and pigments, agricultural chemicals, and rubber; these chemicals have been identified as undesirable by-products in several foods and have been detected in mainstream and sidestream tobacco smoke. The National Cancer Institute nominated 2- and 4-methylimidazole as candidates for toxicity and carcinogenicity studies. Toxicity studies were carried out in male and female F344/N rats and B6C3F1 mice. Animals were exposed to 2- or 4-methylimidazole in feed for 15 days or 14 weeks; clinical pathology studies were conducted in the 14-week studies on days 8, 29, and 86 and at week 14. Genetic toxicity studies were conducted in Salmonella typhimurium, rat and mouse bone marrow, and mouse peripheral blood. Groups of five male and five female rats and mice were fed diets containing 0, 1,200, 3,300, or 10,000 ppm 2-methylimidazole (equivalent to average daily doses of approximately 115, 290, or 770 mg 2-methylimidazole/ kg body weight to rats; 220, 640, or 2,100 mg/kg to male mice; 300, 800, or 2,400 to female mice) for 15 days. Groups of five male and five female rats and mice were fed diets containing 0, 300, 800, or 2,500 ppm 4-methylimidazole (equivalent to average daily doses of approximately 30, 80, or 220 mg/kg for rats and 65, 170, or 500 mg/kg for mice) for 15 days. In the 15-day 2-methylimidazole studies, all animals survived to the end of the studies. The mean body weights of 10,000 ppm male rats and female mice were significantly less than those of the controls. Feed consumption by 10,000 ppm male and female rats was reduced. Enlarged thyroid glands were observed in 3,300 and 10,000 ppm male and female rats. The incidences of diffuse hyperplasia of follicular cells of the thyroid gland in 3,300 and 10,000 ppm male and female rats and pars distalis hypertrophy of the pituitary gland in 3,300 and 10,000 ppm males and 10,000 ppm females were increased compared to the controls. In all exposed groups of male and female mice, the incidences and severities of follicular cell hypertrophy of the thyroid gland and the severities of hematopoietic cell proliferation of the spleen generally increased with increasing exposure concentration. In the 4-methylimidazole studies, all animals survived to the end of the studies, and there were no significant differences in mean body weights, clinical findings, organ weights, or gross or microscopic lesions between exposed and control groups. Groups of 10 male and 10 female rats and mice were fed diets containing 0, 625, 1,250, 2,500, 5,000, or 10,000 ppm 2- or 4-methylimidazole (equivalent to average daily doses of approximately 40, 80, 160, 300, or 560 mg/kg 2- or 4-methylimidazole to rats; and 100, 165, 360, 780, or 1,740 mg/kg 2-methylimidazole or 100, 240, 440, 915, or 1,840 mg/kg 4-methylimidazole to male mice; and 90, 190, 400, 800, or 1,860 mg/kg 2-methylimidazole or 110, 240, 540, 1,130, or 3,180 mg/kg 4-methylimidazole to females) for 14 weeks. All animals survived to the end of the 14-week 2-methylimidazole studies. Compared to the controls, the mean body weights were significantly decreased in groups of male rats and mice exposed to 2,500 ppm or greater and in 5,000 and 10,000 ppm female rats and mice. In rats, 2-methylimidazole induced a transient erythrocytosis in females and a minimal, exposure concentration-related, microcytic, normochromic, nonresponsive anemia. 2-Methylimidazole increased thyroid-stimulating hormone concentrations and decreased thyroxine and triiodothyronine concentrations of male and female rats in an exposure concentration-related manner. 2-Methylimidazole induced a mild to moderate, exposure concentration-related, macrocytic, hyperchromic, responsive anemia in mice. Triiodothyronine concentrations were increased in exposed male and female mice, and thyroxine concentrations were decreased in exposed females. Relative to the control groups, clinical chemistry evaluations on day 29 and at week 14 identified decreases in alanine aminotransferase concentrations and total protein and albumin concentrations of rats. In the 2-methylimidazole studies, absolute spleen weights were significantly increased in all exposed groups of male rats. The heart and liver weights were increased in all exposed groups of male mice, as were the spleen weights of female mice exposed to 2,500 ppm or greater. Spermatid heads per testis and mean spermatid count were significantly decreased in 10,000 ppm male rats. The estrous cycle of 10,000 ppm female rats was significantly increased. Gross pathology observations included enlarged thyroid glands, small uteri, and mottled spleen in 5,000 and 10,000 ppm mice. The incidences of diffuse follicular cell hyperplasia of the thyroid gland were significantly increased in male rats exposed to 1,250 ppm or greater and female rats exposed to 2,500 ppm or greater. The incidence of testicular degeneration was significantly increased in 10,000 ppm male rats, and two males in the 10,000 ppm group had follicular cell adenoma of the thyroid gland. In mice, there were generally significant increases in the incidences of follicular cell hypertrophy of the thyroid gland, hematopoietic cell proliferation of the spleen, and hemosiderin pigmentation of the renal tubule in males exposed to 1,250 ppm or greater and females exposed to 2,500 ppm or greater. In the 14-week 4-methylimidazole studies, one 10,000 ppm male mouse was found dead during week 4, and seven 10,000 ppm female mice were found dead during weeks 1 and 2. Mean body weights were significantly less than those of the controls for male rats exposed to 2,500 ppm or greater, 5,000 and 10,000 ppm female rats, male mice exposed to 1,250 ppm or greater, and all exposed groups of female mice. Reduced feed consumption was observed in 5,000 and 10,000 ppm male and female rats. Clinical findings included nasal/eye discharge, ruffled fur, thinness, ataxia, and abnormal breathing in rats, and ruffled fur and dull coats in female mice. On days 29 and 82, functional observations in 5,000 and 10,000 ppm rats included labored or increased respiration, mild tremors, walking on tiptoes, hunched posture, piloerection, crouching over, impaired coordination of movement, ataxia, and pupillary constriction. 4-Methylimidazole induced a transient erythrocytosis and a minimal, exposure concentration-related, microcytic, normochromic, nonresponsive anemia in male and female rats. Clinical chemistry evaluations generally showed a cholestatic effect in exposed male and female rats. At week 14, there was a significant decrease in total protein and albumin concentrations of female rats exposed to 5,000 or 10,000 ppm. In mice, 4-methylimidazole induced a macrocytic, hyperchromic, responsive anemia and, particularly in males, increases in triiododthyronine concentrations and transient decreases in thyroxine concentrations. In the 4-methylimidazole studies, the liver weights of male rats exposed to 2,500 ppm or greater were significantly increased; spleen weights of female rats exposed to 2,500 ppm or greater were decreased. The absolute liver weight was decreased in 10,000 ppm male mice, and relative weights were significantly increased in all exposed groups of mice. In female mice, there was a significant decrease in the absolute weights and increase in the relative weights of the heart, right kidney, and liver in groups exposed to 2,500 ppm or greater. The epididymal spermatozoal concentration was significantly increased in 5,000 ppm male rats. Gross pathology observations included pale livers in male rats exposed to 2,500 ppm or greater and small testes and uteri in 10,000 ppm male and female rats. Microscopic analysis identified significantly increased incidences of cytoplasmic hepatocyte vacuolization of the liver of male rats exposed to 2,500 ppm or greater and 10,000 ppm female rats, hypospermia of the epididymis in 10,000 ppm male rats, atrophy and inflammation of the prostate gland in 10,000 ppm male rats, and degeneration of the testes in 5,000 and 10,000 ppm male rats. 2-Methylimidazole and 4-methylimidazole were negative in the S. typhimurium mutation assay when tested in strains TA97, TA98, TA100, and TA1535, with and without S9 activation enzymes. Testing of 2-methylimidazole in vivo for induction of chromosomal damage, as measured by micronucleated erythrocyte frequency, produced mixed results. When administered by intraperitoneal injection three times at 24-hour intervals, 2-methylimidazole produced negative results in bone marrow micronucleus tests in rats and mice. However, in the 14-week study of 2-methylimidazole, a significant exposure-related increase in the frequency of micronucleated normochromatic erythrocytes was noted in peripheral blood of male and female mice. In vivo, 4-methylimidazole produced uniformly negative results in three-injection bone marrow micronucleus tests in rats and mice and in 14-week peripheral blood micronucleus tests in male and female mice. JF - Toxicity report series AU - Chan, P C AU - National Toxicology Program, US Department of Health and Human Services, Public Health Service, National Institutes of Health AD - National Toxicology Program, US Department of Health and Human Services, Public Health Service, National Institutes of Health Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 1 EP - G12 IS - 67 SN - 1521-4621, 1521-4621 KW - Imidazoles KW - 0 KW - 4-methylimidazole KW - Q64GF9FV4I KW - 2-methylimidazole KW - T0049Z45LZ KW - Index Medicus KW - Bone Marrow Cells -- drug effects KW - Animals KW - Neoplasms -- epidemiology KW - Mice KW - Organ Size KW - Rats KW - Body Weight KW - Eating KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - Micronucleus Tests KW - Neoplasms -- chemically induced KW - Diet KW - Time Factors KW - Salmonella typhimurium -- genetics KW - Quality Control KW - Bone Marrow Cells -- physiology KW - Bone Marrow Cells -- ultrastructure KW - Female KW - Male KW - Imidazoles -- pharmacokinetics KW - Imidazoles -- toxicity KW - Imidazoles -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71923473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicity+report+series&rft.atitle=NTP+technical+report+on+the+toxicity+studies+of+2-+and+4-Methylimidazole+%28CAS+No.+693-98-1+and+822-36-6%29+administered+in+feed+to+F344%2FN+rats+and+B6C3F1+mice.&rft.au=Chan%2C+P+C%3BNational+Toxicology+Program%2C+US+Department+of+Health+and+Human+Services%2C+Public+Health+Service%2C+National+Institutes+of+Health&rft.aulast=Chan&rft.aufirst=P&rft.date=2004-04-01&rft.volume=&rft.issue=67&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicity+report+series&rft.issn=15214621&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-16 N1 - Date created - 2004-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53: 25 years after its discovery. AN - 71886522; 15116721 AB - Since its discovery 25 years ago, the p53 protein has emerged as a key tumor suppressor protein at the crossroads of cellular stress response pathways. Through these pathways, which can lead to cell-cycle arrest, DNA repair, cellular senescence, differentiation and apoptosis, p53 facilitates the repair and survival of damaged cells or eliminates severely damaged cells from the replicative pool to protect the organism. Because of these dynamic and multiple functions of p53, which are largely lost following mutations in the gene encoding p53, this molecule continues to be studied intensively in biomedical research, including the fields of toxicology and pharmacology. In this article, we briefly review the first 25 years of research on p53. JF - Trends in pharmacological sciences AU - Hofseth, Lorne J AU - Hussain, S Perwez AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 177 EP - 181 VL - 25 IS - 4 SN - 0165-6147, 0165-6147 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - DNA Repair KW - Humans KW - Apoptosis -- physiology KW - Tumor Suppressor Protein p53 -- physiology KW - Tumor Suppressor Protein p53 -- genetics KW - Research -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71886522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacological+sciences&rft.atitle=p53%3A+25+years+after+its+discovery.&rft.au=Hofseth%2C+Lorne+J%3BHussain%2C+S+Perwez%3BHarris%2C+Curtis+C&rft.aulast=Hofseth&rft.aufirst=Lorne&rft.date=2004-04-01&rft.volume=25&rft.issue=4&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Trends+in+pharmacological+sciences&rft.issn=01656147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-11 N1 - Date created - 2004-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lymphoma and myeloma in older patients. AN - 71875338; 15112150 AB - Lymphoma and myeloma represent an increasingly important cause of morbidity and mortality in the older patient group. Studies to date, while limited, suggest that there may be differences in the underlying biology of the tumor cell of some lymphoid malignancies in younger versus older patients. Significant new data will be required to document and elucidate the differences and use them to tailor therapy to discrete disease entities. Increasing numbers of clinical trials are addressing the issues of treatment in the elderly, particularly in the aggressive non-Hodgkin's lymphomas. However, much work remains in improving the participation of older patient groups in current clinical trials and in overcoming inherent treatment biases related to concerns of toxicity simply as a function of age, both of which limit application of existing successful therapy to older patient groups. JF - Seminars in oncology AU - Westin, Eric H AU - Longo, Dan L AD - Section of Hematology/Oncology, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 198 EP - 205 VL - 31 IS - 2 SN - 0093-7754, 0093-7754 KW - Index Medicus KW - Aging -- physiology KW - Neoplasm Staging KW - Humans KW - Prognosis KW - Aged KW - Cytogenetics KW - Lymphoma -- therapy KW - Lymphoma -- epidemiology KW - Multiple Myeloma -- pathology KW - Multiple Myeloma -- epidemiology KW - Multiple Myeloma -- therapy KW - Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71875338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=Lymphoma+and+myeloma+in+older+patients.&rft.au=Westin%2C+Eric+H%3BLongo%2C+Dan+L&rft.aulast=Westin&rft.aufirst=Eric&rft.date=2004-04-01&rft.volume=31&rft.issue=2&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-10 N1 - Date created - 2004-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A laboratory study of hydromorphone and cyclazocine on smoking behavior in residential polydrug users. AN - 71856482; 15099916 AB - The effects of cyclazocine and hydromorphone on spontaneous and laboratory cigarette smoking were compared in a double-blind, placebo-controlled, crossover study. Participants (seven men, one woman) received oral doses of placebo, cyclazocine (0.2, 0.4, and 0.8 mg) and hydromorphone (5 and 15 mg) in a randomized order on experimental days. Spontaneous smoking was recorded during two intervals on the experimental days: a 3-h period 5-8 h after drug administration (Interval 1), and the rest of the day (Interval 2). Measures of smoking topography and subjective and physiologic effects of a single cigarette were obtained on the experimental days. Neither hydromorphone nor cyclazocine significantly changed spontaneous smoking when compared to the placebo condition; however, compared to hydromorphone (5 mg), cyclazocine (0.4 and 0.8 mg) decreased spontaneous smoking during Interval 1. Hydromorphone (5 and 15 mg) and cyclazocine (0.4 and 0.8 mg) diminished smoking-induced increases in heart rate. Compared to the placebo condition, cyclazocine (0.2 and 0.4 mg) reduced exhaled carbon monoxide (CO) boost, a measure of smoke exposure. Further studies of the effects of kappa opioid agonists on smoking behavior may lead to a better understanding of the role of opiates in smoking behavior. JF - Pharmacology, biochemistry, and behavior AU - Pickworth, Wallace B AU - Lee, Eun M AU - Abreu, Mary E AU - Umbricht, Annie AU - Preston, Kenzie L AD - National Institute on Drug Abuse (NIDA), Intramural Research Program, Clinical Pharmacology and Therapeutics Branch, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. wpickwo@intra.nida.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 711 EP - 715 VL - 77 IS - 4 SN - 0091-3057, 0091-3057 KW - Cyclazocine KW - J5W1B1159C KW - Hydromorphone KW - Q812464R06 KW - Index Medicus KW - Analysis of Variance KW - Double-Blind Method KW - Humans KW - Adult KW - Cross-Over Studies KW - Male KW - Female KW - Substance-Related Disorders -- physiopathology KW - Smoking -- physiopathology KW - Hydromorphone -- therapeutic use KW - Substance-Related Disorders -- drug therapy KW - Smoking -- psychology KW - Substance-Related Disorders -- psychology KW - Smoking -- drug therapy KW - Cyclazocine -- therapeutic use KW - Residential Treatment -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71856482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+biochemistry%2C+and+behavior&rft.atitle=A+laboratory+study+of+hydromorphone+and+cyclazocine+on+smoking+behavior+in+residential+polydrug+users.&rft.au=Pickworth%2C+Wallace+B%3BLee%2C+Eun+M%3BAbreu%2C+Mary+E%3BUmbricht%2C+Annie%3BPreston%2C+Kenzie+L&rft.aulast=Pickworth&rft.aufirst=Wallace&rft.date=2004-04-01&rft.volume=77&rft.issue=4&rft.spage=711&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-16 N1 - Date created - 2004-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Successes and risks of gene therapy in primary immunodeficiencies. AN - 71849679; 15100660 AB - Several primary immunodeficiencies are under consideration for gene therapy approaches because of limitations of current standard treatment. Many primary immunodeficiencies are caused by defects in single genes expressed in blood cells; thus addition of a correct copy of the gene to hematopoietic stem cells (HSCs) can generate immune cells with restored function. HSCs can be removed from a patient, treated outside the body, and reinfused. In the last decade, significant improvements have been made in transferring genes by means of retroviruses to HSCs in vitro, and gene therapy trials for patients with X-linked severe combined immunodeficiency (XSCID) and adenosine deaminase-deficient severe combined immunodeficiency have restored immune competence. Gene therapy is actively being pursued in other immunodeficiency disorders, including chronic granulomatous disease and Wiskott-Aldrich syndrome. However, enthusiasm for the correction of XSCID by means of gene therapy has been tempered by the occurrence of 2 cases of leukemia in gene therapy recipients caused by insertion of the retroviral vector in or near the oncogene LMO2. The likelihood of retroviral insertional mutagenesis was estimated to be very low in the past on the basis of theoretic calculations and the absence of observed malignancies in animal studies and early clinical trials. Emerging new findings on retroviral integration both in the patients with XSCID and experimental animals now indicate that the insertion of retroviral sequences into the genome carries significant risk. Understanding the magnitude of risk is now a priority so that safety can be improved for future gene therapy clinical trials. JF - The Journal of allergy and clinical immunology AU - Chinen, Javier AU - Puck, Jennifer M AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, NIH Bldg. 49, 49 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 595 EP - 603; quiz 604 VL - 113 IS - 4 SN - 0091-6749, 0091-6749 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Treatment Outcome KW - Leukemia -- etiology KW - Genetic Therapy -- adverse effects KW - Immunologic Deficiency Syndromes -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71849679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Successes+and+risks+of+gene+therapy+in+primary+immunodeficiencies.&rft.au=Chinen%2C+Javier%3BPuck%2C+Jennifer+M&rft.aulast=Chinen&rft.aufirst=Javier&rft.date=2004-04-01&rft.volume=113&rft.issue=4&rft.spage=595&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 - 2004-05-13 N1 - Date created - 2004-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitivity and predictivity in immunotoxicity testing: immune endpoints and disease resistance. AN - 71846343; 15093255 AB - In spite of extensive laboratory data on the effects of chemicals and drugs on immunologic parameters in laboratory animals, and a well established correlation between suppression of immune function and increased incidence and/or severity of certain infectious and neoplastic diseases, interpreting data from experimental immunotoxicology studies for risk assessment purposes has proved challenging. This is particularly true when the immunological effects are minimal-to-moderate in nature, as might be expected from inadvertent chemical exposures. This review examines the methods used to evaluate immune responses in laboratory rodents and their utility to predict disease outcomes. The available data suggest that if a large enough population is exposed and that the challenge dose or virulence of pathogenic organisms or tumor cells is sufficient, small changes in immune surveillance could increase the background incidence and burden of disease in the human population. JF - Toxicology letters AU - Germolec, D R AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, USA. germolec@niehs.nih.gov Y1 - 2004/04/01/ PY - 2004 DA - 2004 Apr 01 SP - 109 EP - 114 VL - 149 IS - 1-3 SN - 0378-4274, 0378-4274 KW - Immunotoxins KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Endpoint Determination KW - Humans KW - Mice KW - Immunotoxins -- toxicity KW - Immunity, Innate -- drug effects KW - Immunity -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71846343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sensitivity+and+predictivity+in+immunotoxicity+testing%3A+immune+endpoints+and+disease+resistance.&rft.au=Germolec%2C+D+R&rft.aulast=Germolec&rft.aufirst=D&rft.date=2004-04-01&rft.volume=149&rft.issue=1-3&rft.spage=109&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 - 2004-05-24 N1 - Date created - 2004-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aryl-hydrocarbon receptor-dependent pathway and toxic effects of TCDD in humans: a population-based study in Seveso, Italy. AN - 71845784; 15093275 AB - Approximately 20 years after the Seveso, Italy accident, we conducted a population-based study to evaluate the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure upon immune and mechanistically based biomarkers of dioxin response in humans. TCDD toxic effects are known to be mediated by the aryl-hydrocarbon receptor (AhR). We randomly selected 62 study subjects from the highest exposed zones and 59 from the surrounding non-contaminated area. Current lipid-adjusted plasma TCDD concentrations in these subjects ranged from 3.5 to 90 ng/kg (or ppt) and were negatively associated with plasma IgG concentrations (r=-0.35; P = 0.0002). The expression of genes in the AhR-dependent pathway, including AhR, aryl-hydrocarbon receptor nuclear translocator (ARNT), CYP1A1, and CYP1B1 transcripts, and the CYP1A1-associated 7-ethoxyresorufin-O-deethylase (EROD) activity was measured in lymphocytes. AhR mRNA levels in uncultured lymphocytes were negatively associated with plasma TCDD (P=0.03). When mitogen-induced lymphocytes were cultured with 10nM TCDD, all AhR-dependent genes were induced 1.2- to 13-fold. In these cells, plasma TCDD was associated with decreased EROD activity. Markers within the AhR pathway were correlated with one another. Our findings suggest the presence of long-term effects in the subjects exposed to TCDD after the Seveso accident. JF - Toxicology letters AU - Baccarelli, Andrea AU - Pesatori, Angela C AU - Masten, Scott A AU - Patterson, Donald G AU - Needham, Larry L AU - Mocarelli, Paolo AU - Caporaso, Neil E AU - Consonni, Dario AU - Grassman, Jean A AU - Bertazzi, Pier Alberto AU - Landi, Maria Teresa AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892-7236, USA. baccarea@mail.nih.gov Y1 - 2004/04/01/ PY - 2004 DA - 2004 Apr 01 SP - 287 EP - 293 VL - 149 IS - 1-3 SN - 0378-4274, 0378-4274 KW - ARNT protein, human KW - 0 KW - Biomarkers KW - Complement C3 KW - Complement C4 KW - DNA-Binding Proteins KW - Environmental Pollutants KW - Immunoglobulins KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - Transcription Factors KW - Aryl Hydrocarbon Receptor Nuclear Translocator KW - 138391-32-9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1B1 KW - Index Medicus KW - Immunoglobulins -- analysis KW - Humans KW - Body Burden KW - RNA, Messenger -- analysis KW - Complement C4 -- analysis KW - Aged KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Transcription Factors -- biosynthesis KW - RNA, Messenger -- biosynthesis KW - Cytochrome P-450 CYP1A1 -- biosynthesis KW - Complement C3 -- analysis KW - In Vitro Techniques KW - Adult KW - Lymphocytes -- enzymology KW - Population KW - Middle Aged KW - Italy -- epidemiology KW - Male KW - Female KW - Aryl Hydrocarbon Hydroxylases -- biosynthesis KW - Environmental Pollutants -- toxicity KW - Receptors, Aryl Hydrocarbon -- physiology KW - Receptors, Aryl Hydrocarbon -- biosynthesis KW - Polychlorinated Dibenzodioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71845784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aryl-hydrocarbon+receptor-dependent+pathway+and+toxic+effects+of+TCDD+in+humans%3A+a+population-based+study+in+Seveso%2C+Italy.&rft.au=Baccarelli%2C+Andrea%3BPesatori%2C+Angela+C%3BMasten%2C+Scott+A%3BPatterson%2C+Donald+G%3BNeedham%2C+Larry+L%3BMocarelli%2C+Paolo%3BCaporaso%2C+Neil+E%3BConsonni%2C+Dario%3BGrassman%2C+Jean+A%3BBertazzi%2C+Pier+Alberto%3BLandi%2C+Maria+Teresa&rft.aulast=Baccarelli&rft.aufirst=Andrea&rft.date=2004-04-01&rft.volume=149&rft.issue=1-3&rft.spage=287&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 - 2004-05-24 N1 - Date created - 2004-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of GLUR2 alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor subunit differentially affects remaining synaptic glutamate receptors in cerebellum and cochlear nuclei. AN - 71843844; 15090029 AB - The alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) type of ionotropic glutamate receptor is the major mediator of fast neurotransmission in the brain and spinal cord. Most AMPA receptors are impermeable to calcium because they contain the GluR2 subunit. However, some AMPA receptors lack GluR2 and pass calcium which can mediate synaptic plasticity and, in excess, neurotoxicity. Previously, we showed a decrease in the density of synaptic AMPA receptors in the hippocampus of mice lacking GluR2. In this study, using these GluR2-lacking mice, we examined other areas of the brain that differ in the amount of GluR2 normally present. Like hippocampal spines, cerebellar Purkinje spines normally express AMPA receptors with high GluR2 and showed a decrease in synaptic AMPA receptors in mutant mice. In contrast, neurons that normally express AMPA receptors with little or no GluR2, such as in the anteroventral cochlear nucleus, showed no decrease in AMPA receptors and even showed an increase in one AMPA receptor subunit. These two different patterns may relate to preadaptations to prevent calcium neurotoxicity; such mechanisms might be absent in Purkinje and hippocampal spines so that these neurons must decrease their total expression of synaptic AMPA receptors (calcium permeable in mutant mice) to prevent calcium neurotoxicity. In addition, we found that another glutamate receptor, GluRdelta2, which is abundant only in parallel fibre synapses on Purkinje cells and in the dorsal cochlear nucleus, is up-regulated at these synapses in mutant mice; this probably reflects some change in GluRdelta2 targeting to these synapses. JF - The European journal of neuroscience AU - Petralia, Ronald S AU - Sans, Nathalie AU - Wang, Ya-Xian AU - Vissel, Bryce AU - Chang, Kai AU - Noben-Trauth, Konrad AU - Heinemann, Stephen F AU - Wenthold, Robert J AD - Laboratory of Neurochemistry, NIDCD/NIH, 50/4142, 50 South Drive MSC 8027, Bethesda, MD 20892-8027, USA. petralia@nidcd.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 2017 EP - 2029 VL - 19 IS - 8 SN - 0953-816X, 0953-816X KW - Receptors, AMPA KW - 0 KW - Receptors, Glutamate KW - glutamate receptor ionotropic, AMPA 2 KW - Index Medicus KW - Animals KW - Receptors, Glutamate -- analysis KW - Receptors, Glutamate -- biosynthesis KW - Mice KW - Mice, Knockout KW - Receptors, AMPA -- deficiency KW - Synapses -- ultrastructure KW - Receptors, AMPA -- analysis KW - Cochlear Nucleus -- chemistry KW - Cerebellum -- chemistry KW - Receptors, AMPA -- genetics KW - Cochlear Nucleus -- ultrastructure KW - Cochlear Nucleus -- metabolism KW - Synapses -- metabolism KW - Cerebellum -- ultrastructure KW - Synapses -- chemistry KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71843844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+European+journal+of+neuroscience&rft.atitle=Loss+of+GLUR2+alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic+acid+receptor+subunit+differentially+affects+remaining+synaptic+glutamate+receptors+in+cerebellum+and+cochlear+nuclei.&rft.au=Petralia%2C+Ronald+S%3BSans%2C+Nathalie%3BWang%2C+Ya-Xian%3BVissel%2C+Bryce%3BChang%2C+Kai%3BNoben-Trauth%2C+Konrad%3BHeinemann%2C+Stephen+F%3BWenthold%2C+Robert+J&rft.aulast=Petralia&rft.aufirst=Ronald&rft.date=2004-04-01&rft.volume=19&rft.issue=8&rft.spage=2017&rft.isbn=&rft.btitle=&rft.title=The+European+journal+of+neuroscience&rft.issn=0953816X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-18 N1 - Date created - 2004-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9 tetrahydrocannabinol (THC) in squirrel monkeys. AN - 71832148; 14668977 AB - Experimental evidence from animal studies suggests reciprocal functional interactions between endogenous brain cannabinoid and opioid systems. There is recent evidence for a role of the opioid system in the modulation of the reinforcing effects of synthetic cannabinoid CB1 receptor agonists in rodents. Since Delta(9)-tetrahydrocannabinol (THC), the natural psychoactive ingredient in marijuana, is actively and persistently self-administered by squirrel monkeys, this provides an opportunity to directly study involvement of opioid systems in the reinforcing effects of THC in non-human primates. To study the effects of naltrexone, an opioid antagonist, on THC self-administration behavior in squirrel monkeys. Monkeys pressed a lever for intravenous injections of THC under a ten-response, fixed-ratio (FR) schedule with a 60-s time-out after each injection. Effects of pre-session treatment with naltrexone (0.03-0.3 mg/kg intramuscularly, 15 min before session) for 5 consecutive days on self-administration of different doses of THC (2-8 microg/kg per injection) were studied. Self-administration responding for THC was significantly reduced by pretreatment with 0.1 mg/kg naltrexone for five consecutive daily sessions. Naltrexone pretreatment had no significant effect on cocaine self-administration responding under identical conditions. Self-administration behavior under a fixed-ratio schedule of intravenous THC injection was markedly reduced by daily pre-session treatment with naltrexone, but remained above saline self-administration levels. These findings demonstrate for the first time the modulation of the reinforcing effects of THC by an opioid antagonist in a non-human primate model of marijuana abuse. JF - Psychopharmacology AU - Justinova, Zuzana AU - Tanda, Gianluigi AU - Munzar, Patrik AU - Goldberg, Steven R AD - Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 186 EP - 194 VL - 173 IS - 1-2 SN - 0033-3158, 0033-3158 KW - Analgesics, Non-Narcotic KW - 0 KW - Anesthetics, Local KW - Narcotic Antagonists KW - Naltrexone KW - 5S6W795CQM KW - Dronabinol KW - 7J8897W37S KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Saimiri KW - Behavior, Animal -- drug effects KW - Animals KW - Drug Interactions KW - Self Administration KW - Reinforcement Schedule KW - Anesthetics, Local -- pharmacology KW - Dose-Response Relationship, Drug KW - Cocaine -- pharmacology KW - Male KW - Conditioning, Operant -- drug effects KW - Analgesics, Non-Narcotic -- pharmacology KW - Dronabinol -- pharmacology KW - Reinforcement (Psychology) KW - Naltrexone -- pharmacology KW - Narcotic Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71832148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+opioid+antagonist+naltrexone+reduces+the+reinforcing+effects+of+Delta+9+tetrahydrocannabinol+%28THC%29+in+squirrel+monkeys.&rft.au=Justinova%2C+Zuzana%3BTanda%2C+Gianluigi%3BMunzar%2C+Patrik%3BGoldberg%2C+Steven+R&rft.aulast=Justinova&rft.aufirst=Zuzana&rft.date=2004-04-01&rft.volume=173&rft.issue=1-2&rft.spage=186&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-06 N1 - Date created - 2004-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Can HIV be Cured? Mechanisms of HIV persistence and strategies to combat it. AN - 71814635; 15078175 AB - Stable remission is the ultimate goal of HIV therapy. A review of recent studies on the ability of HIV to persist despite highly active antiretroviral therapy (HAART) and immune stimulation suggests that achieving this goal will require four developments in basic and clinical science. First, more effective antiretroviral therapies, targeted at proteins other than reverse transcriptase and protease, in order to eliminate the cryptic replication that continues despite best available HAART. Second, agents that activate latent HIV gene expression in quiescent CD4 memory T cells, thereby exposing this viral reservoir to therapeutic intervention by a "shock and kill" strategy. Third, molecules such as immunotoxins that specifically recognize HIV-encoded membrane proteins and thereby potentiate the destruction of infected cells. Fourth, and still most distant, novel approaches such as genetically engineered cytotoxic T lymphocytes or anti-HIV microbes to suppress rekindling of infection by residual virus sequestered in anatomical and cellular reservoirs. Although each of these steps will be difficult to achieve, the many benefits of a cure for HIV make this a worthwhile pursuit. JF - Current HIV research AU - Hamer, Dean H AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bldg. 37, Rm. 60002, Bethesda, MD 20892, USA. DeanH@helix.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 99 EP - 111 VL - 2 IS - 2 SN - 1570-162X, 1570-162X KW - Anti-HIV Agents KW - 0 KW - Immunotoxins KW - Index Medicus KW - Virus Activation -- drug effects KW - Anti-HIV Agents -- therapeutic use KW - Virus Replication -- drug effects KW - Virus Latency KW - Humans KW - Anti-HIV Agents -- pharmacology KW - Immunotoxins -- therapeutic use KW - Immunity KW - HIV -- growth & development KW - HIV -- drug effects KW - HIV Infections -- virology KW - HIV -- immunology KW - HIV Infections -- therapy KW - HIV Infections -- immunology KW - Antiretroviral Therapy, Highly Active UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71814635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+HIV+research&rft.atitle=Can+HIV+be+Cured%3F+Mechanisms+of+HIV+persistence+and+strategies+to+combat+it.&rft.au=Hamer%2C+Dean+H&rft.aulast=Hamer&rft.aufirst=Dean&rft.date=2004-04-01&rft.volume=2&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Current+HIV+research&rft.issn=1570162X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-14 N1 - Date created - 2004-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peritonectomy and intraperitoneal hyperthermic perfusion (IPHP): a strategy that has confirmed its efficacy in patients with pseudomyxoma peritonei. AN - 71813624; 15070599 AB - Pseudomyxoma peritonei (PMP) is a rare disease with a poor prognosis characterized by a complete redistribution of mucin within the peritoneal cavity. The aim of this multicentric study was to evaluate the survival, morbidity, toxicity, and mortality of patients with PMP treated by cytoreductive surgery (CRS) with intraperitoneal hyperthermic perfusion (IPHP). Thirty-three patients with PMP (21 males and 12 females) were enrolled in a phase II clinical trial. One patient underwent surgery twice because of disease recurrence. CRS was performed with peritonectomy procedures. The closed abdomen technique was employed for IPHP with use of cisplatin (25 mg/m2/L) plus mitomycin-C (3.3 mg/m2/L) for 60 minutes under hyperthermic conditions (42.5 degrees C). Thirty-one patients (92%) were optimally cytoreduced. Five-year overall survival, progression-free survival, and locoregional progression-free survival rates were 97%, 43%, and 59%, respectively. Grade II and grade III morbidity was observed in 5 patient (15%) and 6 patients (18%), respectively. There was one treatment-related death (3%), 21 days after treatment. CRS associated with IPHP permitted complete tumor removal with an acceptable morbidity and mortality for patients with PMP. This study confirms the efficacy of the combined treatment in terms of long-term survival and local disease control. JF - Annals of surgical oncology AU - Deraco, Marcello AU - Baratti, Dario AU - Inglese, Maria Grazia AU - Allaria, Biagino AU - Andreola, Salvatore AU - Gavazzi, Cecilia AU - Kusamura, Shigeki AD - Department of Surgery, Melanoma and Sarcoma Unit, National Cancer Institute of Milan, Italy. marcello.deraco@istitutotumori.mi.it Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 393 EP - 398 VL - 11 IS - 4 SN - 1068-9265, 1068-9265 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Peritoneum -- surgery KW - Humans KW - Treatment Outcome KW - Disease Progression KW - Infusions, Parenteral KW - Male KW - Female KW - Survival Analysis KW - Pseudomyxoma Peritonei -- therapy KW - Pseudomyxoma Peritonei -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Hyperthermia, Induced KW - Adenocarcinoma, Mucinous -- surgery KW - Adenocarcinoma, Mucinous -- drug therapy KW - Pseudomyxoma Peritonei -- surgery KW - Adenocarcinoma, Mucinous -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71813624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgical+oncology&rft.atitle=Peritonectomy+and+intraperitoneal+hyperthermic+perfusion+%28IPHP%29%3A+a+strategy+that+has+confirmed+its+efficacy+in+patients+with+pseudomyxoma+peritonei.&rft.au=Deraco%2C+Marcello%3BBaratti%2C+Dario%3BInglese%2C+Maria+Grazia%3BAllaria%2C+Biagino%3BAndreola%2C+Salvatore%3BGavazzi%2C+Cecilia%3BKusamura%2C+Shigeki&rft.aulast=Deraco&rft.aufirst=Marcello&rft.date=2004-04-01&rft.volume=11&rft.issue=4&rft.spage=393&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-22 N1 - Date created - 2004-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients. AN - 71811329; 15069388 AB - Patients who received pituitary-derived growth hormone (GH) are at excess risk of mortality from Creutzfeldt-Jakob disease. We investigated whether they were at increased risk of death from other conditions, particularly preventable conditions. A cohort (N=6107) from known US pituitary-derived GH recipients (treated 1963-1985) was studied. Deaths were identified by reports from physicians and parents and the National Death Index. Rates were compared with the expected rates for the US population standardized for race, age, and sex. There were 433 deaths versus 114 expected (relative risk [RR], 3.8; 95% confidence interval [CI], 3.4-4.2; P<.0001) from 1963 through 1996. Risk was increased in subjects with GH deficiency caused by any tumor (RR, 10.4; 95% CI, 9.1-12.0; P<.0001). Surprisingly, subjects with hypoglycemia treated within the first 6 months of life were at extremely high risk (RR, 18.3; 95% CI, 9.2-32.8; P<.0001), as were all subjects with adrenal insufficiency (RR, 7.1; 95% CI, 6.2-8.2; P<.0001). A quarter of all deaths were sudden and unexpected. Of the 26 cases of Creutzfeldt-Jakob disease, four cases have died since 2000. The death rate in pituitary-derived GH recipients was almost four times the expected rate. Replacing pituitary-derived GH with recombinant GH has eliminated only the risk of Creutzfeldt-Jakob disease. Hypoglycemia and adrenal insufficiency accounted for far more mortality than Creutzfeldt-Jakob disease. The large number of potentially preventable deaths in patients with adrenal insufficiency and hypoglycemia underscores the importance of early intervention when infection occurs in patients with adrenal insufficiency, and aggressive treatment of panhypopituitarism. JF - The Journal of pediatrics AU - Mills, James L AU - Schonberger, Lawrence B AU - Wysowski, Diane K AU - Brown, Paul AU - Durako, Stephen J AU - Cox, Christopher AU - Kong, Fanhui AU - Fradkin, Judith E AD - National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, 6100 Building Room 7B03, Bethesda, MD 20892, USA. jamesmills@nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 430 EP - 436 VL - 144 IS - 4 SN - 0022-3476, 0022-3476 KW - Human Growth Hormone KW - 12629-01-5 KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Neoplasms -- mortality KW - Humans KW - Child KW - Age Distribution KW - Child, Preschool KW - Neoplasms -- complications KW - Survival Rate KW - Risk Factors KW - Cohort Studies KW - Death Certificates KW - Death, Sudden -- epidemiology KW - Epilepsy -- mortality KW - United States -- epidemiology KW - Female KW - Male KW - Creutzfeldt-Jakob Syndrome -- chemically induced KW - Adrenal Insufficiency -- mortality KW - Hypoglycemia -- etiology KW - Human Growth Hormone -- deficiency KW - Adrenal Insufficiency -- drug therapy KW - Hypoglycemia -- mortality KW - Adrenal Insufficiency -- etiology KW - Human Growth Hormone -- adverse effects KW - Creutzfeldt-Jakob Syndrome -- mortality KW - Hypoglycemia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71811329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatrics&rft.atitle=Long-term+mortality+in+the+United+States+cohort+of+pituitary-derived+growth+hormone+recipients.&rft.au=Mills%2C+James+L%3BSchonberger%2C+Lawrence+B%3BWysowski%2C+Diane+K%3BBrown%2C+Paul%3BDurako%2C+Stephen+J%3BCox%2C+Christopher%3BKong%2C+Fanhui%3BFradkin%2C+Judith+E&rft.aulast=Mills&rft.aufirst=James&rft.date=2004-04-01&rft.volume=144&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pediatrics&rft.issn=00223476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-01 N1 - Date created - 2004-04-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Pediatr. 2004 Apr;144(4):415-6 [15069384] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Childhood tumor risk after treatment with ovulation-stimulating drugs. AN - 71805819; 15066468 AB - To assess childhood cancer risk among children conceived following the use of ovulation-stimulating drugs. Record linkage study. Infertility patients and their offspring as identified through medical records. Cohort of 30,364 Danish women evaluated for infertility beginning in the early 1960s. Standardized incidence ratios (SIRs) compared cancer incidence in the children to the Danish population. Case-cohort techniques calculated rate ratios (RRs) according to prior maternal drug exposures. A total of 51 cancers were identified among the study children, resulting in an SIR of 1.14 (95% confidence interval [CI] 0.8-1.5). Usage of any fertility drug was associated with an RR of 0.82 (95% CI 0.4-1.6) and clomiphene citrate with an RR of 0.77 (95% CI 0.4-1.6). Tumors occurring early in life and nonhematopoietic malignancies (including neuroblastomas) were not associated with drug usage. Nonsignificant elevations in the risk of cancers occurring later in life, especially childhood hematopoietic malignancies (RR for use of any ovulation-stimulating drugs of 2.30, 95% CI 0.8-6.6), may have been related to underlying reasons for medication usage. Although the findings of this study are reassuring, additional adequately powered studies should continue monitoring the effects of ovulation-stimulating drugs on specific tumors, including hematopoietic malignancies. JF - Fertility and sterility AU - Brinton, Louise A AU - Krüger Kjaer, Susanne AU - Thomsen, Birthe L AU - Sharif, Heidi F AU - Graubard, Barry I AU - Olsen, Jørgen H AU - Bock, Johannes E AD - Division of Cancer Epidemiology, National Cancer Institute, Bethesda, Maryland, USA. brinton@nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 1083 EP - 1091 VL - 81 IS - 4 SN - 0015-0282, 0015-0282 KW - Fertility Agents, Female KW - 0 KW - Index Medicus KW - Risk KW - Humans KW - Cohort Studies KW - Adult KW - Male KW - Female KW - Pregnancy KW - Child, Preschool KW - Infertility, Female -- drug therapy KW - Neoplasms -- chemically induced KW - Ovulation Induction -- adverse effects KW - Fertility Agents, Female -- adverse effects KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71805819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fertility+and+sterility&rft.atitle=Childhood+tumor+risk+after+treatment+with+ovulation-stimulating+drugs.&rft.au=Brinton%2C+Louise+A%3BKr%C3%BCger+Kjaer%2C+Susanne%3BThomsen%2C+Birthe+L%3BSharif%2C+Heidi+F%3BGraubard%2C+Barry+I%3BOlsen%2C+J%C3%B8rgen+H%3BBock%2C+Johannes+E&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2004-04-01&rft.volume=81&rft.issue=4&rft.spage=1083&rft.isbn=&rft.btitle=&rft.title=Fertility+and+sterility&rft.issn=00150282&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-24 N1 - Date created - 2004-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factors, insulin-like growth factor-binding proteins, and endometrial cancer in postmenopausal women: results from a U.S. case-control study. AN - 71803095; 15066926 AB - To assess whether circulating insulin-like growth factor-1 (IGF-1), IGF-2, insulin-like growth factor-binding protein-1 (IGFBP-1), or IGFBP-3 were associated with endometrial cancer in postmenopausal women. Between 1987 and 1990, we conducted a case-control study of 405 women with endometrial cancer and 297 matched population-based controls. This analysis included 174 postmenopausal cases and 136 controls. In logistic regression models adjusted for potential confounders, higher IGF-1 levels were not positively associated with endometrial cancer: odds ratio (OR) for the highest tertile versus the lowest tertile = 0.63, 95% confidence interval (CI) = 0.30-1.32. Endometrial cancer was inversely associated with IGF-2 (OR for the highest tertile = 0.35, 95% CI = 0.18-0.69) and IGFBP-3 (OR for the highest tertile = 0.40, 95% CI = 0.21-0.77), and not associated with IGFBP-1. Serum IGF-1, IGF-2, and IGFBP-3, but not IGFBP-1, were inversely associated with endometrial cancer in postmenopausal women. These associations and the potential role of the IGF system in endometrial proliferation and carcinogenesis warrant further research. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Lacey, James V AU - Potischman, Nancy AU - Madigan, M Patricia AU - Berman, Michael L AU - Mortel, Rodrigue AU - Twiggs, Leo B AU - Barrett, Rolland J AU - Wilbanks, George D AU - Lurain, John R AU - Fillmore, Capri-Mara AU - Sherman, Mark E AU - Brinton, Louise A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, MSC 7234, Rockville, MD 20852-7234, USA. jimlacey@nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 607 EP - 612 VL - 13 IS - 4 SN - 1055-9965, 1055-9965 KW - Insulin-Like Growth Factor Binding Protein 1 KW - 0 KW - Insulin-Like Growth Factor Binding Protein 3 KW - Insulin-Like Growth Factor Binding Proteins KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Index Medicus KW - Humans KW - Aged KW - Insulin-Like Growth Factor I -- metabolism KW - Insulin-Like Growth Factor Binding Proteins -- blood KW - Insulin-Like Growth Factor II -- metabolism KW - Postmenopause KW - Logistic Models KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Insulin-Like Growth Factor Binding Protein 1 -- blood KW - Insulin-Like Growth Factor Binding Protein 3 -- blood KW - United States -- epidemiology KW - Female KW - Endometrial Neoplasms -- epidemiology KW - Endometrial Neoplasms -- blood KW - Endometrial Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71803095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Insulin-like+growth+factors%2C+insulin-like+growth+factor-binding+proteins%2C+and+endometrial+cancer+in+postmenopausal+women%3A+results+from+a+U.S.+case-control+study.&rft.au=Lacey%2C+James+V%3BPotischman%2C+Nancy%3BMadigan%2C+M+Patricia%3BBerman%2C+Michael+L%3BMortel%2C+Rodrigue%3BTwiggs%2C+Leo+B%3BBarrett%2C+Rolland+J%3BWilbanks%2C+George+D%3BLurain%2C+John+R%3BFillmore%2C+Capri-Mara%3BSherman%2C+Mark+E%3BBrinton%2C+Louise+A&rft.aulast=Lacey&rft.aufirst=James&rft.date=2004-04-01&rft.volume=13&rft.issue=4&rft.spage=607&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 - 2005-02-14 N1 - Date created - 2004-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phthalate exposure and pulmonary function. AN - 71801654; 15064163 AB - Exposure to phthalates is widespread because of their use in plastics, cosmetics, and other consumer products. Phthalate exposure has been associated with adverse respiratory outcomes in children. With urinary phthalate measures, we assessed the association between phthalate exposure and four pulmonary function parameters [forced vital capacity (FVC), forced expiratory volume at 1 sec (FEV1), peak expiratory flow (PEF), and maximum mid-expiratory flow] among the 240 adult Third National Health and Nutrition Examination Survey (NHANES III) participants with urinary phthalate data. Linear regression models controlled for race, age, age squared, standing height, body mass index, cumulative smoking, and current smoking. Monobutyl phthalate (MBP) was significantly associated with decrements in three measures of pulmonary function (FVC, FEV1, PEF) in males but not in females. For a change from the 25th to the 75th percentile in MBP level among men, FEV1 decreased 112 mL (SE = 51, p = 0.03). Monoethyl phthalate (MEP) was associated with lower FVC and FEV1 values in men. Monoethylhexyl phthalate (MEHP), the metabolite of the plasticizer commonly used in medical tubing, was not adversely associated with any of the pulmonary function parameters evaluated. Our results suggest that MBP and MEP, but not MEHP, may influence pulmonary function among adult males. JF - Environmental health perspectives AU - Hoppin, Jane A AU - Ulmer, Ross AU - London, Stephanie J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, PO Box 12233, Research Triangle Park, NC 27709-2233, USA. hoppin1@niehs.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 571 EP - 574 VL - 112 IS - 5 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Phthalic Acids KW - Index Medicus KW - Respiratory Function Tests KW - Sex Factors KW - Humans KW - Linear Models KW - Adult KW - Environmental Exposure KW - Nutrition Surveys KW - Middle Aged KW - Male KW - Female KW - Lung -- drug effects KW - Lung -- physiology KW - Phthalic Acids -- urine KW - Phthalic Acids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71801654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phthalate+exposure+and+pulmonary+function.&rft.au=Hoppin%2C+Jane+A%3BUlmer%2C+Ross%3BLondon%2C+Stephanie+J&rft.aulast=Hoppin&rft.aufirst=Jane&rft.date=2004-04-01&rft.volume=112&rft.issue=5&rft.spage=571&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 - 2004-11-10 N1 - Date created - 2004-04-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Acta Paediatr. 1999 Oct;88(10):1174-5 [10565474] Am J Public Health. 1999 Feb;89(2):188-92 [9949747] Am J Public Health. 2000 May;90(5):797-9 [10800434] Anal Chem. 2000 Sep 1;72(17):4127-34 [10994974] Environ Health Perspect. 2000 Oct;108(10):979-82 [11049818] Am J Ind Med. 2001 Jan;39(1):100-11 [11148020] J Air Waste Manag Assoc. 2001 Apr;51(4):499-513 [11321907] Occup Environ Med. 2001 Aug;58(8):496-503 [11452043] Int Arch Occup Environ Health. 2001 Sep;74(7):489-94 [11697452] Occup Environ Med. 2001 Dec;58(12):780-5 [11706144] Environ Health Perspect. 2002 May;110(5):515-8 [12003755] Environ Health Perspect. 2002 Aug;110(8):765-70 [12153756] Epidemiology. 2003 Jan;14(1):37-44 [12500044] Occup Environ Med. 2003 Feb;60(2):115-21 [12554839] Occup Environ Med. 2003 Nov;60(11):831-40 [14573713] Environ Sci Technol. 2003 Oct 15;37(20):4543-53 [14594359] Environ Health Perspect. 1997 Sep;105(9):972-8 [9374082] Thorax. 2000 Apr;55(4):277-82 [10722766] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Co-occurrence of 12-month alcohol and drug use disorders and personality disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. AN - 71800396; 15066894 AB - Very little information is available on the co-occurrence of different personality disorders (PDs) and alcohol and drug use disorders in the US population. To present national data on sex differences in the co-occurrence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol and drug use disorders and 7 of the 10 DSM-IV PDs. Face-to-face interviews conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43 093). The United States and the District of Columbia, including Alaska and Hawaii. Household and group-quarters residents, aged 18 years and older. Among individuals with a current alcohol use disorder, 28.6% (95% confidence interval [CI], 26.7-30.6) had at least 1 PD, whereas 47.7% (95% CI, 43.9-51.6) of those with a current drug use disorder had at least 1 PD. Further, 16.4% (95% CI, 15.1-17.6) of individuals with at least 1 PD had a current alcohol use disorder and 6.5% (95% CI, 5.7-7.3) had a current drug use disorder. Associations between PDs and alcohol and drug use disorders were overwhelmingly positive and significant (P <.05). Overall, alcohol use disorders were most strongly related to antisocial (odds ratio [OR], 4.8; 95% CI, 4.1-5.6), histrionic (OR, 4.7; 95% CI, 3.8-5.8), and dependent (OR, 3.0; 95% CI, 1.9-4.8) PDs. Drug use disorders also were more highly associated with antisocial (OR, 11.8; 95% CI, 9.7-14.3), histrionic (OR, 8.0; 95% CI, 6.0-10.7), and dependent (OR, 11.6; 95% CI, 7.1-19.1) PDs. Associations between obsessive-compulsive, histrionic, schizoid, and antisocial PDs and specific alcohol and drug use disorders were significantly stronger (P <.04) among women than men, whereas the association between dependent PD and drug dependence was significantly greater (P <.04) among men than women. The co-occurrence of PDs with alcohol and drug use disorders is pervasive in the US population. Results highlight the need for further research on the underlying structure of these disorders and the treatment implications of these disorders when comorbid. JF - Archives of general psychiatry AU - Grant, Bridget F AU - Stinson, Frederick S AU - Dawson, Deborah A AU - Chou, S Patricia AU - Ruan, W June AU - Pickering, Roger P AD - Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9304, USA. bgrant@willco.niaaa.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 361 EP - 368 VL - 61 IS - 4 SN - 0003-990X, 0003-990X KW - Abridged Index Medicus KW - Index Medicus KW - Odds Ratio KW - Sex Factors KW - Epidemiologic Studies KW - Humans KW - Adult KW - Incidence KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Comorbidity KW - Prevalence KW - Personality Disorders -- epidemiology KW - Substance-Related Disorders -- complications KW - Personality Disorders -- complications KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71800396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Co-occurrence+of+12-month+alcohol+and+drug+use+disorders+and+personality+disorders+in+the+United+States%3A+results+from+the+National+Epidemiologic+Survey+on+Alcohol+and+Related+Conditions.&rft.au=Grant%2C+Bridget+F%3BStinson%2C+Frederick+S%3BDawson%2C+Deborah+A%3BChou%2C+S+Patricia%3BRuan%2C+W+June%3BPickering%2C+Roger+P&rft.aulast=Grant&rft.aufirst=Bridget&rft.date=2004-04-01&rft.volume=61&rft.issue=4&rft.spage=361&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 - 2004-04-27 N1 - Date created - 2004-04-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Evid Based Ment Health. 2004 Nov;7(4):124 [15504812] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis. AN - 71798069; 15059885 AB - p53-mediated apoptosis may involve the induction of redox-controlling genes, resulting in the production of reactive oxygen species. Microarray expression analysis of doxorubicin exposed, related human lymphoblasts, p53 wild-type (WT) Tk6, and p53 mutant WTK1 identified the p53-dependent up-regulation of manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPx). Consensus p53 binding sequences were identified in human MnSOD and GPx promoter regions. A 3-fold increase in the MnSOD promoter activity was observed after the induction of p53 in Li-Fraumeni syndrome (LFS) fibroblast, TR9-7, expressing p53 under the control of a tetracycline-regulated promoter. An increased protein expression of endogenous MnSOD and GPx also positively correlated with the level of p53 induction in TR9-7 cells. However, catalase (CAT) protein expression remained unaltered after p53 induction. We also examined the expression of MnSOD, GPx, and CAT in a panel of normal or LFS fibroblasts, containing either WT or mutant p53. We found increased MnSOD enzymatic activity, MnSOD mRNA expression, and MnSOD and GPx protein in LFS fibroblasts carrying a WT p53 allele when compared with homozygous mutant p53 isogenic cells. The CAT protein level was unchanged in these cells. We observed both the release of cytochrome C and Ca(2+) from the mitochondria into the cytoplasm and an increased frequency of apoptotic cells after p53 induction in the TR9-7 cells that coincided with an increased expression of MnSOD and GPx, and the level of reactive oxygen species. The increase in apoptosis was reduced by the antioxidant N-acetylcysteine. These results identify a novel mechanism of p53-dependent apoptosis in which p53-mediated up-regulation of MnSOD and GPx, but not CAT, produces an imbalance in antioxidant enzymes and oxidative stress. JF - Cancer research AU - Hussain, S Perwez AU - Amstad, Paul AU - He, Peijun AU - Robles, Ana AU - Lupold, Shawn AU - Kaneko, Ichiro AU - Ichimiya, Masato AU - Sengupta, Sagar AU - Mechanic, Leah AU - Okamura, Shu AU - Hofseth, Lorne J AU - Moake, Matthew AU - Nagashima, Makoto AU - Forrester, Kathleen S AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2004/04/01/ PY - 2004 DA - 2004 Apr 01 SP - 2350 EP - 2356 VL - 64 IS - 7 SN - 0008-5472, 0008-5472 KW - RNA, Messenger KW - 0 KW - Reactive Oxygen Species KW - Tumor Suppressor Protein p53 KW - Doxorubicin KW - 80168379AG KW - Cytochromes c KW - 9007-43-6 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 - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Fibroblasts -- enzymology KW - Humans KW - Cytochromes c -- secretion KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Up-Regulation -- physiology KW - Calcium -- metabolism KW - Catalase -- biosynthesis KW - Oxidative Stress -- physiology KW - Doxorubicin -- pharmacology KW - Gene Expression Regulation, Enzymologic -- physiology KW - Enzyme Induction KW - Mitochondria -- secretion KW - Cell Line KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Tumor Suppressor Protein p53 -- physiology KW - Tumor Suppressor Protein p53 -- antagonists & inhibitors KW - Glutathione Peroxidase -- metabolism KW - Apoptosis -- physiology KW - Superoxide Dismutase -- metabolism KW - Superoxide Dismutase -- genetics KW - Glutathione Peroxidase -- biosynthesis KW - Tumor Suppressor Protein p53 -- genetics KW - Glutathione Peroxidase -- genetics KW - Superoxide Dismutase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71798069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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-induced+up-regulation+of+MnSOD+and+GPx+but+not+catalase+increases+oxidative+stress+and+apoptosis.&rft.au=Hussain%2C+S+Perwez%3BAmstad%2C+Paul%3BHe%2C+Peijun%3BRobles%2C+Ana%3BLupold%2C+Shawn%3BKaneko%2C+Ichiro%3BIchimiya%2C+Masato%3BSengupta%2C+Sagar%3BMechanic%2C+Leah%3BOkamura%2C+Shu%3BHofseth%2C+Lorne+J%3BMoake%2C+Matthew%3BNagashima%2C+Makoto%3BForrester%2C+Kathleen+S%3BHarris%2C+Curtis+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=2004-04-01&rft.volume=64&rft.issue=7&rft.spage=2350&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 - 2004-05-19 N1 - Date created - 2004-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - How environmental hazards in childhood have been discovered: carcinogens, teratogens, neurotoxicants, and others. AN - 71796722; 15060186 AB - Review of the literature reveals that environmental hazards cause adverse health effects that include sterility, infertility, embryotoxicity, low birth weight, skin lesions, neurodevelopmental defects, immunologic disorders, cancer, and fear of late effects. They have been identified mostly by astute practitioners but also by a bacteriologist, an animal experimentalist, 5 factory workers in childless marriages, and a tipsy bystander in an economically impoverished area of Baltimore. Dust on a parent's work clothes has transported a hazard at work to a hazard at home (lead, asbestos, and chlordecone). Causality is established by showing a dose-response effect and reproducing the effect in studies of other exposed groups or by using another epidemiologic method, eg, prospective instead of retrospective study. Also, the findings should be biologically plausible and not attributable to a concomitant variable such as cigarette smoking. Contrary to front-page newspaper headlines, incidence rates for childhood leukemia are not rising. Preserving specimens for future studies has been valuable: blood from people who were exposed to dioxin in Seveso, Italy; mummified umbilical cords containing methyl mercury at Minamata Bay, Japan; and Guthrie dried blood spots to screen retrospectively for 43 genetic disorders and a specific prenatal cytogenetic abnormality in some children with 1 form of leukemia. Recommendations are given for enhancing interest in environmental hazards and their discovery by clinicians. JF - Pediatrics AU - Miller, Robert W AD - Clinical Genetics Branch, National Cancer Institute, Bethesda, Maryland, USA. millerro@mail.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 945 EP - 951 VL - 113 IS - 4 Suppl KW - Carcinogens KW - 0 KW - Hazardous Substances KW - Neurotoxins KW - Pesticides KW - Teratogens KW - Abridged Index Medicus KW - Index Medicus KW - Causality KW - Neurotoxins -- history KW - History, 20th Century KW - Humans KW - Child KW - Evidence-Based Medicine -- history KW - Pesticides -- toxicity KW - Epidemiology -- history KW - Neoplasms -- chemically induced KW - Teratogens -- history KW - Teratogens -- toxicity KW - Neurotoxins -- adverse effects KW - Pesticides -- history KW - Carcinogens -- history KW - Carcinogens -- adverse effects KW - Pediatrics -- history KW - Biomedical Research -- history KW - Hazardous Substances -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71796722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=How+environmental+hazards+in+childhood+have+been+discovered%3A+carcinogens%2C+teratogens%2C+neurotoxicants%2C+and+others.&rft.au=Miller%2C+Robert+W&rft.aulast=Miller&rft.aufirst=Robert&rft.date=2004-04-01&rft.volume=113&rft.issue=4+Suppl&rft.spage=945&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-01 N1 - Date created - 2004-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human beta-globin replication initiation region consists of two modular independent replicators. AN - 71796046; 15060158 AB - Previous studies have shown that mammalian cells contain replicator sequences, which can determine where DNA replication initiates. However, the specific sequences that confer replicator activity were not identified. Here we report a detailed analysis of replicator sequences that dictate initiation of DNA replication from the human beta-globin locus. This analysis suggests that the beta-globin replication initiation region contains two adjacent, redundant replicators. Each replicator was capable of initiating DNA replication independently at ectopic sites. Within each of these two replicators, we identified short, discrete, nonredundant sequences, which cooperatively determine replicator activity. Experiments with somatic cell hybrids further demonstrated that the requirements for initiation at ectopic sites were similar to the requirements for initiation within native human chromosomes. The replicator clustering and redundancy exemplified in the human beta-globin locus may account for the extreme difficulty in identifying replicator sequences in mammalian cells and suggest that mammalian replication initiation sites may be determined by cooperative sequence modules. JF - Molecular and cellular biology AU - Wang, Lixin AU - Lin, Chii-Mei AU - Brooks, Sarah AU - Cimbora, Dan AU - Groudine, Mark AU - Aladjem, Mirit I AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 3373 EP - 3386 VL - 24 IS - 8 SN - 0270-7306, 0270-7306 KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Gene Transfer Techniques KW - Humans KW - Molecular Sequence Data KW - Introns KW - Cell Line KW - Regulatory Sequences, Nucleic Acid KW - Replication Origin KW - Globins -- genetics KW - Globins -- metabolism KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71796046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+human+beta-globin+replication+initiation+region+consists+of+two+modular+independent+replicators.&rft.au=Wang%2C+Lixin%3BLin%2C+Chii-Mei%3BBrooks%2C+Sarah%3BCimbora%2C+Dan%3BGroudine%2C+Mark%3BAladjem%2C+Mirit+I&rft.aulast=Wang&rft.aufirst=Lixin&rft.date=2004-04-01&rft.volume=24&rft.issue=8&rft.spage=3373&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 - 2004-05-19 N1 - Date created - 2004-04-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Biochem. 2000;69:829-80 [10966477] Mol Biol Evol. 2000 Jan;17(1):179-88 [10666717] Nucleic Acids Res. 2001 Feb 1;29(3):809-17 [11160905] Mol Cell Biol. 2001 Apr;21(8):2790-801 [11283258] Nucleic Acids Res. 2001 Aug 1;29(15):3181-7 [11470875] Genetics. 2001 Sep;159(1):35-45 [11560885] Science. 2001 Oct 5;294(5540):96-100 [11588251] Mol Cell Biol. 2002 Jan;22(2):442-52 [11756541] Mol Cell Biol. 2002 May;22(9):3053-65 [11940663] Mol Cell Biol. 2002 Jul;22(13):4876-89 [12052893] Mol Cell. 2002 Jul;10(1):207-13 [12150920] EMBO J. 2002 Oct 15;21(20):5567-76 [12374757] Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13693-8 [12370427] J Cell Biochem. 2002;87(3):279-83 [12397609] Mol Cell Biol. 2002 Dec;22(24):8426-37 [12446763] Mol Cell Biol. 2003 Feb;23(3):804-14 [12529386] EMBO J. 2003 Feb 17;22(4):964-74 [12574132] Mol Cell Biol. 2003 Mar;23(5):1832-42 [12589000] Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3281-6 [12629222] Mol Cell Biol. 2003 May;23(10):3536-49 [12724412] Genes Dev. 2003 Aug 1;17(15):1894-908 [12897055] Nature. 1983 Mar 31-Apr 6;302(5907):439-41 [6300683] EMBO J. 1982;1(11):1399-404 [6327267] Mol Cell Biol. 1987 May;7(5):1740-50 [2885742] J Cell Biochem. 1993 May;52(1):23-36 [8320272] EMBO J. 1993 Dec;12(12):4521-31 [8223462] Nature. 1993 Dec 9;366(6455):588-90 [8255298] Curr Opin Genet Dev. 1994 Apr;4(2):196-202 [8032196] Mol Cell Biol. 1994 Sep;14(9):5628-35 [8065299] Mol Cell Biol. 1995 Aug;15(8):4136-48 [7623808] Science. 1995 Nov 3;270(5237):815-9 [7481774] Science. 1995 Nov 10;270(5238):994-7 [7481806] J Cell Physiol. 2000 Aug;184(2):139-50 [10867638] Cell. 1988 Mar 11;52(5):635-8 [3278812] Mol Cell Biol. 1988 May;8(5):2184-94 [3290652] Cell. 1989 Jun 16;57(6):909-20 [2544294] EMBO J. 1989 Dec 20;8(13):4335-44 [2556269] Cell. 1990 Sep 7;62(5):955-65 [2393905] Chromosoma. 1992;102(1 Suppl):S24-31 [1291239] Nat Genet. 1996 Feb;12(2):174-82 [8563756] Genes Dev. 1996 Jul 1;10(13):1595-607 [8682291] J Cell Biochem. 1996 Mar 1;60(3):297-316 [8867806] J Cell Biochem. 1996 Oct;63(1):1-22 [8891900] Science. 1998 Jan 2;279(5347):95-8 [9417033] Methods. 1997 Nov;13(3):211-9 [9441848] Methods. 1997 Nov;13(3):281-92 [9441854] Mol Cell Biol. 1998 Jun;18(6):3266-77 [9584167] Science. 1998 Aug 14;281(5379):1005-9 [9703500] Mol Cell Biol. 1998 Dec;18(12):7294-303 [9819416] Mol Cell. 1998 Dec;2(6):797-806 [9885567] Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):592-7 [9892678] Mol Cell Biol. 1999 Sep;19(9):6098-109 [10454557] Nucleic Acids Res. 1999 Aug 1;27(15):3009-17 [10454594] Mol Cell Biol. 2001 Feb;21(4):1098-110 [11158297] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reconstitution of glucocorticoid receptor-dependent transcription in vivo. AN - 71793512; 15060156 AB - We developed a model system to study glucocorticoid receptor (GR)-mediated chromatin remodeling by the BRG1 complex. Introduction of the BRG1 ATPase into the SW-13 cell line initiates the formation of a functional remodeling complex. This complex is able to induce transcriptional activation from a transiently transfected promoter with wild-type and chromatin-remodeling-deficient BRG1 mutants, suggesting that the complex possesses a coactivator function independent from remodeling. Transactivation from a chromatin template requires the BRG1 remodeling function, which induces regions of hypersensitivity and transcription factor loading onto the integrated MMTV promoter. We report that BRG1 remodeling activity is required for GR-mediated transactivation and that this activity cannot be replaced by other ATP-dependent remodeling proteins. Further characterization of the BRG1-associated factors (BAFs) present in these cells (for example, the expression of BAF250 but not BAF180) reveals that the BAF complex rather than the polybromo-associated BAF complex is the necessary and sufficient chromatin-remodeling component with which the receptor functions in vivo. These results in conjunction with previous findings demonstrate that the GR functions with multiple forms of the SWI/SNF complex in vivo. JF - Molecular and cellular biology AU - Trotter, Kevin W AU - Archer, Trevor K AD - Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 3347 EP - 3358 VL - 24 IS - 8 SN - 0270-7306, 0270-7306 KW - Chromatin KW - 0 KW - Macromolecular Substances KW - Nuclear Proteins KW - Nucleosomes KW - Receptors, Glucocorticoid KW - Transcription Factors KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - SMARCA4 protein, human KW - Smarca4 protein, mouse KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Rats KW - Mammary Tumor Virus, Mouse -- metabolism KW - Animals KW - Promoter Regions, Genetic KW - Humans KW - Nucleosomes -- metabolism KW - Genes, Reporter KW - Adenosine Triphosphatases -- metabolism KW - Cell Line, Tumor KW - Adenosine Triphosphatases -- genetics KW - Mammary Tumor Virus, Mouse -- genetics KW - Nuclear Proteins -- genetics KW - Chromatin -- metabolism KW - Transcription Factors -- metabolism KW - Transcription, Genetic KW - Nuclear Proteins -- metabolism KW - Transcription Factors -- genetics KW - Receptors, Glucocorticoid -- metabolism KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71793512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reconstitution+of+glucocorticoid+receptor-dependent+transcription+in+vivo.&rft.au=Trotter%2C+Kevin+W%3BArcher%2C+Trevor+K&rft.aulast=Trotter&rft.aufirst=Kevin&rft.date=2004-04-01&rft.volume=24&rft.issue=8&rft.spage=3347&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 - 2004-05-19 N1 - Date created - 2004-04-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13015-20 [11078522] Cell. 2000 Nov 10;103(4):667-78 [11106736] Cell. 2000 Dec 8;103(6):843-52 [11136970] J Cell Physiol. 2001 Jan;186(1):136-45 [11147808] Mol Cell. 1999 Jul;4(1):45-54 [10445026] Genes Dev. 1999 Sep 15;13(18):2339-52 [10500090] J Mol Biol. 1999 Oct 22;293(2):187-98 [10529347] Cell Mol Life Sci. 2001 May;58(5-6):673-82 [11437229] Mol Cell Biol. 2001 Aug;21(16):5417-25 [11463824] Mol Biol Cell. 2001 Nov;12(11):3365-74 [11694573] Bioessays. 2001 Dec;23(12):1131-7 [11746232] Nature. 2001 Dec 20-27;414(6866):924-8 [11780067] Curr Opin Genet Dev. 2002 Apr;12(2):142-8 [11893486] Cell. 2002 Feb 22;108(4):475-87 [11909519] FASEB J. 2002 Jun;16(8):761-70 [12039857] Mol Endocrinol. 2002 Jun;16(6):1204-14 [12040008] Annu Rev Biochem. 2002;71:755-81 [12045110] FEBS Lett. 2002 Jun 5;520(1-3):127-32 [12044884] Mol Endocrinol. 2002 Jul;16(7):1449-55 [12089341] Mol Genet Metab. 2002 May;76(1):1-5 [12175774] Mol Cell. 2002 Aug;10(2):227-36 [12191469] Biochim Biophys Acta. 2002 Oct 2;1603(1):19-29 [12242108] Chromosoma. 2003 May;111(8):495-504 [12743713] Mol Cell. 2003 May;11(5):1311-22 [12769854] Mol Cell Biol. 2003 Sep;23(17):6210-20 [12917342] Genes Dev. 2003 Nov 15;17(22):2733-40 [14630937] Cell. 1987 Jan 30;48(2):261-70 [3026639] EMBO J. 1987 Aug;6(8):2321-8 [2822386] Curr Opin Genet Dev. 2001 Apr;11(2):124-9 [11250133] Oncogene. 2001 May 28;20(24):2991-3006 [11420714] Oncogene. 2001 May 28;20(24):3076-85 [11420723] J Biol Chem. 1999 Aug 6;274(32):22373-9 [10428808] Mol Cell Biol. 1991 Feb;11(2):688-98 [1846670] Trends Genet. 1990 Dec;6(12):395-400 [2087781] Nature. 1992 Jan 16;355(6357):219-24 [1731219] Science. 1992 Mar 20;255(5051):1573-6 [1347958] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9372-6 [1409643] Trends Genet. 1992 Nov;8(11):387-91 [1332230] Genes Dev. 1993 Apr;7(4):583-91 [8458575] EMBO J. 1993 Nov;12(11):4279-90 [8223438] Nature. 1993 Nov 11;366(6451):170-4 [8232556] Mol Cell Biol. 1994 Jan;14(1):32-41 [8264599] Nature. 1994 Aug 11;370(6489):477-81 [8047169] Nature. 1994 Aug 11;370(6489):481-5 [8047170] Cell. 1994 Oct 7;79(1):119-30 [7923370] Mol Cell Biol. 1995 Jan;15(1):26-34 [7799933] Mol Endocrinol. 1994 Sep;8(9):1154-62 [7838148] Genes Dev. 1996 Apr 15;10(8):905-20 [8608939] Genes Dev. 1996 Sep 1;10(17):2117-30 [8804307] EMBO J. 1996 Oct 1;15(19):5370-82 [8895581] Mol Cell Biol. 1997 Feb;17(2):895-905 [9001244] Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14389-93 [9405622] J Biol Chem. 1998 Jan 23;273(4):1998-2007 [9442036] Cell. 1998 Feb 6;92(3):307-13 [9476891] Trends Biochem Sci. 1998 Jan;23(1):20-5 [9478131] Nature. 1998 May 7;393(6680):88-91 [9590696] Curr Biol. 1998 Jul 2;8(14):843-6 [9663395] Mol Cell. 1999 Feb;3(2):247-53 [10078207] Cell. 1999 Apr 30;97(3):299-311 [10319811] Nature. 1999 Jun 3;399(6735):491-6 [10365964] EMBO J. 1999 Nov 15;18(22):6407-14 [10562552] J Cell Biol. 1999 Dec 27;147(7):1481-92 [10613906] J Steroid Biochem Mol Biol. 1999 Sep-Oct;70(4-6):203-10 [10622409] Mol Cell Biol. 2000 Mar;20(6):2004-13 [10688647] J Biol Chem. 2000 Jun 9;275(23):17771-7 [10748103] Trends Genet. 2000 Aug;16(8):345-51 [10904263] Mol Cell Biol. 2000 Sep;20(17):6466-75 [10938123] Mol Cell Biol. 2000 Dec;20(23):8879-88 [11073988] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. AN - 71787581; 14991053 AB - Modulation of tumor suppressor activities may provide new opportunities for cancer therapy. Here we show that disruption of the gene Ppm1d encoding Wip1 phosphatase activated the p53 and p16 (also called Ink4a)-p19 (also called ARF) pathways through p38 MAPK signaling and suppressed in vitro transformation of mouse embryo fibroblasts (MEFs) by oncogenes. Disruption of the gene Cdkn2a (encoding p16 and p19), but not of Trp53 (encoding p53), reconstituted cell transformation in Ppm1d-null MEFs. In vivo, deletion of Ppm1d in mice bearing mouse mammary tumor virus (MMTV) promoter-driven oncogenes Erbb2 (also called c-neu) or Hras1 impaired mammary carcinogenesis, whereas reduced expression of p16 and p19 by methylation-induced silencing or inactivation of p38 MAPK correlated with tumor appearance. We conclude that inactivation or depletion of the Wip1 phosphatase with resultant p38 MAPK activation suppresses tumor appearance by modulating the Cdkn2a tumor-suppressor locus. JF - Nature genetics AU - Bulavin, Dmitry V AU - Phillips, Crissy AU - Nannenga, Bonnie AU - Timofeev, Oleg AU - Donehower, Larry A AU - Anderson, Carl W AU - Appella, Ettore AU - Fornace, Albert J AD - Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. bulavin@nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 343 EP - 350 VL - 36 IS - 4 SN - 1061-4036, 1061-4036 KW - Cdkn2a protein, mouse KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Neoplasm Proteins KW - Tumor Suppressor Protein p14ARF KW - Tumor Suppressor Protein p53 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Ppm1d protein, mouse KW - Protein Phosphatase 2C KW - Index Medicus KW - Animals KW - Mice KW - Mice, Transgenic KW - Tumor Suppressor Protein p53 -- metabolism KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Neoplasm Proteins -- antagonists & inhibitors KW - Mitogen-Activated Protein Kinases -- metabolism KW - Phosphoprotein Phosphatases -- metabolism KW - Cyclin-Dependent Kinase Inhibitor p16 -- metabolism KW - Mammary Neoplasms, Experimental -- enzymology KW - Mammary Neoplasms, Experimental -- metabolism KW - Neoplasm Proteins -- metabolism KW - Tumor Suppressor Protein p14ARF -- metabolism KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71787581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inactivation+of+the+Wip1+phosphatase+inhibits+mammary+tumorigenesis+through+p38+MAPK-mediated+activation+of+the+p16%28Ink4a%29-p19%28Arf%29+pathway.&rft.au=Bulavin%2C+Dmitry+V%3BPhillips%2C+Crissy%3BNannenga%2C+Bonnie%3BTimofeev%2C+Oleg%3BDonehower%2C+Larry+A%3BAnderson%2C+Carl+W%3BAppella%2C+Ettore%3BFornace%2C+Albert+J&rft.aulast=Bulavin&rft.aufirst=Dmitry&rft.date=2004-04-01&rft.volume=36&rft.issue=4&rft.spage=343&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 - 2004-08-16 N1 - Date created - 2004-03-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Genet. 2004 Apr;36(4):319-20 [15054481] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factory injuries and progressive reform. AN - 71785654; 15053997 JF - American journal of public health AU - Fee, Elizabeth AU - Brown, Theodore M AD - History of Medicine Division, National Library of Medicine, National Institutes of Health, Bethesda, MD 20984, USA. elizabeth_fee@nlm.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 540 VL - 94 IS - 4 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Humans KW - History, 19th Century KW - Population Surveillance KW - Occupational Health -- history KW - Medicine in Art KW - Engraving and Engravings -- history KW - Accidents, Occupational UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71785654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Factory+injuries+and+progressive+reform.&rft.au=Fee%2C+Elizabeth%3BBrown%2C+Theodore+M&rft.aulast=Fee&rft.aufirst=Elizabeth&rft.date=2004-04-01&rft.volume=94&rft.issue=4&rft.spage=540&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 - 2004-04-28 N1 - Date created - 2004-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isoprostane levels in the urine of patients with prostate cancer receiving radiotherapy are not elevated. AN - 71781801; 15050334 AB - Previous studies have demonstrated that urinary 8-iso-prostaglandin F (PGF)2alpha serves as a powerful biomarker of lipid peroxidation in diseases in which oxidative stress plays an important role in its pathophysiology. The goal of this study was to measure the urinary isoprostane levels in patients with prostate cancer treated with radiotherapy (RT) in an effort to determine whether isoprostane levels are elevated compared with in historical controls, whether the levels increase after RT, and whether such an increase would correlate positively with the degree of GU symptoms during treatment. Urine samples were obtained before and during RT from patients enrolled on a recently reported Phase III trial examining the therapeutic efficacy of ibuprofen in decreasing the acute urinary symptoms of RT. Radioimmunoassays were performed on urine samples for 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha. Fifteen patients provided samples both before and during RT. The levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF2alpha in the urine samples obtained before prostate RT (0.27 and 0.41 nmol/mmol creatinine) did not differ appreciably from the values observed in a normal cohort (0.27 and 0.46 nmol/mmol creatinine) and did not change after RT (0.23 and 0.37 nmol/mmol creatinine). We were unable to detect an increase in either 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha in the urine of patients with prostate cancer compared with in historical normal controls. We were also unable to measure an increase in either of the eicosanoids during RT to the prostate gland. JF - International journal of radiation oncology, biology, physics AU - Camphausen, Kevin AU - Ménard, Cynthia AU - Sproull, Mary AU - Goley, Elizabeth AU - Basu, Samar AU - Coleman, C Norman AD - Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1002, USA. camphauk@mail.nih.gov Y1 - 2004/04/01/ PY - 2004 DA - 2004 Apr 01 SP - 1536 EP - 1539 VL - 58 IS - 5 SN - 0360-3016, 0360-3016 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Biomarkers, Tumor KW - Isoprostanes KW - 15-ketoprostaglandin F2alpha KW - 35850-13-6 KW - Creatinine KW - AYI8EX34EU KW - Dinoprost KW - B7IN85G1HY KW - Ibuprofen KW - WK2XYI10QM KW - Index Medicus KW - Radiation Injuries -- drug therapy KW - Creatinine -- urine KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Ibuprofen -- therapeutic use KW - Humans KW - Oxidative Stress KW - Male KW - Dinoprost -- urine KW - Biomarkers, Tumor -- urine KW - Dinoprost -- analogs & derivatives KW - Prostatic Neoplasms -- urine KW - Prostatic Neoplasms -- radiotherapy KW - Isoprostanes -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71781801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology%2C+biology%2C+physics&rft.atitle=Isoprostane+levels+in+the+urine+of+patients+with+prostate+cancer+receiving+radiotherapy+are+not+elevated.&rft.au=Camphausen%2C+Kevin%3BM%C3%A9nard%2C+Cynthia%3BSproull%2C+Mary%3BGoley%2C+Elizabeth%3BBasu%2C+Samar%3BColeman%2C+C+Norman&rft.aulast=Camphausen&rft.aufirst=Kevin&rft.date=2004-04-01&rft.volume=58&rft.issue=5&rft.spage=1536&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-27 N1 - Date created - 2004-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease. AN - 71769812; 14702090 AB - We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA injection, lithium significantly diminished the loss of neurons immunostained for Neuronal Nuclei (NeuN) in the injured striatum, but failed to prevent the reduction of NADPH-diaphorase-positive striatal interneurons. Lithium also reduced the number of neurons showing DNA damage or activated caspase-3. This neuroprotection was associated with an upregulation of Bcl-2 protein levels in the striatal tissue and an increase in the number and density of Bcl-2 immunostaining in striatal neurons. Bromodeoxyuridinie (BrdU) labeling in the lithium-treated injured striatum revealed the presence of large numbers of proliferating cells near the QA-injection site, with a reduction of BrdU-labeled cells in the subventricular zone (SVZ). All BrdU-labeled cells in the SVZ and the majority of BrdU-labeled cells near the QA-injection site were negative for either NeuN or glial fibrillary acidic protein (GFAP), suggesting that they are undifferentiated progenitor cells. However, a small number of BrdU-positive cells found in the QA-injected and lithium-treated striatum site were positive for either NeuN or GFAP. Our results suggest that lithium is neuroprotective in the QA-injection model of Huntington's disease not only due to its ability to inhibit apoptosis but also because it can stimulate neuronal and astroglial progenitor proliferation in the QA-injected striatum or their migration from the SVZ. JF - Molecular psychiatry AU - Senatorov, V V AU - Ren, M AU - Kanai, H AU - Wei, H AU - Chuang, D-M AD - Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. chuang@mail.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 371 EP - 385 VL - 9 IS - 4 SN - 1359-4184, 1359-4184 KW - Neuroprotective Agents KW - 0 KW - Neurotoxins KW - Proto-Oncogene Proteins c-bcl-2 KW - Lithium KW - 9FN79X2M3F KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cell Survival -- drug effects KW - Dose-Response Relationship, Drug KW - Interneurons -- drug effects KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Apoptosis -- drug effects KW - Cell Division -- drug effects KW - Up-Regulation KW - Male KW - DNA Damage -- drug effects KW - Corpus Striatum -- cytology KW - Huntington Disease -- metabolism KW - Neurons -- drug effects KW - Huntington Disease -- chemically induced KW - Huntington Disease -- drug therapy KW - Neurons -- enzymology KW - Corpus Striatum -- drug effects KW - Huntington Disease -- pathology KW - Corpus Striatum -- enzymology KW - Neuroprotective Agents -- pharmacology KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71769812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychiatry&rft.atitle=Short-term+lithium+treatment+promotes+neuronal+survival+and+proliferation+in+rat+striatum+infused+with+quinolinic+acid%2C+an+excitotoxic+model+of+Huntington%27s+disease.&rft.au=Senatorov%2C+V+V%3BRen%2C+M%3BKanai%2C+H%3BWei%2C+H%3BChuang%2C+D-M&rft.aulast=Senatorov&rft.aufirst=V&rft.date=2004-04-01&rft.volume=9&rft.issue=4&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=13594184&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-22 N1 - Date created - 2004-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy, safety, and plasma pharmacokinetics of escalating dosages of intravenously administered ravuconazole lysine phosphoester for treatment of experimental pulmonary aspergillosis in persistently neutropenic rabbits. AN - 71760964; 15047519 AB - Ravuconazole is a new antifungal triazole with broad-spectrum activity and a long half-life in plasma. We studied the antifungal efficacy, safety, and pharmacokinetics of ravuconazole lysine phosphoester in escalating dosages for the treatment of invasive pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Treatment groups consisted of rabbits treated with ravuconazole at 2.5 (RVC2.5), 5 (RVC5), and 10 (RVC10) mg/kg of body weight/day, rabbits treated with amphotericin B (AMB) at 1 mg/kg/day, or untreated controls. There was a dose-dependent reduction of pulmonary residual fungal burden (CFU per gram) in RVC5-, RVC10-, and AMB-treated rabbits in comparison to untreated controls (P < 0.01, P < 0.001, and P < 0.01, respectively). These findings correlated with progressive galactomannan antigenemia in untreated controls and the RVC2.5-treated rabbits, a lower galactomannan index (GMI) in RVC5- and RVC10-treated rabbits, and a similarly low GMI in AMB-treated rabbits (P < 0.01). Rabbits treated with RVC5, RVC10, and AMB also showed a reduction of organism-mediated pulmonary injury, as measured by infarct scores and lung weights, in comparison to untreated controls (P < 0.001). These results were supported by decreased pulmonary infiltrates detected by computed tomography in RVC5- and RVC10-treated rabbits in comparison to untreated controls (P < 0.05). Survival throughout the entire study was achieved in 95% of RVC5-treated rabbits (P < 0.001), 85% of RVC10-treated rabbits (P < 0.001), and 50% of AMB-treated rabbits (P < 0.05) in comparison to none of the untreated controls. Ravuconazole showed linear plasma pharmacokinetics and a large volume of distribution while maintaining concentrations in plasma above the MIC throughout the dosing interval. There was no evidence of hepatotoxicity or nephrotoxicity among ravuconazole-treated animals. Intravenously administered ravuconazole lysine phosphoester showed dose-dependent efficacy and an excellent safety profile for the treatment of invasive pulmonary aspergillosis in persistently neutropenic rabbits. JF - Antimicrobial agents and chemotherapy AU - Petraitiene, Ruta AU - Petraitis, Vidmantas AU - Lyman, Caron A AU - Groll, Andreas H AU - Mickiene, Diana AU - Peter, Joanne AU - Bacher, John AU - Roussillon, Kristin AU - Hemmings, Melissa AU - Armstrong, Derrek AU - Avila, Nilo A AU - Walsh, Thomas J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 1188 EP - 1196 VL - 48 IS - 4 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - ER 30346 KW - Immunosuppressive Agents KW - Mannans KW - Tetrazolium Salts KW - Thiazoles KW - Triazoles KW - galactomannan KW - 11078-30-1 KW - Amphotericin B KW - 7XU7A7DROE KW - thiazolyl blue KW - EUY85H477I KW - Index Medicus KW - Animals KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Mannans -- blood KW - Tomography, X-Ray Computed KW - Rabbits KW - Lung -- pathology KW - Immunosuppressive Agents -- pharmacology KW - Half-Life KW - Aspergillus fumigatus -- drug effects KW - Microbial Sensitivity Tests KW - Image Processing, Computer-Assisted KW - Amphotericin B -- therapeutic use KW - Female KW - Survival Analysis KW - Lung -- microbiology KW - Antifungal Agents -- adverse effects KW - Antifungal Agents -- pharmacokinetics KW - Neutropenia -- complications KW - Neutropenia -- chemically induced KW - Thiazoles -- adverse effects KW - Triazoles -- adverse effects KW - Triazoles -- pharmacokinetics KW - Antifungal Agents -- therapeutic use KW - Thiazoles -- pharmacokinetics KW - Aspergillosis, Allergic Bronchopulmonary -- drug therapy KW - Aspergillosis, Allergic Bronchopulmonary -- pathology KW - Triazoles -- therapeutic use KW - Aspergillosis, Allergic Bronchopulmonary -- microbiology KW - Thiazoles -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71760964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficacy%2C+safety%2C+and+plasma+pharmacokinetics+of+escalating+dosages+of+intravenously+administered+ravuconazole+lysine+phosphoester+for+treatment+of+experimental+pulmonary+aspergillosis+in+persistently+neutropenic+rabbits.&rft.au=Petraitiene%2C+Ruta%3BPetraitis%2C+Vidmantas%3BLyman%2C+Caron+A%3BGroll%2C+Andreas+H%3BMickiene%2C+Diana%3BPeter%2C+Joanne%3BBacher%2C+John%3BRoussillon%2C+Kristin%3BHemmings%2C+Melissa%3BArmstrong%2C+Derrek%3BAvila%2C+Nilo+A%3BWalsh%2C+Thomas+J&rft.aulast=Petraitiene&rft.aufirst=Ruta&rft.date=2004-04-01&rft.volume=48&rft.issue=4&rft.spage=1188&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 - 2004-05-24 N1 - Date created - 2004-03-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 2002 Apr;46(4):1144-6 [11897610] J Antimicrob Chemother. 2002 Feb;49(2):353-7 [11815579] Curr Opin Investig Drugs. 2002 Apr;3(4):555-61 [12090723] N Engl J Med. 2002 Aug 8;347(6):408-15 [12167683] J Clin Microbiol. 2002 Sep;40(9):3204-8 [12202554] Antimicrob Agents Chemother. 2003 Apr;47(4):1193-9 [12654646] J Clin Microbiol. 2003 Aug;41(8):3623-6 [12904365] J Infect Dis. 1985 Nov;152(5):938-45 [2413145] J Clin Microbiol. 1987 May;25(5):931-2 [3294892] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Rev Infect Dis. 1990 Mar-Apr;12(2):308-29 [2184499] Postgrad Med. 1990 Jul;88(1):151-2, 155-61, 165-6 [2195479] Clin Infect Dis. 1992 Mar;14 Suppl 1:S43-53 [1562695] Cancer. 1992 Jun 1;69(11):2653-62 [1315207] Infect Immun. 1992 Jun;60(6):2237-45 [1375195] J Infect Dis. 1994 Feb;169(2):356-68 [8106769] Antimicrob Agents Chemother. 1995 May;39(5):1065-9 [7625790] Infect Dis Clin North Am. 1996 Jun;10(2):365-400 [8803625] Clin Infect Dis. 2002 Mar 1;34(5):563-71 [11807679] Antimicrob Agents Chemother. 2002 Mar;46(3):922-4 [11850289] Antimicrob Agents Chemother. 2002 Apr;46(4):1032-7 [11897586] Antimicrob Agents Chemother. 1996 Oct;40(10):2243-7 [8891122] J Clin Microbiol. 1997 Jan;35(1):139-43 [8968895] Antimicrob Agents Chemother. 1998 Feb;42(2):313-8 [9527778] Clin Infect Dis. 1998 Apr;26(4):781-803; quiz 804-5 [9564455] Antimicrob Agents Chemother. 1998 Dec;42(12):3242-4 [9835520] Clin Microbiol Rev. 1999 Jan;12(1):40-79 [9880474] J Clin Microbiol. 1999 Mar;37(3):870-2 [9986880] Clin Microbiol Rev. 1999 Apr;12(2):310-50 [10194462] Mycoses. 1999;42(7-8):431-42 [10546484] Drugs R D. 1999 Feb;1(2):170-1 [10566016] Diagn Microbiol Infect Dis. 1999 Oct;35(2):163-7 [10579098] Antimicrob Agents Chemother. 2000 Feb;44(2):441-3 [10639380] J Chemother. 1999 Dec;11(6):504-12 [10678792] Medicine (Baltimore). 2000 Jul;79(4):250-60 [10941354] Antimicrob Agents Chemother. 2000 Oct;44(10):2883-6 [10991880] Expert Opin Investig Drugs. 2000 Mar;9(3):593-605 [11060698] Expert Opin Investig Drugs. 2000 Aug;9(8):1797-813 [11060778] Antimicrob Agents Chemother. 2000 Dec;44(12):3381-8 [11083644] Med Mycol. 2000;38 Suppl 1:335-47 [11204162] Antimicrob Agents Chemother. 2001 Jul;45(7):2151-3 [11408242] Transpl Infect Dis. 1999 Dec;1(4):247-61 [11428996] Clin Infect Dis. 2001 Sep 1;33(5):641-7 [11486286] Pharmacotherapy. 2001 Aug;21(8 Pt 2):165S-174S [11501989] Antimicrob Agents Chemother. 2001 Dec;45(12):3433-6 [11709320] Pediatr Infect Dis J. 2002 Mar;21(3):240-8 [12005089] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Micellar paclitaxel improves severe psoriasis in a prospective phase II pilot study. AN - 71758113; 15034502 AB - Taxanes (eg, paclitaxel) are chemotherapeutic agents that have antiproliferative, antiangiogenic, and antiinflammatory properties. We sought to explore the safety and efficacy of paclitaxel in individuals with severe psoriasis. An open-label, prospective, phase II pilot study was conducted at the National Institutes of Health Clinical Center, a federal government medical research facility, in Bethesda, Maryland. Twelve patients with severe psoriasis, as defined by a baseline Psoriasis Area and Severity Index (PASI) score of >or= 20), were studied. Initially, patients received 6 intravenous infusions of micellar paclitaxel, 75 mg/m(2), at 4-week intervals (stage I). Later patients received 9 intravenous infusions of micellar paclitaxel at 2-week intervals (37.5 mg/m(2) for 3 doses followed by 50 mg/m(2) for six additional doses) (stage II). The primary end point was the percent change in the PASI from week 0 to week 24 in stage I and from week 0 to week 20 in stage II. In stage I, all 5 patients improved (mean = 59.7% decrease in PASI, median = 59.6%, range: 40.3%-79.2%). Four of the 7 patients completed stage II and all of these patients improved (mean = 45.9% decrease in PASI, median = 45.0%, range: 14.6%-79.1%). Micellar paclitaxel was well tolerated by most patients. Micellar paclitaxel demonstrates therapeutic activity in patients with severe psoriasis. JF - Journal of the American Academy of Dermatology AU - Ehrlich, Alison AU - Booher, Susan AU - Becerra, Yvonne AU - Borris, Debra L AU - Figg, W Douglas AU - Turner, Maria L AU - Blauvelt, Andrew AD - Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 533 EP - 540 VL - 50 IS - 4 SN - 0190-9622, 0190-9622 KW - Drug Carriers KW - 0 KW - Micelles KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Adult KW - Pilot Projects KW - Middle Aged KW - Male KW - Female KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Psoriasis -- pathology KW - Psoriasis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71758113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Dermatology&rft.atitle=Micellar+paclitaxel+improves+severe+psoriasis+in+a+prospective+phase+II+pilot+study.&rft.au=Ehrlich%2C+Alison%3BBooher%2C+Susan%3BBecerra%2C+Yvonne%3BBorris%2C+Debra+L%3BFigg%2C+W+Douglas%3BTurner%2C+Maria+L%3BBlauvelt%2C+Andrew&rft.aulast=Ehrlich&rft.aufirst=Alison&rft.date=2004-04-01&rft.volume=50&rft.issue=4&rft.spage=533&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Dermatology&rft.issn=01909622&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-06 N1 - Date created - 2004-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - o-Nitrotoluene-induced large intestinal tumors in B6C3F1 mice model human colon cancer in their molecular pathogenesis. AN - 71745410; 14688030 AB - In the previous 500 2-year chemical bioassays within the National Toxicology Program, large intestinal tumors (cecal carcinomas) related to chemical exposure have not been observed in B6C3F1 mice. The recently completed o-nitrotoluene study provided the first cecal tumor response and an opportunity to evaluate the morphology and molecular profile of oncogenes and tumor suppressor genes that are relevant to humans. Morphologically, the carcinomas were gland-forming tumors lined by tall columnar epithelial cells that were positive for cytokeratin 20 and negative for cytokeratin 7. Using immunohistochemistry beta-catenin (encoded by Catnb) protein accumulation was detected in 80% (8/10) of the cecal carcinomas, while increased cyclin D1 and p53 protein expression was detected in 73% (8/11), respectively. There was no difference in adenomatous polyposis protein expression between normal colon and cecal carcinomas. All tumors examined exhibited mutations in exon 2 (corresponds to exon 3 in humans) in the Catnb gene. Mutations in p53 were identified in nine of 11 carcinomas, and all were in exon 7. Analysis of the K-ras gene revealed mutations in 82% (9/11) of carcinomas; all had specific G --> T transversions (Gly --> Val) at codons 10 or 12. The alterations in cancer genes and proteins found in the mouse large intestinal tumors included mutations that activate signal transduction pathways (K-ras and Catnb) and changes that disrupt the cell-cycle and bypass G(1) arrest (p53, cyclin D1). These alterations, which are hallmarks of human colon cancer, probably contributed to the pathogenesis of the large intestinal carcinomas in mice following o-nitrotoluene exposure. JF - Carcinogenesis AU - Sills, R C AU - Hong, H L AU - Flake, G AU - Moomaw, C AU - Clayton, N AU - Boorman, G A AU - Dunnick, J AU - Devereux, T R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences. PO Box 12233, Research Triangle Park, NC 27709, USA. sills@niehs.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 605 EP - 612 VL - 25 IS - 4 SN - 0143-3334, 0143-3334 KW - CTNNB1 protein, human KW - 0 KW - CTNNB1 protein, mouse KW - Carcinogens KW - Codon KW - Cytoskeletal Proteins KW - Trans-Activators KW - beta Catenin KW - Toluene KW - 3FPU23BG52 KW - 2-nitrotoluene KW - 6Q9N88YIAY KW - Index Medicus KW - Animals KW - Trans-Activators -- deficiency KW - Codon -- genetics KW - Cecal Neoplasms -- pathology KW - Humans KW - Disease Models, Animal KW - Mice KW - Gene Deletion KW - Mice, Inbred Strains KW - Base Sequence KW - Cecal Neoplasms -- chemically induced KW - Trans-Activators -- genetics KW - Intestinal Mucosa -- pathology KW - Cytoskeletal Proteins -- deficiency KW - Male KW - Female KW - Cytoskeletal Proteins -- genetics KW - Toluene -- analogs & derivatives KW - Toluene -- toxicity KW - Colonic Neoplasms -- pathology KW - Colonic Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71745410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=o-Nitrotoluene-induced+large+intestinal+tumors+in+B6C3F1+mice+model+human+colon+cancer+in+their+molecular+pathogenesis.&rft.au=Sills%2C+R+C%3BHong%2C+H+L%3BFlake%2C+G%3BMoomaw%2C+C%3BClayton%2C+N%3BBoorman%2C+G+A%3BDunnick%2C+J%3BDevereux%2C+T+R&rft.aulast=Sills&rft.aufirst=R&rft.date=2004-04-01&rft.volume=25&rft.issue=4&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-14 N1 - Date created - 2004-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinogenic phenotype of human activation-induced cytosine deaminase. AN - 71744874; 15034045 AB - Class switch recombination, gene conversion, and somatic hypermutation that diversify rearranged Ig genes to produce various classes of high affinity Abs are dependent on the enzyme activation-induced cytosine deaminase (AID). Evidence suggests that somatic hypermutation is due to error-prone DNA repair that is initiated by AID-mediated deamination of cytosine in DNA, whereas the mechanism by which AID controls recombination remains to be elucidated. In this study, using a yeast model system, we have observed AID-dependent recombination. Expression of human AID in wild-type yeast is mutagenic for G-C to A-T transitions, and as expected, this mutagenesis is increased upon inactivation of uracil-DNA glycosylase. AID expression also strongly induces intragenic mitotic recombination, but only in a strain possessing uracil-DNA glycosylase. Thus, the initial step of base excision repair is required for AID-dependent recombination and is a branch point for either hypermutagenesis or recombination. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Poltoratsky, Vladimir P AU - Wilson, Samuel H AU - Kunkel, Thomas A AU - Pavlov, Youri I AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/04/01/ PY - 2004 DA - 2004 Apr 01 SP - 4308 EP - 4313 VL - 172 IS - 7 SN - 0022-1767, 0022-1767 KW - Cytosine KW - 8J337D1HZY KW - AICDA (activation-induced cytidine deaminase) KW - EC 3.5.4.- KW - Cytidine Deaminase KW - EC 3.5.4.5 KW - Abridged Index Medicus KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Somatic Hypermutation, Immunoglobulin KW - Enzyme Induction -- immunology KW - DNA Repair KW - Humans KW - Base Pair Mismatch KW - Two-Hybrid System Techniques KW - RNA Editing KW - Immunoglobulin Class Switching KW - Cell Line, Tumor KW - Saccharomyces cerevisiae -- enzymology KW - Mutagenesis KW - Cytosine -- metabolism KW - Cloning, Molecular KW - Phenotype KW - Recombination, Genetic -- immunology KW - Lymphocyte Activation -- genetics KW - Cytidine Deaminase -- biosynthesis KW - Cytidine Deaminase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71744874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinogenic+phenotype+of+human+activation-induced+cytosine+deaminase.&rft.au=Poltoratsky%2C+Vladimir+P%3BWilson%2C+Samuel+H%3BKunkel%2C+Thomas+A%3BPavlov%2C+Youri+I&rft.aulast=Poltoratsky&rft.aufirst=Vladimir&rft.date=2004-04-01&rft.volume=172&rft.issue=7&rft.spage=4308&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 - 2004-07-30 N1 - Date created - 2004-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel protective model against experimental allergic encephalomyelitis in mice expressing a transgenic TCR-specific for myelin oligodendrocyte glycoprotein. AN - 71744202; 15020060 AB - Myelin oligodendrocyte glycoprotein (MOG) is an important autoantigen in multiple sclerosis and in experimental autoimmune encephalomyelitis (EAE). We generated a T cell receptor (TCR) transgenic (Tg) mouse expressing a TCR derived from an encephalitogenic T cell clone specific for MOG(35-55). This mouse failed to develop EAE spontaneously and developed mild EAE at late onset when immunized with MOG(35-55). The Tg T cells produced large amounts of IL-4 when stimulated with MOG(35-55) and underwent FAS/FAS-L-mediated activation-induced cell death when stimulated with MOG(35-55) and IL-12. The unique phenotype of these autoantigen-specific T cells may represent an important mechanism of protection against autoimmune disease. JF - Journal of neuroimmunology AU - Mendel, Itzhak AU - Natarajan, Kannan AU - Ben-Nun, Avraham AU - Shevach, Ethan M AD - Laboratory of Immunology, Cellular Immunology Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N315, 10 Center Drive, Bethesda, MD 20892-1892, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 10 EP - 21 VL - 149 IS - 1-2 SN - 0165-5728, 0165-5728 KW - Antigens, CD4 KW - 0 KW - Antigens, CD8 KW - Glycoproteins KW - Interleukin-2 KW - Ionophores KW - Myelin-Oligodendrocyte Glycoprotein KW - Peptide Fragments KW - Receptors, Antigen, T-Cell KW - myelin oligodendrocyte glycoprotein (35-55) KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Interleukin-12 -- immunology KW - Thymus Gland -- cytology KW - Animals KW - Drug Interactions KW - Spleen -- cytology KW - Cloning, Molecular -- methods KW - Mice KW - Mice, Transgenic KW - Lymph Nodes -- cytology KW - Antigens, CD4 -- metabolism KW - Flow Cytometry -- methods KW - In Situ Nick-End Labeling -- methods KW - Animals, Newborn KW - Ionophores -- pharmacology KW - Cells, Cultured KW - Dose-Response Relationship, Immunologic KW - In Vitro Techniques KW - Mice, Inbred C57BL KW - Antigens, CD8 -- metabolism KW - Interleukin-2 -- immunology KW - Time Factors KW - Glycoproteins -- immunology KW - Encephalomyelitis, Autoimmune, Experimental -- genetics KW - Encephalomyelitis, Autoimmune, Experimental -- immunology KW - Receptors, Antigen, T-Cell -- metabolism KW - Disease Models, Animal KW - Receptors, Antigen, T-Cell -- immunology KW - Receptors, Antigen, T-Cell -- genetics KW - Peptide Fragments -- immunology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71744202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroimmunology&rft.atitle=A+novel+protective+model+against+experimental+allergic+encephalomyelitis+in+mice+expressing+a+transgenic+TCR-specific+for+myelin+oligodendrocyte+glycoprotein.&rft.au=Mendel%2C+Itzhak%3BNatarajan%2C+Kannan%3BBen-Nun%2C+Avraham%3BShevach%2C+Ethan+M&rft.aulast=Mendel&rft.aufirst=Itzhak&rft.date=2004-04-01&rft.volume=149&rft.issue=1-2&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimmunology&rft.issn=01655728&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-10 N1 - Date created - 2004-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Azido-containing diketo acid derivatives inhibit human immunodeficiency virus type 1 integrase in vivo and influence the frequency of deletions at two-long-terminal-repeat-circle junctions. AN - 71740013; 15016842 AB - We previously found that azido-containing beta-diketo acid derivatives (DKAs) are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase (IN) (X. Zhang et al., Bioorg. Med. Chem. Lett., 13:1215-1219, 2003). To characterize the intracellular mechanisms of action of DKAs, we analyzed the antiviral activities of two potent azido-containing DKAs with either a monosubstitution or a disubstitution of azido groups, using single- and multiple-replication-cycle assays. Both azido-containing DKAs significantly inhibited HIV-1 infection in 293T, CEM-SS, and H9 cells (50% inhibitory concentration = 2 to 13 micro M) and exhibited low cytotoxicity (50% cytotoxic concentration = 60 to 600 micro M). Inhibition of HIV-1 IN in vivo was demonstrated by the observation that previously described L-708,906 resistance mutations in HIV-1 IN (T66I and T66I/S153Y) also conferred resistance to the azido-group-containing DKAs. In vitro assays and in vivo analysis indicated that the DKAs did not significantly inhibit the 3' processing and selectively inhibited the strand transfer reaction. In addition, quantitative PCR indicated that two-long-terminal-repeat (2-LTR) circles were elevated in the presence of the azido-containing DKAs, confirming that HIV-1 IN was the intracellular target of viral inhibition. To gain insight into the mechanism by which the DKAs increased 2-LTR-circle formation of 3'-processed viral DNAs, we performed extensive DNA sequencing analysis of 2-LTR-circle junctions. The results indicated that the frequency of deletions at the circle junctions was elevated from 19% for the untreated controls to 32 to 41% in the presence of monosubstituted (but not disubstituted) DKAs. These results indicate that the structure of the DKAs can influence the extent of degradation of viral DNA ends by host nucleases and the frequency of deletions at the 2-LTR-circle junctions. Thus, sequencing analysis of 2-LTR-circle junctions can elucidate the intracellular mechanisms of action of HIV-1 IN inhibitors. JF - Journal of virology AU - Svarovskaia, Evguenia S AU - Barr, Rebekah AU - Zhang, Xuechun AU - Pais, Godwin C G AU - Marchand, Christophe AU - Pommier, Yves AU - Burke, Terrence R AU - Pathak, Vinay K AD - HIV Drug Resistance Program. Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 3210 EP - 3222 VL - 78 IS - 7 SN - 0022-538X, 0022-538X KW - DNA, Circular KW - 0 KW - DNA, Viral KW - HIV Integrase Inhibitors KW - HIV Integrase KW - EC 2.7.7.- KW - Index Medicus KW - HIV-1 -- genetics KW - Base Sequence KW - Virus Replication -- drug effects KW - Humans KW - Drug Resistance, Viral -- genetics KW - HIV-1 -- enzymology KW - Inhibitory Concentration 50 KW - HIV-1 -- physiology KW - HIV-1 -- drug effects KW - Cell Line KW - DNA, Viral -- biosynthesis KW - DNA, Circular -- genetics KW - HIV Integrase Inhibitors -- chemistry KW - DNA, Viral -- analysis KW - Sequence Deletion -- genetics KW - HIV Long Terminal Repeat -- genetics KW - HIV Integrase -- genetics KW - HIV Integrase Inhibitors -- pharmacology KW - DNA, Viral -- genetics KW - HIV Integrase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71740013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Azido-containing+diketo+acid+derivatives+inhibit+human+immunodeficiency+virus+type+1+integrase+in+vivo+and+influence+the+frequency+of+deletions+at+two-long-terminal-repeat-circle+junctions.&rft.au=Svarovskaia%2C+Evguenia+S%3BBarr%2C+Rebekah%3BZhang%2C+Xuechun%3BPais%2C+Godwin+C+G%3BMarchand%2C+Christophe%3BPommier%2C+Yves%3BBurke%2C+Terrence+R%3BPathak%2C+Vinay+K&rft.aulast=Svarovskaia&rft.aufirst=Evguenia&rft.date=2004-04-01&rft.volume=78&rft.issue=7&rft.spage=3210&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 - 2004-04-08 N1 - Date created - 2004-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9564-8 [7937806] Science. 1994 Dec 23;266(5193):1981-6 [7801124] J Med Chem. 2002 Aug 15;45(17):3669-83 [12166940] Curr Opin Pharmacol. 2002 Oct;2(5):523-8 [12324253] J Virol. 2003 Jan;77(1):318-27 [12477837] J Biol Chem. 2003 Jan 31;278(5):2777-80 [12480948] J Med Chem. 2003 Feb 13;46(4):453-6 [12570367] Virology. 2003 Feb 1;306(1):147-61 [12620807] Bioorg Med Chem Lett. 2003 Mar 24;13(6):1215-9 [12643946] Curr Opin Investig Drugs. 2003 Feb;4(2):206-9 [12669383] Mol Pharmacol. 2003 Sep;64(3):600-9 [12920196] Curr Top Med Chem. 2004;4(10):1059-77 [15193139] Cell. 1980 Nov;22(2 Pt 2):379-86 [6256079] Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9742-7 [8790401] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13659-64 [8942990] J Virol. 1997 Jan;71(1):807-11 [8985421] J Virol. 1997 Jul;71(7):5382-90 [9188609] Mol Pharmacol. 1997 Nov;52(5):771-80 [9351967] J Virol. 1998 May;72(5):4116-26 [9557701] J Virol. 1998 Jun;72(6):4841-8 [9573250] J Virol. 1998 Jun;72(6):5046-55 [9573274] J Infect Dis. 1999 Mar;179(3):717-20 [9952385] J Med Chem. 1999 Apr 22;42(8):1401-14 [10212126] Science. 1999 Apr 23;284(5414):644-7 [10213687] Antivir Chem Chemother. 1999 Mar;10(2):63-70 [10335400] J Exp Med. 1999 Jun 7;189(11):1735-46 [10359577] Adv Virus Res. 1999;52:319-33 [10384240] Adv Virus Res. 1999;52:427-58 [10384246] Proteins. 1999 Sep 1;36(4):556-64 [10450096] Proc Natl Acad Sci U S A. 1981 Jan;78(1):124-8 [6264426] J Virol. 1986 Aug;59(2):284-91 [3016298] Biochemistry. 1995 Aug 8;34(31):9826-33 [7632683] J Med Chem. 1995 Oct 13;38(21):4171-8 [7473544] Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13040-3 [10557269] Science. 2000 Jan 28;287(5453):646-50 [10649997] J Virol. 2000 Jul;74(14):6669-74 [10864683] Antiviral Res. 2000 Jun;46(3):223-32 [10867160] Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8233-8 [10890912] Mol Pharmacol. 2000 Sep;58(3):641-8 [10953059] Int J Hematol. 2000 Jul;72(1):20-7 [10979204] J Virol. 2000 Dec;74(23):11191-200 [11070016] J Biol Chem. 2000 Dec 15;275(50):39287-95 [11006285] Nucleic Acids Res. 2000 Dec 15;28(24):4884-92 [11121479] Mol Cell Biol. 2001 Feb;21(4):1164-72 [11158303] Nature. 2001 Apr 19;410(6831):995-1001 [11309630] Nat Med. 2001 May;7(5):631-4 [11329067] EMBO J. 2001 Jul 2;20(13):3565-76 [11432843] DNA Cell Biol. 2001 Aug;20(8):499-508 [11560782] Curr Med Chem. 2001 Nov;8(13):1543-72 [11562282] Curr Opin Drug Discov Devel. 2001 Jul;4(4):402-10 [11727305] EMBO J. 2001 Dec 17;20(24):7333-43 [11743009] Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):134-7 [11756686] Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):4-6 [11782542] J Virol. 2002 Apr;76(8):3739-47 [11907213] J Biol Chem. 2002 Apr 12;277(15):12596-603 [11805103] Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9515-20 [12093908] J Med Chem. 2002 Jul 18;45(15):3184-94 [12109903] J Virol. 1991 Jan;65(1):551-5 [1985217] Virology. 1992 Jun;188(2):459-68 [1585629] J Gen Virol. 1992 Jun;73 ( Pt 6):1537-41 [1607872] J Biol Chem. 1992 Jul 25;267(21):15071-9 [1378844] J Virol. 1992 Nov;66(11):6361-9 [1404595] J Virol. 1992 Dec;66(12):7414-9 [1433523] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2399-403 [8460151] EMBO J. 1993 Aug;12(8):3269-75 [8344264] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):549-53 [7507249] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autosomal dominant hypocalcemia in monozygotic twins caused by a de novo germline mutation near the amino-terminus of the human calcium receptor. AN - 71712857; 15005845 AB - To define the molecular pathogenesis of severe postnatal hypocalcemia in monozygotic twin sisters, we sequenced their CaR gene and identified a missense mutation, K29E. Expression of the mutant receptor in vitro showed a marked increase in Ca2+ sensitivity explaining the observed phenotype. Additional mutagenesis studies lead us to speculate concerning a novel mechanism whereby the K29E mutation may lead to receptor activation. Activating mutations of the Ca(2+)-sensing receptor (CaR) gene have been identified in subjects with autosomal dominant hypocalcemia. Study of such mutations has provided insight into the mechanism of activation of the CaR. We performed biochemical and molecular genetic studies on monozygotic twin sisters who presented with early postnatal hypocalcemia and on their unaffected sister and parents. Functional characterization of mutant CaRs transfected in HEK-293 cells included immunoblots to monitor protein expression and Ca2+ stimulation of phosphoinositide hydrolysis to measure Ca2+ sensitivity. We identified a K29E missense mutation in the twin sisters but not in their parents or unaffected sister. The K29E mutant CaR showed a marked increase in Ca2+ sensitivity, including when it was co-transfected with wildtype CaR cDNA, consistent with a dominant effect. Substitution of K29 by aspartate equivalently increased CaR sensitivity, whereas conservative substitution by arginine did not. Severe postnatal hypocalcemia in the twin sisters was caused by a de novo germline activating mutation. In a model of the Venus flytrap-like domain of the extracellular amino-terminus of the CaR, K29 is located close to a peptide loop, "loop 2," that forms part of the dimer interface and is the site of 10 of the previously reported naturally occurring activating CaR mutations. We speculate that K29E increases Ca2+ sensitivity of the CaR by disrupting a salt bridge between K29 and an acidic residue in loop 2 and thereby changes the normal structure of loop 2 that maintains the CaR in its inactive conformation. JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research AU - Hu, Jianxin AU - Mora, Stefano AU - Weber, Giovanna AU - Zamproni, Ilaria AU - Proverbio, Maria Carla AU - Spiegel, Allen M AD - Molecular Pathophysiology Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. jianxinh@intra.niddk.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 578 EP - 586 VL - 19 IS - 4 SN - 0884-0431, 0884-0431 KW - Receptors, Calcium-Sensing KW - 0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Pedigree KW - Mutagenesis, Site-Directed KW - Protein Structure, Tertiary -- genetics KW - Humans KW - Molecular Sequence Data KW - Gene Expression KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Male KW - Female KW - Cell Line KW - Amino Acid Substitution KW - Hypocalcemia -- blood KW - Hypocalcemia -- metabolism KW - Genes, Dominant KW - Calcium -- blood KW - Hypocalcemia -- congenital KW - Receptors, Calcium-Sensing -- genetics KW - Hypocalcemia -- genetics KW - Germ-Line Mutation KW - Twins, Monozygotic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71712857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bone+and+mineral+research+%3A+the+official+journal+of+the+American+Society+for+Bone+and+Mineral+Research&rft.atitle=Autosomal+dominant+hypocalcemia+in+monozygotic+twins+caused+by+a+de+novo+germline+mutation+near+the+amino-terminus+of+the+human+calcium+receptor.&rft.au=Hu%2C+Jianxin%3BMora%2C+Stefano%3BWeber%2C+Giovanna%3BZamproni%2C+Ilaria%3BProverbio%2C+Maria+Carla%3BSpiegel%2C+Allen+M&rft.aulast=Hu&rft.aufirst=Jianxin&rft.date=2004-04-01&rft.volume=19&rft.issue=4&rft.spage=578&rft.isbn=&rft.btitle=&rft.title=Journal+of+bone+and+mineral+research+%3A+the+official+journal+of+the+American+Society+for+Bone+and+Mineral+Research&rft.issn=08840431&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-28 N1 - Date created - 2004-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective photolabeling of proteins using photoactivatable GFP. AN - 71705820; 15003607 AB - Today's cell biologists rely on an assortment of advances in microscopy methods to study the inner workings of cells and tissues. Among these advances are fluorescent proteins which can be used to tag specifically and, in many cases, non-invasively proteins of interest within a living cell. Introduction of DNA encoding the fluorescently tagged protein of interest into a cell readily allows the visualization of the protein's localization and time-lapse imaging allows the movement of the structure or organelle to which the protein is localized to be observed. To monitor the movement of the protein within the population, researchers generally have to highlight a pool of molecules by perturbing the steady-state fluorescence. This perturbation has traditionally been performed by photobleaching the molecules within a selected region of the cell and monitoring the recovery of molecules into this region or the loss of molecules within other regions. Fluorescent proteins are now available, which allow a pool of molecules to be highlighted directly by photoactivation. Here, we discuss the technical aspects for using one of these recently developed photoactivatable fluorescent proteins, PA-GFP. JF - Methods (San Diego, Calif.) AU - Patterson, George H AU - Lippincott-Schwartz, Jennifer AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 445 EP - 450 VL - 32 IS - 4 SN - 1046-2023, 1046-2023 KW - Recombinant Fusion Proteins KW - 0 KW - Index Medicus KW - Photochemistry KW - Spectrometry, Fluorescence -- methods KW - Mutagenesis, Site-Directed -- genetics KW - Spectrophotometry KW - Microscopy, Fluorescence -- methods KW - Lasers KW - Recombinant Fusion Proteins -- metabolism KW - Staining and Labeling -- methods KW - Recombinant Fusion Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71705820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%28San+Diego%2C+Calif.%29&rft.atitle=Selective+photolabeling+of+proteins+using+photoactivatable+GFP.&rft.au=Patterson%2C+George+H%3BLippincott-Schwartz%2C+Jennifer&rft.aulast=Patterson&rft.aufirst=George&rft.date=2004-04-01&rft.volume=32&rft.issue=4&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=Methods+%28San+Diego%2C+Calif.%29&rft.issn=10462023&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-14 N1 - Date created - 2004-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sites in the fourth membrane-associated domain regulate alcohol sensitivity of the NMDA receptor. AN - 71699374; 14996542 AB - N-methyl-D-aspartate (NMDA) receptors are important target sites of alcohol action in the central nervous system. Alcohol inhibits NMDA receptor current by an action on ion channel gating, apparently through a direct action on a region of the NMDA receptor accessible from the extracellular environment. Our previous studies have revealed an important role for a methionine residue (Met823) in membrane-associated domain 4 (M4) of the NR2A subunit in channel gating as well as alcohol sensitivity of the NMDA receptor. The role of sites in M4 of the NMDA receptor NR2A subunit adjacent to Met823 was investigated using tryptophan-scanning mutagenesis and electrophysiological recording. Receptors containing NR1 and NR2A(V820W) or NR2A(M817W) mutant subunits expressed in HEK 293 cells were not functional. The mutation Ala826Trp modified apparent desensitization, and the mutations Ala825Trp and Ala826Trp changed the mean open time of the channel as determined by fluctuation analysis. In addition, the mutations Tyr822Trp and Ala825Trp significantly altered the concentration-response curves for ethanol inhibition. The changes in mean open time did not appear to be able to account for the observed differences in ethanol sensitivity. These results indicate that this region in M4 of the NR2A subunit may be involved in the action of alcohol. JF - Neuropharmacology AU - Honse, Yumiko AU - Ren, Hong AU - Lipsky, Robert H AU - Peoples, Robert W AD - Unit on Cellular Neuropharmacology, Laboratory of Molecular and Cellular Neurobiology and Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-8115, USA. yhonse@mail.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 647 EP - 654 VL - 46 IS - 5 SN - 0028-3908, 0028-3908 KW - Protein Subunits KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Protein Structure, Tertiary -- genetics KW - Protein Subunits -- genetics KW - Dose-Response Relationship, Drug KW - Amino Acid Substitution -- genetics KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Subunits -- metabolism KW - Cell Line KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Ethanol -- pharmacology KW - Cell Membrane -- genetics KW - Cell Membrane -- physiology KW - Receptors, N-Methyl-D-Aspartate -- genetics KW - Receptors, N-Methyl-D-Aspartate -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71699374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sites+in+the+fourth+membrane-associated+domain+regulate+alcohol+sensitivity+of+the+NMDA+receptor.&rft.au=Honse%2C+Yumiko%3BRen%2C+Hong%3BLipsky%2C+Robert+H%3BPeoples%2C+Robert+W&rft.aulast=Honse&rft.aufirst=Yumiko&rft.date=2004-04-01&rft.volume=46&rft.issue=5&rft.spage=647&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-15 N1 - Date created - 2004-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutamate-induced differential mitochondrial response in young and adult rats. AN - 71555603; 14643754 AB - Excitatory amino acid glutamate is involved in neurotransmission in the nervous system but it becomes a potent neurotoxin under variety of conditions. However, the molecular mechanism of excitotoxicity is not known completely. We have studied the influence of glutamate on intracellular calcium and mitochondrial functions in cortical slices from young and adult rats. The slices from both the age groups exhibited comparable intracellular calcium changes upon glutamate stimulation. Glutamate treatment caused a decrease in adenosine 5'-diphosphate/adenosine 5'-triphosphate (ADP/ATP) and an increase in nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide reduced form (NAD/NADH) ratio in both the age groups but the magnitude and the nature of temporal change was different. Glutamate-induced decrease in ATP/ADP and increase in NAD/NADH ratio was significantly higher in slices from the adult as compared to the young rats. The slices from young rats elicited slightly higher mitochondrial depolarization than adult rats. However, the formation of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release were significantly higher in adult rats as compared to young rats. Glutamate-induced mitochondrial depolarization, ROS formation and LDH release were highly dependent on the presence of Ca(2+) in the extracellular medium. The treatment of slices with mitochondrial inhibitors rotenone and oligomycin inhibited ROS formation and LDH release substantially. Our results suggest that the glutamate-induced increase in intracellular calcium is not the only factor responsible for neuronal cell death but the mitochondrial functions could be crucial in excitotoxicity. JF - Neurochemistry international AU - Kannurpatti, S S AU - Sanganahalli, B G AU - Mishra, Sudha AU - Joshi, Preeti G AU - Joshi, N B AD - Department of Biophysics, National Institute of Mental Health and Neuro Sciences, Bangalore 560 029, India. Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 361 EP - 369 VL - 44 IS - 5 SN - 0197-0186, 0197-0186 KW - Fluorescent Dyes KW - 0 KW - Reactive Oxygen Species KW - NAD KW - 0U46U6E8UK KW - Glutamic Acid KW - 3KX376GY7L KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Calcium KW - SY7Q814VUP KW - Fura-2 KW - TSN3DL106G KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- metabolism KW - Neurons -- drug effects KW - Intracellular Membranes -- drug effects KW - Cerebral Cortex -- ultrastructure KW - Neurons -- pathology KW - Rats KW - Microscopy, Fluorescence KW - Calcium -- metabolism KW - NAD -- metabolism KW - Rats, Sprague-Dawley KW - Calcium Signaling -- drug effects KW - Cell Survival -- drug effects KW - Adenosine Triphosphate -- metabolism KW - Oxidative Stress -- drug effects KW - Intracellular Membranes -- metabolism KW - L-Lactate Dehydrogenase -- metabolism KW - Aging -- physiology KW - Mitochondria -- drug effects KW - Glutamic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71555603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glutamate-induced+differential+mitochondrial+response+in+young+and+adult+rats.&rft.au=Kannurpatti%2C+S+S%3BSanganahalli%2C+B+G%3BMishra%2C+Sudha%3BJoshi%2C+Preeti+G%3BJoshi%2C+N+B&rft.aulast=Kannurpatti&rft.aufirst=S&rft.date=2004-04-01&rft.volume=44&rft.issue=5&rft.spage=361&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 - 2004-02-02 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - VEGF promoter haplotype and amyotrophic lateral sclerosis (ALS). AN - 67276967; 15763997 AB - Vascular endothelial growth factor (VEGF) is a cytokine essential for angiogenesis. A recent study found that haplotypes, determined by three SNPs (-2,578C/A, - 1,154 G/A, and - 634G/C) in the VEGF upstream promoter/leader sequence, were associated with risk of amyotrophic lateral sclerosis(ALS). We used samples and data from a case-control study to examine the relation of ALS to VEGF haplotype. Genotypes at each of the three polymorphic sites were determined using allele-specific primer extension reactions followed by MALDI-TOF. We found a 3-fold increased risk among individuals homozygous for the AAG or AGG haplotypes (95%CI = 0.7 - 13.4), consistent with the findings of the previous study. Given the wide confidence interval, our findings should be interpreted cautiously. JF - Journal of neurogenetics AU - Terry, Paul D AU - Kamel, Freya AU - Umbach, David M AU - Lehman, Teresa A AU - Hu, Howard AU - Sandler, Dale P AU - Taylor, Jack A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, Research Triangle Park, NC 27709, USA. terry2@niehs.nih.gov PY - 2004 SP - 429 EP - 434 VL - 18 IS - 2 SN - 0167-7063, 0167-7063 KW - Vascular Endothelial Growth Factor A KW - 0 KW - Lead KW - 2P299V784P KW - Index Medicus KW - Smoking KW - Homozygote KW - Bone and Bones -- chemistry KW - Haplotypes KW - Humans KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Environmental Exposure KW - Case-Control Studies KW - Genetic Predisposition to Disease KW - Lead -- analysis KW - Lead -- blood KW - Promoter Regions, Genetic KW - Polymorphism, Single Nucleotide KW - Amyotrophic Lateral Sclerosis -- genetics KW - Amyotrophic Lateral Sclerosis -- blood KW - Vascular Endothelial Growth Factor A -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67276967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurogenetics&rft.atitle=VEGF+promoter+haplotype+and+amyotrophic+lateral+sclerosis+%28ALS%29.&rft.au=Terry%2C+Paul+D%3BKamel%2C+Freya%3BUmbach%2C+David+M%3BLehman%2C+Teresa+A%3BHu%2C+Howard%3BSandler%2C+Dale+P%3BTaylor%2C+Jack+A&rft.aulast=Terry&rft.aufirst=Paul&rft.date=2004-04-01&rft.volume=18&rft.issue=2&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurogenetics&rft.issn=01677063&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-13 N1 - Date created - 2005-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of association of CYP1 B1*3 polymorphism and ovarian cancer in a Caucasian population. AN - 66716743; 15255550 AB - CYP1B1 is the enzyme with the highest efficiency of conversion of estradiol to 4-hydroxyestradiol in humans. This metabolite has a well-known carcinogenic effect interacting with genomic DNA and has been hypothesized to be partly responsible for the role played by estrogens in ovarian cancer development. A polymorphism has been described for this enzyme causing a Leu to Val substitution in position 432 (CYP1B1*3). The Val432 allele has a higher efficiency of conversion of estradiol to 4-hydroxyestradiol and has been reported to increase the risk of ovarian cancer. A previous study reported a higher, significant prevalence of CYP1B1*3 polymorphism in ovarian cancer patients of mixed ethnicity. The aim of this study was to investigate the role of CYP1B1*3 polymorphism as a risk factor for ovarian cancer in a Caucasian population. The polymorphism frequency was determined in 223 cases of ovarian cancer and compared with that of 280 healthy female blood donors. Genetic analysis was performed on genomic DNA from PBMC and RFLP methods were used for mutation detection. No significant difference between cases and controls was found. These results do not support a favoring role of CYP1B1*3 in ovarian cancer development in our population. JF - The International journal of biological markers AU - Cecchin, E AU - Russo, A AU - Campagnutta, E AU - Martella, L AU - Toffoli, G AD - Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico-National Cancer Institute, Aviano, Italy. PY - 2004 SP - 160 EP - 163 VL - 19 IS - 2 SN - 0393-6155, 0393-6155 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cytochrome P-450 CYP1B1 KW - Leucine KW - GMW67QNF9C KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Odds Ratio KW - Homozygote KW - Gene Frequency KW - Humans KW - Leucine -- chemistry KW - Alleles KW - Polymorphism, Restriction Fragment Length KW - European Continental Ancestry Group KW - Risk Factors KW - Leukocytes, Mononuclear -- metabolism KW - Valine -- chemistry KW - Female KW - Polymorphism, Genetic KW - Ovarian Neoplasms -- genetics KW - Aryl Hydrocarbon Hydroxylases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66716743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+International+journal+of+biological+markers&rft.atitle=Lack+of+association+of+CYP1+B1*3+polymorphism+and+ovarian+cancer+in+a+Caucasian+population.&rft.au=Cecchin%2C+E%3BRusso%2C+A%3BCampagnutta%2C+E%3BMartella%2C+L%3BToffoli%2C+G&rft.aulast=Cecchin&rft.aufirst=E&rft.date=2004-04-01&rft.volume=19&rft.issue=2&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=The+International+journal+of+biological+markers&rft.issn=03936155&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-13 N1 - Date created - 2004-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of DMBA-croton oil two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate through modulation of cutaneous oxidative stress and inhibition of nitric oxide production. AN - 66691314; 15244517 AB - Selenium, an essential micronutrient, plays important roles against different diseases, including several types of cancer. In the present study, antioxidative and chemopreventive properties of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated with a 7,12-dimethylbenz (a) anthracene - croton oil induced two-stage mouse skin carcinogenesis model. The compound was administered orally to carcinogen-treated mice at two different non-toxic doses, 2mg/kg. b.w. and 3mg/kg. b.w. Significant inhibition in the incidence of papilloma formation (53-80%) as well as in the cumulative numbers of papillomas per papilloma bearing mouse were observed in the treated groups as compared to the carcinogen control group. The compound was also found to upregulate significantly different phase II detoxifying enzymes such as glutathione-S-transferase (p<0.01) and superoxide dismutase (p<0.01) in skin cytosol when measured after 15 days and also after 12 weeks of the first 7,12-dimethylbenz (a) anthracene treatment. Lipid peroxidation measured with reference to thiobarbituric acid reactive substances in skin microsomes was significantly inhibited (p<0.05) in a dose dependent manner by diphenylmethyl selenocyanate. Considerable inhibition of the level of nitric oxide production in peritoneal macrophages was observed after 12 weeks (p<0.05). Thus the compound appears to exert chemopreventive activity in terms of papilloma formation, which may be through modulation of cutaneous lipid peroxidation, the phase II detoxifying enzyme system and nitric oxide production. JF - Asian Pacific journal of cancer prevention : APJCP AU - Das, Rajat Kumar AU - Bhattacharya, Sudin AD - Department of Cancer Chemoprevention, Chittaranajan National Cancer Institute, Kolkata 700 026, India. PY - 2004 SP - 151 EP - 158 VL - 5 IS - 2 SN - 1513-7368, 1513-7368 KW - Cyanates KW - 0 KW - Selenium Compounds KW - Nitric Oxide KW - 31C4KY9ESH KW - selenocyanic acid KW - 5749-48-4 KW - Croton Oil KW - 8001-28-3 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Glutathione Reductase KW - EC 1.8.1.7 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Sensitivity and Specificity KW - Probability KW - Animals KW - Analysis of Variance KW - Drug Administration Schedule KW - Random Allocation KW - Dose-Response Relationship, Drug KW - Glutathione Transferase -- metabolism KW - Superoxide Dismutase -- metabolism KW - Disease Models, Animal KW - Mice KW - Lipid Peroxidation -- physiology KW - Mice, Inbred A KW - Glutathione Reductase -- metabolism KW - Oxidative Stress KW - Carcinogenicity Tests KW - Female KW - Cyanates -- pharmacology KW - Papilloma -- prevention & control KW - Papilloma -- pathology KW - Selenium Compounds -- pharmacology KW - Skin Neoplasms -- pathology KW - Nitric Oxide -- biosynthesis KW - Skin Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66691314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Inhibition+of+DMBA-croton+oil+two-stage+mouse+skin+carcinogenesis+by+diphenylmethyl+selenocyanate+through+modulation+of+cutaneous+oxidative+stress+and+inhibition+of+nitric+oxide+production.&rft.au=Das%2C+Rajat+Kumar%3BBhattacharya%2C+Sudin&rft.aulast=Das&rft.aufirst=Rajat&rft.date=2004-04-01&rft.volume=5&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indian food ingredients and cancer prevention - an experimental evaluation of anticarcinogenic effects of garlic in rat colon. AN - 66688915; 15244513 AB - The major food items of Indian cuisine include rice, wheat, diary products, and abundant fruits and vegetables. Beside these, there are several kinds of herbs and spices as important ingredients, containing many phytochemicals with medicinal properties, adding taste to Indian cuisine. An impressive body of data exists in support of the concept that Indian food ingredients can be used in preventive strategies aimed at reducing the incidence and mortality of different types of cancers because of their antioxidative, antimutagenic and anticarcinogenic properties. Vital ingredients used in Indian cooking include turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic Garlic is an indispensable ingredient of Indian food and this report concerns the chemopreventive efficacy of garlic in an azoxymethane induced rodent colon carcinogenesis model. The effect of garlic was evaluated in terms of aberrant crypt foci, putative preneoplastic lesions in the colon. In addition, cell proliferation and levels of apoptosis were determined and the expression of cyclooxygenase-2 protein was analyzed. Following treatment, significant inhibition of cell proliferation and induction of apoptosis, as well as suppression of cyclooxygenase-2 activity were observed, associated with significant reduction in the incidence of aberrant crypt foci. The study points to combined protective effects of garlic components on colon carcinogenesis. JF - Asian Pacific journal of cancer prevention : APJCP AU - Sengupta, Archana AU - Ghosh, Samit AU - Bhattacharjee, Shamee AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata 700026 India. archanadi1@rediffmail.com PY - 2004 SP - 126 EP - 132 VL - 5 IS - 2 SN - 1513-7368, 1513-7368 KW - Antioxidants KW - 0 KW - Isoenzymes KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Probability KW - Reference Values KW - Analysis of Variance KW - Cell Division -- drug effects KW - Disease Models, Animal KW - India KW - Rats KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Culture Techniques KW - Antioxidants -- pharmacology KW - Apoptosis -- drug effects KW - Male KW - Isoenzymes -- analysis KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- analysis KW - Diet KW - Garlic KW - Colonic Neoplasms -- prevention & control KW - Colonic Neoplasms -- pathology KW - Isoenzymes -- metabolism KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66688915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Indian+food+ingredients+and+cancer+prevention+-+an+experimental+evaluation+of+anticarcinogenic+effects+of+garlic+in+rat+colon.&rft.au=Sengupta%2C+Archana%3BGhosh%2C+Samit%3BBhattacharjee%2C+Shamee%3BDas%2C+Sukta&rft.aulast=Sengupta&rft.aufirst=Archana&rft.date=2004-04-01&rft.volume=5&rft.issue=2&rft.spage=126&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative evaluation of antiproliferative activity and induction of apoptosis by some fluoroquinolones with a human non-small cell lung cancer cell line in culture. AN - 66688820; 15244525 AB - Lung cancer is the leading cause of cancer- related death in the world today. Since the effective management of drug resistant lung cancer, and particularly non-small cell lung carcinomas is a major problem, attempts need to be made to identify new potential anticancer drugs that can kill non-small cell lung cancer cells efficiently. In the present study, a human non-small cell lung carcinoma NCI-H460 cell line was used to evaluate the antiproliferative activity of Fluoroquinolones like Enoxacin, Norfloxacin, Ciprofloxacin and Levofloxacin. As determined by Sulphorodhamine B assay (SRB assay), all Fluoroquinolones caused cellular growth inhibition in a concentration and time-dependent manner. Enoxacin was found to be the most effective Fluoroquinolone followed by Norfloxacin, Ciprofloxacin and Levofloxacin. Growth inhibitory effects were also found to be independent of the concentrations of serum growth factors in culture medium or variation of initial cell seeding density and proved to be irreversible in nature. Appearance of rounded cells with altered morphology and cell surface blebbing indicated cell killing by apoptosis. Cell shrinkage, nuclear condensation & fragmentation, and cytoplasmic blebbing as indicated by MGG staining confirmed this to be the case. Thus, this investigation clearly demonstrated that the NCI-H460 human non-small cell lung carcinoma cell line is highly sensitive to Fluoroquinolone treatment. The Fluoroquinolones used in this study which are clinically used as antibacterial agents, can also inhibit tumor cell growth suggesting their potential use in a strategy for cancer treatment which might help in controlling cancer. JF - Asian Pacific journal of cancer prevention : APJCP AU - Mondal, E R AU - Das, S K AU - Mukherjee, P AD - Dept of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata -700026, India. PY - 2004 SP - 196 EP - 204 VL - 5 IS - 2 SN - 1513-7368, 1513-7368 KW - Fluoroquinolones KW - 0 KW - Enoxacin KW - 325OGW249P KW - Ciprofloxacin KW - 5E8K9I0O4U KW - Levofloxacin KW - 6GNT3Y5LMF KW - Ofloxacin KW - A4P49JAZ9H KW - Norfloxacin KW - N0F8P22L1P KW - Index Medicus KW - Probability KW - Reference Values KW - Dose-Response Relationship, Drug KW - Enoxacin -- pharmacology KW - Humans KW - Cell Line, Tumor KW - Ciprofloxacin -- pharmacology KW - Evaluation Studies as Topic KW - Ofloxacin -- pharmacology KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Lung Neoplasms KW - Norfloxacin -- pharmacology KW - Carcinoma, Non-Small-Cell Lung KW - Apoptosis -- physiology KW - Lung -- cytology KW - Apoptosis -- drug effects KW - Lung -- drug effects KW - Cell Division -- drug effects KW - Fluoroquinolones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66688820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Comparative+evaluation+of+antiproliferative+activity+and+induction+of+apoptosis+by+some+fluoroquinolones+with+a+human+non-small+cell+lung+cancer+cell+line+in+culture.&rft.au=Mondal%2C+E+R%3BDas%2C+S+K%3BMukherjee%2C+P&rft.aulast=Mondal&rft.aufirst=E&rft.date=2004-04-01&rft.volume=5&rft.issue=2&rft.spage=196&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiology of liver cancer: an overview. AN - 66687554; 15244512 AB - The incidence of liver cancer varies widely throughout the world, with high rates in sub - Saharan Africa, eastern and southeastern Asia, and Melanesia and a low incidence in Northern and Western Europe and the Americas. Primary cancers of the liver in adults are of two main histological types: hepatocellular carcinoma, which is derived from hepatocytes, and cholangiocarcinoma, which is derived from the epithelial lining of the intrahepatic bile ducts. Hepatocellular cancer is a frequently occurring tumor in individuals in many developing countries, where several important risk factors have been demonstrated, including chronic infection with hepatitis B and C viruses and other environmental factors, such as exposure to aflatoxin, consumption of alcohol, and cigarette smoking. By contrast, cholangiocarcinoma is less common, accounting for only 7.7% of malignant tumors of the liver in the United States. However, in parts of Southeast Asia, cholangiocarcinoma occurs more frequently; it is responsible for more than 60% of liver tumors in northeastern Thailand. The geographic distribution worldwide coincides with endemic areas of the liver flukes, Opisthorchis viverrini and Clonorchis sinensis. The interaction between genes and the environment and the interplay of environmental factors, which include diet and other lifestyle parameters, illustrate the complexity underlying susceptibility. JF - Asian Pacific journal of cancer prevention : APJCP AU - Srivatanakul, Petcharin AU - Sriplung, Hutcha AU - Deerasamee, Somyos AD - National Cancer Institute, Rajchathewee 10400, Bangkok Thailand. petchar@health.moph.go.th PY - 2004 SP - 118 EP - 125 VL - 5 IS - 2 SN - 1513-7368, 1513-7368 KW - Index Medicus KW - Global Health KW - Alcoholism -- epidemiology KW - Risk Factors KW - Humans KW - Prognosis KW - Asia -- epidemiology KW - Incidence KW - Thailand -- epidemiology KW - Male KW - Female KW - Survival Analysis KW - Hepatitis, Viral, Human -- epidemiology KW - Liver Neoplasms -- pathology KW - Bile Duct Neoplasms -- epidemiology KW - Bile Ducts, Intrahepatic KW - Bile Duct Neoplasms -- pathology KW - Cholangiocarcinoma -- pathology KW - Cholangiocarcinoma -- epidemiology KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms -- epidemiology KW - Cause of Death KW - Carcinoma, Hepatocellular -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66687554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Epidemiology+of+liver+cancer%3A+an+overview.&rft.au=Srivatanakul%2C+Petcharin%3BSriplung%2C+Hutcha%3BDeerasamee%2C+Somyos&rft.aulast=Srivatanakul&rft.aufirst=Petcharin&rft.date=2004-04-01&rft.volume=5&rft.issue=2&rft.spage=118&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicotine dependence criteria of the DIS and DSM-III-R: a factor analysis. AN - 66649101; 15203804 AB - This paper reports a factor analysis of the symptoms of nicotine dependence that were determined in an assessment of 821 current cigarette-smoking research volunteers, according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) of the American Psychiatric Association as well as an analysis of a subset who unsuccessfully attempted to quit (n=636). In the total sample, two factors with eigenvalues greater than 1 accounted for 62.7% of the variance. When the factor analysis was repeated with the subset of research volunteers who unsuccessfully attempted to quit, only one DSM-III-R nicotine dependence symptom loaded on the second factor. This finding suggests that the two-factor structure found in this and a previous factor analysis study of the nicotine dependence segment of the DSM-III-R may be an artifact of the skipout pattern of the DSM-III-R, which assumes that smokers who have not attempted to quit have not experienced withdrawal symptoms or used tobacco to avoid these symptoms. Goodness-of-fit measures suggested that the two-factor structure is a better fit than the one-factor structure for both the total population and the subset who unsuccessfully attempted to quit or cut down. Our sample of current smokers who had not attempted to quit (n=185) was too small to permit factor analyses. Further work with other large samples from the general population of current smokers who have unsuccessfully attempted to quit as well as those who have not attempted to quit will enhance our understanding of the factor structure of the nicotine dependence segment of the DSM-III-R and clarify the effect of the skipout pattern on its factor structure. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Radzius, Aleksandras AU - Gallo, Joseph AU - Gorelick, David AU - Cadet, Jean Lud AU - Uhl, George AU - Henningfield, Jack AU - Moolchan, Eric AD - National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA. a.n.radzius@erols.com Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 303 EP - 308 VL - 6 IS - 2 SN - 1462-2203, 1462-2203 KW - Ganglionic Stimulants KW - 0 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Cross-Sectional Studies KW - Factor Analysis, Statistical KW - Humans KW - Adult KW - Treatment Outcome KW - Prognosis KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Smoking Cessation -- psychology KW - Ganglionic Stimulants -- pharmacology KW - Nicotine -- pharmacology KW - Tobacco Use Disorder -- psychology KW - Diagnostic and Statistical Manual of Mental Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66649101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Nicotine+dependence+criteria+of+the+DIS+and+DSM-III-R%3A+a+factor+analysis.&rft.au=Radzius%2C+Aleksandras%3BGallo%2C+Joseph%3BGorelick%2C+David%3BCadet%2C+Jean+Lud%3BUhl%2C+George%3BHenningfield%2C+Jack%3BMoolchan%2C+Eric&rft.aulast=Radzius&rft.aufirst=Aleksandras&rft.date=2004-04-01&rft.volume=6&rft.issue=2&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-18 N1 - Date created - 2004-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coping Styles among Families of Children with HIV Infection AN - 61495613; 200503319 AB - The primary aim of this study was to examine coping strategies among families of HIV-infected children & how they relate to medical, central nervous system (CNS) & family environment factors. Caregivers of HIV-positive children (N=52) completed a family coping measure (F-COPES) & provided information regarding family environment. Data regarding medical & CNS status were obtained from patient records. Results indicated that families' passive coping & spiritual support were among the coping techniques used most often, & social support was used least often. Medical variables were unrelated to any coping styles. Families of children with CNS impairment endorsed more passive coping techniques than families of children with no apparent deficits. A trend was found for non-biological caregivers to seek out more community resources & support than biological caregivers. Findings suggest the need to target families least likely to utilize resources, & to teach them to effectively seek out & benefit from social & community supports. 2 Tables, 1 Figure, 34 References. Adapted from the source document. JF - AIDS Care AU - Martin, Staci Martin AU - Wolters, P L AU - Klaas, P A AU - Perez, L AU - Wood, L V AD - HIV & AIDS Malignancy Branch, National Cancer Instit, Bethesda martins@mail.nih.gov Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 283 EP - 292 VL - 16 IS - 3 SN - 0954-0121, 0954-0121 KW - Family Relations KW - Acquired Immune Deficiency Syndrome KW - Psychosocial Factors KW - Social Support KW - Children KW - Coping KW - article KW - 6126: acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61495613?accountid=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=AIDS+Care&rft.atitle=Coping+Styles+among+Families+of+Children+with+HIV+Infection&rft.au=Martin%2C+Staci+Martin%3BWolters%2C+P+L%3BKlaas%2C+P+A%3BPerez%2C+L%3BWood%2C+L+V&rft.aulast=Martin&rft.aufirst=Staci&rft.date=2004-04-01&rft.volume=16&rft.issue=3&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=AIDS+Care&rft.issn=09540121&rft_id=info:doi/10.1080%2F09540120410001665295 LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Number of references - 34 N1 - Last updated - 2016-09-28 N1 - CODEN - AIDCEF N1 - SubjectsTermNotLitGenreText - Coping; Acquired Immune Deficiency Syndrome; Family Relations; Social Support; Psychosocial Factors; Children DO - http://dx.doi.org/10.1080/09540120410001665295 ER - TY - JOUR T1 - Epidemiologic profile of symptomatic gastroenteritis in pediatric oncology patients receiving chemotherapy AN - 20743016; 9329582 AB - Background Patients with cancer who receive intensive chemotherapeutic regimens are subject to profound immunosuppression and are susceptible to an extended array of pathogens. Procedure The infectious causes of symptomatic gastroenteritis as evidenced by diarrhea +/- fever, vomiting, and abdominal colic in children following chemotherapy were prospectively monitored at National Cancer Institute, Cairo University. Results A total of 104 diarrhea episodes were recorded in our institution during a 10-month period, of which an infectious cause was detected in 74 (71.1%). Bacterial and fungal pathogens were isolated in culture from 41 (39.4%) and 24 (23.1%), respectively, while Clostridia difficile (C. difficile) and Cryptosporidium parvum (C. parvum) were detected in 15 (14.4%) and 10 (9.6%) of 104 diarrhea episodes following chemotherapy, respectively. Mixed infections were found in 24 of the patients; whereas, no cause was demonstrable in 30. Hospital acquired and mixed infections were the worst as regards morbidity (P = 0.004 and 0.02) and mortality (P = 0.007 and <0.001) of the infectious episode regardless the cause, respectively. On multivariate analysis, C. difficile was associated with the highest mortality rate (OR = 0.04, 95% CI = 0.01-0.19), followed by fungal pathogens (OR = 0.20, 95% CI = 0.05-0.74) and bacterial infections (OR = 0.20, 95% CI = 0.05-0.79). Conclusions Infectious gastroenteritis is an important cause of morbidity and mortality in hospitalized pediatric cancer patients receiving intensified protocols of chemotherapy. JF - Pediatric Blood & Cancer AU - El-Mahallawy, Hadir A AU - El-Din, Nelly H Aly AU - Salah, Fatma AU - El-Arousy, Maha AU - El-Naga, Sherif Abou AD - Clinical Pathology, National Cancer Institute, Cairo University, Egypt, hadir38@hotmail.com Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 338 EP - 342 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 42 IS - 4 SN - 1545-5009, 1545-5009 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Mortality KW - Diarrhea KW - Vomiting KW - Pediatrics KW - Chemotherapy KW - Oncology KW - Pathogens KW - Children KW - Cancer KW - Morbidity KW - Cryptosporidium parvum KW - Fever KW - Blood KW - Multivariate analysis KW - Gastroenteritis KW - Hospitals KW - Mixed infection KW - Immunosuppression KW - K 03400:Human Diseases KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20743016?accountid=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=Pediatric+Blood+%26+Cancer&rft.atitle=Epidemiologic+profile+of+symptomatic+gastroenteritis+in+pediatric+oncology+patients+receiving+chemotherapy&rft.au=El-Mahallawy%2C+Hadir+A%3BEl-Din%2C+Nelly+H+Aly%3BSalah%2C+Fatma%3BEl-Arousy%2C+Maha%3BEl-Naga%2C+Sherif+Abou&rft.aulast=El-Mahallawy&rft.aufirst=Hadir&rft.date=2004-04-01&rft.volume=42&rft.issue=4&rft.spage=338&rft.isbn=&rft.btitle=&rft.title=Pediatric+Blood+%26+Cancer&rft.issn=15455009&rft_id=info:doi/10.1002%2Fpbc.10394 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-10-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Mortality; Vomiting; Diarrhea; Pediatrics; Chemotherapy; Oncology; Pathogens; Children; Morbidity; Cancer; Fever; Blood; Multivariate analysis; Gastroenteritis; Immunosuppression; Mixed infection; Hospitals; Cryptosporidium parvum DO - http://dx.doi.org/10.1002/pbc.10394 ER - TY - JOUR T1 - The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane beta -barrel AN - 20636158; 7492204 AB - Transferrin binding protein A (TbpA) is a TonB-dependent outer membrane protein expressed by pathogenic bacteria for iron acquisition from human transferrin. The N-terminal 160 residues (plug domain) of TbpA were overexpressed in both the periplasm and cytoplasm of Escherichia coli. We found this domain to be soluble and monodisperse in solution, exhibiting secondary structure elements found in plug domains of structurally characterized TonB-dependent transporters. Although the TbpA plug domain is apparently correctly folded, we were not able to observe an interaction with human transferrin by isothermal titration calorimetry or nitrocellulose binding assays. These experiments suggest that the plug domain may fold independently of the beta -barrel, but extracellular loops of the beta -barrel are required for ligand binding. JF - FEBS Letters AU - Oke, M AU - Sarra, R AU - Ghirlando, R AU - Farnaud, S AU - Gorringe, A R AU - Evans, R W AU - Buchanan, S K AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA, skbuchan@helix.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 294 EP - 300 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 564 IS - 3 SN - 0014-5793, 0014-5793 KW - Microbiology Abstracts B: Bacteriology KW - Transferrin binding protein A KW - Iron transport KW - Human transferrin KW - TonB KW - Neisseria meningitidis KW - Protein structure KW - Transferrin KW - Pyroxylin KW - outer membrane proteins KW - Cytoplasm KW - Titration KW - Secondary structure KW - Escherichia coli KW - Calorimetry KW - Iron KW - periplasm KW - J 02330:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20636158?accountid=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=The+plug+domain+of+a+neisserial+TonB-dependent+transporter+retains+structural+integrity+in+the+absence+of+its+transmembrane+beta+-barrel&rft.au=Oke%2C+M%3BSarra%2C+R%3BGhirlando%2C+R%3BFarnaud%2C+S%3BGorringe%2C+A+R%3BEvans%2C+R+W%3BBuchanan%2C+S+K&rft.aulast=Oke&rft.aufirst=M&rft.date=2004-04-01&rft.volume=564&rft.issue=3&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=FEBS+Letters&rft.issn=00145793&rft_id=info:doi/10.1016%2FS0014-5793%2804%2900196-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-06-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Protein structure; Pyroxylin; Transferrin; outer membrane proteins; Cytoplasm; Secondary structure; Titration; Calorimetry; periplasm; Iron; Escherichia coli DO - http://dx.doi.org/10.1016/S0014-5793(04)00196-6 ER - TY - JOUR T1 - An electroelution apparatus for sequential transfer of sodium dodecyl sulfate-proteins into agarose and mass spectrometric identification of Li-Na-dodecyl sulfate-proteins from solubilized agarose AN - 20404129; 7761964 AB - Separated protein bands are sequentially electrophoresed into low melting agarose plugs distributed in an apparatus of original design along the surface of a plastic drum. The rotation of the drum is synchronized to migration of electrophoretic bands to receive each band individually. Agarose plugs are dissolved enzymatically for transfer into the mass spectrometer. One L of the agarose solution containing 1pmol of each of three lithium and natrium salts of dodecyl sulfate (Li-Na-DS)-proteins were applied to matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) without any prepurification. It yields a signal indistinguishable from that obtained in the absence of agarose. JF - Electrophoresis AU - Buzas, Zsuzsanna AU - Antal, Jozsef AU - Gilligan, John J AU - Backlund, Peter S AU - Yergey, Alfred L AU - Chrambach, Andreas AD - Agricultural Biotechnology Center, Godollo, Hungary, acc@helix.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 966 EP - 969 PB - Wiley-VCH, Postfach 101161 Weinheim 69451 Germany, [mailto:info@wiley-vch.de], [URL:http://www.wiley-vch.de/publish/en/] VL - 25 IS - 7-8 SN - 0173-0835, 0173-0835 KW - Biotechnology and Bioengineering Abstracts KW - Melting KW - Salts KW - Lasers KW - Plastics KW - Lithium KW - Sulfate KW - Spectrometry KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20404129?accountid=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=Electrophoresis&rft.atitle=An+electroelution+apparatus+for+sequential+transfer+of+sodium+dodecyl+sulfate-proteins+into+agarose+and+mass+spectrometric+identification+of+Li-Na-dodecyl+sulfate-proteins+from+solubilized+agarose&rft.au=Buzas%2C+Zsuzsanna%3BAntal%2C+Jozsef%3BGilligan%2C+John+J%3BBacklund%2C+Peter+S%3BYergey%2C+Alfred+L%3BChrambach%2C+Andreas&rft.aulast=Buzas&rft.aufirst=Zsuzsanna&rft.date=2004-04-01&rft.volume=25&rft.issue=7-8&rft.spage=966&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/10.1002%2Felps.200305797 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Spectrometry; Salts; Lithium; Lasers; Sulfate; Melting; Plastics DO - http://dx.doi.org/10.1002/elps.200305797 ER - TY - JOUR T1 - Hormetic Versus Toxic Effects of Vegetable Tannin in a Multitest Study AN - 20199473; 6018244 AB - Tannin from mimosa trees (Acacia sp.) utilized intraditional leather tanning was tested for toxicity in sea urchin (Sphaerechinus granularis and Paracentrotus lividus) embryos and sperm, marine, and freshwater algae (Selenastrum capricornutum and Dunaliella tertiolecta), and Daphnia magna. Based on a two-step tanning procedure used in traditional tanneries, two mimosa tannin preparations, i.e., fresh tannin (FT) and used tannin (UT), were tested as suspensions. The early results in S. granularis embryos showed that UT exerted lower acute toxicity than FT, namely, 1 vs 100 mg/L, to obtain 100% mortality, respectively. Subsequent bioassays were conducted on fresh tannin water extracts (TWE) corresponding to nominal tannin concentrations ranging from 0.1 to 30 mg/L. Developmental toxicity, up to embryonic mortality was exerted by TWE at levels >1 mg/L, S. granularis being more sensitive than P. lividus embryos/larvae. At the concentration of 0.1 mg/L, the frequencies of larval malformations were significantly lower than in controls. This positive stimulatory effect (currently termed as hormesis) was observed in extended numbers of culture replicates (up to 14) and was significant in the embryo cultures characterized by a relatively poor control quality (with or = 70% viable larvae in controls). Cytogenetic analysis of S. granularis embryos reared in FT or UT suspensions (1 mg/L to 1 g/L) showed mitotoxic effects (decrease in active mitoses per embryo) in FT-exposed, but not in UT-exposed embryos. Mitotic aberrations were significantly increased by 10 mg/L UT. Sperm fertilization success in both sea urchin species showed an increasing fertilization rate (FR) up to 0.3 mg/L TWE and a dose-related decrease in FR up to 30 mg/L. Again, the offspring of P. lividus sperm exposed to TWE (0.1 and 0.3 mg/L) showed a decrease in larval malformations compared to controls, whereas a dose-related increase in developmental defects was observed in the offspring of P. lividus sperm exposed to higher TWE levels (1 to 30 mg/L). Algal cell growth bioassays in two species (S. capricornutum and D. tertiolecta) also showed a maximum growth at TWE levels ranging from 0.3 to 3 mg/L and a subsequent decline up to 30 mg/L TWE. D. magna bioassays resulted in daphnid immobilization by TWE concentrations ranging from 100 to 300 mg/L. The results demonstrate that tannins utilized in traditional leather tanning industry may raise concern of environmental damage at relatively high concentrations, whereas low-level tannins may result in hormetic effects. The present study also points to the need for bioassay design that should rely on adequate criteria in control quality, allowing to detect both inhibitory and hormetic effects. JF - Archives of Environmental Contamination and Toxicology AU - De Nicola, E AU - Gallo, M AU - Iaccarino, M AU - Meric, S AU - Oral, R AU - Russo, T AU - Sorrentino, T AU - Tuenay, O AU - Vuttariello, E AU - Warnau, M AU - Pagano, G AD - Italian National Cancer Institute, 'G. Pascale" Foundation, v. M. Semmola, I-80131 Naples, and CROP, I-83013 Mercogliano (AV), Italy Y1 - 2004/04// PY - 2004 DA - April 2004 SP - 336 EP - 344 PB - Springer-Verlag VL - 46 IS - 3 SN - 0090-4341, 0090-4341 KW - Acacias KW - tannic acid KW - Ecology Abstracts; Aqualine Abstracts; Oceanic Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; Pollution Abstracts; Water Resources Abstracts; Toxicology Abstracts KW - Echinoderms KW - Vegetables KW - Cell culture KW - Sperm KW - Freshwater KW - Toxicity tests KW - Bioassay KW - Mimosa KW - Fresh water KW - Fertilization KW - Paracentrotus lividu KW - Embryos KW - Algae KW - Larvae KW - Brackish KW - Tannins KW - Sphaerechinus granularis KW - Bioassays KW - hormesis KW - Water Pollution Effects KW - Progeny KW - Echinoidea KW - Toxicity testing KW - Selenastrum capricornutum KW - Leather KW - Marine invertebrates KW - Pollution effects KW - Acute toxicity KW - Embryonic Growth Stage KW - Larval development KW - Acacia KW - Daphnia magna KW - Dunaliella tertiolecta KW - Freshwater crustaceans KW - Tanning KW - Tannic acid KW - Paracentrotus lividus KW - Growth rate KW - Marine KW - Mortality KW - Toxicity KW - Bioaccumulation KW - Cultures KW - Immobilization KW - D 04070:Pollution KW - O 4020:Pollution - Organisms/Ecology/Toxicology KW - X 24172:Plants KW - Q5 08504:Effects on organisms KW - SW 3030:Effects of pollution KW - AQ 00008:Effects of Pollution KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20199473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+Environmental+Contamination+and+Toxicology&rft.atitle=Hormetic+Versus+Toxic+Effects+of+Vegetable+Tannin+in+a+Multitest+Study&rft.au=De+Nicola%2C+E%3BGallo%2C+M%3BIaccarino%2C+M%3BMeric%2C+S%3BOral%2C+R%3BRusso%2C+T%3BSorrentino%2C+T%3BTuenay%2C+O%3BVuttariello%2C+E%3BWarnau%2C+M%3BPagano%2C+G&rft.aulast=De+Nicola&rft.aufirst=E&rft.date=2004-04-01&rft.volume=46&rft.issue=3&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=Archives+of+Environmental+Contamination+and+Toxicology&rft.issn=00904341&rft_id=info:doi/10.1007%2Fs00244-003-2293-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-02-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Growth rate; Bioaccumulation; Bioassays; Marine invertebrates; Freshwater crustaceans; Pollution effects; Larval development; Toxicity tests; Mortality; Vegetables; Leather; Cell culture; Sperm; Acute toxicity; Fertilization; Fresh water; hormesis; Tanning; Progeny; Embryos; Tannic acid; Immobilization; Toxicity testing; Echinoderms; Water Pollution Effects; Cultures; Larvae; Tannins; Toxicity; Embryonic Growth Stage; Bioassay; Paracentrotus lividus; Mimosa; Paracentrotus lividu; Dunaliella tertiolecta; Echinoidea; Sphaerechinus granularis; Daphnia magna; Acacia; Selenastrum capricornutum; Algae; Freshwater; Brackish; Marine DO - http://dx.doi.org/10.1007/s00244-003-2293-5 ER - TY - JOUR T1 - Automated large-scale purification of a G protein-coupled receptor for neurotensin AN - 19877926; 7492203 AB - Structure determination of integral membrane proteins requires milligram amounts of purified, functional protein on a regular basis. Here, we describe a protocol for the purification of a G protein-coupled neurotensin receptor fusion protein at the 3-mg or 10-mg level using immobilized metal affinity chromatography and a neurotensin column in a fully automated mode. Fermentation at a 200-l scale of Escherichia coli expressing functional receptors provides the material needed to feed into the purification routine. Constructs with tobacco etch virus protease recognition sites at either end of the receptor allow the isolation of neurotensin receptor devoid of its fusion partners. The presented expression and purification procedures are simple and robust, and provide the basis for crystallization experiments of receptors on a routine basis. JF - FEBS Letters AU - White, Jim F AU - Trinh, Loc B AU - Shiloach, Joseph AU - Grisshammer, Reinhard AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-8030, USA, rkgriss@helix.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 289 EP - 293 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 564 IS - 3 SN - 0014-5793, 0014-5793 KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Large-scale purification KW - G protein-coupled receptor KW - Automation KW - Detergent KW - Neurotensin receptor KW - Crystallization KW - neurotensin receptors KW - Metals KW - Neurotensin KW - Fermentation KW - double prime G protein-coupled receptors KW - protein purification KW - Membrane proteins KW - Affinity chromatography KW - Escherichia coli KW - Tobacco etch virus KW - Proteinase KW - Fusion protein KW - J 02420:Plant Diseases KW - W 30945:Fermentation & Cell Culture KW - V 22310:Genetics, Taxonomy & Structure KW - N3 11145:Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19877926?accountid=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=Automated+large-scale+purification+of+a+G+protein-coupled+receptor+for+neurotensin&rft.au=White%2C+Jim+F%3BTrinh%2C+Loc+B%3BShiloach%2C+Joseph%3BGrisshammer%2C+Reinhard&rft.aulast=White&rft.aufirst=Jim&rft.date=2004-04-01&rft.volume=564&rft.issue=3&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=FEBS+Letters&rft.issn=00145793&rft_id=info:doi/10.1016%2FS0014-5793%2804%2900195-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-08-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Crystallization; Affinity chromatography; Metals; neurotensin receptors; Neurotensin; double prime G protein-coupled receptors; Fermentation; Proteinase; Membrane proteins; Fusion protein; protein purification; Escherichia coli; Tobacco etch virus DO - http://dx.doi.org/10.1016/S0014-5793(04)00195-4 ER - TY - JOUR T1 - Prevalence and Factors Associated with the Consumption of Betel-Nut Among Military Conscripts in Taiwan AN - 19767650; 5928180 AB - Objective: This study evaluates the prevalence of betel-nut chewing among military personnel stationed on Taiwan's offshore islands. Furthermore, this study examines variables to identify which may predict a greater predilection toward betel-nut chewing among the conscript population studied.Methods: A cross-sectional mass screening was conducted of compulsory military service personnel stationed on Taiwan's offshore islands between August 1 and December 31, 2001. A total of 7574 military employees were included in this survey. Information regarding betel-nut chewing habits were ascertained using a standard structured questionnaire, which including the level and duration of betel-nut chewing as well as respondents' knowledge, attitude and practices with regard to consumption of this product.Results: Conscripts were found to be less likely to chew betel-nut regularly while performing military service. There are 1535 (20.3%) of respondents reporting to habitually chew betel-nut prior to active duty shrank to 1048 (13.8%) after going on active-duty. The most reasons to chew betel-nut among the recruits after military services are curiosity (33.3%) and as a stimulant (29.8%). About 46% of military employees who currently chew betel-nut report an interest to quit in the future. The risk factors for betel-nut chewing include individual factors (e.g., age, education, knowledge, and attitude toward betel-nut chewing), lifestyle habits (e.g., cigarette smoking), and familial factors (e.g., consumption of betel-nut by parents). More interesting, the recruits had the habit of cigarette smoking associated with increase risk for betel-nut chewing (OR: 7.18; 95% CI: 5.66-9.20).Conclusions: Although the military has made considerable progress in reducing betel-nut chewing on military campuses, the prevalence of betel-nut chewing is still relatively high and, in 2001, affected about one quarter of all military personnel stationed on the abovementioned offshore islands. In future efforts to lower betel-nut consumption among high risk groups, targeting the group of conscripted military personnel described in this study should be considered. JF - European Journal of Epidemiology AU - Lin, Y AU - Chu, N AU - Wu, D AU - Shen, M AD - Department of Otolaryngology, Department of Community Medicine, Tri-Service General Hospital, NDMC, P.O. Box 90048-509, Nei-Hu, Taipei, Taiwan, ROC, chuepi@ndmctsgh.edu.tw Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 343 EP - 351 PB - Kluwer Academic Publishers VL - 19 IS - 4 SN - 0393-2990, 0393-2990 KW - Risk Abstracts KW - Taiwan KW - Education KW - Age KW - Islands KW - Cigarette smoking KW - Military KW - attitudes KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19767650?accountid=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=European+Journal+of+Epidemiology&rft.atitle=Prevalence+and+Factors+Associated+with+the+Consumption+of+Betel-Nut+Among+Military+Conscripts+in+Taiwan&rft.au=Lin%2C+Y%3BChu%2C+N%3BWu%2C+D%3BShen%2C+M&rft.aulast=Lin&rft.aufirst=Y&rft.date=2004-04-01&rft.volume=19&rft.issue=4&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Epidemiology&rft.issn=03932990&rft_id=info:doi/10.1023%2FB%3AEJEP.0000024695.87008.ff LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Age; Education; Islands; Cigarette smoking; Military; attitudes; Taiwan DO - http://dx.doi.org/10.1023/B:EJEP.0000024695.87008.ff ER - TY - JOUR T1 - Seeing into cells AN - 19630195; 7362692 AB - The promise of in vivo molecular imaging in oncology. JF - EMBO Reports AU - Sullivan, Daniel C AU - Kelloff, Gary AD - Daniel C. Sullivan and Gary Kelloff are at the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA., ds274k@nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 292 EP - 296. PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 6 IS - 4 SN - 1469-221X, 1469-221X KW - Biotechnology and Bioengineering Abstracts KW - Reviews KW - Oncology KW - imaging KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19630195?accountid=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=EMBO+Reports&rft.atitle=Seeing+into+cells&rft.au=Sullivan%2C+Daniel+C%3BKelloff%2C+Gary&rft.aulast=Sullivan&rft.aufirst=Daniel&rft.date=2004-04-01&rft.volume=6&rft.issue=4&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=EMBO+Reports&rft.issn=1469221X&rft_id=info:doi/10.1038%2Fsj.embor.7400382 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Reviews; imaging; Oncology DO - http://dx.doi.org/10.1038/sj.embor.7400382 ER - TY - JOUR T1 - Pseudomonas aeruginosa from canine otitis externa exhibit a quorum sensing deficiency AN - 19263223; 5847034 AB - Pseudomonas aeruginosa LasB elastase gene (lasB) transcription depends on cell density-dependent quorum-sensing mechanisms of gene activation. Previously, we collected several non-mucoid P. aeruginosa veterinary isolates and showed that the total matrix protease phenotype was similar for isolates regardless of host and site of isolation. In contrast, isolates from chronic canine ear infections (otitis externa) were significantly more likely to exhibit less elastase activity as measured by elastin Congo red than from any other site [Clin. Diag. Lab. Immun. 8 (2001) 632]. In this study, we found that the elastase deficiency phenotype is stable upon passage in broth culture. Transcript amplification analyses indicated that the elastase deficiency appears to be strain-specific, with each isolate exhibiting a unique expression profile relative to strain PAO1. Although a number of strain-specific transcriptional differences were observed, the overall pattern that emerges is a quorum sensing deficiency among canine ear P. aeruginosa isolates. JF - Veterinary Microbiology AU - Tron, EAM AU - Wilke, H L AU - Petermann AU - Rust, L AD - Department of Veterinary and Microbiological Sciences, van Es Laboratories, North Dakota State University, Fargo, ND 58105, USA, lr228v@nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 121 EP - 129 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 99 IS - 2 SN - 0378-1135, 0378-1135 KW - LasB protein KW - dogs KW - Microbiology Abstracts B: Bacteriology KW - Pseudomonas aeruginosa KW - Canine otitis externa KW - Quorum sensing KW - Bacterial gene regulation KW - Elastase KW - Matrix metalloproteinases KW - quorum sensing KW - Cell density KW - Transcription KW - Otitis externa KW - Ear KW - J 02862:Infection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19263223?accountid=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=Veterinary+Microbiology&rft.atitle=Pseudomonas+aeruginosa+from+canine+otitis+externa+exhibit+a+quorum+sensing+deficiency&rft.au=Tron%2C+EAM%3BWilke%2C+H+L%3BPetermann%3BRust%2C+L&rft.aulast=Tron&rft.aufirst=EAM&rft.date=2004-04-01&rft.volume=99&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Veterinary+Microbiology&rft.issn=03781135&rft_id=info:doi/10.1016%2Fj.vetmic.2003.12.005 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - quorum sensing; Elastase; Cell density; Otitis externa; Transcription; Ear; Pseudomonas aeruginosa DO - http://dx.doi.org/10.1016/j.vetmic.2003.12.005 ER - TY - JOUR T1 - State-dependent action of cocaine on brain temperature and movement activity: implications for movement sensitization AN - 18043807; 5887049 AB - Because neural activity is highly energy consuming and heat producing, brain temperature offers a reliable, real-time measure of an animal's activity state and its changes induced by environmental and drug challenges. Therefore, it allows evaluation of the activity state of an animal preceding drug administration and its relation to subsequent drug-induced neural effects. This approach was used to explore the state dependency of cocaine's effects. Brain and body temperatures, as well as locomotion were measured simultaneously in rats during repeated, daily administration of cocaine (15 mg/kg ip, daily for 5 days) under different experimental conditions. The drug was administered via (a) a chronically implanted catheter in quiet resting conditions, (b) an injection made under quiet rest or (c) an injection under activated conditions associated with placement in the cage. Although brain temperature and movement increased after cocaine administration in each condition, cocaine's action (evaluated as cocaine-saline difference for both parameters) was situational. Catheter- administered cocaine induced the strongest movement activation and robust, monophasic temperature increase, which remained relatively stable following each subsequent drug infusion. Cocaine injected during quiet and, especially, activated conditions, induced a weaker locomotor activation, while the temperature response (evaluated as drug-saline difference) had a biphasic pattern. Cocaine initially inhibited the temperature increases seen in saline- treated animals (0-20 min) and then induced a more prolonged hyperthermia, which was about twofold weaker than that seen after catheter-administered drug. Although movement activation gradually increased following repeated treatment in activated conditions, the magnitude of this sensitized motor response barely reached the levels induced by the initial cocaine administration via catheter. These data suggest that both the acute effects of cocaine in the brain and their change following repeated drug administration are dependent upon the ongoing neural activity state of the animal. Cocaine's interaction with this activity state is a crucial factor determining the behavioral effects of this drug, including state-dependent motor sensitization. JF - Pharmacology Biochemistry and Behavior AU - Blech-Hermoni, Y AU - Kiyatkin, E A AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, ekiyatki@intra.nida.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 823 EP - 837 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 77 IS - 4 SN - 0091-3057, 0091-3057 KW - rats KW - Animal Behavior Abstracts; Toxicology Abstracts KW - Temperature effects KW - Hyperthermia KW - Body temperature KW - Brain KW - Behavior KW - Locomotion KW - Motor activity KW - Sensitization KW - Cocaine KW - Y 25777:Mammals (excluding primates) KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18043807?accountid=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=Pharmacology+Biochemistry+and+Behavior&rft.atitle=State-dependent+action+of+cocaine+on+brain+temperature+and+movement+activity%3A+implications+for+movement+sensitization&rft.au=Blech-Hermoni%2C+Y%3BKiyatkin%2C+E+A&rft.aulast=Blech-Hermoni&rft.aufirst=Y&rft.date=2004-04-01&rft.volume=77&rft.issue=4&rft.spage=823&rft.isbn=&rft.btitle=&rft.title=Pharmacology+Biochemistry+and+Behavior&rft.issn=00913057&rft_id=info:doi/10.1016%2Fj.pbb.2004.02.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cocaine; Motor activity; Temperature effects; Brain; Hyperthermia; Body temperature; Sensitization; Locomotion; Behavior DO - http://dx.doi.org/10.1016/j.pbb.2004.02.009 ER - TY - JOUR T1 - Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats AN - 17961635; 5896782 AB - Although circulatory shock related to lethal toxin (LeTx) may play a primary role in lethality due to Bacillus anthracis infection, its mechanisms are unclear. We investigated whether LeTx-induced shock is associated with inflammatory cytokine and nitric oxide (NO) release. Sprague-Dawley rats with central venous and arterial catheters received 24-h infusions of LeTx (lethal factor 100 mu g/kg; protective antigen 200 mu g/kg) that produced death beginning at 9 h and a 7-day mortality rate of 53%. By 9 h, mean arterial blood pressure, heart rate, pH, and base excess were decreased and lactate and hemoglobin levels were increased in LeTx nonsurvivors compared with LeTx survivors and controls (diluent only) (P less than or equal to 0.05 for each comparing the 3 groups). Despite these changes, arterial oxygen and circulating leukocytes and platelets were not decreased and TNF- alpha , IL-1 beta , IL-6, and IL- 10 levels were not increased comparing either LeTx nonsurvivors or survivors to controls. Nitrate/nitrite levels and tissue histology also did not differ comparing LeTx animals and controls. In additional experiments, although 24-h infusions of LeTx and Escherichia coli LPS produced similar mortality rates (54 and 56%, respectively) and times to death (13.2 plus or minus 0.8 vs. 11.0 plus or minus 1.7 h, respectively) compared with controls, only LPS reduced circulating leukocytes, platelets, and IL-2 levels and increased TNF- alpha , IL-1 alpha and -1 beta , IL-6, IL-10, interferon- gamma , granulocyte macrophage-colony stimulating factor, RANTES, migratory inhibitory protein-1 alpha , -2, and -3, and monocyte chemotactic protein-1, as well as nitrate/nitrite levels (all P less than or equal to 0.05 for the effects of LPS). Thus, in contrast to LPS, excessive inflammatory cytokine and NO release does not appear to contribute to the circulatory shock and lethality occurring with LeTx in this rat model. Although therapies to modulate these host mediators may be applicable for shock caused by LPS or other bacterial toxins, they may not with LeTx. JF - American Journal of Physiology: Regulatory, Integrative and Comparative Physiology AU - Cui, Xizhong AU - Moayeri, M AU - Li, Yan AU - Li, Xuemei AU - Haley, M AU - Fitz, Y AU - Correa-Araujo, R AU - Banks, S M AU - Leppla, SH AU - Eichacker, P Q AD - Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - R699 EP - R709 VL - 286 IS - 4 SN - 0363-6119, 0363-6119 KW - rats KW - Toxicology Abstracts KW - Mortality KW - Anthrax lethal toxin KW - Shock KW - Circulation KW - Anthrax KW - Bacillus anthracis KW - Toxins KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17961635?accountid=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+Physiology%3A+Regulatory%2C+Integrative+and+Comparative+Physiology&rft.atitle=Lethality+during+continuous+anthrax+lethal+toxin+infusion+is+associated+with+circulatory+shock+but+not+inflammatory+cytokine+or+nitric+oxide+release+in+rats&rft.au=Cui%2C+Xizhong%3BMoayeri%2C+M%3BLi%2C+Yan%3BLi%2C+Xuemei%3BHaley%2C+M%3BFitz%2C+Y%3BCorrea-Araujo%2C+R%3BBanks%2C+S+M%3BLeppla%2C+SH%3BEichacker%2C+P+Q&rft.aulast=Cui&rft.aufirst=Xizhong&rft.date=2004-04-01&rft.volume=286&rft.issue=4&rft.spage=R699&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Physiology%3A+Regulatory%2C+Integrative+and+Comparative+Physiology&rft.issn=03636119&rft_id=info:doi/10.1152%2Fajpregu.00593.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; Toxins; Anthrax lethal toxin; Shock; Circulation; Anthrax; Mortality DO - http://dx.doi.org/10.1152/ajpregu.00593.2003 ER - TY - JOUR T1 - Organic solvent extraction of proteins and peptides from serum as an effective sample preparation for detection and identification of biomarkers by mass spectrometry AN - 17960364; 5916690 AB - A method to extract peptides and low molecular weight proteins from serum under denaturing conditions using acetonitrile containing 0.1% trifluoroacetic acid has been developed. The extraction procedure precipitates large, abundant proteins to simplify subsequent mass spectral analysis. This sample preparation method provides an efficient way to extract serum peptides, enabling them to be compared and identified using different mass spectrometry approaches. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry analysis of mouse blood serum samples prepared by this method allowed detection of two markers which were significantly reduced in mice with B cell lymphoma tumor. One of these markers has been identified as apolipoprotein A-II. JF - Proteomics AU - Chertov, O AU - Biragyn, A AU - Kwak, L W AU - Simpson, J T AU - Boronina, T AU - Hoang, V M AU - Prieto, DA AU - Conrads, T P AU - Veenstra, T D AU - Fisher, R J AD - P.O. Box B, NCI-Frederick, Bldg 469, Rm 237, Frederick, MD 21702, USA, oleg@ncifcrf.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 1195 EP - 1203 VL - 4 IS - 4 SN - 1615-9853, 1615-9853 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Lymphocytes B KW - Proteins KW - Peptides KW - Mass spectroscopy KW - Apolipoprotein A-II KW - W3 33110:Instruments (devices) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17960364?accountid=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=Proteomics&rft.atitle=Organic+solvent+extraction+of+proteins+and+peptides+from+serum+as+an+effective+sample+preparation+for+detection+and+identification+of+biomarkers+by+mass+spectrometry&rft.au=Chertov%2C+O%3BBiragyn%2C+A%3BKwak%2C+L+W%3BSimpson%2C+J+T%3BBoronina%2C+T%3BHoang%2C+V+M%3BPrieto%2C+DA%3BConrads%2C+T+P%3BVeenstra%2C+T+D%3BFisher%2C+R+J&rft.aulast=Chertov&rft.aufirst=O&rft.date=2004-04-01&rft.volume=4&rft.issue=4&rft.spage=1195&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/10.1002%2Fpmic.200300677 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Proteins; Peptides; Apolipoprotein A-II; Mass spectroscopy; Lymphocytes B DO - http://dx.doi.org/10.1002/pmic.200300677 ER - TY - JOUR T1 - Influence of body composition on physical activity validation studies using doubly labeled water AN - 17954440; 5887869 AB - This study investigated the influence of two approaches (mathematical transformation and statistical procedures), used to account for body composition [body mass or fat-free mass (FFM)], on associations between two measures of physical activity and energy expenditure determined by doubly labeled water (DLW). Complete data for these analyses were available for 136 African American (44.1%) and Hispanic (55.9%) women (mean age 50 plus or minus 7.3 yr). Total energy expenditure (TEE) by DLW was measured over 14 days. Physical activity energy expenditure (PAEE) was computed as 0.90 x TEE - resting metabolic rate. During week 2, participants wore an accelerometer for 7 consecutive days and completed a 7-day diary. Pearson's product-moment correlations and three statistical procedures (multiple regressions, partial correlations, and allometric scaling) were used to assess the effect of body composition on associations. The methods-comparison analysis was used to study the effect of body composition on agreement. The statistical procedures demonstrated that associations improved when body composition was included in the model. The accelerometer explained a small but meaningful portion of the variance in TEE and PAEE after body mass was accounted for. The methods-comparison analysis confirmed that agreement with DLW was affected by the transformation. Agreement between the diary (transformed with body mass) and TEE reflected the association that exists between body mass and TEE. These results suggest that the accelerometer and diary accounted for a small portion of TEE and PAEE. Most of the variance in DLW-measured energy expenditure was explained by body mass or FFM. JF - Journal of Applied Physiology AU - Maasse, L C AU - Fulton, JE AU - Watson, K L AU - Mahar, M T AU - Meyers, M C AU - Wong, W W AD - Behavioral Research Program, Health Promotion Research Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, EPN 4076, MSC 7335, 6130 Executive Blvd., Bethesda, MD 20892-7335, USA Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 1357 EP - 1364 VL - 96 IS - 4 SN - 8750-7587, 8750-7587 KW - Physical Education Index KW - Energy cost KW - Exercise physiology KW - Research (statistical design) KW - Body composition KW - Ethnic groups KW - Modeling KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17954440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Physiology&rft.atitle=Influence+of+body+composition+on+physical+activity+validation+studies+using+doubly+labeled+water&rft.au=Maasse%2C+L+C%3BFulton%2C+JE%3BWatson%2C+K+L%3BMahar%2C+M+T%3BMeyers%2C+M+C%3BWong%2C+W+W&rft.aulast=Maasse&rft.aufirst=L&rft.date=2004-04-01&rft.volume=96&rft.issue=4&rft.spage=1357&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Physiology&rft.issn=87507587&rft_id=info:doi/10.1152%2Fjapplphysiol.00901.2003 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Body composition; Energy cost; Modeling; Exercise physiology; Research (statistical design); Ethnic groups DO - http://dx.doi.org/10.1152/japplphysiol.00901.2003 ER - TY - JOUR T1 - Rapamycin control of exocrine protein levels in saliva after adenoviral vector-mediated gene transfer AN - 17953336; 5893805 AB - Transgene-encoded therapeutic secretory proteins can be efficiently secreted from salivary glands into saliva or the bloodstream after adenoviral (Ad)-mediated gene transfer. Since transgene expression from conventional vectors is typically unregulated, we evaluated the rapamycin-based dimerizer regulation system for control of transgene expression in, and consequent exocrine protein secreted from, rat salivary glands. We used human growth hormone (hGH) as a surrogate exocrine secretory protein. Two Ad vectors, Ad C4ZF3, encoding activation and DNA binding domain fusion polypeptides, and Ad Z12-I-GH-2, encoding hGH, were constructed and shown useful in vitro. Thereafter, both vectors were delivered into submandibular glands by retroductal infusion. After 24 h, rapamycin (0, 1, 3 or 10 mg/kg) was administered, and 20 h later hGH levels in saliva were determined. Salivary hGH levels were rapamycin concentration dependent. At a rapamycin dose of 10 mg/kg, total salivary hGH was 693 plus or minus 197 ng and the hGH concentration in saliva was 4.6 plus or minus 1.3 mu g/ml. Over a 16-day experimental period, three separate administrations of rapamycin (3 mg/kg) induced distinct elevations of salivary hGH ( similar to 100-200 ng total hGH) that were entirely rapamycin dependent. This study demonstrates for the first time pharmacological control of transgenic exocrine protein production and presence in saliva after salivary gland gene transfer, and the potential for its application to the management of oral, oropharyngeal and upper gastrointestinal tract disorders. JF - Gene Therapy AU - Wang, J AU - Voutetakis, A AU - Zheng, C AU - Baum, B J AD - GTTB, NIDCR, NIH, DHHS, Bldg. 10, Rm. 1N113, MSC-1190, Bethesda, MD 20892-1190, USA Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 729 EP - 733 VL - 11 IS - 8 SN - 0969-7128, 0969-7128 KW - man KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Growth hormone KW - Protein biosynthesis KW - Gene therapy KW - Expression vectors KW - Gene transfer KW - Exocrine glands KW - Saliva KW - Rapamycin KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17953336?accountid=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=Gene+Therapy&rft.atitle=Rapamycin+control+of+exocrine+protein+levels+in+saliva+after+adenoviral+vector-mediated+gene+transfer&rft.au=Wang%2C+J%3BVoutetakis%2C+A%3BZheng%2C+C%3BBaum%2C+B+J&rft.aulast=Wang&rft.aufirst=J&rft.date=2004-04-01&rft.volume=11&rft.issue=8&rft.spage=729&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fsj.gt.3302225 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene transfer; Gene therapy; Expression vectors; Exocrine glands; Growth hormone; Saliva; Protein biosynthesis; Rapamycin DO - http://dx.doi.org/10.1038/sj.gt.3302225 ER - TY - JOUR T1 - In Vivo Trafficking and Targeted Delivery of Magnetically Labeled Stem Cells AN - 17951413; 5894797 AB - Targeted delivery of intravenously administered genetically altered cells or stem cells is still in an early stage of investigation. We developed a method of delivering iron oxide (ferumoxide)-labeled mesenchymal stem cells (MSCs) to a targeted area in an animal model by applying an external magnet. Rats with or without an external magnet placed over the liver were injected intravenously with ferumoxide-labeled MSCs and magnetic resonance imaging (MRI) signal intensity (SI) changes, iron concentration, and concentration of MSCs in the liver were monitored at different time points. SI decreased in the liver after injection of MSCs and returned gradually to that of control rat livers at approximately day 29. SI decreases were greater in rats with external magnets. Higher iron concentration and increased labeled cell numbers were detected in rat livers with external magnets. The external magnets influenced the movement of labeled MSCs such that the cells were retained in the region of interest. These results potentially open a new area of investigation for delivering stem cells or genetically altered cells. JF - Human Gene Therapy AU - Arbab, A S AU - Jordan, E K AU - Wilson, L B AU - Yocum, G T AU - Lewis, B K AU - Frank, JA AD - Laboratory of Diagnostic Radiology Research, National Institutes of Health, Building 10, Room # B1N256, Bethesda, MD 20892, USA, saali@cc.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 351 EP - 360 VL - 15 IS - 4 SN - 1043-0342, 1043-0342 KW - ferumoxide KW - iron oxide KW - animal models KW - rats KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Magnetic fields KW - Labelling KW - Stem cells KW - Gene therapy KW - Magnetic resonance imaging KW - Mesenchyme KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17951413?accountid=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+Vivo+Trafficking+and+Targeted+Delivery+of+Magnetically+Labeled+Stem+Cells&rft.au=Arbab%2C+A+S%3BJordan%2C+E+K%3BWilson%2C+L+B%3BYocum%2C+G+T%3BLewis%2C+B+K%3BFrank%2C+JA&rft.aulast=Arbab&rft.aufirst=A&rft.date=2004-04-01&rft.volume=15&rft.issue=4&rft.spage=351&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Stem cells; Mesenchyme; Magnetic fields; Labelling; Magnetic resonance imaging; Gene therapy ER - TY - JOUR T1 - Identification of related gene/protein names based on an HMM of name variations AN - 17946854; 5899650 AB - Gene and protein names follow few, if any, true naming conventions and are subject to great variation in different occurrences of the same name. This gives rise to two important problems in natural language processing. First, can one locate the names of genes or proteins in free text, and second, can one determine when two names denote the same gene or protein? The first of these problems is a special case of the problem of named entity recognition, while the second is a special case of the problem of automatic term recognition (ATR). We study the second problem, that of gene or protein name variation. Here we describe a system which, given a query gene or protein name, identifies related gene or protein names in a large list. The system is based on a dynamic programming algorithm for sequence alignment in which the mutation matrix is allowed to vary under the control of a fully trainable hidden Markov model. JF - Computational Biology and Chemistry AU - Yeganova, L AU - Smith, L AU - Wilbur, W J AD - Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bldg. 38A, 8600 Rockville Pike, Bethesda, MD 20894, USA, yeganova@ncbi.nlm.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 97 EP - 107 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 28 IS - 2 SN - 1476-9271, 1476-9271 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Data processing KW - Mathematical models KW - hidden Markov models KW - Proteins KW - Language KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17946854?accountid=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=Computational+Biology+and+Chemistry&rft.atitle=Identification+of+related+gene%2Fprotein+names+based+on+an+HMM+of+name+variations&rft.au=Yeganova%2C+L%3BSmith%2C+L%3BWilbur%2C+W+J&rft.aulast=Yeganova&rft.aufirst=L&rft.date=2004-04-01&rft.volume=28&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Computational+Biology+and+Chemistry&rft.issn=14769271&rft_id=info:doi/10.1016%2Fj.compbiolchem.2003.12.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Proteins; hidden Markov models; Mathematical models; Language; Data processing DO - http://dx.doi.org/10.1016/j.compbiolchem.2003.12.003 ER - TY - JOUR T1 - Lentivirus Vector-Mediated Expression of Tumor-Associated Epitopes by Human Antigen Presenting Cells AN - 17940742; 5894801 AB - Directing the human immune system to recognize and eliminate tumor cells is the ultimate goal of cancer immunotherapy. Vaccinating patients with autologous antigen presenting cells (APC) expressing tumor-associated antigens (TAA) represents a promising approach for activating tumor-reactive T cells in vivo. In addition, APC expressing TAA provide a means of generating tumor-specific T cells in vitro, for therapeutic and diagnostic applications. Lentiviral vectors are attractive vehicles for introducing TAA-encoding genes into APC. In this study, lentiviral vectors expressing the reporter gene GFP or the melanoma-associated antigen tyrosinase were used to transduce three different kinds of human APC: monocyte-derived dendritic cells (DC), CD40L-activated B lymphocytes, and Epstein Barr virus (EBV)-transformed B lymphocytes. Using optimized transduction conditions for each cell type, tyrosinase was expressed at levels sufficient to stimulate antigen-specific major histocompatibility complex (MHC) class I-restricted T cells from melanoma patients. While transduced EBV-B cells demonstrated the highest level of transgene expression, optimal T-cell recognition was achieved with transduced DC. Substituting the CAG promoter for PGK in lentiviral constructs enhanced transgene expression in DC and EBV-B cells, amplifying T cell recognition. Lentiviruses inducing sustained transgene expression with relatively low cellular toxicity and background viral gene expression may be ideal vectors for immunotherapeutic applications. JF - Human Gene Therapy AU - Lizee, G AU - Gonzales, MI AU - Topalian, S L AD - Surgery Branch, National Cancer Institute, NIH 10/2B47, Bethesda, MD 20892-1502, USA, Suzanne_Topalian@nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 393 EP - 404 VL - 15 IS - 4 SN - 1043-0342, 1043-0342 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - Lentivirus KW - Immunotherapy KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Major histocompatibility complex KW - Antigen-presenting cells KW - Cancer KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17940742?accountid=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=Lentivirus+Vector-Mediated+Expression+of+Tumor-Associated+Epitopes+by+Human+Antigen+Presenting+Cells&rft.au=Lizee%2C+G%3BGonzales%2C+MI%3BTopalian%2C+S+L&rft.aulast=Lizee&rft.aufirst=G&rft.date=2004-04-01&rft.volume=15&rft.issue=4&rft.spage=393&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lentivirus; Cancer; Immunotherapy; Gene therapy; Expression vectors; Antigen-presenting cells; Antigen (tumor-associated); Lymphocytes T; Major histocompatibility complex ER - TY - JOUR T1 - Interplay between Plasmid Partition and Postsegregational Killing Systems AN - 17935103; 5869057 AB - Active partition systems and postsegregational killing (PSK) systems are present together in naturally occurring low-copy-number plasmids. Theory suggests that PSK may act as the ultimate determinant of plasmid retention, whereas the partition system may minimize the growth penalty to the host, resulting in a near-ideal symbiosis when the systems combine. Here, we prove the validity of this principle for a specific case involving the P1par system and the mvp PSK system. JF - Journal of Bacteriology AU - Brendler, T AU - Reaves, L AU - Austin, S AD - NCI: Frederick, GRCBL, P.O. Box B, Frederick, MD 21702-1201 Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 2504 EP - 2507 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 8 SN - 0021-9193, 0021-9193 KW - mvp gene KW - Microbiology Abstracts B: Bacteriology KW - par gene KW - Bacteria KW - Growth KW - Plasmids KW - J 02760:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17935103?accountid=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=Interplay+between+Plasmid+Partition+and+Postsegregational+Killing+Systems&rft.au=Brendler%2C+T%3BReaves%2C+L%3BAustin%2C+S&rft.aulast=Brendler&rft.aufirst=T&rft.date=2004-04-01&rft.volume=186&rft.issue=8&rft.spage=2504&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.186.8.2504-2507.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Plasmids; Growth; Bacteria; par gene DO - http://dx.doi.org/10.1128/JB.186.8.2504-2507.2004 ER - TY - JOUR T1 - A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice AN - 17931927; 5867887 AB - Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model. JF - Nature AU - Yang, Z AU - Kong, W AU - Huang, Y AU - Roberts, A AU - Murphy, B R AU - Subbarao, K AU - Nabel, G J AD - Vaccine Research Center, NIAID, National Institutes of Health, Building 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, Maryland 20892-3005, USA Y1 - 2004/04/01/ PY - 2004 DA - 2004 Apr 01 SP - 561 EP - 564 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 428 IS - 6982 SN - 0028-0836, 0028-0836 KW - double prime S protein KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - S protein KW - ^AS protein KW - Severe acute respiratory syndrome KW - DNA vaccines KW - spike protein KW - Vaccines KW - Glycoproteins KW - Immune response (humoral) KW - SARS coronavirus KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17931927?accountid=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=A+DNA+vaccine+induces+SARS+coronavirus+neutralization+and+protective+immunity+in+mice&rft.au=Yang%2C+Z%3BKong%2C+W%3BHuang%2C+Y%3BRoberts%2C+A%3BMurphy%2C+B+R%3BSubbarao%2C+K%3BNabel%2C+G+J&rft.aulast=Yang&rft.aufirst=Z&rft.date=2004-04-01&rft.volume=428&rft.issue=6982&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2Fnature02463 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - SARS coronavirus; Immune response (humoral); DNA vaccines; Glycoproteins; spike protein; Vaccines; Severe acute respiratory syndrome DO - http://dx.doi.org/10.1038/nature02463 ER - TY - JOUR T1 - Transcription levels of key metabolic genes are the cause for different glucose utilization pathways in E. coli B (BL21) and E. coli K (JM109) AN - 17921933; 5872486 AB - Acetate accumulation is a common problem observed in aerobic high cell density cultures of Escherichia coli. It has been hypothesized in previous reports that the glyoxylate shunt is active in E. coli BL21, the low acetate producer, and inactive in E. coli JM109, the high acetate producer. This hypothesis was further strengthened by incorporating super(13)C from uniformly labeled glucose into TCA cycle intermediates. Using northern blot analyses, the current report demonstrates that the reason for the inactivity of the glyoxylate pathway in E. coli JM109 is the no apparent transcription of isocitrate lyase (aceA) and malate synthase (aceB), and transcription of the isocitrate lyase repressor (iclR). The reverse is seen in E. coli BL21 where the glyoxylate pathway is active due to constitutive transcription of aceA and aceB and no transcription of the iclR. In addition, there is a difference between the two strains in the transcription of the acetyl-CoA synthetase (acs), phosphotransacetylase-acetate kinase (pta-ackA) pathway, and pyruvate oxidase (poxB), pathway. The transcript of acs is higher in E. coli BL21 and lower in the E. coli JM109, while the reverse is true for poxB transcription. JF - Journal of Biotechnology AU - Phue, J-N AU - Shiloach, J AD - Biotechnology Unit, NIH, NIDDK, Building 14A Rm 173, Bethesda, MD 20892, USA, yossi@nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 21 EP - 30 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 109 IS - 1-2 SN - 0168-1656, 0168-1656 KW - phosphotransacetylase-acetate kinase KW - iclR gene KW - aceA gene KW - aceB gene KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology KW - Acetyl CoA synthase KW - Glucose KW - Transcription KW - Cell culture KW - Acetic acid KW - poxB gene KW - Escherichia coli KW - Glyoxylic acid KW - Pyruvate oxidase KW - J 02704:Enumeration KW - W 30965:Miscellaneous, Reviews KW - W4 320:Cell Culture & Batch Fermentation KW - W2 32220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17921933?accountid=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+Biotechnology&rft.atitle=Transcription+levels+of+key+metabolic+genes+are+the+cause+for+different+glucose+utilization+pathways+in+E.+coli+B+%28BL21%29+and+E.+coli+K+%28JM109%29&rft.au=Phue%2C+J-N%3BShiloach%2C+J&rft.aulast=Phue&rft.aufirst=J-N&rft.date=2004-04-01&rft.volume=109&rft.issue=1-2&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biotechnology&rft.issn=01681656&rft_id=info:doi/10.1016%2Fj.jbiotec.2003.10.038 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Recombinant proteins and host cell physiology. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Transcription; Glucose; poxB gene; Acetyl CoA synthase; Pyruvate oxidase; Glyoxylic acid; Acetic acid; Cell culture DO - http://dx.doi.org/10.1016/j.jbiotec.2003.10.038 ER - TY - JOUR T1 - Controlling mRNA stability and translation with small, noncoding RNAs AN - 17919951; 5872795 AB - Recent studies have lead to the identification of more than 50 small regulatory RNAs in Escherichia coli. Only a subset of these RNAs has been characterized. However, it is clear that many of the RNAs, such as the MicF, OxyS, DsrA, Spot42 and RyhB RNAs, act by basepairing to activate or repress translation or to destabilize mRNAs. Basepairing between these regulatory RNAs and their target mRNAs requires the Sm-like Hfq protein which most likely functions as an RNA chaperone to increase RNA unfolding or local target RNA concentration. Here we summarize the physiological roles of the basepairing RNAs, examine their prevalence in bacteria and discuss unresolved questions regarding their mechanisms of action. JF - Current Opinion in Microbiology AU - Storz, G AU - Opdyke, JA AU - Zhang, A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA, storz@helix.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 140 EP - 144 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 7 IS - 2 SN - 1369-5274, 1369-5274 KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Translation KW - snRNA KW - mRNA stability KW - Physiology KW - Regulation KW - Mechanisms KW - Escherichia coli KW - RNA-mediated interference KW - Chaperones KW - Base pairs KW - J 02726:RNA and ribosomes KW - N 14430:Translation initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17919951?accountid=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=Current+Opinion+in+Microbiology&rft.atitle=Controlling+mRNA+stability+and+translation+with+small%2C+noncoding+RNAs&rft.au=Storz%2C+G%3BOpdyke%2C+JA%3BZhang%2C+A&rft.aulast=Storz&rft.aufirst=G&rft.date=2004-04-01&rft.volume=7&rft.issue=2&rft.spage=140&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/10.1016%2Fj.mib.2004.02.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Regulation; Chaperones; snRNA; RNA-mediated interference; Translation; mRNA stability; Physiology; Mechanisms; Base pairs DO - http://dx.doi.org/10.1016/j.mib.2004.02.015 ER - TY - JOUR T1 - MyD88-Deficient Mice Display a Profound Loss in Resistance to Mycobacterium tuberculosis Associated with Partially Impaired Th1 Cytokine and Nitric Oxide Synthase 2 Expression AN - 17901903; 5865132 AB - Mycobacterium tuberculosis possesses agonists for several Toll-like receptors (TLRs), yet mice with single TLR deletions are resistant to acute tuberculosis. MyD88 super(-/-) mice were used to examine whether TLRs play any role in protection against aerogenic M. tuberculosis H37Rv infection. MyD88 super(-/- ) mice failed to control mycobacterial replication and rapidly succumbed. Moreover, expressions of interleukin 12, tumor necrosis factor alpha, gamma interferon, and nitric oxide synthase 2 were markedly decreased in the knockout animals. These results argue that resistance to M. tuberculosis must depend on MyD88-dependent signals mediated by an as-yet-undetermined TLR or a combination of TLRs. JF - Infection and Immunity AU - Scanga, CA AU - Bafica, A AU - Feng, C G AU - Cheever, A W AU - Hieny, S AU - Sher, A AD - Building 50, Room 6148, 50 South Dr., Bethesda, MD 20892-8003, cscanga@niaid.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 2400 EP - 2404 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 4 SN - 0019-9567, 0019-9567 KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Tumor necrosis factor KW - Interleukin 12 KW - Cytokines KW - Tuberculosis KW - g-Interferon KW - Nitric-oxide synthase KW - ^g-Interferon KW - Toll-like receptors KW - Mycobacterium tuberculosis KW - G 07240:Immunogenetics KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17901903?accountid=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=MyD88-Deficient+Mice+Display+a+Profound+Loss+in+Resistance+to+Mycobacterium+tuberculosis+Associated+with+Partially+Impaired+Th1+Cytokine+and+Nitric+Oxide+Synthase+2+Expression&rft.au=Scanga%2C+CA%3BBafica%2C+A%3BFeng%2C+C+G%3BCheever%2C+A+W%3BHieny%2C+S%3BSher%2C+A&rft.aulast=Scanga&rft.aufirst=CA&rft.date=2004-04-01&rft.volume=72&rft.issue=4&rft.spage=2400&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.72.4.2400-2404.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Toll-like receptors; Interleukin 12; Tumor necrosis factor; g-Interferon; Cytokines; Tuberculosis; Nitric-oxide synthase; ^g-Interferon DO - http://dx.doi.org/10.1128/IAI.72.4.2400-2404.2004 ER - TY - JOUR T1 - Flea-Borne Transmission Model To Evaluate Vaccine Efficacy against Naturally Acquired Bubonic Plague AN - 17901829; 5865116 AB - A flea-to-mouse transmission model was developed for use in testing new candidate vaccines for the ability to protect against flea-borne plague. The model was used to evaluate a recombinant fusion protein vaccine consisting of the Yersinia pestis F1 and V antigens. After one to three challenges with Y. pestis-infected fleas, 14 of 15 unvaccinated control mice developed plague, with an average septicemia level of 9.2 x 10 Y. pestis CFU/ml. None of 15 vaccinated mice developed the disease after similar challenges, and serological testing indicated that transmitted bacteria were eliminated by the immune system before extensive replication and systemic infection could occur. The transmission and development of disease in control mice correlated with the number of bites by blocked fleas but not with the total number of fleabites. The model provides a means to directly assess the efficacy of new vaccines to prevent naturally acquired bubonic plague and to study events at the vector-host interface that lead to dissemination and disease. JF - Infection and Immunity AU - Jarrett, C O AU - Sebbane, F AU - Adamovicz, J J AU - Andrews, G P AU - Hinnebusch, B J AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, jhinnebusch@niaid.nih.gov Y1 - 2004/04// PY - 2004 DA - Apr 2004 SP - 2052 EP - 2056 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 4 SN - 0019-9567, 0019-9567 KW - mice KW - Fleas KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Septicemia KW - Yersinia pestis KW - Disease transmission KW - Siphonaptera KW - Vaccines KW - Plague KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17901829?accountid=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=Flea-Borne+Transmission+Model+To+Evaluate+Vaccine+Efficacy+against+Naturally+Acquired+Bubonic+Plague&rft.au=Jarrett%2C+C+O%3BSebbane%2C+F%3BAdamovicz%2C+J+J%3BAndrews%2C+G+P%3BHinnebusch%2C+B+J&rft.aulast=Jarrett&rft.aufirst=C&rft.date=2004-04-01&rft.volume=72&rft.issue=4&rft.spage=2052&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.72.4.2052-2056.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Yersinia pestis; Siphonaptera; Disease transmission; Plague; Vaccines; Septicemia DO - http://dx.doi.org/10.1128/IAI.72.4.2052-2056.2004 ER - TY - JOUR T1 - Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. AN - 71816989; 15070743 AB - Hepatocyte growth factor/scatter factor c-met signaling pathway is of central importance during development as well as in tumorigenesis. Because homozygous null mice for either hgf/sf or c-met die in utero, we used Cre/loxP-mediated gene targeting to investigate the function of c-met specifically in the adult liver. Loss of c-met appeared not to be detrimental to hepatocyte function under physiological conditions. Nonetheless, the adaptive responses of the liver to injury were dramatically affected. Mice lacking c-met gene in hepatocytes were hypersensitive to Fas-induced apoptosis. When injected with a low dose of anti-Fas antibody, the majority of these mice died from massive apoptosis and hemorrhagic necrosis, whereas all wild-type mice survived with signs of minor injury. After a challenge with a single necrogenic dose of CCl4, c-met conditional knockout mice exhibited impaired recovery from centrolobular lesions rather than a deficit in hepatocyte proliferation. The delayed healing was associated with a persistent inflammatory reaction, over-production of osteopontin, early and prominent dystrophic calcification, and impaired hepatocyte scattering/migration into diseased areas. These studies provide direct genetic evidence in support of the critical role of c-met in efficient liver regeneration and suggest that disruption of c-met affects primarily hepatocyte survival and tissue remodeling. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Huh, Chang-Goo AU - Factor, Valentina M AU - Sánchez, Aránzazu AU - Uchida, Koichi AU - Conner, Elizabeth A AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4262, Building 37, Room 4146A, Bethesda, MD 20892-4262, USA. Y1 - 2004/03/30/ PY - 2004 DA - 2004 Mar 30 SP - 4477 EP - 4482 VL - 101 IS - 13 SN - 0027-8424, 0027-8424 KW - Antigens, CD95 KW - 0 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Index Medicus KW - Exons -- genetics KW - Animals KW - Liver -- pathology KW - Carbon Tetrachloride Poisoning KW - Apoptosis KW - Antigens, CD95 -- physiology KW - Mice KW - Hepatocytes -- physiology KW - Hepatocytes -- cytology KW - Signal Transduction KW - Mice, Knockout KW - Cell Division KW - Proto-Oncogene Proteins c-met -- deficiency KW - Proto-Oncogene Proteins c-met -- genetics KW - Hepatocyte Growth Factor -- physiology KW - Proto-Oncogene Proteins c-met -- physiology KW - Liver Regeneration -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71816989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatocyte+growth+factor%2Fc-met+signaling+pathway+is+required+for+efficient+liver+regeneration+and+repair.&rft.au=Huh%2C+Chang-Goo%3BFactor%2C+Valentina+M%3BS%C3%A1nchez%2C+Ar%C3%A1nzazu%3BUchida%2C+Koichi%3BConner%2C+Elizabeth+A%3BThorgeirsson%2C+Snorri+S&rft.aulast=Huh&rft.aufirst=Chang-Goo&rft.date=2004-03-30&rft.volume=101&rft.issue=13&rft.spage=4477&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 - 2004-07-19 N1 - Date created - 2004-04-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Exp Cell Res. 1999 Nov 25;253(1):88-99 [10579914] Nat Med. 1999 Feb;5(2):226-30 [9930873] Transgenic Res. 1999 Aug;8(4):53-4 [10681148] Genesis. 2000 Feb;26(2):149-50 [10686614] J Cell Biochem. 2000 Jun 6;78(3):465-75 [10861844] Matrix Biol. 2000 Dec;19(7):615-22 [11102750] Ann N Y Acad Sci. 2000;926:1-12 [11193023] Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):247-52 [11134526] Am J Pathol. 2001 Mar;158(3):921-9 [11238040] Hepatology. 2001 Mar;33(3):569-76 [11230736] Mol Cell. 2001 Jun;7(6):1293-306 [11430831] Cancer Res. 2001 Aug 1;61(15):5861-8 [11479227] QJM. 2002 Jan;95(1):3-13 [11834767] Mol Cell. 2002 Feb;9(2):411-21 [11864613] J Clin Invest. 2002 Apr;109(7):857-62 [11927611] Nat Rev Cancer. 2002 Apr;2(4):289-300 [12001990] Clin Sci (Lond). 2002 Nov;103(5):441-9 [12401116] Genes Dev. 2002 Dec 1;16(23):3074-86 [12464636] Mech Dev. 2003 Jan;120(1):117-30 [12490302] J Cell Biochem. 2003 Feb 1;88(2):408-17 [12520544] J Pharmacobiodyn. 1980 Jan;3(1):53-64 [6259312] Science. 1989 Jun 16;244(4910):1288-92 [2660260] Somat Cell Mol Genet. 1992 Jul;18(4):325-36 [1440055] Oncogene. 1993 May;8(5):1195-202 [8386824] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6140-4 [8392188] Nature. 1993 Aug 26;364(6440):806-9 [7689176] Cell. 1994 Apr 22;77(2):261-71 [7513258] Science. 1994 Jul 1;265(5168):103-6 [8016642] Nature. 1995 Feb 23;373(6516):699-702 [7854452] Nature. 1995 Feb 23;373(6516):702-5 [7854453] Nature. 1995 Aug 31;376(6543):768-71 [7651534] Biochem Biophys Res Commun. 1996 May 6;222(1):64-70 [8630075] J Cell Biol. 1996 Jun;133(5):1095-1107 [8655582] J Biochem. 1996 Apr;119(4):591-600 [8743556] Cell. 1996 Nov 1;87(3):531-42 [8898205] Science. 1997 Apr 4;276(5309):60-6 [9082986] Ciba Found Symp. 1997;212:119-30; discussion 130-2, 148-54 [9524767] Biochem Biophys Res Commun. 1998 Mar 27;244(3):683-90 [9535725] Trends Cell Biol. 1998 Oct;8(10):404-10 [9789329] Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15143-8 [10611352] N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Interaction between sex and age in the prevalence of current asthma AN - 39914285; 3841071 AU - Arbes, SJ Jr AU - Guo, X AU - Orelien, J AU - Zeldin, D C Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39914285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Interaction+between+sex+and+age+in+the+prevalence+of+current+asthma&rft.au=Arbes%2C+SJ+Jr%3BGuo%2C+X%3BOrelien%2C+J%3BZeldin%2C+D+C&rft.aulast=Arbes&rft.aufirst=SJ&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Academy of Allergy, Asthma & Immunology, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-272-6071; email: info@aaaai.org; URL: www.aaaai.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Dog allergen (Can f 1) and cat allergen (Fel d 1) in U.S. homes AN - 39846475; 3839344 AU - Mehta, J AU - Arbes, SJ Jr AU - Yin, M AU - Cohn, R AU - Zeldin, D C Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39846475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Dog+allergen+%28Can+f+1%29+and+cat+allergen+%28Fel+d+1%29+in+U.S.+homes&rft.au=Mehta%2C+J%3BArbes%2C+SJ+Jr%3BYin%2C+M%3BCohn%2C+R%3BZeldin%2C+D+C&rft.aulast=Mehta&rft.aufirst=J&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Academy of Allergy, Asthma & Immunology, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-272-6071; email: info@aaaai.org; URL: www.aaaai.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Demonstration of the D816V C-kit mutation in basophils in systemic mastocytosis AN - 39824403; 3839076 AU - Kocabas, C N AU - Yavuz, A S AU - Lipsky, P E AU - Metcalfe, D D AU - Akin, C Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39824403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Demonstration+of+the+D816V+C-kit+mutation+in+basophils+in+systemic+mastocytosis&rft.au=Kocabas%2C+C+N%3BYavuz%2C+A+S%3BLipsky%2C+P+E%3BMetcalfe%2C+D+D%3BAkin%2C+C&rft.aulast=Kocabas&rft.aufirst=C&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Academy of Allergy, Asthma & Immunology, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-272-6071; email: info@aaaai.org; URL: www.aaaai.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Introduction: Training programs in pharmacology from the NIH perspective AN - 39824223; 3841159 AU - Preusch, P C Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39824223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Introduction%3A+Training+programs+in+pharmacology+from+the+NIH+perspective&rft.au=Preusch%2C+P+C&rft.aulast=Preusch&rft.aufirst=P&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: ASPET, 9650 Rockville Pike, Bethesda, MD 20814-3995; phone: 301-634-7060; fax: 301-634-7061; email: info@aspet.org; URL: www.aspet.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Home ranges and activity patterns of asiatic black bears (Ursus thibetanus) in Yushan National Park, Taiwan AN - 39810335; 3835617 AU - Hwang, M-H AU - Garshelis, D L Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39810335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Home+ranges+and+activity+patterns+of+asiatic+black+bears+%28Ursus+thibetanus%29+in+Yushan+National+Park%2C+Taiwan&rft.au=Hwang%2C+M-H%3BGarshelis%2C+D+L&rft.aulast=Hwang&rft.aufirst=M-H&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: California Dept. of Fish and Game, 1812 9th Street, Sacramento, CA 95814; phone: 916-445-3652; fax: 916-445-4048; email: DUpdike@dfg.ca.gov; URL: www.dfg.ca.gov N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Selenium delivery proteins can provide relatively non-toxic elemental forms of selenium for in vivo biosynthesis of selenophosphate and specific selenoproteins AN - 39809923; 3843593 AU - Stadtman, T C Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39809923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Selenium+delivery+proteins+can+provide+relatively+non-toxic+elemental+forms+of+selenium+for+in+vivo+biosynthesis+of+selenophosphate+and+specific+selenoproteins&rft.au=Stadtman%2C+T+C&rft.aulast=Stadtman&rft.aufirst=T&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Oxygen Club of California, Univ. of Southern California, Dept. of Molecular Pharmacology & Toxicology, School of Pharmacy, Los Angeles, CA 90098-9192, USA; phone: 323-442-1418 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - IFNg enhances Th2 priming in vivo AN - 39805356; 3840714 AU - Bocek, P Jr AU - Foucras, G L AU - Paul, W E Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39805356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=IFNg+enhances+Th2+priming+in+vivo&rft.au=Bocek%2C+P+Jr%3BFoucras%2C+G+L%3BPaul%2C+W+E&rft.aulast=Bocek&rft.aufirst=P&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Academy of Allergy, Asthma & Immunology, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-272-6071; email: info@aaaai.org; URL: www.aaaai.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Examination of health-related quality of life (HRQL) in patients with peritoneal surface malignancies AN - 39802938; 3839884 AU - Beresnev, T AU - Mavroukakis, S AU - Marden, S AU - White, D AU - Alexander, H R AU - Pingpank, J AU - Libutti, S Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39802938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Examination+of+health-related+quality+of+life+%28HRQL%29+in+patients+with+peritoneal+surface+malignancies&rft.au=Beresnev%2C+T%3BMavroukakis%2C+S%3BMarden%2C+S%3BWhite%2C+D%3BAlexander%2C+H+R%3BPingpank%2C+J%3BLibutti%2C+S&rft.aulast=Beresnev&rft.aufirst=T&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Intl. Soc. f. Quality of Life Research, 6728 Old McLean Village Drive, McLean, VA 22101-3906, USA; phone: 703-556-9222; fax: 703-556-8729; URL: www.isoqol.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - NTAL phosphorylation is a common event in the signaling pathways initiated by antigen and stem cell factor (SCF) in mast cells AN - 39800240; 3842151 AU - Iwaki, S AU - Tkaczyk, C AU - Satterthwaite, AB AU - Draber, P AU - Horejsi, V AU - Metcalfe, D D AU - Gilfillan, A M Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39800240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=NTAL+phosphorylation+is+a+common+event+in+the+signaling+pathways+initiated+by+antigen+and+stem+cell+factor+%28SCF%29+in+mast+cells&rft.au=Iwaki%2C+S%3BTkaczyk%2C+C%3BSatterthwaite%2C+AB%3BDraber%2C+P%3BHorejsi%2C+V%3BMetcalfe%2C+D+D%3BGilfillan%2C+A+M&rft.aulast=Iwaki&rft.aufirst=S&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Academy of Allergy, Asthma & Immunology, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-272-6071; email: info@aaaai.org; URL: www.aaaai.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Dendritic cell expression of FcepsilonRI is regulated by serum IqE AN - 39786449; 3839077 AU - Foster, B AU - Griffith, D T AU - Boesel, K M AU - Lin, H AU - Casale, T B AU - Metcalfe, D D AU - Prussin, C Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39786449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Dendritic+cell+expression+of+FcepsilonRI+is+regulated+by+serum+IqE&rft.au=Foster%2C+B%3BGriffith%2C+D+T%3BBoesel%2C+K+M%3BLin%2C+H%3BCasale%2C+T+B%3BMetcalfe%2C+D+D%3BPrussin%2C+C&rft.aulast=Foster&rft.aufirst=B&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Academy of Allergy, Asthma & Immunology, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-272-6071; email: info@aaaai.org; URL: www.aaaai.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Functional neuroimaging in ADHD AN - 39776759; 3840190 AU - Ernst, M Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39776759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Functional+neuroimaging+in+ADHD&rft.au=Ernst%2C+M&rft.aulast=Ernst&rft.aufirst=M&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: ASPET, 9650 Rockville Pike, Bethesda, MD 20814-3995; phone: 301-634-7060; fax: 301-634-7061; email: info@aspet.org; URL: www.aspet.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Mast cells express multiple regulator of G protein signaling (RGS) proteins AN - 39749441; 3841601 AU - Bansal, G AU - Rao, S AU - Nocka, K AU - Druey, K Y1 - 2004/03/26/ PY - 2004 DA - 2004 Mar 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39749441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Mast+cells+express+multiple+regulator+of+G+protein+signaling+%28RGS%29+proteins&rft.au=Bansal%2C+G%3BRao%2C+S%3BNocka%2C+K%3BDruey%2C+K&rft.aulast=Bansal&rft.aufirst=G&rft.date=2004-03-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Academy of Allergy, Asthma & Immunology, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-272-6071; email: info@aaaai.org; URL: www.aaaai.org N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - STAM: Simple Transmembrane Alignment Method AN - 19727595; 6418262 AB - Motivation: The database of transmembrane protein (TMP) structures is still very small. At the same time, more and more TMP sequences are being determined. Molecular modeling is an interim answer that may bridge the gap between the two databases. The first step in homology modeling is to achieve a good alignment between the target sequences and the template structure. However, since most algorithms to obtain the alignments were constructed with data derived from globular proteins, they perform poorly when applied to TMPs. In our application, we automate the alignment procedure and design it specifically for TMP. We first identify segments likely to form transmembrane alpha -helices. We then apply different sets of criteria for transmembrane and non-transmembrane segments. For example, the penalty for insertion/deletions in the transmembrane segments is much higher than that of a penalty in the loop region. Different substitution matrices are used since the frequencies of occurrence of the various amino acids differ for transmembrane segments and water-soluble domains. Results: This program leads to better models since it does not treat the protein as a single entity with the same properties, but accounts for the different physical properties of the various segments. STAM is the first multisequence alignment program that is directly targeted at transmembrane proteins. JF - Bioinformatics AU - Shafrir, Y AU - Guy, H R AD - National Cancer Institute, LECB, MSC 5677, 12 South Drive, Bethesda, MD 20892-5677, USA, yinon@nih.gov Y1 - 2004/03/22/ PY - 2004 DA - 2004 Mar 22 VL - 20 IS - 5 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Deletion KW - Amino acid substitution KW - Data processing KW - Algorithms KW - Membrane proteins KW - Databases KW - Bioinformatics KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19727595?accountid=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=Bioinformatics&rft.atitle=STAM%3A+Simple+Transmembrane+Alignment+Method&rft.au=Shafrir%2C+Y%3BGuy%2C+H+R&rft.aulast=Shafrir&rft.aufirst=Y&rft.date=2004-03-22&rft.volume=20&rft.issue=5&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Algorithms; Bioinformatics; Deletion; Databases; Membrane proteins; Data processing; Amino acid substitution ER - TY - JOUR T1 - Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier. AN - 80175645; 14972659 AB - Iron homeostasis in the mammalian brain is an important and poorly understood subject. Transferrin-bound iron enters the endothelial cells of the blood-brain barrier from the systemic circulation, and iron subsequently dissociates from transferrin to enter brain parenchyma by an unknown mechanism. In recent years, several iron transporters, including the iron importer DMT1 (Ireg1, MTP, DCT1) and the iron exporter ferroportin (SLC11A3, Ireg, MTP1) have been cloned and characterized. To better understand brain iron homeostasis, we have characterized the distribution of ferroportin, the presumed intestinal iron exporter, and have evaluated its potential role in regulation of iron homeostasis in the central nervous system. We discovered using in situ hybridization and immunohistochemistry that ferroportin is expressed in the endothelial cells of the blood-brain barrier, in neurons, oligodendrocytes, astrocytes, and the choroid plexus and ependymal cells. In addition, we discovered using techniques of immunoelectron microscopy and biochemical purification of synaptic vesicles that ferroportin is associated with synaptic vesicles. In the blood-brain barrier, it is likely that ferroportin serves as a molecular transporter of iron on the abluminal membrane of polarized endothelial cells. The role of ferroportin in synaptic vesicles is unknown, but its presence at that site may prove to be of great importance in neuronal iron toxicity. The widespread representation of ferroportin at sites such as the blood-brain barrier and synaptic vesicles raises the possibility that trafficking of elemental iron may be instrumental in the distribution of iron in the central nervous system. JF - Brain research AU - Wu, Laura Jui-chen AU - Leenders, A G Miriam AU - Cooperman, Sharon AU - Meyron-Holtz, Esther AU - Smith, Sophia AU - Land, William AU - Tsai, Robert Y L AU - Berger, Urs V AU - Sheng, Zu-Hang AU - Rouault, Tracey A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 2004/03/19/ PY - 2004 DA - 2004 Mar 19 SP - 108 EP - 117 VL - 1001 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Cation Transport Proteins KW - 0 KW - Glial Fibrillary Acidic Protein KW - Peptides KW - metal transporting protein 1 KW - Iron KW - E1UOL152H7 KW - Iron Regulatory Protein 2 KW - EC 4.2.1.3 KW - Index Medicus KW - Animals KW - Brain -- cytology KW - Glial Fibrillary Acidic Protein -- metabolism KW - Peptides -- metabolism KW - Peptides -- immunology KW - Brain -- metabolism KW - Immunohistochemistry -- methods KW - Mice KW - Iron -- metabolism KW - Mice, Knockout KW - Blotting, Western KW - Microscopy, Immunoelectron -- methods KW - In Situ Hybridization -- methods KW - Iron Regulatory Protein 2 -- genetics KW - Time Factors KW - Synaptosomes -- metabolism KW - Endothelial Cells -- metabolism KW - Blood-Brain Barrier -- cytology KW - Synaptic Vesicles -- metabolism KW - Blood-Brain Barrier -- metabolism KW - Synaptic Vesicles -- ultrastructure KW - Gene Expression KW - Cation Transport Proteins -- metabolism KW - Cation Transport Proteins -- immunology KW - Cation Transport Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80175645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+the+iron+transporter+ferroportin+in+synaptic+vesicles+and+the+blood-brain+barrier.&rft.au=Wu%2C+Laura+Jui-chen%3BLeenders%2C+A+G+Miriam%3BCooperman%2C+Sharon%3BMeyron-Holtz%2C+Esther%3BSmith%2C+Sophia%3BLand%2C+William%3BTsai%2C+Robert+Y+L%3BBerger%2C+Urs+V%3BSheng%2C+Zu-Hang%3BRouault%2C+Tracey+A&rft.aulast=Wu&rft.aufirst=Laura&rft.date=2004-03-19&rft.volume=1001&rft.issue=1-2&rft.spage=108&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 - 2004-05-28 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A survey of gene-specific methylation in human prostate cancer among black and white men. AN - 71753952; 15036650 AB - Gene methylation is an important molecular event in prostate carcinogenesis that may have diagnostic and prognostic significance. We evaluated the methylation status of eight genes implicated in prostate carcinogenesis. DNA was extracted from archived paraffin-embedded tumor blocks from 90 prostate cancer patients. Gene methylation status of eight genes (GSTP1, RASSF1A, RARbeta2, CD44, EDNRB, E-cadherin, Annexin-2, and Caveolin-1) was determined using real-time methylation-sensitive PCR techniques. Differences in gene methylation among race, tumor grade and disease stage were evaluated by chi-square test. Of the eight genes, GSTP1, RASSF1A, and RARbeta2 methylation was highly prevalent across tumors (>60% for all three genes) whereas CD44, E-cadherin and EDNRB methylation was less prevalent (33, 24 and 29%, respectively). Annexin-2 and Caveolin-1 were not methylated in any of the tumors examined. Methylation of RARbeta2, CD44 and E-cadherin was correlated with tumor grade but not stage. Interestingly, methylation of EDNRB, a gene involved in angiogenesis, was correlated with stage of disease but not tumor grade. With the possible exception of CD44, we did not observe differences in gene methylation between racial categories for the genes under study. In summary, our data suggest that evaluation of the methylation of a panel of genes may have diagnostic and prognostic utility in prostate cancer. JF - Cancer letters AU - Woodson, Karen AU - Hanson, Jeffrey AU - Tangrea, Joseph AD - Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, 6116 Executive Blvd, MSC 8314, Bethesda, MD 20892 USA. kw114v@nih.gov Y1 - 2004/03/18/ PY - 2004 DA - 2004 Mar 18 SP - 181 EP - 188 VL - 205 IS - 2 SN - 0304-3835, 0304-3835 KW - Isoenzymes KW - 0 KW - RASSF1 protein, human KW - Receptors, Retinoic Acid KW - Tumor Suppressor Proteins KW - retinoic acid receptor beta KW - GSTP1 protein, human KW - EC 2.5.1.18 KW - Glutathione S-Transferase pi KW - Glutathione Transferase KW - Index Medicus KW - Receptors, Retinoic Acid -- genetics KW - Humans KW - European Continental Ancestry Group KW - Tumor Suppressor Proteins -- genetics KW - Aged KW - Middle Aged KW - Glutathione Transferase -- genetics KW - Isoenzymes -- genetics KW - African Continental Ancestry Group KW - Male KW - DNA Methylation KW - Prostatic Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71753952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+survey+of+gene-specific+methylation+in+human+prostate+cancer+among+black+and+white+men.&rft.au=Woodson%2C+Karen%3BHanson%2C+Jeffrey%3BTangrea%2C+Joseph&rft.aulast=Woodson&rft.aufirst=Karen&rft.date=2004-03-18&rft.volume=205&rft.issue=2&rft.spage=181&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 - 2004-04-12 N1 - Date created - 2004-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen Signaling in Livers of Male Mice With Hepatocellular Carcinoma Induced by Exposure to Arsenic In Utero AN - 18004393; 5946286 AB - Background: Exposure of pregnant mice to inorganic arsenic induces a spectrum of tumors, including hepatocellular carcinoma (HCC), in their adult offspring similar to that induced by exposing adult mice to estrogenic compounds. To investigate whether arsenic exposure in utero causes altered estrogen signaling, we examined expression of estrogen receptor- (ER-), cyclin D1 (an estrogen-responsive hepatic oncogene), and several cytochrome P450 genes (with sexually dimorphic liver expression patterns) in livers from adult male mice with in utero arsenicinduced HCC. Methods: Quantitative real-time reverse transcriptionpolymerase chain reaction was used to evaluate gene expression in livers of adult male mice that had (i.e., exposed mice; n = 8) or had not (i.e., control mice; n = 5) been exposed to arsenic in utero. DNA methylation status of portions of the ER- and cyclin D1 gene promoters in liver tissue was measured using methylation-specific polymerase chain reaction. Statistical tests were two-sided. Results: ER- mRNA levels were 3.1-fold (95% confidence interval [CI] = 2.0-fold to 4.3-fold) higher in livers of exposed mice than in those of control mice, and cyclin D1 levels were 3.0-fold (95% CI = 1.7-fold to 4.3-fold) higher. Exposed mice showed a feminized expression pattern of several cytochrome P450 genes, expressing the female-dominant CYP2A4 (P = .017 versus control) and CYP2B9 (P<.001) genes at 8.7 and 10.5 times, respectively, the level in control mice and expressing the male-dominant CYP7B1 at approximately one-fourth the level in control mice(P = .0012). Exposed mice exhibited reduced (by approximately 90%) methylation of the ER- gene promoter in liver DNA as compared with control mice; the cyclin D1 gene promoter was not methylated in either exposed or control mice. Conclusion: Altered estrogen signaling may play a role in induction of HCC by arsenic exposure in utero. Specifically, overexpression of ER-, potentially through promoter region hypomethylation, in livers of such mice may be linked to the hepatocarcinogenicity of arsenic. JF - Journal of the National Cancer Institute AU - Waalkes, M P AU - Lui, Jie AU - Chen, Hua AU - Xie, Yaxiong AU - Achanzar, W E AU - Zhou, Yun-Su AU - Cheng, Min-Liang AU - Diwan, BA AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, MD F009, 111 Alexander Dr., Research Triangle Park, NC 27709, waalkes@niehs.nih.gov Y1 - 2004/03/17/ PY - 2004 DA - 2004 Mar 17 SP - 466 EP - 474 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 96 IS - 6 SN - 0027-8874, 0027-8874 KW - mice KW - males KW - Toxicology Abstracts KW - Estrogens KW - Arsenic KW - Prenatal experience KW - Liver KW - Carcinoma KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18004393?accountid=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+the+National+Cancer+Institute&rft.atitle=Estrogen+Signaling+in+Livers+of+Male+Mice+With+Hepatocellular+Carcinoma+Induced+by+Exposure+to+Arsenic+In+Utero&rft.au=Waalkes%2C+M+P%3BLui%2C+Jie%3BChen%2C+Hua%3BXie%2C+Yaxiong%3BAchanzar%2C+W+E%3BZhou%2C+Yun-Su%3BCheng%2C+Min-Liang%3BDiwan%2C+BA&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2004-03-17&rft.volume=96&rft.issue=6&rft.spage=466&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/10.1093%2Fjnci%2Fdjh070 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arsenic; Prenatal experience; Estrogens; Carcinoma; Liver DO - http://dx.doi.org/10.1093/jnci/djh070 ER - TY - JOUR T1 - X-ray and NMR characterization of covalent complexes of trypsin, borate, and alcohols. AN - 71714777; 15005618 AB - An understanding of the physiological and toxicological properties of borate and the utilization of boronic acids in drug development require a basic understanding of borate-enzyme chemistry. We report here the extension of our recent NMR studies indicating the formation of a ternary borate-alcohol-trypsin complex. Crystallographic and solution state NMR studies of porcine trypsin were performed in the presence of borate and either of three alcohols designed to bind to the S1 affinity subsite: 4-aminobutanol, guanidine-3-propanol, and 4-hydroxymethylbenzamidine. Quaternary complexes of trypsin, borate, S1-binding alcohol, and ethylene glycol (a cryoprotectant), as well as a ternary trypsin, borate, and ethylene glycol complex have been observed in the crystalline state. Borate forms ester bonds to Ser195, ethylene glycol (two bonds), and the S1-binding alcohol (if present). Spectra from (1)H and (11)B NMR studies confirm that these complexes also exist in solution and also provide evidence for the formation of ternary trypsin, borate, and S1-subsite alcohol complexes which are not observed in the crystals using our experimental protocols. Analysis of eight crystal structures indicates that formation of an active site borate complex is in all cases accompanied by a significant (approximately 4%) increase in the b-axis dimension of the unit cell. Presumably, our inability to observe the ternary complexes in the crystalline state arises from the lower stability of these complexes and consequent inability to overcome the constraints imposed by the lattice contacts. A mechanism for the coupling of the lattice contacts with the active site that involves a conformational rearrangement of Gln192 is suggested. The structures presented here represent the first crystallographic demonstration of covalent binding of an enzyme by borate. JF - Biochemistry AU - Transue, Thomas R AU - Krahn, Joseph M AU - Gabel, Scott A AU - DeRose, Eugene F AU - London, Robert E AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/03/16/ PY - 2004 DA - 2004 Mar 16 SP - 2829 EP - 2839 VL - 43 IS - 10 SN - 0006-2960, 0006-2960 KW - Amino Alcohols KW - 0 KW - Borates KW - Macromolecular Substances KW - Protons KW - Solutions KW - 4-aminophenylalanine anilide KW - 131025-31-5 KW - 4-aminobutanol KW - 13325-10-5 KW - Phenylalanine KW - 47E5O17Y3R KW - Trypsin KW - EC 3.4.21.4 KW - Boron KW - N9E3X5056Q KW - Index Medicus KW - Swine KW - Crystallization KW - Animals KW - Boron -- chemistry KW - Pancreas -- enzymology KW - Binding Sites KW - Nuclear Magnetic Resonance, Biomolecular KW - Crystallography, X-Ray KW - Substrate Specificity KW - Protein Conformation KW - Trypsin -- chemistry KW - Phenylalanine -- chemistry KW - Phenylalanine -- analogs & derivatives KW - Amino Alcohols -- chemistry KW - Borates -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71714777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=X-ray+and+NMR+characterization+of+covalent+complexes+of+trypsin%2C+borate%2C+and+alcohols.&rft.au=Transue%2C+Thomas+R%3BKrahn%2C+Joseph+M%3BGabel%2C+Scott+A%3BDeRose%2C+Eugene+F%3BLondon%2C+Robert+E&rft.aulast=Transue&rft.aufirst=Thomas&rft.date=2004-03-16&rft.volume=43&rft.issue=10&rft.spage=2829&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-12 N1 - Date created - 2004-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modifying chromatin to permit steroid hormone receptor-dependent transcription. AN - 71756989; 15020043 AB - Lipophilic hormones, including steroids, exert their physiological effects through binding to high-affinity superfamily of steroid hormone receptor (SR) proteins that function as ligand-dependent DNA binding transcription factors. To date, SR proteins are among a few transcription factors shown to directly interact with higher order chromatin structures to regulate gene expression. To perturb chromatin, SRs employ enzymatic multicomplexes that can either remodel or modify chromatin. Here we examine the current state of knowledge concerning multicomplex chromatin remodeling/modification machines and SR-dependent transcription. We will focus on the role of these protein-protein and chromatin-protein interactions in vivo with the MMTV promoter as a primary model. In addition, we discuss emerging evidence implicating chaperone proteins and proteasome degradation machinery in SR-mediated gene regulation within chromatin. JF - Biochimica et biophysica acta AU - Kinyamu, H Karimi AU - Archer, Trevor K AD - Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, PO Box 12233 (MD E4-06), Research Triangle Park, NC 27709, USA. Y1 - 2004/03/15/ PY - 2004 DA - 2004 Mar 15 SP - 30 EP - 45 VL - 1677 IS - 1-3 SN - 0006-3002, 0006-3002 KW - Histones KW - 0 KW - Macromolecular Substances KW - Multienzyme Complexes KW - Receptors, Steroid KW - Ubiquitin KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Index Medicus KW - Multienzyme Complexes -- metabolism KW - Animals KW - Ubiquitin -- metabolism KW - Phosphorylation KW - Cell Nucleus -- metabolism KW - Humans KW - Cysteine Endopeptidases -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Histone Deacetylases -- metabolism KW - Methylation KW - Cell Nucleus -- genetics KW - Histones -- metabolism KW - Chromatin Assembly and Disassembly KW - Receptors, Steroid -- metabolism KW - Transcription, Genetic KW - Receptors, Steroid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71756989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modifying+chromatin+to+permit+steroid+hormone+receptor-dependent+transcription.&rft.au=Kinyamu%2C+H+Karimi%3BArcher%2C+Trevor+K&rft.aulast=Kinyamu&rft.aufirst=H&rft.date=2004-03-15&rft.volume=1677&rft.issue=1-3&rft.spage=30&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 - 2004-05-05 N1 - Date created - 2004-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aberrant Toll receptor expression and endotoxin hypersensitivity in mice lacking a functional TGF-beta 1 signaling pathway. AN - 71703665; 15004187 AB - TGF-beta1 plays a central role in maintaining normal immune function and deficiency of this potent immunosuppressive molecule is linked to uncontrolled inflammation, cachexia, and multiorgan failure as seen in the TGF-beta1 null mouse. Infiltration of inflammatory cells into vital organs of the null mouse is accompanied by increased gene expression of inflammatory cytokines, including TNF-alpha and IL-1beta, as well as inducible NO synthase, each regulated by NF-kappaB. Treatment with the proteasome inhibitor MG132 to prevent NF-kappaB activation dramatically reduced NO production and expression of inflammatory cytokines. This inflammatory phenotype with NF-kappaB activation in the TGF-beta1 null mouse, in the absence of any identifiable pathogen, suggested activation of innate immune responses. Because Toll-like receptors (TLR) are essential in the activation of innate immunity, we examined inflamed tissue from TGF-beta1 null and wild-type mice for expression of TLR4, the receptor that interacts with bacterial cell wall LPS to initiate an NF-kappaB-dependent signaling pathway, leading to gene transcription of inflammatory mediators. Increased TLR4 mRNA expression observed in TGF-beta1 null mice as well as in mice lacking the TGF-beta transcription factor Smad3 was associated with LPS hyperresponsiveness leading to increased expression of inflammatory cytokines and NO and endotoxemia. Furthermore, mice lacking both TGF-beta1 and a functional TLR4 were resistant to endotoxin shock. Constitutive and/or environmental activation of TLR4 and downstream elements, in the absence of TGF-beta suppression, may impact on innate and adaptive immunity and contribute to massive uncontrolled inflammation. JF - Journal of immunology (Baltimore, Md. : 1950) AU - McCartney-Francis, Nancy AU - Jin, Wenwen AU - Wahl, Sharon M AD - Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. nfrancis@dir.nidcr.nih.gov Y1 - 2004/03/15/ PY - 2004 DA - 2004 Mar 15 SP - 3814 EP - 3821 VL - 172 IS - 6 SN - 0022-1767, 0022-1767 KW - Lipopolysaccharides KW - 0 KW - Membrane Glycoproteins KW - NF-kappa B KW - Receptors, Cell Surface KW - Tgfb1 protein, mouse KW - Toll-Like Receptor 4 KW - Toll-Like Receptors KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Nitric Oxide KW - 31C4KY9ESH KW - Abridged Index Medicus KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Inflammation -- genetics KW - Up-Regulation -- genetics KW - Mice KW - Nitric Oxide -- biosynthesis KW - NF-kappa B -- physiology KW - Immunity, Innate -- genetics KW - Mice, Knockout KW - Phenotype KW - Multiple Organ Failure -- genetics KW - Multiple Organ Failure -- immunology KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Inflammation -- immunology KW - Up-Regulation -- immunology KW - Inflammation -- pathology KW - Endotoxemia -- immunology KW - Transforming Growth Factor beta -- physiology KW - Membrane Glycoproteins -- biosynthesis KW - Endotoxemia -- genetics KW - Signal Transduction -- genetics KW - Signal Transduction -- immunology KW - Lipopolysaccharides -- toxicity KW - Transforming Growth Factor beta -- genetics KW - Receptors, Cell Surface -- biosynthesis KW - Transforming Growth Factor beta -- deficiency KW - Endotoxemia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71703665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aberrant+Toll+receptor+expression+and+endotoxin+hypersensitivity+in+mice+lacking+a+functional+TGF-beta+1+signaling+pathway.&rft.au=McCartney-Francis%2C+Nancy%3BJin%2C+Wenwen%3BWahl%2C+Sharon+M&rft.aulast=McCartney-Francis&rft.aufirst=Nancy&rft.date=2004-03-15&rft.volume=172&rft.issue=6&rft.spage=3814&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 - 2004-07-13 N1 - Date created - 2004-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the histidine triad-like motif in nucleotide hydrolysis by the rotavirus RNA-packaging protein NSP2. AN - 71707359; 14699117 AB - Octamers formed by the nonstructural protein NSP2 of rotavirus are proposed to function as molecular motors in the packaging of the segmented double-stranded RNA genome. The octamers have RNA binding, helix unwinding, and Mg(2+)-dependent NTPase activities and play a crucial role in assembly of viral replication factories (viroplasms). Comparison of x-ray structures has revealed significant structural homology between NSP2 and the histidine triad (HIT) family of nucleotidyl hydrolases, which in turn has suggested the location of the active site for NTP hydrolysis in NSP2. Consistent with the structural predictions, we show here using site-specific mutagenesis and ATP docking simulations that the active site for NTP hydrolysis is localized to residues within a 25-A-deep cleft between the C- and N-terminal domains of the NSP2 monomer. Although lacking the precise signature HIT motif (HØHØHØØ where Ø is a hydrophobic residue), our analyses demonstrate that histidines (His(221) and His(225)) represent critical residues of the active site. Similar to events occurring during nucleotide hydrolysis by HIT proteins, NTP hydrolysis by NSP2 was found to produce a short lived phosphorylated intermediate. Evaluation of the biological importance of the NTPase activity of NSP2 by transient expression in mammalian cells showed that such activity has no impact on the ability of NSP2 to induce the hyperphosphorylation of NSP5 or to interact with NSP5 to form viroplasm-like structures. Hence the NTPase activity of NSP2 probably has a role subsequent to the formation of viroplasms, consistent with its suspected involvement in RNA packaging and/or replication. JF - The Journal of biological chemistry AU - Carpio, Rodrigo Vasquez-Del AU - González-Nilo, Fernando D AU - Jayaram, Hariharan AU - Spencer, Eugenio AU - Prasad, B V Venkataram AU - Patton, John T AU - Taraporewala, Zenobia F AD - Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/03/12/ PY - 2004 DA - 2004 Mar 12 SP - 10624 EP - 10633 VL - 279 IS - 11 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - BCAR3 protein, human KW - Carrier Proteins KW - Proteins KW - RNA, Viral KW - Viral Proteins KW - gene 11 protein, Rotavirus B KW - 145715-40-8 KW - Histidine KW - 4QD397987E KW - RNA KW - 63231-63-0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Nucleoside-Triphosphatase KW - EC 3.6.1.15 KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Escherichia coli -- metabolism KW - Models, Molecular KW - Dose-Response Relationship, Drug KW - Viral Proteins -- chemistry KW - Nucleoside-Triphosphatase -- chemistry KW - Amino Acid Sequence KW - Protein Binding KW - Hydrolysis KW - Adenosine Triphosphate -- chemistry KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Microscopy, Fluorescence KW - Phosphorylation KW - Amino Acid Motifs KW - Genetic Vectors KW - Kinetics KW - Molecular Sequence Data KW - RNA -- chemistry KW - Crystallography, X-Ray KW - Sequence Homology, Amino Acid KW - Time Factors KW - Mutation KW - Magnesium -- chemistry KW - Protein Conformation KW - Histidine -- chemistry KW - Proteins -- chemistry KW - Carrier Proteins -- chemistry KW - Rotavirus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71707359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+the+histidine+triad-like+motif+in+nucleotide+hydrolysis+by+the+rotavirus+RNA-packaging+protein+NSP2.&rft.au=Carpio%2C+Rodrigo+Vasquez-Del%3BGonz%C3%A1lez-Nilo%2C+Fernando+D%3BJayaram%2C+Hariharan%3BSpencer%2C+Eugenio%3BPrasad%2C+B+V+Venkataram%3BPatton%2C+John+T%3BTaraporewala%2C+Zenobia+F&rft.aulast=Carpio&rft.aufirst=Rodrigo&rft.date=2004-03-12&rft.volume=279&rft.issue=11&rft.spage=10624&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 - 2004-05-19 N1 - Date created - 2004-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gadd45a regulates matrix metalloproteinases by suppressing DeltaNp63alpha and beta-catenin via p38 MAP kinase and APC complex activation. AN - 71743209; 14647429 AB - The p53-regulated growth arrest and DNA damage-inducible gene product Gadd45a has been recently identified as a key factor protecting the epidermis against ultraviolet radiation (UVR)-induced skin tumors by activating p53 via the stress mitogen-activated protein kinase (MAPK) signaling pathway. Herein we identify Gadd45a as an important negative regulator of two oncogenes commonly over-expressed in epithelial tumors: the p53 homologue DeltaNp63alpha and beta-catenin. DeltaNp63alpha is one of the several p63 isoforms and is the predominant species expressed in basal epidermal keratinocytes. DeltaNp63alpha lacks the N-terminal transactivation domain and behaves as a dominant-negative factor blocking expression of several p53-effector genes. DeltaNp63alpha also associates with and blocks activation of the adenomatous polyposis coli (APC) destruction complex that targets free cytoplasmic beta-catenin for degradation. While most beta-catenin protein is localized to the cell membrane and is involved in cell-cell adhesion, accumulation of free cytoplasmic beta-catenin will translocate into the nucleus where it functions in a bipartite transcription factor complex, whose targets include invasion and metastasis promoting endopeptidases, matrix metalloproteinases (MMP). We show that Gadd45a not only directly associates with two components of the APC complex, namely protein phosphatase 2A (PP2A) and glycogen synthase kinase 3beta (GSK3beta) but also promotes GSK3beta dephosphorylation at Ser9, which is essential for GSK3beta activation, and resultant activation of the APC destruction complex. We demonstrate that lack of Gadd45a not only prevents DeltaNp63alpha suppression and GSK3beta dephosphorylation but also prevents free cytoplasmic beta-catenin degradation after UV irradiation. The inability of Gadd45a-null keratinocytes to suppress beta-catenin may contribute to the resulting observation of increased MMP expression and activity along with significantly faster keratinocyte migration in Matrigel in vitro and accelerated wound closure in vivo. Furthermore, epidermal keratinocytes treated with p38 MAPK inhibitors, both in vivo and in vitro, behave very similarly to Gadd45a-null keratinocytes after UVR. Similarly, Trp53-null mice are unable to attenuate DeltaNp63alpha expression in epidermal keratinocytes after such stress. These findings demonstrate a dependence on Gadd45a-mediated p38 MAPK and p53 activation for proper modulation of DeltaNp63alpha, GSK3beta, and beta-catenin after irradiation. Taken together, our results indicate that Gadd45a is able to repress DeltaNp63alpha, beta-catenin, and consequently MMP expression by two means: by maintaining UVR-induced p38 MAPK and p53 activation and also by associating with the APC complex. This implicates Gadd45a in the negative regulation of cell migration, and invasion. JF - Oncogene AU - Hildesheim, Jeffrey AU - Belova, Galina I AU - Tyner, Stuart D AU - Zhou, Xiwu AU - Vardanian, Lilit AU - Fornace, Albert J AD - Gene Response Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2004/03/11/ PY - 2004 DA - 2004 Mar 11 SP - 1829 EP - 1837 VL - 23 IS - 10 SN - 0950-9232, 0950-9232 KW - Adenomatous Polyposis Coli Protein KW - 0 KW - CTNNB1 protein, mouse KW - Cell Cycle Proteins KW - Cytoskeletal Proteins KW - DNA-Binding Proteins KW - Gadd45a protein, mouse KW - Nuclear Proteins KW - Phosphoproteins KW - Trans-Activators KW - Trp63 protein, mouse KW - beta Catenin KW - L1Hs-encoded protein p40, human KW - 148349-28-4 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Matrix Metalloproteinases KW - EC 3.4.24.- KW - Index Medicus KW - Skin Neoplasms -- genetics KW - Animals KW - Ultraviolet Rays KW - Gene Expression Regulation -- radiation effects KW - Neoplasms, Radiation-Induced -- prevention & control KW - Neoplasms, Radiation-Induced -- genetics KW - Mice KW - Skin Neoplasms -- prevention & control KW - MAP Kinase Signaling System -- genetics KW - Keratinocytes -- radiation effects KW - Adenomatous Polyposis Coli Protein -- metabolism KW - Trans-Activators -- genetics KW - Mitogen-Activated Protein Kinases -- metabolism KW - Keratinocytes -- enzymology KW - DNA-Binding Proteins -- genetics KW - Keratinocytes -- cytology KW - Matrix Metalloproteinases -- genetics KW - Nuclear Proteins -- metabolism KW - Cytoskeletal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71743209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gadd45a+regulates+matrix+metalloproteinases+by+suppressing+DeltaNp63alpha+and+beta-catenin+via+p38+MAP+kinase+and+APC+complex+activation.&rft.au=Hildesheim%2C+Jeffrey%3BBelova%2C+Galina+I%3BTyner%2C+Stuart+D%3BZhou%2C+Xiwu%3BVardanian%2C+Lilit%3BFornace%2C+Albert+J&rft.aulast=Hildesheim&rft.aufirst=Jeffrey&rft.date=2004-03-11&rft.volume=23&rft.issue=10&rft.spage=1829&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-13 N1 - Date created - 2004-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox AN - 17888157; 5856311 AB - The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA. JF - Nature AU - Earl, P L AU - Americo, J L AU - Wyatt, L S AU - Eller, LA AU - Whitbeck, J C AU - Cohen, G H AU - Eisenberg, R J AU - Hartmann, C J AU - Jackson, D L AU - Kulesh, DA AU - Martinez, MJ AU - Miller, D M AU - Mucker, E M AU - Shamblin, J D AU - Zwiers, SH AU - Huggins, J W AU - Jahrling, P B AU - Moss, B AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445, USA Y1 - 2004/03/11/ PY - 2004 DA - 2004 Mar 11 SP - 182 EP - 185 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 428 IS - 6979 SN - 0028-0836, 0028-0836 KW - smallpox virus KW - biological warfare agents KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Bioengineering Abstracts KW - Skin KW - Attenuation KW - Smallpox KW - Immunogenicity KW - Vaccines KW - Monkeypox virus KW - Variola virus KW - F 06807:Active immunization KW - W4 240:Bioterrorism & Biological Warfare KW - V 22098:Immunization: Vaccines & vaccination: Animal KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17888157?accountid=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=Immunogenicity+of+a+highly+attenuated+MVA+smallpox+vaccine+and+protection+against+monkeypox&rft.au=Earl%2C+P+L%3BAmerico%2C+J+L%3BWyatt%2C+L+S%3BEller%2C+LA%3BWhitbeck%2C+J+C%3BCohen%2C+G+H%3BEisenberg%2C+R+J%3BHartmann%2C+C+J%3BJackson%2C+D+L%3BKulesh%2C+DA%3BMartinez%2C+MJ%3BMiller%2C+D+M%3BMucker%2C+E+M%3BShamblin%2C+J+D%3BZwiers%2C+SH%3BHuggins%2C+J+W%3BJahrling%2C+P+B%3BMoss%2C+B&rft.aulast=Earl&rft.aufirst=P&rft.date=2004-03-11&rft.volume=428&rft.issue=6979&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2Fnature02331 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Variola virus; Monkeypox virus; Skin; Vaccines; Immunogenicity; Smallpox; Attenuation DO - http://dx.doi.org/10.1038/nature02331 ER - TY - JOUR T1 - Persistent colonization and the spread of antibiotic resistance in nosocomial pathogens: Resistance is a regional problem AN - 18031437; 5857984 AB - Infections with antibiotic-resistant bacteria (ARB) in hospitalized patients are becoming increasingly frequent despite extensive infection-control efforts. Infections with ARB are most common in the intensive care units of tertiary-care hospitals, but the underlying cause of the increases may be a steady increase in the number of asymptomatic carriers entering hospitals. Carriers may shed ARB for years but remain undetected, transmitting ARB to others as they move among hospitals, long-term care facilities, and the community. We apply structured population models to explore the dynamics of ARB, addressing the following questions: (i) What is the relationship between the proportion of carriers admitted to a hospital, transmission, and the risk of infection with ARB? (ii) How do frequently hospitalized patients contribute to epidemics of ARB? (iii) How do transmission in the community, long-term care facilities, and hospitals interact to determine the proportion of the population that is carrying ARB? We offer an explanation for why ARB epidemics have fast and slow phases and why resistance may continue to increase despite infection-control efforts. To successfully manage ARB at tertiary-care hospitals, regional coordination of infection control may be necessary, including tracking asymptomatic carriers through health-care systems. JF - Proceedings of the National Academy of Sciences, USA AU - Smith, D L AU - Dushoff, J AU - Perencevich, EN AU - Harris, AD AU - Levin, SA AD - Fogarty International Center, National Institutes of Health, Bethesda, MD 20892-2220, smitdave@helix.nih.gov Y1 - 2004/03/09/ PY - 2004 DA - 2004 Mar 09 SP - 3709 EP - 3714 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 10 SN - 0027-8424, 0027-8424 KW - Microbiology Abstracts B: Bacteriology KW - Population Biology KW - Epidemics KW - Transmission KW - Asymptomatic infection KW - Pathogens KW - Infection KW - Dynamics KW - Antibiotic resistance KW - J 02795:Antibiotic resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18031437?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Persistent+colonization+and+the+spread+of+antibiotic+resistance+in+nosocomial+pathogens%3A+Resistance+is+a+regional+problem&rft.au=Smith%2C+D+L%3BDushoff%2C+J%3BPerencevich%2C+EN%3BHarris%2C+AD%3BLevin%2C+SA&rft.aulast=Smith&rft.aufirst=D&rft.date=2004-03-09&rft.volume=101&rft.issue=10&rft.spage=3709&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0400456101 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Epidemics; Transmission; Asymptomatic infection; Pathogens; Infection; Antibiotic resistance; Dynamics DO - http://dx.doi.org/10.1073/pnas.0400456101 ER - TY - JOUR T1 - Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials AN - 198999161; 15016487 AB - Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment. We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage. Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002). The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks. JF - The Lancet AU - Hacke, Werner AU - Donnan, Geoffrey AU - Fieschi, Cesare AU - Kaste, Markku AU - Rudiger von Kummer Y1 - 2004/03/06/ PY - 2004 DA - 2004 Mar 06 SP - 768 EP - 74 CY - London PB - Elsevier Limited VL - 363 IS - 9411 SN - 01406736 KW - Medical Sciences KW - Placebos KW - Recombinant Proteins KW - Tissue Plasminogen Activator KW - Stroke KW - Medical treatment KW - Clinical trials KW - Clinical outcomes KW - Randomized Controlled Trials as Topic KW - Drug Administration Schedule KW - Brain Ischemia -- drug therapy KW - Humans KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Tissue Plasminogen Activator -- administration & dosage KW - Recombinant Proteins -- therapeutic use KW - Recombinant Proteins -- administration & dosage KW - Male KW - Female KW - Stroke -- drug therapy KW - Tissue Plasminogen Activator -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/198999161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Lancet&rft.atitle=Association+of+outcome+with+early+stroke+treatment%3A+pooled+analysis+of+ATLANTIS%2C+ECASS%2C+and+NINDS+rt-PA+stroke+trials&rft.au=Hacke%2C+Werner%3BDonnan%2C+Geoffrey%3BFieschi%2C+Cesare%3BKaste%2C+Markku%3BRudiger+von+Kummer&rft.aulast=Hacke&rft.aufirst=Werner&rft.date=2004-03-06&rft.volume=363&rft.issue=9411&rft.spage=768&rft.isbn=&rft.btitle=&rft.title=The+Lancet&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright Lancet Ltd. Mar 6, 2004 N1 - Document feature - Tables; Graphs; References N1 - Last updated - 2015-02-07 N1 - CODEN - LANCAO ER - TY - JOUR T1 - Escherichia coli Periplasmic Thiol Peroxidase Acts as Lipid Hydroperoxide Peroxidase and the Principal Antioxidative Function during Anaerobic Growth AN - 19265217; 5844890 AB - To clarify the enzymatic property of Escherichia coli periplasmic thiol peroxidase (p20), the specific peroxidase activity toward peroxides was compared with other bacterial thiol peroxidases. p20 has the most substrate preference and peroxidase activity toward organic hydroperoxide. Furthermore, p20 exerted the most potent lipid peroxidase activity. Despite that the mutation of p20 caused the highest susceptibility toward organic hydroperoxide and heat stress, the cellular level of p20 did not respond to the exposure of oxidative stress. Expression level of p20 during anaerobic growth was sustained at the ~50% level compared with that of the aerobic growth. Viability of aerobic p20[Delta] without glucose was reduced to the ~65% level of isogenic strains, whereas viability of aerobic p20[Delta] with 0.5% glucose supplement was sustained. The deletion of p20 resulted in a gradual loss of the cell viability during anaerobic growth. At the stationary phase, the viability of p20[Delta] was down to ~10% level of parent strains. An analysis of the protein carbonyl contents of p20[Delta] as a marker for cellular oxidation indicates that severe reduction of viability of anaerobic p20[Delta] was caused by cumulative oxidative stress. P20[Delta] showed hypersensitivity toward membrane-soluble organic hydroperoxides. An analysis of protein carbonyl and lipid hydroperoxide contents in the membrane of the stress-imposed p20[Delta] demonstrates that the severe reduction of viability was caused by cumulative oxidative stress on the membrane. Taken together, present data uncover in vivo function for p20 as a lipid hydroperoxide peroxidase and demonstrate that, as the result, p20 acts as the principal antioxidant in the anaerobic habitats. JF - Journal of Biological Chemistry AU - Cha, M-K AU - Kim, W-C AU - Lim, C-J AU - Kim, K AU - Kim, I-H AD - Department of Biochemistry, Paichai University, Taejon 302-735, Republic of Korea, Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, ihkim@mail.paichai.ac.kr Y1 - 2004/03/05/ PY - 2004 DA - 2004 Mar 05 SP - 8769 EP - 8778 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 10 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology KW - thiol peroxidase KW - Antioxidants KW - Oxidative stress KW - Glucose KW - Escherichia coli KW - peroxide KW - Viability KW - Anaerobiosis KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19265217?accountid=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=Escherichia+coli+Periplasmic+Thiol+Peroxidase+Acts+as+Lipid+Hydroperoxide+Peroxidase+and+the+Principal+Antioxidative+Function+during+Anaerobic+Growth&rft.au=Cha%2C+M-K%3BKim%2C+W-C%3BLim%2C+C-J%3BKim%2C+K%3BKim%2C+I-H&rft.aulast=Cha&rft.aufirst=M-K&rft.date=2004-03-05&rft.volume=279&rft.issue=10&rft.spage=8769&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M312388200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Anaerobiosis; peroxide; Viability; Glucose; Oxidative stress; Antioxidants; thiol peroxidase DO - http://dx.doi.org/10.1074/jbc.M312388200 ER - TY - JOUR T1 - Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity. AN - 71701313; 14999287 AB - Human DNA polymerase eta (Pol eta) modulates susceptibility to skin cancer by promoting DNA synthesis past sunlight-induced cyclobutane pyrimidine dimers that escape nucleotide excision repair (NER). Here we have determined the efficiency and fidelity of dimer bypass. We show that Pol eta copies thymine dimers and the flanking bases with higher processivity than it copies undamaged DNA, and then switches to less processive synthesis. This ability of Pol eta to sense the dimer location as synthesis proceeds may facilitate polymerase switching before and after lesion bypass. Pol eta bypasses a dimer with low fidelity and with higher error rates at the 3' thymine than at the 5' thymine. A similar bias is seen with Sulfolobus solfataricus DNA polymerase 4, which forms a Watson-Crick base pair at the 3' thymine of a dimer but a Hoogsteen base pair at the 5' thymine (ref. 3). Ultraviolet-induced mutagenesis is also higher at the 3' base of dipyrimidine sequences. Thus, in normal people and particularly in individuals with NER-defective xeroderma pigmentosum who accumulate dimers, errors made by Pol eta during dimer bypass could contribute to mutagenesis and skin cancer. JF - Nature AU - McCulloch, Scott D AU - Kokoska, Robert J AU - Masutani, Chikahide AU - Iwai, Shigenori AU - Hanaoka, Fumio AU - Kunkel, Thomas A AD - Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/03/04/ PY - 2004 DA - 2004 Mar 04 SP - 97 EP - 100 VL - 428 IS - 6978 KW - Pyrimidine Dimers KW - 0 KW - DNA KW - 9007-49-2 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Index Medicus KW - Base Pairing KW - Humans KW - Sulfolobus -- enzymology KW - Hydrogen Bonding KW - Pyrimidine Dimers -- genetics KW - Pyrimidine Dimers -- metabolism KW - DNA Damage KW - DNA -- metabolism KW - DNA -- genetics KW - DNA -- chemistry KW - DNA -- biosynthesis KW - Mutagenesis KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71701313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Preferential+cis-syn+thymine+dimer+bypass+by+DNA+polymerase+eta+occurs+with+biased+fidelity.&rft.au=McCulloch%2C+Scott+D%3BKokoska%2C+Robert+J%3BMasutani%2C+Chikahide%3BIwai%2C+Shigenori%3BHanaoka%2C+Fumio%3BKunkel%2C+Thomas+A&rft.aulast=McCulloch&rft.aufirst=Scott&rft.date=2004-03-04&rft.volume=428&rft.issue=6978&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=1476-4687&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-16 N1 - Date created - 2004-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiovascular consequences of sleep-disordered breathing: past, present and future: report of a workshop from the National Center on Sleep Disorders Research and the National Heart, Lung, and Blood Institute. AN - 212730508; 14993147 JF - Circulation AU - Quan, S F AU - Gersh, B J AU - National Center on Sleep Disorders Research AU - National Heart, Lung, and Blood Institute AD - National Center on Sleep Disorders Research ; National Heart, Lung, and Blood Institute Y1 - 2004///Mar 2 PY - 2004 DA - Mar 2 2004 SP - 951 EP - 7 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 8 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212730508?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Cardiovascular+consequences+of+sleep-disordered+breathing%3A+past%2C+present+and+future%3A+report+of+a+workshop+from+the+National+Center+on+Sleep+Disorders+Research+and+the+National+Heart%2C+Lung%2C+and+Blood+Institute.&rft.au=Quan%2C+S+F%3BGersh%2C+B+J%3BNational+Center+on+Sleep+Disorders+Research%3BNational+Heart%2C+Lung%2C+and+Blood+Institute&rft.aulast=Quan&rft.aufirst=S&rft.date=2004-03-02&rft.volume=109&rft.issue=8&rft.spage=951&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Mar 2 2004 N1 - Last updated - 2014-05-16 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Outer-surface protein C of the Lyme disease spirochete: A protein induced in ticks for infection of mammals AN - 19271029; 5846383 AB - Environmentally responsive synthesis of surface proteins represents a hallmark of the infectious cycle of the Lyme disease agent, Borrelia burgdorferi. Here we created and analyzed a B. burgdorferi mutant lacking outer-surface protein C (OspC), an abundant Osp that spirochetes normally synthesize in the tick vector during the blood meal and down-regulate after transmission to the mammal. We demonstrate that B. burgdorferi strictly requires OspC to infect mice but not to localize or migrate appropriately in the tick. The induction of a spirochetal virulence factor preceding the time and host in which it is required demonstrates a developmental sequence for transmission of this arthropod-borne pathogen. JF - Proceedings of the National Academy of Sciences, USA AU - Grimm, D AU - Tilly, K AU - Byram, R AU - Stewart, P E AU - Krum, J G AU - Bueschel, D M AU - Schwan, T G AU - Policastro, P F AU - Elias, A F AU - Rosa, P A AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South Fourth Street, Hamilton, MT 59840, prosa@niaid.nih.gov Y1 - 2004/03/02/ PY - 2004 DA - 2004 Mar 02 SP - 3142 EP - 3147 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 9 SN - 0027-8424, 0027-8424 KW - mice KW - Microbiology Abstracts B: Bacteriology KW - Virulence KW - Down-regulation KW - Borrelia burgdorferi KW - Vectors KW - Blood meals KW - Lyme disease KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19271029?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Outer-surface+protein+C+of+the+Lyme+disease+spirochete%3A+A+protein+induced+in+ticks+for+infection+of+mammals&rft.au=Grimm%2C+D%3BTilly%2C+K%3BByram%2C+R%3BStewart%2C+P+E%3BKrum%2C+J+G%3BBueschel%2C+D+M%3BSchwan%2C+T+G%3BPolicastro%2C+P+F%3BElias%2C+A+F%3BRosa%2C+P+A&rft.aulast=Grimm&rft.aufirst=D&rft.date=2004-03-02&rft.volume=101&rft.issue=9&rft.spage=3142&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0306845101 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Virulence; Down-regulation; Vectors; Blood meals; Lyme disease DO - http://dx.doi.org/10.1073/pnas.0306845101 ER - TY - JOUR T1 - Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics AN - 17714678; 5846461 AB - The use of critical-for-life organs (e.g., liver or lung) for systemic gene therapeutics can lead to serious safety concerns. To circumvent such issues, we have considered salivary glands (SGs) as an alternative gene therapeutics target tissue. Given the high secretory abilities of SGs, we hypothesized that administration of low doses of recombinant adeno-associated virus (AAV) vectors would allow for therapeutic levels of transgene-encoded secretory proteins in the bloodstream. We administered 10 super(9) particles of an AAV vector encoding human erythropoietin (hEPO) directly to individual mouse submandibular SGs. Serum hEPO reached maximum levels 8-12 weeks after gene delivery and remained relatively stable for 54 weeks (longest time studied). Hematocrit levels were similarly increased. Moreover, these effects proved to be vector dose-dependent, and even a dosage as low as 10 super(8) particles per animal led to significant increases in hEPO and hematocrit levels. Vector DNA was detected only within the targeted SGs, and levels of AAV copies within SGs were highly correlated with serum hEPO levels (r = 0.98). These results show that SGs appear to be promising targets with potential clinical applicability for systemic gene therapeutics. JF - Proceedings of the National Academy of Sciences, USA AU - Voutetakis, A AU - Kok, M R AU - Zheng, C AU - Bossis, I AU - Wang, J AU - Cotrim, A P AU - Marracino, N AU - Goldsmith, C M AU - Chiorini, JA AU - Loh, Y P AU - Nieman, L K AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, and Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, bbaum@dir.nidcr.nih.gov Y1 - 2004/03/02/ PY - 2004 DA - 2004 Mar 02 SP - 3053 EP - 3058 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 9 SN - 0027-8424, 0027-8424 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Gene therapy KW - Salivary gland KW - Adeno-associated virus KW - Expression vectors KW - Erythropoietin KW - Lung KW - Gene transfer KW - Liver KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17714678?accountid=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=Reengineered+salivary+glands+are+stable+endogenous+bioreactors+for+systemic+gene+therapeutics&rft.au=Voutetakis%2C+A%3BKok%2C+M+R%3BZheng%2C+C%3BBossis%2C+I%3BWang%2C+J%3BCotrim%2C+A+P%3BMarracino%2C+N%3BGoldsmith%2C+C+M%3BChiorini%2C+JA%3BLoh%2C+Y+P%3BNieman%2C+L+K%3BBaum%2C+B+J&rft.aulast=Voutetakis&rft.aufirst=A&rft.date=2004-03-02&rft.volume=101&rft.issue=9&rft.spage=3053&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0400136101 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus; Salivary gland; Gene therapy; Gene transfer; Lung; Erythropoietin; Expression vectors; Liver DO - http://dx.doi.org/10.1073/pnas.0400136101 ER - TY - JOUR T1 - Application of sector protein microarrays to clinical samples AN - 954586830; 13860358 AB - Many protein functions are conferred by posttranslational modifications, which allow proteins to perform specific cellular tasks. Protein microarrays enable specific detection of posttranslational modifications not attainable by gene arrays. Reverse-phase protein microarrays have been widely adopted for use with clinical biopsy specimens because they have many advantages including highly reproducible printing of cellular lysates onto array surfaces, buit-in dilution curves, and direct detection using one antibody per analyte. This results in high-sensitivity, broad dynamic range, and favorable precision. Reverse-phase arrays have been restricted to a one slide/one antibody format. Although this is suitable for analyzing treatment effects over populations of samples, it is not well suited to individual patient assessments. One means of reaching this goal is the sector array format. Through the sector array, multiple antibody probes can be multiplexed on a single slide containing replicate immobilized aliquots from one patient. Thus, on one slide, a complete set of analytes can be characterized and used to support a therapy decision. This article describes a method for constructing sector arrays and demonstrates feasibility and adequate sensitivity applied to apoptosis related pathways. JF - Clinical Proteomics AU - Espina, Virginia AU - Petricoin, Emanuel F AU - Liotta, Lance A AU - Geho, David AD - Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, FDA-NCI Clinical Proteomics Program, Bethesda, MD, espinav@mail.nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 91 EP - 99 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 1 IS - 1 SN - 1542-6416, 1542-6416 KW - Biotechnology and Bioengineering Abstracts KW - Antibodies KW - Apoptosis KW - Printing KW - Protein arrays KW - Probes KW - Biopsy KW - proteomics KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954586830?accountid=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+Proteomics&rft.atitle=Application+of+sector+protein+microarrays+to+clinical+samples&rft.au=Espina%2C+Virginia%3BPetricoin%2C+Emanuel+F%3BLiotta%2C+Lance+A%3BGeho%2C+David&rft.aulast=Espina&rft.aufirst=Virginia&rft.date=2004-03-01&rft.volume=1&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Clinical+Proteomics&rft.issn=15426416&rft_id=info:doi/10.1385%2FCP%3A1%3A1%3A091 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-03-30 N1 - SubjectsTermNotLitGenreText - Antibodies; Printing; Apoptosis; Protein arrays; Probes; Biopsy; proteomics DO - http://dx.doi.org/10.1385/CP:1:1:091 ER - TY - JOUR T1 - Development of multiplexed protein profiling and detection using near infrared detection of reverse-phase protein microarrays AN - 954586827; 13860357 AB - Protein microarrays have been recently employed for signal pathway profiling and high-throughput protein expression analysis. Reversephase arrays, where the array consists of immobilized analytes and lysates has especially shown promise in low abundance analyte detection and signal pathway profiling using phospho-specific antibodies. A limitation to current reverse phase array methodology is the inability to multiplex proteomic-based endpoints as each array can only report one analyte endpoint. In this study, we report on the use of a dual dye based approach that can effectively double the number of endpoints observed per array allowing, for example, both phosphospecific and total protein levels to be measured and analyzed at once. The method utilizes antibody bound dyes that emit in the infrared spectral region as a means of sensitive and specific detection. JF - Clinical Proteomics AU - Calvert, Valerie S AU - Tang, Yihui AU - Boveia, Vince AU - Wulfkuhle, Julie AU - Schutz-Geschwender, Amy AU - Michael Olive, D AU - Liotta, Lance A AU - Petricoin, Emanuel F AD - Office of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, NCI/FDA Clinical Proteomics Program, 20892, Bethesda, Maryland, petricoin@cber.fda.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 81 EP - 89 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 1 IS - 1 SN - 1542-6416, 1542-6416 KW - Biotechnology and Bioengineering Abstracts KW - Antibodies KW - Dyes KW - Protein arrays KW - proteomics KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954586827?accountid=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+Proteomics&rft.atitle=Development+of+multiplexed+protein+profiling+and+detection+using+near+infrared+detection+of+reverse-phase+protein+microarrays&rft.au=Calvert%2C+Valerie+S%3BTang%2C+Yihui%3BBoveia%2C+Vince%3BWulfkuhle%2C+Julie%3BSchutz-Geschwender%2C+Amy%3BMichael+Olive%2C+D%3BLiotta%2C+Lance+A%3BPetricoin%2C+Emanuel+F&rft.aulast=Calvert&rft.aufirst=Valerie&rft.date=2004-03-01&rft.volume=1&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Clinical+Proteomics&rft.issn=15426416&rft_id=info:doi/10.1385%2FCP%3A1%3A1%3A081 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-03-30 N1 - SubjectsTermNotLitGenreText - Antibodies; Dyes; Protein arrays; proteomics DO - http://dx.doi.org/10.1385/CP:1:1:081 ER - TY - JOUR T1 - NT-3 replacement with brain-derived neurotrophic factor redirects vestibular nerve fibers to the cochlea. AN - 85305142; pmid-15014133 AB - Survival of inner ear sensory neurons depends on two neurotrophins, BDNF and NT-3, and their respective receptors, TrkB and TrkC. Because both receptors are present in the same neuron, it has been suggested that BDNF and NT-3 are functionally redundant in promoting neuronal survival. Knock-in of one ligand into the locus of the other one confirmed this hypothesis for the cochlea, leaving open the question of why two neurotrophins are required for proper innervation of the mammalian ear. Here, we show that the precise spatiotemporal pattern of expression of the two neurotrophins is essential for proper patterning of the inner ear innervation. Mice expressing BDNF under the control of the NT-3 promoter develop exuberant projections of vestibular sensory neurons to the basal turn of the cochlea. This projection can be enhanced by combining the transgene with a null mutation of BDNF. However, vestibular fibers rerouted into the cochlea do not reach hair cells and remain outside the organ of Corti, suggesting a chemotactic role for neurotrophins on these fibers. Our data provide genetic evidence that neurotrophins in the ear exert both survival and axon guidance roles. JF - The Journal of Neuroscience AU - Tessarollo Lino AU - Coppola Vincenzo AU - Fritzsch Bernd AD - Neural Development Group, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21701, USA. PY - 2004 SP - 2575 EP - 2584 VL - 24 IS - 10 SN - 0270-6474, 0270-6474 KW - Cochlea KW - Animals KW - Promoter Regions (Genetics) KW - Support, U.S. Gov't, P.H.S. KW - Hair Cells KW - Brain-Derived Neurotrophic Factor KW - Gestational Age KW - Mice KW - Fluorescent Dyes KW - Mice, Transgenic KW - Cell Survival KW - Mice, Mutant Strains KW - Mice, Inbred C57BL KW - Axons KW - Neurotrophin 3 KW - Vestibule KW - Gene Expression Regulation, Developmental KW - Nerve Fibers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85305142?accountid=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=NT-3+replacement+with+brain-derived+neurotrophic+factor+redirects+vestibular+nerve+fibers+to+the+cochlea.&rft.au=Tessarollo+Lino%3BCoppola+Vincenzo%3BFritzsch+Bernd&rft.aulast=Tessarollo+Lino&rft.aufirst=&rft.date=2004-03-01&rft.volume=24&rft.issue=10&rft.spage=2575&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 - Application of xylanase from thermomyces lanuginosus IOC-4145 for enzymatic hydrolysis of corncob and sugarcane bagasse AN - 815540364; 13858139 AB - Xylanases have significant current and potential uses for several industries including paper and pulp, food, and biofuel. For the biofuel industry, xylanases can be used to aid in the conversion of lignocellulose to fermentable sugars (e.g., xylose). We investigated the thermophilic fungus Thermomyces lanuginosus was yielded for xylanase production and found that the highest activity (850 U/mL) was yielded after 96 h of semisolid fermentation. The enzyme was used for hydrolyzing agricultural residues with and without pretreatment. Such residues were characterized in relation to the maximum xylose content by total acid hydrolysis. The highest xylose yields realized by enzymatic hydrolysis were 24 and 52%, achieved by using 3000 U/g (dried material) of sugarcane bagasse and corncob, respectively, which received both alkali and thermal pretreatment. JF - Applied Biochemistry and Biotechnology AU - Damaso, Monica Caramez Triches AU - Castro, Aline Machado AU - Castro, Raquel Machado AU - Andrade, Carolina Maria MC AU - Pereira, Nei AD - White Martins Gases Industriais LTDA, Duque de Caxias, CEP 25225-170, Rio de Janeiro, RJ, Brasil, nei@eq.ufrj.br Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 1003 EP - 1012 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 115 IS - 1-3 SN - 0273-2289, 0273-2289 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biotechnology and Bioengineering Abstracts KW - Sugar KW - Xylose KW - Xylan endo-1,3-b-xylosidase KW - Fermentation KW - Food KW - Enzymes KW - Pulp KW - Hydrolysis KW - Xylan endo-1,3- beta -xylosidase KW - lignocellulose KW - Bagasse KW - Thermomyces lanuginosus KW - Alkalis KW - Biofuels KW - A 01330:Food Microbiology KW - W 30935:Food Biotechnology KW - K 03420:Plant Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/815540364?accountid=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=Applied+Biochemistry+and+Biotechnology&rft.atitle=Application+of+xylanase+from+thermomyces+lanuginosus+IOC-4145+for+enzymatic+hydrolysis+of+corncob+and+sugarcane+bagasse&rft.au=Damaso%2C+Monica+Caramez+Triches%3BCastro%2C+Aline+Machado%3BCastro%2C+Raquel+Machado%3BAndrade%2C+Carolina+Maria+MC%3BPereira%2C+Nei&rft.aulast=Damaso&rft.aufirst=Monica+Caramez&rft.date=2004-03-01&rft.volume=115&rft.issue=1-3&rft.spage=1003&rft.isbn=&rft.btitle=&rft.title=Applied+Biochemistry+and+Biotechnology&rft.issn=02732289&rft_id=info:doi/10.1385%2FABAB%3A115%3A1-3%3A1003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2013-12-04 N1 - SubjectsTermNotLitGenreText - Sugar; Xylose; Xylan endo-1,3-b-xylosidase; Fermentation; Food; Pulp; Enzymes; Hydrolysis; Xylan endo-1,3- beta -xylosidase; lignocellulose; Bagasse; Alkalis; Biofuels; Thermomyces lanuginosus DO - http://dx.doi.org/10.1385/ABAB:115:1-3:1003 ER - TY - JOUR T1 - Gene modulation by Cox-1 and Cox-2 specific inhibitors in human colorectal carcinoma cancer cells. AN - 80177919; 14633654 AB - Cox-1 and Cox-2 specific inhibitors exert chemo-preventative activity. However, the exact mechanisms for this activity remain unclear. Increasing evidence suggests that non-steroidal anti-inflammatory drugs regulate gene expression, which may be responsible, in part, for this activity. In this study, human colorectal carcinoma HCT-116 cells were treated with the Cox-1 specific inhibitor SC-560 and the Cox-2 specific inhibitor SC-58125 to evaluate their ability to induce apoptosis, inhibit cell proliferation, inhibit growth on soft agar and modulate gene expression. The Cox-1 specific inhibitor, SC-560 significantly induced apoptosis and inhibited the growth of HCT-116 cells on soft agar, an in vitro assay for tumorigenicity. SC-58125 moderately induced apoptosis and inhibited growth on soft agar at higher concentrations than were required for SC-560. Previously, we reported that the potent chemo-preventative drug sulindac sulfide altered the expression of eight genes including several transcription factors that may be linked to this drug's chemo-preventative activity. HCT-116 cells were treated with various concentrations of SC-560 or SC-58125 and changes in the expression of these eight genes were determined by real-time reverse transcription- polymerase chain reaction. SC-560 modulated mRNA expression of the eight genes studied. In contrast, SC-58125 required approximately 5-10-fold higher concentrations to achieve similar degrees of gene modulation in six of eight genes. Changes in protein expression by SC-560 also occurred for five of these genes with antibodies available (NAG-1, ATF3, C/EBPbeta, MAD2 and MSX1). In conclusion, this is the first report to suggest that like sulindac sulfide, the Cox-1 specific inhibitor SC-560 appears to elicit chemo-preventative activity by altering gene expression, while the chemo-preventative effects of SC-58125 are complex and probably work through these and other mechanisms, such as the inhibition of Cox-2. JF - Carcinogenesis AU - Bottone, Frank G AU - Martinez, Jeanelle M AU - Alston-Mills, Brenda AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 349 EP - 357 VL - 25 IS - 3 SN - 0143-3334, 0143-3334 KW - Cyclooxygenase 2 Inhibitors KW - 0 KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Pyrazoles KW - SC 560 KW - 1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole KW - 162054-19-5 KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - PTGS1 protein, human KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Pyrazoles -- pharmacology KW - Tumor Cells, Cultured KW - Humans KW - Apoptosis -- drug effects KW - Cell Division -- drug effects KW - Prostaglandin-Endoperoxide Synthases -- drug effects KW - Isoenzymes -- antagonists & inhibitors KW - Colorectal Neoplasms -- metabolism KW - Carcinoma -- enzymology KW - Isoenzymes -- drug effects KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- enzymology KW - Carcinoma -- metabolism KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Cyclooxygenase Inhibitors -- pharmacology KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80177919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+modulation+by+Cox-1+and+Cox-2+specific+inhibitors+in+human+colorectal+carcinoma+cancer+cells.&rft.au=Bottone%2C+Frank+G%3BMartinez%2C+Jeanelle+M%3BAlston-Mills%2C+Brenda%3BEling%2C+Thomas+E&rft.aulast=Bottone&rft.aufirst=Frank&rft.date=2004-03-01&rft.volume=25&rft.issue=3&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-14 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The molecular basis of the action of disulfiram as a modulator of the multidrug resistance-linked ATP binding cassette transporters MDR1 (ABCB1) and MRP1 (ABCC1). AN - 80176430; 14978246 AB - The overexpression of multidrug resistance protein 1 (MDR1) and multidrug resistance protein 1 (MRP1) gene products is a major cause of multidrug resistance in cancer cells. A recent study suggested that disulfiram, a drug used to treat alcoholism, might act as a modulator of P-glycoprotein. In this study, we investigated the molecular and chemical basis of disulfiram as a multidrug resistance modulator. We demonstrate that in intact cells, disulfiram reverses either MDR1- or MRP1-mediated efflux of fluorescent drug substrates. Disulfiram inhibits ATP hydrolysis and the binding of [alpha-32P]8-azidoATP to P-glycoprotein and MRP1, with inhibition curves comparable with those of N-ethylmaleimide, a cysteine-modifying agent. However, if the ATP sites are protected with excess ATP, disulfiram stimulates ATP hydrolysis by both transporters in a concentration-dependent manner. Thus, in addition to modifying cysteines at the ATP sites, disulfiram may interact with the drug-substrate binding site. We demonstrate that disulfiram, but not N-ethylmaleimide, inhibits in a concentration-dependent manner the photoaffinity labeling of the multidrug transporter with 125I-iodoarylazidoprazosin and [3H]azidopine. This suggests that the interaction of disulfiram with the drug-binding site is independent of its role as a cysteine-modifying agent. Finally, we have exploited MRP4 (ABCC4) to demonstrate that disulfiram can inhibit ATP binding by forming disulfide bonds between cysteines located in the vicinity of, although not in, the active site. Taken together, our results suggest that disulfiram has unique molecular interactions with both the ATP and/or drug-substrate binding sites of multiple ATP binding cassette transporters, which are associated with drug resistance, and it is potentially an attractive agent to combat multidrug resistance. JF - Molecular pharmacology AU - Sauna, Zuben E AU - Peng, Xiang-Hong AU - Nandigama, Krishnamachary AU - Tekle, Samrawit AU - Ambudkar, Suresh V AD - Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4254, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 675 EP - 684 VL - 65 IS - 3 SN - 0026-895X, 0026-895X KW - Azides KW - 0 KW - Dihydropyridines KW - Enzyme Inhibitors KW - Multidrug Resistance-Associated Proteins KW - P-Glycoprotein KW - Phosphorus Radioisotopes KW - 8-azidoadenosine 5'-triphosphate KW - 53696-59-6 KW - azidopine KW - 63XR70204A KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - azidoprazosin KW - 90990-97-9 KW - Disulfiram KW - TR3MLJ1UAI KW - Prazosin KW - XM03YJ541D KW - multidrug resistance-associated protein 1 KW - Y49M64GZ4Q KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Drug Interactions KW - Dihydropyridines -- pharmacology KW - Cells, Cultured KW - Humans KW - Binding Sites -- drug effects KW - Azides -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Mice KW - Hydrolysis KW - Prazosin -- analogs & derivatives KW - P-Glycoprotein -- metabolism KW - Drug Resistance, Multiple -- physiology KW - Adenosine Triphosphate -- analogs & derivatives KW - Prazosin -- pharmacology KW - Multidrug Resistance-Associated Proteins -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Disulfiram -- pharmacology KW - Adenosine Triphosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80176430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+molecular+basis+of+the+action+of+disulfiram+as+a+modulator+of+the+multidrug+resistance-linked+ATP+binding+cassette+transporters+MDR1+%28ABCB1%29+and+MRP1+%28ABCC1%29.&rft.au=Sauna%2C+Zuben+E%3BPeng%2C+Xiang-Hong%3BNandigama%2C+Krishnamachary%3BTekle%2C+Samrawit%3BAmbudkar%2C+Suresh+V&rft.aulast=Sauna&rft.aufirst=Zuben&rft.date=2004-03-01&rft.volume=65&rft.issue=3&rft.spage=675&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 - 2004-03-23 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. AN - 80175594; 14978253 AB - Clinically, there is a great need for small molecule inhibitors that could control pathogenic effects of transforming growth factor (TGF-beta) and/or modulate effects of TGF-beta in normal responses. Inhibition of TGF-beta signaling would be predicted to enhance re-epithelialization of cutaneous wounds and reduce scarring fibrosis. Selective small molecule inhibitors of the TGF-beta signaling pathway developed for therapeutics will also be powerful tools in experimentally dissecting this complex pathway, especially its cross-talk with other signaling pathways. In this study, we characterized 2-(5-benzo[1,3]dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride (SB-505124), a member of a new class of small molecule inhibitors related to imidazole inhibitors of p38, which inhibit the TGF-beta type I receptor serine/threonine kinase known as activin receptor-like kinase (ALK) 5. We demonstrate that this compound selectively and concentration-dependently inhibits ALK4-, ALK5-, and ALK 7-dependent activation of downstream cytoplasmic signal transducers, Smad2 and Smad3, and of TGF-beta-induced mitogen-activated protein kinase pathway components but does not alter ALK1, ALK2, ALK3 or ALK6-induced Smad signaling. SB-505124 also blocks more complex endpoints of TGF-beta action, as evidenced by its ability to abrogate cell death caused by TGF-beta1 treatment. SB-505124 is three to five times more potent than a related ALK5 inhibitor described previously, SB-431542. JF - Molecular pharmacology AU - DaCosta Byfield, Stacey AU - Major, Christopher AU - Laping, Nicholas J AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-5055, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 744 EP - 752 VL - 65 IS - 3 SN - 0026-895X, 0026-895X KW - 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide KW - 0 KW - Benzamides KW - DNA-Binding Proteins KW - Dioxoles KW - Proteins KW - Receptors, Transforming Growth Factor beta KW - Smad Proteins KW - Trans-Activators KW - Transforming Growth Factor beta KW - Activins KW - 104625-48-1 KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - ACVR1B protein, human KW - EC 2.7.11.30 KW - ACVR1C protein, human KW - Activin Receptors, Type I KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Drug Interactions KW - COS Cells KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Cell Death -- drug effects KW - Dioxoles -- pharmacology KW - Tumor Cells, Cultured KW - Benzamides -- pharmacology KW - Genes, Reporter KW - Activins -- pharmacology KW - DNA-Binding Proteins -- metabolism KW - Activin Receptors, Type I -- antagonists & inhibitors KW - Receptors, Transforming Growth Factor beta -- antagonists & inhibitors KW - Transforming Growth Factor beta -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80175594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=SB-505124+is+a+selective+inhibitor+of+transforming+growth+factor-beta+type+I+receptors+ALK4%2C+ALK5%2C+and+ALK7.&rft.au=DaCosta+Byfield%2C+Stacey%3BMajor%2C+Christopher%3BLaping%2C+Nicholas+J%3BRoberts%2C+Anita+B&rft.aulast=DaCosta+Byfield&rft.aufirst=Stacey&rft.date=2004-03-01&rft.volume=65&rft.issue=3&rft.spage=744&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 - 2004-03-23 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidermal growth factor receptor inhibitors in clinical development. AN - 80165741; 14967462 AB - In cancer cells, aberrant signaling through the epidermal growth factor receptor (EGFR) activates pathways that stimulate many of the properties associated with neoplasia, including proliferation, migration, stromal invasion, tumor angiogenesis, and resistance to cell death-inducing signals. Because of the frequency of abnormalities in receptor signaling in human cancers, the EGFR is an attractive target for therapeutic development. Monoclonal antibodies and small molecule tyrosine kinase inhibitors are the two classes of agents that are the furthest advanced in clinical development. Although pharmacologic and mechanistic differences exist between the two classes, the results of preclinical studies suggest that both inhibit proliferation, have little normal tissue toxicity, and are additive/synergistic with standard therapies. The results from early clinical trials have indicated that both classes of agents are well tolerated and have antitumor activity. However, the first Phase III studies to be completed have not shown an improvement in survival with the addition of the monoclonal antibody C225 to cisplatin in patients with head-and-neck carcinoma or the addition of the kinase inhibitor ZD1839 to chemotherapy in patients with advanced lung cancer. Ongoing and future studies must address issues related to the selection of patients for study, dose and schedule of administration, monotherapy vs. combination treatment, and combinations with standard and investigational agents. JF - International journal of radiation oncology, biology, physics AU - Dancey, Janet AD - Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA. danceyj@ctep.nci.nih.gov Y1 - 2004/03/01/ PY - 2004 DA - 2004 Mar 01 SP - 1003 EP - 1007 VL - 58 IS - 3 SN - 0360-3016, 0360-3016 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Antineoplastic Agents KW - Enzyme Inhibitors KW - Neoplasm Proteins KW - Quinazolines KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, Epidermal Growth Factor KW - Cetuximab KW - PQX0D8J21J KW - gefitinib KW - S65743JHBS KW - Index Medicus KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Humans KW - Quinazolines -- therapeutic use KW - Clinical Trials as Topic KW - Antineoplastic Agents -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Receptor, Epidermal Growth Factor -- antagonists & inhibitors KW - Enzyme Inhibitors -- therapeutic use KW - Neoplasm Proteins -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80165741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology%2C+biology%2C+physics&rft.atitle=Epidermal+growth+factor+receptor+inhibitors+in+clinical+development.&rft.au=Dancey%2C+Janet&rft.aulast=Dancey&rft.aufirst=Janet&rft.date=2004-03-01&rft.volume=58&rft.issue=3&rft.spage=1003&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-24 N1 - Date created - 2004-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effectiveness of nicotine-patch therapy for smoking cessation in patients with schizophrenia. AN - 80165518; 14967189 AB - The purpose of this study was to determine the effectiveness of nicotine-patch therapy for smoking cessation in patients with schizophrenia. This was a longitudinal study and sixty-eight schizophrenic patients were assigned to 8 weeks of a nicotine-patch therapy program or a control group. The generalized estimating equation analysis revealed that there were significant reductions in the subjects' nicotine dependence (Fagerstrom Tolerance Questionnaire), the number of cigarettes per day, and CO levels over an 8-week period of nicotine-patch therapy and 3-month follow-up. The point-prevalence rates of abstinence from smoking were an abstinence of 26.9% at 8 weeks and 26.9% at a 3-month follow-up. At the 3-month follow-up, the rate of continuous smoking abstinence in the nicotine-patch group was 23.1%. JF - International journal of nursing studies AU - Chou, Kuei-Ru AU - Chen, Ruey AU - Lee, Jia-Fu AU - Ku, Chih-Hung AU - Lu, Ru-Band AD - National Defense Medical Center, School of Nursing, Nei-Hu, Taipei 114, Taiwan, ROC. kueiru@ndmctsgh.edu.tw Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 321 EP - 330 VL - 41 IS - 3 SN - 0020-7489, 0020-7489 KW - Ganglionic Stimulants KW - 0 KW - Nicotine KW - 6M3C89ZY6R KW - Carbon Monoxide KW - 7U1EE4V452 KW - Index Medicus KW - Nursing KW - Carbon Monoxide -- blood KW - Administration, Cutaneous KW - Humans KW - Longitudinal Studies KW - Patient Compliance KW - Adult KW - Treatment Outcome KW - Surveys and Questionnaires KW - Schizophrenic Psychology KW - Middle Aged KW - Female KW - Male KW - Prevalence KW - Tobacco Use Disorder -- blood KW - Tobacco Use Disorder -- epidemiology KW - Nicotine -- administration & dosage KW - Smoking -- prevention & control KW - Smoking -- psychology KW - Schizophrenia -- complications KW - Smoking -- epidemiology KW - Smoking Cessation -- psychology KW - Smoking -- blood KW - Smoking Cessation -- methods KW - Tobacco Use Disorder -- psychology KW - Tobacco Use Disorder -- prevention & control KW - Ganglionic Stimulants -- administration & dosage KW - Tobacco Use Disorder -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80165518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nursing+studies&rft.atitle=The+effectiveness+of+nicotine-patch+therapy+for+smoking+cessation+in+patients+with+schizophrenia.&rft.au=Chou%2C+Kuei-Ru%3BChen%2C+Ruey%3BLee%2C+Jia-Fu%3BKu%2C+Chih-Hung%3BLu%2C+Ru-Band&rft.aulast=Chou&rft.aufirst=Kuei-Ru&rft.date=2004-03-01&rft.volume=41&rft.issue=3&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=International+journal+of+nursing+studies&rft.issn=00207489&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-09 N1 - Date created - 2004-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure of the scorpion toxin BmBKTtx1 solved from single wavelength anomalous scattering of sulfur. AN - 80153927; 14960379 AB - This report describes the crystal structure of the K(+) channel-blocking toxin, BmBKTx1, isolated recently from the venom of the scorpion Buthus martensi Karsch. This is only the second structure of the short-chain K(+) channel-blocking toxin from scorpion solved by means of X-ray crystallography. Additionally, reductive dimethylation of folded BmBKTx1 employed to induce its crystallization and solution of the structure based on the anomalous signal from the sulfur atoms make this example quite unique. The monomer of BmBKTx1 is formed by 31 amino acid residues, including 6 cysteines connected in 3 disulfide bridges. Crystals of this toxin belong to the space group P2(1) with two molecules present in the asymmetric unit. The unit cell parameters are a = 21.40 A, b=39.70 A, c=29.37 A, and beta-94.13 grades. Based on the high-quality dataset (anomalous signal) collected to the resolution 1.72A using the conventional X-radiation generator (lambda Cu, K alpha = 1.5478 A), the positions of sulfur atoms contributed by 12 cysteine residues have been identified, and subsequent improvement of the experimental phases have allowed structure solution. The final model was refined to the crystallographic R-factor of 0.166. The methyl groups on several lysine residues could be easily modeled into the electron density. JF - Journal of structural biology AU - Szyk, Agnieszka AU - Lu, Wuyuan AU - Xu, Chenqi AU - Lubkowski, Jacek AD - Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 289 EP - 294 VL - 145 IS - 3 SN - 1047-8477, 1047-8477 KW - Amino Acids KW - 0 KW - Disulfides KW - Insect Proteins KW - Neurotoxins KW - Potassium Channels KW - Scorpion Venoms KW - bukatoxin KW - Sulfur KW - 70FD1KFU70 KW - Lysine KW - K3Z4F929H6 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Scattering, Radiation KW - Electrons KW - Lysine -- chemistry KW - Models, Molecular KW - Amino Acid Sequence KW - Static Electricity KW - Scorpion Venoms -- chemistry KW - Potassium Channels -- metabolism KW - X-Rays KW - Cysteine -- chemistry KW - Amino Acids -- chemistry KW - Protein Folding KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Methylation KW - Protein Conformation KW - Scorpions -- chemistry KW - Sulfur -- chemistry KW - Neurotoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80153927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+structural+biology&rft.atitle=Structure+of+the+scorpion+toxin+BmBKTtx1+solved+from+single+wavelength+anomalous+scattering+of+sulfur.&rft.au=Szyk%2C+Agnieszka%3BLu%2C+Wuyuan%3BXu%2C+Chenqi%3BLubkowski%2C+Jacek&rft.aulast=Szyk&rft.aufirst=Agnieszka&rft.date=2004-03-01&rft.volume=145&rft.issue=3&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Journal+of+structural+biology&rft.issn=10478477&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-19 N1 - Date created - 2004-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction between the immune system and tongue squamous cell carcinoma induced by 4-nitroquinoline N-oxide in mice. AN - 80131329; 14747060 AB - Squamous cell carcinoma of the oral cavity (SCC) accounts for 3% of cancers in the western world and 40% of cancers in India. The overall 5-year survival rate is only 50%. Most of the lesions appear intra-orally on the tongue. Results from a previous study demonstrated a significant increase in T and B-lymphocytes under the transformed epithelium when examining human lesions of hyperkeratosis, dysplasia and carcinoma of the tongue. In order to investigate the interaction between the host immunity and SCC, carcinogen induced SCC of the tongue was studied in mice. The water-soluble carcinogen, 4 nitroquinoline N-oxide (4NQO), was applied to BALB/c mice tongues and produced tongue SCC after a long incubation period of several months. Immunologic properties were examined systemically in the spleens and locally, at the tumor site. Examination of spleen lymphocytes from 4NQO induced mice revealed enlargement of the spleens and a significant decrease in the CD3, CD4, CD8 and CD19 cells. In the tongues, expression of TGF-beta, TNF-alpha, GM-CSF, and IL-1 beta mRNA were detected. TNF-alpha protein was detected in the affected tongues using immunoassays. mRNA expression of TNF-alpha was detected in the cancerous epithelium when extracted from the connective tissue. CD11b and CD3 cells were detected in the connective tissue under the developing carcinoma. CD11b positive cells were more prominent. The infiltrate was very scattered and not prominent as the infiltrate in the human tongue tissues. These results indicate that the growing tumor affected the immune response around the tumor and systemically. Most of the cytokines, which appeared in the affected tongues, originated from the tumor surroundings, but TNF-alpha was found also in the tumor. The interaction between the tumor and immune response components is important for diagnosis and treatment purposes. JF - Oral oncology AU - Gannot, Gallya AU - Buchner, Amos AU - Keisari, Yona AD - Department of Oral Pathology and Oral Medicine, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel-Aviv, Israel. gannotg@pop.nci.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 287 EP - 297 VL - 40 IS - 3 SN - 1368-8375, 1368-8375 KW - Carcinogens KW - 0 KW - Cytokines KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - 4-Nitroquinoline-1-oxide KW - 56-57-5 KW - Index Medicus KW - Animals KW - Cytokines -- genetics KW - Cytokines -- biosynthesis KW - Lymphocyte Subsets -- pathology KW - Spleen -- pathology KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Inbred BALB C KW - Lymphocyte Activation KW - Tumor Necrosis Factor-alpha -- analysis KW - Spleen -- immunology KW - Epithelium -- immunology KW - Male KW - Cell Division KW - Carcinoma, Squamous Cell -- immunology KW - Tongue Neoplasms -- chemically induced KW - Tongue Neoplasms -- immunology KW - Carcinoma, Squamous Cell -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80131329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oral+oncology&rft.atitle=Interaction+between+the+immune+system+and+tongue+squamous+cell+carcinoma+induced+by+4-nitroquinoline+N-oxide+in+mice.&rft.au=Gannot%2C+Gallya%3BBuchner%2C+Amos%3BKeisari%2C+Yona&rft.aulast=Gannot&rft.aufirst=Gallya&rft.date=2004-03-01&rft.volume=40&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Oral+oncology&rft.issn=13688375&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-17 N1 - Date created - 2004-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of liver hemangiosarcoma and secondary iron overload in B6C3F1 mice--the National Toxicology Program experience. AN - 72027231; 15200160 AB - The literature evidencing the role of iron in promoting a range of neoplasms in humans and animals prompted us to search for a possible association between chemically induced hemosiderosis and hemangiosarcomas in the liver of mice in selected studies conducted by the National Toxicology Program (NTP). Its historical control database was examined for studies in which treatment-related liver hemangiosarcoma was noted; 130 consecutive NTP studies in B6C3F1 mice from Technical Report (TR)-340 to TR-493 were evaluated. Three compounds (2-butoxyethanol, p-nitroaniline, and para-chloroaniline) were associated with a relatively high incidence of Kupffer cell pigmentation consisting of hemosiderin in both sexes; only the male mice developed a relatively low incidence of treatment-related hemangiosarcoma. With a fourth compound (o-nitroanisole), a relatively low incidence (16/50, high-dose males) of chemical-related hemosiderosis was noted, with no associated increase of hemangiosarcoma. Two chemicals (pentachlorophenol and tetrafluoroethylene) increased the incidence of liver hemangiosarcoma in male and female mice, with no increase in Kupffer cell pigmentation. The overall association between liver hemangiosarcoma and Kupffer cell pigmentation was highly significant (p < 0.001). The cause for hemosiderosis in all cases was the erythrocytic hemolytic effect of the compounds. The reason for the sex-increased susceptibility for development of hemangiosarcoma is unknown but may be due to a hormone-related, reduced antioxidative defensive capacity through modulation of the activities of antioxidative enzymes. JF - Toxicologic pathology AU - Nyska, Abraham AU - Haseman, Joseph K AU - Kohen, Roni AU - Maronpot, Robert R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-9998, USA. nyska@niehs.nih.gov PY - 2004 SP - 222 EP - 228 VL - 32 IS - 2 SN - 0192-6233, 0192-6233 KW - Aniline Compounds KW - 0 KW - Carcinogens KW - Ethylene Glycols KW - nitroaniline KW - 29757-24-2 KW - Hemosiderin KW - 9011-92-1 KW - Iron KW - E1UOL152H7 KW - n-butoxyethanol KW - I0P9XEZ9WV KW - 4-chloroaniline KW - Z553SGH315 KW - Index Medicus KW - United States KW - Animals KW - Sex Factors KW - Kupffer Cells -- drug effects KW - Mice KW - Aniline Compounds -- toxicity KW - Kupffer Cells -- pathology KW - Hemolysis -- drug effects KW - Mice, Inbred Strains KW - Ethylene Glycols -- toxicity KW - National Institutes of Health (U.S.) KW - Carcinogenicity Tests KW - Kupffer Cells -- metabolism KW - Female KW - Male KW - Hemosiderin -- metabolism KW - Liver Neoplasms -- pathology KW - Hemosiderosis -- chemically induced KW - Hemangiosarcoma -- etiology KW - Cocarcinogenesis KW - Hemosiderosis -- pathology KW - Hemangiosarcoma -- pathology KW - Carcinogens -- toxicity KW - Liver Neoplasms -- etiology KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72027231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+of+liver+hemangiosarcoma+and+secondary+iron+overload+in+B6C3F1+mice--the+National+Toxicology+Program+experience.&rft.au=Nyska%2C+Abraham%3BHaseman%2C+Joseph+K%3BKohen%2C+Roni%3BMaronpot%2C+Robert+R&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2004-03-01&rft.volume=32&rft.issue=2&rft.spage=222&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 - 2004-10-14 N1 - Date created - 2004-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The combination of carboplatin and weekly paclitaxel: a safe and active regimen in advanced non small-cell lung cancer patients. A phase I-II study. AN - 71931175; 15149147 AB - The combination of carboplatin and paclitaxel given every three weeks is a tolerated and reasonably active regimen in advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the maximum tolerated dose (MTD) of a fixed dose of carboplatin with an area under the curve (AUC) of 6 and escalating doses of weekly paclitaxel with an initial dose of 50 mg/m2 with 10 mg/m2 increments at each level in untreated NSCLC patients (phase I study). The study continued with a phase II study. Thirty patients entered the phase I study. The MTD was: carboplatin AUC = 6 on days 1 and 28 plus paclitaxel 100 mg/m2 (1 hour) on days 1, 8,15, 28. The dose-limiting toxicity (DLT) was severe neutropenia and cardiological toxicity. Subsequently, 42 patients entered the phase II study with the same treatment schedule. The 2-drug combination was globally well tolerated. The overall response rate (RR) was 42% [CI 95%: 26.3-57.7], stable disease (SD) 29% and progression (PD) 29%. The median duration of response was 8.0 mos (range: 1.0-19.0). The median time to progression was 8.0 mos (range: 7.0-19.0) and the median survival was 14.0 months (range: 9.0-19.0). The association of carboplatin AUC = 6 and weekly paclitaxel 100 mg/m2 proved to be manageable, active and extremely safe even in elderly patients (one third of all patients in our cohort). The survival results were interesting: the median survival time was 14 months (9-19 months) and the 1- and 2-year survival was 59% and 16%, respectively. JF - Journal of experimental & clinical cancer research : CR AU - Fabi, A AU - Barduagni, M AU - Ferraresi, V AU - Cortesi, E AU - Gamucci, T AU - De Marinis, F AU - Saltarelli, R AU - Gabriele, A AU - Pellicciotta, M AU - Ceribelli, A AU - De Marco, S AU - Facciolo, F AU - Cognetti, F AD - Dept. of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. alessandra.fabi@virgilio.it Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 25 EP - 32 VL - 23 IS - 1 SN - 0392-9078, 0392-9078 KW - Carboplatin KW - BG3F62OND5 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Area Under Curve KW - Humans KW - Disease Progression KW - Aged KW - Adult KW - Cohort Studies KW - Treatment Outcome KW - Neoplasm Metastasis KW - Middle Aged KW - Maximum Tolerated Dose KW - Time Factors KW - Female KW - Male KW - Paclitaxel -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Lung Neoplasms -- drug therapy KW - Lung Neoplasms -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Carboplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71931175?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+clinical+cancer+research+%3A+CR&rft.atitle=The+combination+of+carboplatin+and+weekly+paclitaxel%3A+a+safe+and+active+regimen+in+advanced+non+small-cell+lung+cancer+patients.+A+phase+I-II+study.&rft.au=Fabi%2C+A%3BBarduagni%2C+M%3BFerraresi%2C+V%3BCortesi%2C+E%3BGamucci%2C+T%3BDe+Marinis%2C+F%3BSaltarelli%2C+R%3BGabriele%2C+A%3BPellicciotta%2C+M%3BCeribelli%2C+A%3BDe+Marco%2C+S%3BFacciolo%2C+F%3BCognetti%2C+F&rft.aulast=Fabi&rft.aufirst=A&rft.date=2004-03-01&rft.volume=23&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-19 N1 - Date created - 2004-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TGFbeta1, back to the future: revisiting its role as a transforming growth factor. AN - 71869790; 15034302 AB - TGFbeta1 was initially identified in culture media from transformed cells as part of a factor that could produce a transformed phenotype in a nontransformed cell line. Subsequently this activity was separated into TGFbeta and TGFalpha an EGF receptor ligand. With the discovery that TGFbeta1 was a potent growth inhibitor of epithelial cells, and the identification of inactivating mutations within the TGFbeta1 signaling pathway in cancers it became clear that TGFbeta1 signaling is a tumor suppressor pathway for early stages of cancer. However many human carcinomas overexpress TGFbeta1 and this is associated with poor patient prognosis and increased frequency of metastasis. Similar results have been obtained with tumor cell lines and experimental animal models. Thus stage specific duality of function is the emerging paradigm for the role of TGFbeta1 in cancer. This review will focus on the evidence for TGFbeta1 as a tumor promoting and metastasis factor and examine the biological and molecular basis for these effects. It is proposed that the switch from tumor suppressor to oncogene reflects genetic or epigenetic alterations in signaling pathways in tumor cells that alter the readout from the TGFbeta1 pathway. JF - Cancer biology & therapy AU - Glick, Adam B AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, The Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. glicka@dc37a.nci.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 276 EP - 283 VL - 3 IS - 3 SN - 1538-4047, 1538-4047 KW - TGFB1 protein, human KW - 0 KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Index Medicus KW - Phenotype KW - Neoplasm Invasiveness KW - Animals KW - Humans KW - Prognosis KW - Disease Progression KW - Disease Models, Animal KW - Neovascularization, Pathologic KW - Immune Tolerance KW - Transforming Growth Factor beta -- pharmacology KW - Neoplasms -- physiopathology KW - Carcinoma -- physiopathology KW - Neoplasm Metastasis -- physiopathology KW - Signal Transduction KW - Neoplasms -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71869790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+%26+therapy&rft.atitle=TGFbeta1%2C+back+to+the+future%3A+revisiting+its+role+as+a+transforming+growth+factor.&rft.au=Glick%2C+Adam+B&rft.aulast=Glick&rft.aufirst=Adam&rft.date=2004-03-01&rft.volume=3&rft.issue=3&rft.spage=276&rft.isbn=&rft.btitle=&rft.title=Cancer+biology+%26+therapy&rft.issn=15384047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-26 N1 - Date created - 2004-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclazocine: comparison to hydromorphone and interaction with cocaine. AN - 71843214; 15096909 AB - Kappa-opioid agonists produce neurobiological and behavioral effects opposite to those of cocaine and may be useful for the treatment of cocaine dependence. To evaluate the kappa- and mu-agonist effects of cyclazocine and to test whether cyclazocine pretreatment would attenuate the effects of cocaine, healthy, male and female, experienced opiate and cocaine users (n = 13) were enrolled in a two-phase study. In Phase 1, placebo, cyclazocine (0.2, 0.4 and 0.8 mg) and the mu-agonist hydromorphone (5 and 15 mg) were administered orally in six 4.5-hour sessions separated by at least 72 h. In Phase 2, cocaine (100 mg intranasal) was given 2 h after oral pretreatment with cyclazocine (0, 0.1, 0.2, 0.4, 0.8 and 0 mg, in that order) in each of six sessions conducted daily Monday to Friday and the following Monday. Physiological, subjective and behavioral measures were collected in each session. Nine participants completed Phase 1; eight completed Phase 2. Hydromorphone (15 mg) produced prototypic mu-agonist effects. Cyclazocine exhibited only modest kappa-like effects. Cyclazocine also had only modest, non-dose-related effects on response to cocaine. However, cocaine effects were consistently lower on the last administration (cyclazocine 0 mg pretreatment) following 4 days of cyclazocine pretreatment, compared to the first administration (0 mg pretreatment). This finding is unlikely to be fully attributable to cocaine tolerance and is not accounted for by pharmacokinetic changes; plasma concentrations of cocaine were not altered by cyclazocine. This study is suggestive but not strongly supportive for the use of kappa-opiate drugs to diminish acute effects of cocaine administration or for the use of these kappa agonists in drug abuse treatment applications. Copyright 2004 Lippincott Williams & Wilkins JF - Behavioural pharmacology AU - Preston, K L AU - Umbricht, A AU - Schroeder, J R AU - Abreu, M E AU - Epstein, D H AU - Pickworth, W B AD - National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA. kpreston@intra.nida.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 91 EP - 102 VL - 15 IS - 2 SN - 0955-8810, 0955-8810 KW - Receptors, Opioid, kappa KW - 0 KW - Receptors, Opioid, mu KW - Cocaine KW - I5Y540LHVR KW - Cyclazocine KW - J5W1B1159C KW - Hydromorphone KW - Q812464R06 KW - Index Medicus KW - Administration, Oral KW - Drug Interactions KW - Humans KW - Administration, Intranasal KW - Cocaine-Related Disorders -- drug therapy KW - Adult KW - Time Factors KW - Male KW - Female KW - Receptors, Opioid, kappa -- agonists KW - Hydromorphone -- therapeutic use KW - Receptors, Opioid, mu -- agonists KW - Hydromorphone -- pharmacology KW - Cyclazocine -- pharmacology KW - Cocaine -- pharmacology KW - Cocaine -- administration & dosage KW - Cyclazocine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71843214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=Cyclazocine%3A+comparison+to+hydromorphone+and+interaction+with+cocaine.&rft.au=Preston%2C+K+L%3BUmbricht%2C+A%3BSchroeder%2C+J+R%3BAbreu%2C+M+E%3BEpstein%2C+D+H%3BPickworth%2C+W+B&rft.aulast=Preston&rft.aufirst=K&rft.date=2004-03-01&rft.volume=15&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Behavioural+pharmacology&rft.issn=09558810&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-03 N1 - Date created - 2004-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic interactions of DST1 in Saccharomyces cerevisiae suggest a role of TFIIS in the initiation-elongation transition. AN - 71820396; 15082542 AB - TFIIS promotes the intrinsic ability of RNA polymerase II to cleave the 3'-end of the newly synthesized RNA. This stimulatory activity of TFIIS, which is dependent upon Rpb9, facilitates the resumption of transcription elongation when the polymerase stalls or arrests. While TFIIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability. In this work we used a genetic approach to increase our knowledge of the role of TFIIS in vivo. We showed that: (1) dst1 and rpb9 mutants have a synthetic growth defective phenotype when combined with fyv4, gim5, htz1, yal011w, ybr231c, soh1, vps71, and vps72 mutants that is exacerbated during germination or at high salt concentrations; (2) TFIIS and Rpb9 are essential when the cells are challenged with microtubule-destabilizing drugs; (3) among the SDO (synthetic with Dst one), SOH1 shows the strongest genetic interaction with DST1; (4) the presence of multiple copies of TAF14, SUA7, GAL11, RTS1, and TYS1 alleviate the growth phenotype of dst1 soh1 mutants; and (5) SRB5 and SIN4 genetically interact with DST1. We propose that TFIIS is required under stress conditions and that TFIIS is important for the transition between initiation and elongation in vivo. JF - Genetics AU - Malagon, Francisco AU - Tong, Amy H AU - Shafer, Brenda K AU - Strathern, Jeffrey N AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 1215 EP - 1227 VL - 166 IS - 3 SN - 0016-6731, 0016-6731 KW - DNA-Binding Proteins KW - 0 KW - DST1 protein, S cerevisiae KW - Fungal Proteins KW - Fungicides, Industrial KW - Saccharomyces cerevisiae Proteins KW - Salts KW - Transcriptional Elongation Factors KW - transcription factor S-II KW - Thiabendazole KW - N1Q45E87DT KW - Nocodazole KW - SH1WY3R615 KW - Benomyl KW - TLW21058F5 KW - Index Medicus KW - Benomyl -- pharmacology KW - Genes, Fungal KW - Salts -- pharmacology KW - Nocodazole -- pharmacology KW - Microbial Sensitivity Tests KW - Thiabendazole -- pharmacology KW - Gene Deletion KW - Fungicides, Industrial -- pharmacology KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae Proteins -- drug effects KW - Saccharomyces cerevisiae -- metabolism KW - Saccharomyces cerevisiae Proteins -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- drug effects KW - Transcriptional Elongation Factors -- genetics KW - Fungal Proteins -- genetics KW - Transcriptional Elongation Factors -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71820396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+interactions+of+DST1+in+Saccharomyces+cerevisiae+suggest+a+role+of+TFIIS+in+the+initiation-elongation+transition.&rft.au=Malagon%2C+Francisco%3BTong%2C+Amy+H%3BShafer%2C+Brenda+K%3BStrathern%2C+Jeffrey+N&rft.aulast=Malagon&rft.aufirst=Francisco&rft.date=2004-03-01&rft.volume=166&rft.issue=3&rft.spage=1215&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science 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AN - 71812220; 15072616 AB - For patients with relapsed or refractory Hodgkin's or non-Hodgkin's lymphomas, allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option when autologous HSCT fails to achieve durable remission or is deemed inappropriate. Allogeneic HSCT can result in long-term survival even in patients with refractory lymphomas. The efficacy of allogeneic HSCT is attributed, at least in part, to an immune-mediated graft-versus-lymphoma (GVL) effect that can also be associated with significant toxicity resulting from graft-versus-host disease. However, clinical evidence of a potent GVL effect is inconsistent. Reduced-intensity conditioning before allogeneic HSCT can facilitate the use of this treatment in older patients and those at high risk. The decrease in toxicity with reduced-intensity regimens may be associated with a loss of antitumor effects. Patients with lymphoma should be selected for allogeneic HSCT on the basis of characteristics that strongly influence transplant outcomes, including histology, chemosensitivity, and donor source. JF - Clinical lymphoma AU - Dean, Robert M AU - Bishop, Michael R AD - Experimental Transplantation and Immunology Branch Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. robert.dean@nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 238 EP - 249 VL - 4 IS - 4 SN - 1526-9655, 1526-9655 KW - Index Medicus KW - Multicenter Studies as Topic KW - Graft vs Tumor Effect KW - Disease-Free Survival KW - Lymphoma, Non-Hodgkin -- therapy KW - Humans KW - Treatment Outcome KW - Prognosis KW - Transplantation, Homologous -- methods KW - Lymphoma, Mantle-Cell -- therapy KW - Lymphoma, Large B-Cell, Diffuse -- therapy KW - Hodgkin Disease -- therapy KW - Lymphoma -- therapy KW - Hematopoietic Stem Cell Transplantation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71812220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lymphoma&rft.atitle=Allogeneic+hematopoietic+stem+cell+transplantation+for+lymphoma.&rft.au=Dean%2C+Robert+M%3BBishop%2C+Michael+R&rft.aulast=Dean&rft.aufirst=Robert&rft.date=2004-03-01&rft.volume=4&rft.issue=4&rft.spage=238&rft.isbn=&rft.btitle=&rft.title=Clinical+lymphoma&rft.issn=15269655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-10 N1 - Date created - 2004-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blending prevention research and practice in schools: critical issues and suggestions. AN - 71792769; 15058906 JF - Prevention science : the official journal of the Society for Prevention Research AU - Kaftarian, Shakeh AU - Robertson, Elizabeth AU - Compton, Wilson AU - Davis, Beverly Watts AU - Volkow, Nora AU - Robinson, Elizabeth AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892-9589, USA. jkaftari@nida.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 1 EP - 3 VL - 5 IS - 1 SN - 1389-4986, 1389-4986 KW - Index Medicus KW - United States KW - Humans KW - Cost-Benefit Analysis KW - National Institutes of Health (U.S.) KW - Research Design KW - Health Services Research -- economics KW - School Health Services -- economics KW - Health Services Research -- organization & administration KW - Preventive Health Services -- economics KW - Substance-Related Disorders -- prevention & control KW - School Health Services -- organization & administration KW - Preventive Health Services -- organization & administration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71792769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prevention+science+%3A+the+official+journal+of+the+Society+for+Prevention+Research&rft.atitle=Blending+prevention+research+and+practice+in+schools%3A+critical+issues+and+suggestions.&rft.au=Kaftarian%2C+Shakeh%3BRobertson%2C+Elizabeth%3BCompton%2C+Wilson%3BDavis%2C+Beverly+Watts%3BVolkow%2C+Nora%3BRobinson%2C+Elizabeth&rft.aulast=Kaftarian&rft.aufirst=Shakeh&rft.date=2004-03-01&rft.volume=5&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Prevention+science+%3A+the+official+journal+of+the+Society+for+Prevention+Research&rft.issn=13894986&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-10 N1 - Date created - 2004-04-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Prev Sci. 2004 Jun;5(2):135 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lateral signaling enhances TGF-beta response complexity. AN - 71787156; 15055198 AB - TGF-beta elicits context-dependent and cell-specific effects that often appear conflicting, such as stimulation or inhibition of growth, apoptosis or differentiation. It is puzzling how such a diverse array of responses can result from binding of TGF-beta to a single receptor complex that activates a seemingly straightforward signal-transduction scheme dependent on shuttling of Smad transducer proteins from the receptor to the nucleus. Here, we discuss a novel paradigm for TGF-beta signaling in endothelial cells in which the same ligand can induce opposing effects mediated by activation of two different classes of Smads through a chimeric receptor complex. JF - Trends in cell biology AU - Byfield, Stacey DaCosta AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of health, Bethesda, MD 20892-5055, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 107 EP - 111 VL - 14 IS - 3 SN - 0962-8924, 0962-8924 KW - DNA-Binding Proteins KW - 0 KW - Smad Proteins KW - Trans-Activators KW - Transforming Growth Factor beta KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - anaplastic lymphoma kinase KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Humans KW - Protein-Tyrosine Kinases -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Signal Transduction -- physiology KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71787156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+biology&rft.atitle=Lateral+signaling+enhances+TGF-beta+response+complexity.&rft.au=Byfield%2C+Stacey+DaCosta%3BRoberts%2C+Anita+B&rft.aulast=Byfield&rft.aufirst=Stacey&rft.date=2004-03-01&rft.volume=14&rft.issue=3&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Trends+in+cell+biology&rft.issn=09628924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-21 N1 - Date created - 2004-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized trial of inhaled beclomethasone dipropionate versus theophylline for moderate asthma during pregnancy. AN - 71762500; 15042007 AB - This study was undertaken to compare the efficacy of inhaled beclomethasone dipropionate to oral theophylline for the prevention of asthma exacerbation(s) requiring medical intervention. A prospective, double-blind, double placebo-controlled randomized clinical trial of pregnant women with moderate asthma was performed. There was no significant difference (P=.554) in the proportion of asthma exacerbations among the 194 women in the beclomethasone cohort (18.0%) versus the 191 in the theophylline cohort (20.4%; risk ratio [RR]=0.9, 95% CI=0.6-1.3). The beclomethasone cohort had significantly lower incidences of discontinuing study medications caused by side effects (RR=0.3, 95% CI=0.1-0.9; P=.016), and proportion of study visits with forced expiratory volume expired in 1 second (FEV1) less than 80% predicted (0.284+/-0.331 vs 0.284+/-0.221, P=.039). There were no significant differences in treatment failure, compliance, or proportion of peak expiratory flow rate less than 80% predicted. There were no significant differences in maternal or perinatal outcomes. The treatment of moderate asthma with inhaled beclomethasone versus oral theophylline resulted in similar rates of asthma exacerbations and similar obstetric and perinatal outcomes. These results favor the use of inhaled corticosteroids for moderate asthma during pregnancy because of the improved FEV1 and because theophylline had more side effects and requires serum monitoring. JF - American journal of obstetrics and gynecology AU - Dombrowski, Mitchell P AU - Schatz, Michael AU - Wise, Robert AU - Thom, Elizabeth A AU - Landon, Mark AU - Mabie, William AU - Newman, Roger B AU - McNellis, Donald AU - Hauth, John C AU - Lindheimer, Marshall AU - Caritis, Steve N AU - Leveno, Kenneth J AU - Meis, Paul AU - Miodovnik, Menachem AU - Wapner, Ronald J AU - Varner, Michael W AU - O'Sullivan, Mary Jo AU - Conway, Deborah L AU - National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network AU - National Heart, Lung, and Blood Institute AD - Department of Obstetrics and Gynecology, Wayne State University, Detroit, Mich, USA. Mitchell.Dombrowski@stjohn.org ; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ; National Heart, Lung, and Blood Institute Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 737 EP - 744 VL - 190 IS - 3 SN - 0002-9378, 0002-9378 KW - Anti-Asthmatic Agents KW - 0 KW - Bronchodilator Agents KW - Theophylline KW - C137DTR5RG KW - Beclomethasone KW - KGZ1SLC28Z KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Odds Ratio KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Administration, Inhalation KW - Forced Expiratory Volume -- drug effects KW - Female KW - Pregnancy KW - Beclomethasone -- adverse effects KW - Theophylline -- adverse effects KW - Asthma -- drug therapy KW - Anti-Asthmatic Agents -- administration & dosage KW - Bronchodilator Agents -- administration & dosage KW - Pregnancy Complications -- drug therapy KW - Beclomethasone -- administration & dosage KW - Bronchodilator Agents -- adverse effects KW - Anti-Asthmatic Agents -- adverse effects KW - Pregnancy Complications -- physiopathology KW - Asthma -- physiopathology KW - Theophylline -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71762500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+obstetrics+and+gynecology&rft.atitle=Randomized+trial+of+inhaled+beclomethasone+dipropionate+versus+theophylline+for+moderate+asthma+during+pregnancy.&rft.au=Dombrowski%2C+Mitchell+P%3BSchatz%2C+Michael%3BWise%2C+Robert%3BThom%2C+Elizabeth+A%3BLandon%2C+Mark%3BMabie%2C+William%3BNewman%2C+Roger+B%3BMcNellis%2C+Donald%3BHauth%2C+John+C%3BLindheimer%2C+Marshall%3BCaritis%2C+Steve+N%3BLeveno%2C+Kenneth+J%3BMeis%2C+Paul%3BMiodovnik%2C+Menachem%3BWapner%2C+Ronald+J%3BVarner%2C+Michael+W%3BO%27Sullivan%2C+Mary+Jo%3BConway%2C+Deborah+L%3BNational+Institute+of+Child+Health+and+Human+Development+Maternal-Fetal+Medicine+Units+Network%3BNational+Heart%2C+Lung%2C+and+Blood+Institute&rft.aulast=Dombrowski&rft.aufirst=Mitchell&rft.date=2004-03-01&rft.volume=190&rft.issue=3&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-22 N1 - Date created - 2004-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of cyclophosphamide treatment on the pathogenesis of subgroup J avian leukosis virus (ALV-J) infection in broiler chickens with Marek's disease virus exposure. AN - 71757538; 15028885 AB - Studies were performed to determine the effects of Bcell suppression on the pathogenesis of Subgroup J avian leukosis virus (ALV-J) in broiler chickens. Neonatal chickens were treated with cyclophosphamide (CY) or PBS, and then infected with ALV-J (ADOL-7501) at 2 weeks of age. CY treatment induced B cell specific immunosuppression throughout the experiment confirmed by decreased bursal weight, intact lymphocyte mitogenetic activity stimulated by Con A and increased relative subpopulation of CD3-positive cells as measured by flow cytometry. Chickens in this experiment had Mareks disease virus exposure prior to three weeks of age as determined by the presence of lymphocytic infiltration and antibody. Virus neutralizing antibody against ALV-J was first observed at 6 weeks post-infection in some of the infected chickens in the PBS group. As expected, none of the chickens from the CY group and uninfected chickens developed virus-neutralizing antibody. The viremic status was measured by real time RT-PCR using SYBR green I dye. The percentage of viremic chickens was significantly higher, and more chickens had high titered viremia, in the CY treated group. No neoplastic foci consistent with ALVJ infection were observed in any of the experimental chickens. The frequency and intensity of viral antigen expression determined by immunohistochemistry was significantly higher in tissues from CY treated birds than those of PBS treated chickens at 3 weeks post-infection. This study showed that B cell specific immunosuppression with CY treatment in chickens resulted in increase in viremia and viral antigen load in tissues. JF - Journal of veterinary science AU - Kim, Yongbaek AU - Brown, Thomas P AU - Pantin-Jackwood, Mary J AD - Department of Veterinary Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. kim16@niehs.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 49 EP - 58 VL - 5 IS - 1 SN - 1229-845X, 1229-845X KW - Immunosuppressive Agents KW - 0 KW - Organic Chemicals KW - RNA, Viral KW - Concanavalin A KW - 11028-71-0 KW - SYBR Green I KW - 163795-75-3 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Animals KW - Random Allocation KW - Flow Cytometry -- veterinary KW - Body Weight -- physiology KW - Lymphocyte Activation -- drug effects KW - Organic Chemicals -- chemistry KW - Lymphocyte Activation -- immunology KW - Reverse Transcriptase Polymerase Chain Reaction -- veterinary KW - RNA, Viral -- chemistry KW - Concanavalin A -- immunology KW - Spleen -- immunology KW - Immunocompromised Host KW - Viremia -- veterinary KW - Spleen -- virology KW - RNA, Viral -- genetics KW - Immunohistochemistry -- veterinary KW - Bursa of Fabricius -- immunology KW - Statistics, Nonparametric KW - Immunophenotyping -- veterinary KW - Avian Leukosis Virus -- immunology KW - Chickens KW - Poultry Diseases -- virology KW - Avian Leukosis -- virology KW - Avian Leukosis Virus -- genetics KW - Poultry Diseases -- immunology KW - Immunosuppressive Agents -- pharmacology KW - Cyclophosphamide -- pharmacology KW - Avian Leukosis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71757538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+veterinary+science&rft.atitle=The+effects+of+cyclophosphamide+treatment+on+the+pathogenesis+of+subgroup+J+avian+leukosis+virus+%28ALV-J%29+infection+in+broiler+chickens+with+Marek%27s+disease+virus+exposure.&rft.au=Kim%2C+Yongbaek%3BBrown%2C+Thomas+P%3BPantin-Jackwood%2C+Mary+J&rft.aulast=Kim&rft.aufirst=Yongbaek&rft.date=2004-03-01&rft.volume=5&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Journal+of+veterinary+science&rft.issn=1229845X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-16 N1 - Date created - 2004-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of putative gene based markers of renal toxicity. AN - 71735188; 15033597 AB - This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants--cisplatin, gentamicin, and puromycin--to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity. JF - Environmental health perspectives AU - Amin, Rupesh P AU - Vickers, Alison E AU - Sistare, Frank AU - Thompson, Karol L AU - Roman, Richard J AU - Lawton, Michael AU - Kramer, Jeffrey AU - Hamadeh, Hisham K AU - Collins, Jennifer AU - Grissom, Sherry AU - Bennett, Lee AU - Tucker, C Jeffrey AU - Wild, Stacie AU - Kind, Clive AU - Oreffo, Victor AU - Davis, John W AU - Curtiss, Sandra AU - Naciff, Jorge M AU - Cunningham, Michael AU - Tennant, Raymond AU - Stevens, James AU - Car, Bruce AU - Bertram, Timothy A AU - Afshari, Cynthia A AD - National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, Research Triangle Park, North Carolina, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 465 EP - 479 VL - 112 IS - 4 SN - 0091-6765, 0091-6765 KW - Anti-Bacterial Agents KW - 0 KW - Antimetabolites, Antineoplastic KW - Antineoplastic Agents KW - Genetic Markers KW - Gentamicins KW - Puromycin KW - 4A6ZS6Q2CL KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Rats KW - Gentamicins -- toxicity KW - Animals KW - Rats, Sprague-Dawley KW - Endpoint Determination KW - Dose-Response Relationship, Drug KW - Cisplatin -- toxicity KW - Puromycin -- toxicity KW - Antineoplastic Agents -- toxicity KW - Antimetabolites, Antineoplastic -- toxicity KW - Anti-Bacterial Agents -- toxicity KW - Male KW - Gene Expression Profiling KW - Kidney -- pathology KW - Oligonucleotide Array Sequence Analysis KW - Kidney -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71735188?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+putative+gene+based+markers+of+renal+toxicity.&rft.au=Amin%2C+Rupesh+P%3BVickers%2C+Alison+E%3BSistare%2C+Frank%3BThompson%2C+Karol+L%3BRoman%2C+Richard+J%3BLawton%2C+Michael%3BKramer%2C+Jeffrey%3BHamadeh%2C+Hisham+K%3BCollins%2C+Jennifer%3BGrissom%2C+Sherry%3BBennett%2C+Lee%3BTucker%2C+C+Jeffrey%3BWild%2C+Stacie%3BKind%2C+Clive%3BOreffo%2C+Victor%3BDavis%2C+John+W%3BCurtiss%2C+Sandra%3BNaciff%2C+Jorge+M%3BCunningham%2C+Michael%3BTennant%2C+Raymond%3BStevens%2C+James%3BCar%2C+Bruce%3BBertram%2C+Timothy+A%3BAfshari%2C+Cynthia+A&rft.aulast=Amin&rft.aufirst=Rupesh&rft.date=2004-03-01&rft.volume=112&rft.issue=4&rft.spage=465&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 - 2004-06-08 N1 - Date created - 2004-03-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] Urology. 1999 Jan;53(1):32-7 [9886584] Kidney Int. 1999 Jan;55(1):100-8 [9893118] Vitam Horm. 2000;58:89-120 [10668396] Growth Horm IGF Res. 1998 Feb;8(1):77-82 [10990448] Genomics. 2000 Oct 15;69(2):225-34 [11031105] Biochim Biophys Acta. 2000 Oct 18;1482(1-2):9-24 [11058743] Toxicol Lett. 2001 Mar 31;120(1-3):359-68 [11323195] Nephrol Dial Transplant. 2001 May;16(5):923-31 [11328896] Physiol Chem Phys Med NMR. 2000;32(2):119-25 [11383133] Bioinformatics. 2001 Jun;17(6):564-5 [11395436] Kidney Int. 2001 Aug;60(2):635-40 [11473646] Science. 2001 Aug 3;293(5531):829-34 [11486081] Toxicol Appl Pharmacol. 2001 Aug 15;175(1):28-42 [11509024] Toxicol Sci. 2001 Oct;63(2):196-207 [11568363] J Biol Chem. 2001 Oct 5;276(40):37258-65 [11486009] Kidney Int. 2002 Mar;61(3):1030-9 [11849458] Mol Cell Biol. 2002 Mar;22(6):1893-902 [11865066] Ann Clin Biochem. 2002 Mar;39(Pt 2):89-104 [11928770] Nephron. 2002 Apr;90(4):424-31 [11961401] Kidney Int. 2002 May;61(5):1646-54 [11967014] Clin Chem. 2002 May;48(5):699-707 [11978596] Toxicol Sci. 2002 Jun;67(2):219-31 [12011481] Toxicol Sci. 2002 Jun;67(2):232-40 [12011482] J Cell Mol Med. 2001 Jan-Mar;5(1):18-32 [12067448] Kidney Int. 2002 Jul;62(1):237-44 [12081583] J Urol. 2002 Sep;168(3):1173-81 [12187263] Toxicol Pathol. 2002 Jul-Aug;30(4):470-82 [12187938] Clin Chem. 2002 Sep;48(9):1375-6 [12194910] Clin Chem. 2002 Sep;48(9):1445-53 [12194921] Environ Health Perspect. 2004 Mar;112(4):417-9 [15033589] Environ Health Perspect. 2004 Mar;112(4):460-4 [15033596] Curr Probl Clin Biochem. 1968;2:119-45 [4359230] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6768-72 [3413124] J Lipid Res. 1989 Feb;30(2):171-80 [2469758] Endocr Rev. 1989 Nov;10(4):393-419 [2693081] Kidney Int. 1990 Jun;37(6):1515-21 [2362405] Proc Natl Acad Sci U S A. 1991 May 1;88(9):4020-4 [1902577] Proc Soc Exp Biol Med. 1992 Jan;199(1):93-6 [1728043] Kidney Int. 1992 Jan;41(1):226-46 [1593859] J Neurochem. 1993 Aug;61(2):451-6 [8336134] J Biol Chem. 1994 Feb 4;269(5):3698-702 [8106414] Kidney Int. 1994 Mar;45(3):817-27 [8196284] Exp Nephrol. 1995 Jan-Feb;3(1):9-14 [7712145] J Am Soc Nephrol. 1995 Oct;6(4):1186-96 [8589285] Gut. 1996 Mar;38(3):414-20 [8675096] Biometals. 1996 Apr;9(2):139-42 [8744896] Biochem J. 1996 Aug 15;318 ( Pt 1):1-14 [8761444] Nat Genet. 1996 Dec;14(4):457-60 [8944026] J Am Soc Nephrol. 1997 Feb;8(2):302-5 [9048350] Glycobiology. 1997 Jun;7(4):499-506 [9184830] J Am Soc Nephrol. 1997 Sep;8(9):1383-90 [9294829] J Am Soc Nephrol. 1999 Mar;10(3):444-57 [10073594] Nephrol Dial Transplant. 1999 May;14(5):1139-45 [10344352] Environ Health Perspect. 2004 Mar;112(4):488-94 [15033599] Kidney Int. 2002 Nov;62(5):1601-10 [12371960] J Biol Chem. 2002 Oct 18;277(42):39739-48 [12138159] Antioxid Redox Signal. 2002 Dec;4(6):925-34 [12573141] J Biomed Inform. 2002 Jun;35(3):160-70 [12669979] Am J Physiol Renal Physiol. 2003 Jul;285(1):F9-18 [12788784] Transplantation. 1997 Nov 15;64(9):1236-40 [9371662] J Am Soc Nephrol. 1998 Jan;9(1):33-7 [9440084] J Biol Chem. 1998 Feb 13;273(7):4135-42 [9461608] Kidney Int Suppl. 1998 Feb;64:S19-22 [9475483] Kidney Int. 1998 May;53(5):1305-13 [9573546] Biol Reprod. 1998 Jun;58(6):1437-44 [9623603] Nat Biotechnol. 1996 Dec;14(13):1675-80 [9634850] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized, double-blind, placebo-controlled phase IIb trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia. AN - 71733342; 15014005 AB - Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia. 57 patients were randomized (2:1 ratio) in a double-blind, placebo-controlled study of ketorolac (10 ml of a 0.1% ketorolac rinse solution; n = 38) or placebo (10 ml of rinse solution; n = 19) given twice daily for 30 s over 90 days. Primary end point was evaluated visually obtaining bidimensional measurement of the size of leukoplakia lesion(s) at entry and at 90 days. Secondary end point was histological assessment of the leukoplakia as sampled by serial punch biopsy and independently reviewed by three pathologists. The patients included 67% males, 11% non-Caucasian, and 86% used tobacco with no significant differences between the two arms. Both rinses were well tolerated with good compliance, and there was no significant difference in adverse events (P = 0.27). Major response rate (complete response and partial response) was 30% for ketorolac and 32% for the placebo arm. There was no significant difference in change in histology between the two arms. Local delivery of a COX-containing oral rinse was well tolerated but produced no significant reduction in the extent of leukoplakia compared with the placebo. However, the favorable response rate to placebo arm remains unexplained and additional investigation of the tissue penetration with ketorolac is warranted. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Mulshine, James L AU - Atkinson, Jane C AU - Greer, Robert O AU - Papadimitrakopoulou, Vassiliki A AU - Van Waes, Carter AU - Rudy, Susan AU - Martin, Jack W AU - Steinberg, Seth M AU - Liewehr, David J AU - Avis, Ingalill AU - Linnoila, R Ilona AU - Hewitt, Stephen AU - Lippman, Scott M AU - Frye, Robin AU - Cavanaugh, Paul F AD - Intervention Section, Cell and Cancer Biology Branch, Department of Pathology and Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1906, USA. mulshinj@mail.nih.gov Y1 - 2004/03/01/ PY - 2004 DA - 2004 Mar 01 SP - 1565 EP - 1573 VL - 10 IS - 5 SN - 1078-0432, 1078-0432 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase Inhibitors KW - Mouthwashes KW - Placebos KW - Ketorolac KW - YZI5105V0L KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Smoking -- adverse effects KW - Male KW - Female KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Cyclooxygenase Inhibitors -- adverse effects KW - Oropharyngeal Neoplasms -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Cyclooxygenase Inhibitors -- administration & dosage KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Leukoplakia, Oral -- pathology KW - Leukoplakia, Oral -- drug therapy KW - Ketorolac -- therapeutic use KW - Ketorolac -- adverse effects KW - Ketorolac -- administration & dosage KW - Anti-Inflammatory Agents, Non-Steroidal -- administration & dosage KW - Oropharyngeal Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71733342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Randomized%2C+double-blind%2C+placebo-controlled+phase+IIb+trial+of+the+cyclooxygenase+inhibitor+ketorolac+as+an+oral+rinse+in+oropharyngeal+leukoplakia.&rft.au=Mulshine%2C+James+L%3BAtkinson%2C+Jane+C%3BGreer%2C+Robert+O%3BPapadimitrakopoulou%2C+Vassiliki+A%3BVan+Waes%2C+Carter%3BRudy%2C+Susan%3BMartin%2C+Jack+W%3BSteinberg%2C+Seth+M%3BLiewehr%2C+David+J%3BAvis%2C+Ingalill%3BLinnoila%2C+R+Ilona%3BHewitt%2C+Stephen%3BLippman%2C+Scott+M%3BFrye%2C+Robin%3BCavanaugh%2C+Paul+F&rft.aulast=Mulshine&rft.aufirst=James&rft.date=2004-03-01&rft.volume=10&rft.issue=5&rft.spage=1565&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 - 2004-10-05 N1 - Date created - 2004-03-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Cancer Res. 2005 Feb 1;11(3):1349-51; author reply 1351 [15709209] Clin Cancer Res. 2004 Mar 1;10(5):1561-4 [15014004] Clin Cancer Res. 2004 Mar 1;10(5):1557-8 [15014002] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model. AN - 71732631; 15014035 AB - Radiotherapy is commonly used to treat a majority of patients with head and neck cancers. The long-term radiation-induced reduction of saliva output significantly contributes to the posttreatment morbidity experienced by these patients. The purpose of this study was to test the ability of the stable-free radical Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), an established radioprotector, to prevent radiation-induced salivary hypofunction in mice. The heads of C3H mice were exposed to a range of single radiation doses with or without an i.p. injection of 275 mg/kg Tempol 10 min before treatment. Salivary gland output was assessed 8 weeks postirradiation. Radiation caused a dose-dependent reduction in salivary flow in this model. Tempol treatment alone significantly reduced radiation-induced salivary hypofunction. The combination of Tempol with mouth/nose shielding showed essentially complete radiation protection at 15 Gy and approximately 75% protection at 17.5 Gy. This study demonstrates for the first time that significant radioprotection of the salivary glands is possible with Tempol in C3H mice. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Vitolo, Joseph M AU - Cotrim, Ana P AU - Sowers, Anastasia L AU - Russo, Angelo AU - Wellner, Robert B AU - Pillemer, Stanley R AU - Mitchell, James B AU - Baum, Bruce J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA. Y1 - 2004/03/01/ PY - 2004 DA - 2004 Mar 01 SP - 1807 EP - 1812 VL - 10 IS - 5 SN - 1078-0432, 1078-0432 KW - Antioxidants KW - 0 KW - Cyclic N-Oxides KW - Radiation-Protective Agents KW - Spin Labels KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Animals KW - Mice, Inbred C3H KW - Disease Models, Animal KW - Mice KW - Radiation-Protective Agents -- pharmacology KW - Female KW - Radiotherapy -- adverse effects KW - Cyclic N-Oxides -- therapeutic use KW - Salivary Glands -- radiation effects KW - Salivary Glands -- drug effects KW - Antioxidants -- therapeutic use KW - Head and Neck Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71732631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+stable+nitroxide+tempol+facilitates+salivary+gland+protection+during+head+and+neck+irradiation+in+a+mouse+model.&rft.au=Vitolo%2C+Joseph+M%3BCotrim%2C+Ana+P%3BSowers%2C+Anastasia+L%3BRusso%2C+Angelo%3BWellner%2C+Robert+B%3BPillemer%2C+Stanley+R%3BMitchell%2C+James+B%3BBaum%2C+Bruce+J&rft.aulast=Vitolo&rft.aufirst=Joseph&rft.date=2004-03-01&rft.volume=10&rft.issue=5&rft.spage=1807&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 - 2004-10-05 N1 - Date created - 2004-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of transdermal fentanyl without prior opioid stabilization in patients with cancer pain. AN - 71728143; 15025835 AB - To determine the safety and efficacy of transdermal fentanyl for pain relief in cancer patients and to compare the effects on patients according to whether they had previously received strong opioids, weak opioids or non-opioid analgesia. Cancer patients requiring strong analgesia were recruited into an open-label, multicentre study, conducted in eight countries. Patients received transdermal fentanyl treatment for 28 days. Pain severity, overall satisfaction with pain control, convenience of use of patches and treatment preferences were recorded daily. Of the 292 participants, 135 had previously received a strong opioid, 84 had previously received a weak opioid and 73 had received no regular opioids. Thirty-eight patients did not complete the study, mainly due to adverse events. For all groups the proportion of patients with 'good to excellent' pain control increased after transdermal fentanyl treatment. Transdermal fentanyl was well tolerated, with the most common treatment-related adverse events being nausea, vomiting and constipation. The percentage of strong-opioid-tolerant patients with constipation decreased following transdermal fentanyl treatment and increased slightly in the strong-opioid-naïve groups. Most patients rated the convenience of the patches as 'good to excellent', and most preferred transdermal fentanyl to their previous therapy. Transdermal fentanyl is an effective and well-tolerated treatment for cancer-related pain for patients regardless of whether they have previously received opioids. Previous guidelines have often advocated initial dose finding with short-acting opioids but this study demonstrates that such a complex titration and conversion schedule may not be necessary,and that treatment may be initiated directly with long-acting formulations such as transdermal fentanyl when previous analgesic therapy fails to provide adequate relief. JF - Current medical research and opinion AU - Tawfik, Mohamed Omar AU - Bryuzgin, Vladimir AU - Kourteva, Galina AU - FEN-INT-20 Study Group AD - National Cancer Institute, Cairo University, Cairo, Egypt. tawfik@ie-eg.com ; FEN-INT-20 Study Group Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 259 EP - 267 VL - 20 IS - 3 SN - 0300-7995, 0300-7995 KW - Analgesics, Non-Narcotic KW - 0 KW - Analgesics, Opioid KW - Fentanyl KW - UF599785JZ KW - Index Medicus KW - Severity of Illness Index KW - Administration, Cutaneous KW - Patient Satisfaction KW - Humans KW - Treatment Outcome KW - Gastrointestinal Diseases -- chemically induced KW - Middle Aged KW - Male KW - Female KW - Pain -- etiology KW - Analgesics, Non-Narcotic -- adverse effects KW - Pain -- drug therapy KW - Neoplasms -- complications KW - Analgesics, Non-Narcotic -- therapeutic use KW - Fentanyl -- adverse effects KW - Analgesics, Opioid -- adverse effects KW - Analgesics, Opioid -- administration & dosage KW - Fentanyl -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71728143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medical+research+and+opinion&rft.atitle=Use+of+transdermal+fentanyl+without+prior+opioid+stabilization+in+patients+with+cancer+pain.&rft.au=Tawfik%2C+Mohamed+Omar%3BBryuzgin%2C+Vladimir%3BKourteva%2C+Galina%3BFEN-INT-20+Study+Group&rft.aulast=Tawfik&rft.aufirst=Mohamed&rft.date=2004-03-01&rft.volume=20&rft.issue=3&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Current+medical+research+and+opinion&rft.issn=03007995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-10 N1 - Date created - 2004-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of benchtop microplate beta counters with the traditional gamma counting method for measurement of chromium-51 release in cytotoxic assays. AN - 71719082; 15013972 AB - The most traditional method used to measure the lytic activity of cytotoxic T lymphocytes or natural killer (NK) cells is the chromium release assay (CRA). No study has been reported that systematically compares the traditional gamma counting method with various benchtop microplate scintillation formats to measure chromium release. Here we investigated the utilization of microplate beta counters in comparison with the traditional gamma counting method to quantitate antigen-specific cytolysis, lymphokine-activated killer (LAK) activity, and NK activity in the CRA. Supernatants from standard CRA (n = 7) were directly transferred to a 96-well microplate containing either a solid scintillant (Lumaplate) or a liquid scintillant (flexible beta plate). Samples were quantified by using two benchtop microplate beta counters, Wallac Microbeta Trilux (Lumalux and Trilux methods, respectively) and Packard TopCount instruments (TopCount method). These results were then compared with data from an identical assay run in parallel using the traditional gamma counting method (LKB). The lytic activity for influenza virus-stimulated effectors measured in the benchtop microplate beta counters using Lumalux and Trilux methods exhibited excellent correlations with the one measured in the traditional LKB (r = 0.967 and 0.968, respectively). The TopCount method demonstrated a similar correlation (r = 0.966). Similar findings were observed for LAK and NK activity. The 96-well microplate format, specifically the dry-scintillant Lumaplates, offers several advantages over the traditional gamma counting format. Most notable are the reductions in sample volume needed and in the total sample preparation and counting time. Furthermore, this system reduces the amount of dry and mixed radioactive waste generated while using the same instrument for gamma- and beta-emitting isotopes. JF - Clinical and diagnostic laboratory immunology AU - Wallace, Dora AU - Hildesheim, Allan AU - Pinto, Ligia A AD - National Cancer Institute-Frederick, National Institutes of Health/SAIC-Frederick, Frederick, Maryland 21702, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 255 EP - 260 VL - 11 IS - 2 SN - 1071-412X, 1071-412X KW - Chromium Radioisotopes KW - 0 KW - Index Medicus KW - Orthomyxoviridae -- immunology KW - Influenza, Human -- immunology KW - Gamma Rays KW - Humans KW - CD8-Positive T-Lymphocytes KW - In Vitro Techniques KW - Cell Line, Transformed KW - K562 Cells KW - Lymphocyte Activation KW - Cytotoxicity Tests, Immunologic -- instrumentation KW - Cytotoxicity Tests, Immunologic -- methods KW - Killer Cells, Natural -- virology KW - T-Lymphocytes, Cytotoxic -- immunology KW - T-Lymphocytes, Cytotoxic -- virology KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71719082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+laboratory+immunology&rft.atitle=Comparison+of+benchtop+microplate+beta+counters+with+the+traditional+gamma+counting+method+for+measurement+of+chromium-51+release+in+cytotoxic+assays.&rft.au=Wallace%2C+Dora%3BHildesheim%2C+Allan%3BPinto%2C+Ligia+A&rft.aulast=Wallace&rft.aufirst=Dora&rft.date=2004-03-01&rft.volume=11&rft.issue=2&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Clinical+and+diagnostic+laboratory+immunology&rft.issn=1071412X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-18 N1 - Date created - 2004-03-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Leukoc Biol. 2000 Jun;67(6):817-24 [10857854] J Immunol Methods. 2001 Jun 1;252(1-2):83-92 [11334968] Semin Oncol. 2002 Jun;29(3 Suppl 7):27-30 [12068385] Clin Exp Immunol. 2002 Nov;130(2):172-82 [12390303] Intervirology. 2002;45(4-6):290-9 [12566712] Immunology. 1968 Feb;14(2):181-96 [4966657] Clin Diagn Lab Immunol. 1997 Jan;4(1):43-8 [9008279] J Immunol Methods. 1987 Dec 24;105(2):171-7 [3693905] Biotechniques. 1993 Oct;15(4):744-9 [8251178] J Clin Invest. 1995 Aug;96(2):867-76 [7635981] Science. 1996 Jan 12;271(5246):173-8 [8539616] Curr Opin Immunol. 1996 Aug;8(4):472-7 [8794015] Nature. 1974 Apr 19;248(5450):701-2 [4133807] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutant superoxide dismutase 1 causes motor neuron degeneration independent of cyclin-dependent kinase 5 activation by p35 or p25. AN - 71717753; 15009685 AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective loss of motor neurons in the brain and spinal cord. Neurotoxicity mediated by glutamate is thought to play a role in the neuronal death through intracellular calcium-dependent signaling cascades. Cyclin-dependent kinase 5 (Cdk5) has been proposed as one of the calcium-dependent mediators that may cause neuronal death observed in this disease. Cdk5 is activated in neurons by the association with its activators, p35 or p39. The calcium-activated protease calpain cleaves p35 to its truncated product, p25, which eventually causes the cellular mislocalization and prolonged activation of Cdk5. This deregulated Cdk5 induces cytoskeletal disruption and apoptosis. To examine whether inhibition of the calpain-mediated conversion of p35 to p25 can delay the disease progression of ALS, we generated double transgenic mice in which ALS-linked mutant copper/zinc superoxide dismutase 1 (SOD1G93A) was expressed in a p35-null background. The absence of p35 neither affected the onset and progression of motor neuron disease in the mutant SOD1 mice nor ameliorated the pathological lesions in these mice. Our results provide direct evidence that the pathogenesis of motor neuron disease in the mutant SOD1 mice is independent of the Cdk5 activation by p35 or p25. JF - Journal of neurochemistry AU - Takahashi, Satoru AU - Kulkarni, Ashok B AD - Functional Genomics Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 1295 EP - 1304 VL - 88 IS - 5 SN - 0022-3042, 0022-3042 KW - Nerve Tissue Proteins KW - 0 KW - neuronal Cdk5 activator (p25-p35) KW - SOD1 G93A protein KW - EC 1.15.1.1 KW - Superoxide Dismutase KW - Cyclin-Dependent Kinase 5 KW - EC 2.7.11.1 KW - CDK5 protein, human KW - EC 2.7.11.22 KW - Cdk5 protein, mouse KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Motor Neurons -- pathology KW - Animals KW - Survival Rate KW - Humans KW - Disease Progression KW - Spinal Cord -- pathology KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Cyclin-Dependent Kinases -- metabolism KW - Amyotrophic Lateral Sclerosis -- pathology KW - Nerve Tissue Proteins -- deficiency KW - Amyotrophic Lateral Sclerosis -- enzymology KW - Amyotrophic Lateral Sclerosis -- genetics KW - Superoxide Dismutase -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Nerve Tissue Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71717753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutant+superoxide+dismutase+1+causes+motor+neuron+degeneration+independent+of+cyclin-dependent+kinase+5+activation+by+p35+or+p25.&rft.au=Takahashi%2C+Satoru%3BKulkarni%2C+Ashok+B&rft.aulast=Takahashi&rft.aufirst=Satoru&rft.date=2004-03-01&rft.volume=88&rft.issue=5&rft.spage=1295&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 - 2004-03-30 N1 - Date created - 2004-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A restrictive element 1 (RE-1) in the VIP gene modulates transcription in neuronal and non-neuronal cells in collaboration with an upstream tissue specifier element. AN - 71717213; 15009665 AB - The vasoactive intestinal peptide (VIP) gene has been studied extensively as a prototype neuronal gene containing multiple cis-active elements that confer responsiveness to cell lineage, neurotrophic, and activity-dependent intrinsic and extrinsic cues. However, reporter genes containing the presumptive complete regulatory region 5' to the start of transcription do not confer tissue-specific gene expression in vivo. We therefore sought cis-regulatory elements downstream of the transcriptional start that might confer additional tissue-specific and tissue-restrictive properties to the VIP transcriptional unit. We report here a repressor element, similar to the canonical restrictive element-1 (RE-1), located within the first non-coding exon of the human VIP gene. The ability of this element to regulate VIP reporter gene expression in neuroblastoma and fibroblastic cells was examined. Endogenous VIP expression is high in SH-EP neuroblastoma cells, low but inducible in SH-SY5Y cells, and absent in HeLa cells. Endogenous RE-1 silencer factor (REST) expression was highest in SH-EP and HeLa cells, and significantly lower in SH-SY5Y cells. Transient transfection of a VIP reporter gene containing a mutated RE-1 sequence revealed an RE-1-dependent regulation of VIP gene expression in all three cell types, with regulation greatest in cells (SH-EP, HeLa) with highest levels of REST expression. Serial truncation of the VIP reporter gene further revealed a specific interaction between the RE-1 and a tissue-specifier element located 5 kb upstream in the VIP gene. Thus, REST can regulate VIP gene expression in both neuroblastic and non-neuronal cells, but requires coupling to the upstream tissue specifier element. JF - Journal of neurochemistry AU - Hamelink, Carol AU - Hahm, Sung Ho AU - Huang, Heather AU - Eiden, Lee E AD - Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, NIMH, NIH, Bethesda, MD, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 1091 EP - 1101 VL - 88 IS - 5 SN - 0022-3042, 0022-3042 KW - RE1-silencing transcription factor KW - 0 KW - Repressor Proteins KW - Transcription Factors KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Transfection KW - Transcription Factors -- metabolism KW - HeLa Cells KW - Humans KW - Repressor Proteins -- metabolism KW - Genes, Reporter KW - Neuroblastoma -- metabolism KW - Fibroblasts -- metabolism KW - Cell Line KW - Sequence Deletion KW - Regulatory Sequences, Nucleic Acid -- genetics KW - Neurons -- metabolism KW - Vasoactive Intestinal Peptide -- metabolism KW - Regulatory Sequences, Nucleic Acid -- physiology KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71717213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+restrictive+element+1+%28RE-1%29+in+the+VIP+gene+modulates+transcription+in+neuronal+and+non-neuronal+cells+in+collaboration+with+an+upstream+tissue+specifier+element.&rft.au=Hamelink%2C+Carol%3BHahm%2C+Sung+Ho%3BHuang%2C+Heather%3BEiden%2C+Lee+E&rft.aulast=Hamelink&rft.aufirst=Carol&rft.date=2004-03-01&rft.volume=88&rft.issue=5&rft.spage=1091&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 - 2004-03-30 N1 - Date created - 2004-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rat brain arachidonic acid metabolism is increased by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide. AN - 71715059; 15009672 AB - In a rat model of acute neuroinflammation, produced by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide (LPS), we measured brain activities and protein levels of three phospholipases A2 (PLA2) and of cyclo-oxygenase-1 and -2, and quantified other aspects of brain phospholipid and fatty acid metabolism. The 6-day intracerebral ventricular infusion increased lectin-reactive microglia in the cerebral ventricles, pia mater, and the glial membrane of the cortex and resulted in morphological changes of glial fibrillary acidic protein (GFAP)-positive astrocytes in the cortical mantel and areas surrounding the cerebral ventricles. LPS infusion increased brain cytosolic and secretory PLA2 activities by 71% and 47%, respectively, as well as the brain concentrations of non-esterified linoleic and arachidonic acids, and of prostaglandins E2 and D2. LPS infusion also increased rates of incorporation and turnover of arachidonic acid in phosphatidylethanolamine, plasmenylethanolamine, phosphatidylcholine, and plasmenylcholine by 1.5- to 2.8-fold, without changing these rates in phosphatidylserine or phosphatidylinositol. These observations suggest that selective alterations in brain arachidonic acid metabolism involving cytosolic and secretory PLA2 contribute to early pathology in neuroinflammation. JF - Journal of neurochemistry AU - Rosenberger, Thad A AU - Villacreses, Nelly E AU - Hovda, Jonathan T AU - Bosetti, Francesca AU - Weerasinghe, Gayani AU - Wine, Robert N AU - Harry, G Jean AU - Rapoport, Stanley I AD - Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-1582, USA. plsetn@mail.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 1168 EP - 1178 VL - 88 IS - 5 SN - 0022-3042, 0022-3042 KW - Eicosanoids KW - 0 KW - Isoenzymes KW - Lipopolysaccharides KW - Membrane Proteins KW - Phospholipids KW - Arachidonic Acid KW - 27YG812J1I KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, rat KW - Phospholipases A KW - EC 3.1.1.32 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Index Medicus KW - Animals KW - Brain Chemistry KW - Eicosanoids -- metabolism KW - Phospholipids -- metabolism KW - Disease Models, Animal KW - Infusions, Parenteral KW - Isoenzymes -- metabolism KW - Injections, Intraventricular KW - Rats KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Time Factors KW - Microglia -- pathology KW - Microglia -- drug effects KW - Immunohistochemistry KW - Lipid Metabolism KW - Phospholipases A -- metabolism KW - Microglia -- metabolism KW - Encephalitis -- pathology KW - Lipopolysaccharides -- administration & dosage KW - Brain -- pathology KW - Brain -- metabolism KW - Encephalitis -- chemically induced KW - Encephalitis -- metabolism KW - Arachidonic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71715059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rat+brain+arachidonic+acid+metabolism+is+increased+by+a+6-day+intracerebral+ventricular+infusion+of+bacterial+lipopolysaccharide.&rft.au=Rosenberger%2C+Thad+A%3BVillacreses%2C+Nelly+E%3BHovda%2C+Jonathan+T%3BBosetti%2C+Francesca%3BWeerasinghe%2C+Gayani%3BWine%2C+Robert+N%3BHarry%2C+G+Jean%3BRapoport%2C+Stanley+I&rft.aulast=Rosenberger&rft.aufirst=Thad&rft.date=2004-03-01&rft.volume=88&rft.issue=5&rft.spage=1168&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 - 2004-03-30 N1 - Date created - 2004-03-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Neurochem. 2004 Jul;90(1):255 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Datapoints: Trends in naltrexone use among members of a large private health plan. AN - 71704197; 15001719 JF - Psychiatric services (Washington, D.C.) AU - Harris, Katherine M AU - DeVries, Andrea AU - Dimidjian, Kelli AD - Substance Abuse and Mental Health Services Administration, NIMH/NIH, 5600 Fishers Lane, Room 16-105, Rockville, MD 20857, USA. kharris@samhsa.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 221 VL - 55 IS - 3 SN - 1075-2730, 1075-2730 KW - Naltrexone KW - 5S6W795CQM KW - Index Medicus KW - United States KW - Humans KW - Alcoholism -- drug therapy KW - Insurance, Health KW - Naltrexone -- therapeutic use KW - Drug Therapy -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71704197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatric+services+%28Washington%2C+D.C.%29&rft.atitle=Datapoints%3A+Trends+in+naltrexone+use+among+members+of+a+large+private+health+plan.&rft.au=Harris%2C+Katherine+M%3BDeVries%2C+Andrea%3BDimidjian%2C+Kelli&rft.aulast=Harris&rft.aufirst=Katherine&rft.date=2004-03-01&rft.volume=55&rft.issue=3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Psychiatric+services+%28Washington%2C+D.C.%29&rft.issn=10752730&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-13 N1 - Date created - 2004-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Andrographolide reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuron-glia cultures by inhibiting microglial activation. AN - 71696526; 14718612 AB - Inflammation plays an important role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease. Recent reports have indicated that andrographolide (ANDRO) has an anti-inflammatory effect by modulating macrophage and neutrophil activity. Whereas microglia, the counterpart of macrophages in the brain, are pivotal in the inflammatory process in the central nervous system, the effect of ANDRO on inflammation-mediated neurodegeneration has not been examined. In this study, we show that both pretreatment and post-treatment with ANDRO exhibited a significant protective effect against lipopolysaccharide (LPS)-induced neurotoxicity in mixed neuron-glia cultures, as determined by [(3)H]dopamine uptake and immunocytochemical analysis. In contrast, ANDRO showed no protective effect on 1-methyl-4-phenyl-pyridine (0.5 microM)-induced neurotoxicity in neuron-enriched cultures. ANDRO significantly attenuated LPS-induced microglial activation and production of reactive oxygen species, tumor necrosis factor-alpha, nitric oxide, and prostaglandin E(2). Furthermore, ANDRO dose-dependently attenuated LPS-induced inducible nitric-oxide synthase and cyclooxygenase-2 protein expression in BV-2 microglia, as determined by Western blot. These findings demonstrate that ANDRO reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuron-glia cultures by inhibiting microglial activation. In addition, these results indicate that ANDRO may have clinical utility for the treatment of inflammation-related neurodegenerative disorders such as Parkinson's disease. JF - The Journal of pharmacology and experimental therapeutics AU - Wang, Tongguang AU - Liu, Bin AU - Zhang, Wei AU - Wilson, Belinda AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. wang16@niehs.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 975 EP - 983 VL - 308 IS - 3 SN - 0022-3565, 0022-3565 KW - Diterpenes KW - 0 KW - Isoenzymes KW - Lipopolysaccharides KW - andrographolide KW - 410105JHGR KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Index Medicus KW - Animals KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Neurons -- drug effects KW - Lipopolysaccharides -- pharmacology KW - Neuroglia -- drug effects KW - Isoenzymes -- metabolism KW - Rats KW - Mesencephalon -- drug effects KW - Rats, Inbred F344 KW - Cells, Cultured KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Neurons -- physiology KW - Inflammation -- etiology KW - Microglia -- drug effects KW - Male KW - 1-Methyl-4-phenylpyridinium -- pharmacology KW - Nerve Degeneration -- drug therapy KW - Diterpenes -- pharmacology KW - Diterpenes -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71696526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Andrographolide+reduces+inflammation-mediated+dopaminergic+neurodegeneration+in+mesencephalic+neuron-glia+cultures+by+inhibiting+microglial+activation.&rft.au=Wang%2C+Tongguang%3BLiu%2C+Bin%3BZhang%2C+Wei%3BWilson%2C+Belinda%3BHong%2C+Jau-Shyong&rft.aulast=Wang&rft.aufirst=Tongguang&rft.date=2004-03-01&rft.volume=308&rft.issue=3&rft.spage=975&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 - 2004-04-06 N1 - Date created - 2004-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Thyroid toxicants: assessing reproductive health effects. AN - 71695011; 14998754 AB - A thyroid toxicant workshop sponsored by the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction convened on 28-29 April 2003 in Alexandria, Virginia. The purpose of this workshop was to examine and discuss chemical-induced thyroid dysfunction in experimental animals and the relevance of reproductive and developmental effects observed for prediction of adverse effects in humans. Presentations highlighted and compared reproductive and developmental effects of thyroid hormones in humans and rodents. Rodent models of thyroid system dysfunction were presented. Animal testing protocols were reviewed, taking into account protocol designs that allow extrapolation to possible human health effects. Potential screening methods to assess toxicant-induced thyroid dysfunction were outlined, and postnatal bioassays of thyroid-related effects were discussed. JF - Environmental health perspectives AU - Jahnke, Gloria D AU - Choksi, Neepa Y AU - Moore, John A AU - Shelby, Michael D Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 363 EP - 368 VL - 112 IS - 3 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Rats KW - Biological Assay -- methods KW - Animals KW - Humans KW - Disease Models, Animal KW - Male KW - Female KW - Reproduction -- drug effects KW - Environmental Pollutants -- poisoning KW - Thyroid Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71695011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Thyroid+toxicants%3A+assessing+reproductive+health+effects.&rft.au=Jahnke%2C+Gloria+D%3BChoksi%2C+Neepa+Y%3BMoore%2C+John+A%3BShelby%2C+Michael+D&rft.aulast=Jahnke&rft.aufirst=Gloria&rft.date=2004-03-01&rft.volume=112&rft.issue=3&rft.spage=363&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 - 2004-06-15 N1 - Date created - 2004-03-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Endocrinology. 2003 Sep;144(9):3732-8 [12933641] Endocrinology. 2003 Sep;144(9):3722-31 [12933640] N Engl J Med. 1981 Mar 19;304(12):702-12 [6258072] Clin Exp Obstet Gynecol. 1984;11(3):79-89 [6202441] J Steroid Biochem. 1987 Nov;28(5):575-9 [3682824] Med Clin North Am. 1991 Jan;75(1):121-50 [1987439] Endocr Rev. 1995 Aug;16(4):443-59 [8521789] Reprod Toxicol. 1995 May-Jun;9(3):219-23 [7579905] J Toxicol Environ Health. 1996 Feb 9;47(2):109-14 [8598567] Mol Cell Endocrinol. 1999 May 25;151(1-2):103-19 [10411325] J Endocrinol. 2000 Apr;165(1):1-8 [10750030] Altern Med Rev. 2000 Aug;5(4):306-33 [10956378] Fertil Steril. 2000 Dec;74(6):1063-70 [11119728] J Endocrinol. 2001 Jul;170(1):185-96 [11431151] Rev Endocr Metab Disord. 2000 Jan;1(1-2):97-108 [11704998] Endocr Rev. 2002 Feb;23(1):38-89 [11844744] J Clin Invest. 2002 Feb;109(4):469-73 [11854318] Environ Health Perspect. 2002 Jun;110 Suppl 3:337-48 [12060827] Science. 2002 Dec 20;298(5602):2296-7 [12493875] Nat Struct Biol. 2003 Feb;10(2):91-2 [12536207] Pharmacol Ther B. 1979;5(1-3):305-18 [386373] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation. AN - 71693509; 14993265 AB - Smad7 inhibits responses mediated by transforming growth factor beta (TGF-beta) and acts in a negative-feedback loop to regulate the intensity or duration of the TGF-beta signal. However, the aberrant expression and continued presence of Smad7 may cause TGF-beta resistance. Here we report that Jab1/CSN5, which is a component of the COP9 signalosome complex, associates constitutively with Smad7 and that overexpression of Jab1/CSN5 causes the translocation of Smad7 from the nucleus to the cytoplasm, promoting its degradation. Overexpression of Jab1/CSN5 increases Smad2 phosphorylation and enhances TGF-beta-induced transcriptional activity. The inhibition of endogenous Jab1/CSN5 expression by small interfering RNA (siRNA) induces Smad7 expression. This study thus defines Jab1/CSN5 as an adapter that targets Smad7 for degradation, thus releasing Smad7-mediated suppression of TGF-beta signaling. JF - Molecular and cellular biology AU - Kim, Byung-Chul AU - Lee, Ho-Jae AU - Park, Seok Hee AU - Lee, Sae Ra AU - Karpova, Tatiana S AU - McNally, James G AU - Felici, Angelina AU - Lee, Dug Keun AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 2251 EP - 2262 VL - 24 IS - 6 SN - 0270-7306, 0270-7306 KW - COP9 signalosome complex KW - 0 KW - DNA-Binding Proteins KW - Intracellular Signaling Peptides and Proteins KW - Multiprotein Complexes KW - Proteins KW - RNA, Small Interfering KW - Recombinant Proteins KW - SMAD2 protein, human KW - SMAD7 protein, human KW - Smad2 Protein KW - Smad7 Protein KW - TGFB1 protein, human KW - Trans-Activators KW - Transcription Factors KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Peptide Hydrolases KW - EC 3.4.- KW - COPS5 protein, human KW - EC 3.4.-.- KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - COS Cells KW - Humans KW - Two-Hybrid System Techniques KW - RNA, Small Interfering -- genetics KW - Recombinant Proteins -- genetics KW - Models, Biological KW - Protein Binding KW - Down-Regulation KW - Transfection KW - Recombinant Proteins -- metabolism KW - In Vitro Techniques KW - Subcellular Fractions -- metabolism KW - Signal Transduction KW - Cell Line KW - Transforming Growth Factor beta -- pharmacology KW - Trans-Activators -- metabolism KW - Transcription Factors -- metabolism KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Transcription Factors -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71693509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Jab1%2FCSN5%2C+a+component+of+the+COP9+signalosome%2C+regulates+transforming+growth+factor+beta+signaling+by+binding+to+Smad7+and+promoting+its+degradation.&rft.au=Kim%2C+Byung-Chul%3BLee%2C+Ho-Jae%3BPark%2C+Seok+Hee%3BLee%2C+Sae+Ra%3BKarpova%2C+Tatiana+S%3BMcNally%2C+James+G%3BFelici%2C+Angelina%3BLee%2C+Dug+Keun%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Byung-Chul&rft.date=2004-03-01&rft.volume=24&rft.issue=6&rft.spage=2251&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 - 2004-04-13 N1 - Date created - 2004-03-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trends Genet. 1999 Mar;15(3):98-103 [10203806] J Biol Chem. 2000 Aug 11;275(32):24735-9 [10859299] Nature. 1999 Aug 12;400(6745):687-93 [10458166] Oncogene. 1999 Sep 23;18(39):5363-72 [10498890] EMBO J. 2000 Apr 17;19(8):1745-54 [10775259] Trends Genet. 2000 May;16(5):202-3 [10782111] Curr Biol. 2000 May 4;10(9):535-8 [10801443] J Biol Chem. 2000 Nov 24;275(47):36818-22 [11016919] Nature. 2000 Nov 9;408(6809):211-6 [11089976] J Biol Chem. 2000 Nov 17;275(46):36295-302 [10942775] Semin Cell Dev Biol. 2000 Dec;11(6):495-503 [11145879] Mol Cell. 2000 Dec;6(6):1365-75 [11163210] J Biol Chem. 2001 Apr 20;276(16):12477-80 [11278251] Oncogene. 2001 Feb 15;20(7):879-84 [11314022] J Biol Chem. 2001 Apr 27;276(17):14344-9 [11278814] J Biol Chem. 2002 Jan 4;277(1):9-12 [11707426] J Biol Chem. 2002 Jan 18;277(3):2302-10 [11704659] EMBO Rep. 2002 Feb;3(2):171-6 [11818334] J Cell Sci. 2002 Feb 1;115(Pt 3):467-73 [11861754] Kidney Int. 2002 Oct;62(4):1178-86 [12234288] Nat Rev Genet. 2002 Oct;3(10):737-47 [12360232] J Biol Chem. 2002 Oct 18;277(42):39919-25 [12151385] J Biol Chem. 2003 Mar 21;278(12):10716-21 [12519765] Nucleic Acids Res. 1990 Sep 11;18(17):5322 [1698283] Cell. 1992 Dec 11;71(6):1003-14 [1333888] Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7819-23 [7644498] Science. 1996 Jan 19;271(5247):350-3 [8553070] Cell. 1996 Aug 23;86(4):543-52 [8752209] Nature. 1996 Oct 3;383(6599):453-7 [8837781] Cytokine Growth Factor Rev. 1996 Jun;7(1):93-102 [8864357] Cell. 1997 Jun 27;89(7):1165-73 [9215638] Nature. 1997 Oct 9;389(6651):622-6 [9335505] Nature. 1997 Oct 9;389(6651):631-5 [9335507] Nature. 1997 Dec 4;390(6659):465-71 [9393997] Dev Biol. 1998 Jun 1;198(1):1-12 [9640328] Mol Cell. 1998 Mar;1(4):611-7 [9660945] Biochem Biophys Res Commun. 1998 Aug 19;249(2):505-11 [9712726] J Biol Chem. 1998 Sep 25;273(39):25364-70 [9738003] Cell. 1998 Sep 4;94(5):615-23 [9741626] Annu Rev Biochem. 1998;67:425-79 [9759494] J Biol Chem. 1998 Oct 30;273(44):29195-201 [9786930] Plant Cell. 1998 Nov;10(11):1779-90 [9811788] Cell. 1998 Dec 11;95(6):737-40 [9865691] Annu Rev Cell Dev Biol. 1998;14:19-57 [9891777] Nature. 1999 Feb 25;397(6721):710-3 [10067896] Nature. 1999 Mar 11;398(6723):160-5 [10086358] J Biol Chem. 1999 Nov 5;274(45):32258-64 [10542264] Mol Biol Cell. 1999 Nov;10(11):3801-13 [10564272] Annu Rev Cell Dev Biol. 1999;15:435-67 [10611969] Genes Dev. 2000 Jan 15;14(2):187-97 [10652273] J Cell Sci. 2000 Apr;113 ( Pt 7):1101-9 [10704361] Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):159-68 [10708963] Curr Opin Cell Biol. 2000 Apr;12(2):235-43 [10712925] J Biol Chem. 2000 Mar 24;275(12):8540-8 [10722692] Genes Dev. 2000 Mar 15;14(6):627-44 [10733523] Nature. 2000 Apr 6;404(6778):617-21 [10766246] Nature. 2000 May 25;405(6785):462-6 [10839542] Oncogene. 1999 Jun 3;18(22):3316-23 [10362352] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unconditional hyperactivity and transient reinforcing effects of NMDA administration into the ventral tegmental area in rats. AN - 71686185; 14634715 AB - The dopaminergic projection from the ventral tegmental area (VTA) to the nucleus accumbens plays an important role in positive reinforcement and locomotion. Intra-VTA administration of many drugs capable of activating these neurons has been shown to be reinforcing and induce locomotion. Administration of the excitatory amino acid NMDA (N-methyl-D-aspartate) into the VTA may likewise be positively reinforcing, because it stimulates the meso-accumbens dopamine system and locomotion. Locomotor-rearing experiments were conducted to pinpoint the range of NMDA concentrations that induce significant locomotion and rearing, and to determine whether co-administration of the glycine binding site agonist d-serine would enhance the effects of NMDA administration into the VTA. Reinforcing effects of NMDA were assessed by intracranial self-administration procedures: a lever-press delivered a 75-nl infusion containing NMDA (0.1, 0.3 or 1.0 mM) plus serine into the VTA or an adjacent region, the supramammillary nucleus. Co-administration of serine slightly enhanced rearing induced by NMDA administration. Administration of NMDA at concentrations of 0.3 or 1.0 mM (500 nl) induced vigorous locomotion and rearing. NMDA (0.3 mM) was self-administered into the VTA slightly more than vehicle in the first or second sessions, yet this small reinforcing effect became irregular in subsequent sessions. The rats did not learn to self-administer NMDA into the supramammillary nucleus. Ventral tegmental NMDA injections, in the concentration range that induced marked unconditional hyperactivity, supported only marginal and transient self-administration. JF - Psychopharmacology AU - Ikemoto, Satoshi AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse, Department of Health and Human Services, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. sikemoto@intra.nida.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 202 EP - 210 VL - 172 IS - 2 SN - 0033-3158, 0033-3158 KW - N-Methylaspartate KW - 6384-92-5 KW - Index Medicus KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - Rats, Wistar KW - Male KW - Injections, Intraventricular KW - Reinforcement (Psychology) KW - N-Methylaspartate -- administration & dosage KW - Hyperkinesis -- chemically induced KW - Conditioning (Psychology) -- physiology KW - Ventral Tegmental Area -- drug effects KW - Ventral Tegmental Area -- physiology KW - Conditioning (Psychology) -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71686185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Unconditional+hyperactivity+and+transient+reinforcing+effects+of+NMDA+administration+into+the+ventral+tegmental+area+in+rats.&rft.au=Ikemoto%2C+Satoshi&rft.aulast=Ikemoto&rft.aufirst=Satoshi&rft.date=2004-03-01&rft.volume=172&rft.issue=2&rft.spage=202&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-28 N1 - Date created - 2004-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A reanalysis of thyroid neoplasms in the Israeli tinea capitis study accounting for dose uncertainties. AN - 71674811; 14982478 AB - In the 1940s and 1950s, children in Israel were treated for tinea capitis by irradiation to the scalp to induce epilation. Follow-up studies of these patients and of other radiation- exposed populations show an increased risk of malignant and benign thyroid tumors. Those analyses, however, assume that thyroid dose for individuals is estimated precisely without error. Failure to account for uncertainties in dosimetry may affect standard errors and bias dose-response estimates. For the Israeli tinea capitis study, we discuss sources of uncertainties and adjust dosimetry for uncertainties in the prediction of true dose from X-ray treatment parameters. We also account for missing ages at exposure for patients with multiple X-ray treatments, since only ages at first treatment are known, and for missing data on treatment center, which investigators use to define exposure. Our reanalysis of the dose response for thyroid cancer and benign thyroid tumors indicates that uncertainties in dosimetry have minimal effects on dose-response estimation and for inference on the modifying effects of age at first exposure, time since exposure, and other factors. Since the components of the dose uncertainties we describe are likely to be present in other epidemiological studies of patients treated with radiation, our analysis may provide a model for considering the potential role of these uncertainties. JF - Radiation research AU - Lubin, Jay H AU - Schafer, Daniel W AU - Ron, Elaine AU - Stovall, Marilyn AU - Carroll, Raymond J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. lubinj@mail.nih.gov Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 359 EP - 368 VL - 161 IS - 3 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Sensitivity and Specificity KW - Reproducibility of Results KW - Body Burden KW - Humans KW - Infant, Newborn KW - Models, Statistical KW - Child KW - Dose-Response Relationship, Radiation KW - Models, Biological KW - Thyroid Gland -- radiation effects KW - Child, Preschool KW - Infant KW - Radiotherapy Dosage KW - Incidence KW - Adolescent KW - Female KW - Male KW - Thyroid Neoplasms -- epidemiology KW - Tinea Capitis -- radiotherapy KW - Neoplasms, Radiation-Induced -- epidemiology KW - Tinea Capitis -- epidemiology KW - Data Interpretation, Statistical KW - Risk Assessment -- methods KW - Radiometry -- methods KW - Radiotherapy -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71674811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+reanalysis+of+thyroid+neoplasms+in+the+Israeli+tinea+capitis+study+accounting+for+dose+uncertainties.&rft.au=Lubin%2C+Jay+H%3BSchafer%2C+Daniel+W%3BRon%2C+Elaine%3BStovall%2C+Marilyn%3BCarroll%2C+Raymond+J&rft.aulast=Lubin&rft.aufirst=Jay&rft.date=2004-03-01&rft.volume=161&rft.issue=3&rft.spage=359&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 - 2004-06-01 N1 - Date created - 2004-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer: National Cancer Institute Cairo experience. AN - 67274959; 15716991 AB - The aim of the present study is to document the antitumor activity of the combination of gemcitabine and cisplatin for the treatment of advanced NSCLC, asses the nature and severity of the side effects and elicit the impact of the combination chemotherapy on progression free survival and overall survival. From August 1997 to August 2001, we conducted a phase II study of gemcitabine and cisplatin in 60 chemonaive patients (21 stage IIIB and 39 stage IV). For the first 34 cases, gemcitabine was given at a dose of 1,000 mg/m2 IV on days 1, 8 and 15 with cisplatin 100 mg/m2 on day 15, every 28 days. In the following 26 patients, the regimen was modified to gemcitabine 1,250 mg/m2 days 1 and 8 and cisplatin 80 mg/m2 day 1, every 21 days. Patients included 53 males and 7 females [median age, 52 years (range, 28-69)]. Twenty-nine had adenocarcinoma, 18 large-cell carcinoma and 13 squamous-cell carcinoma. Thirty-one patients had a performance status (PS) of 2 and 22 presented with weight loss. All patients were evaluable for response. Three patients achieved a complete response (CR) and 22 had partial response (PR), giving an overall response of 41.7%, with a median duration of 10 months (range, 4-46 months). The time to progression (TTP) was 8 months (range, 2-46 months), with a median overall survival of 9 months (range, 2-46 months). The one-year survival rate was 30.3% for the entire study population, 44% for responders, and statistically improved in patients with a PS of I and those with no weight loss. A total of 255 cycles were administered (median, four cycles/patient). Myelosuppression was significant (but manageable) with grade 3/4 neutropenia in 32.6% of cases, anemia in 18.6% and thrombocytopenia in 20.4%. Nonhematologic toxicity was limited to grade 3/4 nausea and vomiting in 28.8% of cases and impaired liver enzymes in 13.6%. Inspite of the relatively poor prognostic characteristics in the study population, gemcitabine and cisplatin, was an effective combination with tolerable, manageable toxicity in advanced NSCLC. JF - Journal of the Egyptian National Cancer Institute AU - Gaafar, Rabab M AU - Hamza, Reda AU - Khaled, Hussein M AU - Elserafi, Mostafa AU - Mansour, Osman AU - Karim, Nagla Abdel AU - Abdelmoneim, Doaa AU - Elattar, Inas AU - Soliman, Sherif AD - Department of Medical Oncology, National Cancer Institute, Cairo University. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 1 EP - 7 VL - 16 IS - 1 SN - 1110-0362, 1110-0362 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67274959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Egyptian+National+Cancer+Institute&rft.atitle=Gemcitabine+and+cisplatin+in+the+treatment+of+advanced+non-small+cell+lung+cancer%3A+National+Cancer+Institute+Cairo+experience.&rft.au=Gaafar%2C+Rabab+M%3BHamza%2C+Reda%3BKhaled%2C+Hussein+M%3BElserafi%2C+Mostafa%3BMansour%2C+Osman%3BKarim%2C+Nagla+Abdel%3BAbdelmoneim%2C+Doaa%3BElattar%2C+Inas%3BSoliman%2C+Sherif&rft.aulast=Gaafar&rft.aufirst=Rabab&rft.date=2004-03-01&rft.volume=16&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Egyptian+National+Cancer+Institute&rft.issn=11100362&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-19 N1 - Date created - 2005-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of heterozygosity at BRCA1, TP53, nm-23 and other loci on chromosome 17q in human breast carcinoma. AN - 67235316; 15717000 AB - In Egypt, breast cancer ranks number one among the female malignancies. Activation of oncogenes and inactivation of tumor suppressor genes are thought to play an important role in the development and progression of breast cancer. The present study is a trial to investigate the role of chromosome 17 in sporadic invasive ductal carcinoma of the breast through detection of LOH for 6 highly polymorphic microsatellite loci, two of which are located at BRCA1 gene (D17S855 and D17S856), one at TP53 gene, one at nm-23 gene and finally two at 17q12-12.3 (D17S183 and D17S250). Tissue samples and their corresponding safety margin normal tissues were collected from 25 patients with invasive ductal carcinoma of the breast of grades 2 and 3. LOH was detected for the 6 highly polymorphic microsatellite markers mentioned previously using PCR assay. The percentage of overall LOH recorded was 68% of the cases examined. The highest LOH recorded in D17S855 and D17S856 (43% and 32% respectively), both markers are located at BRCA1 gene, followed by 32% LOH in nm-23 gene. D17S183 and D17S250, which are localised telomeric and centromeric to BRCA1 gene, showed 24% and 28% LOH, respectively. The lowest percentage of LOH was observed in the TP53 gene (14%). No significant correlation was found between each of the six markers used and lymph node status, grade, or menopausal status. LOH at the nm-23 marker exhibited a significant association with lymph node involvement. It can be concluded from the present study that BRCA1 gene may be involved in carcinogenesis of some sporadic breast cancer cases. Deletion in nm-23 gene is associated with advanced stage of the disease. Finally, another gene located at 17q12-12.3 region may be involved in some sporadic breast cancer cases. JF - Journal of the Egyptian National Cancer Institute AU - Saleh, Ekram M AU - Wahab, Abdel Hady A Abdel AU - Elhouseini, Motawa E AU - Eisa, Saad S AD - Department of Cancer Biology, National Cancer Institute, Cairo University. Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 62 EP - 68 VL - 16 IS - 1 SN - 1110-0362, 1110-0362 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67235316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Egyptian+National+Cancer+Institute&rft.atitle=Loss+of+heterozygosity+at+BRCA1%2C+TP53%2C+nm-23+and+other+loci+on+chromosome+17q+in+human+breast+carcinoma.&rft.au=Saleh%2C+Ekram+M%3BWahab%2C+Abdel+Hady+A+Abdel%3BElhouseini%2C+Motawa+E%3BEisa%2C+Saad+S&rft.aulast=Saleh&rft.aufirst=Ekram&rft.date=2004-03-01&rft.volume=16&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Egyptian+National+Cancer+Institute&rft.issn=11100362&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-19 N1 - Date created - 2005-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ectopic Cushing's syndrome caused by an esthesioneuroblastoma. AN - 66711888; 15256328 AB - To report a case of florid Cushing's hormone (ACTH) secretion related to the presence of an esthesioneuroblastoma (ENB). We present clinical, laboratory, and pathologic findings in a 36-year-old Caucasian man presenting with Cushing's syndrome. Results of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) scanning, and somatostatin receptor scintigraphy are presented, along with tumor pathology findings. After initial biochemical studies suggestive of ectopic Cushing's syndrome, CT of the chest and abdomen revealed multiple cavitated pulmonary lesions, an ischiorectal mass, and bilateral adrenal hyperplasia. MRI of the pituitary gland revealed normal findings. Both PET scanning with [18 F]-flurodeoxyglucose (FDG) and somatostatin receptor scintigraphy with 111 indium-penetetreotide (Octreoscan) revealed strong tracer uptake in the ethmoid region. CT and MRI of the sinuses and brain subsequently localized a 5-cm mass in the ethmoid sinuses with intracranial extension. On biopsy, pathology results were consistent with a diagnosis of ENB, and immunohistochemical analysis revealed that tumor cells were strongly positive for ACTH, synaptophysin, and S-100, providing definitive diagnosis of ACTH-producing ENB. Hypercortisolemia was initially controlled by metyrapone, then by external beam radiation therapy (RT). This case illustrates the usefulness of nuclear imaging in the diagnosis of ENB, and the importance of prompt control of hypercortisolemia in Cushing's syndrome. JF - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists AU - Yu, Juan AU - Koch, Christian A AU - Patsalides, Athos AU - Chang, Richard AU - Altemus, Rosemary M AU - Nieman, Lynette K AU - Pacak, Karel AD - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2004 SP - 119 EP - 124 VL - 10 IS - 2 SN - 1530-891X, 1530-891X KW - Antimetabolites KW - 0 KW - Receptors, Somatostatin KW - Metyrapone KW - ZS9KD92H6V KW - Index Medicus KW - Magnetic Resonance Imaging KW - Clinical Laboratory Techniques KW - Receptors, Somatostatin -- analysis KW - Metyrapone -- therapeutic use KW - Combined Modality Therapy KW - Humans KW - Adult KW - Tomography, X-Ray Computed KW - Tomography, Emission-Computed KW - Antimetabolites -- therapeutic use KW - Male KW - Nose Neoplasms -- chemistry KW - Nasal Cavity KW - Nose Neoplasms -- radiotherapy KW - Esthesioneuroblastoma, Olfactory -- radiotherapy KW - ACTH Syndrome, Ectopic -- etiology KW - Nose Neoplasms -- complications KW - Esthesioneuroblastoma, Olfactory -- diagnosis KW - Esthesioneuroblastoma, Olfactory -- chemistry KW - Nose Neoplasms -- diagnosis KW - Esthesioneuroblastoma, Olfactory -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66711888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrine+practice+%3A+official+journal+of+the+American+College+of+Endocrinology+and+the+American+Association+of+Clinical+Endocrinologists&rft.atitle=Ectopic+Cushing%27s+syndrome+caused+by+an+esthesioneuroblastoma.&rft.au=Yu%2C+Juan%3BKoch%2C+Christian+A%3BPatsalides%2C+Athos%3BChang%2C+Richard%3BAltemus%2C+Rosemary+M%3BNieman%2C+Lynette+K%3BPacak%2C+Karel&rft.aulast=Yu&rft.aufirst=Juan&rft.date=2004-03-01&rft.volume=10&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Endocrine+practice+%3A+official+journal+of+the+American+College+of+Endocrinology+and+the+American+Association+of+Clinical+Endocrinologists&rft.issn=1530891X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-09 N1 - Date created - 2004-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raltitrexed plus oxaliplatin in the treatment of metastatic colorectal cancer. AN - 66685805; 15237580 AB - As raltitrexed and oxaliplatin (L-OHP) are both effective in the treatment of colorectal cancer but have different mechanisms of action, we studied the antitumoral activity and safety of their combined use in patients with advanced colorectal cancer. A 15-min intravenous infusion of raltitrexed (2.5 mg/m2) and a 180-min infusion of oxaliplatin (100 mg/m2) were administered on day 1 every three weeks for a maximum of six cycles. The study involved 51 patients (27 males and 24 females) with a median age of 65 years (range, 43-78); 28 were aged > or = 65 years. The primary tumor site was the colon in 35 patients and the rectum in 16. Thirty-four patients had received prior chemotherapy: 20 as adjuvant treatment and 14 as pretreatment. The most frequent metastatic sites were liver (18 cases), lung (10 cases), liver + lung (8 cases) and lymph nodes (3 cases). Twenty-four patients completed the entire treatment plan. The most common toxicities were transaminitis (16 patients, grade 3-4), diarrhea (six patients, grade 3), nausea/vomiting (one patient, grade 4), and asthenia (one patient, grade 3). The treatment was stopped in one patient because of prolonged grade 4 transaminitis. The adverse event profile was similar in the patients aged > 65 years and < 65 years. Complete responses were observed in 2 patients, partial responses in 12, stable disease in 23, and progression in 8. The results of the study suggest that the raltitrexed plus oxaliplatin regimen is feasible and clinically active in advanced colorectal cancer. JF - Tumori AU - Cortinovis, Diego AU - Bajetta, Emilio AU - Di Bartolomeo, Maria AU - Dognini, Giuseppina AU - Beretta, Elena AU - Ferrario, Erminia AU - Ricotta, Riccardo AU - Buzzoni, Roberto AD - Medical Oncology Unit B, National Cancer Institute, Milan, Italy. PY - 2004 SP - 186 EP - 191 VL - 90 IS - 2 SN - 0300-8916, 0300-8916 KW - Antimetabolites, Antineoplastic KW - 0 KW - Organoplatinum Compounds KW - Quinazolines KW - Thiophenes KW - oxaliplatin KW - 04ZR38536J KW - raltitrexed KW - FCB9EGG971 KW - Index Medicus KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Disease-Free Survival KW - Drug Administration Schedule KW - Organoplatinum Compounds -- administration & dosage KW - Infusions, Intravenous KW - Lymphatic Metastasis KW - Lung Neoplasms -- secondary KW - Humans KW - Lung Neoplasms -- drug therapy KW - Aged KW - Patient Selection KW - Liver Neoplasms -- secondary KW - Quinazolines -- administration & dosage KW - Feasibility Studies KW - Liver Neoplasms -- drug therapy KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Thiophenes -- administration & dosage KW - Male KW - Female KW - Survival Analysis KW - Neoplasm Recurrence, Local -- drug therapy KW - Colorectal Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Colorectal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66685805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Raltitrexed+plus+oxaliplatin+in+the+treatment+of+metastatic+colorectal+cancer.&rft.au=Cortinovis%2C+Diego%3BBajetta%2C+Emilio%3BDi+Bartolomeo%2C+Maria%3BDognini%2C+Giuseppina%3BBeretta%2C+Elena%3BFerrario%2C+Erminia%3BRicotta%2C+Riccardo%3BBuzzoni%2C+Roberto&rft.aulast=Cortinovis&rft.aufirst=Diego&rft.date=2004-03-01&rft.volume=90&rft.issue=2&rft.spage=186&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-20 N1 - Date created - 2004-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicoproteomics: serum proteomic pattern diagnostics for early detection of drug induced cardiac toxicities and cardioprotection. AN - 66646990; 15209412 AB - Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry which communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity based processes as cascades of reinforcing information percolate through the system and become reflected in changing proteomic information content of the circulation. Serum Proteomic Pattern Diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. While this approach has shown tremendous promise in early detection of cancers, detection of drug-induced toxicity may also be possible with this same technology. Analysis of serum from rat models of anthracycline and anthracenedione induced cardiotoxicity indicate the potential clinical utility of diagnostic proteomic patterns where low molecular weight peptides and protein fragments may have higher accuracy than traditional biomarkers of cardiotoxicity such as troponins. These fragments may one day be harvested by circulating nanoparticles designed to absorb, enrich and amplify the diagnostic biomarker repertoire generated even at the critical initial stages of toxicity. JF - Toxicologic pathology AU - Petricoin, Emanuel F AU - Rajapaske, Vinodh AU - Herman, Eugene H AU - Arekani, Ali M AU - Ross, Sally AU - Johann, Donald AU - Knapton, Alan AU - Zhang, J AU - Hitt, Ben A AU - Conrads, Thomas P AU - Veenstra, Timothy D AU - Liotta, Lance A AU - Sistare, Frank D AD - FDA-NCI Clinical Proteomics Program, Office of Cell and Gene Therapies, Center for Biologic Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. petricoin@cber.fda.gov PY - 2004 SP - 122 EP - 130 VL - 32 Suppl 1 SN - 0192-6233, 0192-6233 KW - Anthracyclines KW - 0 KW - Anthraquinones KW - Blood Proteins KW - Index Medicus KW - Mass Spectrometry KW - Animals KW - Anthracyclines -- toxicity KW - Humans KW - Molecular Diagnostic Techniques -- instrumentation KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Anthraquinones -- toxicity KW - Time Factors KW - Molecular Diagnostic Techniques -- methods KW - Models, Biological KW - Nanotechnology KW - Proteomics KW - Cardiomyopathies -- prevention & control KW - Cardiomyopathies -- chemically induced KW - Toxicology KW - Blood Proteins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxicoproteomics%3A+serum+proteomic+pattern+diagnostics+for+early+detection+of+drug+induced+cardiac+toxicities+and+cardioprotection.&rft.au=Petricoin%2C+Emanuel+F%3BRajapaske%2C+Vinodh%3BHerman%2C+Eugene+H%3BArekani%2C+Ali+M%3BRoss%2C+Sally%3BJohann%2C+Donald%3BKnapton%2C+Alan%3BZhang%2C+J%3BHitt%2C+Ben+A%3BConrads%2C+Thomas+P%3BVeenstra%2C+Timothy+D%3BLiotta%2C+Lance+A%3BSistare%2C+Frank+D&rft.aulast=Petricoin&rft.aufirst=Emanuel&rft.date=2004-03-01&rft.volume=32+Suppl+1&rft.issue=&rft.spage=122&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 - 2004-10-21 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relevance of animal carcinogenesis findings to human cancer predictions and prevention. AN - 66646902; 15209402 AB - Use of laboratory animals to identify carcinogenic potential of chemicals, mixtures, and other agents has a modern history of greater than 40 years from which much useful scientific and public health information can be derived. While laboratory animals differ from humans in some respects that may affect responses to hazardous exposures, use of such models is based on experimental evidence indicating that there are more genetic, genomic, physiological, biochemical, and metabolic similarities than differences among mammalian species. Issues of concordance of responses between rodent species and between rodents and humans as well as repeatability and site-specificity are important considerations in evaluating laboratory animal carcinogenicity results. Variables in experimental design such as animal strain, diet, route of exposure, and study, duration as well as single-site versus multisite carcinogenic responses all influence interpretation and intelligent use of study data. Similarities and differences in site-specific laboratory animal and corresponding human cancers should also be considered in study evaluation. Recent attempts to explore genetically engineered mice and to humanize the mouse for more relevant identification of carcinogen hazard identification have yielded mixed results. In the end we are confronted by the realization that virtually all animal cancer models are useful but imperfect surrogates for humans. Assuming the percentage of chemicals currently in commerce that are estimated to be potent animal or human carcinogens is quite low, the task of identifying agents with significant carcinogenic potential is daunting and important. The biological conundrum of scientific debate regarding the relevance of carcinogenicity studies in laboratory animals is likely to continue. Nonetheless public health considerations must take precedence when deciding human safety issues. JF - Toxicologic pathology AU - Maronpot, R R AU - Flake, G AU - Huff, J AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. maronpot@niehs.nih.gov PY - 2004 SP - 40 EP - 48 VL - 32 Suppl 1 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Liver Neoplasms -- pathology KW - Carcinogenicity Tests -- trends KW - Humans KW - Carcinogenicity Tests -- methods KW - Predictive Value of Tests KW - Mice KW - Mice, Transgenic KW - Liver Neoplasms -- etiology KW - Species Specificity KW - Cell Transformation, Neoplastic KW - Neoplasms -- prevention & control KW - Neoplasms, Experimental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relevance+of+animal+carcinogenesis+findings+to+human+cancer+predictions+and+prevention.&rft.au=Maronpot%2C+R+R%3BFlake%2C+G%3BHuff%2C+J&rft.aulast=Maronpot&rft.aufirst=R&rft.date=2004-03-01&rft.volume=32+Suppl+1&rft.issue=&rft.spage=40&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 - 2004-10-21 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Application of gene expression profiling for validating models of human breast cancer. AN - 66646359; 15209407 AB - While classical histopathologic approaches are invaluable in classifying tumors and understanding aspects of cellular interactions, genomic approaches provide a means to molecularly dissect tumorigenesis. The relationship of gene expression to the development of neoplasia remains an area of intensive research. With the advent of large-scale genomic platforms, alterations in gene expression can be related to the morphological development of cancer. The feasibility of using large-scale genomic analysis platforms has dramatically changed the landscape of biological sciences, as cellular processes must be considered in the context of complex networks. Alterations in gene expression must now be understood in a systems approach in which the relationships between genes expression changes are studied by considering the interplay of multiple regulatory networks. Ultimately, such changes must be understood at the protein level. We have begun to apply this technology to determine changes in gene expression that differentiate various types of mammary cancers that arise in mouse models that have been initiated by different genetic alterations. Ultimately, a molecular catalogue of similarities and differences between rodent and human tumors can be created which will serve to validate or credential particular models for specific experimental purposes, such as preclinical testing. These approaches have led to new insights into molecular pathways involved in oncogenesis, new classifications of human breast cancer, and the identification of new genes that may be relevant to understanding and treating human cancer. JF - Toxicologic pathology AU - Green, Jeffrey E AU - Desai, Kartiki V AU - Ye, Yumei AU - Kavanaugh, Claudine AU - Calvo, Alfonso AU - Huh, Jung-im AD - Transgenic Oncogenesis Group, Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. JEGreen@nih.gov PY - 2004 SP - 84 EP - 89 VL - 32 Suppl 1 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Oncogenes KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Disease Models, Animal KW - Mice KW - Forecasting KW - Mice, Transgenic KW - Female KW - Genomics KW - Breast Neoplasms -- genetics KW - Gene Expression Profiling KW - Reproducibility of Results KW - Mammary Neoplasms, Animal -- pathology KW - Breast Neoplasms -- pathology KW - Mammary Neoplasms, Animal -- genetics KW - Breast Neoplasms -- metabolism KW - Mammary Neoplasms, Animal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Application+of+gene+expression+profiling+for+validating+models+of+human+breast+cancer.&rft.au=Green%2C+Jeffrey+E%3BDesai%2C+Kartiki+V%3BYe%2C+Yumei%3BKavanaugh%2C+Claudine%3BCalvo%2C+Alfonso%3BHuh%2C+Jung-im&rft.aulast=Green&rft.aufirst=Jeffrey&rft.date=2004-03-01&rft.volume=32+Suppl+1&rft.issue=&rft.spage=84&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 - 2004-10-21 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Application of toxicogenomics to toxicology: basic concepts in the analysis of microarray data. AN - 66644343; 15209406 AB - Toxicology and the practice of pathology are rapidly evolving in the postgenomic era. Observable treatment related changes have been the hallmark of toxicology studies. Toxicogenomics is a powerful new tool that may show gene and protein changes earlier and at treatment levels below the limits of detection of traditional measures of toxicity. It may also aid in the understanding of toxic mechanisms. It is important to remember that it is only a tool and will provide meaningful results only when properly applied. As is often the case with new experimental tools, the initial utilization is driven more by the technology than application to problem solving. Toxicogenomics is interdisciplinary in nature including at a minimum, pathology, toxicology, and genomics. Most studies will require the input from the disciplines of toxicology, pathology, molecular biology, bioinformatics, biochemistry, and others depending on the types of questions being asked. JF - Toxicologic pathology AU - Irwin, Richard D AU - Boorman, Gary A AU - Cunningham, Michael L AU - Heinloth, Alexandra N AU - Malarkey, David E AU - Paules, Richard S AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Irwin@niehs.nih.gov PY - 2004 SP - 72 EP - 83 VL - 32 Suppl 1 SN - 0192-6233, 0192-6233 KW - Acetaminophen KW - 362O9ITL9D KW - Index Medicus KW - Gene Expression Profiling KW - Animals KW - Humans KW - Gene Expression KW - Acetaminophen -- toxicity KW - Genomics KW - Oligonucleotide Array Sequence Analysis KW - Toxicogenetics KW - Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66644343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Application+of+toxicogenomics+to+toxicology%3A+basic+concepts+in+the+analysis+of+microarray+data.&rft.au=Irwin%2C+Richard+D%3BBoorman%2C+Gary+A%3BCunningham%2C+Michael+L%3BHeinloth%2C+Alexandra+N%3BMalarkey%2C+David+E%3BPaules%2C+Richard+S&rft.aulast=Irwin&rft.aufirst=Richard&rft.date=2004-03-01&rft.volume=32+Suppl+1&rft.issue=&rft.spage=72&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 - 2004-10-21 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Future directions in cancer research: impact of the completion of the human genome. AN - 66644328; 15209396 AB - The sequencing of the human genome will have a major impact on the prevention, diagnosis, treatment, monitoring, and outcome of cancer. Progress will most likely occur in a stepwise fashion with the biggest initial impact in diagnosis and molecular targeting of new medicines. Advances in genomics and proteomics have already resulted in major findings that are facilitating earlier cancer diagnosis and disease stratification. New treatments that target specific pathways are well underway for many cancers and likewise, molecular analyses aimed at finding medicines with reduced toxicities are being conducted. Close interaction with the Food and Drug Administration will be very important to integrate these new technologies into product development and the approval of new medicines and diagnostics. Clearly, we are now approaching the era of personalized medicines in which one has the opportunity to maximize the efficacy and minimize the side effects of the cancer treatments. The ability to translate this new technology into improving cancer patient care and outcomes will require that scientists from academia, industry, and govemment work together closely to develop the framework and standards necessary to maximize the benefit of the human genome project. JF - Toxicologic pathology AU - Zoon, Kathryn C AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Zoonk@mail.nih.gov PY - 2004 SP - 1 EP - 2 VL - 32 Suppl 1 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - United States KW - Gene Expression Profiling KW - United States Food and Drug Administration KW - Government Regulation KW - Humans KW - Proteomics KW - Forecasting KW - Research KW - Genomics KW - Neoplasms -- drug therapy KW - Neoplasms -- diagnosis KW - Genome, Human KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66644328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Future+directions+in+cancer+research%3A+impact+of+the+completion+of+the+human+genome.&rft.au=Zoon%2C+Kathryn+C&rft.aulast=Zoon&rft.aufirst=Kathryn&rft.date=2004-03-01&rft.volume=32+Suppl+1&rft.issue=&rft.spage=1&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 - 2004-10-21 N1 - Date created - 2004-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The AMBIENT Project; high school environmental health sciences curriculum AN - 50275234; 2007-046108 JF - Toxicological Sciences AU - Pitman, L AU - Fleming, L E AU - Pitman, T AU - Stephan, W AU - Davis, H AU - Goodman, K Y1 - 2004/03// PY - 2004 DA - March 2004 SP - 359 EP - 360 PB - Academic Press, Orlando, FL VL - 78 IS - S-1 SN - 1096-6080, 1096-6080 KW - United States KW - high school KW - Dade County Florida KW - global KW - education KW - AMBIENT Project KW - Florida KW - teacher education KW - K-12 education KW - Miami-Dade County Florida KW - environmental geology KW - curricula KW - local KW - public health KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/50275234?accountid=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=Toxicological+Sciences&rft.atitle=The+AMBIENT+Project%3B+high+school+environmental+health+sciences+curriculum&rft.au=Pitman%2C+L%3BFleming%2C+L+E%3BPitman%2C+T%3BStephan%2C+W%3BDavis%2C+H%3BGoodman%2C+K&rft.aulast=Pitman&rft.aufirst=L&rft.date=2004-03-01&rft.volume=78&rft.issue=S-1&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ L2 - http://toxsci.oxfordjournals.org/ LA - English DB - GeoRef N1 - Conference title - Society of Toxicology, 43rd annual meeting N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2007-01-01 N1 - PubXState - FL N1 - SuppNotes - Website at http://www.rsmas.miami.edu/groups/niehs/ambient/ N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - AMBIENT Project; curricula; Dade County Florida; education; environmental geology; Florida; global; high school; K-12 education; local; Miami-Dade County Florida; public health; teacher education; United States ER - TY - JOUR T1 - Reaction Trajectory of Pyrophosphoryl Transfer Catalyzed by 6-Hydroxymethyl- 7, 8-Dihydropterin Pyrophosphokinase AN - 21283382; 5872557 AB - 6-hydroxymethyl-7, 8-dihydropterin pyrophosphokinase (HPPK) catalyzes the Mg super(2+)-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7, 8- dihydropterin (HP). The reaction follows a bi-bi mechanism with ATP as the first substrate and AMP and HP pyrophosphate (HPPP) as the two products. HPPK is a key enzyme in the folate biosynthetic pathway and is essential for microorganisms but absent from mammals. For the HPPK-catalyzed pyrophosphoryl transfer, a reaction coordinate is constructed on the basis of the thermodynamic and transient kinetic data we reported previously, and the reaction trajectory is mapped out with five three-dimensional structures of the enzyme at various liganded states. The five structures are apo-HPPK (ligand-free enzyme), HPPK.MgATP sub(analog) (binary complex of HPPK with its first substrate) and HPPK.MgATP sub(analog).HP (ternary complex of HPPK with both substrates), which we reported previously, and HPPK.AMP.HPPP (ternary complex of HPPK with both product molecules) and HPPK.HPPP (binary complex of HPPK with one product), which we present in this study. JF - Structure AU - Blaszczyk, J AU - Shi, G AU - Li, Y AU - Yan, H AU - Ji, X AD - Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA, jix@ncifcrf.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 467 EP - 475 PB - Cell Press, 1100 Massachusetts Avenue Cambridge MA 02138 USA, [mailto:subs@cell.com], [URL:http://www.cellpress.com] VL - 12 IS - 3 SN - 0969-2126, 0969-2126 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Data processing KW - Thermodynamics KW - Kinetics KW - Microorganisms KW - Enzymes KW - ATP KW - AMP KW - Folic acid KW - pyrophosphates KW - A 01490:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21283382?accountid=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=Structure&rft.atitle=Reaction+Trajectory+of+Pyrophosphoryl+Transfer+Catalyzed+by+6-Hydroxymethyl-+7%2C+8-Dihydropterin+Pyrophosphokinase&rft.au=Blaszczyk%2C+J%3BShi%2C+G%3BLi%2C+Y%3BYan%2C+H%3BJi%2C+X&rft.aulast=Blaszczyk&rft.aufirst=J&rft.date=2004-03-01&rft.volume=12&rft.issue=3&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Structure&rft.issn=09692126&rft_id=info:doi/10.1016%2Fj.str.2004.02.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-03-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Data processing; Thermodynamics; Kinetics; Microorganisms; ATP; Enzymes; AMP; Folic acid; pyrophosphates DO - http://dx.doi.org/10.1016/j.str.2004.02.003 ER - TY - JOUR T1 - Botulinum toxin treatment of occupational and focal hand dystonia AN - 21155111; 11343066 AB - Botulinum toxin is now the first-line therapy for writer's cramp and other occupational dystonias, with well-established efficacy and safety. Future studies will allow us to understand better the physiological effects of injection and to refine and enhance our treatment of focal hand dystonia. JF - Movement Disorders AU - Karp, Barbara Illowsky AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA, karpb@ninds.nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - S116 EP - S119 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 19 IS - S8 SN - 0885-3185, 0885-3185 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Muscle contraction KW - Movement disorders KW - Dystonia KW - Hand KW - Botulinum toxin KW - X 24370:Natural Toxins KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21155111?accountid=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=Movement+Disorders&rft.atitle=Botulinum+toxin+treatment+of+occupational+and+focal+hand+dystonia&rft.au=Karp%2C+Barbara+Illowsky&rft.aulast=Karp&rft.aufirst=Barbara&rft.date=2004-03-01&rft.volume=19&rft.issue=S8&rft.spage=S116&rft.isbn=&rft.btitle=&rft.title=Movement+Disorders&rft.issn=08853185&rft_id=info:doi/10.1002%2Fmds.20025 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Muscle contraction; Movement disorders; Hand; Dystonia; Botulinum toxin DO - http://dx.doi.org/10.1002/mds.20025 ER - TY - JOUR T1 - A Phase I Study of Oral CC-5013 (Lenalidomide, Revlimid super(TM)), a Thalidomide Derivative, in Patients with Refractory Metastatic Cancer AN - 21110328; 11332230 AB - CC-5013 (lenalidomide, Revlimid super(TM)), an immunomodulatory thalidomide analogue (IMiD super(TM)), demonstrated greater potency than did thalidomide in the human vein endothelial cell (HUVEC) proliferation and tube formation assays, respectively (unpublished). These assays also indicated a dose-dependet decrease in HUVEC proliferation and tube formation with increasing concentration of CC-5013. In vitro studies have indicated antimigratory effects of CC-5013 and the inhibition of tumor growth in vivo, but the mechanism of action is not believed to be as a result of its immunomodulatory properties. These studies have led to the development of this phase I clinical study of CC-5013 in patients with refractory metastatic cancer. JF - Clinical Genitourinary Cancer AU - Tohnya, T M AU - Ng, SSW AU - Dahut, W L AU - Wright, J J AU - Arlen, P M AU - Gulley, J L AU - Parker, C AU - Zeldis, J AU - Figg, W D AD - Clinical Pharmacology Research Core, National Cancer Institute/National Institutes of Health, Bethesda, MD, wdfigg@helix.nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 241 EP - 243 VL - 2 IS - 4 SN - 1558-7673, 1558-7673 KW - Toxicology Abstracts KW - Metastases KW - Endothelial cells KW - Veins KW - Thalidomide KW - Tumors KW - Immunomodulation KW - Cancer KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21110328?accountid=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=Clinical+Genitourinary+Cancer&rft.atitle=A+Phase+I+Study+of+Oral+CC-5013+%28Lenalidomide%2C+Revlimid+super%28TM%29%29%2C+a+Thalidomide+Derivative%2C+in+Patients+with+Refractory+Metastatic+Cancer&rft.au=Tohnya%2C+T+M%3BNg%2C+SSW%3BDahut%2C+W+L%3BWright%2C+J+J%3BArlen%2C+P+M%3BGulley%2C+J+L%3BParker%2C+C%3BZeldis%2C+J%3BFigg%2C+W+D&rft.aulast=Tohnya&rft.aufirst=T&rft.date=2004-03-01&rft.volume=2&rft.issue=4&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Clinical+Genitourinary+Cancer&rft.issn=15587673&rft_id=info:doi/10.3816%2FCGC.2004.n.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-12-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Endothelial cells; Metastases; Veins; Thalidomide; Tumors; Immunomodulation; Cancer DO - http://dx.doi.org/10.3816/CGC.2004.n.006 ER - TY - JOUR T1 - S11.5: Cancer mortality among workers in formaldehyde industries AN - 21088506; 11132418 AB - Abstract not available. JF - Biometrical Journal AU - Hauptmann, Michael AU - Lubin, Jay H AU - Stewart, Patricia A AU - Hayes, Richard B AU - Blair, Aaron AD - National Cancer Institute. Bethesda, Maryland, USA, hauptmann@nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 25 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 46 IS - S1 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Workers KW - Mortality KW - Formaldehyde KW - Cancer KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21088506?accountid=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=Biometrical+Journal&rft.atitle=S11.5%3A+Cancer+mortality+among+workers+in+formaldehyde+industries&rft.au=Hauptmann%2C+Michael%3BLubin%2C+Jay+H%3BStewart%2C+Patricia+A%3BHayes%2C+Richard+B%3BBlair%2C+Aaron&rft.aulast=Hauptmann&rft.aufirst=Michael&rft.date=2004-03-01&rft.volume=46&rft.issue=S1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200490226 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Formaldehyde; Mortality; Cancer; Workers DO - http://dx.doi.org/10.1002/bimj.200490226 ER - TY - JOUR T1 - Gill Trematodes (Flukes) in Wild-Caught Killifish (Fundulus heteroclitus) AN - 19816020; 6101604 AB - Three wild caught killifish (Fundulus heteroclitus) on an Institutional Animal Care and Use Committee-approved protocol were found dead within 2 days after being received. The fish were housed in two separate aquaria. Aquarium water was evaluated, and pH, salinity, ammonia, nitrate, and nitrite levels were within acceptable parameters. Several remaining fish appeared to be slow-moving and were presented for necropsy. Multiple, scattered, ulcerated skin lesions (diameter, 1 to 5 mm) were noted at necropsy and were cultured. No pathogenic bacteria were isolated. Wet-mount samples of the gills revealed multiple cysts at the gill margins, each containing a motile organism. No other gill parasites were detected. A diagnosis of trematodiasis was made. The cysts were identified as encysted metacercariae of a digenetic trematode. We surmise that the large numbers of gill flukes combined with the stress of recent shipment likely caused the observed morbidity and mortality. JF - Contemporary Topics in Laboratory Animal Science AU - Goulding AU - Blankenship-Paris, T L AU - Lewbart, G A AU - Myers, PH AU - Demianenko, T K AU - Clark, JA AU - Forsythe, D B AD - Comparative Medicine Branch, National Institute of Environmental Health Sciences, MD C1-06, Research Triangle Park, NC 27709, USA Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 32 EP - 34 VL - 43 IS - 2 SN - 1060-0558, 1060-0558 KW - Mummichog KW - Microbiology Abstracts B: Bacteriology; ASFA 1: Biological Sciences & Living Resources KW - Nitrate KW - Autopsy KW - Parasites KW - Marine invertebrates KW - Laboratory animals KW - Morbidity KW - Marine fish KW - Aquaria KW - Interspecific relationships KW - Salinity effects KW - Nitrite KW - pH effects KW - Gills KW - Marine KW - Mortality KW - Fundulus heteroclitus KW - Ammonia KW - Gill disease KW - Cysts KW - Skin diseases KW - Fish diseases KW - Trematoda KW - Mortality causes KW - Q1 08484:Species interactions: parasites and diseases KW - J 02450:Ecology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19816020?accountid=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=Contemporary+Topics+in+Laboratory+Animal+Science&rft.atitle=Gill+Trematodes+%28Flukes%29+in+Wild-Caught+Killifish+%28Fundulus+heteroclitus%29&rft.au=Goulding%3BBlankenship-Paris%2C+T+L%3BLewbart%2C+G+A%3BMyers%2C+PH%3BDemianenko%2C+T+K%3BClark%2C+JA%3BForsythe%2C+D+B&rft.aulast=Goulding&rft.aufirst=&rft.date=2004-03-01&rft.volume=43&rft.issue=2&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Contemporary+Topics+in+Laboratory+Animal+Science&rft.issn=10600558&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Aquaria; Marine fish; Parasites; Interspecific relationships; Fish diseases; Marine invertebrates; Gill disease; Mortality causes; Gills; Autopsy; Mortality; Nitrate; Ammonia; Laboratory animals; Cysts; Morbidity; Skin diseases; Salinity effects; Nitrite; pH effects; Fundulus heteroclitus; Trematoda; Marine ER - TY - JOUR T1 - Increased Dendritic Cell Numbers Impair Protective Immunity to Intracellular Bacteria Despite Augmenting Antigen-Specific CD8 super(+) T Lymphocyte Responses AN - 18040722; 5859947 AB - Dendritic cells (DCs) reside in tissues, where they function as sentinels, providing an essential link between innate and adaptive immunity. Increasing the numbers of DCs in vivo augments T cell responses, and can cause dramatic CTL- dependent tumor regression. To determine whether greater DC numbers promoted T cell-mediated protection in the context of host defense against intracellular bacteria, we treated mice with Flt3 ligand (Flt3-L) to increase DCs in vivo and challenged them with Listeria monocytogenes. Unexpectedly, after primary challenge with Listeria, the overall control of Listeria infection was impaired in Flt3-L-treated mice, which had greater bacterial burden and mortality than controls. Similar results were obtained when DC numbers were increased by treatment with polyethylene glycol-conjugated GM-CSF rather than Flt3-L and in mice infected with Mycobacterium tuberculosis. Impaired protection was not due to dysfunctional T cell responses, as Flt3-L-treated mice had a greater frequency and absolute number of Ag-specific CD8 super(+) T cells, which produced IFN- gamma , exhibited cytolytic activity, and transferred protection. The increased Listeria burden in Flt3-L-treated mice was preferentially associated with DCs, which were unable to kill Listeria and more resistant to CTL lysis compared with macrophages in vitro. Although we cannot exclude the possibility that other potential effects, in addition to increased numbers of DCs, are shared by Flt3-L and polyethylene glycol-conjugated GM-CSF and contributed to the increase in susceptibility observed in treated mice, these results support the notion that DC numbers must be properly controlled within physiological limits to optimize host defense to intracellular bacterial pathogens. JF - Journal of Immunology AU - Alaniz, R C AU - Sandall, S AU - Thomas, E K AU - Wilson, C B AD - Department of Immunology and National Heart, Lung, and Blood Institute Stipends for Training Aspiring Researchers Program, University of Washington, Seattle, WA 98195 Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 3725 EP - 3735 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 172 IS - 6 SN - 0022-1767, 0022-1767 KW - mice KW - CD8 antigen KW - Flt3L protein KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Bacteria KW - Listeria monocytogenes KW - g-Interferon KW - Granulocyte-macrophage colony-stimulating factor KW - Dendritic cells KW - ^g-Interferon KW - FLT3L protein KW - Lymphocytes T KW - Mycobacterium tuberculosis KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18040722?accountid=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+Immunology&rft.atitle=Increased+Dendritic+Cell+Numbers+Impair+Protective+Immunity+to+Intracellular+Bacteria+Despite+Augmenting+Antigen-Specific+CD8+super%28%2B%29+T+Lymphocyte+Responses&rft.au=Alaniz%2C+R+C%3BSandall%2C+S%3BThomas%2C+E+K%3BWilson%2C+C+B&rft.aulast=Alaniz&rft.aufirst=R&rft.date=2004-03-01&rft.volume=172&rft.issue=6&rft.spage=3725&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Listeria monocytogenes; Mycobacterium tuberculosis; CD8 antigen; FLT3L protein; Dendritic cells; Bacteria; Lymphocytes T; Granulocyte-macrophage colony-stimulating factor; g-Interferon; ^g-Interferon ER - TY - JOUR T1 - Multi-species toxicology approaches for oncology drugs: the US perspective AN - 18002294; 5946279 AB - The Toxicology and Pharmacology Branch (T&PB) of the National Cancer Institute (NCI) performs pharmacological and toxicological evaluations of new oncology agents according to an agent-directed paradigm in which all studies are tailored to each agent. The United States Food and Drug Administration (US FDA) requires that preclinical toxicology studies be conducted in two species, a rodent and a non-rodent for all small molecules, and T&PB has successfully used this formula. While pharmacokinetic (PK) studies are considered optional, T&PB routinely develops new methods for plasma/tissue drug analysis and employs this methodology throughout development to determine kinetics in various species and toxicokinetics in the toxicity studies. In the current era of molecular target-based development, the T&PB also develops or employs methodology to evaluate effects of the new chemical entity on appropriate biomarkers in tumour and normal tissues. In this comprehensive programme, T&PB is able to correlate safety and toxicity with both plasma drug levels and biomarker modulation in two species for a seamless entry into Phase I. JF - European Journal of Cancer AU - Tomaszewski, JE AD - Chief, Toxicology & Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Executive Plaza North, Room 8034, 6130 Executive Boulevard, Rockville, MD 20852, USA Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 907 EP - 913 PB - Elsevier Science Ltd., Pergamon, P.O. Box 800 Kidlington Oxford OX5 1DX UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 40 IS - 5 SN - 0959-8049, 0959-8049 KW - toxicokinetics KW - Toxicology Abstracts KW - Animals KW - USA KW - Plasma KW - Chemotherapy KW - Safety KW - Antineoplastic drugs KW - biomarkers KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18002294?accountid=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=European+Journal+of+Cancer&rft.atitle=Multi-species+toxicology+approaches+for+oncology+drugs%3A+the+US+perspective&rft.au=Tomaszewski%2C+JE&rft.aulast=Tomaszewski&rft.aufirst=JE&rft.date=2004-03-01&rft.volume=40&rft.issue=5&rft.spage=907&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Cancer&rft.issn=09598049&rft_id=info:doi/10.1016%2Fj.ejca.2003.11.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; Toxicity testing; Chemotherapy; Plasma; Safety; biomarkers; Antineoplastic drugs; Animals DO - http://dx.doi.org/10.1016/j.ejca.2003.11.024 ER - TY - JOUR T1 - Flow cytometric analysis of vaccine responses: how many colors are enough? AN - 18000728; 5944823 AB - The past 5 years have seen an explosion in technological advances related to measuring immunogenicity. Specifically, two distinct areas of development have led to considerably more detailed analysis of T cell responses: first, the ability to measure over a dozen distinct antigens expressed by individual cells simultaneously (12-color flow cytometry); and second, a host of assays that rapidly and viably identify antigen-specific T cells. Together, these technologies reveal the complex heterogeneity of an immune response generated during infection or after vaccine challenge. The next 5 years will see the determination of which underlying variables will be most important to quantifying vaccine efficacy. In this manuscript, we discuss these technologies, with a focus on assisting in the design and implementation of immunogenicity trials for future vaccine efforts. JF - Clinical Immunology AU - Roederer, M AU - Brenchley, J M AU - Betts, M R AU - De Rosa, SC AD - ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA, Roederer@nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 199 EP - 205 PB - Elsevier Inc. VL - 110 IS - 3 SN - 1521-6616, 1521-6616 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Flow cytometry KW - Infectious diseases KW - Reviews KW - Lymphocytes T KW - Vaccines KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18000728?accountid=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+Immunology&rft.atitle=Flow+cytometric+analysis+of+vaccine+responses%3A+how+many+colors+are+enough%3F&rft.au=Roederer%2C+M%3BBrenchley%2C+J+M%3BBetts%2C+M+R%3BDe+Rosa%2C+SC&rft.aulast=Roederer&rft.aufirst=M&rft.date=2004-03-01&rft.volume=110&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Clinical+Immunology&rft.issn=15216616&rft_id=info:doi/10.1016%2Fj.clim.2003.11.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Analysis of Immune Function Using Flow Cytometry N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccines; Flow cytometry; Lymphocytes T; Reviews; Infectious diseases DO - http://dx.doi.org/10.1016/j.clim.2003.11.015 ER - TY - JOUR T1 - Identification of a novel CD4i human monoclonal antibody Fab that neutralizes HIV-1 primary isolates from different clades AN - 17962427; 5897357 AB - A new human monoclonal antibody (hmAb), designated m16, was selected by sequential antigen panning (SAP) of a human phage display library against recombinant soluble HIV-1 envelope glycoproteins (Envs) (gp140s) and their complexes with soluble CD4. It bound with high (nM) affinity to gp120 and gp140; the binding was further enhanced by interactions of the Envs with CD4. m16 inhibited cell fusion mediated by the Envs of 9 HIV-1 isolates from clades A, B, E and G with potency on average comparable to that of the broadly neutralizing human monoclonal antibody Fab X5. The identification of a new hmAb with broad neutralizing activity that exhibits differential inhibitory profile suggests a potential for its use as a component of anti-HIV-1 treatments. JF - Antiviral Research AU - Zhang, M AU - Shu, Y AU - Sidorov, I AU - Dimitrov, D S AD - Human Immunovirology and Computational Biology Group, LECB, CCR, NCI-Frederick, NIH, Frederick, MD 21702, USA, dimitrov@ncifcrf.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 161 EP - 164 VL - 61 IS - 3 SN - 0166-3542, 0166-3542 KW - man KW - HIV-1 KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Monoclonal antibodies KW - Phage display KW - Cell fusion KW - CD4 antigen KW - Gene libraries KW - Human immunodeficiency virus 1 KW - W3 33375:Antibodies KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17962427?accountid=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=Antiviral+Research&rft.atitle=Identification+of+a+novel+CD4i+human+monoclonal+antibody+Fab+that+neutralizes+HIV-1+primary+isolates+from+different+clades&rft.au=Zhang%2C+M%3BShu%2C+Y%3BSidorov%2C+I%3BDimitrov%2C+D+S&rft.aulast=Zhang&rft.aufirst=M&rft.date=2004-03-01&rft.volume=61&rft.issue=3&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/10.1016%2Fj.antiviral.2003.09.009 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; Monoclonal antibodies; CD4 antigen; Phage display; Gene libraries; Cell fusion DO - http://dx.doi.org/10.1016/j.antiviral.2003.09.009 ER - TY - JOUR T1 - Detailed Exposure Assessment for a Molecular Epidemiology Study of Benzene in Two Shoe Factories in China AN - 17949821; 5887878 AB - Objectives: We carried out a detailed exposure assessment of benzene and toluene in two shoe factories in Tianjin, China. Our goal was to identify workers with a broad range of benzene exposures, for an epidemiologic study relating exposure to early biologic effects. Methods: A comprehensive exposure survey program was initiated. Over a period of 16 months, 2783 personal solvent exposure samples were collected in two workplaces from 250 workers. Mixed-effects models were used to identify factors affecting exposure. Principal component analyses (PCA) and subsequent regression analyses on the scores of the identified principal components were used to relate potential co-exposures to various exposure sources present in the workplace. Results: The mean benzene exposure level was 21.86 p.p.m. (10th-90th percentiles 5.23-50.63 p.p.m.) in the smaller shoe factory (factory A) and 3.46 p.p.m. (10th-90th percentiles 0.20-7.00 p.p.m.) in the larger shoe factory (factory B). Within-factory exposure levels differed among job titles and were higher for subjects directly involved in handling glues. In contrast, mean toluene levels were relatively similar in the two factories (factory A, 9.52 p.p.m.; factory B, 15.88 p.p.m.). A seasonal trend was identified for both benzene and toluene in factory B. This could be explained in part by changes in air movement and ventilation patterns occurring during the year. A seasonal trend was not present in the smaller shoe factory, where general ventilation was absent. Supplemental analysis showed that exposure levels to other hydrocarbons were low ( less than or equal to 5 p.p.m.), less than 5% of their respective ACGIH threshold limit values, and generally comparable in the two factories. PCA showed that co-exposures in factory B could largely be explained by glue sources that were used in distinct areas in the workplace. Conclusions: We demonstrated the occurrence of a broad range of benzene exposure levels in two shoe manufacturing factories in Tianjin, China. Benzene and toluene exposures were determined in part by the degree of contact with glues, the benzene and toluene content of each glue, air movement and ventilation patterns. The availability of long-term monthly personal monitoring data provides an excellent opportunity to estimate individual exposures at different times during the 1 yr period of observation. JF - Annals of Occupational Hygiene AU - Vermeulen, R AU - Li, G AU - Lan, Q AU - Dosemeci, M AU - Rappaport, S M AU - Bohong, X AU - Smith, M T AU - Zhang, L AU - Hayes, R B AU - Linet, M AU - Mu, R AU - Wang, L AU - Xu, J AU - Yin, S AU - Rothman, N AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Boulevard, Rockville, MD 20892, USA Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 105 EP - 116 VL - 48 IS - 2 SN - 0003-4878, 0003-4878 KW - man KW - molecular epidemiology KW - exposure assessment KW - shoe factories KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Ventilation KW - Toluene KW - Solvents KW - benzene KW - Benzene KW - Factories KW - China, People's Rep. KW - Seasonal variations KW - Occupational exposure KW - X 24156:Environmental impact KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17949821?accountid=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=Annals+of+Occupational+Hygiene&rft.atitle=Detailed+Exposure+Assessment+for+a+Molecular+Epidemiology+Study+of+Benzene+in+Two+Shoe+Factories+in+China&rft.au=Vermeulen%2C+R%3BLi%2C+G%3BLan%2C+Q%3BDosemeci%2C+M%3BRappaport%2C+S+M%3BBohong%2C+X%3BSmith%2C+M+T%3BZhang%2C+L%3BHayes%2C+R+B%3BLinet%2C+M%3BMu%2C+R%3BWang%2C+L%3BXu%2C+J%3BYin%2C+S%3BRothman%2C+N&rft.aulast=Vermeulen&rft.aufirst=R&rft.date=2004-03-01&rft.volume=48&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Annals+of+Occupational+Hygiene&rft.issn=00034878&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.; Solvents; Ventilation; Factories; Seasonal variations; Toluene; benzene; Occupational exposure; Benzene ER - TY - JOUR T1 - Occupational Exposures and Salivary Gland Cancer Mortality Among African American and White Workers in the United States AN - 17938681; 5890281 AB - We conducted a large death certificate-based case-control study to assess occupational risks for salivary gland cancer. African American (168 cases, 672 controls) and white (2237 cases, 8748 controls) cases from 24 states (1984-1989) were matched to controls by age, sex, race, and region. Race- and sex-stratified multiple logistic regression models calculated adjusted odds ratios. The proportion of young cases (<50 years) was greatest among African Americans (20.8% vs. 8.8%). Higher socioeconomic status, ionizing radiation, formaldehyde, solvents, outdoor work, and animal contact were associated with elevated risk among white men. Physical activity reduced mortality risks among men, although significantly only among whites. Odds ratios for formaldehyde, solvents, benzene, and animal contact were 2.0 or greater among African American women, although not statistically significant. These findings suggest occupational and demographic factors needing further investigation. JF - Journal of Occupational and Environmental Medicine AU - Wilson, R T AU - Moore, LE AU - Dosemeci, M AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, DHHS, 6120 Executive Blvd., MSC 7240, Bethesda, MD 20892-7240, USA, rw266w@nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 287 EP - 297 VL - 46 IS - 3 SN - 1076-2752, 1076-2752 KW - epidemiology KW - man KW - salivary gland KW - Pollution Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts; Risk Abstracts KW - Mortality KW - Solvents KW - Formaldehyde KW - Race differences KW - Salivary gland KW - Cancer KW - USA KW - Ionizing radiation KW - Risk factors KW - Ethnic groups KW - Occupational exposure KW - R2 23080:Industrial and labor KW - X 24210:Radiation & radioactive materials KW - X 24156:Environmental impact KW - H 1000:Occupational Safety and Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17938681?accountid=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=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Occupational+Exposures+and+Salivary+Gland+Cancer+Mortality+Among+African+American+and+White+Workers+in+the+United+States&rft.au=Wilson%2C+R+T%3BMoore%2C+LE%3BDosemeci%2C+M&rft.aulast=Wilson&rft.aufirst=R&rft.date=2004-03-01&rft.volume=46&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/10.1097%2F01.jom.0000116802.01928.83 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Mortality; Risk factors; Ionizing radiation; Solvents; Formaldehyde; Race differences; Salivary gland; Cancer; Occupational exposure; Ethnic groups; USA DO - http://dx.doi.org/10.1097/01.jom.0000116802.01928.83 ER - TY - JOUR T1 - The role of supervision in child injury risk: definition, conceptual and measurement issues AN - 17925067; 5862892 AB - The purpose of this paper was to examine caregiver supervision and its role as an active strategy in childhood injury prevention. Through a review of the literature, the authors addressed conceptual and methodological issues related to supervision, such as the question of how to define `adequate supervision.' Three critical dimensions (attention, proximity and continuity) of caregiver supervisory behaviors are identified as important areas for measurement. Presented is a framework for understanding the role of passive and active supervisory behaviors within the social context. The framework includes family and community characteristics and policies/regulations that may be important in caregiver decisions to use active or passive injury prevention strategies. Future research directions are discussed. JF - Injury Control and Safety Promotion AU - Saluja, G AU - Brenner, R AU - Morrongiello, BA AU - Haynie, D AU - Rivera, M AU - Cheng, T L AD - NICHD/NIH, Division of Epidemiology, Statistics and Prevention Research, 6100 Executive Blvd, Room 7, B03 MSC 7510, Bethesda, MD 20892-7510, USA, salujag@mail.nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 17 EP - 22 VL - 11 IS - 1 SN - 1566-0974, 1566-0974 KW - caregiver supervision KW - daycare KW - prevention KW - Health & Safety Science Abstracts; Risk Abstracts KW - Injuries KW - decision making KW - Children KW - Behavior KW - Reviews KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17925067?accountid=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=Injury+Control+and+Safety+Promotion&rft.atitle=The+role+of+supervision+in+child+injury+risk%3A+definition%2C+conceptual+and+measurement+issues&rft.au=Saluja%2C+G%3BBrenner%2C+R%3BMorrongiello%2C+BA%3BHaynie%2C+D%3BRivera%2C+M%3BCheng%2C+T+L&rft.aulast=Saluja&rft.aufirst=G&rft.date=2004-03-01&rft.volume=11&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Injury+Control+and+Safety+Promotion&rft.issn=15660974&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 - Children; Injuries; Reviews; Behavior; decision making ER - TY - JOUR T1 - Aurora kinases dawn as cancer drug targets AN - 17909990; 5864772 AB - A new anticancer compound interferes with aurora kinases, regulators of mitosis. We can now hope for the biology of these kinases to inform clinical trials. JF - Nature Medicine AU - Sausville, E A AD - Developmental Therapeutics Program, National Cancer Institute, Rockville, MD 20852, USA, sausville@nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 234 EP - 235 VL - 10 IS - 3 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Drug discovery KW - Mitosis KW - Reviews KW - Aurora kinase KW - Antitumor agents KW - Clinical trials KW - Cancer KW - W3 33374:Antitumor agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17909990?accountid=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+Medicine&rft.atitle=Aurora+kinases+dawn+as+cancer+drug+targets&rft.au=Sausville%2C+E+A&rft.aulast=Sausville&rft.aufirst=E&rft.date=2004-03-01&rft.volume=10&rft.issue=3&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&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 - Cancer; Drug discovery; Clinical trials; Reviews; Antitumor agents; Mitosis; Aurora kinase ER - TY - JOUR T1 - Specificity grouping of the accessory gene regulator quorum-sensing system of Staphylococcus epidermidis is linked to infection AN - 17909058; 5867675 AB - Staphylococcus epidermidis represents the most frequent pathogen involved in nosocomial infections and infections of indwelling medical devices. The strain-to-strain variation of the gene encoding the quorum-sensing pheromone of S. epidermidis as well as the correlation between specificity groups and origin from infection were determined. The pro-pheromone gene was highly conserved and showed infrequent, non-synonymous, single-nucleotide polymorphisms that led to conservative amino acid exchanges only. Importantly, one specificity group was significantly more frequent among strains isolated from infection. The finding that quorum-sensing specificity groups are linked to infection demonstrates the relevance of quorum-sensing for virulence in this critical human pathogen and contributes to the scientific basis needed for the development of quorum-sensing-targeting drugs. JF - Archives of Microbiology AU - Carmody, AB AU - Otto, M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, The National Institutes of Health, 903 S. 4th Street, National Institute of Allergy and Infectious Diseases, MT 59840, Hamilton, USA Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 250 EP - 253 PB - Springer-Verlag VL - 181 IS - 3 SN - 0302-8933, 0302-8933 KW - Microbiology Abstracts B: Bacteriology KW - Virulence KW - Polymorphism KW - Genetic analysis KW - Cell density KW - Nosocomial infection KW - Staphylococcus epidermidis KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17909058?accountid=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=Archives+of+Microbiology&rft.atitle=Specificity+grouping+of+the+accessory+gene+regulator+quorum-sensing+system+of+Staphylococcus+epidermidis+is+linked+to+infection&rft.au=Carmody%2C+AB%3BOtto%2C+M&rft.aulast=Carmody&rft.aufirst=AB&rft.date=2004-03-01&rft.volume=181&rft.issue=3&rft.spage=250&rft.isbn=&rft.btitle=&rft.title=Archives+of+Microbiology&rft.issn=03028933&rft_id=info:doi/10.1007%2Fs00203-003-0644-2 L2 - http://link.springer.de/link/service/journals/00203/bibs/4181003/41810250.htm LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Staphylococcus epidermidis; Nosocomial infection; Cell density; Genetic analysis; Polymorphism; Virulence DO - http://dx.doi.org/10.1007/s00203-003-0644-2 ER - TY - JOUR T1 - Noncatalytic Assembly of Ribonuclease III with Double-Stranded RNA AN - 17905959; 5872555 AB - Ribonuclease III (RNase III) represents a family of double-stranded RNA (dsRNA) endonucleases. The simplest bacterial enzyme contains an endonuclease domain (endoND) and a dsRNA binding domain (dsRBD). RNase III can affect RNA structure and gene expression in either of two ways: as a dsRNA-processing enzyme that cleaves dsRNA, or as a dsRNA binding protein that binds but does not cleave dsRNA. We previously determined the endoND structure of Aquifex aeolicus RNase III (Aa-RNase III) and modeled a catalytic complex of full- length Aa-RNase III with dsRNA. Here, we present the crystal structure of Aa- RNase III in complex with dsRNA, revealing a noncatalytic assembly. The major differences between the two functional forms of RNase III.dsRNA are the conformation of the protein and the orientation and location of dsRNA. The flexibility of a 7 residue linker between the endoND and dsRBD enables the transition between these two forms. JF - Structure AU - Blaszczyk, J AU - Gan, J AU - Tropea, JE AU - Court, D L AU - Waugh, D S AU - Ji, X AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA, jix@ncifcrf.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 457 EP - 466 PB - Cell Press, 1100 Massachusetts Avenue Cambridge MA 02138 USA, [mailto:subs@cell.com], [URL:http://www.cellpress.com] VL - 12 IS - 3 SN - 0969-2126, 0969-2126 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - RNA-binding protein KW - Double-stranded RNA KW - Aquifex aeolicus KW - Ribonuclease III KW - Assembly KW - Endonuclease KW - Cleavage KW - J 02726:RNA and ribosomes KW - N 14711:RNases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17905959?accountid=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=Structure&rft.atitle=Noncatalytic+Assembly+of+Ribonuclease+III+with+Double-Stranded+RNA&rft.au=Blaszczyk%2C+J%3BGan%2C+J%3BTropea%2C+JE%3BCourt%2C+D+L%3BWaugh%2C+D+S%3BJi%2C+X&rft.aulast=Blaszczyk&rft.aufirst=J&rft.date=2004-03-01&rft.volume=12&rft.issue=3&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Structure&rft.issn=09692126&rft_id=info:doi/10.1016%2Fj.str.2004.02.004 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - RNA-binding protein; Double-stranded RNA; Ribonuclease III; Assembly; Endonuclease; Cleavage; Aquifex aeolicus DO - http://dx.doi.org/10.1016/j.str.2004.02.004 ER - TY - JOUR T1 - Apoptosis is essential for the increased efficacy of alphaviral replicase- based DNA vaccines AN - 17904292; 5872580 AB - Alphaviral replicons can increase the efficacy and immunogenicity of naked nucleic acid vaccines. To study the impact of apoptosis on this increased effectiveness, we co-delivered an anti-apoptotic gene (Bcl-X sub(L)) with the melanocyte/melanoma differentiation antigen TRP-1. Although cells co-transfected with Bcl-X sub(L) lived longer, produced more antigen and elicited increased antibody production in vivo, co-delivery of pro-survival Bcl-X sub(L) with antigen significantly reduced the ability of the replicase-based vaccine to protect against an aggressive tumor challenge. These data show for the first time that the induction of apoptotic cell death of transfected cells in vivo is required for the increased effectiveness of replicase-based vaccines. Our findings also provide an explanation for the paradoxical observation that replicase-based DNA vaccines are much more immunogenic than conventional constructs despite reduced antigen production. JF - Vaccine AU - Leitner, W W AU - Hwang, L N AU - Bergmann-Leitner, E S AU - Finkelstein, SE AU - Frank, S AU - Restifo, N P AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, Bethesda, MD 20892-1502, USA, wolfgang_leitner@nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 1537 EP - 1544 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 22 IS - 11-12 SN - 0264-410X, 0264-410X KW - TRP-1 antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Apoptosis KW - Melanocytes KW - replicase KW - Melanoma KW - DNA vaccines KW - Alphavirus KW - Vaccines KW - Bcl-xL gene KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17904292?accountid=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=Vaccine&rft.atitle=Apoptosis+is+essential+for+the+increased+efficacy+of+alphaviral+replicase-+based+DNA+vaccines&rft.au=Leitner%2C+W+W%3BHwang%2C+L+N%3BBergmann-Leitner%2C+E+S%3BFinkelstein%2C+SE%3BFrank%2C+S%3BRestifo%2C+N+P&rft.aulast=Leitner&rft.aufirst=W&rft.date=2004-03-01&rft.volume=22&rft.issue=11-12&rft.spage=1537&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2003.10.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Alphavirus; DNA vaccines; Vaccines; Melanocytes; Melanoma; Apoptosis; Bcl-xL gene; replicase DO - http://dx.doi.org/10.1016/j.vaccine.2003.10.013 ER - TY - JOUR T1 - NTP-CERHR Expert Panel report on the reproductive and developmental toxicity of 1-bromopropane AN - 17903990; 5859109 AB - The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of the CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction, including development, caused by agents to which humans may be exposed. 1-Bromopropane (1- BP) was nominated by NIOSH and selected for evaluation by the CERHR based primarily on documented evidence of worker exposures and published evidence of reproductive and developmental toxicity in rodents. 1-BP is used in spray adhesives and as a precision cleaner and degreaser. It may also be used as an intermediate in the synthesis of pharmaceuticals, insecticides, quaternary ammonium compounds, flavors, and fragrances and as a solvent for fats, waxes, or resins. The evaluation of 1-BP was a 4-month effort by a 10-member panel of academic, private, and government scientists that culminated in a public meeting in December 2001. At that meeting, the Expert Panel reviewed the scientific evidence on 1-BP and reached conclusions regarding its potential effects on human reproduction and development. The background information on 1-BP and findings of the Expert Panel are contained within this report. Expert Panel reports are intended to (1) interpret the strength of scientific evidence that a given exposure or exposure circumstance may pose a hazard to reproduction and the health and welfare of children; (2) provide objective and scientifically thorough assessments of the scientific evidence that adverse reproductive/developmental health effects are associated with exposure to specific chemicals or classes of chemicals, including descriptions of any uncertainties that would diminish confidence in assessment of risks; and (3) identify knowledge gaps to help establish research and testing priorities. Staff scientists from the CERHR and members of the CERHR Core Committee (oversight committee to the CERHR whose members include NTP participating agencies) have reviewed the report and the CERHR will seek public review and comment through a Federal Register notice. Subsequent to this comment period, the NTP will prepare the NTP-CERHR monograph on 1-bromopropane that contains its conclusions regarding the potential for 1-BP to adversely affect human reproduction or development. The NTP will base its conclusions on the Expert Panel report on 1- bromopropane, any public comments received on that report, and any relevant information available since the Expert Panel Meeting. The NTP-CERHR monograph will include the public comments and the Expert Panel report as appendices. The NTP-CERHR report on 1-bromopropane will be made publicly available and transmitted to health and regulatory agencies. The NTP and the CERHR wish to thank the members of the bromopropanes Expert Panel for their contributions to the evaluation of 1-BP. We greatly appreciate their time, effort, and objectivity during this evaluation process. We also wish to thank the contract staff for their support in convening the Expert Panel and preparing the Expert Panel report. The NTP-CERHR is headquartered at NIEHS, Research Triangle Park, NC and is staffed and administered by scientists and support personnel at NIEHS and at Sciences International, Inc. Alexandria, Virginia. JF - Reproductive Toxicology AU - Shelby, MD AD - P.O. Box 12233, Research Triangle Park, NC 27709, USA., shelby@niehs.nih.gov, Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 157 EP - 187 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 18 IS - 2 SN - 0890-6238, 0890-6238 KW - 1-bromopropane KW - development KW - Health & Safety Science Abstracts; Risk Abstracts; Toxicology Abstracts KW - Chemicals KW - Occupational exposure KW - Toxicity KW - USA KW - Hazardous materials KW - Reviews KW - Teratogenicity KW - Reproduction KW - H 14000:Toxicology KW - X 24250:Reviews KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17903990?accountid=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=Reproductive+Toxicology&rft.atitle=NTP-CERHR+Expert+Panel+report+on+the+reproductive+and+developmental+toxicity+of+1-bromopropane&rft.au=Shelby%2C+MD&rft.aulast=Shelby&rft.aufirst=MD&rft.date=2004-03-01&rft.volume=18&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2Fj.reprotox.2004.01.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; Chemicals; Reviews; Occupational exposure; Reproduction; Toxicity; Hazardous materials; Teratogenicity DO - http://dx.doi.org/10.1016/j.reprotox.2004.01.001 ER - TY - JOUR T1 - Taste preferences and body weight changes in an obesity-prone population AN - 17823735; 6019883 AB - Background: Taste preferences for highly palatable foods rich in sugar and fat may underlie the current epidemic of obesity. Objective: This study aimed to determine whether the hedonic response to sweet and creamy solutions differs between whites and Pima Indians and whether a preference for these tastes predicts weight gain. Design: One hundred twenty-three Pima Indian and 64 white volunteers taste tested solutions of nonfat milk (0.1% fat), whole milk (3.5% fat), half and half (11.3% fat), and cream (37.5% fat) containing 0%, 5%, 10%, or 20% sugar by weight. Solutions were rated for perceived sweetness, creaminess, and pleasantness (hedonic response) on a 100-mm visual analogue scale. Follow-up body weight was measured in 75 Pima Indians 5.5 plus or minus 3.0 (x plus or minus SD) after baseline taste testing. Results: The Pima Indians had a significantly (P = 0.006) lower hedonic response than did the whites (repeated-measures analysis of variance). Neither body size (P = 0.56) nor adiposity (P = 0.86) was a significant predictor of the hedonic response. There was a positive correlation (r = 0.28, P = 0.01) between the maximal hedonic response at baseline and subsequent weight gain in the Pima Indians. Conclusion: Although the Pima Indians liked sweet and creamy solutions less than the whites did, a heightened hedonic response for these solutions among the Pima Indians was associated with weight gain. JF - American Journal of Clinical Nutrition AU - Salbe, AD AU - DelParigi, A AU - Pratley, R E AU - Drewnowski, A AU - Tataranni, P A AD - Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA Y1 - 2004/03/01/ PY - 2004 DA - 2004 Mar 01 SP - 372 EP - 378 VL - 79 IS - 3 SN - 0002-9165, 0002-9165 KW - Chemoreception Abstracts; Physical Education Index KW - Obesity KW - Sweet taste KW - Diet (effects) KW - Epidemics KW - Nutrition (effects) KW - Taste preferences KW - Nutrition KW - Public health KW - Weight KW - Cream KW - Fats KW - Carbohydrates KW - Body weight gain KW - Hedonic response KW - R 18023:Chemoreception correlates of human behavior KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17823735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Clinical+Nutrition&rft.atitle=Taste+preferences+and+body+weight+changes+in+an+obesity-prone+population&rft.au=Salbe%2C+AD%3BDelParigi%2C+A%3BPratley%2C+R+E%3BDrewnowski%2C+A%3BTataranni%2C+P+A&rft.aulast=Salbe&rft.aufirst=AD&rft.date=2004-03-01&rft.volume=79&rft.issue=3&rft.spage=372&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Clinical+Nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Public health; Obesity; Weight; Nutrition (effects); Diet (effects); Carbohydrates; Fats; Hedonic response; Taste preferences; Sweet taste; Body weight gain; Epidemics; Nutrition; Cream ER - TY - JOUR T1 - Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system AN - 17270378; 5851930 AB - The skin commensal and opportunistic pathogen Staphylococcus epidermidis is the leading cause of nosocomial and biofilm-associated infections. Little is known about the mechanisms by which S. epidermidis protects itself against the innate human immune system during colonization and infection. We used scanning electron microscopy to demonstrate that the exopolysaccharide intercellular adhesin (PIA) resides in fibrous strands on the bacterial cell surface, and that lack of PIA production results in complete loss of the extracellular matrix material that has been suggested to mediate immune evasion. Phagocytosis and killing by human polymorphonuclear leucocytes was significantly increased in a mutant strain lacking PIA production compared with the wild-type strain. The mutant strain was also significantly more susceptible to killing by major antibacterial peptides of human skin, cationic human beta -defensin 3 and LL-37, and anionic dermcidin. PIA represents the first defined factor of the staphylococcal biofilm matrix that protects against major components of human innate host defence. JF - Cellular Microbiology AU - Vuong, C AU - Voyich, J M AU - Fischer, E R AU - Braughton, K R AU - Whitney, A R AU - Deleo AU - Otto, M AD - Laboratories of Human Bacterial Pathogenesis and Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840, USA., motto@niaid.nih.gov Y1 - 2004/03// PY - 2004 DA - Mar 2004 SP - 269 EP - 275 PB - Blackwell Science Ltd VL - 6 IS - 3 SN - 1462-5814, 1462-5814 KW - Polysaccharide intercellular adhesin KW - Microbiology Abstracts B: Bacteriology KW - Colonization KW - Cell surface KW - Adhesins KW - Scanning electron microscopy KW - Leukocytes (polymorphonuclear) KW - Immune response KW - Phagocytosis KW - Staphylococcus epidermidis KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17270378?accountid=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+Microbiology&rft.atitle=Polysaccharide+intercellular+adhesin+%28PIA%29+protects+Staphylococcus+epidermidis+against+major+components+of+the+human+innate+immune+system&rft.au=Vuong%2C+C%3BVoyich%2C+J+M%3BFischer%2C+E+R%3BBraughton%2C+K+R%3BWhitney%2C+A+R%3BDeleo%3BOtto%2C+M&rft.aulast=Vuong&rft.aufirst=C&rft.date=2004-03-01&rft.volume=6&rft.issue=3&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Cellular+Microbiology&rft.issn=14625814&rft_id=info:doi/10.1046%2Fj.1462-5822.2004.00367.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Staphylococcus epidermidis; Scanning electron microscopy; Adhesins; Cell surface; Immune response; Colonization; Leukocytes (polymorphonuclear); Phagocytosis DO - http://dx.doi.org/10.1046/j.1462-5822.2004.00367.x ER - TY - JOUR T1 - Acetoaminophen-induced accumulation of 8-oxodeoxyguanosine through reduction of Ogg1 DNA repair enzyme in C6 glioma cells. AN - 71746057; 15031674 AB - Large doses of acetaminophen (APAP) could cause oxidative stress and tissue damage through production of reactive oxygen/nitrogen (ROS/RNS) species and quinone metabolites of APAP. Although ROS/RNS are known to modify DNA, the effect of APAP on DNA modifications has not been studied systematically. In this study, we investigate whether large doses of APAP can modify the nuclear DNA in C6 glioma cells used as a model system, because these cells contain cytochrome p450-related enzymes responsible for APAP metabolism and subsequent toxicity (Geng and Strobel, 1995). Our results revealed that APAP produced ROS and significantly elevated the 8-oxo- deoxyguanosine (8-oxodG) levels in the nucleus of C6 glioma cells in a time and concentration dependent manner. APAP significantly reduced the 8- oxodG incision activity in the nucleus by decreasing the activity and content of a DNA repair enzyme, Ogg1. These results indicate that APAP in large doses can increase the 8-oxodG level partly through significant reduction of Ogg1 DNA repair enzyme. JF - Experimental & molecular medicine AU - Wan, Jie AU - Bae, Myung-Ae AU - Song, Byoung-Joon AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism NIH, 12420 Parklawn Drive, Rockville, MD 20852, USA. Y1 - 2004/02/29/ PY - 2004 DA - 2004 Feb 29 SP - 71 EP - 77 VL - 36 IS - 1 SN - 1226-3613, 1226-3613 KW - Analgesics, Non-Narcotic KW - 0 KW - Reactive Nitrogen Species KW - Reactive Oxygen Species KW - Acetaminophen KW - 362O9ITL9D KW - DNA KW - 9007-49-2 KW - DNA Glycosylases KW - EC 3.2.2.- KW - OGG1 protein, rat KW - Deoxyguanosine KW - G9481N71RO KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Rats KW - Reactive Oxygen Species -- metabolism KW - Animals KW - DNA Repair KW - DNA Damage KW - Humans KW - Glutathione -- metabolism KW - DNA -- metabolism KW - Reactive Nitrogen Species -- metabolism KW - Cell Line, Tumor KW - Deoxyguanosine -- metabolism KW - DNA Glycosylases -- metabolism KW - Glioma -- metabolism KW - Deoxyguanosine -- chemistry KW - Acetaminophen -- metabolism KW - Analgesics, Non-Narcotic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71746057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+molecular+medicine&rft.atitle=Acetoaminophen-induced+accumulation+of+8-oxodeoxyguanosine+through+reduction+of+Ogg1+DNA+repair+enzyme+in+C6+glioma+cells.&rft.au=Wan%2C+Jie%3BBae%2C+Myung-Ae%3BSong%2C+Byoung-Joon&rft.aulast=Wan&rft.aufirst=Jie&rft.date=2004-02-29&rft.volume=36&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Experimental+%26+molecular+medicine&rft.issn=12263613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-10 N1 - Date created - 2004-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Position-specific suppression and enhancement of HIV-1 integrase reactions by minor groove benzo[a]pyrene diol epoxide deoxyguanine adducts: implications for molecular interactions between integrase and substrates. AN - 80181882; 14627697 AB - The viral protein HIV-1 integrase is required for insertion of the viral genome into human chromosomes and for viral replication. Integration proceeds in two consecutive integrase-mediated reactions: 3'-processing and strand transfer. To investigate the DNA minor groove interactions of integrase relative to known sites of integrase action, we synthesized oligodeoxynucleotides containing single covalent adducts of known absolute configuration derived from trans-opening of benzo-[a]pyrene 7,8-diol 9,10-epoxide by the exocyclic 2-amino group of deoxyguanosine at specific positions in a duplex sequence corresponding to the terminus of the viral U5 DNA. Because the orientations of the hydrocarbon in the minor groove are known from NMR solution structures of duplex oligonucleotides containing these deoxyguanosine adducts, a detailed analysis of the relationship between the position of minor groove ligands and integrase interactions is possible. Adducts placed in the DNA minor groove two or three nucleotides from the 3'-processing site inhibited both 3'-processing and strand transfer. Inosine substitution showed that the guanine 2-amino group is required for efficient 3'-processing at one of these positions and for efficient strand transfer at the other. Mapping of the integration sites on both strands of the DNA substrates indicated that the adducts both inhibit strand transfer specifically at the minor groove bound sites and enhance integration at sites up to six nucleotides away from the adducts. These experiments demonstrate the importance of position-specific minor groove contacts for both the integrase-mediated 3'-processing and strand transfer reactions. JF - The Journal of biological chemistry AU - Johnson, Allison A AU - Sayer, Jane M AU - Yagi, Haruhiko AU - Kalena, Govind P AU - Amin, Ronak AU - Jerina, Donald M AU - Pommier, Yves AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. Y1 - 2004/02/27/ PY - 2004 DA - 2004 Feb 27 SP - 7947 EP - 7955 VL - 279 IS - 9 SN - 0021-9258, 0021-9258 KW - DNA, Viral KW - 0 KW - Recombinant Proteins KW - benzo(a)pyrene 7,8-diol-9,10-epoxide-N2-deoxyguanosine KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA KW - 9007-49-2 KW - HIV Integrase KW - EC 2.7.7.- KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - DNA, Viral -- chemistry KW - Magnetic Resonance Spectroscopy KW - Binding Sites KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analogs & derivatives KW - DNA -- metabolism KW - DNA -- chemistry KW - Deoxyguanosine -- pharmacology KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- pharmacology KW - Deoxyguanosine -- chemistry KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - HIV Integrase -- metabolism KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80181882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Position-specific+suppression+and+enhancement+of+HIV-1+integrase+reactions+by+minor+groove+benzo%5Ba%5Dpyrene+diol+epoxide+deoxyguanine+adducts%3A+implications+for+molecular+interactions+between+integrase+and+substrates.&rft.au=Johnson%2C+Allison+A%3BSayer%2C+Jane+M%3BYagi%2C+Haruhiko%3BKalena%2C+Govind+P%3BAmin%2C+Ronak%3BJerina%2C+Donald+M%3BPommier%2C+Yves&rft.aulast=Johnson&rft.aufirst=Allison&rft.date=2004-02-27&rft.volume=279&rft.issue=9&rft.spage=7947&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 - 2004-05-03 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of phosphorylation in D1 dopamine receptor desensitization: evidence for a novel mechanism of arrestin association. AN - 80180626; 14660631 AB - Homologous desensitization of D(1) dopamine receptors is thought to occur through their phosphorylation leading to arrestin association which interdicts G protein coupling. In order to identify the relevant domains of receptor phosphorylation, and to determine how this leads to arrestin association, we created a series of mutated D(1) receptor constructs. In one mutant, all of the serine/threonine residues within the 3rd cytoplasmic domain were altered (3rdTOT). A second construct was created in which only three of these serines (serines 256, 258, and 259) were mutated (3rd234). We also created four truncation mutants of the carboxyl terminus (T347, T369, T394, and T404). All of these constructs were comparable with the wild-type receptor with respect to expression and adenylyl cyclase activation. In contrast, both of the 3rd loop mutants exhibited attenuated agonist-induced receptor phosphorylation that was correlated with an impaired desensitization response. Sequential truncation of the carboxyl terminus of the receptor resulted in a sequential loss of agonist-induced phosphorylation. No phosphorylation was observed with the most severely truncated T347 mutant. Surprisingly, all of the truncated receptors exhibited normal desensitization. The ability of the receptor constructs to promote arrestin association was evaluated using arrestin-green fluorescent protein translocation assays and confocal fluorescence microscopy. The 3rd234 mutant receptor was impaired in its ability to induce arrrestin translocation, whereas the T347 mutant was comparable with wild type. Our data suggest a model in which arrestin directly associates with the activated 3rd cytoplasmic domain in an agonist-dependent fashion; however, under basal conditions, this is sterically prevented by the carboxyl terminus of the receptor. Receptor activation promotes the sequential phosphorylation of residues, first within the carboxyl terminus and then the 3rd cytoplasmic loop, thereby dissociating these domains and allowing arrestin to bind to the activated 3rd loop. Thus, the role of receptor phosphorylation is to allow access of arrestin to its receptor binding domain rather than to create an arrestin binding site per se. JF - The Journal of biological chemistry AU - Kim, Ok-Jin AU - Gardner, Benjamin R AU - Williams, Daniel B AU - Marinec, Paul S AU - Cabrera, David M AU - Peters, Jennifer D AU - Mak, Chun C AU - Kim, Kyeong-Man AU - Sibley, David R AD - Molecular Neuropharmacology Section, NINDS, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. Y1 - 2004/02/27/ PY - 2004 DA - 2004 Feb 27 SP - 7999 EP - 8010 VL - 279 IS - 9 SN - 0021-9258, 0021-9258 KW - Arrestin KW - 0 KW - Benzazepines KW - Luminescent Proteins KW - Receptors, Dopamine D1 KW - Recombinant Proteins KW - Tritium KW - 10028-17-8 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - Cyclic AMP -- biosynthesis KW - Electrophoresis, Polyacrylamide Gel KW - Biological Transport KW - Gene Expression KW - Benzazepines -- metabolism KW - Amino Acid Sequence KW - Radioligand Assay KW - Biotinylation KW - Structure-Activity Relationship KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Transfection KW - Molecular Sequence Data KW - Luminescent Proteins -- genetics KW - Cell Line KW - Protein Conformation KW - Arrestin -- metabolism KW - Receptors, Dopamine D1 -- genetics KW - Receptors, Dopamine D1 -- chemistry KW - Arrestin -- genetics KW - Receptors, Dopamine D1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80180626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+phosphorylation+in+D1+dopamine+receptor+desensitization%3A+evidence+for+a+novel+mechanism+of+arrestin+association.&rft.au=Kim%2C+Ok-Jin%3BGardner%2C+Benjamin+R%3BWilliams%2C+Daniel+B%3BMarinec%2C+Paul+S%3BCabrera%2C+David+M%3BPeters%2C+Jennifer+D%3BMak%2C+Chun+C%3BKim%2C+Kyeong-Man%3BSibley%2C+David+R&rft.aulast=Kim&rft.aufirst=Ok-Jin&rft.date=2004-02-27&rft.volume=279&rft.issue=9&rft.spage=7999&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 - 2004-05-03 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Definition of the consensus motif recognized by gamma-adaptin ear domains. AN - 80174713; 14665628 AB - The heterotetrameric adaptor complex 1 (AP-1) and the monomeric Golgi-localized, gamma ear-containing, Arf-binding (GGA) proteins are components of clathrin coats associated with the trans-Golgi network and endosomes. The carboxyl-terminal ear domains (or gamma-adaptin ear (GAE) domains) of two gamma-adaptin subunit isoforms of AP-1 and of the GGAs are structurally similar and bind to a common set of accessory proteins. In this study, we have systematically defined a core tetrapeptide motif PsiG(P/D/E)(Psi/L/M) (where Psi is an aromatic residue), which is responsible for the interactions of accessory proteins with GAE domains. The definition of this motif has allowed us to identify novel GAE-binding partners named NECAP and aftiphilin, which also contain clathrin-binding motifs. These findings shed light on the mechanism of accessory protein recruitment to trans-Golgi network and endosomal clathrin coats. JF - The Journal of biological chemistry AU - Mattera, Rafael AU - Ritter, Brigitte AU - Sidhu, Sachdev S AU - McPherson, Peter S AU - Bonifacino, Juan S AD - Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/02/27/ PY - 2004 DA - 2004 Feb 27 SP - 8018 EP - 8028 VL - 279 IS - 9 SN - 0021-9258, 0021-9258 KW - Adaptor Protein Complex 1 KW - 0 KW - Adaptor Protein Complex gamma Subunits KW - Adaptor Proteins, Vesicular Transport KW - CLINT1 protein, human KW - Carrier Proteins KW - Clathrin KW - Luminescent Proteins KW - Peptide Fragments KW - Peptide Library KW - Recombinant Fusion Proteins KW - SYNRG protein, human KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Clathrin -- metabolism KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Humans KW - Two-Hybrid System Techniques KW - Mice KW - Amino Acid Sequence KW - Glutathione Transferase -- genetics KW - Biotinylation KW - Structure-Activity Relationship KW - Saccharomyces cerevisiae KW - Mutagenesis KW - Binding Sites KW - Microscopy, Fluorescence KW - Peptide Fragments -- chemistry KW - Molecular Sequence Data KW - Consensus Sequence KW - Luminescent Proteins -- genetics KW - Adaptor Protein Complex gamma Subunits -- chemistry KW - Adaptor Protein Complex gamma Subunits -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80174713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Definition+of+the+consensus+motif+recognized+by+gamma-adaptin+ear+domains.&rft.au=Mattera%2C+Rafael%3BRitter%2C+Brigitte%3BSidhu%2C+Sachdev+S%3BMcPherson%2C+Peter+S%3BBonifacino%2C+Juan+S&rft.aulast=Mattera&rft.aufirst=Rafael&rft.date=2004-02-27&rft.volume=279&rft.issue=9&rft.spage=8018&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 - 2004-05-03 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY367088; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Catalytic Domain of Escherichia coli Lon Protease Has a Unique Fold and a Ser-Lys Dyad in the Active Site AN - 19267286; 5837767 AB - ATP-dependent Lon protease degrades specific short-lived regulatory proteins as well as defective and abnormal proteins in the cell. The crystal structure of the proteolytic domain (P domain) of the Escherichia coli Lon has been solved by single-wavelength anomalous dispersion and refined at 1.75-Aa resolution. The P domain was obtained by chymotrypsin digestion of the full-length, proteolytically inactive Lon mutant (S679A) or by expression of a recombinant construct encoding only this domain. The P domain has a unique fold and assembles into hexameric rings that likely mimic the oligomerization state of the holoenzyme. The hexamer is dome-shaped, with the six N termini oriented toward the narrower ring surface, which is thus identified as the interface with the ATPase domain in full-length Lon. The catalytic sites lie in a shallow concavity on the wider distal surface of the hexameric ring and are connected to the proximal surface by a narrow axial channel with a diameter of ~18 Aa. Within the active site, the proximity of Lys super(722) to the side chain of the mutated Ala super(679) and the absence of other potential catalytic side chains establish that Lon employs a Ser super(679)-Lys super(722) dyad for catalysis. Alignment of the P domain catalytic pocket with those of several Ser-Lys dyad peptide hydrolases provides a model of substrate binding, suggesting that polypeptides are oriented in the Lon active site to allow nucleophilic attack by the serine hydroxyl on the si-face of the peptide bond. JF - Journal of Biological Chemistry AU - Botos, I AU - Melnikov, EE AU - Cherry, S AU - Tropea, JE AU - Khalatova, A G AU - Rasulova, F AU - Dauter, Z AU - Maurizi, M R AU - Rotanova, T V AU - Wlodawer, A AU - Gustchina, A AD - Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702-1201, alla@ncifcrf.gov Y1 - 2004/02/27/ PY - 2004 DA - 2004 Feb 27 SP - 8140 EP - 8148 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 9 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology KW - Endopeptidase La KW - Protein folding KW - Crystal structure KW - Escherichia coli KW - Active sites KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19267286?accountid=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=The+Catalytic+Domain+of+Escherichia+coli+Lon+Protease+Has+a+Unique+Fold+and+a+Ser-Lys+Dyad+in+the+Active+Site&rft.au=Botos%2C+I%3BMelnikov%2C+EE%3BCherry%2C+S%3BTropea%2C+JE%3BKhalatova%2C+A+G%3BRasulova%2C+F%3BDauter%2C+Z%3BMaurizi%2C+M+R%3BRotanova%2C+T+V%3BWlodawer%2C+A%3BGustchina%2C+A&rft.aulast=Botos&rft.aufirst=I&rft.date=2004-02-27&rft.volume=279&rft.issue=9&rft.spage=8140&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M312243200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Crystal structure; Endopeptidase La; Active sites; Protein folding DO - http://dx.doi.org/10.1074/jbc.M312243200 ER - TY - CPAPER T1 - CD34+ cells cultured in stem cell factor and IL-2 generate CD56+ cells with antiproliferative effects on tumor cell lines AN - 39882702; 3819500 AU - Sconocchia, G AU - Hiroshi, F AU - Katayoun, R AU - Keyvan, K AU - Frank, E O AU - Mark, A AU - Nancy, H AU - John, B Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39882702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=CD34%2B+cells+cultured+in+stem+cell+factor+and+IL-2+generate+CD56%2B+cells+with+antiproliferative+effects+on+tumor+cell+lines&rft.au=Sconocchia%2C+G%3BHiroshi%2C+F%3BKatayoun%2C+R%3BKeyvan%2C+K%3BFrank%2C+E+O%3BMark%2C+A%3BNancy%2C+H%3BJohn%2C+B&rft.aulast=Sconocchia&rft.aufirst=G&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for Biological Therapy of Cancer, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@isbtc.org; URL: www.isbtc.org. Poster Paper No. 9 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Functional flow cytometry for understanding mechanisms of toxicity AN - 39817690; 3824043 AU - Burchiel, S W Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39817690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Functional+flow+cytometry+for+understanding+mechanisms+of+toxicity&rft.au=Burchiel%2C+S+W&rft.aulast=Burchiel&rft.aufirst=S&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Amer. Coll. f. 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Poster Paper No. 70 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Role of anti-inflammatory and other factors in determining susceptibility to idiosyncratic drug-induced liver disease AN - 39802524; 3822495 AU - Pohl, L Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39802524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Role+of+anti-inflammatory+and+other+factors+in+determining+susceptibility+to+idiosyncratic+drug-induced+liver+disease&rft.au=Pohl%2C+L&rft.aulast=Pohl&rft.aufirst=L&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for the Study of Xenobiotics, URL: www.issx.org. Paper No. 5 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Vascular injury by the Ebola virus glycoprotein AN - 39788981; 3819315 AU - Nabel, G J Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39788981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Vascular+injury+by+the+Ebola+virus+glycoprotein&rft.au=Nabel%2C+G+J&rft.aulast=Nabel&rft.aufirst=G&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Microbiology, 1752 N Street N.W., Washington, DC 20036, USA; URL: www.icaac.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Pre-clinical safety studies to support clinical trials with DNA vaccines to prevent HIV/AIDS AN - 39779740; 3824048 AU - Sheets, R Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39779740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Pre-clinical+safety+studies+to+support+clinical+trials+with+DNA+vaccines+to+prevent+HIV%2FAIDS&rft.au=Sheets%2C+R&rft.aulast=Sheets&rft.aufirst=R&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Amer. Coll. f. Toxicology, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-571-1840; fax: 301-571-1852; email: ekagan@act.faseb.org; URL: www.actox.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Fluorescence-based in vivo models for monitoring and quantitating cytokine- or chemotherapy-induced alterations in the growth, metastasis, angiogenesis and apoptosis of neuroblastoma tumors AN - 39773474; 3819554 AU - Stauffer, J K AU - Hixon, JA AU - Back, T C AU - Lincoln, E AU - Khan, T AU - Wigginton, J M Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39773474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Fluorescence-based+in+vivo+models+for+monitoring+and+quantitating+cytokine-+or+chemotherapy-induced+alterations+in+the+growth%2C+metastasis%2C+angiogenesis+and+apoptosis+of+neuroblastoma+tumors&rft.au=Stauffer%2C+J+K%3BHixon%2C+JA%3BBack%2C+T+C%3BLincoln%2C+E%3BKhan%2C+T%3BWigginton%2C+J+M&rft.aulast=Stauffer&rft.aufirst=J&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for Biological Therapy of Cancer, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@isbtc.org; URL: www.isbtc.org. Poster Paper No. 63 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Metastasis-promoting laminin-1 peptide up-regulates fibronectin expression in malignant cells AN - 39772669; 3818916 AU - Engbring, JA AU - Hossain, R AU - Koblinski, YE AU - Kleinman, H K Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39772669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Metastasis-promoting+laminin-1+peptide+up-regulates+fibronectin+expression+in+malignant+cells&rft.au=Engbring%2C+JA%3BHossain%2C+R%3BKoblinski%2C+YE%3BKleinman%2C+H+K&rft.aulast=Engbring&rft.aufirst=JA&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Magic Touch Consultancies Pty Ltd, P.O. Box 717, Caringbah, Sydney NSW 1495, Australia; URL: www.magicdatabases.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Subclones of a streptozotocin induced renal cell carcinoma as a new model for investigation of treatments for kidney cancer AN - 39769313; 3819583 AU - Eilene Gruys, M AU - Back, T AU - Murphy, W AU - Welniak, L AU - Subleski, J AU - Wiltrout, R Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39769313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Subclones+of+a+streptozotocin+induced+renal+cell+carcinoma+as+a+new+model+for+investigation+of+treatments+for+kidney+cancer&rft.au=Eilene+Gruys%2C+M%3BBack%2C+T%3BMurphy%2C+W%3BWelniak%2C+L%3BSubleski%2C+J%3BWiltrout%2C+R&rft.aulast=Eilene+Gruys&rft.aufirst=M&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for Biological Therapy of Cancer, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@isbtc.org; URL: www.isbtc.org. Poster Paper No. 92 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Induction of human CYP2C9 is regulated by the pregnane X receptor (PXR) AN - 39761275; 3822720 AU - Chen, Y Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39761275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Induction+of+human+CYP2C9+is+regulated+by+the+pregnane+X+receptor+%28PXR%29&rft.au=Chen%2C+Y&rft.aulast=Chen&rft.aufirst=Y&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for the Study of Xenobiotics, URL: www.issx.org. Poster Paper No. 231 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Rationale for independent site clean-up and radiological clearance standards AN - 39746107; 3817764 AU - Genoa, P Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39746107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Rationale+for+independent+site+clean-up+and+radiological+clearance+standards&rft.au=Genoa%2C+P&rft.aulast=Genoa&rft.aufirst=P&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: ICEM'03, c/o Laser Options, Inc.; phone: +1(520) 292-5652; fax: +1(520) 292-9080; email: dmccomb@laser-options.com; URL: www.icemconf.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Elispot assay modifications in immunological monitoring AN - 39734354; 3819606 AU - Malyguine, A AU - Strobl, S AU - Shafer-Weaver, K AU - Derby, E AU - Burkett, M AU - Ulderich, T AU - Baseler, M Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39734354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Elispot+assay+modifications+in+immunological+monitoring&rft.au=Malyguine%2C+A%3BStrobl%2C+S%3BShafer-Weaver%2C+K%3BDerby%2C+E%3BBurkett%2C+M%3BUlderich%2C+T%3BBaseler%2C+M&rft.aulast=Malyguine&rft.aufirst=A&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for Biological Therapy of Cancer, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@isbtc.org; URL: www.isbtc.org. Poster Paper No. 115 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Phase I investigation of dose-intensive intravenous IL-12/pulse IL-2 in adults with advanced solid tumors AN - 39734276; 3819592 AU - Wigginton, J AU - Donovan, C AU - Choyke, P AU - Wiltrout, R AU - Janik, J Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39734276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Phase+I+investigation+of+dose-intensive+intravenous+IL-12%2Fpulse+IL-2+in+adults+with+advanced+solid+tumors&rft.au=Wigginton%2C+J%3BDonovan%2C+C%3BChoyke%2C+P%3BWiltrout%2C+R%3BJanik%2C+J&rft.aulast=Wigginton&rft.aufirst=J&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for Biological Therapy of Cancer, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@isbtc.org; URL: www.isbtc.org. Poster Paper No. 101 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Making mouse memories - The molecular basis of social cognition AN - 39733777; 3824115 AU - Insel, T Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39733777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Making+mouse+memories+-+The+molecular+basis+of+social+cognition&rft.au=Insel%2C+T&rft.aulast=Insel&rft.aufirst=T&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 5th Brain Research Symposium Secretariat, Tracy Collier, 7 Gibbs Road, Banbury OX16 3HJ, 44 (01295) 253 334; phone: 44 (01295) 253 334; fax: tracy2.collier@virgin.net; URL: www.brainres-meeting.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - CD40 signaling in renal cell carcinoma leads to increased cytokine expression and decreased tumor size AN - 39731043; 3819588 AU - Shorts, L AU - Back, T AU - Blazer, B AU - Murphy, W AU - Wiltrout, R Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39731043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=CD40+signaling+in+renal+cell+carcinoma+leads+to+increased+cytokine+expression+and+decreased+tumor+size&rft.au=Shorts%2C+L%3BBack%2C+T%3BBlazer%2C+B%3BMurphy%2C+W%3BWiltrout%2C+R&rft.aulast=Shorts&rft.aufirst=L&rft.date=2004-02-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for Biological Therapy of Cancer, 611 East Wells Street, Milwaukee, WI 53202, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@isbtc.org; URL: www.isbtc.org. Poster Paper No. 97 N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators AN - 17908356; 5866836 AB - Corticotropin (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is a heterogeneous condition in which cortisol secretion may be mediated by gastrointestinal peptide (GIP), vasopressin, catecholamines and other hormones. We studied the expression profile of AIMAH by genomic cDNA microarray analysis. Total RNA was extracted from eight tissues (three GIP-dependent) and compared to total RNA obtained from adrenal glands from 62 normal subjects. Genes had to be altered in 75% of the patients, and be up- or downregulated at a cutoff ratio of at least 2.0; 82 and 31 genes were found to be consistently up- and downregulated, respectively. Among the former were regulators of transcription, chromatin remodeling, and cell cycle and adhesion. Downregulated sequences included genes involved in immune responses and insulin signaling. Hierarchical clustering correlated with the two main AIMAH diagnostic groups: GIP-dependent and non-GIP-dependent. The genes encoding the 7B2 protein (SGNE1) and WNT1-inducible signaling pathway protein 2 (WISP2) were specifically overexpressed in the GIP-dependent AIMAH. For these, and six more genes, the data were validated by semiquantitative amplification in samples from a total of 32 patients (the original eight, six more cases of AIMAH, and 18 other adrenocortical hyperplasias and tumors) and the H295R adrenocortical cancer cell line. In conclusion, our data confirmed AIMAH's clinical heterogeneity by identifying molecularly distinct diagnostic subgroups. Several candidate genes that may be responsible for AIMAH formation and/or progression were also identified, suggesting pathways that affect the cell cycle, adhesion and transcription as possible mediators of adrenocortical hyperplasia. JF - Oncogene AU - Bourdeau, I AU - Antonini AU - Lacroix, A AU - Kirschner, L S AU - Matyakhina, L AU - Lorang, D AU - Libutti, S K AU - Stratakis, CA AD - Section on Genetics and Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 10 Center Dr. MSC1862, Bethesda, MD 20892-1862, USA, stratakc@mail.nih.gov Y1 - 2004/02/26/ PY - 2004 DA - 2004 Feb 26 SP - 1575 EP - 1585 VL - 23 IS - 8 SN - 0950-9232, 0950-9232 KW - adrenocortical hyperplasia KW - gastrointestinal peptide KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - Chromatin remodeling KW - Cell cycle KW - Transcription KW - DNA microarrays KW - Insulin KW - Tumor cell lines KW - Catecholamines KW - Vasopressin KW - W 30965:Miscellaneous, Reviews KW - W3 33130:Genetic based (PCR, etc.) KW - B 26000:ONCOGENES AND GROWTH FACTORS: GENERAL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17908356?accountid=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=Oncogene&rft.atitle=Gene+array+analysis+of+macronodular+adrenal+hyperplasia+confirms+clinical+heterogeneity+and+identifies+several+candidate+genes+as+molecular+mediators&rft.au=Bourdeau%2C+I%3BAntonini%3BLacroix%2C+A%3BKirschner%2C+L+S%3BMatyakhina%2C+L%3BLorang%2C+D%3BLibutti%2C+S+K%3BStratakis%2C+CA&rft.aulast=Bourdeau&rft.aufirst=I&rft.date=2004-02-26&rft.volume=23&rft.issue=8&rft.spage=1575&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/10.1038%2Fsj.onc.1207277 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cell cycle; Transcription; Catecholamines; Insulin; Tumor cell lines; DNA microarrays; Chromatin remodeling; Vasopressin DO - http://dx.doi.org/10.1038/sj.onc.1207277 ER - TY - JOUR T1 - Crystal structure of a benzo[a]pyrene diol epoxide adduct in a ternary complex with a DNA polymerase. AN - 71674026; 14982998 AB - The first occupation-associated cancers to be recognized were the sooty warts (cancers of the scrotum) suffered by chimney sweeps in 18th century England. In the 19th century, high incidences of skin cancers were noted among fuel industry workers. By the early 20th century, malignant skin tumors were produced in laboratory animals by repeatedly painting them with coal tar. The culprit in coal tar that induces cancer was finally isolated in 1933 and determined to be benzo[a]pyrene (BP), a polycyclic aromatic hydrocarbon. A residue of fuel and tobacco combustion and frequently ingested by humans, BP is metabolized in mammals to benzo[a]pyrene diol epoxide (BPDE), which forms covalent DNA adducts and induces tumor growth. In the 70 yr since its isolation, BP has been the most studied carcinogen. Yet, there has been no crystal structure of a BPDE DNA adduct. We report here the crystal structure of a BPDE-adenine adduct base-paired with thymine at a template-primer junction and complexed with the lesion-bypass DNA polymerase Dpo4 and an incoming nucleotide. Two conformations of the BPDE, one intercalated between base pairs and another solvent-exposed in the major groove, are observed. The latter conformation, which can be stabilized by organic solvents that reduce the dielectric constant, seems more favorable for DNA replication by Dpo4. These structures also suggest a mechanism by which mutations are generated during replication of DNA containing BPDE adducts. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Ling, Hong AU - Sayer, Jane M AU - Plosky, Brian S AU - Yagi, Haruhiko AU - Boudsocq, François AU - Woodgate, Roger AU - Jerina, Donald M AU - Yang, Wei AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/02/24/ PY - 2004 DA - 2004 Feb 24 SP - 2265 EP - 2269 VL - 101 IS - 8 SN - 0027-8424, 0027-8424 KW - Mutagens KW - 0 KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Base Pairing KW - Base Sequence KW - Mutagens -- metabolism KW - Crystallography, X-Ray KW - Nucleic Acid Conformation KW - Mutagens -- chemistry KW - Protein Conformation KW - Binding Sites KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- metabolism KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry 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/71674026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Crystal+structure+of+a+benzo%5Ba%5Dpyrene+diol+epoxide+adduct+in+a+ternary+complex+with+a+DNA+polymerase.&rft.au=Ling%2C+Hong%3BSayer%2C+Jane+M%3BPlosky%2C+Brian+S%3BYagi%2C+Haruhiko%3BBoudsocq%2C+Fran%C3%A7ois%3BWoodgate%2C+Roger%3BJerina%2C+Donald+M%3BYang%2C+Wei&rft.aulast=Ling&rft.aufirst=Hong&rft.date=2004-02-24&rft.volume=101&rft.issue=8&rft.spage=2265&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 - 2004-04-09 N1 - Date created - 2004-02-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1S0M; PDB N1 - SuppNotes - Cited By: Cell. 2001 Oct 5;107(1):91-102 [11595188] Mol Cell. 2001 Aug;8(2):427-37 [11545744] J Biol Chem. 2002 Apr 5;277(14):11765-71 [11821420] Biochemistry. 2002 May 14;41(19):6100-6 [11994005] Science. 2002 May 31;296(5573):1627-30 [12040171] J Biol Chem. 2002 Aug 2;277(31):28157-66 [12023283] J Biol Chem. 2002 Aug 23;277(34):30488-94 [12063247] Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15548-53 [12432099] Nucleic Acids Res. 2002 Dec 1;30(23):5284-92 [12466554] Biochemistry. 2003 Feb 18;42(6):1410-20 [12578353] Curr Opin Struct Biol. 2003 Feb;13(1):23-30 [12581656] Nature. 1974 Nov 22;252(5481):326-8 [4473724] Proc Natl Acad Sci U S A. 1978 Nov;75(11):5358-61 [281685] Nature. 1983 Jun 9-15;303(5917):468-72 [6304528] J Biomol Struct Dyn. 1989 Feb;6(4):655-67 [2619933] Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 [2025413] Adv Exp Med Biol. 1991;283:533-53 [2069024] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11227-30 [1763036] Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6498-502 [8341661] Chem Res Toxicol. 1997 Feb;10(2):111-46 [9049424] Biochemistry. 1997 Nov 11;36(45):13780-90 [9374854] Biochemistry. 1998 Jun 23;37(25):9127-37 [9636059] Biochemistry. 1998 Jul 14;37(28):10164-72 [9665722] Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 [9757107] Chem Res Toxicol. 1999 Mar;12(3):258-63 [10077488] Mutat Res. 1999 Jul 15;443(1-2):139-47 [10415437] Biochemistry. 1999 Aug 17;38(33):10831-42 [10451380] Proteins. 1991;11(4):281-96 [1758883] Chem Res Toxicol. 2000 Sep;13(9):811-22 [10995253] Mol Microbiol. 2000 Oct;38(2):299-307 [11069656] Biochemistry. 2001 May 22;40(20):5870-81 [11352722] Chem Res Toxicol. 2001 Jun;14(6):708-19 [11409942] Mol Cell. 2001 Aug;8(2):417-26 [11545743] Nat Struct Biol. 2001 Nov;8(11):984-9 [11685247] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cells adapted to high NaCl have many DNA breaks and impaired DNA repair both in cell culture and in vivo. AN - 71672238; 14983007 AB - Acute exposure of cells in culture to high NaCl damages DNA and impairs its repair. However, after several hours of cell cycle arrest, cells multiply in the hypertonic medium. Here, we show that, although adapted cells proliferate rapidly and do not become apoptotic, they nevertheless contain numerous DNA breaks, which do not elicit a DNA damage response. Thus, in adapted cells, Mre11 exonuclease is mainly present in the cytoplasm, rather than nucleus, and histone H2AX and chk1 are not phosphorylated, as they normally would be in response to DNA damage. Also, the adapted cells are deficient in repair of luciferase reporter plasmids damaged by UV irradiation. On the other hand, the DNA damage response activates rapidly when the level of NaCl is reduced. Then, Mre11 moves into the nucleus, and H2AX and chk1 become phosphorylated. Renal inner medullary cells in vivo are normally exposed to a variable, but always high, level of NaCl. As with adapted cells in culture, inner medullary cells in normal mice exhibit numerous DNA breaks. These DNA breaks are rapidly repaired when the NaCl level is decreased by injection of the diuretic furosemide. Moreover, repair of DNA breaks induced by ionizing radiation is inhibited in the inner medulla. Histone H2AX does not become phosphorylated, and repair synthesis is not detectable in response to total body irradiation unless NaCl is lowered by furosemide. Thus, both in cell culture and in vivo, although cells adapt to high NaCl, their DNA is damaged and its repair is inhibited. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Dmitrieva, Natalia I AU - Cai, Qi AU - Burg, Maurice B AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1603, USA. dmitrien@nhlbi.nih.gov Y1 - 2004/02/24/ PY - 2004 DA - 2004 Feb 24 SP - 2317 EP - 2322 VL - 101 IS - 8 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - Mre11a protein, mouse KW - Sodium Chloride KW - 451W47IQ8X KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Animals KW - Comet Assay KW - Dose-Response Relationship, Drug KW - Kidney -- drug effects KW - Kidney -- physiology KW - Mice KW - Mice, Inbred Strains KW - Cells, Cultured KW - Kinetics KW - DNA-Binding Proteins -- drug effects KW - Mitotic Index KW - Male KW - DNA-Binding Proteins -- metabolism KW - DNA Repair -- genetics KW - DNA Repair -- drug effects KW - Sodium Chloride -- pharmacology KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71672238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cells+adapted+to+high+NaCl+have+many+DNA+breaks+and+impaired+DNA+repair+both+in+cell+culture+and+in+vivo.&rft.au=Dmitrieva%2C+Natalia+I%3BCai%2C+Qi%3BBurg%2C+Maurice+B&rft.aulast=Dmitrieva&rft.aufirst=Natalia&rft.date=2004-02-24&rft.volume=101&rft.issue=8&rft.spage=2317&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 - 2004-04-09 N1 - Date created - 2004-02-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Histochem Cytochem. 1997 Feb;45(2):315-9 [9016320] Cell Prolif. 1995 Nov;28(11):571-9 [8555370] Pflugers Arch. 1998 Feb;435(3):407-14 [9426298] J Biol Chem. 1998 Mar 6;273(10):5858-68 [9488723] Toxicol Pathol. 1998 Jan-Feb;26(1):73-91 [9502390] J Biol Chem. 1998 May 29;273(22):13645-51 [9593703] Am J Physiol. 1998 Jun;274(6 Pt 2):F1167-73 [9841510] Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7376-81 [10377422] Am J Physiol Renal Physiol. 2000 Feb;278(2):F209-18 [10662725] Genes Dev. 2000 Jun 15;14(12):1448-59 [10859164] Am J Physiol Renal Physiol. 2000 Aug;279(2):F345-52 [10919855] Curr Biol. 2000 Jul 27-Aug 10;10(15):886-95 [10959836] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11391-6 [11005832] Nature. 2000 Nov 23;408(6811):433-9 [11100718] Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1999-2004 [11172065] Curr Biol. 2001 Jan 23;11(2):105-9 [11231126] Am J Physiol Renal Physiol. 2001 May;280(5):F768-76 [11292618] Kidney Int. 2001 Aug;60(2):553-67 [11473638] Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):184-9 [11756692] Nat Rev Mol Cell Biol. 2002 May;3(5):317-27 [11988766] Science. 2002 May 3;296(5569):922-7 [11934988] Am J Physiol Renal Physiol. 2002 Aug;283(2):F302-8 [12110514] Am J Physiol Renal Physiol. 2003 Mar;284(3):F564-74 [12409277] J Pharmacol Exp Ther. 2003 Jul;306(1):35-42 [12663684] Am J Physiol Renal Physiol. 2003 Aug;285(2):F266-74 [12684226] Oncogene. 2003 Sep 1;22(37):5834-47 [12947390] Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12871-6 [14566050] Curr Mol Med. 2003 Nov;3(7):589-96 [14601634] Pflugers Arch. 1985;405 Suppl 1:S28-32 [4088836] Physiol Rev. 1991 Oct;71(4):1081-115 [1924548] Am J Physiol. 1993 Sep;265(3 Pt 2):F416-24 [8214101] Nucleic Acids Res. 1997 Aug 1;25(15):2985-91 [9224597] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of NAG-1, a transforming growth factor-beta superfamily member, by troglitazone requires the early growth response gene EGR-1. AN - 80165885; 14662774 AB - Troglitazone (TGZ) and 15-deoxy-Delta(12,14)-prostaglandin J2 (PGJ2) are peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands that have been shown to possess pro-apoptotic activity in human colon cancer. Although these compounds bind to PPARgamma transcription factors as agonists, emerging evidence suggests that TGZ acts independently of PPARgamma in many functions, including apoptosis. We previously reported that TGZ induces an early growth response transcription factor (EGR-1) by the ERK phosphorylation pathway rather than by the PPARgamma pathway (Baek, S. J., Wilson, L. C., Hsi, L. C., and Eling, T. E. (2003) J. Biol. Chem. 278, 5845-5853). In this report, we show that the expression of the antitumorigenic and/or pro-apoptotic gene NAG-1 (nonsteroidal anti-inflammatory drug-activated gene-1) is induced by TGZ and correlates with EGR-1 induction. In cotransfection and gel shift assays, we show that EGR-1-binding sites are located within region -73 to -51 of the NAG-1 promoter and have an important role in the transactivation of TGZ-induced NAG-1 expression. In contrast, PGJ2 induced NAG-1 protein expression, but PGJ2 may not affect the same region that TGZ does in the NAG-1 promoter. The effect of PGJ2 is probably PPARgamma-dependent because a PPARgamma antagonist inhibited the PGJ2-induced expression of NAG-1. TGZ-induced NAG-1 expression was not inhibited by the PPARgamma antagonist. The fact that TGZ-induced NAG-1 expression was accompanied by the biosynthesis of EGR-1 also suggests that EGR-1 plays a pivotal role in TGZ-induced NAG-1 expression. Our results suggest that EGR-1 induction is a unique property of TGZ, but is independent of PPARgamma activation. The up-regulation of NAG-1 may provide a novel explanation for the antitumorigenic property of TGZ. JF - The Journal of biological chemistry AU - Baek, Seung Joon AU - Kim, Jong-Sik AU - Nixon, Jennifer B AU - DiAugustine, Richard P AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/02/20/ PY - 2004 DA - 2004 Feb 20 SP - 6883 EP - 6892 VL - 279 IS - 8 SN - 0021-9258, 0021-9258 KW - 15-deoxy-delta(12,14)-prostaglandin J2 KW - 0 KW - Antineoplastic Agents KW - Chromans KW - Cytokines KW - DNA-Binding Proteins KW - EGR1 protein, human KW - Early Growth Response Protein 1 KW - GDF15 protein, human KW - Growth Differentiation Factor 15 KW - Immediate-Early Proteins KW - Ligands KW - Oligonucleotides KW - Receptors, Cytoplasmic and Nuclear KW - Sp1 Transcription Factor KW - Thiazolidinediones KW - Transcription Factors KW - Transforming Growth Factor beta KW - RNA KW - 63231-63-0 KW - Luciferases KW - EC 1.13.12.- KW - troglitazone KW - I66ZZ0ZN0E KW - Prostaglandin D2 KW - RXY07S6CZ2 KW - Index Medicus KW - Blotting, Northern KW - Apoptosis KW - Cell Nucleus -- metabolism KW - Humans KW - Models, Biological KW - Promoter Regions, Genetic KW - Phosphorylation KW - Oligonucleotides -- chemistry KW - RNA -- metabolism KW - Time Factors KW - Plasmids -- metabolism KW - Dose-Response Relationship, Drug KW - Multigene Family KW - Luciferases -- metabolism KW - Cell Line, Tumor KW - Protein Binding KW - Transcriptional Activation KW - Binding Sites KW - Blotting, Western KW - Transfection KW - Models, Genetic KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Up-Regulation KW - Antineoplastic Agents -- pharmacology KW - Sp1 Transcription Factor -- chemistry KW - Transforming Growth Factor beta -- biosynthesis KW - Transcription Factors -- physiology KW - Prostaglandin D2 -- pharmacology KW - Chromans -- pharmacology KW - Transcription Factors -- metabolism KW - Prostaglandin D2 -- analogs & derivatives KW - Cytokines -- biosynthesis KW - Thiazolidinediones -- pharmacology KW - DNA-Binding Proteins -- physiology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80165885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+NAG-1%2C+a+transforming+growth+factor-beta+superfamily+member%2C+by+troglitazone+requires+the+early+growth+response+gene+EGR-1.&rft.au=Baek%2C+Seung+Joon%3BKim%2C+Jong-Sik%3BNixon%2C+Jennifer+B%3BDiAugustine%2C+Richard+P%3BEling%2C+Thomas+E&rft.aulast=Baek&rft.aufirst=Seung&rft.date=2004-02-20&rft.volume=279&rft.issue=8&rft.spage=6883&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 - 2004-04-30 N1 - Date created - 2004-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of the Smad3 expression increases susceptibility to tumorigenicity in human gastric cancer. AN - 80171038; 14647420 AB - Loss of the tumor suppressive effect of transforming growth factor-beta (TGF-beta) has been commonly found at later stages in carcinogenic progression. Although the genes encoding TGF-beta receptors and Smads have been found genetically altered in certain human cancers, no mutation in Smad3 has been observed. Therefore, suppression of Smad3 expression may mediate key oncogenic properties of TGF-beta. First, we observed that 37.5% of human gastric cancer tissues showed low to undetectable levels of Smad3 and that in nine human gastric cancer cell lines examined, two showed deficient Smad3 expression. Introduction of Smad3 into human gastric cancer cells that did not express Smad3, restored TGF-beta responsiveness: induction of p21 and p15 gene expression, and growth inhibition in response to TGF-beta. Furthermore, these Smad3-expressing cells showed markedly decreased and delayed tumorigenicity in vivo. These findings suggest that Smad3 expression may have a critical role in tumor suppression in the early stages of gastric carcinogenesis. JF - Oncogene AU - Han, Sang-Uk AU - Kim, Heung-Tae AU - Seong, Do Hwan AU - Kim, Yong-Suk AU - Park, Yoon-Soo AU - Bang, Yung-Jue AU - Yang, Han-Kwang AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. Y1 - 2004/02/19/ PY - 2004 DA - 2004 Feb 19 SP - 1333 EP - 1341 VL - 23 IS - 7 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - SMAD3 protein, human KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Stomach -- metabolism KW - Humans KW - Tumor Cells, Cultured -- transplantation KW - Organ Specificity KW - Mice, Nude KW - Mice KW - Transforming Growth Factor beta -- metabolism KW - Signal Transduction KW - Stomach Neoplasms -- metabolism KW - Trans-Activators -- biosynthesis KW - Trans-Activators -- genetics KW - Stomach Neoplasms -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Genetic Predisposition to Disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80171038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+the+Smad3+expression+increases+susceptibility+to+tumorigenicity+in+human+gastric+cancer.&rft.au=Han%2C+Sang-Uk%3BKim%2C+Heung-Tae%3BSeong%2C+Do+Hwan%3BKim%2C+Yong-Suk%3BPark%2C+Yoon-Soo%3BBang%2C+Yung-Jue%3BYang%2C+Han-Kwang%3BKim%2C+Seong-Jin&rft.aulast=Han&rft.aufirst=Sang-Uk&rft.date=2004-02-19&rft.volume=23&rft.issue=7&rft.spage=1333&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-10 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single infusion of brain-derived neurotrophic factor into the ventral tegmental area induces long-lasting potentiation of cocaine seeking after withdrawal. AN - 80173155; 14973246 AB - Cocaine addiction in humans is associated with long-term propensity to relapse. Using a rat relapse model, we found that cocaine seeking induced by exposure to cocaine-associated cues progressively increases after withdrawal. This progressive increase is associated with increases in brain-derived nerve growth factor (BDNF) levels within the mesolimbic dopamine system. Based on these findings, we studied whether BDNF infusions into the ventral tegmental area (VTA), the cell body region of mesolimbic dopamine neurons, would potentiate cocaine seeking after withdrawal. Rats were trained to self-administer cocaine for 10 d, and cocaine seeking was measured in extinction tests 3, 10, or 30 d after withdrawal. During testing, rats were exposed to contextual cues that had predicted cocaine availability during training, and lever presses resulted in contingent presentations of a discrete tone-light cue that was previously temporally paired with cocaine infusions. BDNF (0-0.75 microg/site) or nerve growth factor (NGF; 0-0.75 microg/site) was infused into the VTA 1-2 hr after the last self-administration session. To examine the role of the mitogen-activated protein kinase (MAPK) pathway in BDNF effects, U0126 (1 microg/site), an MEK inhibitor, was used. A single intra-VTA infusion of BDNF, but not NGF, induced long-lasting enhancement of cocaine seeking for up to 30 d, an effect reversed by U0126. In contrast, neither BDNF infusions into the substantia nigra, nor acute intra-VTA BDNF infusions 2 hr before testing on day 3 of withdrawal, were effective. These data suggest that BDNF-mediated neuroadaptations in mesolimbic areas are involved in the persistent cocaine seeking induced by exposure to drug cues after withdrawal. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Lu, Lin AU - Dempsey, Jack AU - Liu, Shirley Y AU - Bossert, Jennifer M AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA. Y1 - 2004/02/18/ PY - 2004 DA - 2004 Feb 18 SP - 1604 EP - 1611 VL - 24 IS - 7 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Enzyme Inhibitors KW - Nerve Growth Factor KW - 9061-61-4 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Conditioning, Operant -- drug effects KW - Animals KW - Rats, Long-Evans KW - Substantia Nigra -- drug effects KW - Disease Models, Animal KW - Infusions, Parenteral KW - Nerve Growth Factor -- pharmacology KW - Rats KW - Nerve Growth Factor -- administration & dosage KW - Cues KW - Enzyme Inhibitors -- pharmacology KW - Extinction, Psychological -- drug effects KW - Time Factors KW - Male KW - Behavior, Animal -- drug effects KW - Substance Withdrawal Syndrome -- physiopathology KW - Brain-Derived Neurotrophic Factor -- administration & dosage KW - Brain-Derived Neurotrophic Factor -- pharmacology KW - Cocaine-Related Disorders -- physiopathology KW - Ventral Tegmental Area -- drug effects KW - Cocaine -- adverse effects KW - Ventral Tegmental Area -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80173155?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+single+infusion+of+brain-derived+neurotrophic+factor+into+the+ventral+tegmental+area+induces+long-lasting+potentiation+of+cocaine+seeking+after+withdrawal.&rft.au=Lu%2C+Lin%3BDempsey%2C+Jack%3BLiu%2C+Shirley+Y%3BBossert%2C+Jennifer+M%3BShaham%2C+Yavin&rft.aulast=Lu&rft.aufirst=Lin&rft.date=2004-02-18&rft.volume=24&rft.issue=7&rft.spage=1604&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-04 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asynchronous basepair openings in transcription initiation: CRP enhances the rate-limiting step AN - 19271350; 5840697 AB - The mechanism of isomerization (basepair openings) during transcription initiation by RNA polymerase at the galP1 promoter of Escherichia coli was investigated by 2-aminopurine (2,AP) fluorescence. The fluorescence of 2,AP is quenched in DNA duplex and enhanced when the basepair is distorted or deformed. The increase of 2,AP fluorescence was used to monitor basepair distortion at several individual positions in the promoter. We observed that basepair distortions during isomerization are a multi-step process. Three distinct hitherto unresolved steps in kinetic terms were observed, where significant fluorescence change occurs: a fast step with a half-life of around 1 s, which is followed by two slower steps occurring with a half-life in the range of minutes at 25 degree C. Contrary to commonly held expectations, basepairs at different positions opened by 2,AP assays without any obvious pattern, suggesting that basepair opening is an asynchronous multi-step process. cAMP super(.)CRP, which activates transcription at galP1, enhanced the rate-limiting step. JF - EMBO Journal AU - Roy, S AU - Lim, H M AU - Liu, M AU - Adhya, S AD - Correspondence to: Sankar Adhya Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, 37 Convent Dr., Rm 5138, Bethesda, MD 20892-4264, USA, sadhya@helix.nih.gov Y1 - 2004/02/18/ PY - 2004 DA - 2004 Feb 18 SP - 869 EP - 875 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 23 IS - 4 SN - 0261-4189, 0261-4189 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Fluorescence KW - Cyclic AMP KW - Escherichia coli KW - CRP protein KW - Transcription initiation KW - J 02726:RNA and ribosomes KW - N 14554:mRNA processing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19271350?accountid=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=Asynchronous+basepair+openings+in+transcription+initiation%3A+CRP+enhances+the+rate-limiting+step&rft.au=Roy%2C+S%3BLim%2C+H+M%3BLiu%2C+M%3BAdhya%2C+S&rft.aulast=Roy&rft.aufirst=S&rft.date=2004-02-18&rft.volume=23&rft.issue=4&rft.spage=869&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/10.1038%2Fsj.emboj.7600098 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; CRP protein; Fluorescence; Cyclic AMP; Transcription initiation DO - http://dx.doi.org/10.1038/sj.emboj.7600098 ER - TY - JOUR T1 - Crystal structure of the broadly cross-reactive HIV-1-neutralizing Fab X5 and fine mapping of its epitope. AN - 80148617; 14769016 AB - The human monoclonal antibody Fab X5 neutralizes a broad range of HIV-1 primary isolates. The crystal structure of X5 has been determined at 1.9 A resolution. There are two crystallographically independent Fab fragments in the asymmetric unit. The crystallographic R value for the final model is 0.22. The antibody-combining site features a long (22 amino acid residues) CDR H3 with a protruding hook-shaped motif. The X5 structure and site-directed mutagenesis data suggest that X5 amino acid residues W100 and Y100F in the CDR H3 motif may be critical for the binding of Fab X5 to gp120. X5 bound to a complex of a CD4 mimetic and gp120 with approximately the same kinetics and affinity as to a CD4-gp120 complex, suggesting that specific interactions between CD4 and X5 are unlikely to contribute to the binding of X5 to gp120-CD4 complexes. Binding of X5 to alanine scanning mutants of gp120JR-CSF complexed with CD4 suggested a critical role of the highly conserved amino acid residues at positions 423 and 432. The X5 structure and fine mapping of its epitope may assist in the elucidation of the mechanisms of viral entry and neutralization, and the development of HIV-1 inhibitors and vaccines. JF - Biochemistry AU - Darbha, Ramalakshmi AU - Phogat, Sanjay AU - Labrijn, Aran F AU - Shu, Yuuei AU - Gu, Yijun AU - Andrykovitch, Michelle AU - Zhang, Mei-Yun AU - Pantophlet, Ralph AU - Martin, Loic AU - Vita, Claudio AU - Burton, Dennis R AU - Dimitrov, Dimiter S AU - Ji, Xinhua AD - Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 2004/02/17/ PY - 2004 DA - 2004 Feb 17 SP - 1410 EP - 1417 VL - 43 IS - 6 SN - 0006-2960, 0006-2960 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD4 KW - Antiviral Agents KW - Epitopes KW - HIV Envelope Protein gp120 KW - Immunoglobulin Fab Fragments KW - Index Medicus KW - Crystallization KW - Antiviral Agents -- genetics KW - Models, Molecular KW - Humans KW - Surface Plasmon Resonance KW - HIV Envelope Protein gp120 -- chemistry KW - Antigens, CD4 -- chemistry KW - HIV Envelope Protein gp120 -- metabolism KW - HIV Envelope Protein gp120 -- genetics KW - Antiviral Agents -- metabolism KW - Antigens, CD4 -- immunology KW - Antigens, CD4 -- metabolism KW - Mutagenesis, Site-Directed KW - Protein Structure, Tertiary -- genetics KW - Antiviral Agents -- chemistry KW - Cross Reactions -- genetics KW - Neutralization Tests KW - Crystallography, X-Ray KW - Binding Sites -- genetics KW - Peptide Mapping -- methods KW - Immunoglobulin Fab Fragments -- chemistry KW - HIV-1 -- immunology KW - HIV-1 -- pathogenicity KW - Antibodies, Monoclonal -- metabolism KW - Antibodies, Monoclonal -- genetics KW - Immunoglobulin Fab Fragments -- genetics KW - Immunoglobulin Fab Fragments -- metabolism KW - Epitopes -- chemistry KW - Antibodies, Monoclonal -- chemistry KW - Epitopes -- immunology KW - Epitopes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80148617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Crystal+structure+of+the+broadly+cross-reactive+HIV-1-neutralizing+Fab+X5+and+fine+mapping+of+its+epitope.&rft.au=Darbha%2C+Ramalakshmi%3BPhogat%2C+Sanjay%3BLabrijn%2C+Aran+F%3BShu%2C+Yuuei%3BGu%2C+Yijun%3BAndrykovitch%2C+Michelle%3BZhang%2C+Mei-Yun%3BPantophlet%2C+Ralph%3BMartin%2C+Loic%3BVita%2C+Claudio%3BBurton%2C+Dennis+R%3BDimitrov%2C+Dimiter+S%3BJi%2C+Xinhua&rft.aulast=Darbha&rft.aufirst=Ramalakshmi&rft.date=2004-02-17&rft.volume=43&rft.issue=6&rft.spage=1410&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-17 N1 - Date created - 2004-02-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1RHH; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Essential roles of a dynamic loop in the catalysis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. AN - 80147970; 14769023 AB - 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphoryl group from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP) following an ordered bi-bi mechanism with ATP as the first substrate. The rate-limiting step of the reaction is product release, and the complete active center is assembled and sealed only upon the binding of both ATP and HP. The assembly of the active center involves large conformational changes in three catalytic loops, among which loop 3 undergoes the most dramatic and unusual changes. To investigate the roles of loop 3 in catalysis, we have made a deletion mutant, which has been investigated by biochemical and X-ray crystallographic analysis. The biochemical data showed that the deletion mutation does not have significant effects on the dissociation constants or the rate constants for the binding of the first substrate MgATP or its analogues. The dissociation constant of HP for the mutant increases by a factor of approximately 100, which is due to a large increase in the dissociation rate constant. The deletion mutation causes a shift of the rate-limiting step in the reaction and a decrease in the rate constant for the chemical step by a factor of approximately 1.1 x 10(5). The crystal structures revealed that the deletion mutation does not affect protein folding, but the catalytic center of the mutant is not fully assembled even upon the formation of the ternary complex and is not properly sealed. The results together suggest that loop 3 is dispensable for the folding of the protein and the binding of the first substrate MgATP, but is required for the assembling and sealing of the active center. The loop plays an important role in the stabilization of the ternary complex and is critical for catalysis. JF - Biochemistry AU - Blaszczyk, Jaroslaw AU - Li, Yue AU - Wu, Yan AU - Shi, Genbin AU - Ji, Xinhua AU - Yan, Honggao AD - Macromolecular Crystallography Laboratory, National Cancer Institute, P.O. Box B, Frederick, Maryland 21702, USA. Y1 - 2004/02/17/ PY - 2004 DA - 2004 Feb 17 SP - 1469 EP - 1477 VL - 43 IS - 6 SN - 0006-2960, 0006-2960 KW - Escherichia coli Proteins KW - 0 KW - Pterins KW - Recombinant Fusion Proteins KW - 7,8-dihydropterin KW - 17838-80-1 KW - 6-hydroxymethylpterin KW - 712-29-8 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Arginine KW - 94ZLA3W45F KW - Diphosphotransferases KW - EC 2.7.6.- KW - 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase KW - EC 2.7.6.3 KW - Index Medicus KW - Pterins -- chemistry KW - Substrate Specificity -- genetics KW - Adenosine Triphosphate -- chemistry KW - Mutagenesis, Site-Directed KW - Protein Structure, Tertiary -- genetics KW - Arginine -- genetics KW - Protein Processing, Post-Translational -- genetics KW - Protein Folding KW - Crystallography, X-Ray KW - Binding Sites -- genetics KW - Catalysis KW - Recombinant Fusion Proteins -- chemical synthesis KW - Sequence Deletion KW - Escherichia coli Proteins -- chemistry KW - Thermodynamics KW - Diphosphotransferases -- chemistry KW - Diphosphotransferases -- genetics KW - Escherichia coli Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80147970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Essential+roles+of+a+dynamic+loop+in+the+catalysis+of+6-hydroxymethyl-7%2C8-dihydropterin+pyrophosphokinase.&rft.au=Blaszczyk%2C+Jaroslaw%3BLi%2C+Yue%3BWu%2C+Yan%3BShi%2C+Genbin%3BJi%2C+Xinhua%3BYan%2C+Honggao&rft.aulast=Blaszczyk&rft.aufirst=Jaroslaw&rft.date=2004-02-17&rft.volume=43&rft.issue=6&rft.spage=1469&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-17 N1 - Date created - 2004-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Women's Ischemic Syndrome Evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2-4, 2002: perspective: new frontiers in detection of ischemic heart disease in women. AN - 212754938; 14970129 JF - Circulation AU - Maseri, A AU - National Heart, Lung and Blood Institute AU - American College of Cardiology Foundation AD - National Heart, Lung and Blood Institute Y1 - 2004///Feb 17 PY - 2004 DA - Feb 17 2004 SP - e62 EP - 3 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 6 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212754938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Women%27s+Ischemic+Syndrome+Evaluation%3A+current+status+and+future+research+directions%3A+report+of+the+National+Heart%2C+Lung+and+Blood+Institute+workshop%3A+October+2-4%2C+2002%3A+perspective%3A+new+frontiers+in+detection+of+ischemic+heart+disease+in+women.&rft.au=Maseri%2C+A%3BNational+Heart%2C+Lung+and+Blood+Institute%3BAmerican+College+of+Cardiology+Foundation&rft.aulast=Maseri&rft.aufirst=A&rft.date=2004-02-17&rft.volume=109&rft.issue=6&rft.spage=e62&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 17 2004 N1 - Last updated - 2014-05-18 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Serum amyloid A as a predictor of coronary artery disease and cardiovascular outcome in women: the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). AN - 212754759; 14970107 AB - BACKGROUND: Serum amyloid-alpha (SAA) is a sensitive marker of an acute inflammatory state. Like high-sensitivity C-reactive protein (hs-CRP), SAA has been linked to atherosclerosis. However, prior studies have yielded inconsistent results, and the independent predictive value of SAA for coronary artery disease (CAD) severity and cardiovascular events remains unclear. METHODS AND RESULTS: A total of 705 women referred for coronary angiography for suspected myocardial ischemia underwent plasma assays for SAA and hs-CRP, quantitative angiographic assessment, and follow-up evaluation. Cardiovascular events were death, myocardial infarction, congestive heart failure, stroke, and other vascular events. The women's mean age was 58 years (range 21 to 86 years), and 18% were nonwhite. SAA and hs-CRP were associated with a broad range of CAD risk factors. After adjustment for these risk factors, SAA levels were independently but moderately associated with angiographic CAD (P=0.004 to 0.04) and highly predictive of 3-year cardiovascular events (P<0.0001). By comparison, hs-CRP was not associated with angiographic CAD (P=0.08 to 0.35) but, like SAA, was strongly and independently predictive of adverse cardiovascular outcome (P<0.0001). CONCLUSIONS: Our results show a strong independent relationship between SAA and future cardiovascular events, similar to that found for hs-CRP. Although SAA was independently but moderately associated with angiographic CAD, this association was not found for hs-CRP. These results are consistent with the hypothesis that systemic inflammation, manifested by high SAA or hs-CRP levels, may promote atherosclerotic plaque destabilization, in addition to exerting a possible direct effect on atherogenesis. JF - Circulation AU - Johnson, B D AU - KE, Kip AU - Marroquin, O C AU - Ridker, P M AU - Kelsey, S F AU - Shaw, L J AU - Pepine, C J AU - Sharaf, B AU - Merz, Bairey AU - Sopko, G AU - Olson, M B AU - Reis SE AU - National Heart, Lung, and Blood Institute AD - National Heart, Lung, and Blood Institute Y1 - 2004///Feb 17 PY - 2004 DA - Feb 17 2004 SP - 726 EP - 32 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 6 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212754759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Serum+amyloid+A+as+a+predictor+of+coronary+artery+disease+and+cardiovascular+outcome+in+women%3A+the+National+Heart%2C+Lung%2C+and+Blood+Institute-Sponsored+Women%27s+Ischemia+Syndrome+Evaluation+%28WISE%29.&rft.au=Johnson%2C+B+D%3BKE%2C+Kip%3BMarroquin%2C+O+C%3BRidker%2C+P+M%3BKelsey%2C+S+F%3BShaw%2C+L+J%3BPepine%2C+C+J%3BSharaf%2C+B%3BMerz%2C+Bairey%3BSopko%2C+G%3BOlson%2C+M+B%3BReis+SE%3BNational+Heart%2C+Lung%2C+and+Blood+Institute&rft.aulast=Johnson&rft.aufirst=B&rft.date=2004-02-17&rft.volume=109&rft.issue=6&rft.spage=726&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 17 2004 N1 - Last updated - 2014-05-18 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Women's Ischemic Syndrome Evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2-4, 2002: Section 2: stable ischemia: pathophysiology and gender differences. AN - 212750033; 14970124 JF - Circulation AU - Redberg, R F AU - Cannon RO 3rd AU - Merz, Bairey AU - Lerman, A AU - Reis SE AU - Sheps, D S AU - National Heart, Lung and Blood Institute AU - American College of Cardiology Foundation AD - National Heart, Lung and Blood Institute Y1 - 2004///Feb 17 PY - 2004 DA - Feb 17 2004 SP - e47 EP - 9 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 6 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212750033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Women%27s+Ischemic+Syndrome+Evaluation%3A+current+status+and+future+research+directions%3A+report+of+the+National+Heart%2C+Lung+and+Blood+Institute+workshop%3A+October+2-4%2C+2002%3A+Section+2%3A+stable+ischemia%3A+pathophysiology+and+gender+differences.&rft.au=Redberg%2C+R+F%3BCannon+RO+3rd%3BMerz%2C+Bairey%3BLerman%2C+A%3BReis+SE%3BSheps%2C+D+S%3BNational+Heart%2C+Lung+and+Blood+Institute%3BAmerican+College+of+Cardiology+Foundation&rft.aulast=Redberg&rft.aufirst=R&rft.date=2004-02-17&rft.volume=109&rft.issue=6&rft.spage=e47&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 17 2004 N1 - Last updated - 2014-05-18 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). AN - 212749868; 14970106 AB - BACKGROUND: Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. METHODS AND RESULTS: As part of the Women's Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (DeltaCSA) in response to acetylcholine (P=0.0006) and nitroglycerin (P=0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P=0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %DeltaCSA with acetylcholine (P=0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %DeltaCSA with acetylcholine remained a significant predictor (P=0.006). CONCLUSIONS: In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity. JF - Circulation AU - Mering, von AU - Arant, C B AU - Wessel, T R AU - McGorray, S P AU - Merz, Bairey AU - Sharaf, B L AU - Smith, K M AU - Olson, M B AU - Johnson, B D AU - Sopko, G AU - Handberg, E AU - Pepine, C J AU - Kerensky, R A AU - National Heart, Lung, and Blood Institute AD - National Heart, Lung, and Blood Institute Y1 - 2004///Feb 17 PY - 2004 DA - Feb 17 2004 SP - 722 EP - 5 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 6 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212749868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Abnormal+coronary+vasomotion+as+a+prognostic+indicator+of+cardiovascular+events+in+women%3A+results+from+the+National+Heart%2C+Lung%2C+and+Blood+Institute-Sponsored+Women%27s+Ischemia+Syndrome+Evaluation+%28WISE%29.&rft.au=Mering%2C+von%3BArant%2C+C+B%3BWessel%2C+T+R%3BMcGorray%2C+S+P%3BMerz%2C+Bairey%3BSharaf%2C+B+L%3BSmith%2C+K+M%3BOlson%2C+M+B%3BJohnson%2C+B+D%3BSopko%2C+G%3BHandberg%2C+E%3BPepine%2C+C+J%3BKerensky%2C+R+A%3BNational+Heart%2C+Lung%2C+and+Blood+Institute&rft.aulast=Mering&rft.aufirst=von&rft.date=2004-02-17&rft.volume=109&rft.issue=6&rft.spage=722&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 17 2004 N1 - Last updated - 2014-05-18 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Women's Ischemic Syndrome Evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2-4, 2002: Section 5: gender-related risk factors for ischemic heart disease. AN - 212737482; 14970127 JF - Circulation AU - Shaw, L J AU - Lewis, J F AU - Hlatky MA AU - Hsueh WA AU - Kelsey, S F AU - Klein, R AU - Manolio, T A AU - Sharrett, A R AU - Tracy, R P AU - National Heart, Lung and Blood Institute AU - American College of Cardiology Foundation AD - National Heart, Lung and Blood Institute Y1 - 2004///Feb 17 PY - 2004 DA - Feb 17 2004 SP - e56 EP - 8 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 6 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212737482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Women%27s+Ischemic+Syndrome+Evaluation%3A+current+status+and+future+research+directions%3A+report+of+the+National+Heart%2C+Lung+and+Blood+Institute+workshop%3A+October+2-4%2C+2002%3A+Section+5%3A+gender-related+risk+factors+for+ischemic+heart+disease.&rft.au=Shaw%2C+L+J%3BLewis%2C+J+F%3BHlatky+MA%3BHsueh+WA%3BKelsey%2C+S+F%3BKlein%2C+R%3BManolio%2C+T+A%3BSharrett%2C+A+R%3BTracy%2C+R+P%3BNational+Heart%2C+Lung+and+Blood+Institute%3BAmerican+College+of+Cardiology+Foundation&rft.aulast=Shaw&rft.aufirst=L&rft.date=2004-02-17&rft.volume=109&rft.issue=6&rft.spage=e56&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 17 2004 N1 - Last updated - 2014-05-18 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Women's Ischemic Syndrome Evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2-4, 2002 : Section 4: lessons from hormone replacement trials. AN - 212733074; 14970126 JF - Circulation AU - Waters, D D AU - Gordon, D AU - Rossouw JE AU - Cannon RO 3rd AU - Collins, P AU - Herrington, D M AU - Hsia, J AU - Langer, R AU - Mosca, L AU - Ouyang, P AU - Sopko, G AU - Stefanick, M L AU - National Heart, Lung and Blood Institute AU - American College of Cardiology Foundation AD - National Heart, Lung and Blood Institute Y1 - 2004///Feb 17 PY - 2004 DA - Feb 17 2004 SP - e53 EP - 5 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 6 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212733074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Women%27s+Ischemic+Syndrome+Evaluation%3A+current+status+and+future+research+directions%3A+report+of+the+National+Heart%2C+Lung+and+Blood+Institute+workshop%3A+October+2-4%2C+2002+%3A+Section+4%3A+lessons+from+hormone+replacement+trials.&rft.au=Waters%2C+D+D%3BGordon%2C+D%3BRossouw+JE%3BCannon+RO+3rd%3BCollins%2C+P%3BHerrington%2C+D+M%3BHsia%2C+J%3BLanger%2C+R%3BMosca%2C+L%3BOuyang%2C+P%3BSopko%2C+G%3BStefanick%2C+M+L%3BNational+Heart%2C+Lung+and+Blood+Institute%3BAmerican+College+of+Cardiology+Foundation&rft.aulast=Waters&rft.aufirst=D&rft.date=2004-02-17&rft.volume=109&rft.issue=6&rft.spage=e53&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 17 2004 N1 - Last updated - 2014-05-18 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Women's Ischemic Syndrome Evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2-4, 2002: Section 3: diagnosis and treatment of acute cardiac ischemia: gender issues. AN - 212733024; 14970125 JF - Circulation AU - Nabel, E G AU - Selker, H P AU - Califf, R M AU - Canto, J G AU - Cao, J J AU - Desvigne-Nikkens, P AU - Goldberg, R J AU - Finnegan JR Jr AU - Vaccarino, V AU - Virmani, R AU - National Heart, Lung and Blood Institute AU - American College of Cardiology Foundation AD - National Heart, Lung and Blood Institute Y1 - 2004///Feb 17 PY - 2004 DA - Feb 17 2004 SP - e50 EP - 2 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 6 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212733024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Women%27s+Ischemic+Syndrome+Evaluation%3A+current+status+and+future+research+directions%3A+report+of+the+National+Heart%2C+Lung+and+Blood+Institute+workshop%3A+October+2-4%2C+2002%3A+Section+3%3A+diagnosis+and+treatment+of+acute+cardiac+ischemia%3A+gender+issues.&rft.au=Nabel%2C+E+G%3BSelker%2C+H+P%3BCaliff%2C+R+M%3BCanto%2C+J+G%3BCao%2C+J+J%3BDesvigne-Nikkens%2C+P%3BGoldberg%2C+R+J%3BFinnegan+JR+Jr%3BVaccarino%2C+V%3BVirmani%2C+R%3BNational+Heart%2C+Lung+and+Blood+Institute%3BAmerican+College+of+Cardiology+Foundation&rft.aulast=Nabel&rft.aufirst=E&rft.date=2004-02-17&rft.volume=109&rft.issue=6&rft.spage=e50&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 17 2004 N1 - Last updated - 2014-05-18 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Women's Ischemic Syndrome Evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2-4, 2002: Section 1: diagnosis of stable ischemia and ischemic heart disease. AN - 212719514; 14970123 JF - Circulation AU - Pepine, C J AU - Balaban, R S AU - RO, Bonow AU - Diamond, G A AU - Johnson, B D AU - Johnson, P A AU - Mosca, L AU - Nissen SE AU - Pohost, G M AU - National Heart, Lung and Blood Institute AU - American College of Cardiology Foundation AD - National Heart, Lung and Blood Institute Y1 - 2004///Feb 17 PY - 2004 DA - Feb 17 2004 SP - e44 EP - 6 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 6 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212719514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Women%27s+Ischemic+Syndrome+Evaluation%3A+current+status+and+future+research+directions%3A+report+of+the+National+Heart%2C+Lung+and+Blood+Institute+workshop%3A+October+2-4%2C+2002%3A+Section+1%3A+diagnosis+of+stable+ischemia+and+ischemic+heart+disease.&rft.au=Pepine%2C+C+J%3BBalaban%2C+R+S%3BRO%2C+Bonow%3BDiamond%2C+G+A%3BJohnson%2C+B+D%3BJohnson%2C+P+A%3BMosca%2C+L%3BNissen+SE%3BPohost%2C+G+M%3BNational+Heart%2C+Lung+and+Blood+Institute%3BAmerican+College+of+Cardiology+Foundation&rft.aulast=Pepine&rft.aufirst=C&rft.date=2004-02-17&rft.volume=109&rft.issue=6&rft.spage=e44&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 17 2004 N1 - Last updated - 2014-05-18 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - In vitro and in vivo cytotoxic activities of recombinant immunotoxin 8H9(Fv)-PE38 against breast cancer, osteosarcoma, and neuroblastoma. AN - 80170510; 14973056 AB - The 8H9 monoclonal antibody (MAb) is highly reactive with a cell surface glycoprotein expressed on human breast cancers, childhood sarcomas, and neuroblastomas but is not reactive with the cell surface of normal human tissues. This specific reactivity suggests that MAb 8H9 may be useful for targeted cancer therapy. To explore this possibility, we generated two recombinant immunotoxins (ITs) using the single-chain Fv (scFv) of MAb 8H9. Initially the 8H9(scFv) cDNA was fused to a DNA encoding a 38-kDa truncated form of Pseudomonas exotoxin (PE38) to generate the IT 8H9(scFv)-PE38. The fusion gene was expressed in Escherichia coli, and the IT was purified to near homogeneity from inclusion bodies. The purified IT showed specific cytotoxicity on nine different cancer cell lines derived from breast cancer, osteosarcoma, and neuroblastomas, known to react with MAb 8H9. The cytotoxic activity was inhibited by MAb 8H9, showing the cytotoxic activity is specific. The antitumor activity of 8H9(scFv)-PE38 was evaluated in severe combined immunodeficient mice bearing MCF-7 breast cancers or OHS-M1 osteosarcomas. The IT showed a specific dose-dependent antitumor activity at 0.075 and 0.15 mg/kg. Next, a more stable disulfide-linked IT, 8H9(dsFv)-PE38, was constructed. It was produced in high yield (16%) and showed cytotoxic and antitumor activities similar to those of 8H9(scFv)-PE38. 8H9(dsFv)-PE38 was given to two cynomolgus monkeys at doses of 0.1 and 0.2 mg/kg i.v. QOD x 3 and was well tolerated. This shows that a dose that causes significant tumor regressions in mice is well tolerated by monkeys. These results make 8H9(dsFv)-PE38 a candidate for further development as a therapeutic agent for breast cancers, osteosarcomas, and neuroblastomas. JF - Cancer research AU - Onda, Masanori AU - Wang, Qing-cheng AU - Guo, Hong-fen AU - Cheung, Nai-Kong V AU - Pastan, Ira AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute/NIH, 37 Convent Drive, Bethesda, MD 20892-4264, USA. Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 1419 EP - 1424 VL - 64 IS - 4 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunotoxins KW - Recombinant Fusion 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 - Animals KW - Macaca fascicularis KW - Humans KW - Mice KW - Cell Line, Tumor KW - Mice, SCID KW - Female KW - Breast Neoplasms -- drug therapy KW - Osteosarcoma -- drug therapy KW - Antibodies, Monoclonal -- blood KW - Exotoxins -- blood KW - Virulence Factors -- therapeutic use KW - Bacterial Toxins -- blood KW - ADP Ribose Transferases -- therapeutic use KW - Immunotoxins -- blood KW - Antibodies, Monoclonal -- therapeutic use KW - Recombinant Fusion Proteins -- blood KW - Immunoglobulin Fragments -- therapeutic use KW - Virulence Factors -- blood KW - Neuroblastoma -- drug therapy KW - Bacterial Toxins -- therapeutic use KW - Bone Neoplasms -- drug therapy KW - Immunotoxins -- therapeutic use KW - ADP Ribose Transferases -- blood KW - Exotoxins -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80170510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+and+in+vivo+cytotoxic+activities+of+recombinant+immunotoxin+8H9%28Fv%29-PE38+against+breast+cancer%2C+osteosarcoma%2C+and+neuroblastoma.&rft.au=Onda%2C+Masanori%3BWang%2C+Qing-cheng%3BGuo%2C+Hong-fen%3BCheung%2C+Nai-Kong+V%3BPastan%2C+Ira&rft.aulast=Onda&rft.aufirst=Masanori&rft.date=2004-02-15&rft.volume=64&rft.issue=4&rft.spage=1419&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 - 2004-04-02 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Herceptin-geldanamycin immunoconjugates: pharmacokinetics, biodistribution, and enhanced antitumor activity. AN - 80169598; 14973048 AB - The efficacy of monoclonal antibodies (mAbs) as single agents in targeted cancer therapy has proven to be limited. Arming mAbs with a potent toxic drug could enhance their activity. Here we report that conjugating geldanamycin (GA) to the anti-HER2 mAb Herceptin improved the activity of Herceptin. The IC(50)s of the immunoconjugate H-GA were 10-200-fold lower than that of Herceptin in antiproliferative assays, depending on the cell line. The H-GA mode of action involved HER2 degradation, which was partially lactacystin sensitive and thus proteasome dependent. The linkage between GA and Herceptin remained stable in the circulation, as suggested by the pharmacokinetics of Herceptin and conjugated GA, which were almost identical and significantly different from that of free GA. Tumor uptake of Herceptin and H-GA were similar (52 +/- 7 and 43 +/- 7% of the initial injected dose per gram tissue, respectively; P = 0.077), indicating no apparent damage attributable to conjugation. Therapy experiments in xenograft-bearing mice consisted of weekly i.p. doses, 4 mg/kg for 4 months. H-GA showed a greater antitumor effect than Herceptin because it induced tumor regression in 69% of the recipients compared with 7% by Herceptin alone. Median survival time was 145 days as opposed to 78 days, and 31% of the recipients remained tumor free 2 months after therapy was terminated versus 0% in the Herceptin group. Enhancement of Herceptin activity could be of significant clinical value. In addition, the chemical linkage and the considerations in therapeutic regimen described here could be applied to other immunoconjugates for targeted therapy of a broad spectrum of cancers. JF - Cancer research AU - Mandler, Raya AU - Kobayashi, Hisataka AU - Hinson, Ella R AU - Brechbiel, Martin W AU - Waldmann, Thomas A AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute/NIH, 6701 Rockledge Drive, Room 5217, MSC 7840, Bethesda, MD 20892, USA. rayam@mail.nih.gov Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 1460 EP - 1467 VL - 64 IS - 4 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Antineoplastic Agents KW - Benzoquinones KW - Immunoconjugates KW - Lactams, Macrocyclic KW - Multienzyme Complexes KW - Quinones KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Trastuzumab KW - P188ANX8CK KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - Animals KW - Receptor, ErbB-2 -- metabolism KW - Cysteine Endopeptidases -- physiology KW - Humans KW - Mice KW - Tissue Distribution KW - NIH 3T3 Cells KW - Neoplasm Transplantation KW - Transplantation, Heterologous KW - Multienzyme Complexes -- physiology KW - Neoplasms, Experimental -- drug therapy KW - Quinones -- administration & dosage KW - Quinones -- pharmacokinetics KW - Immunoconjugates -- pharmacokinetics KW - Antibodies, Monoclonal -- pharmacokinetics KW - Antineoplastic Agents -- pharmacokinetics KW - Antibodies, Monoclonal -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80169598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Herceptin-geldanamycin+immunoconjugates%3A+pharmacokinetics%2C+biodistribution%2C+and+enhanced+antitumor+activity.&rft.au=Mandler%2C+Raya%3BKobayashi%2C+Hisataka%3BHinson%2C+Ella+R%3BBrechbiel%2C+Martin+W%3BWaldmann%2C+Thomas+A&rft.aulast=Mandler&rft.aufirst=Raya&rft.date=2004-02-15&rft.volume=64&rft.issue=4&rft.spage=1460&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 - 2004-04-02 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dendritic cell maturation requires STAT1 and is under feedback regulation by suppressors of cytokine signaling. AN - 80154799; 14764699 AB - In this study we show that activation of STAT pathways is developmentally regulated and plays a role in dendritic cell (DC) differentiation and maturation. The STAT6 signaling pathway is constitutively activated in immature DC (iDC) and declines as iDCs differentiate into mature DCs (mDCs). However, down-regulation of this pathway during DC differentiation is accompanied by dramatic induction of suppressors of cytokine signaling 1 (SOCS1), SOCS2, SOCS3, and cytokine-induced Src homology 2-containing protein expression, suggesting that inhibition of STAT6 signaling may be required for DC maturation. In contrast, STAT1 signaling is most robust in mDCs and is not inhibited by the up-regulated SOCS proteins, indicating that STAT1 and STAT6 pathways are distinctly regulated in maturing DC. Furthermore, optimal activation of STAT1 during DC maturation requires both IL-4 and GM-CSF, suggesting that synergistic effects of both cytokines may in part provide the requisite STAT1 signaling intensity for DC maturation. Analyses of STAT1(-/-) DCs reveal a role for STAT1 in repressing CD86 expression in precursor DCs and up-regulating CD40, CD11c, and SOCS1 expression in mDCs. We further show that SOCS proteins are differentially induced by IL-4 and GM-CSF in DCs. SOCS1 is primarily induced by IL-4 through a STAT1-dependent mechanism, whereas SOCS3 is induced mainly by GM-CSF. Taken together, these results suggest that cytokine-induced maturation of DCs is under feedback regulation by SOCS proteins and that the switch from constitutive activation of the STAT6 pathway in iDCs to predominant use of STAT1 signals in mDC is mediated in part by STAT1-induced SOCS expression. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Jackson, Sharon H AU - Yu, Cheng-Rong AU - Mahdi, Rashid M AU - Ebong, Samuel AU - Egwuagu, Charles E AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 2307 EP - 2315 VL - 172 IS - 4 SN - 0022-1767, 0022-1767 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Lipopolysaccharides KW - Proteins KW - Repressor Proteins KW - STAT1 Transcription Factor KW - Socs1 protein, mouse KW - Socs3 protein, mouse KW - Socs6 protein, mouse KW - Stat1 protein, mouse KW - Suppressor of Cytokine Signaling 1 Protein KW - Suppressor of Cytokine Signaling 3 Protein KW - Suppressor of Cytokine Signaling Proteins KW - Trans-Activators KW - Transcription Factors KW - Interleukin-4 KW - 207137-56-2 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Abridged Index Medicus KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Myeloid Progenitor Cells -- immunology KW - Lipopolysaccharides -- pharmacology KW - Interleukin-4 -- pharmacology KW - Cell Differentiation -- genetics KW - Up-Regulation -- genetics KW - Myeloid Progenitor Cells -- metabolism KW - Mice KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Cell Differentiation -- immunology KW - Mice, Knockout KW - Transcriptional Activation -- immunology KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Myeloid Progenitor Cells -- cytology KW - Up-Regulation -- immunology KW - Drug Synergism KW - Repressor Proteins -- biosynthesis KW - Trans-Activators -- deficiency KW - Carrier Proteins -- genetics KW - Repressor Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - Proteins -- physiology KW - Dendritic Cells -- metabolism KW - Trans-Activators -- genetics KW - Carrier Proteins -- physiology KW - Signal Transduction -- immunology KW - Transcription Factors -- physiology KW - Dendritic Cells -- immunology KW - Feedback, Physiological -- genetics KW - Carrier Proteins -- metabolism KW - Feedback, Physiological -- immunology KW - Proteins -- genetics KW - Repressor Proteins -- genetics KW - Transcription Factors -- biosynthesis KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- deficiency KW - Repressor Proteins -- physiology KW - Signal Transduction -- genetics KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Dendritic Cells -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80154799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dendritic+cell+maturation+requires+STAT1+and+is+under+feedback+regulation+by+suppressors+of+cytokine+signaling.&rft.au=Jackson%2C+Sharon+H%3BYu%2C+Cheng-Rong%3BMahdi%2C+Rashid+M%3BEbong%2C+Samuel%3BEgwuagu%2C+Charles+E&rft.aulast=Jackson&rft.aufirst=Sharon&rft.date=2004-02-15&rft.volume=172&rft.issue=4&rft.spage=2307&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 - 2004-06-15 N1 - Date created - 2004-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum vitamin levels and the risk of asthma in children. AN - 80154514; 14769638 AB - Dietary intake, especially of antioxidant vitamins A, C, E, and the carotenoids, has been linked with the presence and severity of asthma. From the Third National Health and Nutrition Examination Survey (NHANES III), conducted in the United States between 1988 and 1994, the authors selected 4,093 children (aged 6-17 years) for whom relevant medical, socioeconomic, and anthropometric data were complete. The children were 50.6% female, and 9.7% reported a diagnosis of asthma. Bivariate analyses showed that asthma diagnosis was associated with lower levels of serum vitamin C, alpha-carotene, beta-carotene, and beta-cryptoxanthin. However, antioxidant levels may be surrogate markers for socioeconomic variables such as race, poverty, tobacco exposure, or general nutritional status. In logistic models that included age, body mass index, socioeconomic variables, antioxidant levels, parental asthma, and household smoking, the only antioxidants significantly associated with asthma were vitamin C (odds ratio = 0.72 per mg/dl, 95% confidence interval = 0.55, 0.95) and alpha-carotene (odds ratio = 0.95 per micro g/dl, 95% confidence interval = 0.90, 0.99). The odds ratio for asthma in the highest quintile of serum vitamin C relative to the lowest was 0.65 (p < 0.05), whereas it was 0.74 for alpha-carotene (p = 0.066). The authors concluded that low vitamin C and alpha-carotene intakes are associated with asthma risk in children. JF - American journal of epidemiology AU - Harik-Khan, Raida I AU - Muller, Denis C AU - Wise, Robert A AD - Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 351 EP - 357 VL - 159 IS - 4 SN - 0002-9262, 0002-9262 KW - Tobacco Smoke Pollution KW - 0 KW - Vitamins KW - Vitamin A KW - 11103-57-4 KW - Vitamin E KW - 1406-18-4 KW - Carotenoids KW - 36-88-4 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Vitamin A -- blood KW - Reference Values KW - Urban Population -- statistics & numerical data KW - Humans KW - Child KW - Vitamin E -- blood KW - Ethnic Groups -- statistics & numerical data KW - Risk Assessment KW - Socioeconomic Factors KW - Body Weight KW - Carotenoids -- blood KW - Logistic Models KW - Risk Factors KW - Tobacco Smoke Pollution -- statistics & numerical data KW - Ascorbic Acid -- blood KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Asthma -- epidemiology KW - Vitamins -- blood KW - Asthma -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80154514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Serum+vitamin+levels+and+the+risk+of+asthma+in+children.&rft.au=Harik-Khan%2C+Raida+I%3BMuller%2C+Denis+C%3BWise%2C+Robert+A&rft.aulast=Harik-Khan&rft.aufirst=Raida&rft.date=2004-02-15&rft.volume=159&rft.issue=4&rft.spage=351&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 completed - 2004-04-06 N1 - Date created - 2004-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of discoidin domain receptor 1 isoform b with collagen up-regulates chemokine production in human macrophages: role of p38 mitogen-activated protein kinase and NF-kappa B. AN - 80149872; 14764702 AB - Macrophages produce an array of proinflammatory mediators at sites of inflammation and contribute to the development of inflammatory responses. Important roles for cytokines, such as IL-1 or TNF-alpha, and bacterial products, such as LPS, in this process have been well documented; however, the role for the extracellular matrix proteins, such as collagen, remains unclear. We previously reported that discoidin domain receptor 1 (DDR1), a nonintegrin collagen receptor, is expressed during differentiation of human monocytes into macrophages, and the interaction of the DDR1b isoform with collagen facilitates their differentiation via the p38 mitogen-activated protein kinase (MAPK) pathway. In this study, we report that the interaction of DDR1b with collagen up-regulates the production of IL-8, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 in human macrophages in a p38 MAPK- and NF-kappaB-dependent manner. p38 MAPK was critical for DDR1b-mediated, increased NF-kappaB trans-activity, but not for IkappaB degradation or NF-kappaB nuclear translocation, suggesting a role for p38 MAPK in the modification of NF-kappaB. DDR1b-mediated IkappaB degradation was mediated through the recruitment of the adaptor protein Shc to the LXNPXY motif of the receptor and the downstream TNFR-associated factor 6/NF-kappaB activator 1 signaling cascade. Taken together, our study has identified NF-kappaB as a novel target of DDR1b signaling and provided a novel mechanism by which tissue-infiltrating macrophages produce large amounts of chemokines during the development of inflammatory diseases. Intervention of DDR1b signaling may be useful to control inflammatory diseases in which these proteins play an important role. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Matsuyama, Wataru AU - Wang, Lihua AU - Farrar, William L AU - Faure, Michel AU - Yoshimura, Teizo AD - Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 2332 EP - 2340 VL - 172 IS - 4 SN - 0022-1767, 0022-1767 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - Carrier Proteins KW - Chemokine CCL2 KW - Chemokine CCL4 KW - Chemokines KW - Collagen Type I KW - I-kappa B Proteins KW - Interleukin-1 KW - Interleukin-8 KW - Macrophage Inflammatory Proteins KW - NF-kappa B KW - Protein Isoforms KW - Proteins KW - Receptors, Mitogen KW - SHC1 protein, human KW - Shc Signaling Adaptor Proteins KW - Src Homology 2 Domain-Containing, Transforming Protein 1 KW - TNF Receptor-Associated Factor 6 KW - TRAF3IP2 protein, human KW - Trans-Activators KW - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins KW - Discoidin Domain Receptors KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - src Homology Domains -- physiology KW - I-kappa B Proteins -- metabolism KW - Humans KW - Protein Isoforms -- physiology KW - Proteins -- physiology KW - Cell Differentiation -- immunology KW - Trans-Activators -- biosynthesis KW - Chemokine CCL2 -- biosynthesis KW - Carrier Proteins -- physiology KW - Protein Structure, Tertiary -- physiology KW - Adaptor Proteins, Vesicular Transport -- physiology KW - Interleukin-8 -- secretion KW - Interleukin-1 -- biosynthesis KW - Protein Isoforms -- metabolism KW - Cell Line, Tumor KW - Cattle KW - Interleukin-8 -- biosynthesis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - I-kappa B Proteins -- antagonists & inhibitors KW - Trans-Activators -- physiology KW - Macrophage Inflammatory Proteins -- biosynthesis KW - Macrophage Inflammatory Proteins -- secretion KW - Macrophage Activation -- immunology KW - Macrophages -- enzymology KW - Macrophages -- secretion KW - Macrophages -- immunology KW - Chemokines -- biosynthesis KW - NF-kappa B -- physiology KW - Receptor Protein-Tyrosine Kinases -- physiology KW - Receptors, Mitogen -- physiology KW - Mitogen-Activated Protein Kinases -- physiology KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Collagen Type I -- physiology KW - NF-kappa B -- biosynthesis KW - Receptors, Mitogen -- metabolism KW - Up-Regulation -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80149872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+discoidin+domain+receptor+1+isoform+b+with+collagen+up-regulates+chemokine+production+in+human+macrophages%3A+role+of+p38+mitogen-activated+protein+kinase+and+NF-kappa+B.&rft.au=Matsuyama%2C+Wataru%3BWang%2C+Lihua%3BFarrar%2C+William+L%3BFaure%2C+Michel%3BYoshimura%2C+Teizo&rft.aulast=Matsuyama&rft.aufirst=Wataru&rft.date=2004-02-15&rft.volume=172&rft.issue=4&rft.spage=2332&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 - 2004-06-15 N1 - Date created - 2004-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in endosomal targeting of human (beta)1- and (beta)2-adrenergic receptors following clathrin-mediated endocytosis. AN - 80137621; 14734649 AB - The beta(2)-adrenergic receptor (beta(2)AR) undergoes agonist-mediated endocytosis via clathrin-coated pits by a process dependent on both arrestins and dynamin. Internalization of some G protein-coupled receptors, however, is independent of arrestins and/or dynamin and through other membrane microdomains such as caveolae or lipid rafts. The human beta(1)AR is less susceptible to agonist-mediated internalization than the beta(2)-subtype, and its endocytic route, which is unknown, may be different. We have found that (i) co-expression of arrestin-2 or -3 enhanced the internalization of both subtypes whereas co-expression of dominant-negative mutants of arrestin-2 or dynamin impaired their internalization, as did inhibitors of clathrin-mediated endocytosis. (ii) Agonist stimulation increased the phosphorylation of beta(2)AR but not beta(1)AR. (iii) In response to agonist, each subtype redistributed from the cell surface to a distinct population of cytoplasmic vesicles; those containing beta(1)AR were smaller and closer to the plasma membrane whereas those containing beta(2)AR were larger and more perinuclear. (iv) When subcellular fractions from agonist-treated cells were separated by sucrose density gradient centrifugation, all of the internalized beta(2)AR appeared in the lighter endosomal-containing fractions whereas some of the internalized beta(1)AR remained in the denser plasma membrane-containing fractions. (v) Both subtypes recycled with similar kinetics back to the cell surface upon removal of agonist; however, recycling of beta(2)AR but not beta(1)AR was inhibited by monensin. Based on these results, we propose that the internalization of beta(1)AR is both arrestin- and dynamin-dependent and follows the same clathrin-mediated endocytic pathway as beta(2)AR. But during or after endocytosis, beta(1)AR and beta(2)AR are sorted into different endosomal compartments. JF - Journal of cell science AU - Liang, Wei AU - Curran, Patricia K AU - Hoang, Quang AU - Moreland, R Travis AU - Fishman, Peter H AD - Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 723 EP - 734 VL - 117 SN - 0021-9533, 0021-9533 KW - Adrenergic beta-1 Receptor Agonists KW - 0 KW - Adrenergic beta-2 Receptor Agonists KW - Arrestins KW - Clathrin KW - Hypertonic Solutions KW - Macrolides KW - Receptors, Adrenergic, beta-1 KW - Receptors, Adrenergic, beta-2 KW - Recombinant Fusion Proteins KW - Sucrose KW - 57-50-1 KW - concanamycin A KW - 80890-47-7 KW - Cholera Toxin KW - 9012-63-9 KW - Monensin KW - 906O0YJ6ZP KW - Dynamins KW - EC 3.6.5.5 KW - Isoproterenol KW - L628TT009W KW - Index Medicus KW - Animals KW - Hypertonic Solutions -- pharmacology KW - Macrolides -- pharmacology KW - Arrestins -- genetics KW - Cell Membrane -- drug effects KW - Protein Transport -- drug effects KW - Humans KW - Cholera Toxin -- pharmacology KW - Monensin -- pharmacology KW - Isoproterenol -- pharmacology KW - Recombinant Fusion Proteins -- metabolism KW - Dynamins -- metabolism KW - Phosphorylation KW - Kinetics KW - Recombinant Fusion Proteins -- genetics KW - Mutation -- genetics KW - Cell Membrane -- metabolism KW - Sucrose -- pharmacology KW - Arrestins -- metabolism KW - Cell Line KW - Cricetinae KW - Receptors, Adrenergic, beta-1 -- metabolism KW - Clathrin -- physiology KW - Receptors, Adrenergic, beta-1 -- genetics KW - Endocytosis -- drug effects KW - Receptors, Adrenergic, beta-2 -- genetics KW - Endosomes -- metabolism KW - Receptors, Adrenergic, beta-2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80137621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+science&rft.atitle=Differences+in+endosomal+targeting+of+human+%28beta%291-+and+%28beta%292-adrenergic+receptors+following+clathrin-mediated+endocytosis.&rft.au=Liang%2C+Wei%3BCurran%2C+Patricia+K%3BHoang%2C+Quang%3BMoreland%2C+R+Travis%3BFishman%2C+Peter+H&rft.aulast=Liang&rft.aufirst=Wei&rft.date=2004-02-15&rft.volume=117&rft.issue=&rft.spage=723&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-29 N1 - Date created - 2004-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic active Epstein-Barr virus infection associated with mutations in perforin that impair its maturation. AN - 80136851; 14576041 AB - Chronic active Epstein-Barr virus infection (CAEBV) is a rare disease in which previously healthy persons develop severe, life-threatening illness. Mutations in the perforin gene have been found in familial hemophagocytic lymphohistiocytosis, which shares some features with CAEBV. We studied a patient who died at age 18, 10 years after the onset of CAEBV. The patient had high titers of antibodies to EBV, EBV RNA in lymph nodes, T-cell lymphoproliferative disease, and hemophagocytic lymphohistiocytosis. DNA sequencing showed novel mutations in both alleles of the perforin gene that resulted in amino acid changes in the protein. The quantity of the native form of perforin from the patient's stimulated peripheral blood mononuclear cells (PBMCs) was extremely low and immunoblotting showed accumulation of an uncleaved precursor form of perforin. Stimulated PBMCs from the patient were defective for Fas-independent cytotoxicity. These data imply that mutations in this patient resulted in reduced perforin-mediated cytotoxicity by his lymphocytes. This is the first case in which perforin mutations have been shown to result in accumulation of the uncleaved, immature form of perforin. Mutations in the perforin gene are associated with some cases of CAEBV with hemophagocytic lymphohistiocytosis. JF - Blood AU - Katano, Harutaka AU - Ali, Mir A AU - Patera, Andriani C AU - Catalfamo, Marta AU - Jaffe, Elaine S AU - Kimura, Hiroshi AU - Dale, Janet K AU - Straus, Stephen E AU - Cohen, Jeffrey I AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 1244 EP - 1252 VL - 103 IS - 4 SN - 0006-4971, 0006-4971 KW - Antibodies KW - 0 KW - Interleukin-2 KW - Membrane Glycoproteins KW - Phytohemagglutinins KW - Pore Forming Cytotoxic Proteins KW - Perforin KW - 126465-35-8 KW - Abridged Index Medicus KW - Index Medicus KW - Lymph Nodes -- virology KW - Fatal Outcome KW - Interleukin-2 -- pharmacology KW - Humans KW - Gene Expression KW - Lymph Nodes -- pathology KW - Child KW - Phytohemagglutinins -- pharmacology KW - Phenotype KW - Adult KW - Cytotoxicity Tests, Immunologic KW - Chronic Disease KW - Parents KW - Adolescent KW - Mutation KW - Lymphocytes -- drug effects KW - Male KW - Female KW - Lymphocytes -- virology KW - Epstein-Barr Virus Infections -- pathology KW - Epstein-Barr Virus Infections -- genetics 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/80136851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+active+Epstein-Barr+virus+infection+associated+with+mutations+in+perforin+that+impair+its+maturation.&rft.au=Katano%2C+Harutaka%3BAli%2C+Mir+A%3BPatera%2C+Andriani+C%3BCatalfamo%2C+Marta%3BJaffe%2C+Elaine+S%3BKimura%2C+Hiroshi%3BDale%2C+Janet+K%3BStraus%2C+Stephen+E%3BCohen%2C+Jeffrey+I&rft.aulast=Katano&rft.aufirst=Harutaka&rft.date=2004-02-15&rft.volume=103&rft.issue=4&rft.spage=1244&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-18 N1 - Date created - 2004-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A screen for drugs that protect against the cytotoxicity of polyglutamine-expanded androgen receptor. AN - 80120573; 14709594 AB - Spinobulbar muscular atrophy is a neurodegenerative disorder caused by expansion of a CAG triplet repeat sequence encoding a polyglutamine tract in the androgen receptor. It has been shown that the mutant protein is toxic in cell culture and triggers an apoptotic cascade resulting in activation of caspase-3. We developed an assay of caspase-3 activation in cells expressing the mutant androgen receptor. This assay was used to screen 1040 drugs, most of which are approved for clinical use. Drugs that inhibit polyglutamine-dependent activation of caspase-3 were subjected to follow-up screens to identify compounds that reproducibly prevent polyglutamine-induced cytotoxicity. Four drugs satisfied these criteria. Three of these (digitoxin, nerifolin and peruvoside) are structurally and functionally related compounds of the cardiac glycoside class and known inhibitors of Na(+)K(+)-ATPase. The fourth compound, suloctidil, is a calcium channel blocker. JF - Human molecular genetics AU - Piccioni, Federica AU - Roman, Benjamin R AU - Fischbeck, Kenneth H AU - Taylor, J Paul AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MS 20892-1250, USA. Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 437 EP - 446 VL - 13 IS - 4 SN - 0964-6906, 0964-6906 KW - Calcium Channels KW - 0 KW - Cardenolides KW - Enzyme Inhibitors KW - Peptides KW - Receptors, Androgen KW - cannogenin thevetoside KW - 1182-87-2 KW - polyglutamine KW - 26700-71-0 KW - neriifolin KW - 5RD2ADS9WV KW - Digitoxin KW - E90NZP2L9U KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Suloctidil KW - XV1N1XY17K KW - Index Medicus KW - Cardenolides -- pharmacology KW - Sodium-Potassium-Exchanging ATPase -- antagonists & inhibitors KW - Suloctidil -- pharmacology KW - Cells, Cultured KW - Humans KW - Calcium Channels -- drug effects KW - Digitoxin -- pharmacology KW - Trinucleotide Repeats -- genetics KW - Enzyme Inhibitors -- pharmacology KW - Drug Evaluation, Preclinical KW - Muscular Disorders, Atrophic -- genetics KW - Receptors, Androgen -- genetics KW - Apoptosis -- drug effects KW - Peptides -- chemistry KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80120573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+screen+for+drugs+that+protect+against+the+cytotoxicity+of+polyglutamine-expanded+androgen+receptor.&rft.au=Piccioni%2C+Federica%3BRoman%2C+Benjamin+R%3BFischbeck%2C+Kenneth+H%3BTaylor%2C+J+Paul&rft.aulast=Piccioni&rft.aufirst=Federica&rft.date=2004-02-15&rft.volume=13&rft.issue=4&rft.spage=437&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 - 2005-03-22 N1 - Date created - 2004-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topoisomerase I-mediated inhibition of hypoxia-inducible factor 1: mechanism and therapeutic implications. AN - 71673481; 14983893 AB - We have shown previously that the camptothecin analogue topotecan (TPT), a topoisomerase I (Top 1) poison, inhibits hypoxia-inducible factor 1 (HIF-1) transcriptional activity and HIF-1alpha protein accumulation in hypoxia-treated U251 human glioma cells. In this article, we demonstrate that TPT does not affect HIF-1alpha protein accumulation but inhibits its translation. In addition, we demonstrate that Top 1 is required for the inhibition of HIF-1alpha protein accumulation by TPT as shown by experiments performed using camptothecin-resistant cell lines with known Top 1 alterations. Experiments performed with aphidicolin indicated that TPT inhibited HIF-1alpha protein accumulation in the absence of DNA replication. DNA-damaging agents, such as ionizing radiation and doxorubicin, did not affect HIF-1alpha protein accumulation. Ongoing transcription was essential for the inhibition of HIF-1alpha protein accumulation by TPT. Our results demonstrate the existence of a novel pathway connecting Top 1-dependent signaling events and the regulation of HIF-1alpha protein expression and function. In addition, our findings dissociate the cytotoxic activity of TPT from the inhibition of the HIF-1 pathway and raise the possibility of novel clinical applications of TPT aimed at targeting HIF-1-dependent responses. JF - Cancer research AU - Rapisarda, Annamaria AU - Uranchimeg, Badarch AU - Sordet, Olivier AU - Pommier, Yves AU - Shoemaker, Robert H AU - Melillo, Giovanni AD - Developmental Therapeutics Program, Tumor Hypoxia Laboratory, Science Applications Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702, USA. Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 1475 EP - 1482 VL - 64 IS - 4 SN - 0008-5472, 0008-5472 KW - HIF1A protein, human KW - 0 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Multienzyme Complexes KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Topoisomerase I Inhibitors KW - Transcription Factors KW - Topotecan KW - 7M7YKX2N15 KW - Protein Kinases KW - EC 2.7.- KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - MTOR protein, human KW - EC 2.7.1.1 KW - TOR Serine-Threonine Kinases KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-akt KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Protein Biosynthesis KW - Protein Kinases -- physiology KW - Cysteine Endopeptidases -- physiology KW - DNA Damage KW - Dose-Response Relationship, Drug KW - Humans KW - Phosphatidylinositol 3-Kinases -- physiology KW - RNA, Messenger -- analysis KW - Transcription, Genetic KW - Cell Line, Tumor KW - Topotecan -- therapeutic use KW - Proto-Oncogene Proteins -- physiology KW - Topotecan -- pharmacology KW - Multienzyme Complexes -- physiology KW - DNA Replication KW - Transcription Factors -- antagonists & inhibitors KW - DNA Topoisomerases, Type I -- physiology KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71673481?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topoisomerase+I-mediated+inhibition+of+hypoxia-inducible+factor+1%3A+mechanism+and+therapeutic+implications.&rft.au=Rapisarda%2C+Annamaria%3BUranchimeg%2C+Badarch%3BSordet%2C+Olivier%3BPommier%2C+Yves%3BShoemaker%2C+Robert+H%3BMelillo%2C+Giovanni&rft.aulast=Rapisarda&rft.aufirst=Annamaria&rft.date=2004-02-15&rft.volume=64&rft.issue=4&rft.spage=1475&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 - 2004-04-02 N1 - Date created - 2004-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer Incidence among Pesticide Applicators Exposed to Alachlor in the Agricultural Health Study AN - 17901974; 5869803 AB - The authors evaluated the incidence of cancer among pesticide applicators with exposure to alachlor in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 49,980 pesticide applicators are included in this analysis; 26,510 applicators (53%) reported use of alachlor on the enrollment questionnaire. Detailed pesticide exposure and other information were obtained from a self-administered questionnaire completed at the time of enrollment (1993-1997). Poisson regression analysis was used to evaluate the exposure-response relations between alachlor and cancer incidence controlled for the effects of potential confounding factors. A total of 1,466 incident malignant neoplasms were diagnosed during the study period, 1993-2000. Among alachlor-exposed applicators, the authors found a significant increasing trend for incidence of all lymphohematopoietic cancers associated with lifetime exposure-days (p for trend = 0.02) and intensity-weighted exposure-days (p for trend = 0.03) to alachlor. The risks of leukemia (rate ratio = 2.83, 95% confidence interval: 0.74, 10.9) and multiple myeloma (rate ratio = 5.66, 95% confidence interval: 0.70, 45.7) were increased among applicators in the highest alachlor exposure category. Our findings suggest a possible association between alachlor application and incidence of lymphohematopoietic cancers among applicators in the Agricultural Health Study. JF - American Journal of Epidemiology AU - Lee, Won Jin AU - Hoppin, JA AU - Blair, A AU - Lubin, J H AU - Dosemeci, M AU - Sandler, D P AU - Alavanja, MCR AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Rockville, MD, USA Y1 - 2004/02/15/ PY - 2004 DA - 2004 Feb 15 SP - 373 EP - 380 VL - 159 IS - 4 SN - 0002-9262, 0002-9262 KW - alachlor KW - farming KW - Health & Safety Science Abstracts; Toxicology Abstracts KW - USA, North Carolina KW - Farms KW - Alachlor KW - Agrochemicals KW - Cancer KW - USA, Iowa KW - Pesticides KW - Occupational exposure KW - H 5000:Pesticides KW - X 24132:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17901974?accountid=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+Epidemiology&rft.atitle=Cancer+Incidence+among+Pesticide+Applicators+Exposed+to+Alachlor+in+the+Agricultural+Health+Study&rft.au=Lee%2C+Won+Jin%3BHoppin%2C+JA%3BBlair%2C+A%3BLubin%2C+J+H%3BDosemeci%2C+M%3BSandler%2C+D+P%3BAlavanja%2C+MCR&rft.aulast=Lee&rft.aufirst=Won&rft.date=2004-02-15&rft.volume=159&rft.issue=4&rft.spage=373&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 - USA, Iowa; USA, North Carolina; Occupational exposure; Agrochemicals; Pesticides; Cancer; Alachlor; Farms ER - TY - JOUR T1 - 12-O-tetradecanoylphorbol-13-acetate and UV radiation-induced nucleoside diphosphate protein kinase B mediates neoplastic transformation of epidermal cells. AN - 80150319; 14623877 AB - The molecular changes associated with early skin carcinogenesis are largely unknown. We have previously identified 11 genes whose expression was up- or down-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin keratinocyte progenitor cells (Wei, S.-J., Trempus, C. S., Cannon, R. E., Bortner, C. D., and Tennant, R. W. (2003) J. Biol. Chem. 278, 1758-1768). Here, we show an induction of a nucleoside diphosphate protein kinase B (NDPK-B) gene in response to TPA or UV radiation (UVR). TPA or UVR significantly induced the expression of NDPK-B both in vivo hyperplastic mouse skin and in vitro mouse JB6 Cl 41-5a epidermal cells. Indeed, this gene was also up-regulated in TPA or UVR-mediated skin tumors including papillomas, spindle cell tumors, and squamous cell carcinomas, relative to adjacent normal skins. Functional studies by constitutive expression of nm23-M2/NDPK-B in TPA susceptible JB6 Cl 41-5a and TPA-resistant JB6 Cl 30-7b preneoplastic epidermal cell lines showed a remarkable gene dosage-dependent increase in foci-forming activity, as well as an enhancement in the efficiency of neoplastic transformation of these cells in soft agar but no effect on proliferation in monolayer cultures. Interestingly, stable transfection of the nm23-M2/NDPK-B del-RGD or G106A mutant gene in JB6 Cl 41-5a cells selectively abrogated NDPK-B-induced cellular transformation, implicating a possible Arg105-Gly106-Asp107 regulatory role in early skin carcinogenesis. JF - The Journal of biological chemistry AU - Wei, Sung-Jen AU - Trempus, Carol S AU - Ali, Robin C AU - Hansen, Laura A AU - Tennant, Raymond W AD - National Center for Toxicogenomics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. wei2@niehs.nih.gov Y1 - 2004/02/13/ PY - 2004 DA - 2004 Feb 13 SP - 5993 EP - 6004 VL - 279 IS - 7 SN - 0021-9258, 0021-9258 KW - Antigens, CD34 KW - 0 KW - Culture Media, Serum-Free KW - DNA, Complementary KW - Proto-Oncogene Proteins KW - Aspartic Acid KW - 30KYC7MIAI KW - Arginine KW - 94ZLA3W45F KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-akt KW - Nucleoside-Diphosphate Kinase KW - EC 2.7.4.6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Animals KW - Glycine -- chemistry KW - Ultraviolet Rays KW - Skin -- metabolism KW - Humans KW - Epidermis -- metabolism KW - Tissue Distribution KW - Aspartic Acid -- chemistry KW - Rats KW - Mutagenesis, Site-Directed KW - In Situ Hybridization KW - Keratinocytes -- metabolism KW - Gene Dosage KW - Time Factors KW - Immunoblotting KW - Homozygote KW - Arginine -- chemistry KW - Epidermis -- cytology KW - Antigens, CD34 -- biosynthesis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Skin Neoplasms -- metabolism KW - Cloning, Molecular KW - Transfection KW - Cells, Cultured KW - DNA, Complementary -- metabolism KW - Kinetics KW - Up-Regulation KW - Culture Media, Serum-Free -- pharmacology KW - Protein Structure, Tertiary KW - Mutation KW - Female KW - Proto-Oncogene Proteins -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Nucleoside-Diphosphate Kinase -- chemistry KW - Cell Transformation, Neoplastic KW - Nucleoside-Diphosphate Kinase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80150319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=12-O-tetradecanoylphorbol-13-acetate+and+UV+radiation-induced+nucleoside+diphosphate+protein+kinase+B+mediates+neoplastic+transformation+of+epidermal+cells.&rft.au=Wei%2C+Sung-Jen%3BTrempus%2C+Carol+S%3BAli%2C+Robin+C%3BHansen%2C+Laura+A%3BTennant%2C+Raymond+W&rft.aulast=Wei&rft.aufirst=Sung-Jen&rft.date=2004-02-13&rft.volume=279&rft.issue=7&rft.spage=5993&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 - 2004-03-30 N1 - Date created - 2004-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasmid P1 RepA Is Homologous to the F Plasmid RepE Class of Initiators AN - 19248373; 5825655 AB - DNA replication of plasmid P1 requires a plasmid-encoded origin DNA-binding protein, RepA. RepA is an inactive dimer and is converted by molecular chaperones into an active monomer that binds RepA binding sites. Although the sequence of RepA is not homologous to that of F plasmid RepE, we found by using fold-recognition programs that RepA shares structural homology with RepE and built a model based on the RepE crystal structure. We constructed mutants in the two predicted DNA binding domains to test the model. As expected, the mutants were defective in P1 DNA binding. The model predicted that RepA binds the first half of the binding site through interactions with the C-terminal DNA binding domain and the second half through interactions with the N-terminal domain. The experiments supported the prediction. The model was further supported by the observation that mutants defective in dimerization map to the predicted subunit interface region, based on the crystal structure of pPS10 RepA, a RepE family member. These results suggest P1 RepA is structurally homologous to plasmid initiators, including those of F, R6K, pSC101, pCU1, pPS10, pFA3, pGSH500, Rts1, RepHI1B, RepFIB, and RSF1010. JF - Journal of Biological Chemistry AU - Sharma, S AU - Sathyanarayana, B K AU - Bird, J G AU - Hoskins, J R AU - Lee, B AU - Wickner, S AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, suewick@helix.nih.gov Y1 - 2004/02/13/ PY - 2004 DA - 2004 Feb 13 SP - 6027 EP - 6034 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 7 SN - 0021-9258, 0021-9258 KW - RepA protein KW - RepE protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Replication KW - Dimerization KW - Crystal structure KW - Plasmids KW - Mutants KW - J 02760:Plasmids KW - N 14650:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19248373?accountid=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=Plasmid+P1+RepA+Is+Homologous+to+the+F+Plasmid+RepE+Class+of+Initiators&rft.au=Sharma%2C+S%3BSathyanarayana%2C+B+K%3BBird%2C+J+G%3BHoskins%2C+J+R%3BLee%2C+B%3BWickner%2C+S&rft.aulast=Sharma&rft.aufirst=S&rft.date=2004-02-13&rft.volume=279&rft.issue=7&rft.spage=6027&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M310917200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Replication; Plasmids; Mutants; Dimerization; Crystal structure DO - http://dx.doi.org/10.1074/jbc.M310917200 ER - TY - JOUR T1 - Analysis of the Plasmodium and Anopheles Transcriptomes during Oocyst Differentiation AN - 17509077; 5825735 AB - Understanding the life cycle of the malaria parasite in its mosquito vector is essential for developing new strategies to combat this disease. Subtractive hybridization cDNA libraries were constructed that are enriched for Plasmodium berghei and Anopheles stephensi genes expressed during oocyst differentiation on the midgut. Sequencing of 1485 random clones led to the identification of 1137 unique expressed sequence tags. Of the 608 expressed sequence tags with data base hits, 320 (53%) had significant matches to the non-redundant protein data base, whereas 288 (47%) with matches only to genomic data bases represent novel Plasmodium and Anopheles genes. Transcription of six novel parasite genes and two previously identified asexual stage genes was up-regulated during oocyst differentiation. In addition, the mRNA for an Anopheles fibrinogen domain gene was induced on day 2 after an infectious blood meal, at the time of ookinete to oocyst differentiation. The subcellular distribution of MAEBL, a sporozoite surface protein, is developmentally regulated from presumed storage organelles in day 15 oocysts to uniform distribution on the surface in day 22 oocysts. This redistribution may reflect a sporozoite maturation program in preparation for salivary gland invasion. Furthermore, apical membrane antigen 1, another parasite surface molecule, is translationally regulated late in sporozoite development, suggesting a role during infection of the vertebrate host. The present results and those of an accompanying report (Abraham, E. G., Islam, S., Srinivasan, P., Ghosh, A. K., Valenzuela, J., Ribeiro, J. M., Kafatos, F. C., Dimopoulos, G., & Jacobs-Lorena, M. (2003) J. Biol. Chem. 279, 5573-5580) provide the foundation for studies seeking to understand at the molecular level Plasmodium development and its interactions with the mosquito. JF - Journal of Biological Chemistry AU - Srinivasan, P AU - Abraham, E G AU - Ghosh, A K AU - Valenzuela, J AU - Ribeiro, JMC AU - Dimopoulos, G AU - Kafatos, F C AU - Adams, J H AU - Fujioka, H AU - Jacobs-Lorena, M AD - Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106, Medical Entomology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892, mlorena@jhsph.edu Y1 - 2004/02/13/ PY - 2004 DA - 2004 Feb 13 SP - 5581 EP - 5587 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org] VL - 279 IS - 7 SN - 0021-9258, 0021-9258 KW - MAEBL protein KW - Oocysts KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids KW - Parasites KW - Human diseases KW - Nucleotide sequence KW - Anopheles stephensi KW - Disease control KW - Life cycle KW - Malaria KW - Hosts KW - Disease transmission KW - Public health KW - Gene expression KW - Differentiation KW - Antigens KW - Glands KW - Aquatic insects KW - Surface chemistry KW - Biological vectors KW - Vectors KW - Developmental stages KW - Transcription KW - Plasmodium berghei KW - Sexual maturity KW - Cell differentiation KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03017:Protozoa KW - N 14550:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17509077?accountid=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=Journal+of+Biological+Chemistry&rft.atitle=Analysis+of+the+Plasmodium+and+Anopheles+Transcriptomes+during+Oocyst+Differentiation&rft.au=Srinivasan%2C+P%3BAbraham%2C+E+G%3BGhosh%2C+A+K%3BValenzuela%2C+J%3BRibeiro%2C+JMC%3BDimopoulos%2C+G%3BKafatos%2C+F+C%3BAdams%2C+J+H%3BFujioka%2C+H%3BJacobs-Lorena%2C+M&rft.aulast=Srinivasan&rft.aufirst=P&rft.date=2004-02-13&rft.volume=279&rft.issue=7&rft.spage=5581&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M307587200 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Biological vectors; Parasites; Human diseases; Nucleotide sequence; Disease control; Life cycle; Transcription; Developmental stages; Malaria; Hosts; Public health; Disease transmission; Gene expression; Antigens; Sexual maturity; Glands; Cell differentiation; Aquatic insects; Surface chemistry; Differentiation; Oocysts; Vectors; Anopheles stephensi; Plasmodium berghei DO - http://dx.doi.org/10.1074/jbc.M307587200 ER - TY - JOUR T1 - Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells. AN - 80155437; 14647417 AB - The gene deleted in liver cancer-1 (DLC-1) is located on human chromosome 8p21-22, a region thought to harbor tumor suppressor genes on the basis of its frequent deletion or loss of heterozygosity in a variety of human cancers, including hepatocellular carcinoma (HCC). Deletion or altered expression of DLC-1 is common in HCC. In the current study, the subcellular localization of Dlc-1 protein was determined by immunostaining with antibody to DLC-1 and the possible tumor growth suppressor activity of DLC-1 was investigated by examining the effects of of DLC-1 cDNA transfection in two human HCC cell lines lacking expression of the endogenous gene. The results show that Dlc-1protein is localized in the cell cytoplasm, and the restoration of DLC-1 expression in HCC cells resulted in caspase-3-mediated apoptosis, inhibition of cell growth and invasiveness in vitro as well as in reduction of the ability of the cells to form tumors in athymic nude mice. These observations thus support the notion that Dlc-1 protein is involved in hepatocarcinogenesis and has oncosuppressive activity in HCC. JF - Oncogene AU - Zhou, Xiaoling AU - Thorgeirsson, Snorri S AU - Popescu, Nicholas C AD - 1Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004/02/12/ PY - 2004 DA - 2004 Feb 12 SP - 1308 EP - 1313 VL - 23 IS - 6 SN - 0950-9232, 0950-9232 KW - DLC1 protein, human KW - 0 KW - GTPase-Activating Proteins KW - Tumor Suppressor Proteins KW - CASP3 protein, human KW - EC 3.4.22.- KW - Casp3 protein, mouse KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Animals KW - Apoptosis KW - Tumor Cells, Cultured KW - Humans KW - Caspases -- analysis KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Cell Cycle -- genetics KW - Cytoplasm -- pathology KW - Cell Division -- genetics KW - Gene Deletion KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- genetics KW - Tumor Suppressor Proteins -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80155437?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Restoration+of+DLC-1+gene+expression+induces+apoptosis+and+inhibits+both+cell+growth+and+tumorigenicity+in+human+hepatocellular+carcinoma+cells.&rft.au=Zhou%2C+Xiaoling%3BThorgeirsson%2C+Snorri+S%3BPopescu%2C+Nicholas+C&rft.aulast=Zhou&rft.aufirst=Xiaoling&rft.date=2004-02-12&rft.volume=23&rft.issue=6&rft.spage=1308&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-09 N1 - Date created - 2004-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Importance of clustered 2'-O-(2-aminoethyl) residues for the gene targeting activity of triple helix-forming oligonucleotides. AN - 80138026; 14756571 AB - We are developing triple helix-forming oligonucleotides (TFOs) as gene targeting reagents in living mammalian cells. We have described psoralen-linked TFOs with 2'-O-methyl and 2'-O-(2-aminoethyl) (2'-AE) substitutions that are active in a gene knockout assay in cultured cells. The assay is based on mutagenesis by psoralen, a photoactive DNA cross-linker. Previous work showed that TFOs with three or four 2'-AE residues were disproportionately more active than those with one or two substitutions. Here we demonstrate that for optimal bioactivity the 2'-AE residues must be clustered rather than dispersed. We have further characterized bioactive and inactive TFOs in an effort to identify biochemical and biophysical correlates of biological activity. While thermal stability is a standard monitor of TFO biophysical activity, we find that T(m) values do not distinguish bioactive and inactive TFOs. In contrast, measurements of TFO association rates appear to correlate well with bioactivity, in that triplex formation occurs disproportionately faster with the TFOs containing three or four 2'-AE residues. We asked if extending the incubation time prior to photoactivation would enhance the bioactivity of a TFO with a slow on rate relative to the TFO with a faster association rate. However, there was no change in bioactivity differential. These results are compatible with a model in which TFO binding in vivo is followed by relatively rapid elution by cellular functions, similar to that described for transcription factors. Under these circumstances, TFOs with faster on rates would be favored because they would be more likely to be in triplexes at the time of photoactivation. JF - Biochemistry AU - Puri, Nitin AU - Majumdar, Alokes AU - Cuenoud, Bernard AU - Miller, Paul S AU - Seidman, Michael M AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2004/02/10/ PY - 2004 DA - 2004 Feb 10 SP - 1343 EP - 1351 VL - 43 IS - 5 SN - 0006-2960, 0006-2960 KW - Cross-Linking Reagents KW - 0 KW - Furocoumarins KW - Mutagens KW - Nucleic Acid Heteroduplexes KW - Oligodeoxyribonucleotides KW - Organophosphorus Compounds KW - phosphoramidite KW - triplex DNA KW - DNA KW - 9007-49-2 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Thioguanine KW - FTK8U1GZNX KW - Index Medicus KW - Animals KW - Thermodynamics KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Mutagenicity Tests -- methods KW - DNA -- metabolism KW - Furocoumarins -- chemical synthesis KW - Thioguanine -- chemistry KW - Mutagens -- metabolism KW - Kinetics KW - DNA -- genetics KW - Organophosphorus Compounds -- chemical synthesis KW - CHO Cells KW - Cross-Linking Reagents -- chemical synthesis KW - DNA -- chemistry KW - Time Factors KW - Mutagens -- chemistry KW - Cricetinae KW - Nucleic Acid Heteroduplexes -- genetics KW - Nucleic Acid Heteroduplexes -- metabolism KW - Gene Targeting -- methods KW - Oligodeoxyribonucleotides -- chemistry KW - Nucleic Acid Heteroduplexes -- chemistry KW - Oligodeoxyribonucleotides -- genetics KW - Oligodeoxyribonucleotides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80138026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clustered+2%27-O-%282-aminoethyl%29+residues+for+the+gene+targeting+activity+of+triple+helix-forming+oligonucleotides.&rft.au=Puri%2C+Nitin%3BMajumdar%2C+Alokes%3BCuenoud%2C+Bernard%3BMiller%2C+Paul+S%3BSeidman%2C+Michael+M&rft.aulast=Puri&rft.aufirst=Nitin&rft.date=2004-02-10&rft.volume=43&rft.issue=5&rft.spage=1343&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-08 N1 - Date created - 2004-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulating functional loop movements: the role of highly conserved residues in the correlated loop motions. AN - 80136394; 14760744 AB - Loop flexibility in enzymes plays a vital role in correctly positioning catalytically important residues. This strong relationship between enzyme flexibility and function provides an opportunity to engineer new substrates and inhibitors. It further allows the design of site-directed mutagenesis experiments to explore enzymatic activity through the control of flexibility of a functional loop. Earlier, we described a novel mechanism in which a small loop triggers the motions of a functional loop in three enzymes (beta-1,4-galactosyltransferase, lipase, and enolase) unrelated in sequence, structure, or function. Here, we further address the question of how the interactions between various flexible loops modulate the movements of the functional loop. We examine beta-1,4-galactosyltransferase as a model system in which a Long loop undergoes a large conformational change (moves in space up to 20 A) upon substrate binding in addition to a small loop (Trp loop) that shows a considerably smaller conformational change. Our molecular-dynamics simulations carried out in implicit and explicit solvent show that, in addition to these two loops, two other neighboring loops are also highly flexible. These loops are in contact with either the Long loop or the Trp loop. Analysis of the covariance of the spatial displacement of the residues reveals that coupled motions occur only in one of these two loops. Sequence analysis indicates that loops correlated in their motions also have highly conserved residues involved in the loop-loop interactions. Further, analysis of crystal structures and simulations in explicit water open the possibility that the Trp loop that triggers the movement of the Long loop in the unbound conformation may also play the same role in the substrate-bound conformation through its contact with the conserved and correlated third loop. Our proposition is supported by the observation that four of the five conserved positions in the third loop are at the interface with the Trp loop. Evolution appears to select residues that drive the functional Long loop to a large conformational change. These observations suggest that altering selected loop-loop interactions might modulate the movements of the functional loop. JF - Chembiochem : a European journal of chemical biology AU - Gunasekaran, Kannan AU - Nussinov, Ruth AD - Basic Research Program, SAIC-Frederick, Inc Laboratory of Experimental and Computational Biology, NCI-Frederick, building 469, room 151, Frederick, MD 21702, USA. Y1 - 2004/02/06/ PY - 2004 DA - 2004 Feb 06 SP - 224 EP - 230 VL - 5 IS - 2 SN - 1439-4227, 1439-4227 KW - Galactosyltransferases KW - EC 2.4.1.- KW - beta-1,4-galactosyltransferase I KW - Index Medicus KW - Sequence Alignment KW - Models, Molecular KW - Protein Folding KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Protein Structure, Tertiary KW - Movement KW - Galactosyltransferases -- metabolism KW - Conserved Sequence KW - Galactosyltransferases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80136394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chembiochem+%3A+a+European+journal+of+chemical+biology&rft.atitle=Modulating+functional+loop+movements%3A+the+role+of+highly+conserved+residues+in+the+correlated+loop+motions.&rft.au=Gunasekaran%2C+Kannan%3BNussinov%2C+Ruth&rft.aulast=Gunasekaran&rft.aufirst=Kannan&rft.date=2004-02-06&rft.volume=5&rft.issue=2&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Chembiochem+%3A+a+European+journal+of+chemical+biology&rft.issn=14394227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-21 N1 - Date created - 2004-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective. AN - 80128028; 14627698 AB - Lewy bodies (LBs), which are the hallmark pathologic features of Parkinson's disease and of dementia with LBs, have several morphologic and molecular similarities to aggresomes. Whether such cytoplasmic inclusions contribute to neuronal death or protect cells from the toxic effects of misfolded proteins remains controversial. In this report, the role of aggresomes in cell viability was addressed in the context of over-expressing alpha-synuclein and its interacting partner synphilin-1 using engineered 293T cells. Inhibition of proteasome activity elicited the formation of juxtanuclear aggregates with characteristics of aggresomes including immunoreactivity for vimentin, gamma-tubulin, ubiquitin, proteasome subunit, and hsp70. As expected from the properties of aggresomes, the microtubule disrupting agents, vinblastin and nocodazole, markedly prevented the formation of these inclusions. Similar to LBs, the phosphorylated form of alpha-synuclein co-localized in these synphilin-1-containing aggresomes. Although the caspase inhibitor z-VAD-fmk significantly reduced the number of apoptotic cells, it had no impact on the percentage of aggresome-positive cells. Finally, quantitative analysis revealed aggresomes in 60% of nonapoptotic cells but only in 10% of apoptotic cells. Additionally, alpha-synuclein-induced apoptosis was not coupled with increased prevalence of aggresome-bearing cells. Taken together, these observations indicate a disconnection between aggresome formation and apoptosis, and support a protective role for these inclusions from the toxicity associated with the combined over-expression of alpha-synuclein and synphilin-1. JF - The Journal of biological chemistry AU - Tanaka, Mikiei AU - Kim, Yong Man AU - Lee, Gwang AU - Junn, Eunsung AU - Iwatsubo, Takeshi AU - Mouradian, M Maral AD - Genetic Pharmacology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. Y1 - 2004/02/06/ PY - 2004 DA - 2004 Feb 06 SP - 4625 EP - 4631 VL - 279 IS - 6 SN - 0021-9258, 0021-9258 KW - Amino Acid Chloromethyl Ketones KW - 0 KW - Carrier Proteins KW - Cysteine Proteinase Inhibitors KW - Macromolecular Substances KW - Nerve Tissue Proteins KW - Neuroprotective Agents KW - Recombinant Proteins KW - SNCA protein, human KW - SNCAIP protein, human KW - Synucleins KW - alpha-Synuclein KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - Vinblastine KW - 5V9KLZ54CY KW - Nocodazole KW - SH1WY3R615 KW - Index Medicus KW - Humans KW - Apoptosis -- physiology KW - Neurons -- drug effects KW - Nocodazole -- pharmacology KW - Cell Survival KW - Neurons -- pathology KW - Neuroprotective Agents -- pharmacology KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Recombinant Proteins -- metabolism KW - Lewy Body Disease -- metabolism KW - Apoptosis -- drug effects KW - Recombinant Proteins -- chemistry KW - Vinblastine -- pharmacology KW - Neurons -- metabolism KW - Parkinson Disease -- metabolism KW - Microtubules -- drug effects KW - Recombinant Proteins -- genetics KW - Parkinson Disease -- pathology KW - Transfection KW - Lewy Bodies -- metabolism KW - Lewy Body Disease -- pathology KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Cell Line KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Inclusion Bodies -- metabolism KW - Carrier Proteins -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry KW - Inclusion Bodies -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80128028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aggresomes+formed+by+alpha-synuclein+and+synphilin-1+are+cytoprotective.&rft.au=Tanaka%2C+Mikiei%3BKim%2C+Yong+Man%3BLee%2C+Gwang%3BJunn%2C+Eunsung%3BIwatsubo%2C+Takeshi%3BMouradian%2C+M+Maral&rft.aulast=Tanaka&rft.aufirst=Mikiei&rft.date=2004-02-06&rft.volume=279&rft.issue=6&rft.spage=4625&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 - 2004-04-01 N1 - Date created - 2004-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The organellular chloride channel protein CLIC4/mtCLIC translocates to the nucleus in response to cellular stress and accelerates apoptosis. AN - 80126024; 14610078 AB - CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to the mitochondria and cytoplasm of keratinocytes and participates in the apoptotic response to stress. We now show that multiple stress inducers cause the translocation of cytoplasmic CLIC4 to the nucleus. Immunogold electron microscopy and confocal analyses indicate that nuclear CLIC4 is detected prior to the apoptotic phenotype. CLIC4 associates with the Ran, NTF2, and Importin-alpha nuclear import complexes in immunoprecipitates of lysates from cells treated with apoptotic/stress-inducing agents. Deletion or mutation of the nuclear localization signal in the C terminus of CLIC4 eliminates nuclear translocation, whereas N terminus deletion enhances nuclear localization. Targeting CLIC4 to the nucleus via adenoviral transduction accelerates apoptosis when compared with cytoplasmic CLIC4, and only nuclear-targeted CLIC4 causes apoptosis in Apaf null mouse fibroblasts or in Bcl-2-overexpressing keratinocytes. These results indicate that CLIC4 nuclear translocation is an integral part of the cellular response to stress and may contribute to the initiation of nuclear alterations that are associated with apoptosis. JF - The Journal of biological chemistry AU - Suh, Kwang S AU - Mutoh, Michihiro AU - Nagashima, Kunio AU - Fernandez-Salas, Ester AU - Edwards, Lindsay E AU - Hayes, Daniel D AU - Crutchley, John M AU - Marin, Keith G AU - Dumont, Rebecca A AU - Levy, Joshua M AU - Cheng, Christina AU - Garfield, Susan AU - Yuspa, Stuart H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, NCI, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. Y1 - 2004/02/06/ PY - 2004 DA - 2004 Feb 06 SP - 4632 EP - 4641 VL - 279 IS - 6 SN - 0021-9258, 0021-9258 KW - CLIC protein, mouse KW - 0 KW - Chloride Channels KW - Mitochondrial Proteins KW - Nuclear Localization Signals KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Active Transport, Cell Nucleus KW - Animals KW - Humans KW - Mice KW - Recombinant Proteins -- genetics KW - Nuclear Localization Signals -- metabolism KW - Mutagenesis, Site-Directed KW - Organelles -- metabolism KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - DNA -- genetics KW - Keratinocytes -- cytology KW - Keratinocytes -- metabolism KW - Nuclear Localization Signals -- genetics KW - Sequence Deletion KW - Apoptosis -- physiology KW - Mitochondrial Proteins -- genetics KW - Chloride Channels -- metabolism KW - Mitochondrial Proteins -- metabolism KW - Chloride Channels -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80126024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+organellular+chloride+channel+protein+CLIC4%2FmtCLIC+translocates+to+the+nucleus+in+response+to+cellular+stress+and+accelerates+apoptosis.&rft.au=Suh%2C+Kwang+S%3BMutoh%2C+Michihiro%3BNagashima%2C+Kunio%3BFernandez-Salas%2C+Ester%3BEdwards%2C+Lindsay+E%3BHayes%2C+Daniel+D%3BCrutchley%2C+John+M%3BMarin%2C+Keith+G%3BDumont%2C+Rebecca+A%3BLevy%2C+Joshua+M%3BCheng%2C+Christina%3BGarfield%2C+Susan%3BYuspa%2C+Stuart+H&rft.aulast=Suh&rft.aufirst=Kwang&rft.date=2004-02-06&rft.volume=279&rft.issue=6&rft.spage=4632&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 - 2004-04-01 N1 - Date created - 2004-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Two inhibitor molecules bound in the active site of Pseudomonas sedolisin: a model for the bi-product complex following cleavage of a peptide substrate AN - 18054587; 5877440 AB - High-resolution crystallographic analysis of a complex of the serine-carboxyl proteinase sedolisin with pseudo-iodotyrostatin revealed two molecules of this inhibitor bound in the active site of the enzyme, marking subsites from S3 to S3 super(). The mode of binding represents two products of the proteolytic reaction. Substrate specificity of sedolisin was investigated using peptide libraries and a new peptide substrate for sedolisin, MCA-Lys-Pro-Pro-Leu-Glu#Tyr-Arg-Leu-Gly-Lys(DNP)-Gly, was synthesized based on the results of the enzymatic and crystallographic studies and was shown to be efficiently cleaved by the enzyme. The kinetic parameters for the substrate, measured by the increase in fluorescence upon relief of quenching, were: kcat=73 plus or minus 5s super(-1), Km=0.12 plus or minus 0.011 mu M, and kcat /Km=608 plus or minus 85s super(-1) mu M super(-1). JF - Biochemical and Biophysical Research Communications AU - Wlodawer, A AU - Li, M AU - Gustchina, A AU - Oyama, H AU - Oda, K AU - Beyer, B B AU - Clemente, J AU - Dunn, B M AD - Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA, wlodawer@ncifcrf.gov Y1 - 2004/02/06/ PY - 2004 DA - 2004 Feb 06 SP - 638 EP - 645 VL - 314 IS - 2 SN - 0006-291X, 0006-291X KW - sedolisin KW - Microbiology Abstracts B: Bacteriology KW - Fluorescence KW - Crystallography KW - Pseudomonas KW - Proteinase KW - Enzymatic activity KW - Synthesis KW - Binding KW - Serine KW - Proteolytic enzymes KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18054587?accountid=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=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Two+inhibitor+molecules+bound+in+the+active+site+of+Pseudomonas+sedolisin%3A+a+model+for+the+bi-product+complex+following+cleavage+of+a+peptide+substrate&rft.au=Wlodawer%2C+A%3BLi%2C+M%3BGustchina%2C+A%3BOyama%2C+H%3BOda%2C+K%3BBeyer%2C+B+B%3BClemente%2C+J%3BDunn%2C+B+M&rft.aulast=Wlodawer&rft.aufirst=A&rft.date=2004-02-06&rft.volume=314&rft.issue=2&rft.spage=638&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1016%2Fj.bbrc.2003.12.130 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Fluorescence; Crystallography; Proteinase; Enzymatic activity; Synthesis; Binding; Proteolytic enzymes; Serine; Pseudomonas DO - http://dx.doi.org/10.1016/j.bbrc.2003.12.130 ER - TY - JOUR T1 - Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. AN - 212672793; 14757684 JF - Circulation AU - Grundy, S M AU - Hansen, B AU - SC, Smith, Jr AU - Cleeman JI AU - Kahn, R A AU - American Heart Association AU - National Heart, Lung, and Blood Institute AU - American Diabetes Association AD - American Heart Association ; National Heart, Lung, and Blood Institute ; American Diabetes Association Y1 - 2004///Feb 3 PY - 2004 DA - Feb 3 2004 SP - 551 EP - 6 CY - Baltimore PB - American Heart Association, Inc. VL - 109 IS - 4 SN - 00097322 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/212672793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Clinical+management+of+metabolic+syndrome%3A+report+of+the+American+Heart+Association%2FNational+Heart%2C+Lung%2C+and+Blood+Institute%2FAmerican+Diabetes+Association+conference+on+scientific+issues+related+to+management.&rft.au=Grundy%2C+S+M%3BHansen%2C+B%3BSC%2C+Smith%2C+Jr%3BCleeman+JI%3BKahn%2C+R+A%3BAmerican+Heart+Association%3BNational+Heart%2C+Lung%2C+and+Blood+Institute%3BAmerican+Diabetes+Association&rft.aulast=Grundy&rft.aufirst=S&rft.date=2004-02-03&rft.volume=109&rft.issue=4&rft.spage=551&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 3 2004 N1 - Last updated - 2014-05-16 N1 - CODEN - CIRCAZ ER - TY - JOUR T1 - Functional markers and the "homogeneity" of human mesenchymal stem cells. AN - 85298178; pmid-14634205 JF - The Journal of Physiology AU - Boheler, Kenneth R AD - Laboratory of Cardiovascular Science, National Institute on Aging/NIH, Baltimore, MD 21113, USA. Y1 - 2004/02/01/ PY - 2004 DA - 2004 Feb 01 VL - 554 IS - Pt 3 SN - 0022-3751, 0022-3751 KW - Human KW - Electrophysiology KW - Stem Cells KW - Biological Markers KW - Mesoderm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85298178?accountid=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+Physiology&rft.atitle=Functional+markers+and+the+%22homogeneity%22+of+human+mesenchymal+stem+cells.&rft.au=Boheler%2C+Kenneth+R&rft.aulast=Boheler&rft.aufirst=Kenneth&rft.date=2004-02-01&rft.volume=554&rft.issue=Pt+3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Physiology&rft.issn=00223751&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316. AN - 80181171; 14981398 AB - The purpose of this study was to evaluate rates of maternal toxicity, pregnancy complications, and peripartum morbidity by type and duration of antiretroviral therapy (ART) during pregnancy. The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 316 (PACTG 316) study evaluated the addition of intrapartum/neonatal nevirapine to background ART to reduce perinatal transmission of human immunodeficiency virus-1 (HIV-1). For this secondary analysis, women were categorized into one of six groups on the basis of ART during pregnancy (monotherapy [monoRx], combination without protease inhibitor [PI], combination with PI), and start time (early: before or during first trimester; late: second or third trimester). One thousand four hundred seven women were included: 288 monoRx late, 34 monoRx early, 327 combo, no PI late, 175 combo, no PI early, 320 combo, PI late, and 263 combo, PI early. Symptoms and laboratory abnormalities of moderate grade or more occurred in less than 5% of women. Only gestational diabetes (highest in combo PI early) varied significantly by therapy group. In HIV-infected women receiving prenatal care and ART, adverse events were uncommon. JF - American journal of obstetrics and gynecology AU - Watts, D Heather AU - Balasubramanian, Rajalakshmi AU - Maupin, Robert T AU - Delke, Isaac AU - Dorenbaum, Alejandro AU - Fiore, Simone AU - Newell, Marie-Louise AU - Delfraissy, Jean-Francois AU - Gelber, Richard D AU - Mofenson, Lynne M AU - Culnane, Mary AU - Cunningham, Coleen K AU - PACTG 316 Study Team AD - National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. hw59I@nih.gov ; PACTG 316 Study Team Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 506 EP - 516 VL - 190 IS - 2 SN - 0002-9378, 0002-9378 KW - Anti-HIV Agents KW - 0 KW - Anti-Retroviral Agents KW - HIV Protease Inhibitors KW - Nevirapine KW - 99DK7FVK1H KW - Abridged Index Medicus KW - Index Medicus KW - Nevirapine -- adverse effects KW - Randomized Controlled Trials as Topic KW - Nevirapine -- therapeutic use KW - Humans KW - Anti-HIV Agents -- adverse effects KW - HIV Protease Inhibitors -- therapeutic use KW - Comorbidity KW - Pregnancy KW - Anti-HIV Agents -- therapeutic use KW - Hospitalization KW - Adult KW - HIV Protease Inhibitors -- adverse effects KW - Female KW - Pregnancy Outcome KW - HIV Infections -- drug therapy KW - Anti-Retroviral Agents -- adverse effects KW - Pregnancy Complications, Infectious -- epidemiology KW - Pregnancy Complications, Infectious -- drug therapy KW - HIV Infections -- epidemiology KW - Anti-Retroviral Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80181171?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+obstetrics+and+gynecology&rft.atitle=Maternal+toxicity+and+pregnancy+complications+in+human+immunodeficiency+virus-infected+women+receiving+antiretroviral+therapy%3A+PACTG+316.&rft.au=Watts%2C+D+Heather%3BBalasubramanian%2C+Rajalakshmi%3BMaupin%2C+Robert+T%3BDelke%2C+Isaac%3BDorenbaum%2C+Alejandro%3BFiore%2C+Simone%3BNewell%2C+Marie-Louise%3BDelfraissy%2C+Jean-Francois%3BGelber%2C+Richard+D%3BMofenson%2C+Lynne+M%3BCulnane%2C+Mary%3BCunningham%2C+Coleen+K%3BPACTG+316+Study+Team&rft.aulast=Watts&rft.aufirst=D&rft.date=2004-02-01&rft.volume=190&rft.issue=2&rft.spage=506&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-30 N1 - Date created - 2004-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional inactivation of STAT3 by PPARgamma suppresses IL-6-responsive multiple myeloma cells. AN - 80178598; 14975242 AB - Multiple myeloma (MM) remains largely incurable despite conventional and high-dose therapies. Therefore, novel biologically based treatment approaches are urgently required. Here we demonstrate that expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in MM cells and its agonists 15-d-PGJ2 and troglitazone completely abolished IL-6-inducible MM cell proliferation and induced apoptosis through affecting expression of multiple cell cycle or apoptosis genes, whereas PPARgamma antagonist GW9662 and PPARalpha agonist WY14643 did not display this inhibitory effect. These PPARgamma agonists significantly inhibited DNA binding and transactivation of STAT3 bound to the promoter of target genes in chromatin, but did not affect the expression of IL-6 receptor and phosphorylation of JAK/STAT3, MAPK, and PI3K/Akt. Interestingly, although inactivation of STAT3 by PPARgamma agonists is in a PPARgamma-dependent manner, the molecular mechanism by which two structurally distinct PPARgamma agonists suppress IL-6-activated STAT3 shows the divergent interactions between PPARgamma and STAT3 including direct or SMRT-mediated association. JF - Immunity AU - Wang, Li Hua AU - Yang, Xiao Yi AU - Zhang, Xiaohu AU - Huang, Jiaqiang AU - Hou, Jian AU - Li, Jie AU - Xiong, Hong AU - Mihalic, Kelly AU - Zhu, Heming AU - Xiao, Weihua AU - Farrar, William L AD - Basic Research Program, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, MD 21702, USA. lhwang@ncifcrf.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 205 EP - 218 VL - 20 IS - 2 SN - 1074-7613, 1074-7613 KW - 2-chloro-5-nitrobenzanilide KW - 0 KW - Anilides KW - Antineoplastic Agents KW - Chromans KW - DNA-Binding Proteins KW - Interleukin-6 KW - Peroxisome Proliferators KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - Thiazolidinediones KW - Trans-Activators KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - troglitazone KW - I66ZZ0ZN0E KW - Index Medicus KW - Bone Marrow Cells -- drug effects KW - Gene Expression -- drug effects KW - Apoptosis -- physiology KW - Humans KW - Electrophoretic Mobility Shift Assay KW - Peroxisome Proliferators -- pharmacology KW - Transcriptional Activation -- drug effects KW - Down-Regulation KW - Apoptosis -- drug effects KW - Thiazolidinediones -- pharmacology KW - Enzyme-Linked Immunosorbent Assay KW - Bone Marrow Cells -- physiology KW - Cell Division -- drug effects KW - Pyrimidines -- pharmacology KW - Precipitin Tests KW - Reverse Transcriptase Polymerase Chain Reaction KW - Anilides -- pharmacology KW - Signal Transduction -- physiology KW - Blotting, Western KW - Chromans -- pharmacology KW - Transfection KW - Cells, Cultured KW - Signal Transduction -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Receptors, Cytoplasmic and Nuclear -- agonists KW - Transcription Factors -- agonists KW - Interleukin-6 -- physiology KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Multiple Myeloma -- metabolism KW - DNA-Binding Proteins -- drug effects KW - Interleukin-6 -- pharmacology KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Trans-Activators -- drug effects KW - Transcription, Genetic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80178598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transcriptional+inactivation+of+STAT3+by+PPARgamma+suppresses+IL-6-responsive+multiple+myeloma+cells.&rft.au=Wang%2C+Li+Hua%3BYang%2C+Xiao+Yi%3BZhang%2C+Xiaohu%3BHuang%2C+Jiaqiang%3BHou%2C+Jian%3BLi%2C+Jie%3BXiong%2C+Hong%3BMihalic%2C+Kelly%3BZhu%2C+Heming%3BXiao%2C+Weihua%3BFarrar%2C+William+L&rft.aulast=Wang&rft.aufirst=Li&rft.date=2004-02-01&rft.volume=20&rft.issue=2&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Immunity&rft.issn=10747613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-31 N1 - Date created - 2004-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peptic ulcer disease and the risk of bladder cancer in a prospective study of male health professionals. AN - 80175826; 14973090 AB - Helicobacter pylori is a risk factor for gastric and duodenal ulcers, but gastric ulcers generally occur in individuals who have low acid production and diffuse gastritis, whereas duodenal ulcers are more likely to occur with high acid output and antrum-predominant gastritis. Low acid production, gastritis, and ulcer healing each contribute to poor antioxidant absorption, oxidative stress, and elevated nitrite levels in the stomach. N-Nitrosamines are known carcinogens, and nitrate ingestion has been related to bladder cancer risk. Consequently, we hypothesized that the gastric conditions associated with gastric ulcers may contribute to elevated bladder cancer risk. We thus examined the association between self-reported history of peptic ulcer disease and the risk of bladder cancer (414 cases) over 14 years of follow-up in the Health Professional Follow-Up Study. Cox proportional hazards models were performed to adjust for known risk factors of bladder cancer. Men who reported a gastric ulcer before 1986 had a significantly higher risk of bladder cancer compared with those with no history of gastric ulcer (relative risk = 1.55, 95% confidence interval = 1.03-2.33, controlling for smoking and other potential confounders). No association was observed for duodenal ulcers (multivariate relative risk = 0.97, 95% confidence interval = 0.68-1.38). The ulcers in this study were based solely on self-report and not medical records; consequently, misclassification of ulcers may have occurred. Although intriguing, these findings need to be replicated. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Michaud, Dominique S AU - Mysliwiec, Pauline A AU - Aldoori, Walid AU - Willett, Walter C AU - Giovannucci, Edward AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA. dmichaud@hsph.harvard.edu Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 250 EP - 254 VL - 13 IS - 2 SN - 1055-9965, 1055-9965 KW - Index Medicus KW - Helicobacter pylori KW - Prospective Studies KW - Humans KW - Duodenal Ulcer -- etiology KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Duodenal Ulcer -- complications KW - Male KW - Risk Assessment KW - Urinary Bladder Neoplasms -- etiology KW - Peptic Ulcer -- complications KW - Health Personnel KW - Peptic Ulcer -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80175826?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Peptic+ulcer+disease+and+the+risk+of+bladder+cancer+in+a+prospective+study+of+male+health+professionals.&rft.au=Michaud%2C+Dominique+S%3BMysliwiec%2C+Pauline+A%3BAldoori%2C+Walid%3BWillett%2C+Walter+C%3BGiovannucci%2C+Edward&rft.aulast=Michaud&rft.aufirst=Dominique&rft.date=2004-02-01&rft.volume=13&rft.issue=2&rft.spage=250&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 - 2004-05-27 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):550 [15734988] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relative validity of a food frequency questionnaire with a meat-cooking and heterocyclic amine module. AN - 80171520; 14973110 AB - The nutrient and heterocyclic amine (HCA) intake of 165 healthy participants was assessed using a self-administered food frequency questionnaire (FFQ), which included a meat-cooking practices module. A database containing the HCA [2-amino-3,8-dimethylimadazo [4,5-f] quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimadazo [4,5-b] pyridine (PhIP)] composition of various types of meat, cooked by different methods and to varying degrees, was developed and validated in conjunction with this module. The relative validity of dietary and HCA intake estimated by the FFQ was investigated using multiple food diaries (3 sets of 4 nonconsecutive day diaries completed over a 3-month period) as the reference method. Crude correlation coefficients of HCA intake assessed by the FFQ and food diaries were 0.43 [95% confidence interval (CI) 0.30-0.55] for MeIQx and 0.22 (95% CI 0.07-0.36) for PhIP intake. Deattenuated correlations were 0.60 (95% CI 0.49-0.69) and 0.36 (95% CI 0.22-0.49), respectively. Absolute MeIQx and PhIP intake was, however, underestimated by the FFQ (21.9 and 78.1 ng/day) compared with the food diaries (34.9 and 263.8 ng/day). The FFQ underestimated total red meat intake, the percentage of consumers, and the median intake of roast/baked and microwaved red meat. PhIP intake was severely underestimated by the FFQ and was most likely because of an underestimation of the percentage of people who cooked chicken using PhIP-producing cooking methods such as broiling and pan-frying. Additionally, the FFQ overestimated the percentage of consumers of baked chicken, a cooking method that produces less PhIP. In conclusion, although the FFQ and meat module underestimated absolute MeIQx and PhIP intake, its ability to rank individuals according to intake was acceptable. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Cantwell, Marie AU - Mittl, Beth AU - Curtin, Jane AU - Carroll, Ray AU - Potischman, Nancy AU - Caporaso, Neil AU - Sinha, Rashmi AD - Nutrition Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 293 EP - 298 VL - 13 IS - 2 SN - 1055-9965, 1055-9965 KW - Amines KW - 0 KW - Heterocyclic Compounds KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Truth Disclosure KW - Neoplasms -- etiology KW - Male KW - Female KW - Meat KW - Amines -- analysis KW - Heterocyclic Compounds -- analysis KW - Cooking KW - Surveys and Questionnaires KW - Diet Surveys KW - Heterocyclic Compounds -- adverse effects KW - Amines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80171520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relative+validity+of+a+food+frequency+questionnaire+with+a+meat-cooking+and+heterocyclic+amine+module.&rft.au=Cantwell%2C+Marie%3BMittl%2C+Beth%3BCurtin%2C+Jane%3BCarroll%2C+Ray%3BPotischman%2C+Nancy%3BCaporaso%2C+Neil%3BSinha%2C+Rashmi&rft.aulast=Cantwell&rft.aufirst=Marie&rft.date=2004-02-01&rft.volume=13&rft.issue=2&rft.spage=293&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 - 2004-05-27 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunoablative reduced-intensity stem cell transplantation: potential role of donor Th2 and Tc2 cells. AN - 80169493; 14970938 AB - Allogeneic reduced-intensity stem cell transplantation (RISCT) decreases regimen-associated morbidity and mortality, but it is unfortunately still constrained by the same immune T-cell reactions that limit myeloablative transplantation, including graft rejection, graft-versus-host disease (GVHD), and suboptimal graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects. Graft rejection is mediated by host T cells, whereas GVHD and GVL/GVT effects are initiated by donor T cells, and to this extent, future advances in RISCT will likely benefit from an ability to modulate both donor and host T-cell immunity. As a step in this direction, we have developed a RISCT approach that first involves chemotherapy-induced host T-cell ablation, and second involves administration of allogeneic inocula enriched for donor CD4(+) Th2 and CD8(+) Tc2 T-cell subsets that in murine studies mediate reduced GVHD. In a pilot clinical trial, "immunoablative" RISCT with human leukocyte antigen (HLA)-matched related allografts resulted in rapid and complete donor chimerism and GVL effects early post-transplant, with GVHD being the primary toxicity. Using this immunoablative RISCT approach, we are now evaluating the feasibility and safety of augmenting allografts with additional donor CD4(+) Th2 cells that are generated in vitro via CD3/CD28 costimulation in the presence of interleukin (IL)-4. We review the biology of host and donor T-cell immunity during allogeneic RISCT and discuss the strategies of host immunoablation and donor Th2 and Tc2 cell therapy as potential means to improve the clinical results in RISCT. JF - Seminars in oncology AU - Fowler, Daniel H AU - Bishop, Michael R AU - Gress, Ronald E AD - National Institutes of Health, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 56 EP - 67 VL - 31 IS - 1 SN - 0093-7754, 0093-7754 KW - Index Medicus KW - Transplantation Immunology KW - Animals KW - Graft vs Host Disease -- immunology KW - Humans KW - Cell Culture Techniques -- methods KW - Mice KW - Graft vs Host Disease -- prevention & control KW - Immunosuppression -- methods KW - Stem Cell Transplantation -- methods KW - T-Lymphocytes, Cytotoxic -- transplantation KW - Th2 Cells -- transplantation KW - Stem Cell Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80169493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=Immunoablative+reduced-intensity+stem+cell+transplantation%3A+potential+role+of+donor+Th2+and+Tc2+cells.&rft.au=Fowler%2C+Daniel+H%3BBishop%2C+Michael+R%3BGress%2C+Ronald+E&rft.aulast=Fowler&rft.aufirst=Daniel&rft.date=2004-02-01&rft.volume=31&rft.issue=1&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-10 N1 - Date created - 2004-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fast-flow EPR spectroscopic observation of the isoniazid, iproniazid, and phenylhydrazine hydrazyl radicals. AN - 80162137; 14967010 AB - Hydrazyl radical intermediates have been suggested as important intermediates in the biochemistry of hydrazides and hydrazines. Although spin-trapping studies have intercepted those species previously, there has been no report of the direct observation of the unstable hydrazyl radicals of isoniazid and iproniazid. We have employed the fast-flow technique in electron paramagnetic resonance (EPR) spectroscopy to measure spectra for the short-lived hydrazyl radicals of a family of hydrazides, including the pharmacologically important compounds isoniazid and iproniazid, as well as for a series of phenylhydrazines. Our investigations of the phenylhydrazine radical and the related chloro-substituted analogues have allowed definitive assignments of the hyperfine coupling constants of that toxicologically important free radical. Theoretical values of hyperfine coupling constants, calculated by density functional formalism, provided a guide to assignments for the hydrazyl species and confirmed the experimentally based assignments for phenylhydrazyl radical. JF - Chemical research in toxicology AU - Sipe, Herbert J AU - Jaszewski, Adrian R AU - Mason, Ronald P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 226 EP - 233 VL - 17 IS - 2 SN - 0893-228X, 0893-228X KW - Free Radicals KW - 0 KW - Phenylhydrazines KW - phenylhydrazine KW - 064F424C9K KW - Iproniazid KW - D892HFI3XA KW - Isoniazid KW - V83O1VOZ8L KW - Index Medicus KW - Electron Spin Resonance Spectroscopy -- methods KW - Isoniazid -- analysis KW - Iproniazid -- analysis KW - Phenylhydrazines -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80162137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fast-flow+EPR+spectroscopic+observation+of+the+isoniazid%2C+iproniazid%2C+and+phenylhydrazine+hydrazyl+radicals.&rft.au=Sipe%2C+Herbert+J%3BJaszewski%2C+Adrian+R%3BMason%2C+Ronald+P&rft.aulast=Sipe&rft.aufirst=Herbert&rft.date=2004-02-01&rft.volume=17&rft.issue=2&rft.spage=226&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 - 2004-10-13 N1 - Date created - 2004-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expressions of hepatic genes, especially IGF-binding protein-1, correlating with serum corticosterone in microarray analysis. AN - 80155886; 14766007 AB - Microarray technology was evaluated for usefulness in assessing relationships between serum corticosterone and hepatic gene expression. Nine pairs of female Swiss mice were chosen to provide a wide range of serum corticosterone ratios; cDNA microarray analysis (approximately 8000 genes) was performed on their livers. A statistical method based on calculation of 99% confidence intervals discovered 32 genes which varied significantly among the livers. Five of these ratios correlated significantly with serum corticosterone ratio, including tyrosine aminotransferase, stress-induced protein, pleiotropic regulator 1 and insulin-like growth factor-binding protein-1; the latter has a potential role in cancer development. Secondly, linear regression of gene expression vs corticosterone ratios was screened for those with r> or =0.8 (P<0.01), yielding 141 genes, including some known to be corticosterone regulated and others of interest as possible glucocorticoid targets. Half of these significant correlations involved data sets where no microarray ratio exceeded +/- 1.5. These results showed that microarray may be used to survey tissues for changes in gene expression related to serum hormones, and that even small changes in expression can be of statistical significance in a study with adequate numbers of replicate samples. JF - Journal of molecular endocrinology AU - Cheng, R Y S AU - Birely, L A AU - Lum, N L AU - Perella, C M AU - Cherry, J M AU - Bhat, N K AU - Kasprzak, K S AU - Powell, D A AU - Alvord, W G AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Building 538, Ft Detrick, Frederick, Maryland 21701, USA. rcheng@mail.ncifcrf.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 257 EP - 278 VL - 32 IS - 1 SN - 0952-5041, 0952-5041 KW - Carrier Proteins KW - 0 KW - Heat-Shock Proteins KW - Insulin-Like Growth Factor Binding Protein 1 KW - Nuclear Proteins KW - Trp53inp1 protein, mouse KW - Tyrosine Transaminase KW - EC 2.6.1.5 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Heat-Shock Proteins -- metabolism KW - Animals KW - Tyrosine Transaminase -- metabolism KW - Nuclear Proteins -- genetics KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Tyrosine Transaminase -- genetics KW - Oligonucleotide Array Sequence Analysis -- methods KW - Mice KW - Nuclear Proteins -- metabolism KW - Heat-Shock Proteins -- genetics KW - Gene Expression Profiling -- methods KW - Female KW - Corticosterone -- blood KW - Insulin-Like Growth Factor Binding Protein 1 -- genetics KW - Liver -- metabolism KW - Insulin-Like Growth Factor Binding Protein 1 -- metabolism KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80155886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expressions+of+hepatic+genes%2C+especially+IGF-binding+protein-1%2C+correlating+with+serum+corticosterone+in+microarray+analysis.&rft.au=Cheng%2C+R+Y+S%3BBirely%2C+L+A%3BLum%2C+N+L%3BPerella%2C+C+M%3BCherry%2C+J+M%3BBhat%2C+N+K%3BKasprzak%2C+K+S%3BPowell%2C+D+A%3BAlvord%2C+W+G%3BAnderson%2C+L+M&rft.aulast=Cheng&rft.aufirst=R+Y&rft.date=2004-02-01&rft.volume=32&rft.issue=1&rft.spage=257&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 - 2005-03-17 N1 - Date created - 2004-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxane-mediated antiangiogenesis in vitro: influence of formulation vehicles and binding proteins. AN - 80153448; 14871806 AB - Paclitaxel (Taxol) and docetaxel (Taxotere) have been shown to inhibit angiogenesis at low concentrations that do not affect cancer cell proliferation. Here, we used rat aortic rings and human umbilical vein endothelial cells to evaluate the influence of their formulation vehicles Cremophor EL and polysorbate 80, as well as serum binding proteins on taxane-mediated antiangiogenesis. The data show that clinically relevant concentrations of the vehicles and binding proteins nullify the antiangiogenic activity of both taxanes. It is suggested that these agents may need to be used at much higher doses than anticipated for effective antiangiogenic chemotherapy. JF - Cancer research AU - Ng, Sylvia S W AU - Figg, William D AU - Sparreboom, Alex AD - Molecular Pharmacology Section, Cancer Therapeutics Branch, Center for Cancer Research, and Clinical Pharmacology Research Core, Medical Oncology Clinical Research Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/02/01/ PY - 2004 DA - 2004 Feb 01 SP - 821 EP - 824 VL - 64 IS - 3 SN - 0008-5472, 0008-5472 KW - Angiogenesis Inhibitors KW - 0 KW - Blood Proteins KW - Excipients KW - Pharmaceutical Vehicles KW - Polysorbates KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - cremophor EL KW - 6D4M1DAL6O KW - Paclitaxel KW - P88XT4IS4D KW - Glycerol KW - PDC6A3C0OX KW - Index Medicus KW - Animals KW - Drug Interactions KW - Endothelium, Vascular -- cytology KW - Excipients -- pharmacology KW - Aorta, Thoracic -- cytology KW - Chemistry, Pharmaceutical KW - Humans KW - Cell Division -- drug effects KW - Protein Binding KW - Rats KW - Pharmaceutical Vehicles -- pharmacology KW - Rats, Sprague-Dawley KW - Aorta, Thoracic -- drug effects KW - Endothelium, Vascular -- drug effects KW - In Vitro Techniques KW - Excipients -- chemistry KW - Blood Proteins -- metabolism KW - Pharmaceutical Vehicles -- chemistry KW - Male KW - Paclitaxel -- chemistry KW - Angiogenesis Inhibitors -- pharmacology KW - Neovascularization, Pathologic -- drug therapy KW - Polysorbates -- pharmacology KW - Glycerol -- analogs & derivatives KW - Paclitaxel -- pharmacology KW - Polysorbates -- chemistry KW - Angiogenesis Inhibitors -- chemistry KW - Taxoids -- pharmacology KW - Taxoids -- chemistry KW - Glycerol -- pharmacology KW - Glycerol -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80153448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Taxane-mediated+antiangiogenesis+in+vitro%3A+influence+of+formulation+vehicles+and+binding+proteins.&rft.au=Ng%2C+Sylvia+S+W%3BFigg%2C+William+D%3BSparreboom%2C+Alex&rft.aulast=Ng&rft.aufirst=Sylvia+S&rft.date=2004-02-01&rft.volume=64&rft.issue=3&rft.spage=821&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 - 2004-04-09 N1 - Date created - 2004-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer-associated molecular signature in the tissue samples of patients with cirrhosis. AN - 80149479; 14768006 AB - Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P <.001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P <.001). Many genes were previously known to be related to HCC. The 273-gene signature was validated as cancer-associated genes by matching this set to additional independent tumor tissue samples from 163 patients with HCC, 56 patients with lung carcinoma, and 38 patients with breast carcinoma. From this signature, 30 genes were altered most significantly in tissue samples from high-risk individuals with cirrhosis and from patients with HCC. Among them, 12 genes encoded secretory proteins found in sera. In conclusion, we identified a unique gene signature in the tissue samples of patients with cirrhosis, which may be used as candidate markers for diagnosing the early onset of HCC in high-risk populations and may guide new strategies for chemoprevention. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). JF - Hepatology (Baltimore, Md.) AU - Kim, Jin Woo AU - Ye, Qinghai AU - Forgues, Marshonna AU - Chen, Yidong AU - Budhu, Anuradha AU - Sime, Jessica AU - Hofseth, Lorne J AU - Kaul, Rashmi AU - Wang, Xin Wei AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 518 EP - 527 VL - 39 IS - 2 SN - 0270-9139, 0270-9139 KW - Antigens, Neoplasm KW - 0 KW - Cell Adhesion Molecules KW - Epithelial Cell Adhesion Molecule KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Cell Adhesion Molecules -- genetics KW - Risk Factors KW - Humans KW - Antigens, Neoplasm -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- epidemiology KW - Liver Cirrhosis -- etiology KW - Liver Cirrhosis -- epidemiology KW - Liver Cirrhosis -- genetics KW - Carcinoma, Hepatocellular -- epidemiology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80149479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cancer-associated+molecular+signature+in+the+tissue+samples+of+patients+with+cirrhosis.&rft.au=Kim%2C+Jin+Woo%3BYe%2C+Qinghai%3BForgues%2C+Marshonna%3BChen%2C+Yidong%3BBudhu%2C+Anuradha%3BSime%2C+Jessica%3BHofseth%2C+Lorne+J%3BKaul%2C+Rashmi%3BWang%2C+Xin+Wei&rft.aulast=Kim&rft.aufirst=Jin&rft.date=2004-02-01&rft.volume=39&rft.issue=2&rft.spage=518&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 - 2004-03-11 N1 - Date created - 2004-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of NF-kappaB and STAT3 in rat oval cells during 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration. AN - 80147574; 14767990 AB - Proliferation and differentiation of hepatic stem cell progenies (i.e., oval cells) sustain liver regeneration when the replicative and functional capacity of hepatocytes is impaired. The signaling pathways that control stem cell activation remain poorly understood. In this study, we investigated the involvement of nuclear factor-kappa B (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) in oval cell-mediated liver regeneration induced by 2-acetylaminofluorene/partial hepatectomy (AAF/PH) protocol. Using OV1 as a marker for identification and sorting of oval cells, we established that both NF-kappaB and STAT3 were highly activated in the OV1(+) cell population. Three distinct subpopulations of oval cells were defined as OV1(low), OV1(medium), and OV1(high), based on the intensity of OV1 staining. Quantitative polymerase chain reaction analysis revealed that they represent different stages of oval cell differentiation along hepatocyte lineage. OV1(low) cells displayed the least differentiated phenotype as judged by high expression of c-kit and lack of hepatocytic differentiation markers, whereas OV1(high) cells lost c-kit expression, were more proliferative, and acquired more mature hepatocytic phenotype. Notably, NF-kappaB was activated uniformly in all three subpopulations of oval cells. In contrast, phosphorylation of STAT3 was detected only in OV1(high) cells. In conclusion, transcriptional activity supported by NF-kappaB and STAT3 is required for oval cell activation, expansion, and differentiation. The differential induction of NF-kappaB and STAT3 point to a distinct role for these transcription factors at different stages of hepatic stem cell differentiation. JF - Hepatology (Baltimore, Md.) AU - Sánchez, Aránzazu AU - Factor, Valentina M AU - Schroeder, Insa S AU - Nagy, Peter AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 376 EP - 385 VL - 39 IS - 2 SN - 0270-9139, 0270-9139 KW - Carcinogens KW - 0 KW - DNA-Binding Proteins KW - NF-kappa B KW - STAT3 Transcription Factor KW - Stat3 protein, rat KW - Trans-Activators KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Gene Expression KW - Cell Differentiation KW - Disease Models, Animal KW - Rats KW - Phenotype KW - Rats, Inbred F344 KW - Phosphorylation KW - Hepatectomy KW - Male KW - Cell Division KW - Trans-Activators -- metabolism KW - Stem Cells -- cytology KW - Stem Cells -- metabolism KW - Liver Regeneration -- physiology KW - Hepatocytes -- cytology KW - NF-kappa B -- metabolism KW - Hepatocytes -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80147574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+NF-kappaB+and+STAT3+in+rat+oval+cells+during+2-acetylaminofluorene%2Fpartial+hepatectomy-induced+liver+regeneration.&rft.au=S%C3%A1nchez%2C+Ar%C3%A1nzazu%3BFactor%2C+Valentina+M%3BSchroeder%2C+Insa+S%3BNagy%2C+Peter%3BThorgeirsson%2C+Snorri+S&rft.aulast=S%C3%A1nchez&rft.aufirst=Ar%C3%A1nzazu&rft.date=2004-02-01&rft.volume=39&rft.issue=2&rft.spage=376&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 - 2004-03-11 N1 - Date created - 2004-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug onset cues, conditioned withdrawal, and drug relapse: comment on McDonald and Siegel (2004). AN - 80143245; 14769093 AB - Previous research has shown that under certain conditions environmental cues associated with morphine administration induce drug-opposite conditioned effects that mimic symptoms of opiate withdrawal. R. V. McDonald and S. Siegel (see record 2004-10475-001) extend these observations by demonstrating that acute exposure to a low dose of morphine induces symptoms of opiate withdrawal in rats previously exposed to a high dose of morphine. They hypothesized that early drug onset cues, repeatedly paired with later, larger drug effects, mediate the paradoxical effect of the low drug dose on behavior. They also hypothesized that conditioned withdrawal symptoms induced by the early drug onset cues may mediate the "priming" effect of drugs on relapse and craving. The authors of this comment discuss the degree to which the literature supports this hypothesis. JF - Experimental and clinical psychopharmacology AU - Bossert, Jennifer M AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, MD 21224, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 15 EP - 7; discussion 23-6 VL - 12 IS - 1 SN - 1064-1297, 1064-1297 KW - Index Medicus KW - Rats KW - Animals KW - Self Administration KW - Affect -- drug effects KW - Injections, Intravenous KW - Humans KW - Recurrence KW - Cues KW - Substance Withdrawal Syndrome -- psychology KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80143245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+psychopharmacology&rft.atitle=Drug+onset+cues%2C+conditioned+withdrawal%2C+and+drug+relapse%3A+comment+on+McDonald+and+Siegel+%282004%29.&rft.au=Bossert%2C+Jennifer+M%3BShaham%2C+Yavin&rft.aulast=Bossert&rft.aufirst=Jennifer&rft.date=2004-02-01&rft.volume=12&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-08 N1 - Date created - 2004-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Exp Clin Psychopharmacol. 2004 Feb;12(1):3-11 [14769091] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of paclitaxel cytotoxicity in lung and esophageal cancer cells by pharmacologic inhibition of the phosphoinositide 3-kinase/protein kinase B (Akt)-mediated signaling pathway. AN - 80137995; 14762343 AB - Constitutive activation of the phosphoinositide 3-kinase/protein kinase B survival signal transduction pathway influences the intrinsic chemoresistance of cancer cells. This study evaluates the effect of LY294002, a pharmacologic inhibitor of phosphoinositide 3-kinase, on the sensitivity of lung and esophageal cancer cells to paclitaxel (Taxol) in vitro. Materials and methods Cell viability and apoptosis of cancer cells treated with paclitaxel + LY294002 combinations were quantitated by methyl-thiazol-diphenyl-tetrazolium and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling-based ApoBrdU assays, respectively. The effect of LY294002-mediated phosphoinositide 3-kinase inhibition on protein kinase B (Akt) activation and nuclear factor-kappaB signaling was determined by Western blot analysis. Nuclear factor-kappaB transcription activity in cultured cancer cells either at baseline or after treatments with LY294002 or BAY11-0782 (a pharmacologic inhibitor of nuclear factor-kappaB) was determined by the nuclear factor-kappaB-Luciferase reporter system. A 4- to more than 20-fold reduction of paclitaxel IC(50) values was observed in cancer cells treated with paclitaxel + LY294002 combinations. This was paralleled with synergistic induction of apoptosis. LY294002 treatment caused a significant dose-dependent inhibition of protein kinase B (Akt) activation and suppression of nuclear factor-kappaB transcriptional activity that was accompanied by elevation of IkappaB, the intrinsic inhibitor of nuclear factor-kappaB, and concomitant reduction of nuclear factor-kappaB-regulated antiapoptotic proteins cIAP1, cIAP2, and BclXL. Direct inhibition of nuclear factor-kappaB activity by BAY11-0782 also resulted in profound enhancement of paclitaxel sensitivity and paclitaxel-mediated induction of apoptosis in lung and esophageal cancer cells. LY294002-mediated inhibition of the phosphoinositide 3-kinase/protein kinase B-dependent survival pathway with secondary suppression of nuclear factor-kappaB transcriptional activity was associated with enhancement of paclitaxel cytotoxicity in lung and esophageal cancer cells. Direct inhibition of nuclear factor-kappaB by BAY11-0782 also sensitized these cancer cells to paclitaxel, indicating that nuclear factor-kappaB may be the crucial intermediary step connecting phosphoinositide 3-kinase/protein kinase B (Akt) to the intrinsic susceptibility of cancer cells to chemotherapeutic agents. JF - The Journal of thoracic and cardiovascular surgery AU - Nguyen, Dao M AU - Chen, G Aaron AU - Reddy, Rishindra AU - Tsai, Wilson AU - Schrump, William D AU - Cole, George AU - Schrump, David S AD - Section of Throacic Oncology, Surgery Branch, Center for Cancer Research, National Cancer Center, National Institutes of Health, Bethesda, MD, USA. Dao_Nguyen@nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 365 EP - 375 VL - 127 IS - 2 SN - 0022-5223, 0022-5223 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Chromones KW - Enzyme Inhibitors KW - Morpholines KW - NF-kappa B KW - Proto-Oncogene Proteins KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Paclitaxel KW - P88XT4IS4D KW - Abridged Index Medicus KW - Index Medicus KW - Treatment Failure KW - Enzyme Inhibitors -- administration & dosage KW - Dose-Response Relationship, Drug KW - Humans KW - Morpholines -- administration & dosage KW - Chromones -- administration & dosage KW - Phosphorylation -- drug effects KW - Drug Therapy, Combination KW - NF-kappa B -- drug effects KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Apoptosis -- drug effects KW - Enzyme Activation -- drug effects KW - Statistics as Topic KW - Down-Regulation -- drug effects KW - Time Factors KW - NF-kappa B -- metabolism KW - Paclitaxel -- administration & dosage KW - Lung Neoplasms -- enzymology KW - Phosphatidylinositol 3-Kinases -- drug effects KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Lung Neoplasms -- drug therapy KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- antagonists & inhibitors KW - Antineoplastic Agents, Phytogenic -- toxicity KW - Paclitaxel -- toxicity KW - Proto-Oncogene Proteins -- drug effects KW - Esophageal Neoplasms -- enzymology KW - Signal Transduction -- drug effects KW - Carcinoma, Non-Small-Cell Lung -- enzymology KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Esophageal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80137995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+thoracic+and+cardiovascular+surgery&rft.atitle=Potentiation+of+paclitaxel+cytotoxicity+in+lung+and+esophageal+cancer+cells+by+pharmacologic+inhibition+of+the+phosphoinositide+3-kinase%2Fprotein+kinase+B+%28Akt%29-mediated+signaling+pathway.&rft.au=Nguyen%2C+Dao+M%3BChen%2C+G+Aaron%3BReddy%2C+Rishindra%3BTsai%2C+Wilson%3BSchrump%2C+William+D%3BCole%2C+George%3BSchrump%2C+David+S&rft.aulast=Nguyen&rft.aufirst=Dao&rft.date=2004-02-01&rft.volume=127&rft.issue=2&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.issn=00225223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-25 N1 - Date created - 2004-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - L-histidine is a beneficial adjuvant for antiepileptic drugs against maximal electroshock-induced seizures in mice. AN - 80137022; 14752621 AB - Endogenous histamine has been reported to be involved in regulation of seizure susceptibility. Enhancement of histamine neurotransmission engendered by L-histidine treatment produces anticonvulsant effects in experimental animals. The present study investigated the influence of L-histidine on the protective effects of carbamazepine and phenytoin against maximal electroshock-induced seizures in mice.L-Histidine, administered at the doses that did not influence the threshold for electroconvulsions (250-500 mg/kg), enhanced by nearly 30% the protective effects of carbamazepine against maximal electroshock-induced seizures. D-Histidine (1000 mg/kg), an inactive isomer of histidine, was without any effect in this regard. L-Histidine (500 mg/kg) also augmented the protective effects of phenytoin. Importantly, the enhancement of the anticonvulsant effects of these antiepileptic drugs produced by L-histidine co-administration was not associated with augmentation of their unwanted effects on memory and motor performance. A pharmacokinetic interaction was also excluded since the free plasma levels of these antiepileptics remained unchanged in the presence of L-histidine. It may be suggested that L-histidine could serve as a beneficial adjuvant for selected antiepileptic drugs. JF - Amino acids AU - Kamiński, R M AU - Zółkowska, D AU - Kozicka, M AU - Kleinrok, Z AU - Czuczwar, S J AD - Isotope Laboratory, Institute of Agricultural Medicine, Lublin, Poland. kamiskr@ninds.nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 85 EP - 89 VL - 26 IS - 1 SN - 0939-4451, 0939-4451 KW - Anticonvulsants KW - 0 KW - Carbamazepine KW - 33CM23913M KW - Histidine KW - 4QD397987E KW - Phenytoin KW - 6158TKW0C5 KW - Index Medicus KW - Animals KW - Mice KW - Electroshock KW - Drug Synergism KW - Histidine -- administration & dosage KW - Seizures -- blood KW - Carbamazepine -- blood KW - Phenytoin -- blood KW - Carbamazepine -- administration & dosage KW - Seizures -- drug therapy KW - Anticonvulsants -- administration & dosage KW - Anticonvulsants -- blood KW - Phenytoin -- administration & dosage KW - Histidine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80137022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Amino+acids&rft.atitle=L-histidine+is+a+beneficial+adjuvant+for+antiepileptic+drugs+against+maximal+electroshock-induced+seizures+in+mice.&rft.au=Kami%C5%84ski%2C+R+M%3BZ%C3%B3%C5%82kowska%2C+D%3BKozicka%2C+M%3BKleinrok%2C+Z%3BCzuczwar%2C+S+J&rft.aulast=Kami%C5%84ski&rft.aufirst=R&rft.date=2004-02-01&rft.volume=26&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Amino+acids&rft.issn=09394451&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-11 N1 - Date created - 2004-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Eighteenth Aspen Cancer Conference: mechanisms of toxicity, carcinogenesis, cancer prevention, and cancer therapy. AN - 80132053; 14750211 JF - Molecular carcinogenesis AU - Tennant, Raymond AU - Sander, Miriam AU - Harris, Curtis AU - Trump, Benjamin Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 61 EP - 78 VL - 39 IS - 2 KW - Index Medicus KW - Animals KW - Humans KW - Drug-Related Side Effects and Adverse Reactions KW - Chromatin Assembly and Disassembly KW - Molecular Diagnostic Techniques KW - Stem Cells -- pathology KW - Neoplasms -- pathology KW - Neoplasms -- prevention & control KW - Neoplasms -- therapy KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80132053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Eighteenth+Aspen+Cancer+Conference%3A+mechanisms+of+toxicity%2C+carcinogenesis%2C+cancer+prevention%2C+and+cancer+therapy.&rft.au=Tennant%2C+Raymond%3BSander%2C+Miriam%3BHarris%2C+Curtis%3BTrump%2C+Benjamin&rft.aulast=Tennant&rft.aufirst=Raymond&rft.date=2004-02-01&rft.volume=39&rft.issue=2&rft.spage=61&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 - 2004-03-10 N1 - Date created - 2004-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of reactive oxygen species in LPS-induced production of prostaglandin E2 in microglia. AN - 80129903; 14756815 AB - We determined the roles of reactive oxygen species (ROS) in the expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated microglia. LPS treatment increased intracellular ROS in rat microglia dose-dependently. Pre-treatment with superoxide dismutase (SOD)/catalase, or SOD/catalase mimetics that can scavenge intracellular ROS, significantly attenuated LPS-induced release in PGE2. Diphenylene iodonium (DPI), a non-specific NADPH oxidase inhibitor, decreased LPS-induced PGE2 production. In addition, microglia from NADPH oxidase-deficient mice produced less PGE2 than those from wild-type mice following LPS treatment. Furthermore, LPS-stimulated expression of COX-2 (determined by RT-PCR analysis of COX-2 mRNA and western blot for its protein) was significantly reduced by pre-treatment with SOD/catalase or SOD/catalase mimetics. SOD/catalase mimetics were more potent than SOD/catalase in reducing COX-2 expression and PGE2 production. As a comparison, scavenging ROS had no effect on LPS-induced nitric oxide production in microglia. These results suggest that ROS play a regulatory role in the expression of COX-2 and the subsequent production of PGE2 during the activation process of microglia. Thus, inhibiting NADPH oxidase activity and subsequent ROS generation in microglia can reduce COX-2 expression and PGE2 production. These findings suggest a potential therapeutic intervention strategy for the treatment of inflammation-mediated neurodegenerative diseases. JF - Journal of neurochemistry AU - Wang, Tongguang AU - Qin, Liya AU - Liu, Bin AU - Liu, Yuxin AU - Wilson, Belinda AU - Eling, Thomas E AU - Langenbach, Robert AU - Taniura, Seijiro AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina 27709, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 939 EP - 947 VL - 88 IS - 4 SN - 0022-3042, 0022-3042 KW - Catecholamines KW - 0 KW - EUK-134 KW - EUK-189 KW - Fluoresceins KW - Imidazolines KW - Isoenzymes KW - Lipopolysaccharides KW - Organometallic Compounds KW - RNA, Messenger KW - Reactive Oxygen Species KW - Salicylates KW - Tetrazolium Salts KW - Thiazoles KW - diacetyldichlorofluorescein KW - 2044-85-1 KW - Nitric Oxide KW - 31C4KY9ESH KW - (3,4-dihydroxyphenylamino)-2-imidazoline KW - DEA5VW1N6R KW - Catalase KW - EC 1.11.1.6 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Nos2 protein, rat KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - thiazolyl blue KW - EUY85H477I KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Animals KW - Drug Interactions KW - Brain -- cytology KW - Nitric Oxide -- metabolism KW - Blotting, Western -- methods KW - Tetrazolium Salts -- pharmacology KW - Catalase -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Fluoresceins -- pharmacology KW - Isoenzymes -- metabolism KW - Salicylates -- pharmacology KW - Mice, Knockout KW - Rats KW - Rats, Inbred F344 KW - Superoxide Dismutase -- pharmacology KW - Intracellular Space -- drug effects KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Nitric Oxide Synthase -- metabolism KW - Extracellular Space -- drug effects KW - Catecholamines -- pharmacology KW - Organometallic Compounds -- pharmacology KW - Cell Count KW - Dose-Response Relationship, Drug KW - Intracellular Space -- metabolism KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - Isoenzymes -- genetics KW - Pregnancy KW - Thiazoles -- pharmacology KW - Animals, Newborn KW - Cells, Cultured KW - Extracellular Space -- metabolism KW - Mice, Inbred C57BL KW - NADPH Oxidase -- genetics KW - Female KW - Reactive Oxygen Species -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Dinoprostone -- metabolism KW - Microglia -- drug effects KW - Microglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80129903?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reactive+oxygen+species+in+LPS-induced+production+of+prostaglandin+E2+in+microglia.&rft.au=Wang%2C+Tongguang%3BQin%2C+Liya%3BLiu%2C+Bin%3BLiu%2C+Yuxin%3BWilson%2C+Belinda%3BEling%2C+Thomas+E%3BLangenbach%2C+Robert%3BTaniura%2C+Seijiro%3BHong%2C+Jau-Shyong&rft.aulast=Wang&rft.aufirst=Tongguang&rft.date=2004-02-01&rft.volume=88&rft.issue=4&rft.spage=939&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 - 2004-03-15 N1 - Date created - 2004-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Forced homodimerization by site-directed mutagenesis alters guanylyl cyclase activity of natriuretic peptide receptor B. AN - 80128219; 14691198 AB - Natriuretic peptides mediate their physiologic effects through activation of membrane-bound, guanylyl cyclase-coupled receptors (NPRs). Receptor dimerization is an important feature of signal transduction. This study was aimed at characterizing structurally important residues of the extracellular ligand-binding domain of NPR-B for receptor dimerization and cGMP generation. Deletion mutagenesis was used to replace cysteine residues at positions 53 (C53S), 417 (C417S), and 426 (C426S) by serine. Receptor expression, dimerization, whole-cell cGMP response, and guanylyl cyclase activity of membrane fractions were determined in stably transfected COS-7 cells. C53S, C417S, and C426S mutants were expressed and found to form disulfide-bridged covalent dimers. In contrast to NPR-B and C53S, C417S and C426S mutants displayed constitutive activity in whole cells (C417S, 146+/-12%, P<0.01; C426S, 153+/-7% of ligand-independent NPR-B cGMP generation, P<0.01). The cGMP response of C417S and C426S mutants in whole cells was dose dependent and approximately 4 times lower than that in NPR-B, whereas it was blunted in C53S-transfected cells (1 micromol/L CNP, NPR-B 2868+/-436%; C53S, 206+/-16% of control, P<0.001 vs NPR-B, C417S, and C426S). Guanylyl cyclase assay in transfected cells confirmed the constitutive activity of C417S and C426S mutants. These data suggest that receptor dimerization by covalent disulfide bridges alters ligand-independent as well as ligand-dependent receptor activity. Localization of the crosslink in relation to the cell membrane is important for configuration of the extracellular domain and the consecutive signal transduction. JF - Hypertension (Dallas, Tex. : 1979) AU - Langenickel, Thomas AU - Buttgereit, Jens AU - Pagel, Ines AU - Dietz, Rainer AU - Willenbrock, Roland AU - Bader, Michael AD - Max-Delbrueck-Center for Molecular Medicine, Berlin-Buch, Berlin, Germany. langenit@nhlbi.nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 460 EP - 465 VL - 43 IS - 2 KW - RNA, Messenger KW - 0 KW - Guanylate Cyclase KW - EC 4.6.1.2 KW - Receptors, Atrial Natriuretic Factor KW - atrial natriuretic factor receptor B KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - RNA, Messenger -- metabolism KW - COS Cells KW - Dimerization KW - Cercopithecus aethiops KW - Protein Structure, Tertiary KW - Guanylate Cyclase -- metabolism KW - Receptors, Atrial Natriuretic Factor -- genetics KW - Receptors, Atrial Natriuretic Factor -- metabolism KW - Receptors, Atrial Natriuretic Factor -- chemistry KW - Guanylate Cyclase -- chemistry KW - Guanylate Cyclase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80128219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Forced+homodimerization+by+site-directed+mutagenesis+alters+guanylyl+cyclase+activity+of+natriuretic+peptide+receptor+B.&rft.au=Langenickel%2C+Thomas%3BButtgereit%2C+Jens%3BPagel%2C+Ines%3BDietz%2C+Rainer%3BWillenbrock%2C+Roland%3BBader%2C+Michael&rft.aulast=Langenickel&rft.aufirst=Thomas&rft.date=2004-02-01&rft.volume=43&rft.issue=2&rft.spage=460&rft.isbn=&rft.btitle=&rft.title=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.issn=1524-4563&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-12 N1 - Date created - 2004-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Susceptibility of common fibroblast cell lines to transmissible spongiform encephalopathy agents. AN - 80126391; 14745700 AB - The risk of contamination of tissue culture cells with transmissible spongiform encephalopathy (TSE) agents as a result of the use of animal products as medium components has been considered to be low, in part, because only a few brain-derived cell lines have been reported to be susceptible to TSE infection. In the present study, we demonstrate that the common laboratory fibroblast cell lines NIH/3T3 and L929, which express low levels of cellular mouse prion protein, are susceptible to infection with mouse-adapted scrapie. Our results show that the susceptibility of a cell line to TSE infection cannot be predicted on the basis of its tissue origin or its level of expression of the cellular prion protein, and they suggest that any cell line expressing normal host prion protein could have the potential to support propagation of TSE agents. Thus, testing of cells for TSE susceptibility might be necessary for all cell lines that are routinely used in vaccine production and in other medical applications. JF - The Journal of infectious diseases AU - Vorberg, Ina AU - Raines, Anne AU - Story, Brian AU - Priola, Suzette A AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. vorberg@lrz.tum.de Y1 - 2004/02/01/ PY - 2004 DA - 2004 Feb 01 SP - 431 EP - 439 VL - 189 IS - 3 SN - 0022-1899, 0022-1899 KW - PrPC Proteins KW - 0 KW - PrPSc Proteins KW - Prions KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - PrPC Proteins -- biosynthesis KW - Animals KW - 3T3 Cells KW - Mice, Inbred C57BL KW - Mice KW - Fibroblasts -- metabolism KW - PrPSc Proteins -- biosynthesis KW - PrPSc Proteins -- toxicity KW - Prions -- metabolism KW - PrPSc Proteins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80126391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Susceptibility+of+common+fibroblast+cell+lines+to+transmissible+spongiform+encephalopathy+agents.&rft.au=Vorberg%2C+Ina%3BRaines%2C+Anne%3BStory%2C+Brian%3BPriola%2C+Suzette+A&rft.aulast=Vorberg&rft.aufirst=Ina&rft.date=2004-02-01&rft.volume=189&rft.issue=3&rft.spage=431&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 - 2004-04-05 N1 - Date created - 2004-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human exposure monitoring and evaluation in the Arctic: the importance of understanding exposures to the development of public health policy. AN - 80125833; 14757538 AB - Arctic indigenous peoples face significant challenges resulting from the contamination of Arctic air, water, and soil by persistent organic pollutants, heavy metals, and radionuclides. International cooperative efforts among governments and research institutions are under way to collect the information needed by environmental health scientists and public health officials to address environmental contamination in the Arctic. However, the climatic, political, and cultural conditions of the land and its native populations combine to present a unique set of scientific and logistic challenges to addressing this important public health issue. Public health officials have the responsibility to respect the cultural traditions of indigenous communities, while simultaneously designing strategies that will reduce their exposure to environmental contaminants and rates of disease and dysfunction. Researchers can better understand the link between environmental exposures and disease through monitoring programs for both the subsistence diets and health status of the indigenous populations. We suggest that the incorporation of community-based participatory research methods into programs designed to assess biomarkers of contaminant exposure in children and adults may be a valuable addition to ongoing and newly developed research programs. This approach could serve as a model for international environmental health initiatives, because it involves the participation of the local communities and seeks to builds trust between all stakeholders. JF - Environmental health perspectives AU - Suk, William A AU - Avakian, Maureen D AU - Carpenter, David AU - Groopman, John D AU - Scammell, Madeleine AU - Wild, Christopher P AD - Center for Risk and Integrated Strategies, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. suk@niehs.nih.edu Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 113 EP - 120 VL - 112 IS - 2 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Humans KW - Adult KW - Community Participation KW - Child KW - Diet KW - Research Design KW - Child Welfare KW - Arctic Regions KW - Policy Making KW - Environmental Pollutants -- poisoning KW - Environmental Exposure KW - Health Policy KW - Environmental Pollutants -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80125833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+exposure+monitoring+and+evaluation+in+the+Arctic%3A+the+importance+of+understanding+exposures+to+the+development+of+public+health+policy.&rft.au=Suk%2C+William+A%3BAvakian%2C+Maureen+D%3BCarpenter%2C+David%3BGroopman%2C+John+D%3BScammell%2C+Madeleine%3BWild%2C+Christopher+P&rft.aulast=Suk&rft.aufirst=William&rft.date=2004-02-01&rft.volume=112&rft.issue=2&rft.spage=113&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 - 2004-05-06 N1 - Date created - 2004-02-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Public Health. 2001 Nov;91(11):1776-82 [11684600] Environ Health Perspect. 2002 Apr;110 Suppl 2:145-8 [11929722] Annu Rev Public Health. 1998;19:173-202 [9611617] Environ Sci Technol. 2002 May 1;36(9):1886-92 [12026966] Am J Clin Nutr. 1975 Sep;28(9):958-66 [1163480] Soc Sci Med. 1987;24(10):791-804 [3616676] Soc Sci Med. 1989;29(8):965-74 [2814583] Sci Total Environ. 1992 Jul 15;122(1-2):1-74 [1514103] Arctic Med Res. 1991;Suppl:747-51 [1365288] Sci Total Environ. 1995 Jan 15;160-161:529-37 [7892583] Can J Physiol Pharmacol. 1995 Jun;73(6):765-71 [7585351] Environ Health Perspect. 2000 Apr;108(4):279-81 [10753083] Sci Total Environ. 1999 Jun 1;230(1-3):1-82 [10466227] Health Educ Behav. 1999 Aug;26(4):563-78 [10435238] Environ Health Perspect. 1999 Jul;107(7):A338-9 [10379011] Environ Health Perspect. 1998 Feb;106(2):A64-9 [9456342] Carcinogenesis. 1999 Jan;20(1):1-11 [9934843] Neurotoxicology. 1996 Spring;17(1):251-6 [8784836] Am J Public Health. 2001 Oct;91(10):1549-52 [11574301] Environ Health Perspect. 2001 Jun;109 Suppl 3:449-55 [11427395] J Occup Environ Med. 2001 Jun;43(6):526-33 [11411324] Neurology. 2000 Oct 24;55(8):1144-50 [11071492] Environ Health Perspect. 2000 Sep;108(9):907-10 [11017898] Risk Anal. 2000 Feb;20(1):101-11 [10795343] J Natl Cancer Inst. 2000 Apr 19;92(8):602-12 [10772677] Int J Hyg Environ Health. 2002 Mar;205(1-2):137-41 [12018007] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor. AN - 80119711; 14600250 AB - Human CYP2C9 is important in the metabolism of numerous clinically used drugs such as the anticoagulant warfarin, the anticonvulsant phenytoin, antidiabetic drugs such as tolbutamide and glipizide, the hypertensive agent losartan, and numerous nonsteroidal anti-inflammatory drugs. Several studies have reported that certain drugs such as rifampicin and phenobarbital induce CYP2C9, but the molecular basis for this induction remains unknown. In the present study, we demonstrate that the human pregnane X receptor (hPXR) mediates induction of CYP2C9 by the prototype drugs rifampicin, hyperforin (found in St. John's Wart), and phenobarbital. Deletion and mutagenesis studies with luciferase reporter constructs showed that a functional PXR-responsive element located -1839/-1824 base pairs upstream from the translation start site was the primary binding site mediating the rifampicin induction of CYP2C9. This site was previously described as a constitutive androstane receptor-responsive element (CAR-RE). Mutational analysis of 3- and 12-kilobase CYP2C9 promoter fragments indicated that this proximal binding site was essential for rifampicin inducibility, although a cooperative effect could be attributed to a second CAR-RE located at -2899/-2883. In summary, we have demonstrated rifampicin induction of CYP2C9 promoter constructs that is consistent with the magnitude of induction of CYP2C9 protein and mRNA reported in vivo and in primary human hepatocytes, and we have identified the cis-element essential for this response. This is the first report to demonstrate that the nuclear receptor PXR mediates induction of CYP2C9 with rifampicin, phenobarbital, and hyperforin. JF - The Journal of pharmacology and experimental therapeutics AU - Chen, Yuping AU - Ferguson, Stephen S AU - Negishi, Masahiko AU - Goldstein, Joyce A AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 495 EP - 501 VL - 308 IS - 2 SN - 0022-3565, 0022-3565 KW - Anti-Bacterial Agents KW - 0 KW - Bridged Bicyclo Compounds KW - Excitatory Amino Acid Antagonists KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Steroid KW - Terpenes KW - pregnane X receptor KW - Phloroglucinol KW - DHD7FFG6YS 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 - hyperforin KW - RM741E34FP KW - Rifampin KW - VJT6J7R4TR KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Phloroglucinol -- analogs & derivatives KW - Tumor Cells, Cultured KW - Promoter Regions, Genetic -- drug effects KW - Humans KW - Anti-Bacterial Agents -- pharmacology KW - Enzyme Induction KW - Transcriptional Activation KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Binding Sites KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Phenobarbital -- pharmacology KW - Receptors, Steroid -- physiology KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Terpenes -- pharmacology KW - Rifampin -- pharmacology KW - Aryl Hydrocarbon Hydroxylases -- genetics KW - Aryl Hydrocarbon Hydroxylases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80119711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+human+CYP2C9+by+rifampicin%2C+hyperforin%2C+and+phenobarbital+is+mediated+by+the+pregnane+X+receptor.&rft.au=Chen%2C+Yuping%3BFerguson%2C+Stephen+S%3BNegishi%2C+Masahiko%3BGoldstein%2C+Joyce+A&rft.aulast=Chen&rft.aufirst=Yuping&rft.date=2004-02-01&rft.volume=308&rft.issue=2&rft.spage=495&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 - 2004-03-11 N1 - Date created - 2004-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Do drugs of abuse impact on HIV disease? AN - 80119481; 14741417 AB - Drug abuse, certain lifestyles, access and adherence to drug abuse treatment, and medical consequences of drug abuse remain as important factors that impact on HIV disease among AIDS patients worldwide. Most in vitro and in vivo studies show a significant impact on HIV disease. Epidemiological studies in the past have failed to support these observations. However, new and limited evidence shows that drug abuse may accelerate HIV disease in humans. Research is needed to design new or refine known techniques that more closely mimic natural conditions of HIV disease, and perform additional assessments of basic laboratory, clinical, and epidemiological data to determine whether drug abuse significantly impacts on HIV disease. JF - Journal of neuroimmunology AU - Khalsa, Jag H AU - Royal, Walter AD - Center on AIDS and Other Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Boulevard, Bethesda, MD 20892-9593, USA. jk98p@nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 6 EP - 8 VL - 147 IS - 1-2 SN - 0165-5728, 0165-5728 KW - Index Medicus KW - Humans KW - Disease Progression KW - Acquired Immunodeficiency Syndrome -- pathology KW - Acquired Immunodeficiency Syndrome -- complications KW - HIV Infections -- complications KW - Substance-Related Disorders -- pathology KW - Acquired Immunodeficiency Syndrome -- psychology KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- psychology KW - HIV UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80119481?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroimmunology&rft.atitle=Do+drugs+of+abuse+impact+on+HIV+disease%3F&rft.au=Khalsa%2C+Jag+H%3BRoyal%2C+Walter&rft.aulast=Khalsa&rft.aufirst=Jag&rft.date=2004-02-01&rft.volume=147&rft.issue=1-2&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimmunology&rft.issn=01655728&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-15 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protective effect of the SOD/catalase mimetic MnTMPyP on inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuronal-glial cultures. AN - 80117350; 14741430 AB - Reactive oxygen species (ROS) produced by activated microglia are deleterious to neurons. In this study, we studied the effect of Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a superoxide dismutase/catalase mimetic, on the lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons in rat mesencephalic neuroglia cultures. MnTMPyP exhibited a significantly protective effect against LPS (5 ng/ml)-induced neurotoxicity as determined by [3H]dopamine uptake and immunocytochemical analysis. MnTMPyP significantly attenuated LPS-induced production of superoxide free radical and prostaglandin E(2) (PGE(2)) in microglia. These results indicate that MnTMPyP may potentially be used for the treatment of inflammation-related degenerative neurological disorders. JF - Journal of neuroimmunology AU - Wang, Tongguang AU - Liu, Bin AU - Qin, Liya AU - Wilson, Belinda AU - Hong, Jau Shong AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 68 EP - 72 VL - 147 IS - 1-2 SN - 0165-5728, 0165-5728 KW - Free Radical Scavengers KW - 0 KW - Lipopolysaccharides KW - Metalloporphyrins KW - Tritium KW - 10028-17-8 KW - Superoxides KW - 11062-77-4 KW - tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex KW - 70649-54-6 KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Dinoprostone KW - K7Q1JQR04M KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Drug Interactions KW - Tritium -- metabolism KW - Dose-Response Relationship, Drug KW - Nerve Degeneration -- chemically induced KW - Catalase -- pharmacology KW - Rats KW - Nerve Degeneration -- drug therapy KW - Animals, Newborn KW - Superoxides -- metabolism KW - Rats, Inbred F344 KW - Superoxide Dismutase -- pharmacology KW - Nerve Degeneration -- metabolism KW - Cells, Cultured KW - Dinoprostone -- metabolism KW - Molecular Mimicry KW - Immunohistochemistry KW - Neuroglia -- metabolism KW - Mesencephalon -- metabolism KW - Mesencephalon -- drug effects KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Metalloporphyrins -- pharmacology KW - Dopamine -- metabolism KW - Neuroglia -- drug effects KW - Mesencephalon -- cytology KW - Free Radical Scavengers -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80117350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroimmunology&rft.atitle=Protective+effect+of+the+SOD%2Fcatalase+mimetic+MnTMPyP+on+inflammation-mediated+dopaminergic+neurodegeneration+in+mesencephalic+neuronal-glial+cultures.&rft.au=Wang%2C+Tongguang%3BLiu%2C+Bin%3BQin%2C+Liya%3BWilson%2C+Belinda%3BHong%2C+Jau+Shong&rft.aulast=Wang&rft.aufirst=Tongguang&rft.date=2004-02-01&rft.volume=147&rft.issue=1-2&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimmunology&rft.issn=01655728&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-15 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Design of a high-affinity competitive antagonist of the vanilloid receptor selective for the calcium entry-linked receptor population. AN - 80114620; 14742669 AB - We describe the synthesis and characterization of N-(4-chlorobenzyl) -N'-(4-hydroxy-3-iodo-5-methoxybenzyl)thiourea (IBTU), a novel antagonist of the vanilloid receptor 1 (TRPV1 or VR1). IBTU competitively inhibited 45Ca2+ uptake into CHO cells heterologously expressing rat TRPV1, whether induced by capsaicin or resiniferatoxin (Ki = 99 +/- 23 and 93 +/- 34 nM, respectively). IBTU was thus somewhat more potent (5-fold) than capsazepine. In contrast to its antagonism of vanilloid-induced calcium uptake, IBTU (30 microM) inhibited [3H]resiniferatoxin binding to TRPV1 by less than 10%. We hypothesize that these dramatically distinct potencies reflect different fractions of TRPV1 in this system: namely, a minor plasma membrane fraction controlling 45Ca2+ uptake, and the predominant intracellular fraction that dominates the [3H]resiniferatoxin binding measurements. Intracellular Ca2+ imaging supports this explanation. IBTU antagonized the elevation in intracellular Ca2+ in response to 50 nM capsaicin with an IC50 of 106 +/- 35 nM. Likewise, 600 nM IBTU was able to antagonize the elevation in intracellular Ca2+ in response to 100 pM resiniferatoxin in the presence of normal (1.8 mM) extracellular Ca2+, where the increase in intracellular calcium reflects calcium influx. In contrast, in the absence of extracellular Ca2+, where in this system resiniferatoxin induces a modest increase in calcium from intracellular stores, IBTU was unable to block the response to resiniferatoxin, although the TRPV1 antagonist 5-iodoresiniferatoxin was able to do so. In summary, IBTU is a novel, potent TRPV1 antagonist with marked selectivity between subpopulations of TRPV1 and may permit the function of these distinct pools to be explored and potentially exploited. JF - Molecular pharmacology AU - Tóth, Attila AU - Blumberg, Peter M AU - Chen, Zili AU - Kozikowski, Alan P AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 282 EP - 291 VL - 65 IS - 2 SN - 0026-895X, 0026-895X KW - N-(4-chlorobenzyl) -N'-(4-hydroxy-3-iodo-5-methoxybenzyl)thiourea KW - 0 KW - Receptors, Calcium-Sensing KW - Receptors, Drug KW - TRPV Cation Channels KW - TRPV1 receptor KW - Thiourea KW - GYV9AM2QAG KW - capsazepine KW - LFW48MY844 KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Binding, Competitive KW - CHO Cells KW - Drug Design KW - Cricetinae KW - Calcium -- metabolism KW - Receptors, Drug -- metabolism KW - Capsaicin -- chemistry KW - Thiourea -- pharmacology KW - Receptors, Calcium-Sensing -- metabolism KW - Capsaicin -- metabolism KW - Thiourea -- chemical synthesis KW - Capsaicin -- analogs & derivatives KW - Thiourea -- analogs & derivatives KW - Receptors, Drug -- antagonists & inhibitors KW - Thiourea -- metabolism KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80114620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Design+of+a+high-affinity+competitive+antagonist+of+the+vanilloid+receptor+selective+for+the+calcium+entry-linked+receptor+population.&rft.au=T%C3%B3th%2C+Attila%3BBlumberg%2C+Peter+M%3BChen%2C+Zili%3BKozikowski%2C+Alan+P&rft.aulast=T%C3%B3th&rft.aufirst=Attila&rft.date=2004-02-01&rft.volume=65&rft.issue=2&rft.spage=282&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 - 2004-03-12 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Preferential transcription of rabbit Aldh1a1 in the cornea: implication of hypoxia-related pathways. AN - 80098485; 14729976 AB - Here we examine the molecular basis for the known preferential expression of rabbit aldehyde dehydrogenase class 1 (ALDH1A1) in the cornea. The rabbit Aldh1a1 promoter-firefly luciferase reporter transgene (-3519 to +43) was expressed preferentially in corneal cells in transfection tests and in transgenic mice, with an expression pattern resembling that of rabbit Aldh1a1. The 5' flanking region of the rabbit Aldh1a1 gene resembled that in the human gene (60.2%) more closely than that in the mouse (46%) or rat (51.5%) genes. We detected three xenobiotic response elements (XREs) and one E-box consensus sequence in the rabbit Aldh1a1 upstream region; these elements are prevalent in other highly expressed corneal genes and can mediate stimulation by dioxin and repression by CoCl(2), which simulates hypoxia. The rabbit Aldh1a1 promoter was stimulated fourfold by dioxin in human hepatoma cells and repressed threefold by CoCl(2) treatment in rabbit corneal stromal and epithelial cells. Cotransfection, mutagenesis, and gel retardation experiments implicated the hypoxia-inducible factor 3alpha/aryl hydrocarbon nuclear translocator heterodimer for Aldh1a1 promoter activation via the XREs and stimulated by retinoic acid protein 13 for promoter repression via the E-box. These experiments suggest that XREs, E-boxes, and PAS domain/basic helix-loop-helix transcription factors (bHLH-PAS) contribute to preferential rabbit Aldh1a1 promoter activity in the cornea, implicating hypoxia-related pathways. JF - Molecular and cellular biology AU - Hough, R B AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 1324 EP - 1340 VL - 24 IS - 3 SN - 0270-7306, 0270-7306 KW - Environmental Pollutants KW - 0 KW - Isoenzymes KW - Polychlorinated Dibenzodioxins KW - Cobalt KW - 3G0H8C9362 KW - aldehyde dehydrogenase 1 KW - EC 1.2.1.- KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Retinal Dehydrogenase KW - EC 1.2.1.36 KW - cobaltous chloride KW - EVS87XF13W KW - Index Medicus KW - Rats KW - Environmental Pollutants -- pharmacology KW - Animals KW - Promoter Regions, Genetic -- drug effects KW - Humans KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Genes, Reporter KW - Rabbits KW - Organ Specificity KW - Mice KW - Cobalt -- pharmacology KW - Mice, Transgenic KW - Aldehyde Dehydrogenase -- genetics KW - Aldehyde Dehydrogenase -- drug effects KW - Isoenzymes -- biosynthesis KW - Cornea -- enzymology KW - Hypoxia -- metabolism KW - Cornea -- drug effects KW - Isoenzymes -- drug effects KW - Isoenzymes -- genetics KW - Aldehyde Dehydrogenase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80098485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Preferential+transcription+of+rabbit+Aldh1a1+in+the+cornea%3A+implication+of+hypoxia-related+pathways.&rft.au=Hough%2C+R+B%3BPiatigorsky%2C+J&rft.aulast=Hough&rft.aufirst=R&rft.date=2004-02-01&rft.volume=24&rft.issue=3&rft.spage=1324&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 - 2004-02-24 N1 - Date created - 2004-01-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4 [7539918] J Biol Chem. 1995 Jul 21;270(29):17521-7 [7615557] J Biol Chem. 1995 Nov 3;270(44):26292-302 [7592839] Nucleic Acids Res. 1995 Dec 11;23(23):4878-84 [8532532] Nature. 1996 Jan 25;379(6563):333-5 [8552186] Eur J Biochem. 1996 Feb 1;235(3):449-65 [8654388] J Biol Chem. 1996 Mar 1;271(9):5150-7 [8617795] J Biol Chem. 1996 Jun 28;271(26):15623-8 [8663049] Mol Cell Biol. 1996 Oct;16(10):5221-31 [8816435] J Biol Chem. 1996 Dec 27;271(52):33568-74 [8969223] Genes Dev. 1997 Jan 1;11(1):72-82 [9000051] Eur J Biochem. 1996 Dec 15;242(3):512-8 [9022676] Genes Dev. 1997 Aug 15;11(16):2052-65 [9284045] Nature. 2001 Nov 29;414(6863):550-4 [11734856] Mol Cell Biol. 2002 Feb;22(3):849-55 [11784860] CLAO J. 2002 Jan;28(1):12-27 [11838985] Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2848-53 [11880636] Cornea. 2002 Jul;21(5):453-7 [12072718] J Biol Chem. 2002 Sep 6;277(36):32405-8 [12119283] J Biol Chem. 2002 Nov 29;277(48):46544-51 [12297495] Blood. 1998 Oct 1;92(7):2260-8 [9746763] Gene Expr. 1998;7(3):205-13 [9840812] Arch Biochem Biophys. 1999 Jan 15;361(2):223-30 [9882450] J Cell Sci. 1999 Mar;112 ( Pt 5):613-22 [9973596] Invest Ophthalmol Vis Sci. 1999 Aug;40(9):1959-67 [10440249] Nucleic Acids Res. 1999 Aug 1;27(15):3205-12 [10454619] Biochem Pharmacol. 2000 Jan 1;59(1):65-85 [10605936] Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4058-63 [10737769] Genome Res. 2000 Apr;10(4):577-86 [10779500] Annu Rev Pharmacol Toxicol. 2000;40:519-61 [10836146] Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10442-7 [10973493] Biochemistry. 2000 Sep 12;39(36):11170-6 [10998257] Cornea. 2000 Nov;19(6):833-41 [11095059] J Biol Chem. 2002 Dec 6;277(49):47014-21 [12354771] Nature. 2002 Dec 5;420(6915):578-82 [12466853] Mol Vis. 2003 Jan 2;9:1-9 [12533723] J Biol Chem. 2003 Apr 25;278(17):15001-6 [12566446] J Biol Chem. 2003 May 2;278(18):15911-6 [12606543] J Biol Chem. 1997 Nov 28;272(48):30025-31 [9374477] Genes Dev. 1998 Mar 1;12(5):607-20 [9499397] J Biol Chem. 1998 Mar 20;273(12):6632-42 [9506959] Science. 1998 Jun 5;280(5369):1564-9 [9616112] Exp Eye Res. 1998 May;66(5):669-74 [9628812] Prog Retin Eye Res. 1998 Apr;17(2):145-74 [9695791] J Biol Chem. 1998 Aug 28;273(35):22584-8 [9712886] J Exp Zool. 1998 Sep-Oct 1;282(1-2):12-7 [9723161] Biochem Biophys Res Commun. 1998 Aug 28;249(3):709-12 [9731202] J Biol Chem. 2000 Dec 29;275(52):41064-73 [10961997] Curr Opin Cell Biol. 2001 Apr;13(2):167-71 [11248550] Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1698-706 [11431431] J Biol Chem. 2001 Aug 31;276(35):32896-904 [11438538] Biochem Biophys Res Commun. 2001 Oct 5;287(4):808-13 [11573933] J Biol Chem. 2001 Oct 19;276(42):38527-35 [11486006] J Biol Chem. 2001 Nov 2;276(44):40537-44 [11502749] Cornea. 2001 Nov;20(8):853-8 [11685065] J Biol Chem. 2001 Nov 16;276(46):43407-12 [11557773] DNA Cell Biol. 2003 May;22(5):329-38 [12941160] Nature. 1965 Oct 16;208(5007):292-3 [5882459] Proc Soc Exp Biol Med. 1966 Jul;122(3):783-6 [5918951] Dev Biol. 1973 Nov;35(1):83-96 [4362668] Science. 1980 Jul 25;209(4455):497-9 [6248960] Differentiation. 1986;33(2):168-74 [3569698] Biochem Biophys Res Commun. 1987 Aug 14;146(3):1439-49 [3040002] J Biol Chem. 1988 Aug 25;263(24):11994-2001 [3403559] Annu Rev Biochem. 1988;57:479-504 [3052280] Science. 1988 Dec 9;242(4884):1412-5 [2849206] J Biol Chem. 1989 Aug 5;264(22):13057-65 [2753900] Trends Biochem Sci. 1989 Sep;14(9):365-8 [2688200] Exp Eye Res. 1990 Oct;51(4):419-26 [2209753] Science. 1991 May 17;252(5008):954-8 [1852076] Biol Neonate. 1992;61(2):118-23 [1567930] Dev Biol. 1992 May;151(1):18-26 [1577187] Cornea. 1993 Mar;12(2):146-54 [8500322] Biochim Biophys Acta. 1993 Dec 8;1203(2):251-9 [8268208] Curr Eye Res. 1993 Nov;12(11):963-74 [7508359] Adv Enzymol Relat Areas Mol Biol. 1994;69:155-201 [7817868] J Biol Chem. 1995 Jun 9;270(23):13968-72 [7775458] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of blocking individual maturation cleavages in murine leukemia virus gag. AN - 80092476; 14722296 AB - A single protein, termed Gag, is responsible for retrovirus particle assembly. After the assembled virion is released from the cell, Gag is cleaved at several sites by the viral protease (PR). The cleavages catalyzed by PR bring about a wide variety of physical changes in the particle, collectively termed maturation, and convert the particle into an infectious virion. In murine leukemia virus (MLV) maturation, Gag is cleaved at three sites, resulting in formation of the matrix (MA), p12, capsid (CA), and nucleocapsid (NC) proteins. We introduced mutations into MLV that inhibited cleavage at individual sites in Gag. All mutants had lost the intensely staining ring characteristic of immature particles; thus, no single cleavage event is required for this feature of maturation. Mutant virions in which MA was not cleaved from p12 were still infectious, with a specific infectivity only approximately 10-fold below that of the wild type. Particles in which p12 and CA could not be separated from each other were noninfectious and lacked a well-delineated core despite the presence of dense material in their interiors. In both of these mutants, the dimeric viral RNA had undergone the stabilization normally associated with maturation, suggesting that this change may depend upon the separation of CA from NC. Alteration of the C-terminal end of CA blocked CA-NC cleavage but also reduced the efficiency of particle formation and, in some cases, severely disrupted the ability of Gag to assemble into regular structures. This observation highlights the critical role of this region of Gag in assembly. JF - Journal of virology AU - Oshima, Masamichi AU - Muriaux, Delphine AU - Mirro, Jane AU - Nagashima, Kunio AU - Dryden, Kelly AU - Yeager, Mark AU - Rein, Alan AD - HIV Drug Resistance Program. Image Analysis Laboratory, SAIC Frederick, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 1411 EP - 1420 VL - 78 IS - 3 SN - 0022-538X, 0022-538X KW - Detergents KW - 0 KW - Gene Products, gag KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Humans KW - Endopeptidases -- metabolism KW - Microscopy, Electron KW - Mice KW - Detergents -- pharmacology KW - NIH 3T3 Cells KW - Cell Line KW - Virus Assembly KW - Virion -- ultrastructure KW - Leukemia Virus, Murine -- metabolism KW - Leukemia Virus, Murine -- genetics KW - Virion -- pathogenicity KW - Virion -- metabolism KW - Leukemia Virus, Murine -- pathogenicity KW - Mutation KW - Gene Products, gag -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80092476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+blocking+individual+maturation+cleavages+in+murine+leukemia+virus+gag.&rft.au=Oshima%2C+Masamichi%3BMuriaux%2C+Delphine%3BMirro%2C+Jane%3BNagashima%2C+Kunio%3BDryden%2C+Kelly%3BYeager%2C+Mark%3BRein%2C+Alan&rft.aulast=Oshima&rft.aufirst=Masamichi&rft.date=2004-02-01&rft.volume=78&rft.issue=3&rft.spage=1411&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 - 2004-02-24 N1 - Date created - 2004-01-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1994 Dec;68(12):8017-27 [7966591] Virology. 1993 Jun;194(2):843-50 [8503189] Virology. 2000 Mar 15;268(2):294-307 [10704338] Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5246-51 [11320254] J Virol. 2001 Oct;75(19):9156-64 [11533179] J Virol. 2001 Oct;75(19):9357-66 [11533199] Nat Struct Biol. 2002 Jul;9(7):537-43 [12032547] J Virol. 2002 Oct;76(19):10050-5 [12208984] J Virol. 2002 Nov;76(22):11405-13 [12388701] J Virol. 2003 Feb;77(3):1772-83 [12525611] J Virol. 2003 Mar;77(5):3339-44 [12584360] J Virol. 2003 Jun;77(12):7058-66 [12768025] Nature. 1971 Feb 19;229(5286):564-6 [4925356] Virology. 1973 Apr;52(2):456-67 [4705382] J Virol. 1975 Nov;16(5):1161-70 [171447] J Cell Biol. 1976 Sep;70(3):608-21 [783172] Proc Natl Acad Sci U S A. 1977 Aug;74(8):3446-50 [410020] Biochem Biophys Res Commun. 1977 Nov 7;79(1):319-25 [921804] Cell. 1977 Nov;12(3):709-19 [72613] J Virol. 1979 Oct;32(1):187-98 [94357] Virology. 1983 May;127(1):134-48 [6305011] J Virol. 1995 Jun;69(6):3407-19 [7745687] Science. 1996 Jul 12;273(5272):231-5 [8662505] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7577-81 [8755517] J Virol. 1996 Aug;70(8):4966-72 [8764002] Nat Struct Biol. 1996 Sep;3(9):763-70 [8784350] J Biol Chem. 1996 Dec 27;271(52):33686-92 [8969239] Cell. 1996 Dec 27;87(7):1285-94 [8980234] J Virol. 1998 Mar;72(3):2072-8 [9499062] EMBO J. 1998 Mar 16;17(6):1555-68 [9501077] EMBO J. 1998 May 1;17(9):2699-708 [9564051] Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7299-304 [9636143] Trends Biochem Sci. 1998 Aug;23(8):297-301 [9757830] Hum Gene Ther. 1999 Jan 1;10(1):5-14 [10022526] J Virol. 1999 May;73(5):4251-6 [10196321] EMBO J. 1999 Sep 1;18(17):4700-10 [10469649] J Virol. 1984 Nov;52(2):492-500 [6333515] J Virol. 1986 Oct;60(1):267-74 [2427747] J Virol. 1993 Sep;67(9):5163-74 [8350394] J Virol. 1993 Sep;67(9):5443-9 [8350405] J Virol. 1994 Mar;68(3):1773-81 [8107239] J Virol. 1994 May;68(5):3220-31 [8151784] J Virol. 1994 Aug;68(8):5013-8 [8035501] Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246-50 [3489936] Anal Biochem. 1986 Nov 15;159(1):227-32 [2433961] J Virol. 1989 May;63(5):2370-3 [2649693] J Virol. 1989 May;63(5):2405-10 [2784837] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 [2788277] J Virol. 1990 Oct;64(10):5076-92 [1697912] Antimicrob Agents Chemother. 1994 Dec;38(12):2929-33 [7695287] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Context of deletions and insertions in human coding sequences. AN - 80091363; 14722921 AB - We studied the dependence of the rate of short deletions and insertions on their contexts using the data on mutations within coding exons at 19 human loci that cause mendelian diseases. We confirm that periodic sequences consisting of three to five or more nucleotides are mutagenic. Mutability of sequences with strongly biased nucleotide composition is also elevated, even when mutations within homonucleotide runs longer than three nucleotides are ignored. In contrast, no elevated mutation rates have been detected for imperfect direct or inverted repeats. Among known candidate contexts, the indel context GTAAGT and regions with purine-pyrimidine imbalance between the two DNA strands are mutagenic in our sample, and many others are not mutagenic. Data on mutation hot spots suggest two novel contexts that increase the deletion rate. Comprehensive analysis of mutability of all possible contexts of lengths four, six, and eight indicates a substantially elevated deletion rate within YYYTG and similar sequences, which is one of the two contexts revealed by the hot spots. Possible contexts that increase the insertion rate (AT(A/C)(A/C)GCC and TACCRC) and decrease deletion (TATCGC) or insertion (GCGG) rates have also been identified. Two-thirds of deletions remove a repeat, and over 80% of insertions create a repeat, i.e., they are duplications. JF - Human mutation AU - Kondrashov, Alexey S AU - Rogozin, Igor B AD - National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland 20894, USA. kondrashov@ncbi.nlm.nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 177 EP - 185 VL - 23 IS - 2 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Microsatellite Repeats -- genetics KW - Genetic Markers -- genetics KW - Terminal Repeat Sequences -- genetics KW - Databases, Genetic -- statistics & numerical data KW - Recombination, Genetic -- genetics KW - Humans KW - Repetitive Sequences, Nucleic Acid -- genetics KW - Chromosome Deletion KW - Mutagenesis, Insertional -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80091363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+mutation&rft.atitle=Context+of+deletions+and+insertions+in+human+coding+sequences.&rft.au=Kondrashov%2C+Alexey+S%3BRogozin%2C+Igor+B&rft.aulast=Kondrashov&rft.aufirst=Alexey&rft.date=2004-02-01&rft.volume=23&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=1098-1004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-08 N1 - Date created - 2004-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio. AN - 80088045; 14713758 AB - We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute. JF - The Journal of urology AU - Parnes, Howard L AU - House, Margaret G AU - Kagan, Jacob AU - Kausal, David J AU - Lieberman, Ronald AD - Prostate and Urologic Cancer Researh Group, Division of Cancer Prevention, National Cancer Institute, National Institute of Health, Bethesda, Maryland, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - S68 EP - 74; discussion S75 VL - 171 IS - 2 Pt 2 SN - 0022-5347, 0022-5347 KW - Anticarcinogenic Agents KW - 0 KW - Biomarkers, Tumor KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Male KW - Randomized Controlled Trials as Topic KW - Anticarcinogenic Agents -- therapeutic use KW - Prostatic Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80088045?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+urology&rft.atitle=Prostate+cancer+chemoprevention+agent+development%3A+the+National+Cancer+Institute%2C+Division+of+Cancer+Prevention+portfolio.&rft.au=Parnes%2C+Howard+L%3BHouse%2C+Margaret+G%3BKagan%2C+Jacob%3BKausal%2C+David+J%3BLieberman%2C+Ronald&rft.aulast=Parnes&rft.aufirst=Howard&rft.date=2004-02-01&rft.volume=171&rft.issue=2+Pt+2&rft.spage=S68&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+urology&rft.issn=00225347&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-17 N1 - Date created - 2004-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeting topoisomerase I to inhibit hypoxia inducible factor 1. AN - 80085443; 14712084 AB - HIF-1 is a key factor in cancer progression. Efforts are underway to identify and develop small molecules that inhibit HIF-1 transcriptional activity. What are the best targets and the best ways to develop HIF-1 inhibitors are open questions. However, several "nonselective" HIF-1 inhibitors have been identified, which are either in the clinic or under development. In this article, we discuss how topoisomerase I poisons, which inhibit HIF-1a protein accumulation and transcriptional activity, can be "rationally" used to target HIF-1 for cancer therapy. JF - Cell cycle (Georgetown, Tex.) AU - Rapisarda, Annamaria AU - Shoemaker, Robert H AU - Melillo, Giovanni AD - Developmental Therapeutics Program, Science Applications International Corporation, Frederick, Inc; National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 172 EP - 175 VL - 3 IS - 2 SN - 1538-4101, 1538-4101 KW - Antineoplastic Agents KW - 0 KW - DNA-Binding Proteins KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Isoenzymes KW - Membrane Proteins KW - Nuclear Proteins KW - Topoisomerase I Inhibitors KW - Transcription Factors KW - Vascular Endothelial Growth Factor A KW - Topotecan KW - 7M7YKX2N15 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Humans KW - Gene Expression Regulation, Neoplastic -- physiology KW - Cell Hypoxia -- physiology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Isoenzymes -- metabolism KW - Signal Transduction -- physiology KW - Helix-Loop-Helix Motifs -- physiology KW - Tumor Cells, Cultured KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Vascular Endothelial Growth Factor A -- metabolism KW - Topotecan -- pharmacology KW - DNA-Binding Proteins -- antagonists & inhibitors KW - Nuclear Proteins -- metabolism KW - DNA Topoisomerases, Type I -- metabolism KW - Nuclear Proteins -- antagonists & inhibitors KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80085443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cycle+%28Georgetown%2C+Tex.%29&rft.atitle=Targeting+topoisomerase+I+to+inhibit+hypoxia+inducible+factor+1.&rft.au=Rapisarda%2C+Annamaria%3BShoemaker%2C+Robert+H%3BMelillo%2C+Giovanni&rft.aulast=Rapisarda&rft.aufirst=Annamaria&rft.date=2004-02-01&rft.volume=3&rft.issue=2&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Cell+cycle+%28Georgetown%2C+Tex.%29&rft.issn=15384101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-21 N1 - Date created - 2004-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - High-throughput proteomics for alcohol research. AN - 71877402; 15112927 AB - This report summarizes the proceedings of a satellite symposium of the 2003 Research Society on Alcoholism meeting held on June 21, 2003, in Fort Lauderdale, FL. The goal of this symposium, sponsored by the NIAAA, was to identify new proteomic directions in alcohol research that will (1) enable studies that focus on characterizing protein function, biochemical pathways, and networks to understand alcohol-related illnesses; (2) identify protein-protein interactions, posttranslational modifications, and subcellular localizations; (3) identify molecular targets for medication development; (4) develop biomarkers for susceptibility, dependence, consumption, and relapse, as well as alcohol-induced pathologies; and (5) develop high-throughput drug screens to test the efficacy of therapeutics that control alcohol-induced diseases. The purpose of the symposium was also to promote the application of high-throughput proteomic approaches, including isolation of membrane-bound proteins, in situ proteomics, large-scale two-dimensional separations, protein microarray platforms, mass spectrometry, matrix-assisted laser desorption/ionization, matrix-assisted laser desorption/ionization time-of-flight, liquid chromatography-tandem mass spectrometry, and isotope-coded affinity tags. In addition, the development of protein network maps by using new bioinformatics approaches for database mining was also discussed. JF - Alcoholism, clinical and experimental research AU - Neuhold, Lisa A AU - Guo, Q Max AU - Alper, Joseph AU - Velazquez, Jose M Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 203 EP - 210 VL - 28 IS - 2 KW - Index Medicus KW - United States KW - Animals KW - Humans KW - Computational Biology -- methods KW - Societies, Medical KW - Research Design KW - Proteomics -- methods KW - Alcohol Drinking -- metabolism KW - Alcoholism -- metabolism KW - Alcohol Drinking -- genetics KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71877402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=High-throughput+proteomics+for+alcohol+research.&rft.au=Neuhold%2C+Lisa+A%3BGuo%2C+Q+Max%3BAlper%2C+Joseph%3BVelazquez%2C+Jose+M&rft.aulast=Neuhold&rft.aufirst=Lisa&rft.date=2004-02-01&rft.volume=28&rft.issue=2&rft.spage=203&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 - 2004-05-17 N1 - Date created - 2004-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Pharmacological treatment of alcohol abuse/dependence with psychiatric comorbidity. AN - 71872565; 15112938 AB - This article represents the proceedings of a symposium at the 2003 annual meeting RSA in Fort Lauderdale, FL. It was organized and cochaired by Charlene E. Le Fauve and Carrie L. Randall. The presentations were (1) Introduction, by Charlene E. Le Fauve and Raye Z. Litten; (2) Treatment of co-occurring alcohol use and anxiety disorders, by Carrie L. Randall and Sarah W. Book; (3) Pharmacological treatment of alcohol dependent patients with comorbid depression, by Darlene H. Moak; (4) Efficacy of valproate in bipolar alcoholics: a double blind, placebo-controlled study, by Ihsan M. Salloum, Jack R. Cornelius, Dennis C. Daley, Levent Kirisci, Johnathan Himmelhoch, and Michael E. Thase; (5) Alcoholism and schizophrenia: effects of antipsychotics, by Alan I. Green, Robert E. Drake, Suzannah V. Zimmet, Rael D. Strous, Melinda Salomon, and Mark Brenner; and (6) Conclusions, by Charlene E. Le Fauve; discussant, Raye Z. Litten. Alcohol-dependent individuals have exceptionally high rates of co-occurring psychiatric disorders. Although this population is more likely to seek alcoholism treatment than noncomorbid alcoholics, the prognosis for treatment is often poor, particularly among patients with more severe psychiatric illnesses. Development of effective interventions to treat this population is in the early stages of research. Although the interaction between the psychiatric condition and alcoholism is complex, progress has been made. The NIAAA has supported a number of state-of-the-art pharmacological and behavioral trials in a variety of comorbid psychiatric disorders. Some of these trials have been completed and are presented here. The symposium presented some new research findings from clinical studies with the aim of facilitating the development of treatments that improve alcohol and psychiatric outcomes among individuals with alcohol-use disorders and co-occurring psychiatric disorders. The panel focused on social anxiety disorder, depression, bipolar disorder, and schizophrenia. JF - Alcoholism, clinical and experimental research AU - Le Fauve, Charlene E AU - Litten, Raye Z AU - Randall, Carrie L AU - Moak, Darlene H AU - Salloum, Ihsan M AU - Green, Alan I Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 302 EP - 312 VL - 28 IS - 2 KW - Antipsychotic Agents KW - 0 KW - Valproic Acid KW - 614OI1Z5WI KW - Index Medicus KW - United States KW - Diagnosis, Dual (Psychiatry) -- methods KW - Animals KW - Humans KW - Antipsychotic Agents -- therapeutic use KW - Valproic Acid -- therapeutic use KW - Societies, Medical KW - Comorbidity KW - Alcoholism -- epidemiology KW - Mental Disorders -- epidemiology KW - Mental Disorders -- drug therapy KW - Mental Disorders -- psychology KW - Alcoholism -- psychology KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71872565?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Pharmacological+treatment+of+alcohol+abuse%2Fdependence+with+psychiatric+comorbidity.&rft.au=Le+Fauve%2C+Charlene+E%3BLitten%2C+Raye+Z%3BRandall%2C+Carrie+L%3BMoak%2C+Darlene+H%3BSalloum%2C+Ihsan+M%3BGreen%2C+Alan+I&rft.aulast=Le+Fauve&rft.aufirst=Charlene&rft.date=2004-02-01&rft.volume=28&rft.issue=2&rft.spage=302&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 - 2004-05-17 N1 - Date created - 2004-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cystine-glutamate transporter in the accumbens: a novel role in cocaine relapse. AN - 71861145; 15106652 AB - Baker et al. have recently studied the potential role of cocaine-induced alterations in accumbens cystine-glutamate transporter activity (which controls basal extracellular glutamate levels) during cocaine-induced relapse to drug seeking in rats. Their data provide new evidence that neuroadaptations induced by repeated exposure to cocaine and subsequent withdrawal can play a causal role in drug relapse. These data also suggest the cystine-glutamate transporter as a novel target for medication that could prevent cocaine relapse. JF - Trends in neurosciences AU - Lu, Lin AU - Hope, Bruce T AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, IRP, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 74 EP - 76 VL - 27 IS - 2 SN - 0166-2236, 0166-2236 KW - Amino Acid Transport System y+ KW - 0 KW - Carrier Proteins KW - Receptors, AMPA KW - Receptors, N-Methyl-D-Aspartate KW - SLC7A11 protein, human KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Neurons -- enzymology KW - Adaptation, Physiological KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Receptors, AMPA -- metabolism KW - Recurrence KW - Nucleus Accumbens -- enzymology KW - Cocaine-Related Disorders -- physiopathology KW - Carrier Proteins -- physiology KW - Nucleus Accumbens -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71861145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurosciences&rft.atitle=The+cystine-glutamate+transporter+in+the+accumbens%3A+a+novel+role+in+cocaine+relapse.&rft.au=Lu%2C+Lin%3BHope%2C+Bruce+T%3BShaham%2C+Yavin&rft.aulast=Lu&rft.aufirst=Lin&rft.date=2004-02-01&rft.volume=27&rft.issue=2&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Trends+in+neurosciences&rft.issn=01662236&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-17 N1 - Date created - 2004-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer. AN - 71849284; 15102462 AB - Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity-based processes. Serum proteomic pattern diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. This approach has recently shown tremendous promise in the detection of early-stage cancers. The biomarkers found by SELDI-TOF-based pattern recognition analysis are mostly low molecular weight fragments produced at the specific tumor microenvironment. JF - Current opinion in biotechnology AU - Petricoin, Emanuel F AU - Liotta, Lance A AD - FDA-NCI Clinical Proteomics Program, Office of Cell and Gene Therapies, Center for Biologic Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. petricoin@cber.fda.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 24 EP - 30 VL - 15 IS - 1 SN - 0958-1669, 0958-1669 KW - Biomarkers, Tumor KW - 0 KW - Neoplasm Proteins KW - Index Medicus KW - Equipment Design KW - Artificial Intelligence KW - Humans KW - Blood Chemical Analysis -- methods KW - Algorithms KW - Blood Chemical Analysis -- instrumentation KW - Sequence Analysis, Protein -- methods KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization -- instrumentation KW - Neoplasms -- diagnosis KW - Biomarkers, Tumor -- chemistry KW - Neoplasms -- blood KW - Neoplasm Proteins -- blood KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization -- methods KW - Neoplasm Proteins -- chemistry KW - Biomarkers, Tumor -- blood KW - Gene Expression Profiling -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71849284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biotechnology&rft.atitle=SELDI-TOF-based+serum+proteomic+pattern+diagnostics+for+early+detection+of+cancer.&rft.au=Petricoin%2C+Emanuel+F%3BLiotta%2C+Lance+A&rft.aulast=Petricoin&rft.aufirst=Emanuel&rft.date=2004-02-01&rft.volume=15&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+biotechnology&rft.issn=09581669&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-28 N1 - Date created - 2004-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Current situation on drug abuse in Japan: using a general population survey and a junior high school students survey]. AN - 71792363; 15058091 JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Wada, Kiyoshi AU - Kikuchi, Akiko AU - Nakano, Ryogo AU - Ozaki, Shigeru AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Ichikawa-shi, Chiba 272-0827, Japan. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 28 EP - 34 VL - 39 IS - 1 SN - 1341-8963, 1341-8963 KW - Index Medicus KW - Japan -- epidemiology KW - Schools KW - Random Allocation KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Aged KW - Middle Aged KW - Adolescent KW - Time Factors KW - Prevalence KW - Students -- psychology KW - Students -- statistics & numerical data KW - Substance-Related Disorders -- epidemiology KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71792363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=%5BCurrent+situation+on+drug+abuse+in+Japan%3A+using+a+general+population+survey+and+a+junior+high+school+students+survey%5D.&rft.au=Wada%2C+Kiyoshi%3BKikuchi%2C+Akiko%3BNakano%2C+Ryogo%3BOzaki%2C+Shigeru&rft.aulast=Wada&rft.aufirst=Kiyoshi&rft.date=2004-02-01&rft.volume=39&rft.issue=1&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=13418963&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-06 N1 - Date created - 2004-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular therapeutics: promise and challenges. AN - 71789003; 15052542 AB - The ability to analyze the genetic and epigenetic aberrations present in a particular patient's tumor on a global basis is rapidly maturing. The emerging fields of functional genomics and functional proteomics offer the opportunity to translate these advances into a full comprehension of the pathophysiology of cancer. Linking these approaches to chemical genomics and molecular therapeutics should provide an expanding repertoire of targeted therapeutics for clinical evaluation. Novel clinical trial designs that can determine the efficacy of targeted therapeutics in patients selected for aberrations in the target are needed to evaluate the wealth of new drugs becoming available. The promise of these technologies and advances in our understanding of cancer is immense, making it our responsibility to see them to fruition. These technologies should lead to a new era of individualized molecular medicine, wherein we will treat each patient with a "prescription" based on the genetic changes in each patient's tumor and their own genetic make-up, resulting in more effective and less toxic therapy. JF - Seminars in oncology AU - Kohn, Elise C AU - Lu, Yiling AU - Wang, Hongwei AU - Yu, Qinghua AU - Yu, Shuangxing AU - Hall, Hassan AU - Smith, Debra L AU - Meric-Bernstam, Funda AU - Hortobagyi, Gabriel N AU - Mills, Gordon B AD - Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 39 EP - 53 VL - 31 IS - 1 Suppl 3 SN - 0093-7754, 0093-7754 KW - Antineoplastic Agents KW - 0 KW - Neoplasm Proteins KW - Index Medicus KW - Gene Expression Profiling KW - Animals KW - Genomic Instability KW - Humans KW - Neoplasms -- drug therapy KW - Signal Transduction -- drug effects KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Pharmacogenetics KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71789003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=Molecular+therapeutics%3A+promise+and+challenges.&rft.au=Kohn%2C+Elise+C%3BLu%2C+Yiling%3BWang%2C+Hongwei%3BYu%2C+Qinghua%3BYu%2C+Shuangxing%3BHall%2C+Hassan%3BSmith%2C+Debra+L%3BMeric-Bernstam%2C+Funda%3BHortobagyi%2C+Gabriel+N%3BMills%2C+Gordon+B&rft.aulast=Kohn&rft.aufirst=Elise&rft.date=2004-02-01&rft.volume=31&rft.issue=1+Suppl+3&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-27 N1 - Date created - 2004-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a purine-rich intronic enhancer element in the mouse eosinophil-associated ribonuclease 2 (mEar 2) gene. AN - 71784590; 15058383 AB - The Mus musculus eosinophil-associated ribonuclease (mEar) gene cluster includes multiple distinct coding sequences that are highly divergent orthologs of the human eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3). We present a transcriptional analysis of the gene encoding mEar 2, the only member of this cluster with a well-defined expression profile. In this work, we demonstrate that the presence of non-coding exon 1 and the intron in tandem with a 361-bp 5' promoter of mEar 2 results in enhanced reporter gene expression, as much as 6-to 10-fold over the activity observed with the 5' promoter alone. We have identified a conserved purine-rich element in the intron of the mEar 2 gene that is necessary for maximum transcription and that interacts specifically with NFAT-binding proteins in nuclear extracts derived from the mouse LA4 epithelial cell line. Similar intronic enhancers have been described as regulating transcription of the human EDN gene, suggesting an overall conservation of an important regulatory strategy. JF - Mammalian genome : official journal of the International Mammalian Genome Society AU - Dyer, Kimberly D AU - Nitto, Takeaki AU - Moreau, Joanne M AU - McDevitt, Amanda L AU - Rosenberg, Helene F AD - Eosinophil Pathophysiology Section, LHD, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. kdyer@niaid.nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 126 EP - 134 VL - 15 IS - 2 SN - 0938-8990, 0938-8990 KW - Blood Proteins KW - 0 KW - DNA Primers KW - Eosinophil Granule Proteins KW - Purines KW - Ear2 protein, mouse KW - EC 3.1.- KW - Eosinophil-Derived Neurotoxin KW - Ribonucleases KW - Index Medicus KW - Phylogeny KW - Animals KW - Electrophoretic Mobility Shift Assay KW - Cell Line, Tumor KW - Sequence Analysis, DNA KW - Blood Proteins -- genetics KW - Introns -- genetics KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Genes, Reporter -- genetics KW - Molecular Sequence Data KW - Binding Sites -- genetics KW - Databases, Genetic KW - Purines -- analysis KW - Mice -- genetics KW - Ribonucleases -- genetics KW - Gene Expression KW - Enhancer Elements, Genetic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71784590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.atitle=Identification+of+a+purine-rich+intronic+enhancer+element+in+the+mouse+eosinophil-associated+ribonuclease+2+%28mEar+2%29+gene.&rft.au=Dyer%2C+Kimberly+D%3BNitto%2C+Takeaki%3BMoreau%2C+Joanne+M%3BMcDevitt%2C+Amanda+L%3BRosenberg%2C+Helene+F&rft.aulast=Dyer&rft.aufirst=Kimberly&rft.date=2004-02-01&rft.volume=15&rft.issue=2&rft.spage=126&rft.isbn=&rft.btitle=&rft.title=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.issn=09388990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-17 N1 - Date created - 2004-04-02 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY324806; GENBANK; AF408692; AY324805; AY316150; AY316149 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxygen therapeutics: can we tame haemoglobin? AN - 71760761; 15043006 AB - Chemically modified or genetically engineered haemoglobins (Hbs) developed as oxygen therapeutics (often termed 'blood substitutes') are designed to correct oxygen deficit due to ischaemia in a variety of clinical settings. These modifications are intended to stabilize Hb outside its natural environment--red blood cells--in a functional tetrameric and/or polymeric form. Uncontrolled haem-mediated oxidative reactions of cell-free Hb and its reactions with various oxidant/antioxidant and cell signalling systems have emerged as an important pathway of toxicity. Current protective strategies designed to produce safe Hb-based products are focused on controlling or suppressing the 'radical' nature of Hb while retaining its oxygen-carrying function. JF - Nature reviews. Drug discovery AU - Alayash, Abdu I AD - Laboratory of Biochemistry, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, National Institutes of Health, Bethesda, Maryland 20892, USA. alayash@cber.fda.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 152 EP - 159 VL - 3 IS - 2 SN - 1474-1776, 1474-1776 KW - Antioxidants KW - 0 KW - Blood Substitutes KW - Hemoglobins KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Antioxidants -- metabolism KW - Humans KW - Genomics KW - Blood Substitutes -- adverse effects KW - Hemoglobins -- metabolism KW - Hemoglobins -- toxicity KW - Oxygen -- therapeutic use KW - Hemoglobins -- genetics KW - Blood Substitutes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71760761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reviews.+Drug+discovery&rft.atitle=Oxygen+therapeutics%3A+can+we+tame+haemoglobin%3F&rft.au=Alayash%2C+Abdu+I&rft.aulast=Alayash&rft.aufirst=Abdu&rft.date=2004-02-01&rft.volume=3&rft.issue=2&rft.spage=152&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Drug+discovery&rft.issn=14741776&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-06 N1 - Date created - 2004-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of patients with unresectable primary hepatic malignancies using hyperthermic isolated hepatic perfusion. AN - 71745268; 15036196 AB - Primary hepatocellular carcinoma is one of the most common malignancies worldwide. Isolated hepatic perfusion (IHP) is a regional treatment technique that isolates the organ to allow delivery of high-dose chemotherapy, biological agents, and hyperthermia directly to unresectable cancers confined to the liver. This study presents our experience using IHP with melphalan with or without tumor necrosis factor (TNF) to treat patients with hepatocellular carcinoma or adenocarcinoma of hepatobiliary origin. Nine patients with unresectable primary hepatic malignancies underwent a 60-minute IHP with 1.5 mg/kg melphalan with or without 1.0 mg TNF. Four patients failed one or more previous treatment regimens, and the mean hepatic replacement by tumor was 41% (range 10% to 75%). Patients were monitored for response, toxicity, time to recurrence, and survival. Six (67%) of nine patients experienced greater than 50% regression of tumor by objective radiographic imaging and an additional patient had a 45% reduction in tumor burden. Mean time to progression was 7.7 months for those who responded to treatment. Patients who had a response to therapy had an average overall survival of 16.3 months. IHP can be performed safely and has significant antitumor activity in patients with unresectable primary hepatic malignancies. Hepatic progression continues to be the dominant factor influencing survival in this group of patients. JF - Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract AU - Feldman, Elizabeth D AU - Wu, Peter C AU - Beresneva, Tatiana AU - Helsabeck, Cynthia AU - Rodriguez, Montessa AU - Bartlett, David L AU - Libutti, Steven K AU - Pingpank, James F AU - Alexander, H Richard AD - Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 200 EP - 207 VL - 8 IS - 2 SN - 1091-255X, 1091-255X KW - Antineoplastic Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Hyperthermia, Induced -- methods KW - Male KW - Female KW - Survival Analysis KW - Antineoplastic Agents -- administration & dosage KW - Carcinoma, Hepatocellular -- drug therapy KW - Melphalan -- administration & dosage KW - Liver Neoplasms -- drug therapy KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Adenocarcinoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71745268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gastrointestinal+surgery+%3A+official+journal+of+the+Society+for+Surgery+of+the+Alimentary+Tract&rft.atitle=Treatment+of+patients+with+unresectable+primary+hepatic+malignancies+using+hyperthermic+isolated+hepatic+perfusion.&rft.au=Feldman%2C+Elizabeth+D%3BWu%2C+Peter+C%3BBeresneva%2C+Tatiana%3BHelsabeck%2C+Cynthia%3BRodriguez%2C+Montessa%3BBartlett%2C+David+L%3BLibutti%2C+Steven+K%3BPingpank%2C+James+F%3BAlexander%2C+H+Richard&rft.aulast=Feldman&rft.aufirst=Elizabeth&rft.date=2004-02-01&rft.volume=8&rft.issue=2&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Journal+of+gastrointestinal+surgery+%3A+official+journal+of+the+Society+for+Surgery+of+the+Alimentary+Tract&rft.issn=1091255X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-01 N1 - Date created - 2004-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A potent anti-HIV immunotoxin blocks spreading infection by primary HIV type 1 isolates in multiple cell types. AN - 71739764; 15018701 AB - Although several immunotoxins that selectively kill HIV-1-infected cells have been described, their clinical utility is limited by low potency against spreading viral infection. We show here that changing the carboxyterminal sequence of an anti-HIV-1 envelope immunotoxin to the consensus endoplasmic reticulum retention sequence KDEL substantially improves its ability to block infection of peripheral blood mononuclear cells by primary HIV-1 isolates without increasing nonspecific toxicity. Polychromatic flow cytometry of peripheral blood mononuclear cells (PBMC) infected with an HIV-1-GFP reporter virus demonstrated that the improved immunotoxin is active against a variety of primary cell types including memory T cells, NK-T cells, and monocyte/macrophages. The subnanomolar potency of this agent suggests that it could be clinically useful either as an adjuvant to highly active antiretroviral therapy (HAART) in drug-resistant patients or to reduce the reservoir of latently infected cells that is implicated in HIV-1 persistence. JF - AIDS research and human retroviruses AU - Lueders, Kira K AU - De Rosa, Stephen C AU - Valentin, Antonio AU - Pavlakis, George N AU - Roederer, Mario AU - Hamer, Dean H AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 145 EP - 150 VL - 20 IS - 2 SN - 0889-2229, 0889-2229 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - HIV Antibodies KW - Immunotoxins KW - Luminescent Proteins KW - Oligopeptides KW - Protein Sorting Signals KW - Virulence Factors KW - lysyl-aspartyl-glutamyl-leucine KW - 113516-56-6 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - HIV Infections -- virology KW - Humans KW - ADP Ribose Transferases -- pharmacology KW - ADP Ribose Transferases -- genetics KW - Bacterial Toxins -- genetics KW - Lymphocyte Subsets -- virology KW - In Vitro Techniques KW - Antiretroviral Therapy, Highly Active KW - Genes, Reporter KW - CHO Cells KW - Chemotherapy, Adjuvant KW - Exotoxins -- genetics KW - Exotoxins -- pharmacology KW - Lymphocyte Subsets -- drug effects KW - HIV Antibodies -- genetics KW - Virulence Factors -- genetics KW - Bacterial Toxins -- pharmacology KW - Virulence Factors -- pharmacology KW - Leukocytes, Mononuclear -- virology KW - Cells, Cultured KW - HIV Infections -- drug therapy KW - Leukocytes, Mononuclear -- drug effects KW - Luminescent Proteins -- genetics KW - HIV Antibodies -- pharmacology KW - Cricetinae KW - HIV-1 -- genetics KW - HIV-1 -- pathogenicity KW - Immunotoxins -- genetics KW - Immunotoxins -- pharmacology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71739764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+potent+anti-HIV+immunotoxin+blocks+spreading+infection+by+primary+HIV+type+1+isolates+in+multiple+cell+types.&rft.au=Lueders%2C+Kira+K%3BDe+Rosa%2C+Stephen+C%3BValentin%2C+Antonio%3BPavlakis%2C+George+N%3BRoederer%2C+Mario%3BHamer%2C+Dean+H&rft.aulast=Lueders&rft.aufirst=Kira&rft.date=2004-02-01&rft.volume=20&rft.issue=2&rft.spage=145&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 - 2004-05-19 N1 - Date created - 2004-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The accelerated biased coin up-and-down design in phase I trials. AN - 71732626; 15027512 AB - The biased coin up-and-down design (BCD) is used to allocate doses in phase I clinical trials. The BCD requires that the treatment response or the toxicity evaluation is observed quickly. In trials with a long treatment evaluation, the BCD will lead to long trial duration because a new patient cannot be enrolled until the preceding patient has completed the evaluation period. We propose a simple method to modify the BCD that will reduce the trial duration without significantly affecting the estimate of the target dose. The idea is to allocate a dose to each patient as he or she arrives based on the toxicity information of the last completed subject. This allows multiple patients to be concurrently under evaluation. A simulation study shows that this modification does not adversely affect the precision of the recommended dose, as estimated by isotonic regression, but it does significantly reduce the total time to complete the study. JF - Journal of biopharmaceutical statistics AU - Stylianou, Mario AU - Follmann, Dean A AD - Office of Biostatistics Research, NHLBI, Bethesda, Maryland 20892-7938, USA. StylianM@nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 249 EP - 260 VL - 14 IS - 1 SN - 1054-3406, 1054-3406 KW - Index Medicus KW - Humans KW - Monte Carlo Method KW - Clinical Trials, Phase I as Topic -- methods KW - Clinical Trials, Phase I as Topic -- statistics & numerical data KW - Bias (Epidemiology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71732626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biopharmaceutical+statistics&rft.atitle=The+accelerated+biased+coin+up-and-down+design+in+phase+I+trials.&rft.au=Stylianou%2C+Mario%3BFollmann%2C+Dean+A&rft.aulast=Stylianou&rft.aufirst=Mario&rft.date=2004-02-01&rft.volume=14&rft.issue=1&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=Journal+of+biopharmaceutical+statistics&rft.issn=10543406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-12 N1 - Date created - 2004-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - P-glycoprotein-based drug-drug interactions: preclinical methods and relevance to clinical observations. AN - 71727123; 15022711 AB - Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities. JF - Archives of pharmacal research AU - Aszalos, Adorjan AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4254, USA. aszalosa@mail.nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 127 EP - 135 VL - 27 IS - 2 SN - 0253-6269, 0253-6269 KW - P-Glycoprotein KW - 0 KW - Index Medicus KW - Humans KW - Cell Line KW - P-Glycoprotein -- physiology KW - Drug Interactions KW - Drug Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71727123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacal+research&rft.atitle=P-glycoprotein-based+drug-drug+interactions%3A+preclinical+methods+and+relevance+to+clinical+observations.&rft.au=Aszalos%2C+Adorjan&rft.aulast=Aszalos&rft.aufirst=Adorjan&rft.date=2004-02-01&rft.volume=27&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Archives+of+pharmacal+research&rft.issn=02536269&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-28 N1 - Date created - 2004-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression profiling of human keratinocyte response to ultraviolet A: implications in apoptosis. AN - 71717740; 15009741 AB - Ultraviolet A radiation from sunlight is a major human health concern, as it is not absorbed by the ozone layer and can deeply penetrate into the skin causing skin damage. To study the molecular mechanism involved in the ultraviolet A effect, human HaCaT keratinocytes were exposed to ultraviolet A at doses of 10 J per cm2 and 30 J per cm2. Ultraviolet A irradiation caused dose- and time-dependent apoptotic cell death, as evidenced by DNA fragmentation, flow cytometry, and the activation of caspase-3. To study the genes altered by ultraviolet A at an apoptosis-inducing dose (30 J per cm2), cells were harvested immediately after ultraviolet A treatment (0 h), and 6 h and 24 h after ultraviolet A exposure. Total RNA was extracted for microarray and real-time RT-PCR analysis, and cellular proteins were extracted for western blot analysis. Of the selected critical genes/proteins, the induction of c-Jun, c-myc, and p33ING1, and the repression of epidermal growth factor receptor, inhibitor of apoptosis protein, and survivin pathways, could be involved in ultraviolet-A-induced apoptosis. On the other hand, the late induction of cyclin D1 and cyclin-dependent kinase 4 was indicative of possible cell cycle recovery in surviving cells. Real-time RT-PCR analysis confirmed these results and a majority of the protein levels paralleled their corresponding RNA levels. In addition, ultraviolet A treatment altered the expression of genes involved in signal transduction, RNA processing, structural proteins, and metabolism in a time-dependent manner. This initial microarray analysis could advance our understanding of cellular responses to ultraviolet A exposure, and provide a platform from which to further study ultraviolet-A-induced apoptosis and carcinogenesis. JF - The Journal of investigative dermatology AU - He, Yu-Ying AU - Huang, Jian-Li AU - Sik, Robert H AU - Liu, Jie AU - Waalkes, Michael P AU - Chignell, Colin F AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. he3@niehs.nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 533 EP - 543 VL - 122 IS - 2 SN - 0022-202X, 0022-202X KW - Index Medicus KW - Protein Biosynthesis KW - DNA Repair KW - Cells, Cultured KW - Humans KW - Signal Transduction -- genetics KW - Signal Transduction -- radiation effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cell Division -- genetics KW - Cell Division -- radiation effects KW - Keratinocytes -- radiation effects KW - Keratinocytes -- physiology KW - Gene Expression Profiling KW - Ultraviolet Rays KW - Apoptosis -- genetics KW - Apoptosis -- radiation effects KW - Keratinocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71717740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+profiling+of+human+keratinocyte+response+to+ultraviolet+A%3A+implications+in+apoptosis.&rft.au=He%2C+Yu-Ying%3BHuang%2C+Jian-Li%3BSik%2C+Robert+H%3BLiu%2C+Jie%3BWaalkes%2C+Michael+P%3BChignell%2C+Colin+F&rft.aulast=He&rft.aufirst=Yu-Ying&rft.date=2004-02-01&rft.volume=122&rft.issue=2&rft.spage=533&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 - 2004-04-02 N1 - Date created - 2004-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p38 Mitogen-activated protein kinase inhibitor protects the epidermis against the acute damaging effects of ultraviolet irradiation by blocking apoptosis and inflammatory responses. AN - 71715243; 15009736 AB - The primary function of the epidermis is to provide a protective barrier against numerous environmental insults, including ultraviolet radiation (UVR). UVR, particularly in the UVB spectrum, is a potent carcinogen known to damage DNA directly or through the generation of free radicals. Although in the long term, protective measures such as apoptosis and inflammation may prove beneficial in safeguarding the epidermis against the propagation of potentially tumorigenic cells, after high-dose UV irradiation these biologic events may be acutely detrimental to the architectural and functional integrity of the tissue owing to rampant cell death and inflammatory responses, which can culminate in epidermal erosion and consequently loss of barrier functions. The mitogen-activated protein kinase (MAPK) signaling pathway is known to be activated by UVR and herein we identify p38 MAPK as a key modulator of these physiologic events. Mice treated with the p38 MAPK inhibitor SB202190 are protected against several detrimental effects of acute UV irradiation, namely, sunburn cell/apoptosis, inflammation, and a hyperproliferation response. Based on our results, selectively blocking p38 activation with the SB202190 inhibitor could prove beneficial in treating victims from severe sunburn or exposure to other chemical agents known to trigger the p38 pathway. JF - The Journal of investigative dermatology AU - Hildesheim, Jeffrey AU - Awwad, Rania T AU - Fornace, Albert J AD - Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 497 EP - 502 VL - 122 IS - 2 SN - 0022-202X, 0022-202X KW - Enzyme Inhibitors KW - 0 KW - Imidazoles KW - Pyridines KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole KW - PVX798P8GI KW - Index Medicus KW - Acute Disease KW - Dermatitis -- immunology KW - Animals KW - Dermatitis -- pathology KW - MAP Kinase Signaling System -- drug effects KW - Mice KW - Epidermis -- immunology KW - Ultraviolet Rays -- adverse effects KW - Mice, Inbred C57BL KW - Epidermis -- enzymology KW - Epidermis -- pathology KW - Dermatitis -- enzymology KW - Male KW - Sunburn -- pathology KW - Imidazoles -- pharmacology KW - Sunburn -- drug therapy KW - Mitogen-Activated Protein Kinases -- metabolism KW - Apoptosis -- drug effects KW - Apoptosis -- radiation effects KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Sunburn -- immunology KW - Pyridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71715243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p38+Mitogen-activated+protein+kinase+inhibitor+protects+the+epidermis+against+the+acute+damaging+effects+of+ultraviolet+irradiation+by+blocking+apoptosis+and+inflammatory+responses.&rft.au=Hildesheim%2C+Jeffrey%3BAwwad%2C+Rania+T%3BFornace%2C+Albert+J&rft.aulast=Hildesheim&rft.aufirst=Jeffrey&rft.date=2004-02-01&rft.volume=122&rft.issue=2&rft.spage=497&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 - 2004-04-02 N1 - Date created - 2004-03-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Invest Dermatol. 2004 Aug;123(2):415 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adolescent menthol smokers: will they be a harder target for cessation? AN - 71696015; 14982712 AB - Menthol smoking may influence the development of tobacco addiction and related health consequences, yet limited data on menthol smoking by youth are available. We assessed usual brand menthol preference by Baltimore-area teenage smokers applying to a smoking cessation study between September 1999 and December 2002. Of a biethnic (Black and White) sample of 593 youths (mean age=15.5+/-1.4 years, 51% female, 45% African American), the overwhelming majority (93%) were menthol smokers. Menthol preference rates were highest among African American girls and lowest among White boys. Overall, a statistically significant association was found between ethnicity and menthol preference, chi2 (df=1)=19.4, p<.001. This association also was observed separately for girls, chi2 (df=1)=9.21, p=.0024, and for boys, chi2 (df=1)=9.59, p=.0020. Menthol smoking did not vary with age in either ethnic group. These findings of overwhelming menthol preference in a treatment-seeking sample of adolescents warrant further research on the developmental trajectory, cessation, and health-related impact of menthol smoking by youth. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Moolchan, Eric T AD - Teen Tobacco Addiction Treatment Research Clinic, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. emoolcha@intra.nida.nih.gov Y1 - 2004/02// PY - 2004 DA - February 2004 SP - S93 EP - S95 VL - 6 Suppl 1 SN - 1462-2203, 1462-2203 KW - Menthol KW - 1490-04-6 KW - Index Medicus KW - Humans KW - Health Status KW - African Americans -- statistics & numerical data KW - Adolescent KW - Administration, Inhalation KW - Male KW - Female KW - Menthol -- adverse effects KW - Adolescent Behavior KW - Menthol -- administration & dosage KW - Smoking Cessation -- methods KW - Smoking -- ethnology KW - Smoking -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71696015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Adolescent+menthol+smokers%3A+will+they+be+a+harder+target+for+cessation%3F&rft.au=Moolchan%2C+Eric+T&rft.aulast=Moolchan&rft.aufirst=Eric&rft.date=2004-02-01&rft.volume=6+Suppl+1&rft.issue=&rft.spage=S93&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-14 N1 - Date created - 2004-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parkin and alpha-synuclein: opponent actions in the pathogenesis of Parkinson's disease. AN - 71684838; 14987449 AB - Dominant mutations in the gene for alpha-synuclein, a small presynaptic protein, can cause Parkinson's disease. Although there is still substantial debate about the precise mechanisms, alpha-synuclein is toxic to vulnerable neurons, probably as a result of its tendency to aggregate. Opposing this is another gene product that, when mutated, causes a recessive form of parkinsonism, parkin. Parkin has been recently shown to protect cells against alpha-synuclein toxicity. However, the precise details of the mechanism are unclear. This review will discuss the concept that there are multiple neuronal functions that are targeted by mutant alpha-synuclein, and in many cases, there is evidence that parkin can protect cells against damage to the same systems. The authors will also discuss ways in which to test some of these ideas, by using newly identified genes such as DJ-1 that cause similar phenotypes. JF - The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry AU - Baptista, Melisa J AU - Cookson, Mark R AU - Miller, David W AD - Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 63 EP - 72 VL - 10 IS - 1 SN - 1073-8584, 1073-8584 KW - Nerve Tissue Proteins KW - 0 KW - SNCA protein, human KW - Synucleins KW - alpha-Synuclein KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - parkin protein KW - Index Medicus KW - Animals KW - Humans KW - Ubiquitin-Protein Ligases -- chemistry KW - Ubiquitin-Protein Ligases -- genetics KW - Parkinson Disease -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - Ubiquitin-Protein Ligases -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry KW - Parkinson Disease -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71684838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Neuroscientist+%3A+a+review+journal+bringing+neurobiology%2C+neurology+and+psychiatry&rft.atitle=Parkin+and+alpha-synuclein%3A+opponent+actions+in+the+pathogenesis+of+Parkinson%27s+disease.&rft.au=Baptista%2C+Melisa+J%3BCookson%2C+Mark+R%3BMiller%2C+David+W&rft.aulast=Baptista&rft.aufirst=Melisa&rft.date=2004-02-01&rft.volume=10&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=The+Neuroscientist+%3A+a+review+journal+bringing+neurobiology%2C+neurology+and+psychiatry&rft.issn=10738584&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-09 N1 - Date created - 2004-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitative comparisons between a nicotine delivery device (Eclipse) and conventional cigarette smoking. AN - 71680634; 14982693 AB - In 1997, R. J. Reynolds introduced Eclipse, a nicotine delivery device (NDD) purported to deliver lower levels of smoke than conventional cigarettes. This NDD uses a carbon fuel element to vaporize the nicotine in the rod; the user then inhales the nicotine vapor. In the present study, the effects of this NDD on smoking topography; substance delivery factors; and physiological, subjective, and biochemical markers of smoking were compared with commercial cigarettes (referred to as Own Brand). All smoking occurred ad lib with the cigarette or NDD hand-held (conventional) or held in a topography mouthpiece. A total of 10 adults (seven males) smoked on five occasions: NDD conventional, NDD topography, Own Brand conventional, Own Brand topography (twice). Sessions were separated by at least 24 hr. Measures were taken before and 2, 5, 10, 15, 30, and 60 min after smoking. The NDD took longer to smoke (366 s vs. 292 s), required more puffs (14.8 vs. 10.8), and caused a larger increase in exhaled carbon monoxide (CO; 7.3 ppm vs. 4.2 ppm) than Own Brand. However, venous plasma nicotine boost was significantly larger 2 min after smoking Own Brand as compared with the NDD (16.4 ng/ml vs. 10.7 ng/ml). Puff volume (90.7 ml vs. 63.0 ml) and puff velocity (81.6 ml/s vs. 58.2 ml/s) were greater after the NDD than Own Brand, whereas inter-puff interval and puff duration were similar. Subjects rated the NDD as less satisfying (5.2 vs. 9.8), less rewarding (9.5 vs. 14.3), and more aversive (5.0 vs. 3.1) than their own brand. The results of this study indicate that this NDD exposes the user to significant quantities of nicotine, CO, and possibly other harmful components of tobacco smoke. The findings further validate the use of a topography device as an effective instrument to quantify smoke exposure. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Lee, Eun M AU - Malson, Jennifer L AU - Moolchan, Eric T AU - Pickworth, Wallace B AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 95 EP - 102 VL - 6 IS - 1 SN - 1462-2203, 1462-2203 KW - Nicotine KW - 6M3C89ZY6R KW - Carbon Monoxide KW - 7U1EE4V452 KW - Index Medicus KW - Heart Rate -- drug effects KW - Equipment Design KW - Carbon Monoxide -- analysis KW - Humans KW - Adult KW - Volatilization KW - Middle Aged KW - Blood Pressure -- drug effects KW - Male KW - Female KW - Tobacco Use Disorder -- epidemiology KW - Nicotine -- adverse effects KW - Smoking Cessation -- methods KW - Nicotine -- administration & dosage KW - Nicotine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71680634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Quantitative+comparisons+between+a+nicotine+delivery+device+%28Eclipse%29+and+conventional+cigarette+smoking.&rft.au=Lee%2C+Eun+M%3BMalson%2C+Jennifer+L%3BMoolchan%2C+Eric+T%3BPickworth%2C+Wallace+B&rft.aulast=Lee&rft.aufirst=Eun&rft.date=2004-02-01&rft.volume=6&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-01 N1 - Date created - 2004-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The V5 domain of protein kinase C plays a critical role in determining the isoform-specific localization, translocation, and biological function of protein kinase C-delta and -epsilon. AN - 71679736; 14985469 AB - The catalytic domain of overexpressed protein kinase C (PKC)-delta mediates phorbol 12-myristate 13-acetate (PMA)-induced differentiation or apoptosis in appropriate model cell lines. To define the portions of the catalytic domain that are critical for these isozyme-specific functions, we constructed reciprocal chimeras, PKC-delta/epsilonV5 and -epsilon/deltaV5, by swapping the V5 domains of PKC-delta and -epsilon. PKC-delta/epsilonV5 failed to mediate PMA-induced differentiation of 32D cells, showing the essential nature of the V5 domain for PKC-delta's functionality. The other chimera, PKC-epsilon/deltaV5, endowed inactive PKC-epsilon with nearly all PKC-delta's apoptotic ability, confirming the importance of PKC-delta in this function. Green fluorescent protein (GFP)-tagged PKC-deltaV5 and -epsilon/deltaV5 in A7r5 cells showed substantial basal nuclear localization, while GFP-tagged PKC-epsilon and -delta/epsilonV5 showed significantly less, indicating that the V5 region of PKC-delta contains determinants critical to its nuclear distribution. PKC-epsilon/deltaV5-GFP showed much slower kinetics of translocation to membranes in response to PMA than parental PKC-epsilon, implicating the PKC-epsilonV5 domain in membrane targeting. Thus, the V5 domain is critical in several of the isozyme-specific functions of PKC-delta and -epsilon. JF - Molecular cancer research : MCR AU - Wang, Qiming Jane AU - Lu, Ganwei AU - Schlapkohl, Walter A AU - Goerke, Axel AU - Larsson, Christer AU - Mischak, Harald AU - Blumberg, Peter M AU - Mushinski, J Frederic AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 129 EP - 140 VL - 2 IS - 2 SN - 1541-7786, 1541-7786 KW - Peptide Fragments KW - 0 KW - Protein Isoforms KW - Recombinant Fusion Proteins KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkcd protein, rat KW - Prkce protein, mouse KW - Prkce protein, rat KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Protein Kinase C-epsilon KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Cell Membrane -- enzymology KW - Peptide Fragments -- genetics KW - Cell Membrane -- drug effects KW - Protein Transport -- drug effects KW - Protein Isoforms -- metabolism KW - Catalytic Domain KW - Cell Nucleus -- drug effects KW - Mice KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Cell Nucleus -- enzymology KW - Peptide Fragments -- chemistry KW - Protein Isoforms -- chemistry KW - Apoptosis -- drug effects KW - Recombinant Fusion Proteins -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Structure, Tertiary KW - Protein Isoforms -- genetics KW - Cell Differentiation -- drug effects KW - Cell Line KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- genetics KW - Protein Kinase C -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71679736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+research+%3A+MCR&rft.atitle=The+V5+domain+of+protein+kinase+C+plays+a+critical+role+in+determining+the+isoform-specific+localization%2C+translocation%2C+and+biological+function+of+protein+kinase+C-delta+and+-epsilon.&rft.au=Wang%2C+Qiming+Jane%3BLu%2C+Ganwei%3BSchlapkohl%2C+Walter+A%3BGoerke%2C+Axel%3BLarsson%2C+Christer%3BMischak%2C+Harald%3BBlumberg%2C+Peter+M%3BMushinski%2C+J+Frederic&rft.aulast=Wang&rft.aufirst=Qiming&rft.date=2004-02-01&rft.volume=2&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+research+%3A+MCR&rft.issn=15417786&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-24 N1 - Date created - 2004-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preparation of human epidermal keratinocyte cultures. AN - 67316074; 18228450 AB - Cultured keratinocytes have been used by a number of investigators in studies investigating wound repair and carcinogenesis, and they have also proven useful as a model for differentiation. This unit describes a protocol for establishing human keratinocytes in tissue culture. Human newborn foreskins are proteolytically digested to separate the epidermis and the dermis, and keratinocytes are obtained from the epidermis. JF - Current protocols in cell biology AU - Yamada, Susan S AD - National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 VL - Chapter 2 KW - Culture Media KW - 0 KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Humans KW - Epidermis -- cytology KW - Infant, Newborn KW - Foreskin -- cytology KW - Cell Separation KW - Male KW - Keratinocytes -- cytology KW - Cell Culture Techniques -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67316074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+protocols+in+cell+biology&rft.atitle=Preparation+of+human+epidermal+keratinocyte+cultures.&rft.au=Yamada%2C+Susan+S&rft.aulast=Yamada&rft.aufirst=Susan&rft.date=2004-02-01&rft.volume=Chapter+2&rft.issue=&rft.spage=Unit+2.6&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+cell+biology&rft.issn=1934-2616&rft_id=info:doi/10.1002%2F0471143030.cb0206s21 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-03-07 N1 - Date created - 2008-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/0471143030.cb0206s21 ER - TY - JOUR T1 - Protein chaperones as anticancer therapy targets. AN - 67295129; 16163168 JF - Clinical advances in hematology & oncology : H&O AU - Sausville, Edward AD - Developmental Therapeutics Program, National Cancer Institute. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 92 EP - 93 VL - 2 IS - 2 SN - 1543-0790, 1543-0790 KW - Antineoplastic Agents KW - 0 KW - Benzoquinones KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Molecular Chaperones KW - Neoplasm Proteins KW - tanespimycin KW - 4GY0AVT3L4 KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - Benzoquinones -- therapeutic use KW - Neoplasms -- drug therapy KW - Chemical and Drug Induced Liver Injury -- prevention & control KW - Chemical and Drug Induced Liver Injury -- etiology KW - Benzoquinones -- pharmacology KW - Lactams, Macrocyclic -- therapeutic use KW - Humans KW - HSP90 Heat-Shock Proteins -- physiology KW - Clinical Trials as Topic KW - Lactams, Macrocyclic -- pharmacology KW - HSP90 Heat-Shock Proteins -- antagonists & inhibitors KW - Drug Design KW - Neoplasms -- metabolism KW - Drug Delivery Systems KW - Molecular Chaperones -- physiology KW - Molecular Chaperones -- antagonists & inhibitors KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- antagonists & inhibitors KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67295129?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+advances+in+hematology+%26+oncology+%3A+H%26O&rft.atitle=Protein+chaperones+as+anticancer+therapy+targets.&rft.au=Sausville%2C+Edward&rft.aulast=Sausville&rft.aufirst=Edward&rft.date=2004-02-01&rft.volume=2&rft.issue=2&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=Clinical+advances+in+hematology+%26+oncology+%3A+H%26O&rft.issn=15430790&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-09-18 N1 - Date created - 2005-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hydrodynamic gene delivery of interleukin-22 protects the mouse liver from concanavalin A-, carbon tetrachloride-, and Fas ligand-induced injury via activation of STAT3. AN - 67294824; 16212920 AB - Interleukin-22 (IL-22) is a recently identified T cell-derived cytokine whose biological significance remains obscure. Previously, we have shown that IL-22 plays a protective role in T cell-mediated hepatitis induced by Concanavalin A (Con A), acting as a survival factor for hepatocytes. In the present paper, we demonstrate that hydrodynamic gene delivery of IL-22 cDNA driven either by a liver-specific albumin promoter or a human cytomegalovirus (CMV) promoter results in IL-22 protein expression, STAT3 activation, and expression of several anti-apoptotic proteins, including Bcl-xL, Bcl-2, and Mcl-1 in the liver. Immunohistochemical analysis reveals that IL-22 protein expression is mainly detected in the cytoplasm of hepatocytes. Overexpression of IL-22 by hydrodynamic gene delivery significantly protects against liver injury, necrosis, and apoptosis induced by administration of Con A, carbon tetrachloride (CCl4), or the Fas agonist Jo-2 mAb. Western blot analyses show that overexpression of IL-22 significantly enhances activation of STAT3 and expression of Bcl-xL, Bcl-2, and Mcl-1 proteins in liver injury induced by Con A. In conclusion, hydrodynamic gene delivery of IL-22 protects against liver injury induced by a variety of toxins, suggesting the therapeutic potential of IL-22 in treating human liver disease. JF - Cellular & molecular immunology AU - Pan, Hongna AU - Hong, Feng AU - Radaeva, Svetlana AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/02// PY - 2004 DA - February 2004 SP - 43 EP - 49 VL - 1 IS - 1 SN - 1672-7681, 1672-7681 KW - Bcl2l1 protein, mouse KW - 0 KW - FASLG protein, human KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Interleukins KW - Mcl1 protein, mouse KW - Membrane Glycoproteins KW - Myeloid Cell Leukemia Sequence 1 Protein KW - Neoplasm Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - STAT3 Transcription Factor KW - Tumor Necrosis Factors KW - bcl-X Protein KW - interleukin-22 KW - Concanavalin A KW - 11028-71-0 KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - Index Medicus KW - Chemical and Drug Induced Liver Injury -- prevention & control KW - Animals KW - Chemical and Drug Induced Liver Injury -- pathology KW - Humans KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Mice, Inbred C57BL KW - Mice KW - Neoplasm Proteins -- metabolism KW - bcl-X Protein -- metabolism KW - Liver -- pathology KW - Concanavalin A -- metabolism KW - Tumor Necrosis Factors -- metabolism KW - Gene Transfer Techniques KW - Interleukins -- metabolism KW - STAT3 Transcription Factor -- metabolism KW - Carbon Tetrachloride -- toxicity KW - Liver -- physiology KW - Interleukins -- genetics KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67294824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+molecular+immunology&rft.atitle=Hydrodynamic+gene+delivery+of+interleukin-22+protects+the+mouse+liver+from+concanavalin+A-%2C+carbon+tetrachloride-%2C+and+Fas+ligand-induced+injury+via+activation+of+STAT3.&rft.au=Pan%2C+Hongna%3BHong%2C+Feng%3BRadaeva%2C+Svetlana%3BGao%2C+Bin&rft.aulast=Pan&rft.aufirst=Hongna&rft.date=2004-02-01&rft.volume=1&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Cellular+%26+molecular+immunology&rft.issn=16727681&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-27 N1 - Date created - 2005-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV Prevention Research for African Americans: Current and Future Directions AN - 21338123; 11616007 AB - African Americans experience HIV and AIDS at a rate 10 times greater than the U.S. White population. Although there have been advances in HIV risk-reduction strategies, these efforts have not been as successful in decreasing HIV infection in the African American population. This article reviews the research base of HIV prevention interventions to identify research that will lead to the development of more effective prevention strategies for African Americans. Major limitations found in the research include the exclusion of African Americans in studies, particularly those at higher risk, and the lack of using culturally based theory to guide research. Recommendations for improving research are offered. They include conducting research that focuses on structural interventions rather than individuals, controlling for diversity within the African American population, defining culture when using it in research, and developing a cadre of African American researchers involved in prevention intervention studies. JF - Journal of Black Psychology AU - Beatty, Lula A AU - Wheeler, Darrell AU - Gaiter, Juarlyn AD - National Institutes of Health Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 40 EP - 58 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 30 IS - 1 SN - 0095-7984, 0095-7984 KW - Risk Abstracts KW - Acquired immune deficiency syndrome KW - risk reduction KW - USA KW - Human immunodeficiency virus KW - intervention KW - Reviews KW - prevention KW - infection KW - Africa KW - Ethnic groups KW - R2 23110:Psychological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21338123?accountid=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=Journal+of+Black+Psychology&rft.atitle=HIV+Prevention+Research+for+African+Americans%3A+Current+and+Future+Directions&rft.au=Beatty%2C+Lula+A%3BWheeler%2C+Darrell%3BGaiter%2C+Juarlyn&rft.aulast=Beatty&rft.aufirst=Lula&rft.date=2004-02-01&rft.volume=30&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=Journal+of+Black+Psychology&rft.issn=00957984&rft_id=info:doi/10.1177%2F0095798403259245 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - risk reduction; Acquired immune deficiency syndrome; Human immunodeficiency virus; Reviews; intervention; infection; prevention; Ethnic groups; USA; Africa DO - http://dx.doi.org/10.1177/0095798403259245 ER - TY - JOUR T1 - HIV Risk-Reduction Strategies for Substance Abusers: Effecting Behavior Change AN - 21303976; 11616009 AB - Substance abuse has a strong link to HIV/AIDS in the United States. Use and abuse of alcohol and other drugs often reduce inhibitions and encourage engagement in high-risk sexual behaviors that can ultimately result in HIV and AIDS. The HIV/AIDS epidemic in the United States has disproportionately affected minorities with African Americans being the group hardest hit. This article presents some of the behavioral, social, and psychological factors that influence the risk for drug use. It highlights and assesses the effectiveness of HIV risk-reduction strategies developed for drug-using populations and makes recommendations for a more holistic and integrated approach utilizing multiple interventions at multiple levels. JF - Journal of Black Psychology AU - Jones, Dionne J AD - National Institute on Drug Abuse, National Institutes of Health Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 59 EP - 77 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 30 IS - 1 SN - 0095-7984, 0095-7984 KW - Risk Abstracts KW - sexual behavior KW - Acquired immune deficiency syndrome KW - Psychology KW - Drug abuse KW - substance abuse KW - risk reduction KW - intervention KW - Drugs KW - Ethnic groups KW - Alcohol KW - USA KW - Behavior KW - Human immunodeficiency virus KW - Africa KW - R2 23110:Psychological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21303976?accountid=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=Journal+of+Black+Psychology&rft.atitle=HIV+Risk-Reduction+Strategies+for+Substance+Abusers%3A+Effecting+Behavior+Change&rft.au=Jones%2C+Dionne+J&rft.aulast=Jones&rft.aufirst=Dionne&rft.date=2004-02-01&rft.volume=30&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Journal+of+Black+Psychology&rft.issn=00957984&rft_id=info:doi/10.1177%2F0095798403259246 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - substance abuse; sexual behavior; Alcohol; risk reduction; Acquired immune deficiency syndrome; Behavior; Psychology; Human immunodeficiency virus; intervention; Drug abuse; Drugs; Ethnic groups; USA; Africa DO - http://dx.doi.org/10.1177/0095798403259246 ER - TY - JOUR T1 - HIV Treatment in African Americans: Challenges and Opportunities AN - 21247815; 11616006 AB - This article reviews the current standard of care for HIV infection as well as how health disparities in the HIV care of African Americans present challenges for both providers and patients. The potential side effects in these antiretroviral treatment regimens that may be a source of additional challenges in treating African Americans are highlighted. A brief review of these issues as they relate to treatment adherence further demonstrates how adherence is closely linked to the medical and psychosocial issues African Americans face including access to HIV care services. The article concludes with a discussion of gender-related issues that affect treatment and that may confound effective behavioral interventions aimed at reducing HIV risk and increasing treatment adherence. JF - Journal of Black Psychology AU - Cargill, Victoria A AU - Stone, Valerie E AU - Robinson, MRenee AD - National Institutes of Health Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 24 EP - 39 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 30 IS - 1 SN - 0095-7984, 0095-7984 KW - Virology & AIDS Abstracts; Risk Abstracts KW - HIV treatment KW - African Americans KW - Antiviral agents KW - Human immunodeficiency virus KW - intervention KW - Reviews KW - antiretroviral agents KW - infection KW - Africa KW - Infection KW - Ethnic groups KW - Side effects KW - V 22360:AIDS and HIV KW - R2 23110:Psychological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21247815?accountid=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=Journal+of+Black+Psychology&rft.atitle=HIV+Treatment+in+African+Americans%3A+Challenges+and+Opportunities&rft.au=Cargill%2C+Victoria+A%3BStone%2C+Valerie+E%3BRobinson%2C+MRenee&rft.aulast=Cargill&rft.aufirst=Victoria&rft.date=2004-02-01&rft.volume=30&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Journal+of+Black+Psychology&rft.issn=00957984&rft_id=info:doi/10.1177%2F0095798403259243 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Antiviral agents; Reviews; Infection; Side effects; Human immunodeficiency virus; intervention; antiretroviral agents; infection; Ethnic groups; Africa DO - http://dx.doi.org/10.1177/0095798403259243 ER - TY - JOUR T1 - Exercise-induced dystonia as a preceding symptom of familial Parkinson's disease AN - 21143318; 11343346 AB - Paroxysmal exercise-induced dystonia can occur with Parkinson's disease (PD), and in rare cases, this can also be the presenting symptom. We report on 2 second cousins (no known consanguinity) who presented with paroxysmal exercise-induced dystonia who later developed clinical features of PD. Although autosomal recessive inheritance was suggested, and the dystonic features further suggest parkin as a possible cause, ssequencing for parkin mutations was negative and this family may represent a genetic variant of PD. Further genotype-phenotype studies in this and similar families may give clues to pre-symptomatic symptoms in PD and may reflect a particular phenotype of interest for genetics studies in the future. JF - Movement Disorders AU - Bruno, Michiko K AU - Ravina, Bernard AU - Garraux, Gaetan AU - Hallett, Mark AU - Ptacek, Louis AU - Singleton, Amanda AU - Johnson, Janel AU - Singleton, Andrew AU - Hanson, Melissa AU - Considinen, Elaine AU - Gwinn-Hardy, Katrina AD - Parkinson's Unit, Division of Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA, brunom@ninds.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 228 EP - 230 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 19 IS - 2 SN - 0885-3185, 0885-3185 KW - Physical Education Index; CSA Neurosciences Abstracts KW - Parkin protein KW - Neurodegenerative diseases KW - Genetics KW - Consanguinity KW - Movement disorders KW - Heredity KW - Parkinson's disease KW - Dystonia KW - Family KW - Mutation KW - N3 11023:Neurogenetics KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21143318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+Disorders&rft.atitle=Exercise-induced+dystonia+as+a+preceding+symptom+of+familial+Parkinson%27s+disease&rft.au=Bruno%2C+Michiko+K%3BRavina%2C+Bernard%3BGarraux%2C+Gaetan%3BHallett%2C+Mark%3BPtacek%2C+Louis%3BSingleton%2C+Amanda%3BJohnson%2C+Janel%3BSingleton%2C+Andrew%3BHanson%2C+Melissa%3BConsidinen%2C+Elaine%3BGwinn-Hardy%2C+Katrina&rft.aulast=Bruno&rft.aufirst=Michiko&rft.date=2004-02-01&rft.volume=19&rft.issue=2&rft.spage=228&rft.isbn=&rft.btitle=&rft.title=Movement+Disorders&rft.issn=08853185&rft_id=info:doi/10.1002%2Fmds.10626 LA - English DB - Physical Education Index N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Genetics; Parkinson's disease; Family; Parkin protein; Neurodegenerative diseases; Consanguinity; Movement disorders; Heredity; Dystonia; Mutation DO - http://dx.doi.org/10.1002/mds.10626 ER - TY - JOUR T1 - Adjusting for Ordinal Covariates by Inducing a Partial Ordering AN - 21103339; 11132359 AB - In the context of randomized clinical trials, multiplicity arises in many forms. One prominent example is when a key endpoint is measured and analyzed both at baseline and after treatment. It is common to analyze each separately, but more efficient to adjust the post-treatment comparisons for the baseline values. Adjustment techniques generally treat the covariate (baseline value, in this case) as either nominal or continuous. Either is problematic when applied to an ordinal covariate, the former because it fails to exploit the natural ordering and the latter because it relies on an artifical notion of linear prediction and differences between values. We propose new methods for adjusting for ordinal covariates without having to treat them as nominal or continuous. Specifically, the information-preserving composite endpoint consists of the pair of values for each patient, one at baseline and one after treatment. Some of these patterns will indicate more improvement than others, yet some pairs of patterns are not comparable. Hence, the ordering is only partial. We develop an approach to testing and deriving estimators of magnitudes of the treatment effect based on comparing each observation in one group to each observation in the other group to which it is comparable. JF - Biometrical Journal AU - Berger, Vance W AU - Zhou, Yanyan AU - Ivanova, Anastasia AU - Tremmel, Lothar AD - NCI; University of Maryland, Baltimore County, vb78c@nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 48 EP - 55 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 46 IS - 1 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Clinical trials KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21103339?accountid=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=Biometrical+Journal&rft.atitle=Adjusting+for+Ordinal+Covariates+by+Inducing+a+Partial+Ordering&rft.au=Berger%2C+Vance+W%3BZhou%2C+Yanyan%3BIvanova%2C+Anastasia%3BTremmel%2C+Lothar&rft.aulast=Berger&rft.aufirst=Vance&rft.date=2004-02-01&rft.volume=46&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200410012 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Clinical trials DO - http://dx.doi.org/10.1002/bimj.200410012 ER - TY - JOUR T1 - Trapping radioactive carbon dioxide during cellular metabolic assays under standard culture conditions: description of a unique gas-capturing device AN - 20960640; 8432467 AB - Measurement of carbon dioxide levels has been employed to follow cellular metabolic reactions for quite some time. By radio-labeling substrate molecules and evaluating the radioactivity levels of the carbon dioxide released, insight into metabolic pathways can be gleaned. Currently, no carbon dioxide capturing device is available that can be used with large volume cell monolayers growing under standard conditions within a regular commercially available culture flask. In this note we describe a simple device for collecting radio-labeled carbon dioxide from a standard culture flask. The device is independent of the culture flask, but can be attached for metabolic measurements allowing cells to be grown under standard conditions prior to study. The presented design permits convenient transfer of the device between flasks without contaminating or disturbing cells growing within the flasks. Data are presented demonstrating the reproducibility of measurements made with multiple devices with different substrate concentrations and varying periods of time, ranging up to 3 h. JF - Journal of Biochemical and Biophysical Methods AU - Krieg, Rene C AU - Liotta, Lance A AU - Petricoin, Emanuel F AU - Herrmann, Paul C AD - FDA-NCI Clinical Proteomics Program, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10 Room 2n212, Bethesda, MD 20892, USA, herrmanp@mail.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 119 EP - 124 PB - Elsevier Science, The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 58 IS - 2 SN - 0165-022X, 0165-022X KW - Biotechnology and Bioengineering Abstracts KW - Author Keywords: Metabolism KW - Physiological KW - Carbon dioxide KW - Radioactivity KW - Data processing KW - Metabolic pathways KW - Cell culture KW - Trapping KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20960640?accountid=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+Biochemical+and+Biophysical+Methods&rft.atitle=Trapping+radioactive+carbon+dioxide+during+cellular+metabolic+assays+under+standard+culture+conditions%3A+description+of+a+unique+gas-capturing+device&rft.au=Krieg%2C+Rene+C%3BLiotta%2C+Lance+A%3BPetricoin%2C+Emanuel+F%3BHerrmann%2C+Paul+C&rft.aulast=Krieg&rft.aufirst=Rene&rft.date=2004-02-01&rft.volume=58&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biochemical+and+Biophysical+Methods&rft.issn=0165022X&rft_id=info:doi/10.1016%2Fj.jbbm.2003.10.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-10-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Data processing; Metabolic pathways; Cell culture; Radioactivity; Carbon dioxide; Trapping DO - http://dx.doi.org/10.1016/j.jbbm.2003.10.002 ER - TY - JOUR T1 - The Salk Polio Vaccine Trial of 1954: risks, randomization and public involvement in research AN - 20798442; 10893720 AB - The year 2004 marks the 'ftieth anniversary of the celebrated 1954 Salk polio vaccine trial. This enormous clinical trial, involving 1.8 million children, was carried out with the co-operation and assistance of hundreds of thousands of lay volunteers, along with medical professionals and local health departments throughout the USA. While the trial was an impressive public health achievement, 'rmly establishing the ef'cacy of the killed virus vaccine and paving the way for eradication of the disease, it was not without controversy. This article recounts the story of this important early clinical trial and how the social and political conditions at the time affected its planning and execution. JF - Clinical Trials AU - Dawson, Liza AD - The Phoebe R. Berman Bioethics Institute, The John Hopkins University, 624 N. Broadway, Hampton House Rm. 352, Baltimore, MD 21205, USA, dawsonl@mail.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 122 EP - 130 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU VL - 1 IS - 1 SN - 1740-7745, 1740-7745 KW - Virology & AIDS Abstracts; Risk Abstracts KW - vaccines KW - Politics KW - public involvement KW - clinical trials KW - Children KW - Clinical trials KW - Medical personnel KW - Public health KW - USA KW - Vaccines KW - R2 23060:Medical and environmental health KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20798442?accountid=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=Clinical+Trials&rft.atitle=The+Salk+Polio+Vaccine+Trial+of+1954%3A+risks%2C+randomization+and+public+involvement+in+research&rft.au=Dawson%2C+Liza&rft.aulast=Dawson&rft.aufirst=Liza&rft.date=2004-02-01&rft.volume=1&rft.issue=1&rft.spage=122&rft.isbn=&rft.btitle=&rft.title=Clinical+Trials&rft.issn=17407745&rft_id=info:doi/10.1191%2F1740774504cn010xx LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-09-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Vaccines; Children; Clinical trials; Public health; vaccines; Politics; public involvement; clinical trials; Medical personnel; USA DO - http://dx.doi.org/10.1191/1740774504cn010xx ER - TY - JOUR T1 - Diet, nutrition and the prevention of cancer AN - 20777383; 10837950 AB - To assess the epidemiological evidence on diet and cancer and make public health recommendations. Review of published studies, concentrating on recent systematic reviews, meta-analyses and large prospective studies. Overweight/obesity increases the risk for cancers of the oesophagus (adenocarcinoma), colorectum, breast (postmenopausal), endometrium and kidney; body weight should be maintained in the body mass index range of 18.5-25 kg/m2, and weight gain in adulthood avoided. Alcohol causes cancers of the oral cavity, pharynx, oesophagus and liver, and a small increase in the risk for breast cancer; if consumed, alcohol intake should not exceed 2?units/d. Aflatoxin in foods causes liver cancer, although its importance in the absence of hepatitis virus infections is not clear; exposure to aflatoxin in foods should be minimised. Chinese-style salted fish increases the risk for nasopharyngeal cancer, particularly if eaten during childhood, and should be eaten only in moderation. Fruits and vegetables probably reduce the risk for cancers of the oral cavity, oesophagus, stomach and colorectum, and diets should include at least 400?g/d of total fruits and vegetables. Preserved meat and red meat probably increase the risk for colorectal cancer; if eaten, consumption of these foods should be moderate. Salt preserved foods and high salt intake probably increase the risk for stomach cancer; overall consumption of salt preserved foods and salt should be moderate. Very hot drinks and foods probably increase the risk for cancers of the oral cavity, pharynx and oesophagus; drinks and foods should not be consumed when they are scalding hot. Physical activity, the main determinant of energy expenditure, reduces the risk for colorectal cancer and probably reduces the risk for breast cancer; regular physical activity should be taken. JF - Public Health Nutrition AU - Key, Timothy J AU - Schatzkin, Arthur AU - Willett, Walter C AU - Allen, Naomi E AU - Spencer, Elizabeth A AU - Travis, Ruth C AD - Nutritional Epidemiology Branch, Division of Cancer, Epidemiology and Genetics, National Cancer Institute, Bethesda, USA, tim.key@cancer.org.uk Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 187 EP - 200 PB - Cambridge University Press, 32 Avenue of the Americas New York NY 10013-2473 USA VL - 7 IS - 1a SN - 1368-9800, 1368-9800 KW - Virology & AIDS Abstracts; Risk Abstracts KW - Vegetables KW - Pharynx KW - Physical activity KW - Colorectal cancer KW - Oral cavity KW - Public health KW - risk reduction KW - Body weight KW - prevention KW - alcohols KW - Gastric cancer KW - Esophagus KW - Diets KW - Alcoholic beverages KW - Aflatoxins KW - Salts KW - colorectal carcinoma KW - Body mass index KW - Fruits KW - Liver cancer KW - Food KW - obesity KW - Infection KW - Nutrition KW - Food consumption KW - body mass KW - infection KW - physical activity KW - body weight KW - Alcohol KW - Endometrium KW - Beverages KW - fruits KW - Children KW - Cancer KW - Meat KW - Reviews KW - Liver KW - Kidney KW - Breast cancer KW - Adenocarcinoma KW - Stomach KW - R2 23060:Medical and environmental health KW - V 22370:Oncology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20777383?accountid=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=Public+Health+Nutrition&rft.atitle=Diet%2C+nutrition+and+the+prevention+of+cancer&rft.au=Key%2C+Timothy+J%3BSchatzkin%2C+Arthur%3BWillett%2C+Walter+C%3BAllen%2C+Naomi+E%3BSpencer%2C+Elizabeth+A%3BTravis%2C+Ruth+C&rft.aulast=Key&rft.aufirst=Timothy&rft.date=2004-02-01&rft.volume=7&rft.issue=1a&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Public+Health+Nutrition&rft.issn=13689800&rft_id=info:doi/10.1079%2FPHN2003588 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-09-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Fruits; Vegetables; Pharynx; Physical activity; Food; Liver cancer; Colorectal cancer; Infection; Nutrition; Oral cavity; Public health; Food consumption; Body weight; alcohols; Gastric cancer; Diets; Esophagus; Endometrium; Beverages; Alcoholic beverages; Aflatoxins; Children; Meat; Salts; Reviews; Kidney; Breast cancer; Adenocarcinoma; Body mass index; Stomach; Alcohol; fruits; obesity; Cancer; risk reduction; body mass; colorectal carcinoma; infection; Liver; prevention; physical activity; body weight DO - http://dx.doi.org/10.1079/PHN2003588 ER - TY - JOUR T1 - Obesity and cancer risk among white and black United States veterans AN - 20708581; 5861548 AB - Background: Obesity has been linked to excess risk for many cancers, but the evidence remains tenuous for some types. Although the prevalence of obesity varies by race, few studies of obesity-related cancer risk have included non-white subjects. Methods: In a large cohort of male US veterans (3,668,486 whites; 832,214 blacks) hospitalized with a diagnosis of obesity between 1969 and 1996, we examined risk for all major cancer sites and subsites. Person-years accrued from the date of first obesity diagnosis until the occurrence of a first cancer, death, or the end of the observation period (September 30, 1996). We calculated age- and calendar-year adjusted relative risks (RR) and 95% confidence intervals (CI) for cancer among white and black veterans, comparing obese men to men hospitalized for other reasons, with obesity status as time-dependent. For selected cancers, we performed additional analyses stratified by specific medical conditions related to both obesity and risk of those cancers. To determine whether obesity-related cancer risks differed significantly between white and black men, we evaluated heterogeneity of risk for each cancer site. Results: Among white veterans, risk was significantly elevated for several cancers, including cancers of the lower esophagus, gastric cardia, small intestine, colon, rectum, gallbladder and ampulla of vater, male breast, prostate, bladder, thyroid, and connective tissue, and for malignant melanoma, multiple myeloma, chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML). Excess risks initially observed for cancers of the liver and pancreas persisted among men without a history of diabetes or alcoholism. Among black veterans, risks were significantly elevated for cancers of the colon, extrahepatic bile ducts, prostate, thyroid, and for malignant melanoma, multiple myeloma, CLL and AML. Conclusions: Obese men are at increased risk for several major cancers as well as a number of uncommon malignancies, a pattern generally similar for white and black men. Due to the increasing prevalence of obesity and overweight worldwide, it is important to clarify the impact of excess body weight on cancer and to elucidate the mechanisms involved. JF - Cancer Causes & Control AU - Samanic, C AU - Gridley, G AU - Chow, W AU - Lubin, J AU - Hoover, R N AU - Fraumeni, Jr JF AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Boulevard, Room 8115, Bethesda, MD 20892, USA; Ph.: +1-301-402-7824, samanicc@mail.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 35 EP - 44 PB - Kluwer Academic Publishers VL - 15 IS - 1 SN - 0957-5243, 0957-5243 KW - Risk Abstracts KW - Mortality KW - Historical account KW - multiple myeloma KW - obesity KW - Thyroid KW - melanoma KW - Cancer KW - Leukemia KW - USA KW - diabetes mellitus KW - Liver KW - body weight KW - alcoholism KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20708581?accountid=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=Cancer+Causes+%26+Control&rft.atitle=Obesity+and+cancer+risk+among+white+and+black+United+States+veterans&rft.au=Samanic%2C+C%3BGridley%2C+G%3BChow%2C+W%3BLubin%2C+J%3BHoover%2C+R+N%3BFraumeni%2C+Jr+JF&rft.aulast=Samanic&rft.aufirst=C&rft.date=2004-02-01&rft.volume=15&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/10.1023%2FB%3ACACO.0000016573.79453.ba LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-10-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Historical account; Mortality; Leukemia; diabetes mellitus; multiple myeloma; Liver; Thyroid; obesity; melanoma; body weight; Cancer; alcoholism; USA DO - http://dx.doi.org/10.1023/B:CACO.0000016573.79453.ba ER - TY - JOUR T1 - Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. AN - 204288487; 14766739 JF - Arteriosclerosis, Thrombosis and Vascular Biology AU - Grundy, S M AU - Brewer HB Jr AU - Cleeman JI AU - SC, Smith, Jr AU - Lenfant, C AU - National Heart, Lung, and Blood Institute AU - American Heart Association AD - National Heart, Lung, and Blood Institute ; American Heart Association Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - e13 EP - 8 CY - Hagerstown PB - American Heart Association, Inc. VL - 24 IS - 2 SN - 10795642 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/204288487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arteriosclerosis%2C+Thrombosis+and+Vascular+Biology&rft.atitle=Definition+of+metabolic+syndrome%3A+report+of+the+National+Heart%2C+Lung%2C+and+Blood+Institute%2FAmerican+Heart+Association+conference+on+scientific+issues+related+to+definition.%3A+An+Official+Journal+of+the+American+Heart+Association%2C+Inc.&rft.au=Grundy%2C+S+M%3BBrewer+HB+Jr%3BCleeman+JI%3BSC%2C+Smith%2C+Jr%3BLenfant%2C+C%3BNational+Heart%2C+Lung%2C+and+Blood+Institute%3BAmerican+Heart+Association&rft.aulast=Grundy&rft.aufirst=S&rft.date=2004-02-01&rft.volume=24&rft.issue=2&rft.spage=e13&rft.isbn=&rft.btitle=&rft.title=Arteriosclerosis%2C+Thrombosis+and+Vascular+Biology&rft.issn=10795642&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 2004 N1 - Last updated - 2014-05-21 ER - TY - JOUR T1 - Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. AN - 204283728; 14766740 JF - Arteriosclerosis, Thrombosis and Vascular Biology AU - Grundy, S M AU - Hansen, B AU - SC, Smith, Jr AU - Cleeman JI AU - Kahn, R A AU - American Heart Association AU - National Heart, Lung, and Blood Institute AU - American Diabetes Association AD - American Heart Association ; National Heart, Lung, and Blood Institute ; American Diabetes Association Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - e19 EP - 24 CY - Hagerstown PB - American Heart Association, Inc. VL - 24 IS - 2 SN - 10795642 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/204283728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arteriosclerosis%2C+Thrombosis+and+Vascular+Biology&rft.atitle=Clinical+management+of+metabolic+syndrome%3A+report+of+the+American+Heart+Association%2FNational+Heart%2C+Lung%2C+and+Blood+Institute%2FAmerican+Diabetes+Association+conference+on+scientific+issues+related+to+management.%3A+An+Official+Journal+of+the+American+Heart+Association%2C+Inc.&rft.au=Grundy%2C+S+M%3BHansen%2C+B%3BSC%2C+Smith%2C+Jr%3BCleeman+JI%3BKahn%2C+R+A%3BAmerican+Heart+Association%3BNational+Heart%2C+Lung%2C+and+Blood+Institute%3BAmerican+Diabetes+Association&rft.aulast=Grundy&rft.aufirst=S&rft.date=2004-02-01&rft.volume=24&rft.issue=2&rft.spage=e19&rft.isbn=&rft.btitle=&rft.title=Arteriosclerosis%2C+Thrombosis+and+Vascular+Biology&rft.issn=10795642&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Feb 2004 N1 - Last updated - 2014-05-21 ER - TY - JOUR T1 - Altered p16 super(INK4a) and Fhit expression in carcinogenesis and progression of human oral cancer AN - 19862353; 7438821 AB - To further characterize the biological and clinical role of molecular alterations involved in oral squamous carcinogenesis, the immunohistochemical expression level of two tumor suppressor genes, fragile histidine triad and p16 super(INK4a), in non-carcinomatous squamous epithelia and head and neck squamous cell carcinoma was determined. In addition, human papillomavirus infection determined by PCR assay and the use of alcohol and cigarettes were evaluated. In this study 28 non-carcinomatous squamous epithelia and 57 head and neck squamous cell carcinoma were considered. The expression levels of fragile histidine triad were lower in head and neck squamous cell carcinoma than in non-carcinomatous squamous epithelia. In contrast, p16 super(INK4a) is expressed in malignant lesions (51% of the cases analyzed), but not in non-carcinomatous squamous epithelia. No correlation between gene expression alterations of the two tumor suppressors was observed. PCR analysis showed that HPV DNA was present in 5 of the 57 malignant lesions analyzed (8.8%). None of the factors described above, despite changes in gene expression and HPV infection, appears to be associated with alcohol use and/or tobacco smoking and clinical outcome. Our data showed that fragile histidine triad and p16 super(INK4a) expression are altered in malignant lesions. Most likely, the decreasing levels of fragile histidine triad is directly involved in cancer development, while the accumulation of p16 super(INK4a) in head and neck squamous cell carcinoma may be the consequence of loss of functional tumor suppressor retinoblastoma pathway. JF - International Journal of Oncology AU - Paradiso, A AU - Ranieri, G AU - Stea, B AU - Zito, A AU - Zehbe, I AU - Tommasino, M AU - Grammatica, L AU - De Lena, M AD - Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola 209, 70126 Bari, Italy, paradiso.io.bari@virgilio.it Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 249 EP - 255 VL - 24 IS - 2 SN - 1019-6439, 1019-6439 KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - Tobacco smoking KW - Tumor suppressor genes KW - Data processing KW - Cigarettes KW - INK4a protein KW - squamous cell carcinoma KW - Infection KW - retinoblastoma KW - Gene expression KW - p16 protein KW - Carcinogenesis KW - alcohols KW - Polymerase chain reaction KW - Head and neck cancer KW - FHIT protein KW - Human papillomavirus KW - X 24380:Social Poisons & Drug Abuse KW - B 26670:Tumor Suppressors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19862353?accountid=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+Oncology&rft.atitle=Altered+p16+super%28INK4a%29+and+Fhit+expression+in+carcinogenesis+and+progression+of+human+oral+cancer&rft.au=Paradiso%2C+A%3BRanieri%2C+G%3BStea%2C+B%3BZito%2C+A%3BZehbe%2C+I%3BTommasino%2C+M%3BGrammatica%2C+L%3BDe+Lena%2C+M&rft.aulast=Paradiso&rft.aufirst=A&rft.date=2004-02-01&rft.volume=24&rft.issue=2&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Tumor suppressor genes; Tobacco smoking; Data processing; Cigarettes; INK4a protein; squamous cell carcinoma; Infection; retinoblastoma; Gene expression; p16 protein; Carcinogenesis; alcohols; Head and neck cancer; Polymerase chain reaction; FHIT protein; Human papillomavirus ER - TY - JOUR T1 - Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades AN - 19271654; 5849695 AB - Methamphetamine (METH) is an illicit drug that causes neurodegenerative effects in humans. In rodents, METH induces apoptosis of striatal glutamic acid decarboxylase (GAD) -containing neurons. This paper provides evidence that METH-induced cell death occurs consequent to interactions of ER stress and mitochondrial death pathways. Specifically, injections of METH are followed by an almost immediate activation of proteases calpain and caspase-12, events consistent with drug-induced ER stress. Involvement of ER stress was further supported by observations of increases in the expression of GRP78/BiP and CHOP. Participation of the mitochondrial pathway was demonstrated by the transition of AIF, smac/DIABLO, and cytochrome c from mitochondrial into cytoplasmic fractions. These changes occur before the apoptosome-associated pro-caspase-9 cleavage. Effector caspases-3 and -6, but not -7, were cleaved with the initial time of caspase-3 activation occurring before caspase 9 cleavage; this suggests possible earlier cleavage of caspase-3 by caspase-12. These events preceded proteolysis of the caspase substrates DFF-45, lamin A, and PARP in nuclear fractions. These findings indicate that METH causes neuronal apoptosis in part via cross-talks between ER- and mitochondria-generated processes, which cause activation of both caspase-dependent and -independent pathways. JF - FASEB Journal AU - Jayanthi, S AU - Deng, X AU - Noailles, P-AH AU - Ladenheim, B AU - Cadet, J L AD - Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, Intramural Research Program, National Institute of Health, DHHS, 5500 Nathan Shock Dr., Baltimore, MD 21224, USA, jcadet@intra.nida.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 238 EP - 251 VL - 18 IS - 2 SN - 0892-6638, 0892-6638 KW - Toxicology Abstracts KW - Endoplasmic reticulum KW - Cell death KW - Methamphetamine KW - Apoptosis KW - Neurons KW - Mitochondria KW - Caspase KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19271654?accountid=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=FASEB+Journal&rft.atitle=Methamphetamine+induces+neuronal+apoptosis+via+cross-talks+between+endoplasmic+reticulum+and+mitochondria-dependent+death+cascades&rft.au=Jayanthi%2C+S%3BDeng%2C+X%3BNoailles%2C+P-AH%3BLadenheim%2C+B%3BCadet%2C+J+L&rft.aulast=Jayanthi&rft.aufirst=S&rft.date=2004-02-01&rft.volume=18&rft.issue=2&rft.spage=238&rft.isbn=&rft.btitle=&rft.title=FASEB+Journal&rft.issn=08926638&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 - Methamphetamine; Apoptosis; Neurons; Endoplasmic reticulum; Mitochondria; Caspase; Cell death ER - TY - JOUR T1 - Genetic, cellular and immune approaches to disease therapy: past and future AN - 19270362; 5847159 AB - Advances in immunology and molecular genetics have accelerated our understanding of the genetic and cellular basis of many diseases. At the same time, remarkable progress in recombinant DNA technology has enabled the development of molecular and cellular treatments for infectious diseases, inherited disorders and cancer. This Perspective is intended to give a sample of the progress over the past ten years in cellular, genetic and immune therapy of disease. During this time, monoclonal antibody technology and cellular transplantation have begun to come of age in biomedicine. Innovations in gene delivery have not only catalyzed the nascent field of human gene therapy, but may also ultimately impact human health by advancing recombinant vaccine technology. JF - Nature Medicine AU - Nabel, G J AD - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, USA, gnabel@nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 135 EP - 141 VL - 10 IS - 2 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Hereditary diseases KW - Transplantation KW - Gene therapy KW - Monoclonal antibodies KW - Immunotherapy KW - Infectious diseases KW - Reviews KW - Vaccines KW - F 06739:Reviews 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/19270362?accountid=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+Medicine&rft.atitle=Genetic%2C+cellular+and+immune+approaches+to+disease+therapy%3A+past+and+future&rft.au=Nabel%2C+G+J&rft.aulast=Nabel&rft.aufirst=G&rft.date=2004-02-01&rft.volume=10&rft.issue=2&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/10.1038%2Fnm990 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Gene therapy; Immunotherapy; Transplantation; Vaccines; Infectious diseases; Hereditary diseases; Monoclonal antibodies DO - http://dx.doi.org/10.1038/nm990 ER - TY - JOUR T1 - AIR-SPAMM: alternative inversion recovery spatial modulation of magnetization for myocardial tagging AN - 19269606; 5828343 AB - Alternate inversion recovery spatial modulation of magnetization (AIR-SPAMM) can be used either for doubling the number of tags for a given tagging encoding gradient strength or for improving tagging contrast ratio. AIR-SPAMM requires only a single acquisition and utilizes inversion pulses spaced throughout the gradient recalled echo (GRE) cine acquisition to 'lock' the recovering magnetization at a desired level. The theory of AIR-SPAMM is presented along with simulations and results from phantoms. AIR-SPAMM can be used either for imaging systole as demonstrated by initial in vivo results or potentially for imaging the entire cardiac cycle in a slice-interleaved manner. JF - Journal of Magnetic Resonance AU - Aletras, AH AU - Freidlin, R Z AU - Navon, G AU - Arai, A E AD - Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10, Room B1D416, MSC 1061, Bethesda, MD 20892-1061, USA, Anthony_Aletras@nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 236 EP - 245 PB - Academic Press, Inc., 525 B St. Ste. 1900 San Diego CA 92101-4495 USA, [mailto:apsubs@acad.com] VL - 166 IS - 2 SN - 1090-7807, 1090-7807 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Magnetic fields KW - Magnetic resonance imaging KW - Myocardium KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19269606?accountid=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+Magnetic+Resonance&rft.atitle=AIR-SPAMM%3A+alternative+inversion+recovery+spatial+modulation+of+magnetization+for+myocardial+tagging&rft.au=Aletras%2C+AH%3BFreidlin%2C+R+Z%3BNavon%2C+G%3BArai%2C+A+E&rft.aulast=Aletras&rft.aufirst=AH&rft.date=2004-02-01&rft.volume=166&rft.issue=2&rft.spage=236&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance&rft.issn=10907807&rft_id=info:doi/10.1016%2Fj.jmr.2003.10.021 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Myocardium; Magnetic fields DO - http://dx.doi.org/10.1016/j.jmr.2003.10.021 ER - TY - JOUR T1 - Chronic methamphetamine increases fighting in mice AN - 19266329; 5827844 AB - A propensity for violent behaviors to develop in chronic methamphetamine (METH) abusers has been noted. The idea that increased aggressiveness might result from chronic METH administration was tested in mice after chronic (long- term intermittent, 8 weeks) or single exposures to the drug. A single injection of METH (6 mg/kg) did not augment fighting. In contrast, chronic METH administration significantly increased the number of animals that initiated bite attacks. This regimen also shortened the latency before the first attack. Latency before the first attack was shorter at 20 h after the METH injection than at 15 min after injection. Locomotor activity was not different at 20 h after METH injection, indicating that increased fighting was not secondary to METH-induced hyperactivity. METH-induced increases in fighting were not related to the duration of persistent sniffing after the initial encounter with an intruder since the duration of this behavior was significantly increased at 15 min after METH but not at 20 h post drug. These results indicate that repeated injections of METH can increase fighting behaviors and also alter social interactions in mice. Thus, intermittent administration of METH might be useful as a pharmacological model to study the biochemical and molecular bases of aggressiveness. JF - Pharmacology Biochemistry and Behavior AU - Sokolov, B P AU - Schindler, C W AU - Cadet, J L AD - Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, jcadet@intra.nida.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 319 EP - 326 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 77 IS - 2 SN - 0091-3057, 0091-3057 KW - mice KW - fighting KW - Animal Behavior Abstracts; Toxicology Abstracts KW - Methamphetamine KW - Behavior KW - Aggressive behavior KW - Aggression KW - Drug abuse KW - Fighting KW - X 24180:Social poisons & drug abuse KW - Y 25817:Mammals (excluding primates) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19266329?accountid=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=Pharmacology+Biochemistry+and+Behavior&rft.atitle=Chronic+methamphetamine+increases+fighting+in+mice&rft.au=Sokolov%2C+B+P%3BSchindler%2C+C+W%3BCadet%2C+J+L&rft.aulast=Sokolov&rft.aufirst=B&rft.date=2004-02-01&rft.volume=77&rft.issue=2&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Pharmacology+Biochemistry+and+Behavior&rft.issn=00913057&rft_id=info:doi/10.1016%2Fj.pbb.2003.11.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Methamphetamine; Drug abuse; Fighting; Aggressive behavior; Behavior; Aggression DO - http://dx.doi.org/10.1016/j.pbb.2003.11.006 ER - TY - JOUR T1 - Structure of the OmpA-like domain of RmpM from Neisseria meningitidis AN - 19264396; 5851411 AB - RmpM is a putative peptidoglycan binding protein from Neisseria meningitidis that has been shown to interact with integral outer membrane proteins such as porins and TonB-dependent transporters. Here we report the 1.9 Aa crystal structure of the C-terminal domain of RmpM. The 150-residue domain adopts a beta alpha beta alpha beta beta fold, as first identified in Bacillus subtilis chorismate mutase. The C-terminal RmpM domain is homologous to the periplasmic, C-terminal domain of Escherichia coli OmpA; these domains are thought to be responsible for non-covalent interactions with peptidoglycan. From the structure of the OmpA-like domain of RmpM, we suggest a putative peptidoglycan binding site and identify residues that may be essential for binding. Both the crystal structure and solution experiments indicate that RmpM may exist as a dimer. This would promote more efficient peptidoglycan binding, by allowing RmpM to interact simultaneously with two glycan chains through its C-terminal, OmpA-like binding domain, while its (structurally uncharacterized) N-terminal domain could stabilize oligomers of porins and TonB-dependent transporters in the outer membrane. JF - Molecular Microbiology AU - Grizot, S AU - Buchanan, S K AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA., skbuchan@helix.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 1027 EP - 1037 PB - Blackwell Science Ltd VL - 51 IS - 4 SN - 0950-382X, 0950-382X KW - RmpM protein KW - Microbiology Abstracts B: Bacteriology KW - OmpA protein KW - C-Terminus KW - Outer membranes KW - Crystal structure KW - peptidoglycans KW - Neisseria meningitidis KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19264396?accountid=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=Structure+of+the+OmpA-like+domain+of+RmpM+from+Neisseria+meningitidis&rft.au=Grizot%2C+S%3BBuchanan%2C+S+K&rft.aulast=Grizot&rft.aufirst=S&rft.date=2004-02-01&rft.volume=51&rft.issue=4&rft.spage=1027&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2003.03903.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria meningitidis; Outer membranes; Crystal structure; C-Terminus; OmpA protein; peptidoglycans DO - http://dx.doi.org/10.1111/j.1365-2958.2003.03903.x ER - TY - JOUR T1 - Growth Characteristics of Bartonella henselae in a Novel Liquid Medium: Primary Isolation, Growth-Phase-Dependent Phage Induction, and Metabolic Studies AN - 19259547; 5831337 AB - Bartonella henselae is a zoonotic pathogen that usually causes a self- limiting infection in immunocompetent individuals but often causes potentially life-threatening infections, such as bacillary angiomatosis, in immunocompromised patients. Both diagnosis of infection and research into the molecular mechanisms of pathogenesis have been hindered by the absence of a suitable liquid growth medium. It has been difficult to isolate B. henselae directly from the blood of infected humans or animals or to grow the bacteria in liquid culture media under laboratory conditions. Therefore, we have developed a liquid growth medium that supports reproducible in vitro growth (3-h doubling time and a growth yield of approximately 5 x 10 CFU/ml) and permits the isolation of B. henselae from the blood of infected cats. During the development of this medium, we observed that B. henselae did not derive carbon and energy from the catabolism of glucose, which is consistent with genome nucleotide sequence data suggesting an incomplete glycolytic pathway. Of interest, B. henselae depleted amino acids from the culture medium and accumulated ammonia in the medium, an indicator of amino acid catabolism. Analysis of the culture medium throughout the growth cycle revealed that oxygen was consumed and carbon dioxide was generated, suggesting that amino acids were catabolized in a tricarboxylic acid (TCA) cycle-dependent mechanism. Additionally, phage particles were detected in the culture supernatants of stationary-phase B. henselae, but not in mid-logarithmic-phase culture supernatants. Enzymatic assays of whole-cell lysates revealed that B. henselae has a complete TCA cycle. Taken together, these data suggest B. henselae may catabolize amino acids but not glucose to derive carbon and energy from its host. Furthermore, the newly developed culture medium should improve isolation of B. henselae and basic research into the pathogenesis of the bacterium. JF - Applied and Environmental Microbiology AU - Chenoweth, M R AU - Somerville, G A AU - Krause, D C AU - O'Reilly, K L AU - Gherardini, F C AD - Rocky Mountain Labs, 903 S. 4th St., Hamilton, MT 59840, Fgherardini@niaid.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 656 EP - 663 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 70 IS - 2 SN - 0099-2240, 0099-2240 KW - ammonia KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - Growth KW - Amino acids KW - Colony-forming cells KW - Bartonella henselae KW - Media (culture) KW - Catabolism KW - A 01116:Bacteria KW - J 02703:Culture KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19259547?accountid=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=Applied+and+Environmental+Microbiology&rft.atitle=Growth+Characteristics+of+Bartonella+henselae+in+a+Novel+Liquid+Medium%3A+Primary+Isolation%2C+Growth-Phase-Dependent+Phage+Induction%2C+and+Metabolic+Studies&rft.au=Chenoweth%2C+M+R%3BSomerville%2C+G+A%3BKrause%2C+D+C%3BO%27Reilly%2C+K+L%3BGherardini%2C+F+C&rft.aulast=Chenoweth&rft.aufirst=M&rft.date=2004-02-01&rft.volume=70&rft.issue=2&rft.spage=656&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&rft_id=info:doi/10.1128%2FAEM.70.2.656-663.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Growth; Amino acids; Colony-forming cells; Media (culture); Catabolism; Bartonella henselae DO - http://dx.doi.org/10.1128/AEM.70.2.656-663.2004 ER - TY - JOUR T1 - In vivo tumor imaging using a near-infrared-labeled endostatin molecule AN - 19254268; 5827260 AB - Endostatin is a 20-kD C-terminal fragment of collagen XVIII and is a potent inhibitor of angiogenesis. Imaging technologies that use near-infrared (NIR) fluorescent probes are well suited to the laboratory setting. The goal of this study was to determine whether endostatin labeled with a NIR probe (Cy5.5) could be detected in an animal after intraperitoneal injection and whether it would selectively localize in a tumor. Endostatin was conjugated to Cy5.5 monofunctional dye and purified from free dye by gel filtration. LLC, a murine tumor, was implanted in C57BL/6 mice. The tumors were allowed to grow to 350 mm, at which point the mice were injected with 100 mu g/100 mu L endostatin-Cy5.5 and imaged at various points under sedation. Imaging was performed using a lightproof box affixed to a fluorescent microscope mounted with a filter in the NIR bandwidth (absorbance maximum 675 nm and emission maximum 694 nm). Images were captured by a CCD and desktop computer and stored as 16-bit Tiff files. The mice were also serially imaged for uptake into the tumor and washout from the tumor. After intraperitoneal injection, endostatin-Cy5.5 was quickly absorbed, producing a NIR fluorescent image of the tumors at 24 h that persisted through 7 days. However, the signal peaked at 42 h after injection. Control animals included mice containing green fluorescent protein (GFP) under the control of an actin promotor, which expresses GFP in every cell; tumor-free mice injected with endostatin-Cy5.5; mice with tumors that were not injected with endostatin-Cy5.5; and mice with tumors injected with dye alone. In the four sets of control animals, no NIR photon emissions were detected at 24 hours or 5 days. Only the GFP mouse was detected using the GFP filter. Unlike previous analogous studies with 4-N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO)-Cy5.5 in which the tumor image faded with time, the endostatin-Cy5.5 NIR signal was emitted from the tumor up to 7 days after injection, the last time point examined. The results of this study demonstrated that endostatin covalently bound to Cy5.5 will migrate from a distant intraperitoneal injection site to a tumor. These data indicate that endostatin-Cy5.5 is appropriate for selectively imaging tumors in experimental animals. Furthermore, data suggest that the anti- angiogenic effect of endostatin occurs through a local mechanism of action, within the tumor or tumor vasculature, rather than through a systemic mechanism. JF - International Journal of Radiation Oncology, Biology, & Physics AU - Citrin, D AU - Scott, T AU - Sproull, M AU - Menard, C AU - Tofilon, P J AU - Camphausen, K AD - Imaging and Molecular Therapeutics Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD, USA, camphauk@mail.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 536 EP - 541 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 58 IS - 2 SN - 0360-3016, 0360-3016 KW - mice KW - endostatin KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - I.R. spectroscopy KW - Probes KW - Image processing KW - Tumors KW - Vascular system KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19254268?accountid=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=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=In+vivo+tumor+imaging+using+a+near-infrared-labeled+endostatin+molecule&rft.au=Citrin%2C+D%3BScott%2C+T%3BSproull%2C+M%3BMenard%2C+C%3BTofilon%2C+P+J%3BCamphausen%2C+K&rft.aulast=Citrin&rft.aufirst=D&rft.date=2004-02-01&rft.volume=58&rft.issue=2&rft.spage=536&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/10.1016%2Fj.ijrobp.2003.09.068 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tumors; Image processing; Vascular system; Probes; I.R. spectroscopy DO - http://dx.doi.org/10.1016/j.ijrobp.2003.09.068 ER - TY - JOUR T1 - Proteomic approaches in cancer risk and response assessment AN - 19248424; 5828906 AB - Proteomics is more than just a list-generating exercise where increases or decreases in protein expression are identified. Proteomic technologies will ultimately characterize information-flow through the protein circuitry that interconnects the extracellular microenvironment to the serum or plasma macroenvironment through intracellular signaling systems and their control of gene transcription. The nature of this information can be a cause or a consequence of disease processes and how patients respond to therapy. Analysis of human cancer as a model for how proteomics can have an impact at the bedside can take advantage of several promising new proteomic technologies. These technologies are being developed for early detection and risk assessment, therapeutic targeting and patient-tailored therapy. JF - Trends in Molecular Medicine AU - Petricoin, E F AU - Liotta, LA AD - FDA-NCI, Clinical Proteomics Program, Building 29A, Room 2D12, 8800 Rockville Pike, Bethesda, MD 20892, USA, petricoin@cber.fda.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 59 EP - 64 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 10 IS - 2 SN - 1471-4914, 1471-4914 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Risk assessment KW - Gene therapy KW - Reviews KW - Transcription KW - Microenvironments KW - Cancer 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/19248424?accountid=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=Trends+in+Molecular+Medicine&rft.atitle=Proteomic+approaches+in+cancer+risk+and+response+assessment&rft.au=Petricoin%2C+E+F%3BLiotta%2C+LA&rft.aulast=Petricoin&rft.aufirst=E&rft.date=2004-02-01&rft.volume=10&rft.issue=2&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Trends+in+Molecular+Medicine&rft.issn=14714914&rft_id=info:doi/10.1016%2Fj.molmed.2003.12.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Gene therapy; Microenvironments; Transcription; Risk assessment; Reviews DO - http://dx.doi.org/10.1016/j.molmed.2003.12.006 ER - TY - JOUR T1 - Joint moment control of mechanical energy flow during normal gait AN - 19237189; 5817073 AB - The study purpose was to estimate the ability of joint moments to transfer mechanical energy through the leg and trunk during gait. A segmental power analysis of five healthy adult subjects revealed that internal joint extensor moments removed energy from the leg and added energy to the trunk, while flexor moments and gravity produced the opposite effects. The only exception to this pattern was during the push off phase of gait when the ankle plantar flexor moment added energy to both the leg and the trunk. Pairs of joint moments with opposite energetic effects (knee extensor vs gravity, hip flexor vs ankle plantar flexor) worked together to balance energy flows through the segments. This intralimb coordination suggests that moments with contradictory effects are generated simultaneously to control mechanical energy flow within the body during walking. JF - Gait and Posture AU - Siegel, K L AU - Kepple, T M AU - Stanhope, S J AD - National Institutes of Health, Physical Disabilities Branch, Bldg 10, Rm 6s235, 10 Center Drive, MSC 1604, Bethesda, MD 20892-1604, USA, karen_siegel@nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 69 EP - 75 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 19 IS - 1 SN - 0966-6362, 0966-6362 KW - Physical Education Index KW - Energy cost KW - Coordination KW - Gait KW - Mechanical analysis KW - Movement KW - Joints KW - PE 100:Kinesiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19237189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gait+and+Posture&rft.atitle=Joint+moment+control+of+mechanical+energy+flow+during+normal+gait&rft.au=Siegel%2C+K+L%3BKepple%2C+T+M%3BStanhope%2C+S+J&rft.aulast=Siegel&rft.aufirst=K&rft.date=2004-02-01&rft.volume=19&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Gait+and+Posture&rft.issn=09666362&rft_id=info:doi/10.1016%2FS0966-6362%2803%2900010-9 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Energy cost; Mechanical analysis; Coordination; Gait; Joints; Movement DO - http://dx.doi.org/10.1016/S0966-6362(03)00010-9 ER - TY - JOUR T1 - The NeuC Protein of Escherichia coli K1 Is a UDP N-Acetylglucosamine 2-Epimerase AN - 19233533; 5810467 AB - The K1 capsule is an essential virulence determinant of Escherichia coli strains that cause meningitis in neonates. Biosynthesis and transport of the capsule, an alpha -2,8-linked polymer of sialic acid, are encoded by the 17-kb kps gene cluster. We deleted neuC, a K1 gene implicated in sialic acid synthesis, from the chromosome of EV36, a K-12-K1 hybrid, by allelic exchange. Exogenously added sialic acid restored capsule expression to the deletion strain ([Delta] neuC), confirming that NeuC is necessary for sialic acid synthesis. The deduced amino acid sequence of NeuC showed similarities to those of UDP- N-acetylglucosamine (GlcNAc) 2-epimerases from both prokaryotes and eukaryotes. The NeuC homologue from serotype III Streptococcus agalactiae complements [Delta] neuC. We cloned the neuC gene into an intein expression vector to facilitate purification. We demonstrated by paper chromatography that the purified neuC gene product catalyzed the formation of (2- super(14)C)acetamidoglucal and (N- super(14)C)acetylmannosamine (ManNAc) from UDP-( super(14)C)GlcNAc. The formation of reaction intermediate 2-acetamidoglucal with the concomitant release of UDP was confirmed by proton and phosphorus nuclear magnetic resonance spectroscopy. NeuC could not use GlcNAc as a substrate. These data suggest that neuC encodes an epimerase that catalyzes the formation of ManNAc from UDP-GlcNAc via a 2-acetamidoglucal intermediate. The unexpected release of the glucal intermediate and the extremely low rate of ManNAc formation likely were a result of the in vitro assay conditions, in which a key regulatory molecule or protein was absent. JF - Journal of Bacteriology AU - Vann, W F AU - Daines, DA AU - Murkin, A S AU - Tanner, ME AU - Chaffin, DO AU - Rubens, CE AU - Vionnet, J AU - Silver, R P AD - Laboratory of Bacterial Toxins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, wvann@helix.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 706 EP - 712 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 3 SN - 0021-9193, 0021-9193 KW - K1 capsule KW - NeuC gene KW - NeuC protein KW - amino acid sequence prediction KW - cDNA KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Virulence KW - Capsules KW - Nucleotide sequence KW - Escherichia coli KW - UDP-N-acetylglucosamine 2-epimerase KW - Sialic acids KW - Meningitis KW - J 02728:Enzymes KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19233533?accountid=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=The+NeuC+Protein+of+Escherichia+coli+K1+Is+a+UDP+N-Acetylglucosamine+2-Epimerase&rft.au=Vann%2C+W+F%3BDaines%2C+DA%3BMurkin%2C+A+S%3BTanner%2C+ME%3BChaffin%2C+DO%3BRubens%2C+CE%3BVionnet%2C+J%3BSilver%2C+R+P&rft.aulast=Vann&rft.aufirst=W&rft.date=2004-02-01&rft.volume=186&rft.issue=3&rft.spage=706&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.186.3.706-712.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Virulence; Capsules; Nucleotide sequence; UDP-N-acetylglucosamine 2-epimerase; Sialic acids; Meningitis; Escherichia coli DO - http://dx.doi.org/10.1128/JB.186.3.706-712.2004 ER - TY - JOUR T1 - Alveolar macrophage cytotoxicity for normal lung fibroblasts is mediated by nitric oxide release AN - 19221431; 5777886 AB - Nitric oxide (NO) released by activated alveolar macrophages (AM) can mediate effects on target cells and can also react with superoxide anion (O sub(2)-) to form peroxynitrite (PN), a highly cytotoxic product. The role of NO and PN in AM cytotoxicity for normal lung cells was investigated using co- cultures of rat lung fibroblasts (FB) and rat AM treated with lipopolysaccharide+interferon- gamma (LI). AM and FB, alone and in co-culture, were treated with LI for 5 days and cell viability measured. The culture media was analyzed for NO, TNF- alpha , O sub(2)-, and IL-1 beta . A decreased FB viability was correlated with increased NO release by LI-activated AM. Pretreatment of co-cultures with the inducible NOS inhibitor L-NAME caused dose- related decreases in NO release by AM and increases in FB viability. Although TNF- alpha release was increased in co-cultures treated with LI, the viability of FB was not affected when cultures were treated with similar concentrations of TNF- alpha in the absence of AM. O sub(2)- could not be detected in the media and addition of superoxide dismutase (SOD) did not protect FB. These data suggest that neither O sub(2)- nor PN contributed to the loss of cell viability. Activated AM may kill normal rat lung FB through a NO-mediated pathway that does not involve PN. JF - Toxicology In Vitro AU - Morgan, D L AU - Shines, C J AD - Respiratory Toxicology, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC, USA, morgand@niehs.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 139 EP - 146 PB - Elsevier Science Ltd., Pergamon, P.O. Box 800 Kidlington Oxford OX5 1DX UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 18 IS - 1 SN - 0887-2333, 0887-2333 KW - cytotoxicity KW - rats KW - Toxicology Abstracts KW - Alveolar macrophage KW - Lung fibroblast KW - Lipopolysaccharide KW - Cytotoxicity KW - Nitric oxide KW - Macrophages KW - Lung KW - Fibroblasts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19221431?accountid=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+In+Vitro&rft.atitle=Alveolar+macrophage+cytotoxicity+for+normal+lung+fibroblasts+is+mediated+by+nitric+oxide+release&rft.au=Morgan%2C+D+L%3BShines%2C+C+J&rft.aulast=Morgan&rft.aufirst=D&rft.date=2004-02-01&rft.volume=18&rft.issue=1&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Toxicology+In+Vitro&rft.issn=08872333&rft_id=info:doi/10.1016%2Fj.tiv.2003.08.007 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Macrophages; Lung; Nitric oxide; Fibroblasts DO - http://dx.doi.org/10.1016/j.tiv.2003.08.007 ER - TY - JOUR T1 - Tracking the General': tagging skin-derived dendritic cells AN - 17960096; 5897448 AB - Dendritic cells (DCs) are the sentinels of the immune system; their migration, maturation and mobilization are fundamental to immunity and tolerance. The recent tracking of DCs from the skin to lymph node (LN) and their enumeration using a Cre/loxP system demonstrate the recruitment of a higher than expected number of DCs to the draining LN after cutaneous administration of DNA-coated gold particles. The longevity of the migrated DCs was also longer than previously reported. JF - Trends in Biotechnology AU - Raju, R AD - Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10 Room 4N252, 10 Center Drive, Bethesda, MD 20892, USA Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 58 EP - 59 VL - 22 IS - 2 SN - 0167-7799, 0167-7799 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Dendritic cells KW - Skin KW - Immune system KW - Reviews KW - Immunity KW - Immunological tolerance KW - Lymph nodes 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/17960096?accountid=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=Trends+in+Biotechnology&rft.atitle=Tracking+the+General%27%3A+tagging+skin-derived+dendritic+cells&rft.au=Raju%2C+R&rft.aulast=Raju&rft.aufirst=R&rft.date=2004-02-01&rft.volume=22&rft.issue=2&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Trends+in+Biotechnology&rft.issn=01677799&rft_id=info:doi/10.1016%2Fj.tibtech.2003.11.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Skin; Dendritic cells; Lymph nodes; Reviews; Immune system; Immunity; Immunological tolerance DO - http://dx.doi.org/10.1016/j.tibtech.2003.11.005 ER - TY - JOUR T1 - Preparative Separation of Proteins Using Centrifugal Precipitation Chromatography Based on Solubility in Ammonium Sulfate Solution AN - 17910527; 5869947 AB - A preparative modification of the centrifugal precipitation chromatography (CPC) is described. The sample-loading capacity is improved in the present system by the use of convoluted tubing containing dialysis tubing instead of a dialysis membrane placed between a pair of disks equipped with mirror-imaged spiral grooves as in the original design. The system uses, basically, the same principle of as the original CPC, in that a concentration gradient of precipitant is generated under a centrifugal force field. The protein sample injected into the CPC column is exposed to an increasing concentration of the precipitant where it precipitates at various portions of the column according to its solubility. The gradient is then gradually lowered so that the sample undergoes dissolution and precipitation many times within the column; the proteins finally elute from the column according to their solubilities. A basic study was performed using this machine to separate human albumin and 3-globulin using ammonium sulfate (AS) as precipitant. Preliminary results indicate that this method can separate 500 mg of protein. JF - Preparative Biochemistry and Biotechnology AU - Yu, H AU - Ito, Y AD - Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 50, Rm 3334, South Drive MSC 8014, Bethesda, MD 20892-8014, USA, itoy@nhlbi.nith.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 1 EP - 12 VL - 34 IS - 1 SN - 1082-6068, 1082-6068 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Centrifugation KW - Chromatography KW - Column chromatography KW - Precipitation KW - W3 33215:Chromatography KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17910527?accountid=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=Preparative+Biochemistry+and+Biotechnology&rft.atitle=Preparative+Separation+of+Proteins+Using+Centrifugal+Precipitation+Chromatography+Based+on+Solubility+in+Ammonium+Sulfate+Solution&rft.au=Yu%2C+H%3BIto%2C+Y&rft.aulast=Yu&rft.aufirst=H&rft.date=2004-02-01&rft.volume=34&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Preparative+Biochemistry+and+Biotechnology&rft.issn=10826068&rft_id=info:doi/10.1081%2FPB-120027109 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Centrifugation; Chromatography; Precipitation; Column chromatography DO - http://dx.doi.org/10.1081/PB-120027109 ER - TY - JOUR T1 - Patients with Classic Congenital Adrenal Hyperplasia Have Decreased Epinephrine Reserve and Defective Glucose Elevation in Response to High-Intensity Exercise AN - 17900476; 5863427 AB - Classic congenital hyperplasia (CAH) is characterized by impaired adrenocortical function with a decrease in cortisol and aldosterone secretion and an increase in androgen secretion. Adrenomedullary function is also compromised due to developmental defects in the formation of the adrenal medulla, leading to decreased production of epinephrine. To examine the response to a natural stressful stimulus in patients with classic CAH, we studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with CAH and nine healthy controls matched for gender, age, and percent body fat. The same relative workload was applied, based on individual maximal aerobic capacity, and all patients received their usual glucocorticoid and mineralocorticoid replacement. When compared with their normal counterparts, patients with CAH had significantly lower epinephrine levels both at baseline and at peak exercise (P < 0.01), whereas norepinephrine levels did not differ. Blood glucose concentrations were similar at baseline, but the normal exercise-induced rise observed in the healthy controls was significantly blunted in the CAH patients (P < 0.01). Peak heart rate was also lower in CAH patients than healthy controls (P < 0.05). As expected, the normal exercise-induced increase in cortisol was not observed in patients with CAH. No significant differences were found in serum levels of insulin, glucagon, GH, lactate and free fatty acids, blood pressure, or ability to sustain exercise between the two groups. Patients with CAH replaced with glucocorticoids have decreased adrenomedullary reserve and impaired exercise-induced changes in glucose but normal short-term high-intensity exercise performance. Whether the combination of epinephrine and cortisol deficiency poses a risk for hypoglycemia and/or decreased endurance during long-term physical stress has to be determined. JF - Journal of Clinical Endocrinology and Metabolism AU - Weise, M AU - Mehlinger, S L AU - Drinkard, B AU - Rawson, E AU - Charmandari, E AU - Hiroi, M AU - Eisenhofer, G AU - Yanovski, JA AU - Chrousos, G P AU - Merke, D P AD - National Institutes of Health Clinical Center, Building 10, Room 13S260, 10 Center Drive MSC 1932, Bethesda, Maryland 20892-1932, USA, dmerke@nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 591 EP - 597 VL - 89 IS - 2 SN - 0021-972X, 0021-972X KW - Physical Education Index KW - Exercise physiology KW - Congenital diseases KW - Exercise (intensity) KW - Blood glucose KW - Stress KW - Exercise (effects) KW - Endocrine system KW - Hormones KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17900476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.atitle=Patients+with+Classic+Congenital+Adrenal+Hyperplasia+Have+Decreased+Epinephrine+Reserve+and+Defective+Glucose+Elevation+in+Response+to+High-Intensity+Exercise&rft.au=Weise%2C+M%3BMehlinger%2C+S+L%3BDrinkard%2C+B%3BRawson%2C+E%3BCharmandari%2C+E%3BHiroi%2C+M%3BEisenhofer%2C+G%3BYanovski%2C+JA%3BChrousos%2C+G+P%3BMerke%2C+D+P&rft.aulast=Weise&rft.aufirst=M&rft.date=2004-02-01&rft.volume=89&rft.issue=2&rft.spage=591&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Exercise (intensity); Congenital diseases; Stress; Blood glucose; Endocrine system; Hormones; Exercise physiology; Exercise (effects) ER - TY - JOUR T1 - The roles of anthrax toxin in pathogenesis AN - 17891264; 5856799 AB - Anthrax lethal toxin is a multi-functional virulence factor that has evolved to target multiple host functions to allow for optimal establishment of Bacillus anthracis infection. The toxin appears to play a role in all stages of infection, from germination to the induction of vascular collapse leading to host death. Early in infection, at sublethal doses, it acts to suppress immune cell and cytokine responses, thereby promoting bacterial outgrowth. Later in the disease, lethal levels of toxin induce the cytokine-independent shock-like death associated with anthrax. The understanding of the molecular events induced by anthrax toxin in different target cells at each stage of infection will aid in deciphering the pathogenesis of this bacterium and developing therapies. JF - Current Opinion in Microbiology AU - Moayeri, M AU - Leppla, SH AD - Building 30, Room 307, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-4350, USA, sleppla@niaid.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 19 EP - 24 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 7 IS - 1 SN - 1369-5274, 1369-5274 KW - pathogenesis KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - Reviews KW - Anthrax KW - Bacillus anthracis KW - Toxins KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17891264?accountid=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=Current+Opinion+in+Microbiology&rft.atitle=The+roles+of+anthrax+toxin+in+pathogenesis&rft.au=Moayeri%2C+M%3BLeppla%2C+SH&rft.aulast=Moayeri&rft.aufirst=M&rft.date=2004-02-01&rft.volume=7&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/10.1016%2Fj.mib.2003.12.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; Reviews; Toxins; Anthrax DO - http://dx.doi.org/10.1016/j.mib.2003.12.001 ER - TY - JOUR T1 - Chromatin remodelling and the interaction between enhancers and promoters in the [beta]-globin locus AN - 1434026080; 18513461 AB - The beta -globin genes are among the most studied families of tissue-specific and developmentally regulated genes. Even before genome-wide sequencing was a reality, the sequences of extensive regions of the human, rabbit and mouse beta -globin loci were available through the individual efforts of several research groups. Many of the genomic approaches now being pursued in order to understand the control of gene expression were applied early to this gene family with success. Higher levels of regulation attributable to networks of transcription factor interaction, chromatin remodelling and enhancer-promoter communication remain as challenges in the post-genomic era. JF - Briefings in Functional Genomics and Proteomics AU - Dean, Ann AD - Senior investigator in the Laboratory of Cellular and Developmental Biology at the National Institute of Diabetes, Digestive and Kidney Diseases., anndean@helix.nih.gov Y1 - 2004/02// PY - 2004 DA - Feb 2004 SP - 344 EP - 354 PB - Oxford University Press VL - 2 IS - 4 SN - 1473-9550, 1473-9550 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Promoters KW - Enhancers KW - Chromatin remodeling KW - Transcription factors KW - Communication KW - proteomics KW - genomics KW - G 07730:Development & Cell Cycle KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1434026080?accountid=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=Briefings+in+Functional+Genomics+and+Proteomics&rft.atitle=Chromatin+remodelling+and+the+interaction+between+enhancers+and+promoters+in+the+%5Bbeta%5D-globin+locus&rft.au=Dean%2C+Ann&rft.aulast=Dean&rft.aufirst=Ann&rft.date=2004-02-01&rft.volume=2&rft.issue=4&rft.spage=344&rft.isbn=&rft.btitle=&rft.title=Briefings+in+Functional+Genomics+and+Proteomics&rft.issn=14739550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-09-01 N1 - Last updated - 2013-09-20 N1 - SubjectsTermNotLitGenreText - Enhancers; Promoters; Chromatin remodeling; Transcription factors; Communication; genomics; proteomics ER - TY - JOUR T1 - Mouse liver CYP2C39 is a novel retinoic acid 4-hydroxylase. Its down-regulation offers a molecular basis for liver retinoid accumulation and fibrosis in aryl hydrocarbon receptor-null mice. AN - 80120766; 14623888 AB - Livers of aryl hydrocarbon receptor (AHR)-null mice have high levels of retinoic acid (RA), retinol, and retinyl palmitate. Hepatic accumulation of RA in these mice may be responsible in part for the hepatic phenotype characterized by small liver size and fibrosis. The increased levels of hepatic RA may be due to decreased metabolism of RA to 4-hydroxyretinoic acid. To identify the P450 isoform(s) involved in RA metabolism, liver microsomes from AHR-null and wild-type mice were subjected to Western blotting and probed with antibodies to rat P450s that cross-react with murine forms. Signal intensity in Western blots probed with anti-rat CYP2C6 antibodies correlated with levels of RA 4-hydroxylation. Furthermore, this anti-rat CYP2C6 antibody inhibited RA 4-hydroxylase activity of wild-type mouse liver microsomes to the levels of AHR-null mouse liver. When used to screen a mouse liver cDNA expression library, this antibody exclusively recognized the murine P450 CYP2C39. Catalytic assays of five recombinant mouse CYP2Cs expressed in Escherichia coli revealed that only CYP2C39 was competent for RA 4-hydroxylation (K(m) = 812.3 nm and V(max) 47.85 (fmol/min/pmol P450)). Real time reverse transcriptase-PCR used to assess the Cyp2C39 mRNA expression showed decreased levels (30%) of this transcript in AHR-null compared with wild-type liver, consistent with decreased protein levels observed by Western blot analysis using an antibody to a CYP2C39-specific peptide. These data show that CYP2C39 catalyzes RA catabolism and thus possibly controls RA levels in mouse liver. Down-regulation of Cyp2C39 is hypothesized to be responsible for the liver phenotype in the AHR-null mouse. JF - The Journal of biological chemistry AU - Andreola, Fausto AU - Hayhurst, Graham P AU - Luo, Gang AU - Ferguson, Stephen S AU - Gonzalez, Frank J AU - Goldstein, Joyce A AU - De Luca, Luigi M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/01/30/ PY - 2004 DA - 2004 Jan 30 SP - 3434 EP - 3438 VL - 279 IS - 5 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - DNA, Complementary KW - Peptides KW - Polychlorinated Dibenzodioxins KW - Protein Isoforms KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - Recombinant Proteins KW - cytochrome P-450 CYP2C subfamily KW - Tretinoin KW - 5688UTC01R KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Cyp2c39 protein, mouse KW - EC 1.14.14.1 KW - Cytochrome P450 Family 2 KW - Retinoic Acid 4-Hydroxylase KW - Index Medicus KW - Animals KW - Microsomes, Liver -- metabolism KW - Fibrosis -- metabolism KW - Mice, Transgenic KW - Chromatography, High Pressure Liquid KW - Phenotype KW - Rats KW - Mixed Function Oxygenases -- chemistry KW - Peptides -- chemistry KW - Receptors, Aryl Hydrocarbon -- genetics KW - Recombinant Proteins -- chemistry KW - Male KW - Tretinoin -- chemistry KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Polymerase Chain Reaction KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Kinetics KW - DNA, Complementary -- metabolism KW - Models, Chemical KW - DNA Primers -- chemistry KW - Catalysis KW - Liver -- enzymology KW - Down-Regulation KW - Cytochrome P-450 Enzyme System -- physiology KW - Cytochrome P-450 Enzyme System -- chemistry KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80120766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mouse+liver+CYP2C39+is+a+novel+retinoic+acid+4-hydroxylase.+Its+down-regulation+offers+a+molecular+basis+for+liver+retinoid+accumulation+and+fibrosis+in+aryl+hydrocarbon+receptor-null+mice.&rft.au=Andreola%2C+Fausto%3BHayhurst%2C+Graham+P%3BLuo%2C+Gang%3BFerguson%2C+Stephen+S%3BGonzalez%2C+Frank+J%3BGoldstein%2C+Joyce+A%3BDe+Luca%2C+Luigi+M&rft.aulast=Andreola&rft.aufirst=Fausto&rft.date=2004-01-30&rft.volume=279&rft.issue=5&rft.spage=3434&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 - 2004-03-11 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of TRP14, a thioredoxin-related protein of 14 kDa. New insights into the specificity of thioredoxin function. AN - 80120707; 14607844 AB - We have identified and characterized a 14-kDa human thioredoxin (Trx)-related protein designated TRP14. This cytosolic protein was expressed in all tissues and cell types examined, generally in smaller amounts than Trx1. Although TRP14 contains five cysteines, only the two Cys residues in its WCPDC motif were exposed and redox sensitive. Unlike Trx1, which was an equally good substrate for both Trx reductase 1 (TrxR1) and TrxR2, oxidized TRP14 was reduced by TrxR1 but not by TrxR2. Biochemical characterization of TRP14 suggested that, like Trx1, TRP14 is a disulfide reductase; its active site cysteine is sufficiently nucleophilic with the pK(a) value of 6.1; and its redox potential (-257 mV) is similar to those of other cellular thiol reductants. However, although TRP14 reduced small disulfide-containing peptides, it did not reduce the disulfides of known Trx1 substrates, ribonucleotide reductase, peroxiredoxin, and methionine sulfoxide reductase. These results suggest that TRP14 and Trx1 might act on distinct substrate proteins. JF - The Journal of biological chemistry AU - Jeong, Woojin AU - Yoon, Hae Won AU - Lee, Seung-Rock AU - Rhee, Sue Goo AD - Laboratory of Cell Signaling, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/01/30/ PY - 2004 DA - 2004 Jan 30 SP - 3142 EP - 3150 VL - 279 IS - 5 SN - 0021-9258, 0021-9258 KW - Disulfides KW - 0 KW - Insulin KW - Membrane Proteins KW - Peptides KW - Recombinant Proteins KW - TXNDC17 protein, human KW - Vasopressins KW - 11000-17-2 KW - Oxytocin KW - 50-56-6 KW - Thioredoxins KW - 52500-60-4 KW - Hydrogen Peroxide KW - BBX060AN9V KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - Cysteine KW - K848JZ4886 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Spectrometry, Fluorescence KW - Oxygen -- metabolism KW - Humans KW - Hydrogen-Ion Concentration KW - Hydrogen Peroxide -- pharmacology KW - Liver -- metabolism KW - Tissue Distribution KW - Mutagenesis KW - Rats KW - Oxidation-Reduction KW - Cysteine -- chemistry KW - Amino Acid Motifs KW - Molecular Sequence Data KW - Peptides -- chemistry KW - Oxytocin -- chemistry KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Time Factors KW - Signal Transduction KW - Cytosol -- metabolism KW - Escherichia coli -- metabolism KW - HeLa Cells KW - Membrane Proteins -- chemistry KW - NADH, NADPH Oxidoreductases -- chemistry KW - Insulin -- chemistry KW - Cell Line, Tumor KW - Amino Acid Sequence KW - Binding Sites KW - Vasopressins -- chemistry KW - Base Sequence KW - Kinetics KW - Substrate Specificity KW - NADH, NADPH Oxidoreductases -- physiology KW - Cell Line KW - Thioredoxins -- metabolism KW - Thioredoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80120707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+characterization+of+TRP14%2C+a+thioredoxin-related+protein+of+14+kDa.+New+insights+into+the+specificity+of+thioredoxin+function.&rft.au=Jeong%2C+Woojin%3BYoon%2C+Hae+Won%3BLee%2C+Seung-Rock%3BRhee%2C+Sue+Goo&rft.aulast=Jeong&rft.aufirst=Woojin&rft.date=2004-01-30&rft.volume=279&rft.issue=5&rft.spage=3142&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 - 2004-03-11 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirement of protein kinase C micro activation and calpain-mediated proteolysis for arachidonic acid-stimulated adhesion of MDA-MB-435 human mammary carcinoma cells to collagen type IV. AN - 80118724; 14607845 AB - Arachidonic acid (AA) stimulation of adhesion of human metastatic breast carcinoma cells to collagen type IV depends on the protein kinase C (PKC) pathway(s) and is associated with the translocation of PKC mu from the cytoplasm to the membrane. In the present study, we have further explored the role of PKC mu in AA-stimulated adhesion. PKC mu activation site serines 738/742 and autophosphorylation site serine 910 are rapidly phosphorylated, and in vitro PKC mu kinase activity is enhanced in response to AA treatment. Inhibition of PKC mu activation blocks AA-stimulated adhesion. A phosphorylated, truncated species of PKC mu was detected in AA-treated cells. This 77-kDa protein contains the kinase domain but lacks a significant portion of the regulatory domains. Inhibition of calpain protease activity blocks generation of the truncated protein, promotes accumulation of the activated, full-length protein in the membrane, and blocks the AA-mediated increase in adhesion. p38 MAPK activity is also required for AA-stimulated adhesion. Activation of PKC mu and p38 are independent events. However, inhibition of p38 activity reduces calpain-mediated proteolysis of PKC mu and in vivo calpain activity, suggesting a role for p38 in regulation of calpain activity and a point for cross-talk between the PKC and MAPK pathways. These results support the hypothesis that AA stimulates activation of PKC mu, which is cleaved by calpain at the cell membrane. The resulting truncated kinase, as well as the full-length kinase, may be required for increased cell adhesion to collagen type IV. Additionally, these studies present the first evidence for calpain cleavage of a non-structural protein leading to the promotion of tumor cell adhesion. JF - The Journal of biological chemistry AU - Kennett, Sarah B AU - Roberts, John D AU - Olden, Kenneth AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/01/30/ PY - 2004 DA - 2004 Jan 30 SP - 3300 EP - 3307 VL - 279 IS - 5 SN - 0021-9258, 0021-9258 KW - Collagen Type IV KW - 0 KW - Enzyme Inhibitors KW - Arachidonic Acid KW - 27YG812J1I KW - protein kinase D KW - EC 2.7.10.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Calpain KW - EC 3.4.22.- KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Cell Line, Tumor KW - Protein Binding KW - Models, Biological KW - Calpain -- metabolism KW - Blotting, Western KW - Phosphorylation KW - Enzyme Inhibitors -- pharmacology KW - Subcellular Fractions -- metabolism KW - Cell Membrane -- metabolism KW - Calpain -- chemistry KW - Time Factors KW - Signal Transduction KW - Cell Adhesion KW - Protein Kinase C -- metabolism KW - Collagen Type IV -- chemistry KW - Arachidonic Acid -- pharmacology KW - Breast Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80118724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+protein+kinase+C+micro+activation+and+calpain-mediated+proteolysis+for+arachidonic+acid-stimulated+adhesion+of+MDA-MB-435+human+mammary+carcinoma+cells+to+collagen+type+IV.&rft.au=Kennett%2C+Sarah+B%3BRoberts%2C+John+D%3BOlden%2C+Kenneth&rft.aulast=Kennett&rft.aufirst=Sarah&rft.date=2004-01-30&rft.volume=279&rft.issue=5&rft.spage=3300&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 - 2004-03-11 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel E1A-like inhibitor of differentiation (EID) family member, EID-2, suppresses transforming growth factor (TGF)-beta signaling by blocking TGF-beta-induced formation of Smad3-Smad4 complexes. AN - 80101225; 14612439 AB - Smad proteins play key roles in intracellular signaling of the transforming growth factor-beta (TGF-beta) superfamily. E1A, an adenoviral oncoprotein, is known to inhibit TGF-beta-induced transactivation through binding to Smad proteins. Recently, an EID-1 (E1A-like inhibitor of differentiation-1) and EID-2 (EID-1-like inhibitor of differentiation-2) were identified. In this study, we examined the effect of EID-2 on Smad-mediated TGF-beta signaling. Here, we show that EID-2 inhibits TGF-beta/Smad transcriptional responses. EID-2 interacts constitutively with Smad proteins, and most strongly with Smad3. Stable expression of EID-2 in the TGF-beta1-responsive cell line inhibits endogenous Smad3-Smad4 complex formation and TGF-beta1-induced expression of p21 and p15. These results suggest that EID-2 may function as an endogenous suppressor of TGF-beta signaling. JF - The Journal of biological chemistry AU - Lee, Ho-Jae AU - Lee, Jin Kyung AU - Miyake, Satoshi AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 2004/01/23/ PY - 2004 DA - 2004 Jan 23 SP - 2666 EP - 2672 VL - 279 IS - 4 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - EID2 protein, human KW - Inhibitor of Differentiation Protein 2 KW - Intracellular Signaling Peptides and Proteins KW - SMAD3 protein, human KW - SMAD4 protein, human KW - Smad3 Protein KW - Smad4 Protein KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - COS Cells KW - Humans KW - Cercopithecus aethiops KW - Protein Binding KW - Transcriptional Activation KW - Trans-Activators -- metabolism KW - Carrier Proteins -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Signal Transduction KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80101225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+novel+E1A-like+inhibitor+of+differentiation+%28EID%29+family+member%2C+EID-2%2C+suppresses+transforming+growth+factor+%28TGF%29-beta+signaling+by+blocking+TGF-beta-induced+formation+of+Smad3-Smad4+complexes.&rft.au=Lee%2C+Ho-Jae%3BLee%2C+Jin+Kyung%3BMiyake%2C+Satoshi%3BKim%2C+Seong-Jin&rft.aulast=Lee&rft.aufirst=Ho-Jae&rft.date=2004-01-23&rft.volume=279&rft.issue=4&rft.spage=2666&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 - 2004-04-23 N1 - Date created - 2004-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Energetics of domain-domain interactions and entropy driven association of beta-crystallins. AN - 80095396; 14717595 AB - Beta-crystallins are major protein constituents of the mammalian lens, where their stability and association into higher order complexes are critical for lens clarity and refraction. They undergo modification as the lens ages, including cleavage of their terminal extensions. The energetics of betaA3- and betaB2-crystallin association was studied using site-directed mutagenesis and analytical ultracentrifugation. Recombinant (r) murine wild type betaA3- and betaB2-crystallins were modified by removal of either the N-terminal extension of betaA3 (rbetaA3Ntr) or betaB2 (rbetaB2Ntr), or both the N- and C-terminal extensions of betaB2 (rbetaB2NCtr). The proteins were expressed in Sf9 insect cells or Escherichia coli and purified by gel-filtration and ion-exchange chromatography. All beta-crystallins studied demonstrated fast reversible monomer-dimer equilibria over the temperature range studied (5-35 degrees C) with a tendency to form tighter dimers at higher temperatures. The N-terminal deletion of rbetaA3 (rbetaA3Ntr) significantly increases the enthalpy (+10.9 kcal/mol) and entropy (+40.7 cal/deg mol) of binding relative to unmodified protein. Removal of both N- and C-terminal extensions of rbetaB2 also increases these parameters but to a lesser degree. Deletion of the betaB2-crystallin N-terminal extension alone (rbetaB2Ntr) gave almost no change relative to rbetaB2. The resultant net negative changes in the binding energy suggest that betaAlpha3- and betaB2-crystallin association is entropically driven. The thermodynamic consequences of the loss of betaAlpha3-crystallin terminal extensions by in vivo proteolytic processing could increase their tendency to associate and so promote the formation of higher order associates in the aging and cataractous lens. JF - Biochemistry AU - Sergeev, Y V AU - Hejtmancik, J F AU - Wingfield, P T AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20982, USA. sergeev@helix.nih.gov Y1 - 2004/01/20/ PY - 2004 DA - 2004 Jan 20 SP - 415 EP - 424 VL - 43 IS - 2 SN - 0006-2960, 0006-2960 KW - Cryba1 protein, mouse KW - 0 KW - Crystallins KW - Recombinant Proteins KW - beta-Crystallin B Chain KW - beta-Crystallins KW - beta-crystallin B2 KW - Index Medicus KW - Animals KW - Dimerization KW - Temperature KW - Crystallins -- chemistry KW - Amino Acid Sequence KW - Mice KW - Crystallins -- genetics KW - Ultracentrifugation KW - Mutagenesis, Site-Directed KW - Protein Structure, Tertiary -- genetics KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Entropy KW - Sequence Deletion KW - beta-Crystallin B Chain -- chemistry KW - Thermodynamics KW - beta-Crystallin B Chain -- genetics KW - beta-Crystallins -- genetics KW - beta-Crystallins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80095396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Energetics+of+domain-domain+interactions+and+entropy+driven+association+of+beta-crystallins.&rft.au=Sergeev%2C+Y+V%3BHejtmancik%2C+J+F%3BWingfield%2C+P+T&rft.aulast=Sergeev&rft.aufirst=Y&rft.date=2004-01-20&rft.volume=43&rft.issue=2&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-25 N1 - Date created - 2004-01-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Biochemistry. 2007 Feb 6;46(5):1456 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. AN - 80085042; 14706761 AB - To evaluate the effect of soy isoflavones and melatonin in relieving menopausal symptoms. Double-blind, multicenter, randomized trial performed according to a 2 x 2 factorial design. Treatment groups: (1) soy isoflavones+melatonin; (2) soy isoflavones alone; (3) melatonin alone; (4) placebo. 80 mg of soy isoflavones, 3 mg of pure melatonin or placebo were supplemented to participants for 3 months. Severity of menopausal symptoms was recorded at baseline and after 3 months using the Greene Climacteric Scale. 388 consecutive women were screened: not eligible 98, refused informed consent 28. Randomized 262 and analyzed 232; twelve women withdrew because of adverse events. Median percent differences between basal and final scores were 39% in the isoflavones + melatonin group, 38% in the isoflavones alone group, 26% in the melatonin alone group and 38% in the placebo group. Placebo response was much higher than planned, making it meaningless to perform any statistical test. With regard to somatic and vasomotor symptoms, outcome was similar among the four groups, whereas improvement of psychological symptoms was higher in the isoflavones+melatonin group than in the other three. Present data do not show any advantage of isoflavones or melatonin over placebo for the relief of menopausal symptoms. However, the effect in psychological symptoms in the isoflavones + melatonin group should be further investigated. JF - Maturitas AU - Secreto, Giorgio AU - Chiechi, Luigi Mario AU - Amadori, Andrea AU - Miceli, Rosalba AU - Venturelli, Elisabetta AU - Valerio, Teresa AU - Marubini, Ettore AD - Endocrinology Unit, Hormone Research Laboratory, National Cancer Institute, Via Venezian 1, 20133 Milan, Italy. secreto@istitutotumori.it Y1 - 2004/01/20/ PY - 2004 DA - 2004 Jan 20 SP - 11 EP - 20 VL - 47 IS - 1 SN - 0378-5122, 0378-5122 KW - Antioxidants KW - 0 KW - Isoflavones KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Hot Flashes -- drug therapy KW - Double-Blind Method KW - Patient Compliance KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Female KW - Climacteric -- psychology KW - Antioxidants -- adverse effects KW - Melatonin -- adverse effects KW - Melatonin -- therapeutic use KW - Climacteric -- drug effects KW - Antioxidants -- therapeutic use KW - Soybeans -- chemistry KW - Isoflavones -- adverse effects KW - Isoflavones -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80085042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Maturitas&rft.atitle=Soy+isoflavones+and+melatonin+for+the+relief+of+climacteric+symptoms%3A+a+multicenter%2C+double-blind%2C+randomized+study.&rft.au=Secreto%2C+Giorgio%3BChiechi%2C+Luigi+Mario%3BAmadori%2C+Andrea%3BMiceli%2C+Rosalba%3BVenturelli%2C+Elisabetta%3BValerio%2C+Teresa%3BMarubini%2C+Ettore&rft.aulast=Secreto&rft.aufirst=Giorgio&rft.date=2004-01-20&rft.volume=47&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Maturitas&rft.issn=03785122&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-20 N1 - Date created - 2004-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prominent roles of the NorR and Fur regulators in the Escherichia coli transcriptional response to reactive nitrogen species AN - 19248829; 5831922 AB - We examined the genomewide transcriptional responses of Escherichia coli treated with nitrosylated glutathione or the nitric oxide (NO)-generator acidified sodium nitrite (NaNO sub(2)) during aerobic growth. These assays showed that NorR, a homolog of NO-responsive transcription factors in Ralstonia eutrophus, and Fur, the global repressor of ferric ion uptake, are major regulators of the response to reactive nitrogen species. In contrast, SoxR and OxyR, regulators of the E. coli defenses against superoxide-generating compounds and hydrogen peroxide, respectively, have minor roles. Moreover, additional regulators of the E. coli response to reactive nitrogen species remain to be identified because several of the induced genes were regulated normally in norR, fur, soxRS, and oxyR mutant strains. We propose that the E. coli transcriptional response to reactive nitrogen species is a composite response mediated by the modification of multiple transcription factors containing iron or redox-active cysteines, some specifically designed to sense NO and its derivatives and others that are collaterally activated by the reactive nitrogen species. JF - Proceedings of the National Academy of Sciences, USA AU - Mukhopadhyay, P AU - Zheng, M AU - Bedzyk, LA AU - LaRossa, R A AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, storz@helix.nih.gov Y1 - 2004/01/20/ PY - 2004 DA - 2004 Jan 20 SP - 745 EP - 750 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 3 SN - 0027-8424, 0027-8424 KW - FurR protein KW - NorR protein KW - reactive nitrogen species KW - sodium nitrite KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Glutathione KW - nitric oxide KW - Escherichia coli KW - glutathione KW - transcription factors KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19248829?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Prominent+roles+of+the+NorR+and+Fur+regulators+in+the+Escherichia+coli+transcriptional+response+to+reactive+nitrogen+species&rft.au=Mukhopadhyay%2C+P%3BZheng%2C+M%3BBedzyk%2C+LA%3BLaRossa%2C+R+A%3BStorz%2C+G&rft.aulast=Mukhopadhyay&rft.aufirst=P&rft.date=2004-01-20&rft.volume=101&rft.issue=3&rft.spage=745&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0307741100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; glutathione; transcription factors; nitric oxide; Glutathione DO - http://dx.doi.org/10.1073/pnas.0307741100 ER - TY - JOUR T1 - Uptake of Botulinum Neurotoxin into Cultured Neurons AN - 17983769; 5915056 AB - Botulinum neurotoxins (BoNTs) act within the synaptic terminal to block neurotransmitter release. The toxin enters the neuron by binding to neuronal membrane receptor(s), being taken up into an endosome-like compartment, and penetrating the endosome membrane via a pH-dependent translocation process. Once within the synaptic cytoplasm, BoNT serotypes A and E cleave separate sites on the C-terminus of the neuronal protein SNAP-25, one of the SNARE proteins required for synaptic vesicle fusion. In this study, we measured the effect of brief toxin exposure on SNAP-25 proteolysis in neuronal cell cultures as an indicator of toxin translocation. The results indicate that (1) uptake of both BoNT-A and -E is enhanced with synaptic activity induced by K super(+) depolarization in the presence of Ca super(2+) and (2) translocation of BoNT-A from the acidic endosomal compartment is slow relative to that of BoNT-E. Polyclonal antisera against each toxin protect cells when applied with the toxin during stimulation but has no effect when added immediately after toxin exposure, indicating that toxin endocytosis occurs with synaptic activity. Both serotypes cleave SNAP-25 at concentrations between 50 pM and 4 nM. IC sub(50) values for SNAP-25 cleavage are approximately 0.5 nM for both serotypes. Inhibition of the pH-dependent translocation process by pretreating cultures with concanamycin A (Con A) prevents cleavage of SNAP-25 with IC sub(50) values of similar to 25 nM. Addition of Con A at times up to 15 min after toxin exposure abrogated BoNT-A action; however, addition of Con A after 40 min was no longer protective. In contrast, Con A inhibited, but did not prevent, translocation of BoNT-E even when added immediately after toxin exposure, indicating that pH-dependent translocation of BoNT-E is rapid relative to that of BoNT-A. This study demonstrates that uptake of both BoNT-A and -E is enhanced with synaptic activity and that translocation of the toxin catalytic moiety into the cytosol occurs at different rates for these two serotypes. JF - Biochemistry (Washington) AU - Keller, JE AU - Cai, F AU - Neale, E A AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 2004/01/20/ PY - 2004 DA - 2004 Jan 20 SP - 526 EP - 532 VL - 43 IS - 2 SN - 0006-2960, 0006-2960 KW - tissue culture KW - uptake KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Proteolysis KW - Calcium KW - Potassium KW - Clostridium botulinum KW - Toxins KW - Endocytosis KW - endosomes KW - Concanavalin A KW - Neurons KW - SNAP-25 protein KW - Cytosol KW - Botulinum toxin KW - Neurotoxins KW - X 24171:Microbial KW - N3 11101:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17983769?accountid=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=Biochemistry+%28Washington%29&rft.atitle=Uptake+of+Botulinum+Neurotoxin+into+Cultured+Neurons&rft.au=Keller%2C+JE%3BCai%2C+F%3BNeale%2C+E+A&rft.aulast=Keller&rft.aufirst=JE&rft.date=2004-01-20&rft.volume=43&rft.issue=2&rft.spage=526&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi0356698 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Clostridium botulinum; Calcium; Potassium; Concanavalin A; Endocytosis; Botulinum toxin; endosomes; SNAP-25 protein; Proteolysis; Neurotoxins; Cytosol; Neurons; Toxins DO - http://dx.doi.org/10.1021/bi0356698 ER - TY - JOUR T1 - Gene therapy insertional mutagenesis insights. AN - 80102113; 14726584 JF - Science (New York, N.Y.) AU - Davé, Utpal P AU - Jenkins, Nancy A AU - Copeland, Neal G AD - Mouse Cancer Genetics Program, National Cancer Institute, Center for Cancer Research, Frederick, MD 21702, USA. Y1 - 2004/01/16/ PY - 2004 DA - 2004 Jan 16 SP - 333 VL - 303 IS - 5656 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - DNA-Binding Proteins KW - LIM Domain Proteins KW - LMO2 protein, human KW - Lmo2 protein, mouse KW - Metalloproteins KW - Proto-Oncogene Proteins KW - Receptors, Interleukin-2 KW - Index Medicus KW - Animals KW - Severe Combined Immunodeficiency -- therapy KW - Humans KW - Genetic Vectors KW - Gene Expression KW - Mice KW - Virus Integration KW - Severe Combined Immunodeficiency -- genetics KW - Leukemia, T-Cell -- genetics KW - Genetic Therapy -- adverse effects KW - Leukemia, T-Cell -- etiology KW - DNA-Binding Proteins -- genetics KW - Retroviridae -- genetics KW - Metalloproteins -- genetics KW - Receptors, Interleukin-2 -- genetics KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80102113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+therapy+insertional+mutagenesis+insights.&rft.au=Dav%C3%A9%2C+Utpal+P%3BJenkins%2C+Nancy+A%3BCopeland%2C+Neal+G&rft.aulast=Dav%C3%A9&rft.aufirst=Utpal&rft.date=2004-01-16&rft.volume=303&rft.issue=5656&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=1095-9203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-09 N1 - Date created - 2004-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A select group of perpetrators of domestic violence: evidence of decreased metabolism in the right hypothalamus and reduced relationships between cortical/subcortical brain structures in position emission tomography. AN - 80174518; 14972365 AB - In an earlier study, we reported that some perpetrators of domestic violence evidenced exaggerated fear-related responses to the panicogenic agent sodium lactate. In the current study, we employed positron emission tomography (PET) to investigate our hypothesis that there are differences in the neural structures and/or pathways that mediate and control the expression of fear-induced aggression in perpetrators of domestic violence. Regional cerebral glucose metabolism was measured in eight male perpetrators of domestic violence who fulfilled DSM-III-R criteria for alcohol dependence (DV-ALC), 11 male participants who fulfilled DSM-III-R criteria for alcohol dependence and had no history of interpersonal aggression (ALC) and 10 healthy male participants who did not fulfill criteria for any DSM-III-R axis I diagnosis and had no history of interpersonal aggression (HCS). DV-ALC had a significantly lower mean glucose uptake in the right hypothalamus compared to ALC and HCS. Correlations were performed between measures of glucose utilization in the brain structures involved in fear-induced aggression. The comparison of DV-ALC to HCS and to ALC differed in six and seven comparisons, respectively, involving various cortical and subcortical structures. HCS and ALC differed between the left thalamus and the left posterior orbitofrontal cortex. These PET findings show that some perpetrators of domestic violence differ from control participants in showing lower metabolism in the right hypothalamus and decreased correlations between cortical and subcortical brain structures. A possible psychological covariate of these changes in regional activity might be fear-induced aggression, but this hypothesis should be examined in larger study groups that undergo provocation during imaging. JF - Psychiatry research AU - George, David T AU - Rawlings, Robert R AU - Williams, Wendol A AU - Phillips, Monte J AU - Fong, Grace AU - Kerich, Michael AU - Momenan, Reza AU - Umhau, John C AU - Hommer, Daniel AD - Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, 10 Center Drive, MSC-1610, Building 10, Room 6S-240, Bethesda, MD 20892-1610, USA. tedg@niaaa.nih.gov Y1 - 2004/01/15/ PY - 2004 DA - 2004 Jan 15 SP - 11 EP - 25 VL - 130 IS - 1 SN - 0165-1781, 0165-1781 KW - Radiopharmaceuticals KW - 0 KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - Index Medicus KW - Cerebral Cortex -- metabolism KW - Alcoholism -- diagnosis KW - Fear KW - Humans KW - Depression -- diagnosis KW - Amygdala -- metabolism KW - Aggression -- psychology KW - Adult KW - Surveys and Questionnaires KW - Diagnostic and Statistical Manual of Mental Disorders KW - Male KW - Basal Ganglia -- metabolism KW - Hypothalamus -- metabolism KW - Tomography, Emission-Computed KW - Domestic Violence -- psychology KW - Functional Laterality -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80174518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=A+select+group+of+perpetrators+of+domestic+violence%3A+evidence+of+decreased+metabolism+in+the+right+hypothalamus+and+reduced+relationships+between+cortical%2Fsubcortical+brain+structures+in+position+emission+tomography.&rft.au=George%2C+David+T%3BRawlings%2C+Robert+R%3BWilliams%2C+Wendol+A%3BPhillips%2C+Monte+J%3BFong%2C+Grace%3BKerich%2C+Michael%3BMomenan%2C+Reza%3BUmhau%2C+John+C%3BHommer%2C+Daniel&rft.aulast=George&rft.aufirst=David&rft.date=2004-01-15&rft.volume=130&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-04 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Moderate hypermutability of a transgenic lacZ reporter gene in Myc-dependent inflammation-induced plasma cell tumors in mice. AN - 80124440; 14744766 AB - Mutator phenotypes, a common and largely unexplained attribute of human cancer, might be better understood in mouse tumors containing reporter genes for accurate mutation enumeration and analysis. Previous work on peritoneal plasmacytomas (PCTs) in mice suggested that PCTs have a mutator phenotype caused by Myc-deregulating chromosomal translocations and/or phagocyte-induced mutagenesis due to chronic inflammation. To investigate this hypothesis, we generated PCTs that harbored the transgenic shuttle vector, pUR288, with a lacZ reporter gene for the assessment of mutations in vivo. PCTs exhibited a 5.5 times higher mutant frequency in lacZ (40.3 +/- 5.1 x 10(-5)) than in normal B cells (7.36 +/- 0.77 x 10(-5)), demonstrating that the tumors exhibit the phenotype of increased mutability. Studies on lacZ mutant frequency in serially transplanted PCTs and phagocyte-induced lacZ mutations in B cells in vitro indicated that mutant levels in tumors are not determined by exogenous damage inflicted by inflammatory cells. In vitro studies with a newly developed transgenic model of inducible Myc expression (Tet-off/MYC) showed that deregulated Myc sensitizes B cells to chemically induced mutations, but does not cause, on its own, mutations in lacZ. These findings suggested that the hypermutability of PCT is governed mainly by intrinsic features of tumor cells, not by deregulated Myc or chronic inflammation. JF - Cancer research AU - Felix, Klaus AU - Polack, Axel AU - Pretsch, Walter AU - Jackson, Sharon H AU - Feigenbaum, Lionel AU - Bornkamm, Georg-Wilhelm AU - Janz, Siegfried AD - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA. Y1 - 2004/01/15/ PY - 2004 DA - 2004 Jan 15 SP - 530 EP - 537 VL - 64 IS - 2 SN - 0008-5472, 0008-5472 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Animals KW - Genetic Predisposition to Disease -- genetics KW - Kinetics KW - Genetic Vectors KW - Genes, Reporter KW - Mice KW - Mice, Transgenic KW - B-Lymphocytes -- physiology KW - Plasmacytoma -- etiology KW - Plasmacytoma -- genetics KW - Plasmacytoma -- pathology KW - beta-Galactosidase -- genetics KW - Mutagenesis -- genetics KW - Genes, myc -- genetics KW - Inflammation -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80124440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Moderate+hypermutability+of+a+transgenic+lacZ+reporter+gene+in+Myc-dependent+inflammation-induced+plasma+cell+tumors+in+mice.&rft.au=Felix%2C+Klaus%3BPolack%2C+Axel%3BPretsch%2C+Walter%3BJackson%2C+Sharon+H%3BFeigenbaum%2C+Lionel%3BBornkamm%2C+Georg-Wilhelm%3BJanz%2C+Siegfried&rft.aulast=Felix&rft.aufirst=Klaus&rft.date=2004-01-15&rft.volume=64&rft.issue=2&rft.spage=530&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 - 2004-04-02 N1 - Date created - 2004-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional activation of p21(waf1/cip1) by alkylphospholipids: role of the mitogen-activated protein kinase pathway in the transactivation of the human p21(waf1/cip1) promoter by Sp1. AN - 80122090; 14744793 AB - Alkylphospholipids (ALKs) are a novel class of antitumor agents with an unknown mechanism of action. The first ALK tested in the clinic, miltefosine, has been approved recently in Europe for the local treatment of patients with cutaneous metastasis. Perifosine, the only available oral ALK, is being studied currently in human cancer clinical trials. We have shown previously that perifosine induces p21(waf1/cip1) in a p53-independent fashion and that induction of p21(waf1/cip1) is required for the perifosine-induced cell cycle arrest because cell lines lacking p21(waf1/cip1) are refractory to perifosine. In this report, we investigated the mechanism by which perifosine induces p21(waf1/cip1) protein expression. We observed that perifosine induces the accumulation of p21(waf1/cip1) mRNA without affecting p21(waf1/cip1) mRNA stability. Using several p21(waf1/cip1) promoter-driven luciferase reporter plasmids, we observed that perifosine activates the 2.4-kb full-length p21(waf1/cip1) promoter as well as a p21 promoter construct lacking p53-binding sites, suggesting that perifosine activates the p21(waf1/cip1) promoter independent of p53. The minimal p21 promoter region required for perifosine-induced p21 promoter activation contains four consensus Sp1-binding sites. Mutations in each particular Sp1 site block perifosine-induced p21(waf1/cip1) expression. Moreover, we showed that perifosine activates the mitogen-activated protein/extracellular signal-regulated kinase pathway, and this activation promotes the phosphorylation of Sp1 in known mitogen-activated protein kinase residues (threonine 453 and 739), thereby leading to increased Sp1 binding and enhanced p21(waf1/cip1) transcription. These results represent a novel mechanism by which alkylphospholipids modulate transcription, and may contribute to the discovery of new signal transduction pathways crucial for normal and neoplastic cell cycle control. JF - Cancer research AU - De Siervi, Adriana AU - Marinissen, Maria AU - Diggs, Jessica AU - Wang, Xiao-Fan AU - Pages, Gilles AU - Senderowicz, Adrian AD - Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA. Y1 - 2004/01/15/ PY - 2004 DA - 2004 Jan 15 SP - 743 EP - 750 VL - 64 IS - 2 SN - 0008-5472, 0008-5472 KW - CDKN1A protein, human KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Phospholipids KW - Sp1 Transcription Factor KW - Phosphorylcholine KW - 107-73-3 KW - perifosine KW - 2GWV496552 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 - Base Sequence KW - Mitogen-Activated Protein Kinases -- metabolism KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Humans KW - Transcriptional Activation -- drug effects KW - Keratinocytes KW - Cell Line KW - Mutagenesis KW - Binding Sites KW - Alkylation KW - MAP Kinase Signaling System -- drug effects KW - MAP Kinase Signaling System -- physiology KW - Promoter Regions, Genetic -- drug effects KW - Phospholipids -- pharmacology KW - Sp1 Transcription Factor -- metabolism KW - Promoter Regions, Genetic -- genetics KW - Phosphorylcholine -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Cyclins -- genetics KW - Phosphorylcholine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80122090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transcriptional+activation+of+p21%28waf1%2Fcip1%29+by+alkylphospholipids%3A+role+of+the+mitogen-activated+protein+kinase+pathway+in+the+transactivation+of+the+human+p21%28waf1%2Fcip1%29+promoter+by+Sp1.&rft.au=De+Siervi%2C+Adriana%3BMarinissen%2C+Maria%3BDiggs%2C+Jessica%3BWang%2C+Xiao-Fan%3BPages%2C+Gilles%3BSenderowicz%2C+Adrian&rft.aulast=De+Siervi&rft.aufirst=Adriana&rft.date=2004-01-15&rft.volume=64&rft.issue=2&rft.spage=743&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 - 2004-04-02 N1 - Date created - 2004-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - E6 and E7 oncoproteins induce distinct patterns of chromosomal aneuploidy in skin tumors from transgenic mice. AN - 80120111; 14744767 AB - Inactivation of the tumor suppressor genes p53 and Rb are two of the most common genetic alterations in cancer cells. We use a mouse model to dissect the consequences of compromising the function of either of these genes on the maintenance of genomic stability. Thirteen cell lines established from skin tumors of mice expressing either the E6 or E7 oncoprotein of the human papillomavirus (HPV) type 16 under control of the keratin 14 promoter were analyzed by comparative genomic hybridization, spectral karyotyping and fluorescence in situ hybridization, reverse transcription-PCR, and mutation analysis. Deducing from the wealth of molecular cytogenetic data available from human cancers, we hypothesized that the more benign tumors in mice expressing E7 would be distinct from the more aggressive lesions in E6 transgenic mice. Tumorigenesis in E6-expressing mice required specifically the selection and maintenance of cells with extra copies of chromosome 6. Aneuploidy of chromosome 6 was independent of activating mutations in H-ras on chromosome 7. Expression of either E6 or E7 resulted in centrosome aberrations, indicating that each viral oncoprotein interferes independently with the centrosome cycle. Although centrosome aberrations are consistent with development of aneuploidy, no direct correlation was evident between the degree of aneuploidy and the percentage of cells with aberrant centrosomes. Our results show that although aneuploidy and centrosome aberrations are present in tumor cells from mice expressing either E6 or E7, tumorigenesis via E6 requires copy number increases of mouse chromosome 6, which is partially orthologous to human chromosome 3q, a region gained in HPV-associated carcinomas. JF - Cancer research AU - Schaeffer, Anthony J AU - Nguyen, Marie AU - Liem, Amy AU - Lee, Denis AU - Montagna, Cristina AU - Lambert, Paul F AU - Ried, Thomas AU - Difilippantonio, Michael J AD - Genetics Branch, Center for Cancer Research, National Cancer Institute/NIH, Bethesda, Maryland, USA. Y1 - 2004/01/15/ PY - 2004 DA - 2004 Jan 15 SP - 538 EP - 546 VL - 64 IS - 2 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - DNA Primers KW - E6 protein, Human papillomavirus type 16 KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Repressor Proteins KW - oncogene protein E7, Human papillomavirus type 16 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Karyotyping KW - Animals KW - Cell Line, Tumor KW - Mice KW - Mice, Transgenic KW - Chromosome Mapping KW - Polymerase Chain Reaction KW - Genes, ras -- genetics KW - Polymorphism, Restriction Fragment Length KW - Genes, p53 -- genetics KW - Mutation KW - Genes, Retinoblastoma -- genetics KW - Skin Neoplasms -- genetics KW - Aneuploidy KW - Oncogene Proteins, Viral -- genetics KW - Papillomaviridae -- genetics KW - Chromosomes -- genetics KW - Skin Neoplasms -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80120111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=E6+and+E7+oncoproteins+induce+distinct+patterns+of+chromosomal+aneuploidy+in+skin+tumors+from+transgenic+mice.&rft.au=Schaeffer%2C+Anthony+J%3BNguyen%2C+Marie%3BLiem%2C+Amy%3BLee%2C+Denis%3BMontagna%2C+Cristina%3BLambert%2C+Paul+F%3BRied%2C+Thomas%3BDifilippantonio%2C+Michael+J&rft.aulast=Schaeffer&rft.aufirst=Anthony&rft.date=2004-01-15&rft.volume=64&rft.issue=2&rft.spage=538&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 - 2004-04-02 N1 - Date created - 2004-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco carcinogen-induced cellular transformation increases activation of the phosphatidylinositol 3'-kinase/Akt pathway in vitro and in vivo. AN - 80120079; 14744754 AB - The role of the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway during tobacco carcinogen-induced transformation is unknown. To address this question, we evaluated this pathway in isogenic immortalized or tumorigenic human bronchial epithelial cells in vitro, as well as in progressive murine lung lesions induced by a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Compared with immortalized cells, tumorigenic cells had greater activation of the PI3K/Akt pathway, enhanced survival, and increased apoptosis in response to inhibition of the pathway. In vivo, increased activation of Akt and mammalian target of rapamycin was observed with increased phenotypic progression. Collectively, these results support the hypothesis that maintenance of Akt activity is necessary for survival of preneoplastic as well as transformed lung epithelial cells and suggest that inhibition of the PI3K/Akt pathway might be a useful approach to arrest lung tumorigenesis. JF - Cancer research AU - West, Kip A AU - Linnoila, Ilona R AU - Belinsky, Steven A AU - Harris, Curtis C AU - Dennis, Phillip A AD - Cancer Therapeutics Branch, Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA. Y1 - 2004/01/15/ PY - 2004 DA - 2004 Jan 15 SP - 446 EP - 451 VL - 64 IS - 2 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Proto-Oncogene Proteins KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Index Medicus KW - Respiratory Mucosa KW - Animals KW - Lung Neoplasms -- enzymology KW - Enzyme Activation KW - Humans KW - Cell Line, Tumor KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - Precancerous Conditions -- enzymology KW - Precancerous Conditions -- pathology KW - Lung KW - Cell Line KW - Lung Neoplasms -- pathology KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Carcinogens -- toxicity KW - Cell Transformation, Neoplastic -- drug effects KW - Tobacco -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80120079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tobacco+carcinogen-induced+cellular+transformation+increases+activation+of+the+phosphatidylinositol+3%27-kinase%2FAkt+pathway+in+vitro+and+in+vivo.&rft.au=West%2C+Kip+A%3BLinnoila%2C+Ilona+R%3BBelinsky%2C+Steven+A%3BHarris%2C+Curtis+C%3BDennis%2C+Phillip+A&rft.aulast=West&rft.aufirst=Kip&rft.date=2004-01-15&rft.volume=64&rft.issue=2&rft.spage=446&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 - 2004-04-02 N1 - Date created - 2004-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of toxic equivalency factors for induction of cytochromes P450 CYP1A1 and CYP1A2 enzyme activity by dioxin-like compounds. AN - 80115694; 14736496 AB - The toxic equivalency factor (TEF) method has been used to characterize the toxicity of human mixtures of dioxin-like compounds and is being considered for use with other classes of potentially toxic agents. TEFs are estimated by examining the relative potencies of the various congeners for a series of biological and toxicological effects. In this paper, we consider changes in activity for two enzymes, cytochrome P450 1A1 (CYP1A1)-associated 7-ethoxyresorufin-O-deethylase (EROD) and CYP1A2-associated acetanilide-4-hydroxylase (A4H) activity, resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) or a mixture of these agents. The ratio of median effective dose (ED50) is one way to estimate the relative potencies, especially for gene expression and protein endpoints. ED50's were estimated with a nonlinear regression model in which dose-related changes in mean responses are described by a Hill function. ED50's along with other model parameters were estimated by fitting this model to a given data set. Significant differences in estimated model parameters were tested by likelihood ratio methods. The estimated parameters indicated that congener-specific dose-response shapes were significantly different, that additivity failed for these congeners, and that the ratios of ED50's did not predict the response seen for the mixture. These results indicate that for some biological responses, the use of a single relative potency factor (RPF) is not appropriate for the comparison of the dose response behavior of different dioxin-like congeners. JF - Toxicology and applied pharmacology AU - Toyoshiba, Hiroyoshi AU - Walker, Nigel J AU - Bailer, A John AU - Portier, Christopher J AD - National Institute of Environmental Health Sciences, 27709, Durham, NC, USA Y1 - 2004/01/15/ PY - 2004 DA - 2004 Jan 15 SP - 156 EP - 168 VL - 194 IS - 2 SN - 0041-008X, 0041-008X KW - Carcinogens, Environmental KW - 0 KW - Dioxins KW - Polychlorinated Dibenzodioxins KW - 1,2,3,7,8-pentachlorodibenzo-p-dioxin KW - 2NE6H0QPCH KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1A2 KW - acetanilide hydroxylase KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Enzyme Induction -- drug effects KW - Dose-Response Relationship, Drug KW - Enzyme Induction -- physiology KW - Carcinogens, Environmental -- toxicity KW - Drug Evaluation, Preclinical -- methods KW - Female KW - Polychlorinated Dibenzodioxins -- analogs & derivatives KW - Polychlorinated Dibenzodioxins -- toxicity KW - Toxicity Tests -- methods KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Dioxins -- toxicity KW - Cytochrome P-450 CYP1A2 -- biosynthesis KW - Cytochrome P-450 CYP1A1 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80115694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evaluation+of+toxic+equivalency+factors+for+induction+of+cytochromes+P450+CYP1A1+and+CYP1A2+enzyme+activity+by+dioxin-like+compounds.&rft.au=Toyoshiba%2C+Hiroyoshi%3BWalker%2C+Nigel+J%3BBailer%2C+A+John%3BPortier%2C+Christopher+J&rft.aulast=Toyoshiba&rft.aufirst=Hiroyoshi&rft.date=2004-01-15&rft.volume=194&rft.issue=2&rft.spage=156&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 - 2004-03-05 N1 - Date created - 2004-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Successful pregnancies and abortions in symptomatic and asymptomatic Wilson's disease. AN - 71569037; 14675607 AB - There are only a few reports regarding the fertility and outcome of pregnancy in Wilson's disease (WD) and none from India. The authors in this study discuss various aspects of fertility in 16 women with WD. Retrospective analysis of data from a large cohort of WD, being followed at a tertiary care center. Sixteen patients had conceived on 59 occasions with 30 successful pregnancies, 24 spontaneous abortions, 2 medical terminations of pregnancy and 3 still births. Diagnosis of WD was established after conception in 10 presymptomatic patients while six patients were already on treatment. Among these 16 patients, 9 had history of spontaneous abortions and 12 had successful pregnancies. None of the clinical features of WD changed during pregnancy, with or without treatment. All the 30 babies were full-term and delivered healthy. Recurrent abortions are common especially in women with untreated Wilson's disease. However, successful pregnancies and uneventful full-term delivery may occur in mothers of WD on treatment and in undiagnosed, undetected presymptomatic patients. Pregnancy does not seem to have adverse effect on the clinical course of Wilson's disease. Teratogenecity was not seen in the present series with low-dose penicillamine and zinc sulphate. JF - Journal of the neurological sciences AU - Sinha, Sanjib AU - Taly, A B AU - Prashanth, L K AU - Arunodaya, G R AU - Swamy, H S AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India. Y1 - 2004/01/15/ PY - 2004 DA - 2004 Jan 15 SP - 37 EP - 40 VL - 217 IS - 1 SN - 0022-510X, 0022-510X KW - Index Medicus KW - Abortion, Induced KW - Humans KW - Cohort Studies KW - Adult KW - Middle Aged KW - Follow-Up Studies KW - Adolescent KW - Female KW - Pregnancy KW - Hepatolenticular Degeneration -- therapy KW - Hepatolenticular Degeneration -- physiopathology KW - Hepatolenticular Degeneration -- classification KW - Fertilization -- physiology KW - Abortion, Spontaneous -- physiopathology KW - Pregnancy Outcome KW - Hepatolenticular Degeneration -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71569037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Successful+pregnancies+and+abortions+in+symptomatic+and+asymptomatic+Wilson%27s+disease.&rft.au=Sinha%2C+Sanjib%3BTaly%2C+A+B%3BPrashanth%2C+L+K%3BArunodaya%2C+G+R%3BSwamy%2C+H+S&rft.aulast=Sinha&rft.aufirst=Sanjib&rft.date=2004-01-15&rft.volume=217&rft.issue=1&rft.spage=37&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 - 2004-03-08 N1 - Date created - 2003-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot trial of 1-octanol in essential tremor. AN - 80104861; 14718713 AB - 1-Octanol (an 8-C alcohol currently used as a food-flavoring agent) is known to inhibit tremor in essential tremor (ET) animal models at a much lower dose than ethyl alcohol. The authors conducted a randomized, placebo-controlled pilot trial of a single oral dose of 1 mg/kg of 1-octanol in 12 patients with ET. No significant side effects or signs of intoxication were observed. 1-Octanol significantly decreased tremor amplitude for up to 90 minutes. The results suggest 1-octanol as a well-tolerated and safe potential treatment for ET. Further trials are warranted. JF - Neurology AU - Bushara, K O AU - Goldstein, S R AU - Grimes, G J AU - Burstein, A H AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. busha001@umn.edu Y1 - 2004/01/13/ PY - 2004 DA - 2004 Jan 13 SP - 122 EP - 124 VL - 62 IS - 1 KW - 1-Octanol KW - NV1779205D KW - Abridged Index Medicus KW - Index Medicus KW - Diagnostic Techniques, Neurological -- instrumentation KW - Humans KW - Safety KW - Adult KW - Treatment Outcome KW - Aged KW - Pilot Projects KW - Middle Aged KW - Male KW - Female KW - Essential Tremor -- diagnosis KW - Essential Tremor -- drug therapy KW - 1-Octanol -- therapeutic use KW - 1-Octanol -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80104861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pilot+trial+of+1-octanol+in+essential+tremor.&rft.au=Bushara%2C+K+O%3BGoldstein%2C+S+R%3BGrimes%2C+G+J%3BBurstein%2C+A+H%3BHallett%2C+M&rft.aulast=Bushara&rft.aufirst=K&rft.date=2004-01-13&rft.volume=62&rft.issue=1&rft.spage=122&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=1526-632X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-04 N1 - Date created - 2004-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Medication use and risk of ovarian carcinoma: a prospective study. AN - 71558630; 14639616 AB - Inflammation and gonadotropins are hypothesized to influence ovarian carcinogenesis. In a prospective study, we evaluated ovarian cancer risk associated with self-reported use of medications that influence inflammation or gonadotropin levels. The Breast Cancer Detection Demonstration Project Follow-Up Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed questionnaires through 1998 to update risk factor information and identify incident ovarian cancers. The 1992-95 questionnaire ascertained medication use, including duration and frequency of use for aspirin, acetaminophen, other nonsteroidal anti-inflammatory drugs (NSAIDs), tranquilizers and histamine-receptor antagonists. A Poisson regression analysis generated rate ratios (RRs) and 95% confidence intervals (CIs) for the 31,364 women who were at risk of ovarian cancer and responded to the questionnaire that queried regular medication use. One hundred sixteen women developed ovarian cancer during follow-up. None of the anti-inflammatory medications was associated with ovarian cancer, but the RR for more than 1 aspirin per day for 1 year or longer was 0.56 (95% CI 0.20-1.5) and the RR for more than 5 years of regular "other NSAID" use was 2.0 (95% CI 0.95-4.2). Regular tranquilizer use was not associated with ovarian cancer, but histamine-receptor antagonists used regularly for more than 5 years (RR = 3.6, 95% CI 1.4-9.1) or more than once daily (RR = 3.1, 95% CI 1.5-6.5) appeared to increase risk. In our study, neither anti-inflammatory medications nor anti-psychotic medications were associated with ovarian cancer. Potential associations with histamine-receptor antagonists may warrant further study. Copyright 2003 Wiley-Liss, Inc. JF - International journal of cancer AU - Lacey, James V AU - Sherman, Mark E AU - Hartge, Patricia AU - Schatzkin, Arthur AU - Schairer, Catherine AD - Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD 20852-7234, USA. jimlacey@nih.gov Y1 - 2004/01/10/ PY - 2004 DA - 2004 Jan 10 SP - 281 EP - 286 VL - 108 IS - 2 SN - 0020-7136, 0020-7136 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Histamine Antagonists KW - Tranquilizing Agents KW - Acetaminophen KW - 362O9ITL9D KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - Prospective Studies KW - Aged, 80 and over KW - Risk Factors KW - Humans KW - Cohort Studies KW - Aspirin -- therapeutic use KW - Surveys and Questionnaires KW - Aged KW - Acetaminophen -- therapeutic use KW - Middle Aged KW - Follow-Up Studies KW - United States -- epidemiology KW - Female KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Histamine Antagonists -- therapeutic use KW - Tranquilizing Agents -- therapeutic use KW - Ovarian Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71558630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Medication+use+and+risk+of+ovarian+carcinoma%3A+a+prospective+study.&rft.au=Lacey%2C+James+V%3BSherman%2C+Mark+E%3BHartge%2C+Patricia%3BSchatzkin%2C+Arthur%3BSchairer%2C+Catherine&rft.aulast=Lacey&rft.aufirst=James&rft.date=2004-01-10&rft.volume=108&rft.issue=2&rft.spage=281&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 - 2004-01-08 N1 - Date created - 2003-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. AN - 80080014; 14578353 AB - Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. We have previously reported that lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons is mediated by the release of proinflammatory factors from activated microglia. Here, we report the pivotal role of NADPH oxidase in inflammation-mediated neurotoxicity, where the LPS-induced loss of nigral dopaminergic neurons in vivo was significantly less pronounced in NADPH oxidase-deficient (PHOX-/-) mice when compared with control (PHOX+/+) mice. Dopaminergic neurons in primary mensencephalic neuron-glia cultures from PHOX+/+ mice were significantly more sensitive to LPS-induced neurotoxicity in vitro when compared with PHOX-/- mice. Further, PHOX+/+ neuron-glia cultures chemically depleted of microglia failed to show dopaminergic neurotoxicity with the addition of LPS. Neuron-enriched cultures from both PHOX+/+ mice and PHOX-/- mice also failed to show any direct LPS-induced dopaminergic neurotoxicity. However, the addition of PHOX+/+ microglia to neuron-enriched cultures from either strain resulted in reinstatement of LPS-induced dopaminergic neurotoxicity, supporting the role of microglia as the primary source of NADPH oxidase-generated insult and neurotoxicity. Immunostaining for F4/80 in mensencephalic neuron-glia cultures revealed that PHOX-/- microglia failed to show activated morphology at 10 h, suggesting an important role of reactive oxygen species (ROS) generated from NADPH oxidase in the early activation of microglia. LPS also failed to elicit extracellular superoxide and produced low levels of intracellular ROS in microglia-enriched cultures from PHOX-/- mice. Gene expression and release of tumor necrosis factor alpha was much lower in PHOX-/- mice than in control PHOX+/+ mice. Together, these results demonstrate the dual neurotoxic functions of microglial NADPH oxidase: 1) the production of extracellular ROS that is toxic to dopamine neurons and 2) the amplification of proinflammatory gene expression and associated neurotoxicity. JF - The Journal of biological chemistry AU - Qin, Liya AU - Liu, Yuxin AU - Wang, Tongguang AU - Wei, Sung-Jen AU - Block, Michelle L AU - Wilson, Belinda AU - Liu, Bin AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, NIEHS, NIH, Research Triangle Park, NC 27709, USA. Y1 - 2004/01/09/ PY - 2004 DA - 2004 Jan 09 SP - 1415 EP - 1421 VL - 279 IS - 2 SN - 0021-9258, 0021-9258 KW - Lipopolysaccharides KW - 0 KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Superoxides KW - 11062-77-4 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Neuroglia -- cytology KW - Animals KW - Neurons -- metabolism KW - Dose-Response Relationship, Drug KW - Neurons -- drug effects KW - Transgenes KW - Dopamine -- metabolism KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Inflammation KW - Substantia Nigra -- metabolism KW - Superoxides -- metabolism KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Tumor Necrosis Factor-alpha -- metabolism KW - Time Factors KW - Immunohistochemistry KW - Female KW - Male KW - NADPH Oxidase -- metabolism KW - Lipopolysaccharides -- metabolism KW - NADPH Oxidase -- physiology KW - Gene Expression Regulation KW - Microglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80080014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=NADPH+oxidase+mediates+lipopolysaccharide-induced+neurotoxicity+and+proinflammatory+gene+expression+in+activated+microglia.&rft.au=Qin%2C+Liya%3BLiu%2C+Yuxin%3BWang%2C+Tongguang%3BWei%2C+Sung-Jen%3BBlock%2C+Michelle+L%3BWilson%2C+Belinda%3BLiu%2C+Bin%3BHong%2C+Jau-Shyong&rft.aulast=Qin&rft.aufirst=Liya&rft.date=2004-01-09&rft.volume=279&rft.issue=2&rft.spage=1415&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 - 2004-02-10 N1 - Date created - 2004-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genes malH and pagL of Clostridium acetobutylicum ATCC 824 Encode NAD super(+)- and Mn super(2+)-dependent Phospho- alpha -glucosidase(s) AN - 19236188; 5801654 AB - The genome of Clostridium acetobutylicum 824 contains two genes encoding NAD super(+), Mn super(2+), and dithiothreitol-dependent phospho- alpha -glucosidases that can be assigned to family 4 of the glycosylhydrolase superfamily. The two genes, designated malh (maltose 6-phosphate hydrolase) and pagl (phospho- alpha -glucosidase), respectively, reside in separate operons that also encode proteins of the phosphoenolpyruvate-dependent:sugar phosphotransferase system. C. acetobutylicum grows on a variety of alpha -linked glucosides, including maltose, methyl- alpha -D-glucoside, and the five isomers of sucrose. In the presence of the requisite cofactors, extracts of these cells readily hydrolyzed the chromogenic substrate p-nitrophenyl- alpha -D-glucopyranoside 6-phosphate, but whether hydrolysis reflected expression of enzymes encoded by the malh or pagl genes was not discernible by spectrophotometric analysis or polyacrylamide gel electrophoresis. Resolution of this question required the cloning of the malh and pagl genes, and subsequent high expression, purification, and characterization of maltose-6'-phosphate hydrolase (MalH) and phospho- alpha -glucosidase (PagL), respectively. MalH and PagL exhibit 50% residue identity, and in solution are tetramers comprising similar sized (~50 kDa) subunits. The two proteins cross-react with polyclonal rabbit antibody against phospho- alpha -glucosidase from Fusobacterium mortiferum. Purified MalH and PagL cleaved p-nitrophenyl- alpha -D-glucopyranoside 6-phosphate with comparable efficiency, but only MalH catalyzed the hydrolysis of disaccharide 6'-phosphates formed via the phosphoenolpyruvate-dependent:sugar phosphotransferase system. Importantly, analysis of the proteome of C. acetobutylicum 824 by electrospray ionization-mass spectrometry confirmed expression of MalH during growth on many alpha -glucosides tested. Site-directed changes C169S and D170N yielded full-length, but catalytically inactive MalH. Of the two putative operons, our findings suggest that only proteins encoded by the mal operon participate in the dissimilation of maltose and related O- alpha -linked glucosides by C. acetobutylicum 824. JF - Journal of Biological Chemistry AU - Thompson, J AU - Hess, S AU - Pikis, A AD - Microbial Biochemistry and Genetics Unit, Oral Infection and Immunity Branch, NIDCR and the Proteomics and Mass Spectrometry Facility, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, jthompson@dir.nidcr.nih.gov Y1 - 2004/01/09/ PY - 2004 DA - 2004 Jan 09 SP - 1553 EP - 1561 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 2 SN - 0021-9258, 0021-9258 KW - NAD KW - malH gene KW - maltose KW - maltose 6-phosphate hydrolase KW - methyl- alpha -D-glucoside KW - pagL gene KW - phosphoenolpyruvate:sugar phosphotransferase KW - sucrose KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Site-directed mutagenesis KW - phosphoenolpyruvate-sugar phosphotransferase KW - Maltose-6'-phosphate glucosidase KW - Clostridium acetobutylicum KW - Dithiothreitol KW - Manganese KW - Fusobacterium mortiferum KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19236188?accountid=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=Genes+malH+and+pagL+of+Clostridium+acetobutylicum+ATCC+824+Encode+NAD+super%28%2B%29-+and+Mn+super%282%2B%29-dependent+Phospho-+alpha+-glucosidase%28s%29&rft.au=Thompson%2C+J%3BHess%2C+S%3BPikis%2C+A&rft.aulast=Thompson&rft.aufirst=J&rft.date=2004-01-09&rft.volume=279&rft.issue=2&rft.spage=1553&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M310733200 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Site-directed mutagenesis; phosphoenolpyruvate-sugar phosphotransferase; Maltose-6'-phosphate glucosidase; Dithiothreitol; Manganese; Clostridium acetobutylicum; Fusobacterium mortiferum DO - http://dx.doi.org/10.1074/jbc.M310733200 ER - TY - JOUR T1 - Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage. AN - 80085819; 14712210 AB - The p53 tumor suppressor protein plays a critical role in mediating cellular response to stress. Upon DNA damage, post-translational modifications stabilize and activate this nuclear phosphoprotein. To determine the effect of phosphorylation site mutants in the context of the whole p53 protein, we performed reporter assays in p53 and MDM2 knockout mouse embryonic fibroblasts transfected with full-length p53 constructs. We show that mutation of S37 causes a decrease in p53 transcriptional activity compared to wild-type p53. Our data further suggest that the dephosphorylation of p53 at S37 is a regulated event involving protein phosphatase 2A (PP2A). Coimmunoprecipitation and immunofluorescence microscopy studies demonstrate that PP2A and p53 associate with one another in vivo following gamma-irradiation. Consistent with these observations, phosphorylated S37 accumulates in cell extracts prepared from gamma-irradiated Molt-4 cells in the presence of okadaic acid. Furthermore, in vitro phosphatase assays show that PP2A dephosphorylates p53 at S37. These results suggest that dephosphorylation of p53 at S37 plays a role in the transcriptional regulation of the p53 protein in response to DNA damage. JF - Oncogene AU - Dohoney, Kathleen M AU - Guillerm, Claire AU - Whiteford, Craig AU - Elbi, Cem AU - Lambert, Paul F AU - Hager, Gordon L AU - Brady, John N AD - Basic Research Laboratory, Virus Tumor Biology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/01/08/ PY - 2004 DA - 2004 Jan 08 SP - 49 EP - 57 VL - 23 IS - 1 SN - 0950-9232, 0950-9232 KW - Tumor Suppressor Protein p53 KW - 0 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Serine KW - 452VLY9402 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 2 KW - Index Medicus KW - Phosphoprotein Phosphatases -- physiology KW - Phosphorylation KW - Gamma Rays KW - Humans KW - Okadaic Acid -- pharmacology KW - Catalytic Domain KW - Phosphoprotein Phosphatases -- chemistry KW - Cell Line KW - DNA Damage KW - Tumor Suppressor Protein p53 -- chemistry KW - Transcription, Genetic KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80085819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+of+p53+at+serine+37+is+important+for+transcriptional+activity+and+regulation+in+response+to+DNA+damage.&rft.au=Dohoney%2C+Kathleen+M%3BGuillerm%2C+Claire%3BWhiteford%2C+Craig%3BElbi%2C+Cem%3BLambert%2C+Paul+F%3BHager%2C+Gordon+L%3BBrady%2C+John+N&rft.aulast=Dohoney&rft.aufirst=Kathleen&rft.date=2004-01-08&rft.volume=23&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-28 N1 - Date created - 2004-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of Malignant Mixed Mullerian Tumors After Tamoxifen Therapy for Breast Cancer AN - 18012502; 5946283 AB - Recent studies have indicated that the tamoxifen-related risk of uterine corpus cancer may be especially high for some uncommon cell types, although the magnitude of risk has not been quantified. We evaluated data from 39 451 breast cancer patients diagnosed from 1980 through 2000 who were initially treated with tamoxifen and found that the overall risk of subsequent uterine corpus cancer was increased more than twofold (observed-to-expected ratio [O/E] = 2.17, 95% confidence interval [CI] = 1.95 to 2.41) relative to the general SEER population. The relative risk was substantially higher for malignant mixed mullerian tumors (MMMTs) (O/E = 4.62, O = 34, 95% CI = 3.20 to 6.46) than for endometrial adenocarcinomas (O/E = 2.07, O = 306, 95% CI = 1.85 to 2.32), although the excess absolute risk was smalleran additional 1.4 versus 8.4 cancers per 10 000 women per year, respectively. Among those who survived for 5 years or longer, there was an eightfold relative risk for MMMTs and a 2.3-fold risk for endometrial adenocarcinomas, with patients developing MMMTs having a worse prognosis. These findings indicate that tamoxifen may have delayed effects, such as the increased risk of MMMTs, rare but aggressive tumors of unclear pathogenesis. JF - Journal of the National Cancer Institute AU - Curtis, R E AU - Freedman, D M AU - Sherman, ME AU - Fraumeni, JF Jr AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Executive Plaza South, Rm. 7042, Bethesda, MD 20892-7362, rcurtis@mail.nih.gov Y1 - 2004/01/07/ PY - 2004 DA - 2004 Jan 07 SP - 70 EP - 74 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 96 IS - 1 SN - 0027-8874, 0027-8874 KW - man KW - Toxicology Abstracts KW - Antineoplastic drugs KW - Tumors KW - Tamoxifen KW - Side effects KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18012502?accountid=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+the+National+Cancer+Institute&rft.atitle=Risk+of+Malignant+Mixed+Mullerian+Tumors+After+Tamoxifen+Therapy+for+Breast+Cancer&rft.au=Curtis%2C+R+E%3BFreedman%2C+D+M%3BSherman%2C+ME%3BFraumeni%2C+JF+Jr&rft.aulast=Curtis&rft.aufirst=R&rft.date=2004-01-07&rft.volume=96&rft.issue=1&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/10.1093%2Fjnci%2Fdjh007 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Side effects; Tamoxifen; Antineoplastic drugs; Tumors DO - http://dx.doi.org/10.1093/jnci/djh007 ER - TY - JOUR T1 - Homoepiboxidines: further potent agonists for nicotinic receptors. AN - 80076686; 14697783 AB - Homoepiboxidine (3) and the corresponding N-methyl (4) and N-benzyl (5) derivatives were prepared from a 6beta-carbomethoxynortropane (8). Affinities and functional activities at neuromuscular, central neuronal and ganglionic-type nicotinic receptors were compared to those of epibatidine 1, and epiboxidine 2. Homoepiboxidine had equivalent affinity/activity to epiboxidine at neuromuscular, neuronal alpha4beta2, and most alpha3-containing ganglionic-type nicotinic receptors. The N-substituted derivatives showed reduced affinity/activity at most receptor subtypes. Replacement of the methylisoxazole moiety of 3 and 4 with a methyloxadiazole moiety provided analogues 6 and 7, which had greatly reduced affinity/activity in virtually all assays at nicotinic receptors. Marked analgetic activity in mice occurred at the following ip doses: epibatidine 10 microg/kg; epiboxidine 25 microg/kg; homoepiboxidine 100 microg/kg; N-methylhomoepiboxidine 100 microg/kg; the methyloxadiazole (6) 100 microg/kg. The time course at such ip doses was significantly longer for homoepiboxidine 3 with marked analgesia still manifest at 30 min post-injection. Epiboxidine and the homoepiboxidines were less toxic than epibatidine. JF - Bioorganic & medicinal chemistry AU - Fitch, Richard W AU - Pei, Xue-Feng AU - Kaneko, Yumika AU - Gupta, Tara AU - Shi, Dan AU - Federova, Irina AU - Daly, John W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/01/02/ PY - 2004 DA - 2004 Jan 02 SP - 179 EP - 190 VL - 12 IS - 1 SN - 0968-0896, 0968-0896 KW - Analgesics KW - 0 KW - Bridged Bicyclo Compounds, Heterocyclic KW - Isoxazoles KW - Nicotinic Agonists KW - Pyridines KW - Receptors, Nicotinic KW - epiboxidine KW - epibatidine KW - M6K314F1XX KW - Index Medicus KW - Animals KW - Pyridines -- chemistry KW - Humans KW - Cell Line, Tumor KW - Mice KW - Rats KW - Bridged Bicyclo Compounds, Heterocyclic -- chemistry KW - Protein Binding -- physiology KW - Bridged Bicyclo Compounds, Heterocyclic -- toxicity KW - Pyridines -- toxicity KW - Analgesics -- chemistry KW - Analgesics -- toxicity KW - Cell Line KW - Male KW - PC12 Cells KW - Nicotinic Agonists -- toxicity KW - Receptors, Nicotinic -- physiology KW - Nicotinic Agonists -- chemistry KW - Isoxazoles -- toxicity KW - Isoxazoles -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80076686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Homoepiboxidines%3A+further+potent+agonists+for+nicotinic+receptors.&rft.au=Fitch%2C+Richard+W%3BPei%2C+Xue-Feng%3BKaneko%2C+Yumika%3BGupta%2C+Tara%3BShi%2C+Dan%3BFederova%2C+Irina%3BDaly%2C+John+W&rft.aulast=Fitch&rft.aufirst=Richard&rft.date=2004-01-02&rft.volume=12&rft.issue=1&rft.spage=179&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 - 2004-09-16 N1 - Date created - 2003-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improved breadth and potency of an HIV-1-neutralizing human single-chain antibody by random mutagenesis and sequential antigen panning. AN - 71597780; 14659751 AB - Several human monoclonal antibodies can neutralize a range of human immunodeficiency virus type 1 (HIV-1) primary isolates but their potency and related ability to suppress generation of HIV-1 escape mutants is significantly lower than the activity of antiretroviral drugs currently in clinical use. Recently, a human Fab, X5, was identified and found to neutralize primary isolates from different clades. Further improvement of the potency and breadth of HIV-1 neutralization by this antibody could be critical for its potential use in the treatment of HIV-1-infected patients. However, increasing potency of an antibody by selection from libraries may lead to a decrease in the breadth of neutralization. In an attempt to solve this problem, we subjected a random mutagenesis library of the scFv X5 to sequential rounds of selection on non-homologous HIV-1 envelope glycoproteins (Envs) dubbed sequential antigen panning (SAP). By using SAP, we identified two scFv antibodies, m6 and m9, that were tested with a panel of 33 diverse primary HIV-1 infectious isolates in an assay based on a reporter cell-line expressing high levels of CD4, CCR5 and CXCR4. The IC(50) was less than 50 microg/ml for 21 (m6) and 19 (m9) out of 29 isolates from group M (subtypes A-C, F, G and CRF-01AE) and one isolate from group N; three isolates from group O were not significantly inhibited at 50 microg/ml. The average IC(50) values for the two antibodies were significantly (p<0.001, n=29) lower compared to scFv X5. Their inhibitory activity does not appear to be related to the HIV-1 subtype, coreceptor usage or the disease stage. m9 inhibited infection of peripheral blood mononuclear cells by the primary isolates JRCSF, 89.6 and BR020 with IC(90) of 4, 6 and 25 microg/ml, respectively; for a single-round infection by pseudovirus, the IC(90) for JRSCF, 89.6, YU2 and HXBc2 was 15, 5, 15 and 5 microg/ml, respectively. In these two assays the IC(90) for m9 was, on average, two- to threefold lower than for scFv X5. These results demonstrate that both the potency and the breadth of HIV-1 neutralization of one of the few known potent broadly cross-reactive human monoclonal antibodies, scFv X5, could be improved significantly. However, only experiments in animal models and clinical trials in humans will show whether these new scFvs and the approach for their identification have potential in the development of prophylactics and therapeutics for HIV-1 infections. JF - Journal of molecular biology AU - Zhang, Mei Yun AU - Shu, Yuuei AU - Rudolph, Donna AU - Prabakaran, Ponraj AU - Labrijn, Aran F AU - Zwick, Michael B AU - Lal, Renu B AU - Dimitrov, Dimiter S AD - Human Immunovirology and Computational Biology Group, LECB, CCR, National Cancer Institute-Frederick, NIH, Frederick, MD 21702, USA. Y1 - 2004/01/02/ PY - 2004 DA - 2004 Jan 02 SP - 209 EP - 219 VL - 335 IS - 1 SN - 0022-2836, 0022-2836 KW - Antigens, CD4 KW - 0 KW - HIV Antibodies KW - HIV Antigens KW - HIV Envelope Protein gp120 KW - Immunoglobulin Fragments KW - Peptide Library KW - immunoglobulin Fv KW - Index Medicus KW - Antibody Specificity KW - HIV Envelope Protein gp120 -- immunology KW - Humans KW - Inhibitory Concentration 50 KW - Antibody Affinity KW - Drug Evaluation, Preclinical -- methods KW - Mutation KW - Antigens, CD4 -- immunology KW - HIV-1 -- immunology KW - HIV Antibodies -- immunology KW - Immunoglobulin Fragments -- genetics KW - HIV Antibodies -- genetics KW - Immunoglobulin Fragments -- immunology KW - HIV Antigens -- immunology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71597780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Improved+breadth+and+potency+of+an+HIV-1-neutralizing+human+single-chain+antibody+by+random+mutagenesis+and+sequential+antigen+panning.&rft.au=Zhang%2C+Mei+Yun%3BShu%2C+Yuuei%3BRudolph%2C+Donna%3BPrabakaran%2C+Ponraj%3BLabrijn%2C+Aran+F%3BZwick%2C+Michael+B%3BLal%2C+Renu+B%3BDimitrov%2C+Dimiter+S&rft.aulast=Zhang&rft.aufirst=Mei&rft.date=2004-01-02&rft.volume=335&rft.issue=1&rft.spage=209&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 - 2004-01-30 N1 - Date created - 2003-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Shared and Distinct Neurophysiological Components of the Digits Forward and Backward Tasks as Revealed by Functional Neuroimaging AN - 85603067; 200502904 AB - The digits forward (DF) & backward (DB) tasks are widely used neuropsychological measures believed to tap overlapping systems of phonological processing & working memory. Studies of focal brain lesions have partially elucidated the brain regions essential for these tasks; however relatively little information exists on the underlying functional neuroanatomy in the intact brain. We therefore examined the shared & separate neural systems of these tasks in two positron emission tomography (PET) experiments. In Experiment 1, eight healthy participants performed verbal DF, DB, & a sensorimotor control task during measurement of regional cerebral blood flow (rCBF). DF & DB each activated frontal, parietal, & cerebellar regions as well as prominently activating medial occipital cortex. To eliminate possible visuospatial confounds, Experiment 2 replicated the first experiment in six additional healthy participants who were blindfolded during the study. No differences in activation were found between the two experimental groups. Combined data from both experiments demonstrate that DF & DB rely upon a largely overlapping functional neural system associated with working memory, most notably right dorsolateral prefrontal cortex (DLPFC) & bilateral inferior parietal lobule (IPL) as well as the anterior cingulate, a region associated with attentional effort. The degree of activation increased linearly with increasing task difficulty in DF. DB additionally recruited bilateral DLPFC, left IPL, & Broca's area. Medial occipital cortex (including higher & lower visual processing areas) was robustly activated in both DF & DB & could not be attributed to visual processing per se, suggesting a possible visual imagery strategy for these aural-verbal tasks. 2 Tables, 3 Figures, 37 References. [Copyright 2004 Elsevier Ltd.] JF - Neuropsychologia AU - Gerton, Brooke K AU - Brown, Timothy T AU - Meyer-Lindenberg, Andreas AU - Kohn, Philip AU - Holt, John L AU - Olsen, Rosanna K AU - Berman, Karen Faith AD - c/o Berman-Unit Integrative Neuroimaging, Clinical Brain Disorders Branch, Intramural Research Program, National Instit Mental Health, Bethesda, MD karen.berman@nih.gov Y1 - 2004///0, PY - 2004 DA - 0, 2004 SP - 1781 EP - 1787 VL - 42 IS - 13 SN - 0028-3932, 0028-3932 KW - Visual Processing (94640) KW - Phonological Processing (65110) KW - Brain (09350) KW - Short Term Memory (78150) KW - Attention (05350) KW - Neuroimaging Techniques (57245) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85603067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychologia&rft.atitle=Shared+and+Distinct+Neurophysiological+Components+of+the+Digits+Forward+and+Backward+Tasks+as+Revealed+by+Functional+Neuroimaging&rft.au=Gerton%2C+Brooke+K%3BBrown%2C+Timothy+T%3BMeyer-Lindenberg%2C+Andreas%3BKohn%2C+Philip%3BHolt%2C+John+L%3BOlsen%2C+Rosanna+K%3BBerman%2C+Karen+Faith&rft.aulast=Gerton&rft.aufirst=Brooke&rft.date=2004-01-01&rft.volume=42&rft.issue=13&rft.spage=1781&rft.isbn=&rft.btitle=&rft.title=Neuropsychologia&rft.issn=00283932&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2005-04-01 N1 - Last updated - 2016-09-27 N1 - CODEN - NUPSA6 N1 - SubjectsTermNotLitGenreText - Phonological Processing (65110); Short Term Memory (78150); Brain (09350); Attention (05350); Visual Processing (94640); Neuroimaging Techniques (57245) ER - TY - JOUR T1 - Reduced Fhit protein expression in nickel-transformed mouse cells and in nickel-induced murine sarcomas AN - 815542121; 13862259 AB - Nickel compounds are carcinogenic and induce malignant transformation of cultured cells. Since nickel has low mutagenic potential, it may act predominantly through epigenetic mechanisms, including down-regulation of tumor suppressor genes. FHIT is a tumor suppressor gene whose expression is frequently reduced or lost in tumors and pre-malignant lesions. Previously, we have shown that the phosphohydrolase activity of Fhit protein, associated with its tumor suppressor action, is inhibited by nickel [12]. In cells, such effect would assist in carcinogenesis. The latter could be further enhanced if nickel also lowered cellular levels of Fhit protein itself, e.g. by down-regulation of FHIT gene. To test this possibility, we determined Fhit protein and Fhit-mRNA levels in a nickel-transformed mouse cell line and in nickel-induced murine sarcomas. In B200 cells, derived by nickel treatment of BALB/c-3T3 cells and exhibiting a malignant phenotype, Fhit protein levels were 50% of those in the parental cells, while Fhit-mRNA expression remained unchanged. A decrease of up to > 90percnt; in Fhit protein levels was also observed in 22 local sarcomas (mostly fibrosarcomas) induced by i.m. injection of nickel subsulfide in C57BL/6 and MT+ (C57BL/6 overexpressing metallothionein) mice, as compared with normal muscles. Moreover, Fhit was absent in 3 out of 10 sarcomas from MT+ mice and in 1 of 12 sarcomas from C57BL/6 mice. The lack of Fhit protein coincided with the absence of the Fhit-mRNA transcript in these tumors. However, in the other tumors, the decreased Fhit levels were not always accompanied by reduced expression of Fhit-mRNA. Thus, the observed lowering of Fhit protein levels is mostly associated with changes in mRNA expression and protein translation or turnover rates, and rarely with a full silencing of the gene itself. Overall, the decline of Fhit in cells or tissues malignantly transformed by nickel may indicate possible involvement of this effect in the mechanisms of nickel carcinogenesis. JF - Molecular and Cellular Biochemistry AU - Kowara, Renata AU - Salnikow, Konstantin AU - Diwan, Bhalchandra A AU - Bare, Robert M AU - Waalkes, Michael P AU - Kasprzak, Kazimierz S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD, 21702, USA, kasprkaz@mail.ncifcrf.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 195 EP - 202 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 255 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Toxicology Abstracts KW - Transformation KW - Translation KW - Tumor suppressor genes KW - Fibrosarcoma KW - Metallothionein KW - Nickel KW - Muscles KW - Transcription KW - Tumors KW - Gene expression KW - epigenetics KW - Carcinogenesis KW - Sarcoma KW - Protein turnover KW - FHIT protein KW - phosphohydrolase KW - Gene silencing KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/815542121?accountid=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=Molecular+and+Cellular+Biochemistry&rft.atitle=Reduced+Fhit+protein+expression+in+nickel-transformed+mouse+cells+and+in+nickel-induced+murine+sarcomas&rft.au=Kowara%2C+Renata%3BSalnikow%2C+Konstantin%3BDiwan%2C+Bhalchandra+A%3BBare%2C+Robert+M%3BWaalkes%2C+Michael+P%3BKasprzak%2C+Kazimierz+S&rft.aulast=Kowara&rft.aufirst=Renata&rft.date=2004-01-01&rft.volume=255&rft.issue=1-2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Cellular+Biochemistry&rft.issn=03008177&rft_id=info:doi/10.1023%2FB%3AMCBI.0000007275.22785.91 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Transformation; Fibrosarcoma; Tumor suppressor genes; Translation; Metallothionein; Nickel; Muscles; Transcription; Tumors; Gene expression; epigenetics; Carcinogenesis; Sarcoma; Protein turnover; FHIT protein; phosphohydrolase; Gene silencing DO - http://dx.doi.org/10.1023/B:MCBI.0000007275.22785.91 ER - TY - JOUR T1 - Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug-resistance mdr1a/1b(-/-) double knockout mice AN - 815541948; 13862240 AB - Multidrug-resistance gene knockout mdr1a/1b(-/-) mice, which are deficient in P-glycoproteins, are more sensitive than wild-type (WT) mice to acute arsenic toxicity. This study assessed toxic manifestations of chronic oral arsenic in mdr1a/1b(-/-) mice, including oxidative stress and altered gene expression, and investigated altered toxicokinetics as a potential basis of enhanced arsenic toxicity. Thus, mdr1a/1b(-/-) and WT mice were exposed to sodium arsenite (0-80 ppm as arsenic) in the drinking water for 10 weeks at which time hepatic arsenic accumulation, lipid peroxidation (LPO), redox status and change in gene expression level were assessed. All mice survived the arsenic exposure, but body weight gain in the highest dose group was reduced in both mdr1a/1b(-/-) and WT mice. Arsenic induced pathological changes, elevated LPO levels and enhanced glutathione S-transferase (GST) activity, in the liver to a greater extent in mdr1a/1b(-/-) than in WT mice. Arsenic also decreased Cu/Zn superoxide dismutase activity in both mdr1a/1b(-/-) and WT mice. The expressions of certain genes, such as those encoding cell proliferation, GST, acute-phase proteins and metabolic enzymes, were modestly altered in arsenic-exposed mice. The expression of cyclin D1, a potential hepatic oncogene, was enhanced in arsenic-exposed mdr1a/1b(-/-) mice only. At the highest level of exposure, hepatic arsenic content was higher in mdr1a/1b(-/-) than in WT mice, suggesting that enhanced accumulation due to transport deficiency may, in part, account for the enhanced toxicity in these mice. In summary, this study shows that chronic arsenic toxicity, including liver pathology and oxidative stress, is enhanced in mdr1a/1b(-/-) mice, possibly due to enhanced accumulation of arsenic as a result of transport system deficiency. JF - Molecular and Cellular Biochemistry AU - Xie, Yaxiong AU - Liu, Jie AU - Liu, Yaping AU - Klaassen, Curtis D AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA, waalkes@niehs.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 11 EP - 18 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 255 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Genetics Abstracts; Toxicology Abstracts KW - Arsenic KW - Sodium arsenite KW - Enzymes KW - Toxicity KW - Glutathione transferase KW - Lipid peroxidation KW - Gene expression KW - Acute phase substances KW - P-Glycoprotein KW - Oncogenes KW - Oxidative stress KW - Superoxide dismutase KW - Genomic analysis KW - Zinc KW - Liver KW - Multidrug resistance KW - Cell proliferation KW - Drinking water KW - Body weight gain KW - cyclin D1 KW - X 24360:Metals KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/815541948?accountid=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=Molecular+and+Cellular+Biochemistry&rft.atitle=Toxicokinetic+and+genomic+analysis+of+chronic+arsenic+exposure+in+multidrug-resistance+mdr1a%2F1b%28-%2F-%29+double+knockout+mice&rft.au=Xie%2C+Yaxiong%3BLiu%2C+Jie%3BLiu%2C+Yaping%3BKlaassen%2C+Curtis+D%3BWaalkes%2C+Michael+P&rft.aulast=Xie&rft.aufirst=Yaxiong&rft.date=2004-01-01&rft.volume=255&rft.issue=1-2&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Cellular+Biochemistry&rft.issn=03008177&rft_id=info:doi/10.1023%2FB%3AMCBI.0000007256.44450.8c LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Arsenic; Sodium arsenite; Enzymes; Toxicity; Glutathione transferase; Lipid peroxidation; Gene expression; Acute phase substances; P-Glycoprotein; Oncogenes; Superoxide dismutase; Oxidative stress; Zinc; Genomic analysis; Liver; Multidrug resistance; Body weight gain; Drinking water; Cell proliferation; cyclin D1 DO - http://dx.doi.org/10.1023/B:MCBI.0000007256.44450.8c ER - TY - JOUR T1 - Introduction to Trx-G and Pc-G genes. AN - 80183093; 14979018 JF - Methods in enzymology AU - Kennison, James A AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Marlyland 20892-2785, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 61 EP - 70 VL - 377 SN - 0076-6879, 0076-6879 KW - Chromatin KW - 0 KW - DNA-Binding Proteins KW - Drosophila Proteins KW - Polycomb protein, Drosophila KW - Transcription Factors KW - Trl protein, Drosophila KW - Polycomb Repressive Complex 1 KW - EC 2.3.2.27 KW - Index Medicus KW - Phenotype KW - Genes, Homeobox KW - Animals KW - Gene Silencing KW - Chromatin Assembly and Disassembly KW - Transcription, Genetic KW - Mutagenesis KW - Drosophila melanogaster -- genetics KW - DNA-Binding Proteins -- genetics KW - Drosophila melanogaster -- anatomy & histology KW - Drosophila Proteins -- genetics KW - Chromatin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80183093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Introduction+to+Trx-G+and+Pc-G+genes.&rft.au=Kennison%2C+James+A&rft.aulast=Kennison&rft.aufirst=James&rft.date=2004-01-01&rft.volume=377&rft.issue=&rft.spage=61&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 - 2004-04-09 N1 - Date created - 2004-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Viable infectious cell sorting in a BSL-3 facility. AN - 80173929; 14976381 AB - With the increase in demand for high-speed cell sorting of viable infectious and now therapeutic cell samples, safety concerns for the protection of flow cytometer operators have increased. This chapter describes a quick, sensitive, and reproducible procedure to assure sample containment before sorting these samples. This procedure includes aerosol containment, physical barriers, environmental controls, and personal protection. An aerosol management system produces a negative pressure within the sort chamber where aerosols are vacuumed directly into a HEPA filter. Physical barriers include the manufacturer's standard plastic shield and panels. The flow cytometer is contained in a BSL-3 laboratory for maximum environmental control and the operator is protected using a respiratory system. Containment is measured using highly fluorescent Glo-Germ particles under the same conditions as the cell sort but with the sorter adjusted to produce large amounts of aerosols. These aerosols are collected by a vacuum air sampling system for 10 min in three locations onto a glass slide and examined microscopically. With this system in place, aerosol containment can be measured quickly and efficiently, therefore reducing the risk to the operator when sorting viable infectious cells. JF - Methods in molecular biology (Clifton, N.J.) AU - Perfetto, Stephen P AU - Ambrozak, David R AU - Roederer, Mario AU - Koup, Richard A AD - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 419 EP - 424 VL - 263 SN - 1064-3745, 1064-3745 KW - Aerosols KW - 0 KW - Hazardous Substances KW - Plastics KW - Index Medicus KW - Equipment Design KW - Air Microbiology KW - Containment of Biohazards KW - Equipment Contamination KW - Flow Cytometry -- instrumentation KW - Cell Separation -- instrumentation KW - Hazardous Substances -- analysis KW - Flow Cytometry -- methods KW - Cell Separation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80173929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Viable+infectious+cell+sorting+in+a+BSL-3+facility.&rft.au=Perfetto%2C+Stephen+P%3BAmbrozak%2C+David+R%3BRoederer%2C+Mario%3BKoup%2C+Richard+A&rft.aulast=Perfetto&rft.aufirst=Stephen&rft.date=2004-01-01&rft.volume=263&rft.issue=&rft.spage=419&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 - 2004-07-02 N1 - Date created - 2004-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations. AN - 80173571; 14977040 AB - This review addresses many of the chemical aspects of nitrosative stress mediated by N2O3. From a cellular perspective, N2O3 and the resulting reactive nitrogen oxide species target specific motifs such as thiols, lysine active sites, and zinc fingers and is dependant upon both the rates of production as well as consumption of NO and must be taken into account in order to access the nitrosative environment. Since production and consumption are integral parts of N2O3 generation, we predict that nitrosative stress occurs under specific conditions, such as chronic inflammation. In contrast to conditions of stress, nitrosative chemistry may also provide cellular protection through the regulation of critical signaling pathways. Therefore, a careful evaluation of the chemistry of nitrosation based upon specific experimental conditions may provide a better understanding of how the subtle balance between oxidative and nitrosative stress may be involved in the etiology and control of various disease processes. JF - Biological chemistry AU - Ridnour, Lisa A AU - Thomas, Douglas D AU - Mancardi, Daniele AU - Espey, Michael G AU - Miranda, Katrina M AU - Paolocci, Nazareno AU - Feelisch, Martin AU - Fukuto, Jon AU - Wink, David A AD - Tumor Biology Section, Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 1 EP - 10 VL - 385 IS - 1 SN - 1431-6730, 1431-6730 KW - Amines KW - 0 KW - Nitrates KW - Reactive Nitrogen Species KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Humans KW - Oxidative Stress KW - Amines -- chemistry KW - Nitrosation KW - Nitrates -- chemistry KW - Nitric Oxide -- toxicity KW - Reactive Nitrogen Species -- metabolism KW - Nitric Oxide -- chemistry KW - Nitric Oxide -- biosynthesis KW - Reactive Nitrogen Species -- chemistry KW - Reactive Nitrogen Species -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80173571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemistry&rft.atitle=The+chemistry+of+nitrosative+stress+induced+by+nitric+oxide+and+reactive+nitrogen+oxide+species.+Putting+perspective+on+stressful+biological+situations.&rft.au=Ridnour%2C+Lisa+A%3BThomas%2C+Douglas+D%3BMancardi%2C+Daniele%3BEspey%2C+Michael+G%3BMiranda%2C+Katrina+M%3BPaolocci%2C+Nazareno%3BFeelisch%2C+Martin%3BFukuto%2C+Jon%3BWink%2C+David+A&rft.aulast=Ridnour&rft.aufirst=Lisa&rft.date=2004-01-01&rft.volume=385&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Biological+chemistry&rft.issn=14316730&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins in the treatment of cancer. AN - 80173284; 14970517 JF - Methods in molecular biology (Clifton, N.J.) AU - Pastan, Ira AU - Beers, Richard AU - Bera, Tapan K AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 503 EP - 518 VL - 248 SN - 1064-3745, 1064-3745 KW - DNA Primers KW - 0 KW - DNA, Complementary KW - Immunotoxins KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Base Sequence KW - Cell Line, Tumor KW - Recombinant Proteins -- therapeutic use KW - Neoplasms -- drug therapy KW - Immunotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80173284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+immunotoxins+in+the+treatment+of+cancer.&rft.au=Pastan%2C+Ira%3BBeers%2C+Richard%3BBera%2C+Tapan+K&rft.aulast=Pastan&rft.aufirst=Ira&rft.date=2004-01-01&rft.volume=248&rft.issue=&rft.spage=503&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 - 2004-03-29 N1 - Date created - 2004-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Psychiatric comorbidity and not completing jail-based substance abuse treatment. AN - 80142770; 14766441 AB - Many jail inmates have a history of mental illness, substance use, and drug-related crime. This article assesses the effect of psychiatric comorbidity on retention in jail-based substance abuse treatment. Secondary data from five jail-based substance abuse treatment programs were studied using descriptive and multivariate analyses. Controlling for age, sex, race, education, and program, the odds of an offender with a history of mental illness being terminated from treatment were nearly three times that of those with no such history. The data suggest that psychiatric comorbidity may be an important correlate of retention in jail-based substance abuse treatment. JF - The American journal on addictions AU - Brady, Thomas M AU - Krebs, Christopher P AU - Laird, Glen AD - The Substance Abuse and Mental Health Services Administration/NIMH/NIH, Office of Applied Studies, 5600 Fishers Lane, Room 16-105, Rockville, MD 20857, USA. tbrady@samhsa.gov PY - 2004 SP - 83 EP - 101 VL - 13 IS - 1 SN - 1055-0496, 1055-0496 KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Retrospective Studies KW - Male KW - Female KW - Comorbidity KW - Multivariate Analysis KW - Substance-Related Disorders -- therapy KW - Patient Compliance KW - Mental Disorders KW - Prisoners -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80142770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+on+addictions&rft.atitle=Psychiatric+comorbidity+and+not+completing+jail-based+substance+abuse+treatment.&rft.au=Brady%2C+Thomas+M%3BKrebs%2C+Christopher+P%3BLaird%2C+Glen&rft.aulast=Brady&rft.aufirst=Thomas&rft.date=2004-01-01&rft.volume=13&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=The+American+journal+on+addictions&rft.issn=10550496&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-22 N1 - Date created - 2004-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence. AN - 80130486; 14749690 AB - Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P =.0135 for 8 mg and P <.001 for 16 mg) or benzoylecgonine concentrations (P =.0277 for 8 mg and P =.006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events. A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use. JF - Clinical pharmacology and therapeutics AU - Montoya, Ivan D AU - Gorelick, David A AU - Preston, Kenzie L AU - Schroeder, Jennifer R AU - Umbricht, Annie AU - Cheskin, Lawrence J AU - Lange, W Robert AU - Contoreggi, Carlo AU - Johnson, Rolley E AU - Fudala, Paul J AD - Division of Treatment Research and Development and Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 34 EP - 48 VL - 75 IS - 1 SN - 0009-9236, 0009-9236 KW - Narcotic Antagonists KW - 0 KW - Buprenorphine KW - 40D3SCR4GZ KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Double-Blind Method KW - Patient Compliance KW - Humans KW - Adult KW - Treatment Outcome KW - Administration, Sublingual KW - Male KW - Female KW - Narcotic Antagonists -- administration & dosage KW - Buprenorphine -- therapeutic use KW - Narcotic Antagonists -- therapeutic use KW - Opioid-Related Disorders -- complications KW - Cocaine-Related Disorders -- drug therapy KW - Buprenorphine -- administration & dosage KW - Opioid-Related Disorders -- urine KW - Opioid-Related Disorders -- drug therapy KW - Cocaine-Related Disorders -- complications KW - Cocaine-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80130486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology+and+therapeutics&rft.atitle=Randomized+trial+of+buprenorphine+for+treatment+of+concurrent+opiate+and+cocaine+dependence.&rft.au=Montoya%2C+Ivan+D%3BGorelick%2C+David+A%3BPreston%2C+Kenzie+L%3BSchroeder%2C+Jennifer+R%3BUmbricht%2C+Annie%3BCheskin%2C+Lawrence+J%3BLange%2C+W+Robert%3BContoreggi%2C+Carlo%3BJohnson%2C+Rolley+E%3BFudala%2C+Paul+J&rft.aulast=Montoya&rft.aufirst=Ivan&rft.date=2004-01-01&rft.volume=75&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=00099236&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-12 N1 - Date created - 2004-01-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Drug Alcohol Depend. 2001 Mar 1;62(1):97-104 [11173173] J Biopharm Stat. 2001 Feb-May;11(1-2):9-21 [11459446] Int J Epidemiol. 2001 Dec;30(6):1332-41 [11821342] Addiction. 2003 Jan;98(1):7-22 [12492751] Arch Gen Psychiatry. 1999 Sep;56(9):812-20 [12884887] Br J Addict Alcohol Other Drugs. 1971 Nov;66(3):195-204 [5289286] Int J Addict. 1973;8(1):49-57 [4713704] Br J Soc Clin Psychol. 1977 Nov;16(4):347-56 [588890] J Nerv Ment Dis. 1980 Jan;168(1):26-33 [7351540] Psychol Med. 1982 Nov;12(4):855-70 [7156256] Am J Drug Alcohol Abuse. 1985;11(3-4):171-91 [4091157] Life Sci. 1989;44(13):887-92 [2927249] Science. 1989 Aug 25;245(4920):859-62 [2772637] Biol Psychiatry. 1989 Oct;26(6):637-9 [2790101] Int J Addict. 1990-1991;25(11A):1295-315 [2132715] J Pharmacol Exp Ther. 1992 Mar;260(3):1185-93 [1545386] JAMA. 1992 May 27;267(20):2750-5 [1578593] Drug Alcohol Depend. 2000 Jul 1;60(1):51-4 [10821989] Drug Alcohol Depend. 2000 Jun 1;59(3):223-33 [10812283] Drug Alcohol Depend. 2000 Feb 1;58(1-2):143-52 [10669065] JAMA. 2001 Jan 3;285(1):45 [11150107] Mt Sinai J Med. 2001 Jan;68(1):62-74 [11135508] N Engl J Med. 2000 Nov 2;343(18):1290-7 [11058673] Psychopharmacology (Berl). 1992;106(4):439-46 [1579619] J Clin Pharmacol. 1999 Jun;39(6):619-23 [10354966] Am J Med. 1998 Aug;105(2):100-5 [9727815] Drug Alcohol Depend. 1999 Aug 2;56(1):55-60 [10462093] Drug Alcohol Depend. 1999 Jun 1;55(1-2):157-63 [10402160] Neuropsychopharmacology. 1992 Sep;7(2):157-62 [1329800] J Nerv Ment Dis. 1993 Jun;181(6):358-64 [8501457] Biol Psychiatry. 1993 Jul 1-15;34(1-2):66-74 [8373940] J Clin Psychopharmacol. 1993 Aug;13(4):243-50 [8376611] Am J Psychiatry. 1993 Nov;150(11):1755 [8214197] J Pharmacol Exp Ther. 1995 Feb;272(2):505-10 [7853163] Psychopharmacology (Berl). 1994 Dec;116(4):401-6 [7701040] Biol Psychiatry. 1995 Jul 15;38(2):135-6 [7578651] Clin Pharmacol Ther. 1996 Jul;60(1):105-14 [8689806] Drug Alcohol Depend. 1995 Nov;40(1):27-35 [8746921] J Pharmacol Exp Ther. 1996 Sep;278(3):1153-64 [8819498] Biol Psychiatry. 1996 Oct 1;40(7):617-28 [8886295] J Consult Clin Psychol. 1997 Apr;65(2):252-61 [9086688] Drug Alcohol Depend. 1997 Apr 14;45(1-2):81-91 [9179510] Addiction. 1997 Mar;92(3):297-302 [9219391] Arch Gen Psychiatry. 1997 Aug;54(8):713-20 [9283506] Psychopharmacology (Berl). 1998 Apr;136(3):217-25 [9566806] J Pharmacol Exp Ther. 1998 May;285(2):444-56 [9580582] Addiction. 1998 Apr;93(4):475-86 [9684386] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. AN - 80128724; 14752837 AB - Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there is no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolic syndrome in which insulin resistance plays a central role. This prospective study evaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteen nondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mg daily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liver biopsies were performed before and at the end of treatment. By 48 weeks, serum alanine aminotransferase values fell to normal in 72% of patients. Hepatic fat content and size as determined by magnetic resonance imaging decreased, and glucose and free fatty acid sensitivity to insulin were uniformly improved. Histological features of steatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis were significantly improved from baseline (all P < 0.05). Using strict criteria, histological improvement occurred in two-thirds of patients. Pioglitazone was well tolerated; the main side effects were weight gain (averaging 4%) and an increase in total body adiposity. In conclusion, these results indicate that treatment with an insulin-sensitizing agent can lead to improvement in biochemical and histological features of NASH and support the role of insulin resistance in the pathogenesis of this disease. The long-term safety and benefits of pioglitazone require further study. JF - Hepatology (Baltimore, Md.) AU - Promrat, Kittichai AU - Lutchman, Glen AU - Uwaifo, Gabriel I AU - Freedman, Renee J AU - Soza, Alejandro AU - Heller, Theo AU - Doo, Edward AU - Ghany, Marc AU - Premkumar, Ahalya AU - Park, Yoon AU - Liang, T Jake AU - Yanovski, Jack A AU - Kleiner, David E AU - Hoofnagle, Jay H AD - Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 188 EP - 196 VL - 39 IS - 1 SN - 0270-9139, 0270-9139 KW - Hypoglycemic Agents KW - 0 KW - Thiazolidinediones KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - pioglitazone KW - X4OV71U42S KW - Index Medicus KW - Glucose Tolerance Test KW - Aspartate Aminotransferases -- blood KW - Alanine Transaminase -- blood KW - Prospective Studies KW - Humans KW - Adult KW - Treatment Outcome KW - Pilot Projects KW - Middle Aged KW - Insulin Resistance KW - Male KW - Female KW - Fatty Liver -- drug therapy KW - Hypoglycemic Agents -- administration & dosage KW - Hepatitis -- drug therapy KW - Thiazolidinediones -- adverse effects KW - Hypoglycemic Agents -- adverse effects KW - Thiazolidinediones -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80128724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+pilot+study+of+pioglitazone+treatment+for+nonalcoholic+steatohepatitis.&rft.au=Promrat%2C+Kittichai%3BLutchman%2C+Glen%3BUwaifo%2C+Gabriel+I%3BFreedman%2C+Renee+J%3BSoza%2C+Alejandro%3BHeller%2C+Theo%3BDoo%2C+Edward%3BGhany%2C+Marc%3BPremkumar%2C+Ahalya%3BPark%2C+Yoon%3BLiang%2C+T+Jake%3BYanovski%2C+Jack+A%3BKleiner%2C+David+E%3BHoofnagle%2C+Jay+H&rft.aulast=Promrat&rft.aufirst=Kittichai&rft.date=2004-01-01&rft.volume=39&rft.issue=1&rft.spage=188&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 - 2004-03-04 N1 - Date created - 2004-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversal of liver fibrosis in aryl hydrocarbon receptor null mice by dietary vitamin A depletion. AN - 80127885; 14752834 AB - Aryl hydrocarbon receptor (AHR)-null mice display a liver fibrosis phenotype that is associated with a concomitant increase in liver retinoid concentration, tissue transglutaminase type II (TGaseII) activity, transforming growth factor beta (TGF beta) overexpression, and accumulation of collagen. To test the hypothesis that this phenotype might be triggered by the observed increase in liver retinoid content, we induced the condition of retinoid depletion by feeding AHR-null mice a vitamin A- deficient diet with the purpose to reverse the phenotype. Liver retinoid content decreased sharply within the first few weeks on the retinoid-deficient diet. Analysis of TGF beta 1, TGF beta 2, and TGF beta 3 expression revealed a reduction to control levels in the AHR -/- mice accompanied by parallel changes in TGaseII protein levels. In addition, we observed an increase in the TGF beta receptors, TGF beta RI and TGF beta RII, as well as in Smad4, and their reduction to wild-type mouse liver levels in AHR -/- mice fed the retinoid-deficient diet. Reduction of peroxisomal proliferator-activated receptor gamma (PPAR gamma) messenger RNA (mRNA) and protein levels in AHR -/- mice was consistent with the presence of hepatic stellate cell (HSC) activation and liver fibrosis. Vitamin A deficiency normalized PPAR gamma expression in AHR -/- mice. In conclusion, livers from AHR -/- mice fed the vitamin A-deficient diet showed a decrease in collagen deposition, consistent with the absence of liver fibrosis. JF - Hepatology (Baltimore, Md.) AU - Andreola, Fausto AU - Calvisi, Diego F AU - Elizondo, Guillermo AU - Jakowlew, Sonia B AU - Mariano, Jennifer AU - Gonzalez, Frank J AU - De Luca, Luigi M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 157 EP - 166 VL - 39 IS - 1 SN - 0270-9139, 0270-9139 KW - DNA-Binding Proteins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Transforming Growth Factor beta KW - Smad4 Protein KW - Smad4 protein, mouse KW - Tgfb1 protein, mouse KW - Tgfb3 protein, mouse KW - Trans-Activators KW - Transcription Factors KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Transforming Growth Factor beta2 KW - Transforming Growth Factor beta3 KW - Vitamin A KW - 11103-57-4 KW - Collagen KW - 9007-34-5 KW - transglutaminase 2 KW - EC 2.3.2.- KW - Transglutaminases KW - EC 2.3.2.13 KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Activin Receptors, Type I KW - EC 2.7.11.30 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Collagen -- metabolism KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Liver -- metabolism KW - Mice KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Transcription Factors -- genetics KW - Phenotype KW - Mice, Mutant Strains KW - Transglutaminases -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Mice, Inbred C57BL KW - Activin Receptors, Type I -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Vitamin A Deficiency -- metabolism KW - Liver Cirrhosis -- diet therapy KW - Vitamin A Deficiency -- physiopathology KW - Vitamin A -- pharmacology KW - Liver Cirrhosis -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Liver Cirrhosis -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80127885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reversal+of+liver+fibrosis+in+aryl+hydrocarbon+receptor+null+mice+by+dietary+vitamin+A+depletion.&rft.au=Andreola%2C+Fausto%3BCalvisi%2C+Diego+F%3BElizondo%2C+Guillermo%3BJakowlew%2C+Sonia+B%3BMariano%2C+Jennifer%3BGonzalez%2C+Frank+J%3BDe+Luca%2C+Luigi+M&rft.aulast=Andreola&rft.aufirst=Fausto&rft.date=2004-01-01&rft.volume=39&rft.issue=1&rft.spage=157&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 - 2004-03-04 N1 - Date created - 2004-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Implementing a research agenda for complementary and alternative medicine. AN - 80125115; 14746520 AB - Complementary and alternative medicine (CAM) consists of diverse clinical interventions that are practiced because of their popularity rather than the prior demonstration of safety and efficacy required for conventional agents. CAM therapies can be grouped into five categories: biologically based therapies, manipulative and body-based interventions, mind-body interventions, "energy" therapies, and alternative medical systems. The present evidence that individual CAM interventions are efficacious is largely anecdotal, but hundreds of small trials have yielded positive results. For a few modalities, existing data are either very encouraging or else sufficient to conclude that they are ineffective. CAM interventions are presumed to be safe, yet they may not be, particularly in the case of botanical agents with inherent toxicities, significant drug interactions, or potent adulterants. The public health questions regarding CAM can only be addressed through a research agenda that defines which interventions have favorable therapeutic indices. Implementation of this agenda involves adequate characterization and standardization of the product or practice, with rigorous investigation to demonstrate its safety, mechanism of action, and efficacy. JF - Annual review of medicine AU - Berman, Jonathan D AU - Straus, Stephen E AD - National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA. Bermanjo@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 239 EP - 254 VL - 55 SN - 0066-4219, 0066-4219 KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Complementary Therapies KW - Biomedical Research UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80125115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Implementing+a+research+agenda+for+complementary+and+alternative+medicine.&rft.au=Berman%2C+Jonathan+D%3BStraus%2C+Stephen+E&rft.aulast=Berman&rft.aufirst=Jonathan&rft.date=2004-01-01&rft.volume=55&rft.issue=&rft.spage=239&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 - 2004-05-25 N1 - Date created - 2004-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cholinergic modulation of visual attention and working memory: dissociable effects of basal forebrain 192-IgG-saporin lesions and intraprefrontal infusions of scopolamine. AN - 80120848; 14747520 AB - Two experiments examined the effects of reductions in cortical cholinergic function on performance of a novel task that allowed for the simultaneous assessment of attention to a visual stimulus and memory for that stimulus over a variable delay within the same test session. In the first experiment, infusions of the muscarinic receptor antagonist scopolamine into the medial prefrontal cortex (mPFC) produced many omissions but did not impair rats' ability to correctly detect a brief visual stimulus. However, these animals were highly impaired in remembering the location of that stimulus following a delay period, although in a delay-independent manner. In the second experiment, another group of animals with selective 192 IgG-saporin lesions of the nucleus basalis magnocellularis (nBM) were not impaired under conditions of low-attentional demand. However, when the stimulus duration was reduced, a significant memory impairment was observed, but similar to the results of the first experiment, the nBM-lesioned animals were not impaired in attentional accuracy, although aspects of attention were compromised (e.g., omissions). These findings demonstrate that (1) cortical cholinergic depletion produces dissociable deficits in attention and memory, depending on the task demands, (2) delay-independent mnemonic deficits produced by scopolamine are probably due to impairments other than simple inattention, and (3) working memory deficits are not simply dependent on attentional difficulties per se. Together, these findings implicate the nBM cortical cholinergic system in both attentional and mnemonic processing. JF - Learning & memory (Cold Spring Harbor, N.Y.) AU - Chudasama, Yogita AU - Dalley, Jeffrey W AU - Nathwani, Falguni AU - Bouger, Pascale AU - Robbins, Trevor W AU - Nathwani, Falgyni AD - Cambridge University, Department of Experimental Psychology, Cambridge CB2 3EB, UK. Yogita@ln.nimh.nih.gov PY - 2004 SP - 78 EP - 86 VL - 11 IS - 1 SN - 1072-0502, 1072-0502 KW - 192 IgG-saporin KW - 0 KW - Adjuvants, Anesthesia KW - Antibodies, Monoclonal KW - Cholinergic Agents KW - Immunotoxins KW - Ribosome Inactivating Proteins, Type 1 KW - Scopolamine Hydrobromide KW - 451IFR0GXB KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Animals KW - Scopolamine Hydrobromide -- pharmacology KW - Memory -- physiology KW - Antibodies, Monoclonal -- pharmacology KW - Rats KW - Rats, Inbred Strains KW - Adjuvants, Anesthesia -- pharmacology KW - Cholinergic Agents -- pharmacology KW - Immunotoxins -- pharmacology KW - Basal Nucleus of Meynert -- physiology KW - Male KW - Visual Perception -- physiology KW - Acetylcholine -- physiology KW - Prosencephalon -- drug effects KW - Prefrontal Cortex -- physiology KW - Attention -- physiology KW - Prosencephalon -- physiology KW - Memory, Short-Term -- physiology KW - Attention -- drug effects KW - Prefrontal Cortex -- drug effects KW - Memory, Short-Term -- drug effects KW - Visual Perception -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80120848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Learning+%26+memory+%28Cold+Spring+Harbor%2C+N.Y.%29&rft.atitle=Cholinergic+modulation+of+visual+attention+and+working+memory%3A+dissociable+effects+of+basal+forebrain+192-IgG-saporin+lesions+and+intraprefrontal+infusions+of+scopolamine.&rft.au=Chudasama%2C+Yogita%3BDalley%2C+Jeffrey+W%3BNathwani%2C+Falguni%3BBouger%2C+Pascale%3BRobbins%2C+Trevor+W%3BNathwani%2C+Falgyni&rft.aulast=Chudasama&rft.aufirst=Yogita&rft.date=2004-01-01&rft.volume=11&rft.issue=1&rft.spage=78&rft.isbn=&rft.btitle=&rft.title=Learning+%26+memory+%28Cold+Spring+Harbor%2C+N.Y.%29&rft.issn=10720502&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-30 N1 - Date created - 2004-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Learn Mem. 2002 Jul-Aug;9(4):191-201 [12177232] J Consult Psychol. 1956 Oct;20(5):343-50 [13367264] Psychopharmacology (Berl). 2002 Oct;164(1):71-81 [12373421] Cereb Cortex. 2002 Dec;12(12):1254-68 [12427677] Behav Brain Res. 2003 Nov 30;146(1-2):105-19 [14643464] Arch Neurol. 1974 Feb;30(2):113-21 [4359364] Lancet. 1977 Jan 22;1(8004):189 [64712] Psychopharmacology (Berl). 1977 May 9;52(3):283-9 [406632] Br Med J. 1978 Nov 25;2(6150):1457-9 [719462] Br J Clin Pharmacol. 1979 May;7(5):479-83 [475944] Science. 1982 Mar 5;215(4537):1237-9 [7058341] Science. 1982 Jul 30;217(4558):408-14 [7046051] J Comp Neurol. 1983 Feb 20;214(2):170-97 [6841683] J Neurol Sci. 1983 May;59(2):277-89 [6854353] Neuropsychobiology. 1983;9(2-3):154-7 [6621852] Behav Brain Res. 1983 Sep;9(3):361-80 [6639741] Neuroscience. 1983 Dec;10(4):1185-201 [6320048] J Comp Neurol. 1984 Jan 20;222(3):313-42 [6699210] Psychopharmacology (Berl). 1984;82(3):147-50 [6425892] Ann N Y Acad Sci. 1985;444:359-69 [2990294] Pharmacol Biochem Behav. 1985 Jul;23(1):125-35 [4041042] Brain Res. 1987 Jun 16;413(2):229-50 [3300852] Neuropsychologia. 1988;26(5):685-700 [3211287] Trends Neurosci. 1988 Jun;11(6):264-7 [2465623] Behav Brain Res. 1989 Dec 1;35(3):221-40 [2688683] Neuropsychologia. 1990;28(11):1197-213 [2290494] Trends Neurosci. 1991 Jun;14(6):220-3 [1716012] Neuroreport. 1990 Sep;1(1):61-4 [2129859] Trends Neurosci. 1991 Nov;14(11):494-501 [1726766] J Neurosci. 1994 Oct;14(10):5986-95 [7523630] Behav Neurosci. 1994 Oct;108(5):883-91 [7826511] Neuroscience. 1994 Nov;63(1):95-122 [7898665] J Neurosci Res. 1995 Jan 1;40(1):31-43 [7714924] Psychopharmacology (Berl). 1995 May;119(2):139-44 [7659760] Behav Neurosci. 1995 Aug;109(4):714-22 [7576215] J Neurosci. 1995 Nov;15(11):7315-22 [7472485] Behav Neurosci. 1996 Apr;110(2):247-65 [8731052] Cereb Cortex. 1996 May-Jun;6(3):470-81 [8670672] Brain Res Cogn Brain Res. 1996 Jun;3(3-4):215-25 [8806024] Prog Brain Res. 1996;109:253-64 [9009714] Annu Rev Psychol. 1997;48:649-84 [9046571] Neurobiol Learn Mem. 1997 Mar;67(2):85-95 [9075237] Neurobiol Learn Mem. 1997 May;67(3):214-27 [9159760] Psychopharmacology (Berl). 1997 Nov;134(1):73-82 [9399369] Psychopharmacology (Berl). 1997 Nov;134(1):95-106 [9399372] Brain Res Cogn Brain Res. 1997 Oct;6(2):147-58 [9450608] Behav Neurosci. 1998 Apr;112(2):293-303 [9588479] Ann N Y Acad Sci. 1998 Jun 21;846:222-37 [9668410] Psychopharmacology (Berl). 2002 Oct;163(3-4):362-80 [12373437] Neuroreport. 1999 Sep 29;10(14):3119-23 [10549833] Behav Neurosci. 1999 Oct;113(5):941-55 [10571477] Br J Ind Med. 1962 Oct;19:287-95 [14022450] Eur J Neurosci. 2000 Dec;12(12):4457-66 [11122356] Brain Res Cogn Brain Res. 2001 Dec;12(3):353-70 [11689296] J Neurosci. 2002 Mar 1;22(5):1905-13 [11880520] Neuroscience. 2002;111(4):815-35 [12031406] Neuropharmacology. 1998 Apr-May;37(4-5):481-7 [9704989] Trends Neurosci. 1999 Feb;22(2):67-74 [10092046] Neurobiol Learn Mem. 1999 May;71(3):325-52 [10196110] Curr Opin Neurobiol. 1999 Apr;9(2):178-83 [10322180] Erratum In: Learn Mem. 2004 Mar-Apr;11(2):227 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Secretory granule biogenesis and neuropeptide sorting to the regulated secretory pathway in neuroendocrine cells. AN - 80118314; 14742911 AB - Neuropeptide precursors synthesized at the rough endoplasmic reticulum are transported and sorted at the trans-Golgi network (TGN) to the granules of the regulated secretory pathway (RSP) of neuroendocrine cells. They are then processed into active peptides and stored in large dense-core granules (LDCGs) until secreted upon stimulation. We have studied the regulation of biogenesis of the LDCGs and the mechanism by which neuropeptide precursors, such as pro-opiomelanocortin (POMC), are sorted into these LDCGs of the RSP in neuroendocrine and endocrine cells. We provide evidence that chromogranin A (CgA), one of the most abundant acidic glycoproteins ubiquitously present in neuroendocrine/endocrine cells, plays an important role in the regulation of LDCG biogenesis. Specific depletion of CgA expression by antisense RNAs in PC12 cells led to a profound loss of secretory granule formation. Exogenously expressed POMC was neither stored nor secreted in a regulated manner in these CgA-deficient PC12 cells. Overexpression of CgA in a CgA- and LDCG-deficient endocrine cell line, 6T3, restored regulated secretion of transfected POMC and the presence of immunoreactive CgA at the tips of the processes of these cells. Unlike CgA, CgB, another granin protein, could not substitute for the role of CgA in regulating LDCG biogenesis. Thus, we conclude that CgA is a key player in the regulation of the biogenesis of LDCGs in neuroendocrine cells. To examine the mechanism of sorting POMC to the LDCGs, we carried out site-directed mutagenesis, transfected the POMC mutants into PC12 cells, and assayed for regulated secretion. Our previous molecular modeling studies predicted a three-dimensional sorting motif in POMC that can bind to a sorting receptor, membrane carboxypeptidase E (CPE). The sorting signal consists of four conserved residues at the N-terminal loop structure of POMC: two acidic residues and two hydrophobic residues. The two acidic residues were predicted to bind to a domain on CPE (CPE254-273) containing two basic residues (R255 and K260) to effect sorting into immature secretory granules. Site-directed mutagenesis of the motif on POMC resulted in accumulation of the mutant in the Golgi, as well as high basal secretion, indicating that the mutant POMC was inefficiently sorted to the RSP. These results support the model that POMC is actively sorted to the RSP granules for processing and secretion by a sorting signal-mediated mechanism. JF - Journal of molecular neuroscience : MN AU - Loh, Y Peng AU - Kim, Taeyoon AU - Rodriguez, Yazmin M AU - Cawley, Niamh X AD - Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. lohp@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 63 EP - 71 VL - 22 IS - 1-2 SN - 0895-8696, 0895-8696 KW - Chromogranin A KW - 0 KW - Chromogranins KW - Neuropeptides KW - Pro-Opiomelanocortin KW - 66796-54-1 KW - Index Medicus KW - Animals KW - Models, Molecular KW - Mutagenesis, Site-Directed -- genetics KW - Amino Acid Sequence -- genetics KW - Pro-Opiomelanocortin -- genetics KW - Chromogranins -- metabolism KW - Pro-Opiomelanocortin -- metabolism KW - Rats KW - Protein Structure, Tertiary -- genetics KW - Signal Transduction -- genetics KW - Mutation -- genetics KW - Microscopy, Electron KW - Binding Sites -- genetics KW - PC12 Cells KW - Neurosecretory Systems -- metabolism KW - Neuropeptides -- metabolism KW - Secretory Vesicles -- ultrastructure KW - Secretory Vesicles -- secretion KW - Secretory Vesicles -- metabolism KW - Neurosecretion -- physiology KW - Neurosecretory Systems -- cytology KW - Neuropeptides -- secretion KW - Protein Transport -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80118314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroscience+%3A+MN&rft.atitle=Secretory+granule+biogenesis+and+neuropeptide+sorting+to+the+regulated+secretory+pathway+in+neuroendocrine+cells.&rft.au=Loh%2C+Y+Peng%3BKim%2C+Taeyoon%3BRodriguez%2C+Yazmin+M%3BCawley%2C+Niamh+X&rft.aulast=Loh&rft.aufirst=Y&rft.date=2004-01-01&rft.volume=22&rft.issue=1-2&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+neuroscience+%3A+MN&rft.issn=08958696&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-12 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RNase H2 of Saccharomyces cerevisiae is a complex of three proteins. AN - 80113559; 14734815 AB - The composition of RNase H2 has been a long-standing problem. Whereas bacterial and archaeal RNases H2 are active as single polypeptides, the Saccharomyces cerevisiae homolog, Rnh2Ap, when expressed in Escherichia coli, fails to produce an active RNase H2. By affinity chromatography purification and identification of polypeptides associated with a tagged S.cerevisiae Rnh2Ap, we obtained a complex of three proteins [Rnh2Ap (Rnh201p), Ydr279p (Rnh202p) and Ylr154p (Rnh203p)] that together are necessary and sufficient for RNase H2 activity [correction]. Deletion of the gene encoding any one of the proteins or mutations in the catalytic site in Rnh2A led to loss of RNase H2 activity. Even when S.cerevisiae RNase H2 is catalytically compromised, it still exhibits a preference for cleavage of the phosphodiester bond on the 5' side of a ribonucleotide-deoxyribonucleotide sequence in substrates mimicking RNA-primed Okazaki fragments or a single ribonucleotide embedded in a duplex DNA. Interestingly, Ydr279p and Ylr154p have homologous proteins only in closely related species. The multisubunit nature of S.cerevisiae RNase H2 may be important both for structural purposes and to provide a means of interacting with other proteins involved in DNA replication/repair and transcription. JF - Nucleic acids research AU - Jeong, Ho-Sang AU - Backlund, Peter S AU - Chen, Hao-Chia AU - Karavanov, Alexander A AU - Crouch, Robert J AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2790, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 407 EP - 414 VL - 32 IS - 2 KW - Peptides KW - 0 KW - Protein Subunits KW - Saccharomyces cerevisiae Proteins KW - DNA KW - 9007-49-2 KW - ribonuclease HII KW - EC 3.1.26.- KW - Ribonuclease H KW - EC 3.1.26.4 KW - ribonuclease HI KW - Index Medicus KW - Mutagenesis, Site-Directed -- genetics KW - DNA -- metabolism KW - Peptides -- metabolism KW - Peptides -- chemistry KW - Substrate Specificity KW - Peptides -- genetics KW - Ultracentrifugation KW - Species Specificity KW - Protein Structure, Quaternary KW - Gene Deletion KW - Catalysis KW - Binding Sites KW - Saccharomyces cerevisiae -- genetics KW - Ribonuclease H -- chemistry KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Protein Subunits -- genetics KW - Saccharomyces cerevisiae Proteins -- genetics KW - Protein Subunits -- isolation & purification KW - Saccharomyces cerevisiae -- enzymology KW - Ribonuclease H -- genetics KW - Saccharomyces cerevisiae Proteins -- chemistry KW - Protein Subunits -- metabolism KW - Ribonuclease H -- metabolism KW - Protein Subunits -- chemistry KW - Ribonuclease H -- isolation & purification KW - Saccharomyces cerevisiae Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80113559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=RNase+H2+of+Saccharomyces+cerevisiae+is+a+complex+of+three+proteins.&rft.au=Jeong%2C+Ho-Sang%3BBacklund%2C+Peter+S%3BChen%2C+Hao-Chia%3BKaravanov%2C+Alexander+A%3BCrouch%2C+Robert+J&rft.aulast=Jeong&rft.aufirst=Ho-Sang&rft.date=2004-01-01&rft.volume=32&rft.issue=2&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-21 N1 - Date created - 2004-01-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 2003 May 15;423(6937):241-54 [12748633] Mol Cell. 2003 Mar;11(3):807-15 [12667461] Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11529-34 [12972632] Nat Genet. 2003 Nov;35(3):277-86 [14566339] J Bacteriol. 1980 Oct;144(1):28-35 [6998952] Proc Natl Acad Sci U S A. 1990 Nov;87(21):8587-91 [2172991] J Biol Chem. 1991 Apr 5;266(10):6472-9 [1706718] Biochimie. 1993;75(1-2):123-6 [8389211] Nucleic Acids Res. 1994 Dec 11;22(24):5247-54 [7816613] Nucleic Acids Res. 1995 Jul 11;23(13):2526-30 [7630731] FEBS Lett. 1998 Jan 2;421(1):23-6 [9462832] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2244-9 [9482870] Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12872-7 [9789007] Biochemistry. 1999 Jan 12;38(2):605-18 [9888800] Science. 2003 Jul 4;301(5629):71-6 [12775844] Mol Cell Biol. 1999 Dec;19(12):8361-71 [10567561] Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1143-7 [10655498] Nucleic Acids Res. 2000 Sep 15;28(18):3674-83 [10982891] Genes Cells. 2000 Oct;5(10):789-802 [11029655] J Mol Biol. 2001 Mar 23;307(2):541-56 [11254381] Protein Sci. 2001 Apr;10(4):707-14 [11274461] Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4569-74 [11283351] Mol Genet Genomics. 2001 Jul;265(5):771-7 [11523794] Biochem Biophys Res Commun. 2001 Sep 7;286(5):1073-81 [11527410] Methods Enzymol. 2001;341:395-413 [11582793] Methods Enzymol. 2001;341:430-40 [11582796] Nature. 2002 Jan 10;415(6868):141-7 [11805826] Nature. 2002 Jan 10;415(6868):180-3 [11805837] J Biol Chem. 2002 Jul 19;277(29):26632-41 [12004053] Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16654-9 [12475934] J Biol Chem. 2003 Jan 17;278(3):1618-25 [12424238] Nat Rev Cancer. 2003 Mar;3(3):169-78 [12612652] Erratum In: Nucleic Acids Res. 2004 Feb 24;32(4):1616 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic damage detected in CD-1 mouse pups exposed perinatally to 3'-azido-3'-deoxythymidine and dideoxyinosine via maternal dosing, nursing, and direct gavage. AN - 80111996; 14743340 AB - Human immunodeficiency virus (HIV)-infected pregnant women are administered nucleoside-analogue antiretrovirals to reduce maternal-infant viral transmission. The current protocol recommends treating newborns for 6 additional weeks postpartum. The treatment is effective, but the risk of drug-induced chromosomal damage in neonates remains undefined. We used a mouse model to investigate this concern. In a multigeneration reproductive toxicity study, female CD-1 mice received 3'-azido-3'-deoxythymidine (AZT) and dideoxyinosine (ddI) (50/250, 75/375, 150/750 mg/kg/day AZT/ddI) by gavage twice daily in equal fractions beginning prior to mating and continuing throughout gestation and lactation. Direct pup dosing (same regimen) began on postnatal day (PND) 4. Peripheral blood erythrocytes of male pups were screened for micronuclei, markers of chromosomal damage, on PNDs 1, 4, 8, and 21. Extraordinary increases in micronucleated cells were noted in pups for each treatment group at each sampling time; treated dams exhibited smaller yet significant increases in micronucleated erythrocytes. The frequencies of micronucleated cells in untreated pups were higher than in the untreated dams, and all pups had markedly elevated levels of circulating reticulocytes compared to dams. These observations suggest that fetal and neonatal mouse hematopoietic precursor cells have heightened sensitivity to genotoxic agents, perhaps due to rapid cell proliferation during the perinatal period of development. The amount of genetic damage observed in treated pups raises concern for the potential of similar damage in humans. Investigations of chromosomal integrity in exposed newborns and children are recommended. Copyright 2004 Wiley-Liss, Inc. JF - Environmental and molecular mutagenesis AU - Bishop, Jack B AU - Witt, Kristine L AU - Tice, Raymond R AU - Wolfe, Gary W AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. bishop@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 3 EP - 9 VL - 43 IS - 1 SN - 0893-6692, 0893-6692 KW - Anti-HIV Agents KW - 0 KW - Mutagens KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - Drug Therapy, Combination KW - Administration, Oral KW - Mice, Inbred Strains KW - Erythrocytes -- drug effects KW - Animals KW - Micronucleus Tests KW - Dose-Response Relationship, Drug KW - Mice KW - Time Factors KW - Male KW - Female KW - Pregnancy KW - Lactation KW - Didanosine -- toxicity KW - Anti-HIV Agents -- toxicity KW - Micronuclei, Chromosome-Defective -- drug effects KW - Zidovudine -- toxicity KW - Mutagens -- toxicity KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80111996?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+damage+detected+in+CD-1+mouse+pups+exposed+perinatally+to+3%27-azido-3%27-deoxythymidine+and+dideoxyinosine+via+maternal+dosing%2C+nursing%2C+and+direct+gavage.&rft.au=Bishop%2C+Jack+B%3BWitt%2C+Kristine+L%3BTice%2C+Raymond+R%3BWolfe%2C+Gary+W&rft.aulast=Bishop&rft.aufirst=Jack&rft.date=2004-01-01&rft.volume=43&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 - 2004-03-22 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pretreatment with rituximab does not inhibit the human immune response against the immunogenic protein LMB-1. AN - 80109442; 14734446 AB - Rituximab, a humanized monoclonal antibody directed to the CD20 antigen present on B lymphocytes, could potentially abrogate the humoral immune response to murine monoclonal antibodies or immunotoxins by depleting antibody-producing B cells. A Phase II study of LMB-1, an immunotoxin targeting the Lewis Y tumor antigen, in combination with rituximab was conducted to test the hypothesis that rituximab could abolish or diminish the development of human antibodies to LMB-1. Five patients were treated in this study and received 375 mg/m(2) rituximab on days 1 and 7 followed by 45 micro g/kg/day LMB-1 on days 10, 12, and 14. The development of human antibodies against LMB-1 was detected using a serum neutralization and ELISA. All five of the patients had a total suppression of circulating CD20/CD19 B-cell population before the administration of the first dose of the immunotoxin. Before rituximab treatment, the mean percentage of CD20/CD19-positive B cells in the five treated patients was 19.8% (range, 4.5-29.8%) of the total peripheral lymphocytes. After two doses of rituximab, CD20/CD19-positive B lymphocytes constituted A transition in chemically induced lung neoplasms in B6C3F1 mice. AN - 80090292; 14713543 AB - Based on long-term toxicity and carcinogenicity studies in B6C3F1 mice conducted by the National Toxicology Program, 2,2-Bis(bromomethyl)-1,3-propanediol (BMP) and tetranitromethane (TNM) have been identified as carcinogens. Following 2 yr of exposure to 312, 625, or 1,250 ppm BMP in feed, or exposure to 0.5 or 2 ppm TNM by inhalation, increased incidences of lung neoplasms were observed in B6C3F1 mice at all exposure concentrations compared to unexposed mice. The present study characterizes genetic alterations in the K-ras protooncogene in BMP- and TNM-induced lung neoplasms, respectively, and compares the findings to spontaneous lung neoplasms from corresponding control mice. The frequencies of the K-ras mutations were 57% (29/51) in BMP-induced lung neoplasms compared to 15% (3/20) in lung neoplasms from dosed feed control mice, and 54% (14/26) in TNM-induced lung neoplasms compared to 60% (3/5) in lung neoplasms from inhalation control mice. G --> A transitions at the second base of the K-ras codon 12 (GGT --> GAT) were the most frequent pattern of K-ras mutations identified in BMP-induced (20/29) and TNM-induced lung neoplasms (13/14), which differed from the mutational patterns identified in the lung neoplasms from unexposed control mice. These results indicate that mutations in the K-ras gene are involved in B6C3F1 lung carcinogenesis following BMP- and TNM-exposure, and the high frequency and specificity of the ras mutation profile in lung neoplasms (G --> A transition) may be due to in vivo genotoxicity by the parent compounds or their metabolites. JF - Toxicologic pathology AU - Ton, Thai-Vu T AU - Hong, Hue-Hua L AU - Anna, Colleen H AU - Dunnick, June K AU - Devereux, Theodora R AU - Sills, Robert C AU - Kim, Yongbaek AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2004 SP - 16 EP - 21 VL - 32 IS - 1 SN - 0192-6233, 0192-6233 KW - Codon KW - 0 KW - Flame Retardants KW - Oxidants KW - Propylene Glycols KW - 2,2-bis(bromomethyl)-1,3-propanediol KW - 3296-90-0 KW - DNA KW - 9007-49-2 KW - Tetranitromethane KW - K1G7CKU98F KW - Index Medicus KW - Animals KW - Codon -- genetics KW - Dose-Response Relationship, Drug KW - DNA Mutational Analysis KW - DNA -- analysis KW - Mice KW - Polymorphism, Single-Stranded Conformational KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Propylene Glycols -- toxicity KW - Oxidants -- toxicity KW - Diet KW - Tetranitromethane -- toxicity KW - Female KW - Flame Retardants -- toxicity KW - Male KW - Genes, ras -- genetics KW - Point Mutation KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Mutation, Missense KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80090292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Predominant+K-ras+codon+12+G+--%26gt%3B+A+transition+in+chemically+induced+lung+neoplasms+in+B6C3F1+mice.&rft.au=Ton%2C+Thai-Vu+T%3BHong%2C+Hue-Hua+L%3BAnna%2C+Colleen+H%3BDunnick%2C+June+K%3BDevereux%2C+Theodora+R%3BSills%2C+Robert+C%3BKim%2C+Yongbaek&rft.aulast=Ton&rft.aufirst=Thai-Vu&rft.date=2004-01-01&rft.volume=32&rft.issue=1&rft.spage=16&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 - 2004-09-28 N1 - Date created - 2004-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Follicular epithelial cell hypertrophy induced by chronic oral administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats. AN - 80087201; 14713547 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) affects the thyroid morphologically and/or functionally in adult animals. Recently, the National Toxicology Program conducted a 2-year gavage study of TCDD in female Harlan Sprague-Dawley rats. The only treatment-related alterations found in thyroid follicles were decreased luminal size and increased height of the follicular epithelial cells, without prominent protrusion into the lumen. The present study elucidated the nature of these follicular lesions. Thyroid glands of 10 rats each from the control, high (100 ng/kg/day)-dose, and stop-study (100 ng/kg/day, 30 weeks; vehicle to study termination) groups in the 2-year study were evaluated microscopically. Twenty randomly selected follicles were measured morphometrically in each animal. TCDD treatment significantly decreased the mean ratio of luminal/epithelial areas and increased the mean sectional epithelial height of the high-dose group compared to controls. Thyroid sections were immunostained with antibody against minichromosome maintenance (MCM) proteins, a novel cell-cycle biomarker. The MCM labeling index of the high-dose group was significantly higher than that of the control; however, the TUNEL labeling index was also higher in the high-dose group than the control. All data from the stop group were comparable to those from controls. These results indicate that the follicular cell response was hypertrophic and reversible. This information should contribute to diagnosis of nonneoplastic thyroid follicular lesions in rats. JF - Toxicologic pathology AU - Tani, Yoshiro AU - Maronpot, Robert R AU - Foley, Julie F AU - Haseman, Joseph K AU - Walker, Nigel J AU - Nyska, Abraham AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. PY - 2004 SP - 41 EP - 49 VL - 32 IS - 1 SN - 0192-6233, 0192-6233 KW - Biomarkers KW - 0 KW - Nuclear Proteins KW - Polychlorinated Dibenzodioxins KW - Minichromosome Maintenance Complex Component 2 KW - EC 3.6.4.12 KW - Index Medicus KW - Administration, Oral KW - Animals KW - Drug Administration Schedule KW - Rats KW - In Situ Nick-End Labeling KW - Rats, Sprague-Dawley KW - Hypertrophy -- pathology KW - Biomarkers -- analysis KW - Hypertrophy -- chemically induced KW - Withholding Treatment KW - Nuclear Proteins -- metabolism KW - Female KW - Immunoenzyme Techniques KW - Epithelial Cells -- drug effects KW - Thyroid Gland -- drug effects KW - Thyroid Gland -- pathology KW - Epithelial Cells -- pathology KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Polychlorinated Dibenzodioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80087201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Follicular+epithelial+cell+hypertrophy+induced+by+chronic+oral+administration+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+in+female+Harlan+Sprague-Dawley+rats.&rft.au=Tani%2C+Yoshiro%3BMaronpot%2C+Robert+R%3BFoley%2C+Julie+F%3BHaseman%2C+Joseph+K%3BWalker%2C+Nigel+J%3BNyska%2C+Abraham&rft.aulast=Tani&rft.aufirst=Yoshiro&rft.date=2004-01-01&rft.volume=32&rft.issue=1&rft.spage=41&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 - 2004-09-28 N1 - Date created - 2004-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abatement of cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban housing: month 12 continuation results. AN - 80086061; 14713915 AB - In the first 6 months of this previously published, randomized trial, the combined intervention of occupant education, insecticide bait application, and professional cleaning significantly reduced cockroach numbers and Bla g 1 allergen levels in inner-city homes. This continuation study investigated whether the cockroach allergen reductions achieved by month 6 could be maintained through month 12 with insecticide application alone. Because we had agreed to place insecticide bait in control homes at the conclusion of the first study, intervention and control homes were treated with insecticide bait at months 6 and 9. No other intervention was conducted in either arm. Vacuumed dust and swab samples were collected at month 12. Twenty-one of the 31 original homes completed the 12-month study. Among the original intervention homes, Bla g 1 concentrations remained essentially unchanged from months 6 to 12. However, among the crossed-over control homes, the geometric mean Bla g 1 concentrations (Units per gram of dust) decreased from 287 to 14.4 for kitchen floors (95% reduction), from 28.8 to 5.6 for living room floors/sofas (81% reduction), from 26.7 to 4.7 for bedroom floors (82% reduction), and from 7.2 to 2.4 for beds (67% reduction). At month 12, Bla g 1 concentrations did not significantly differ between intervention and crossed-over control homes (P >.64 at each location). Similar results were seen for the allergen Bla g 2. Reductions in cockroach allergen concentrations achieved through the combined intervention of occupant education, insecticide application, and professional cleaning can be maintained with continued cockroach control. Surprisingly, and in contrast to other studies, insecticide application alone significantly lowered allergen concentrations in the crossed-over control homes. This unexpected result is being tested further in another randomized trial. JF - The Journal of allergy and clinical immunology AU - Arbes, Samuel J AU - Sever, Michelle AU - Mehta, Jigna AU - Gore, J Chad AU - Schal, Coby AU - Vaughn, Ben AU - Mitchell, Herman AU - Zeldin, Darryl C AD - Division of Intramural Research, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle, NC 27709, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 109 EP - 114 VL - 113 IS - 1 SN - 0091-6749, 0091-6749 KW - Allergens KW - 0 KW - Antigens, Plant KW - Insecticides KW - allergen Bla g 1 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - allergen Bla g 2 KW - Abridged Index Medicus KW - Index Medicus KW - Osmolar Concentration KW - Animals KW - Patient Education as Topic KW - Humans KW - North Carolina KW - Cross-Over Studies KW - Clinical Trials as Topic KW - Follow-Up Studies KW - Poverty Areas KW - Insecticides -- pharmacology KW - Allergens -- immunology KW - Housing KW - Cockroaches -- immunology KW - Aspartic Acid Endopeptidases -- analysis KW - Insect Control -- methods KW - Urban Population KW - Allergens -- analysis KW - Aspartic Acid Endopeptidases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80086061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Abatement+of+cockroach+allergens+%28Bla+g+1+and+Bla+g+2%29+in+low-income%2C+urban+housing%3A+month+12+continuation+results.&rft.au=Arbes%2C+Samuel+J%3BSever%2C+Michelle%3BMehta%2C+Jigna%3BGore%2C+J+Chad%3BSchal%2C+Coby%3BVaughn%2C+Ben%3BMitchell%2C+Herman%3BZeldin%2C+Darryl+C&rft.aulast=Arbes&rft.aufirst=Samuel&rft.date=2004-01-01&rft.volume=113&rft.issue=1&rft.spage=109&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 - 2004-02-17 N1 - Date created - 2004-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses. AN - 80082961; 14706940 AB - Recent anatomical brain magnetic resonance imaging (MRI) studies show a striking postpsychotic progressive loss of cortical gray matter (GM) in patients with childhood-onset schizophrenia (COS), which appears greater than that seen for adult patients. However, the diagnostic specificity and the relationship of these changes to drug treatment and cognitive functioning remain unclear. We performed a comparative prospective brain MRI study in patients with COS and pediatric patients with transient psychosis with behavior problems (psychosis not otherwise specified) provisionally considered multidimensionally impaired (MDI). We hypothesized that cortical GM loss would occur in patients with COS but not in adolescents with atypical psychoses. Anatomical brain MRI was performed at baseline and follow-up in 19 patients in the MDI group (mean [SD] age of 13.3 [3.1] years); in 23 patients with COS matched for age, sex, IQ score, and drug treatment (mean [SD] age of 13.9 [2.5] years); and 38 healthy control subjects matched for age and sex (mean [SD] age of 13.3 [3.1] years). The mean (SD) follow-up was 2.5 (0.8) years. Volumes of the cerebrum and total and regional GM were obtained by using automated analysis, and percent change in volume across time was calculated. One-way analyses of variance with post hoc Tukey Honestly Significantly Different comparisons were performed to examine group differences in the percent change in GM across follow-up. The COS group had significantly greater total, frontal, temporal, and parietal GM loss than did the MDI or healthy control groups; analysis of variance post hoc P values ranged from.03 to.001. The MDI and control groups did not differ significantly from each other. The cortical GM volume loss in COS appears diagnostically specific; it was not seen in children and adolescents with atypical psychosis. Because both patient groups had similar early developmental patterns, cognitive functioning, medications, and hospitalizations, this progressive loss appears to be intrinsic to COS. An ongoing neurodevelopmental process and/or brain response specific to the illness could account for these changes. JF - Archives of general psychiatry AU - Gogtay, Nitin AU - Sporn, Alexandra AU - Clasen, Liv S AU - Nugent, Tom F AU - Greenstein, Deanna AU - Nicolson, Rob AU - Giedd, Jay N AU - Lenane, Marge AU - Gochman, Pete AU - Evans, Alan AU - Rapoport, Judith L AD - Child Psychiatry Branch, National Institute of Mental Health/NIH, Building 10, Room 3N202, 10 Center Drive, MSC 1600, Bethesda, MD 20892-1600, USA. nitin@codon.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 17 EP - 22 VL - 61 IS - 1 SN - 0003-990X, 0003-990X KW - Antimanic Agents KW - 0 KW - Antipsychotic Agents KW - Abridged Index Medicus KW - Index Medicus KW - Reference Values KW - Diagnosis, Differential KW - Humans KW - Antipsychotic Agents -- therapeutic use KW - Antimanic Agents -- adverse effects KW - Disease Progression KW - Child KW - Psychiatric Status Rating Scales KW - Prospective Studies KW - Antimanic Agents -- therapeutic use KW - Atrophy KW - Chronic Disease KW - Follow-Up Studies KW - Adolescent KW - Antipsychotic Agents -- adverse effects KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Image Interpretation, Computer-Assisted KW - Psychotic Disorders -- psychology KW - Cerebral Cortex -- pathology KW - Schizophrenia -- diagnosis KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Psychotic Disorders -- diagnosis KW - Psychotic Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80082961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+progressive+cortical+gray+matter+loss+in+childhood-onset+schizophrenia+with+that+in+childhood-onset+atypical+psychoses.&rft.au=Gogtay%2C+Nitin%3BSporn%2C+Alexandra%3BClasen%2C+Liv+S%3BNugent%2C+Tom+F%3BGreenstein%2C+Deanna%3BNicolson%2C+Rob%3BGiedd%2C+Jay+N%3BLenane%2C+Marge%3BGochman%2C+Pete%3BEvans%2C+Alan%3BRapoport%2C+Judith+L&rft.aulast=Gogtay&rft.aufirst=Nitin&rft.date=2004-01-01&rft.volume=61&rft.issue=1&rft.spage=17&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 - 2004-02-17 N1 - Date created - 2004-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-acetyl transferase genotypes in relation to risk of developing systemic lupus erythematosus. AN - 80082056; 14705222 AB - To examine the association between N-acetyl transferase (NAT) genotype (NAT1 and NAT2) and risk of developing systemic lupus erythematosus (SLE). DNA samples were collected from 243 recently diagnosed cases and 298 controls enrolled in a population based case-control study conducted in 60 counties in North Carolina and South Carolina, USA. There was no association between SLE and NAT1 genotype (OR 0.96, 95% CI 0.65, 1.4 for the presence of a *10 allele) or NAT2 genotype (OR 1.1, 95% CI 0.73, 1.6 for the slow- compared with fast-acetylation genotype). We saw some evidence of interaction between NAT genotypes and use of hair dyes (a source of arylamines), with higher risk seen among hair dye users who had both the *10 NAT1 allele and the NAT2 slow-acetylation genotype (OR 2.9, 95% CI 1.2, 6.9 in this subgroup compared with all others). Our results suggest that although there is little overall association between NAT genotypes and risk of developing SLE, the interaction between NAT1 and NAT2 and specific exposures such as hair dyes may be important. This finding highlights the need to consider exposure when assessing genetic susceptibility. JF - The Journal of rheumatology AU - Cooper, Glinda S AU - Treadwell, Edward L AU - Dooley, Mary Anne AU - St Clair, E William AU - Gilkeson, Gary S AU - Taylor, Jack A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina 27709, USA. cooper1@niehs.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 76 EP - 80 VL - 31 IS - 1 SN - 0315-162X, 0315-162X KW - Hair Dyes KW - 0 KW - Isoenzymes KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - N-acetyltransferase 1 KW - NAT2 protein, human KW - Index Medicus KW - Genotype KW - Risk Factors KW - Humans KW - Adult KW - Genetic Predisposition to Disease -- epidemiology KW - Hair Dyes -- adverse effects KW - Male KW - Female KW - Prevalence KW - Lupus Erythematosus, Systemic -- genetics KW - Lupus Erythematosus, Systemic -- epidemiology KW - Isoenzymes -- genetics KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80082056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=N-acetyl+transferase+genotypes+in+relation+to+risk+of+developing+systemic+lupus+erythematosus.&rft.au=Cooper%2C+Glinda+S%3BTreadwell%2C+Edward+L%3BDooley%2C+Mary+Anne%3BSt+Clair%2C+E+William%3BGilkeson%2C+Gary+S%3BTaylor%2C+Jack+A&rft.aulast=Cooper&rft.aufirst=Glinda&rft.date=2004-01-01&rft.volume=31&rft.issue=1&rft.spage=76&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 - 2004-04-27 N1 - Date created - 2004-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The emerging role of bisphosphonates in prostate cancer. AN - 80078442; 14704597 AB - Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density. It has been shown that the primary mechanism of action is inhibition of osteoclastic activity. Accumulating data show that these drugs are useful in diseases with propensities toward osseous metastases. In particular, they are effective in diseases in which there is clear upregulation of osteoclastic or osteolytic activity such as breast cancer and multiple myeloma. Despite the fact that osseous metastases in prostate cancer manifest as osteosclerosis rather than osteolysis, studies now show that bisphosphonates are useful in the management of this disease. In particular, they have demonstrated an impact on osteoporosis associated with hormonal therapy, bone pain from metastases, and skeleton-related events from prostatic adenocarcinoma. This review briefly summarizes the available clinical data on the utilization of bisphosphonates in the disease of prostate cancer. JF - American journal of therapeutics AU - Posadas, Edwin M AU - Dahut, William L AU - Gulley, James AD - Medical Oncology Clinical Research Unit, Laboratory of Tumor Immunology and Biology, Center for Cancer Research National Cancer Institute, National Institutes of Health, 10 Center Drive, MSC 1750, Building 10, Room 5B52, Bethesda, MD 20892, USA. PY - 2004 SP - 60 EP - 73 VL - 11 IS - 1 SN - 1075-2765, 1075-2765 KW - Diphosphonates KW - 0 KW - Index Medicus KW - Pain -- etiology KW - Animals KW - Randomized Controlled Trials as Topic KW - Pain -- drug therapy KW - Bone Remodeling KW - Breast Neoplasms -- pathology KW - Humans KW - Cohort Studies KW - Disease Progression KW - Osteoporosis -- etiology KW - Osteoporosis -- drug therapy KW - Male KW - Prostatic Neoplasms -- pathology KW - Diphosphonates -- therapeutic use KW - Diphosphonates -- adverse effects KW - Prostatic Neoplasms -- complications KW - Bone Neoplasms -- drug therapy KW - Bone Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80078442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapeutics&rft.atitle=The+emerging+role+of+bisphosphonates+in+prostate+cancer.&rft.au=Posadas%2C+Edwin+M%3BDahut%2C+William+L%3BGulley%2C+James&rft.aulast=Posadas&rft.aufirst=Edwin&rft.date=2004-01-01&rft.volume=11&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=American+journal+of+therapeutics&rft.issn=10752765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-04 N1 - Date created - 2004-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reassessing the molecular biology of sperm-egg recognition with mouse genetics. AN - 80076097; 14696038 AB - The zona pellucida is an extracellular coat that surrounds mammalian eggs and early embryos. This insoluble matrix separates germ from somatic cells during folliculogenesis and plays critical roles during fertilization and early development. The mouse and human zona pellucida contain three glycoproteins (ZP1 or ZPB, ZP2, ZP3), the primary structures of which have been deduced by molecular cloning. Targeted mutagenesis of endogenous mouse genes and transgenesis with human homologues provide models to investigate the roles of individual zona components. Collectively, the genetic data indicate that no single mouse zona pellucida protein is obligatory for taxon-specific sperm binding and that two human proteins are not sufficient to support human sperm binding. An observed post-fertilization persistence of mouse sperm binding to "humanized" zona pellucida correlates with uncleaved ZP2. These observations are consistent with a model for sperm binding in which the supramolecular structure of the zona pellucida necessary for sperm binding is modulated by the cleavage status of ZP2. Copyright 2003 Wiley Periodicals Inc. JF - BioEssays : news and reviews in molecular, cellular and developmental biology AU - Dean, Jurrien AD - Laboratory of Cellular and Developmental Biology, NIDDK, Building 50, Room 3134, National Institutes of Health, 50 South Drive, Bethesda, Maryland 20892, USA. jurrien@helix.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 29 EP - 38 VL - 26 IS - 1 SN - 0265-9247, 0265-9247 KW - Egg Proteins KW - 0 KW - Membrane Glycoproteins KW - Receptors, Cell Surface KW - ZP1 protein, human KW - ZP2 protein, human KW - ZP3 protein, human KW - Zona Pellucida Glycoproteins KW - Zp1 protein, mouse KW - Zp2 protein, mouse KW - Zp3 protein, mouse KW - Index Medicus KW - Animals KW - Egg Proteins -- physiology KW - Membrane Glycoproteins -- physiology KW - Humans KW - Transgenes KW - Mice KW - Models, Biological KW - Zona Pellucida -- physiology KW - Mutagenesis, Site-Directed KW - Spermatozoa -- physiology KW - Zona Pellucida -- pathology KW - Female KW - Male KW - Cricetinae KW - Sperm-Ovum Interactions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80076097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reassessing+the+molecular+biology+of+sperm-egg+recognition+with+mouse+genetics.&rft.au=Dean%2C+Jurrien&rft.aulast=Dean&rft.aufirst=Jurrien&rft.date=2004-01-01&rft.volume=26&rft.issue=1&rft.spage=29&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 - 2004-03-15 N1 - Date created - 2003-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospective pregnancy study designs for assessing reproductive and developmental toxicants. AN - 80071616; 14698935 AB - The determinants of successful human reproduction and development may act as early as periconceptionally, underscoring the need to capture exposures during these critical windows when assessing potential toxicants. To identify such toxicants, couples must be studied longitudinally prior to conception without regard to a couple's ability to ascertain a clinically recognized pregnancy. We examined the utility and feasibility of prospective pregnancy study designs by conducting a systematic review of the literature to summarize relevant information regarding the planning, implementation, and success of previously published prospective pregnancy studies. Information concerning design elements and participation was abstracted from 15 eligible studies (from a total of 20 identified studies) using a standardized form. The primary author of each study was contacted to review our summary of their work and obtain missing information. Our findings confirm the ability to recruit women/couples from diverse populations using a variety of recruitment strategies. Among the studies we reviewed, 4-97% of eligible individuals were successfully contacted, with enrollment rates ranging from 42 to 100%. Length of follow-up varied from 3 to 12 months. A high percentage of women provided urine (57-98%) and blood (86-91%) specimens and most male partners (94-100%) provided semen samples. These data support the feasibility of this design. JF - Environmental health perspectives AU - Buck, Germaine M AU - Lynch, Courtney D AU - Stanford, Joseph B AU - Sweeney, Anne M AU - Schieve, Laura A AU - Rockett, John C AU - Selevan, Sherry G AU - Schrader, Steven M AD - Epidemiology Branch, National Institute of Child Health and Human Development, National Institutes of Health/DHHS, 6100 Executive Boulevard, Rm. 7B03, Rockville, MD 20852, USA. gb156i@nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 79 EP - 86 VL - 112 IS - 1 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Prospective Studies KW - Embryonic and Fetal Development KW - Patient Compliance KW - Humans KW - Adult KW - Reproduction KW - Patient Selection KW - Research Design KW - Female KW - Prenatal Exposure Delayed Effects KW - Environmental Pollutants -- poisoning KW - Pregnancy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80071616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prospective+pregnancy+study+designs+for+assessing+reproductive+and+developmental+toxicants.&rft.au=Buck%2C+Germaine+M%3BLynch%2C+Courtney+D%3BStanford%2C+Joseph+B%3BSweeney%2C+Anne+M%3BSchieve%2C+Laura+A%3BRockett%2C+John+C%3BSelevan%2C+Sherry+G%3BSchrader%2C+Steven+M&rft.aulast=Buck&rft.aufirst=Germaine&rft.date=2004-01-01&rft.volume=112&rft.issue=1&rft.spage=79&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 - 2004-04-22 N1 - Date created - 2003-12-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Fam Plann Perspect. 1999 Sep-Oct;31(5):248-9 [10723651] Lancet. 2002 Sep 7;360(9335):772-7 [12241836] Demography. 2000 Feb;37(1):83-94 [10748991] J Androl. 2000 May-Jun;21(3):478-84 [10819457] Environ Health Perspect. 2000 Jun;108 Suppl 3:451-5 [10852844] Am J Epidemiol. 2000 Oct 1;152(7):609-16 [11032155] Matern Child Health J. 2000 Sep;4(3):155-62 [11097502] Hum Reprod. 2000 Dec;15(12):2478-82 [11098014] Paediatr Perinat Epidemiol. 2001 Jan;15(1):74-87 [11237119] J Occup Med. 1989 Dec;31(12):980-5 [2614538] Am J Epidemiol. 1989 Feb;129(2):415-21 [2643303] Ann Epidemiol. 2001 Apr;11(3):186-93 [11248582] Environ Health Perspect. 1993 Oct;101 Suppl 3:203-6 [8143617] J Psychosom Obstet Gynaecol. 1994 Jun;15(2):67-75 [7921008] Reprod Toxicol. 1995 Jan-Feb;9(1):61-95 [8520133] Am J Ind Med. 1995 Dec;28(6):817-31 [8588566] Hum Reprod. 1996 Feb;11(2):406-12 [8671233] Obstet Gynecol. 2002 Dec;100(6):1333-41 [12468181] Paediatr Perinat Epidemiol. 2003 Jan;17(1):1-2 [12562465] Fertil Steril. 2003 Mar;79(3):577-84 [12620443] Environ Health Perspect. 2004 Jan;112(1):69-78 [14698934] Environ Health Perspect. 2004 Jan;112(1):87-93 [14698936] Acta Obstet Gynecol Scand. 1968;47(1):22-6 [5669831] Obstet Gynecol. 1978 Nov;52(5):575-82 [724176] Lancet. 1980 Sep 13;2(8194):554-6 [6106737] Drug Metab Rev. 1983;14(2):137-68 [6301793] Fertil Steril. 1984 Jun;41(6):894-900 [6586497] Am J Epidemiol. 1988 Apr;127(4):843-50 [3354549] N Engl J Med. 1988 Jul 28;319(4):189-94 [3393170] Int J Epidemiol. 1988 Jun;17(2):378-84 [3403134] Fam Plann Perspect. 1999 Sep-Oct;31(5):246-7, 260 [10723650] Fertil Steril. 1996 Mar;65(3):503-9 [8774277] Am J Epidemiol. 1997 May 1;145(9):810-6 [9143211] Paediatr Perinat Epidemiol. 1997 Jul;11(3):345-58 [9246695] Am J Phys Anthropol. 1997 Sep;104(1):1-21 [9331450] Hum Reprod. 1997 Oct;12(10):2324-9 [9402304] Reprod Toxicol. 1998 Jan-Feb;12(1):19-27 [9431569] AAOHN J. 1998 Jan;46(1):29-40; quiz 41-2 [9481217] Fam Plann Perspect. 1998 Jan-Feb;30(1):4-10, 46 [9494809] Fam Plann Perspect. 1998 Jan-Feb;30(1):24-9, 46 [9494812] Fam Plann Perspect. 1998 Mar-Apr;30(2):79-88 [9561873] J Nurse Midwifery. 1998 Mar-Apr;43(2):117-20 [9581098] Cancer Epidemiol Biomarkers Prev. 1998 Aug;7(8):719-24 [9718225] Am J Obstet Gynecol. 1995 May;172(5):1510-7 [7755065] J Androl. 2000 Jan-Feb;21(1):145-53 [10670528] Am J Epidemiol. 2001 Apr 1;153(7):647-52 [11282791] J Assist Reprod Genet. 2001 Mar;18(3):144-50 [11411429] Fertil Steril. 2001 Aug;76(2):384-7 [11476792] JAMA. 2001 Oct 10;286(14):1759-61 [11594902] Am J Epidemiol. 2001 Nov 15;154(10):883-8 [11700240] Epidemiology. 2002 Jan;13(1):9-20 [11805581] Lancet. 2002 Jan 19;359(9302):248-52 [11812579] Environ Health Perspect. 2002 Apr;110 Suppl 2:149-54 [11929723] Environ Health Perspect. 2002 Apr;110 Suppl 2:195-201 [11929728] Environ Health Perspect. 2002 Apr;110 Suppl 2:277-88 [11929739] Ann Epidemiol. 2002 May;12(4):248-56 [11988413] MMWR Surveill Summ. 2002 Apr 26;51(2):1-27 [12004983] Fertil Steril. 2002 May;77(5):961-6 [12009351] Arch Environ Contam Toxicol. 2002 Jul;43(1):121-6 [12045882] Epidemiology. 2002 May;13 Suppl 3:S15-8 [12071477] Fertil Steril. 2002 Jul;78(1):96-101 [12095497] J Occup Environ Med. 2002 Aug;44(8):708-13 [12185791] Fam Plann Perspect. 1999 Sep-Oct;31(5):249-50 [10723652] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutamate carboxypeptidase II gene expression in the human frontal and temporal lobe in schizophrenia. AN - 80070594; 14560319 AB - There is decreased activity of glutamate carboxypeptidase II (GCP II) in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of patients with schizophrenia. GCP II hydrolzses N-acetyl-alpha L-aspartyl-L-glutamate (NAAG), a peptide in the mammalian brain that binds to the N-methyl D-aspartate (NMDA) receptor and a group II metabotropic glutamate receptor, both of which have been implicated in the pathophysiology of schizophrenia. We examined the expression of GCP II mRNA in the DLPFC, entorhinal cortex (ERC), and hippocampus in postmortem samples from patients with schizophrenia and normal controls using in situ hybridization followed by silver grain detection. GCP II mRNA was detected in glial cells. Glial-rich regions, specifically the DLPFC and ERC white matter and the molecular and polymorphic layers in the hippocampus, express high levels of GCP II mRNA. Given the earlier finding of decreased GCP II activity in brains of subjects with schizophrenia, we expected to find lower GCP II mRNA levels in schizophrenia. Contrary to this expectation, we found a significantly higher expression of GCP II mRNA in one of the brain areas examined, the hippocampal CA3 polymorphic region. This may reflect a compensatory increase to correct for the decreased activity of GCP II activity. Our findings support the notion that the hydrolysis of NAAG is disrupted in schizophrenia and that specific anatomical regions may show discrete abnormalities in GCP II synthesis. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Ghose, Subroto AU - Weickert, Cynthia Shannon AU - Colvin, Sarah M AU - Coyle, Joseph T AU - Herman, Mary M AU - Hyde, Thomas M AU - Kleinman, Joel E AD - Clinical Brain Disorders Branch, IRP, NIMH, NIH, Bethesda, MD 20892, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 117 EP - 125 VL - 29 IS - 1 SN - 0893-133X, 0893-133X KW - Antipsychotic Agents KW - 0 KW - DNA, Complementary KW - Dipeptides KW - Neurotoxins KW - RNA, Messenger KW - isospaglumic acid KW - 1W8M12WXYL KW - Carboxypeptidases KW - EC 3.4.- KW - glutamate carboxypeptidase KW - EC 3.4.17.11 KW - Chlorpromazine KW - U42B7VYA4P KW - Index Medicus KW - Animals KW - Humans KW - Hydrogen-Ion Concentration KW - Gene Expression KW - Aged KW - Autoradiography KW - In Situ Hybridization KW - Dipeptides -- pharmacokinetics KW - Aged, 80 and over KW - Adult KW - Chlorpromazine -- therapeutic use KW - Hippocampus -- enzymology KW - Adolescent KW - Male KW - Neural Networks (Computer) KW - Neuroglia -- enzymology KW - Antipsychotic Agents -- therapeutic use KW - Haplorhini KW - Binding Sites KW - RNA, Messenger -- metabolism KW - Neurotoxins -- pharmacokinetics KW - DNA, Complementary -- metabolism KW - Cohort Studies KW - Hippocampus -- cytology KW - Middle Aged KW - Silver Staining KW - Female KW - Schizophrenia -- enzymology KW - Schizophrenia -- metabolism KW - Carboxypeptidases -- genetics KW - Frontal Lobe -- enzymology KW - Carboxypeptidases -- metabolism KW - Temporal Lobe -- enzymology KW - Schizophrenia -- pathology KW - Schizophrenia -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80070594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glutamate+carboxypeptidase+II+gene+expression+in+the+human+frontal+and+temporal+lobe+in+schizophrenia.&rft.au=Ghose%2C+Subroto%3BWeickert%2C+Cynthia+Shannon%3BColvin%2C+Sarah+M%3BCoyle%2C+Joseph+T%3BHerman%2C+Mary+M%3BHyde%2C+Thomas+M%3BKleinman%2C+Joel+E&rft.aulast=Ghose&rft.aufirst=Subroto&rft.date=2004-01-01&rft.volume=29&rft.issue=1&rft.spage=117&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 - 2004-02-17 N1 - Date created - 2003-12-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of tumors of the liver, lung, ovary and adrenal in adult mice after brief maternal gestational exposure to inorganic arsenic: promotional effects of postnatal phorbol ester exposure on hepatic and pulmonary, but not dermal cancers. AN - 80070328; 14514661 AB - Arsenic is a recognized human carcinogen and development of rodent models remains a critically important research objective. Since gestation can be a period of high sensitivity to chemical carcinogenesis, we have performed a series of transplacental carcinogenicity studies in mice with inorganic arsenic. In this study, groups of pregnant C3H mice received drinking water containing sodium arsenite (NaAsO2) at 0, 42.5 and 85 p.p.m. arsenic ad libitum from days 8 to 18 of gestation. These doses of arsenic were well tolerated. Dams delivered normally and at weaning (4 weeks) offspring were randomly put into groups (n = 25) of males or females according to maternal dose. In an attempt to promote skin cancers initiated by transplacental arsenic, duplicate groups of control or arsenic exposed offspring were topically exposed to 12-O-tetradecanoyl phorbol-13-acetate (TPA; 2 micro g/0.1 ml acetone, twice/week) from 4 to 25 weeks of age. Irrespective of TPA exposure, male offspring showed arsenic-induced dose-related increases in hepatocellular carcinoma incidence and multiplicity, as well as increases in adrenal tumor incidence and multiplicity. In female offspring, an increase in epithelial ovarian tumors occurred with arsenic exposure regardless of TPA exposure. Females also showed pre-neoplastic lesions of the reproductive tract, including hyperplasia of the uterus and oviduct, after arsenic but independent of TPA exposure. Although TPA had no effect on skin tumors, it promoted arsenic initiated liver tumors in females and lung tumors in both sexes. Thus, inorganic arsenic, as a single agent, can consistently act as a complete transplacental carcinogen in mice, inducing tumors at multiple sites, and as a tumor initiator in some tissues. Skin tumors were not initiated by arsenic in mouse fetuses possibly indicating tissue-specific mechanisms of action. This study indicates that gestation is a period of high sensitivity to arsenic carcinogenesis. JF - Carcinogenesis AU - Waalkes, Michael P AU - Ward, Jerrold M AU - Diwan, Bhalchandra A AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. waalkes@niehs.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 133 EP - 141 VL - 25 IS - 1 SN - 0143-3334, 0143-3334 KW - Arsenic KW - N712M78A8G KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Mice, Inbred C3H KW - Organ Specificity KW - Mice KW - Male KW - Female KW - Tetradecanoylphorbol Acetate -- toxicity KW - Fetus -- drug effects KW - Arsenic -- toxicity KW - Skin Neoplasms -- chemically induced KW - Adrenal Gland Neoplasms -- chemically induced KW - Ovarian Neoplasms -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced KW - Lung Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80070328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+tumors+of+the+liver%2C+lung%2C+ovary+and+adrenal+in+adult+mice+after+brief+maternal+gestational+exposure+to+inorganic+arsenic%3A+promotional+effects+of+postnatal+phorbol+ester+exposure+on+hepatic+and+pulmonary%2C+but+not+dermal+cancers.&rft.au=Waalkes%2C+Michael+P%3BWard%2C+Jerrold+M%3BDiwan%2C+Bhalchandra+A&rft.aulast=Waalkes&rft.aufirst=Michael&rft.date=2004-01-01&rft.volume=25&rft.issue=1&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-26 N1 - Date created - 2003-12-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children. AN - 80070040; 14693529 AB - Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m(2); the median administered dose was 208 mg/m(2). Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) was 2,150 ng. h/ml and the geometric mean maximum concentration (C(max)) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng. h/ml and was significantly higher than the AUC(0- infinity ) after the first dose (P = 0.0004). The geometric mean C(max) at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, approximately 3,000 ng. h/ml; C(max), approximately 300 ng/ml) treated with tenofovir DF at 300 mg. JF - Antimicrobial agents and chemotherapy AU - Hazra, Rohan AU - Balis, Frank M AU - Tullio, Antonella N AU - DeCarlo, Ellen AU - Worrell, Carol J AU - Steinberg, Seth M AU - Flaherty, John F AU - Yale, Kitty AU - Poblenz, Marianne AU - Kearney, Brian P AU - Zhong, Lijie AU - Coakley, Dion F AU - Blanche, Stephane AU - Bresson, Jean Louis AU - Zuckerman, Judith A AU - Zeichner, Steven L AD - HIV and AIDS Malignancy Branch, Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 124 EP - 129 VL - 48 IS - 1 SN - 0066-4804, 0066-4804 KW - Anti-HIV Agents KW - 0 KW - Drug Combinations KW - Organophosphonates KW - Organophosphorus Compounds KW - Tenofovir KW - 99YXE507IL KW - Adenine KW - JAC85A2161 KW - Index Medicus KW - Half-Life KW - Area Under Curve KW - Humans KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Anti-HIV Agents -- pharmacokinetics KW - HIV Infections -- metabolism KW - Anti-HIV Agents -- adverse effects KW - Organophosphorus Compounds -- adverse effects KW - Adenine -- pharmacokinetics KW - Adenine -- analogs & derivatives KW - Adenine -- adverse effects KW - Organophosphorus Compounds -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80070040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Single-dose+and+steady-state+pharmacokinetics+of+tenofovir+disoproxil+fumarate+in+human+immunodeficiency+virus-infected+children.&rft.au=Hazra%2C+Rohan%3BBalis%2C+Frank+M%3BTullio%2C+Antonella+N%3BDeCarlo%2C+Ellen%3BWorrell%2C+Carol+J%3BSteinberg%2C+Seth+M%3BFlaherty%2C+John+F%3BYale%2C+Kitty%3BPoblenz%2C+Marianne%3BKearney%2C+Brian+P%3BZhong%2C+Lijie%3BCoakley%2C+Dion+F%3BBlanche%2C+Stephane%3BBresson%2C+Jean+Louis%3BZuckerman%2C+Judith+A%3BZeichner%2C+Steven+L&rft.aulast=Hazra&rft.aufirst=Rohan&rft.date=2004-01-01&rft.volume=48&rft.issue=1&rft.spage=124&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 - 2004-02-20 N1 - Date created - 2003-12-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 1999 Mar;43(3):609-15 [10049275] Antimicrob Agents Chemother. 1993 Feb;37(2):332-8 [8452366] Pediatrics. 1995 Aug;96(2 Pt 1):247-52 [7630678] Science. 1995 Nov 17;270(5239):1197-9 [7502044] J Infect Dis. 1996 Jul;174(1):16-25 [8655986] AIDS Res Hum Retroviruses. 1998 Jun 10;14(9):761-73 [9643376] AIDS. 2002 Jun 14;16(9):1257-63 [12045491] J Infect Dis. 1992 Jan;165(1):99-104 [1727902] JAMA. 2000 Jan 26;283(4):492-8 [10659875] Antimicrob Agents Chemother. 2000 Apr;44(4):1041-6 [10722509] Antimicrob Agents Chemother. 2001 Oct;45(10):2733-9 [11557462] N Engl J Med. 2001 Nov 22;345(21):1522-8 [11794218] AIDS. 2002 Jun 14;16(9):1227-35 [12045487] Antimicrob Agents Chemother. 1998 Sep;42(9):2380-4 [9736567] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro inactivation of the rabies virus by ascorbic acid. AN - 80067542; 14690777 AB - The current recommended inactivating agent for the rabies virus, beta propiolactone (BPL) is very expensive and potentially carcinogenic. There is a need to evaluate alternative chemicals, which will inactivate the virus without affecting its antigenicity. In this study the effect of ascorbic acid on the infectivity of the rabies virus has been investigated. Vero cell grown fixed rabies virus CVS strain was treated with 0.1 mg/ml, 0.5 mg/ml and 1mg/ml final concentrations of ascorbic acid and 5 microg/ml of copper sulfate and kept at 4 degrees C along with untreated virus material. Each aliquot was titrated after various intervals for viral infectivity using both mice inoculation and titration in vero cells. The antigenicity of the virus material was determined by antibody induction in mice and modified NIH tests in parallel with virus material inactivated with a 1:4000 concentration of BPL. An optimal concentration of 0.5 mg/ml of ascorbic acid and 5 microg/ml of copper sulfate completely inactivated the virus after 72 hours. The inactivated virus retained good antigenicity and potency value, which was comparable with using BPL. These findings suggest that ascorbic acid can be used as an inactivating agent for fixed rabies virus grown in cell culture particularly for the preparation of diagnostic reagents. Further studies are required to evaluate its effect on the cell associated virus, probable therapeutic potential and feasibility of replacing BPL in production of inactivated rabies vaccine. JF - International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases AU - Madhusudana, Shampur Narayan AU - Shamsundar, Ranjini AU - Seetharaman, Saraswati AD - Department of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), Post Box 2900, Hosur Road, Bangalore 560029, India. mshampur@hotmail.com Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 21 EP - 25 VL - 8 IS - 1 SN - 1201-9712, 1201-9712 KW - Antibodies, Viral KW - 0 KW - Rabies Vaccines KW - Vaccines, Inactivated KW - Copper Sulfate KW - LRX7AJ16DT KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Animals KW - Rabies -- immunology KW - Biological Assay KW - Mice KW - Rabies -- prevention & control KW - Antibodies, Viral -- blood KW - Vaccines, Inactivated -- immunology KW - Virus Activation -- drug effects KW - Virus Replication -- drug effects KW - Cercopithecus aethiops KW - Copper Sulfate -- pharmacology KW - Vero Cells KW - Virus Replication -- immunology KW - Female KW - Rabies Vaccines -- immunology KW - Rabies virus -- physiology KW - Rabies virus -- immunology KW - Rabies virus -- pathogenicity KW - Rabies virus -- drug effects KW - Ascorbic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80067542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+infectious+diseases+%3A+IJID+%3A+official+publication+of+the+International+Society+for+Infectious+Diseases&rft.atitle=In+vitro+inactivation+of+the+rabies+virus+by+ascorbic+acid.&rft.au=Madhusudana%2C+Shampur+Narayan%3BShamsundar%2C+Ranjini%3BSeetharaman%2C+Saraswati&rft.aulast=Madhusudana&rft.aufirst=Shampur&rft.date=2004-01-01&rft.volume=8&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=International+journal+of+infectious+diseases+%3A+IJID+%3A+official+publication+of+the+International+Society+for+Infectious+Diseases&rft.issn=12019712&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-05 N1 - Date created - 2003-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three novel pigmentation mutants generated by genome-wide random ENU mutagenesis in the mouse. AN - 733664102; 18629060 AB - Three mutant mice with pigmentation phenotypes were recovered from a genomewide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome-wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes. JF - Comparative and functional genomics AU - Tsipouri, Vicky AU - Curtin, John A AU - Nolan, Pat M AU - Vizor, Lucie AU - Parsons, Claire A AU - Clapham, Colin M AU - Latham, Ian D AU - Rooke, Lesley J AU - Martin, Jo E AU - Peters, Jo AU - Hunter, A Jackie AU - Rogers, Derek AU - Rastan, Sohaila AU - Brown, Steve D M AU - Fisher, Elizabeth M C AU - Spurr, Nigel K AU - Gray, Ian C AD - GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Harlow CM19 5AW, UK. vtsip@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 123 EP - 127 VL - 5 IS - 2 SN - 1531-6912, 1531-6912 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/733664102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comparative+and+functional+genomics&rft.atitle=Three+novel+pigmentation+mutants+generated+by+genome-wide+random+ENU+mutagenesis+in+the+mouse.&rft.au=Tsipouri%2C+Vicky%3BCurtin%2C+John+A%3BNolan%2C+Pat+M%3BVizor%2C+Lucie%3BParsons%2C+Claire+A%3BClapham%2C+Colin+M%3BLatham%2C+Ian+D%3BRooke%2C+Lesley+J%3BMartin%2C+Jo+E%3BPeters%2C+Jo%3BHunter%2C+A+Jackie%3BRogers%2C+Derek%3BRastan%2C+Sohaila%3BBrown%2C+Steve+D+M%3BFisher%2C+Elizabeth+M+C%3BSpurr%2C+Nigel+K%3BGray%2C+Ian+C&rft.aulast=Tsipouri&rft.aufirst=Vicky&rft.date=2004-01-01&rft.volume=5&rft.issue=2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Comparative+and+functional+genomics&rft.issn=15316912&rft_id=info:doi/10.1002%2Fcfg.382 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2011-07-14 N1 - Date created - 2008-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Hum Mol Genet. 2000 Jul 22;9(12):1865-71 [10915775] Nat Genet. 2000 Aug;25(4):440-3 [10932191] Am J Med Genet. 2000 Winter;97(4):280-8 [11376439] Curr Opin Genet Dev. 2001 Jun;11(3):268-73 [11377962] Nature. 2001 Oct 25;413(6858):856-60 [11677610] Annu Rev Genomics Hum Genet. 2001;2:463-92 [11701658] J Dermatol Sci. 2002 Jan;28(1):1-33 [11916127] Trends Neurosci. 2003 Jan;26(1):40-5 [12495862] Semin Cell Dev Biol. 2003 Feb;14(1):19-24 [12524003] Genes Dev. 2003 Jan 15;17(2):214-28 [12533510] Cell. 1991 Nov 15;67(4):767-74 [1682057] Anat Embryol (Berl). 1989;180(5):457-64 [2619088] Genet Res. 1981 Feb;37(1):95-103 [7203014] Mamm Genome. 1995 Aug;6(8):546-8 [8589526] Dev Biol. 1997 May 15;185(2):139-47 [9187079] J Inherit Metab Dis. 1998 Aug;21(5):532-9 [9728333] N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/cfg.382 ER - TY - JOUR T1 - Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease. AN - 72031181; 15199542 AB - Nitric oxide (NO(.)), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO(.) can activate p53, which can result in anti-carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO(.) induced p53 activation in vitro and found that NO(.) induced p53 accumulation and phosphorylation, particularly at ser-15, via ATM and ATR kinases, which then led to cell cycle arrest at G(2)/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53-P-ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM-2 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher p53 mutant frequencies of both G:C --> A:T transitions at the CpG site of codon 248 and C:G --> T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5-methylcytosine, p53 mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO(.) and p53 in UC and sporadic colon cancer. JF - Environmental and molecular mutagenesis AU - Goodman, Julie E AU - Hofseth, Lorne J AU - Hussain, S Perwez AU - Harris, Curtis C AD - Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 3 EP - 9 VL - 44 IS - 1 SN - 0893-6692, 0893-6692 KW - CDKN1A protein, human KW - 0 KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - Nitric Oxide KW - 31C4KY9ESH KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - ATM protein, human KW - EC 2.7.11.1 KW - ATR protein, human KW - Ataxia Telangiectasia Mutated Proteins KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Protein-Serine-Threonine Kinases -- metabolism KW - Cell Cycle -- physiology KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Cell Cycle Proteins -- metabolism KW - Phosphorylation KW - Cyclins -- metabolism KW - Mutation -- genetics KW - Nitric Oxide Synthase -- metabolism KW - Nuclear Proteins -- metabolism KW - Colonic Neoplasms -- physiopathology KW - Colitis, Ulcerative -- physiopathology KW - Colitis, Ulcerative -- metabolism KW - Nitric Oxide -- metabolism KW - Colonic Neoplasms -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72031181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nitric+oxide+and+p53+in+cancer-prone+chronic+inflammation+and+oxyradical+overload+disease.&rft.au=Goodman%2C+Julie+E%3BHofseth%2C+Lorne+J%3BHussain%2C+S+Perwez%3BHarris%2C+Curtis+C&rft.aulast=Goodman&rft.aufirst=Julie&rft.date=2004-01-01&rft.volume=44&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 - 2004-09-16 N1 - Date created - 2004-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thalidomide-based TNF-alpha inhibitors for neurodegenerative diseases. AN - 72012775; 15190675 AB - Inflammatory processes associated with the over-production of cytokines, particularly of TNF-alpha, accompany numerous neurodegenerative diseases, such as Alzheimer's disease, in addition to numerous systemic conditions, exemplified by rheumatoid arthritis and erythema nodosum leprosum (ENL). TNF-alpha has been validated as a drug target with Remicade and Enbrel available as prescription medications. Both, however, are large macromolecules, require injection and have limited brain access. The classical drug, thalidomide is being increasingly used in the clinical management of a wide spectrum of diseases. As its clinical value in treating ENL derives from its TNF-alpha inhibitory activity, thalidomide was chosen for structural modification for the discovery of novel and more potent isosteric analogues with appropriate lipophilicity to insure high brain penetration. TNF-alpha inhibitory activity was evaluated against lipopolysacharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in cell culture, whose viability was quantified to differentiate reductions in TNF-alpha secretion from that associated with cellular toxicity. Specific analogues potently inhibited TNF-alpha secretion, compared to thalidomide. This involved a post-transcriptional mechanism, as they decreased TNF-alpha mRNA stability via its 3'-untranslated region (UTR), as determined by luciferase activity in stably transfected cells with and without the 3'-UTR of human TNF-alpha. JF - Acta neurobiologiae experimentalis AU - Greig, Nigel H AU - Giordano, Tony AU - Zhu, Xiaoxiang AU - Yu, Qian-sheng AU - Perry, Tracy Ann AU - Holloway, Harold W AU - Brossi, Arnold AU - Rogers, Jack T AU - Sambamurti, Kumar AU - Lahiri, Debomoy K AD - Drug Design and Development Section, Lab. of Neurosciences, Intramural Research Prog., National Inst. on Aging, National Inst. of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224, USA. GreigN@vax.grc.nia.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 1 EP - 9 VL - 64 IS - 1 SN - 0065-1400, 0065-1400 KW - Immunosuppressive Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - Cells, Cultured KW - Humans KW - Neurodegenerative Diseases -- drug therapy KW - Immunosuppressive Agents -- chemistry KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Thalidomide -- chemistry KW - Thalidomide -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72012775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurobiologiae+experimentalis&rft.atitle=Thalidomide-based+TNF-alpha+inhibitors+for+neurodegenerative+diseases.&rft.au=Greig%2C+Nigel+H%3BGiordano%2C+Tony%3BZhu%2C+Xiaoxiang%3BYu%2C+Qian-sheng%3BPerry%2C+Tracy+Ann%3BHolloway%2C+Harold+W%3BBrossi%2C+Arnold%3BRogers%2C+Jack+T%3BSambamurti%2C+Kumar%3BLahiri%2C+Debomoy+K&rft.aulast=Greig&rft.aufirst=Nigel&rft.date=2004-01-01&rft.volume=64&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Acta+neurobiologiae+experimentalis&rft.issn=00651400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-06 N1 - Date created - 2004-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isoflavones in soy infant formula: a review of evidence for endocrine and other activity in infants. AN - 72004998; 15189112 AB - Soy infant formulas are widely used, but few studies have evaluated long-term safety or examined specific forms of toxicity, such as to the endocrine or immune systems. This review focuses on newer experimental studies of the effects on estrogen activity, immune function, and thyroid economy of genistein and daidzein, two isoflavones in soy infant formula, and existing human studies of soy formula use. In order to judge the likelihood that an endpoint seen in laboratory studies might occur in soy-fed infants, we examined the doses and the resulting serum or plasma concentrations from the laboratory studies and compared them with doses and concentrations seen in soy-fed infants. We also summarized the estimates of the potency of the isoflavone compounds relative to estradiol. Given the scarcity and inconsistency of existing human data and the substantial laboratory evidence of hormonal and other activity at doses relevant to the soy-fed infant, we conclude that more clinical and epidemiological study is warranted. JF - Annual review of nutrition AU - Chen, Aimin AU - Rogan, Walter J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. chen17@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 33 EP - 54 VL - 24 SN - 0199-9885, 0199-9885 KW - Estrogens, Non-Steroidal KW - 0 KW - Isoflavones KW - daidzein KW - 6287WC5J2L KW - Genistein KW - DH2M523P0H KW - Index Medicus KW - Infant KW - Immune System -- drug effects KW - Dose-Response Relationship, Drug KW - Soy Milk -- chemistry KW - Humans KW - Infant, Newborn KW - Genistein -- analysis KW - Genistein -- administration & dosage KW - Isoflavones -- analysis KW - Isoflavones -- administration & dosage KW - Estrogens, Non-Steroidal -- administration & dosage KW - Infant Formula -- chemistry KW - Estrogens, Non-Steroidal -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72004998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nutrition&rft.atitle=Isoflavones+in+soy+infant+formula%3A+a+review+of+evidence+for+endocrine+and+other+activity+in+infants.&rft.au=Chen%2C+Aimin%3BRogan%2C+Walter+J&rft.aulast=Chen&rft.aufirst=Aimin&rft.date=2004-01-01&rft.volume=24&rft.issue=&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+nutrition&rft.issn=01999885&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-01 N1 - Date created - 2004-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurobiology of seizures and behavioral abnormalities. AN - 72003425; 15186339 AB - Seizures are both caused by and induce a complex set of neurobiological alterations and adaptations. The animal model of amygdala kindling provides insight into the spatiotemporal evolution of these changes as a function of seizure development and progression. Intracellular, synaptic, and microstructural changes are revealed as related to both the primary pathophysiology of kindled seizure evolution and compensatory secondary, or endogenous anticonvulsant adaptations. At the level of gene expression, the balance of these pathological and adaptive processes (as augmented by exogenous medications) probably determines whether seizures will be manifest or suppressed and could account for aspects of their intermittency. As anxiety and emotion modulation are subserved by many of the same neuroanatomic substrates involved in the evolution of complex partial seizures, particularly those of the medial temporal lobe, it is readily conceptualized how vulnerability to a range of psychiatric disorders could be related to the primary or secondary neurochemical alterations associated with seizure disorders. The discrete and methodologically controlled elucidation of the cascades and spatiotemporal distributions of neurobiological alterations that accompany seizure evolution in the kindling model may help resolve some of the difficulty and complexity of elucidating these biobehavioral relationships in the clinic. JF - Epilepsia AU - Post, R M AD - Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-1272, USA. Robert.Post@NIH.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 5 EP - 14 VL - 45 Suppl 2 SN - 0013-9580, 0013-9580 KW - Anticonvulsants KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Bipolar Disorder -- physiopathology KW - Humans KW - Brain -- drug effects KW - Disease Models, Animal KW - Anticonvulsants -- therapeutic use KW - Cocaine -- administration & dosage KW - Mental Disorders -- physiopathology KW - Rats KW - Brain -- physiopathology KW - Anticonvulsants -- pharmacology KW - Drug Tolerance -- physiology KW - Cats KW - Amygdala KW - Cocaine -- pharmacology KW - Seizures -- chemically induced KW - Behavior, Animal -- drug effects KW - Seizures -- physiopathology KW - Behavior, Animal -- physiology KW - Seizures -- drug therapy KW - Kindling, Neurologic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72003425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neurobiology+of+seizures+and+behavioral+abnormalities.&rft.au=Post%2C+R+M&rft.aulast=Post&rft.aufirst=R&rft.date=2004-01-01&rft.volume=45+Suppl+2&rft.issue=&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=00139580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-13 N1 - Date created - 2004-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Engineering lysine reactivity as a conformational sensor in the Dictyostelium myosin II motor domain. AN - 71966651; 15160493 AB - Lys84 of skeletal muscle myosin located at the interface between the motor and neck domains has long been utilized as a useful chemical probe sensing motor domain conformational changes and tilting of the lever arm. Here we report the first site-directed mutagenesis study on this side chain and its immediate chemical environment. We made Dictyostelium myosin II motor domain constructs in which Lys84 was replaced by either a methionine or a glutamic acid residue and another mutant containing an Arg704Glu substitution. By following trinitrophenylation of the mutant constructs, we first unambiguously identify Lys84 as the reactive lysine in Dictyostelium myosin. Analysis of the reaction profiles also reveals that the Lys84-Arg704 interaction at the interface of two subdomains of the myosin head has a significant effect on Lys84 reactivity, but it is not the only determinant of this property. Our findings imply that the nucleotide sensitivity of the trinitrophenylation reaction is a general feature of conventional myosins that reflects similar changes in the conformational dynamics of the different orthologs during the ATPase cycle. JF - Journal of muscle research and cell motility AU - Kovács, Mihály AU - Tóth, Judit AU - Málnási-Csizmadia, András AU - Bagshaw, Clive R AU - Nyitray, László AD - Department of Biochemistry, Eötvös Loránd University, H-1117 Budapest, Pázmány P. sétány 1/C, Hungary. kovacsm@nhlbi.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 95 EP - 102 VL - 25 IS - 1 SN - 0142-4319, 0142-4319 KW - Trinitrobenzenes KW - 0 KW - Ca(2+) Mg(2+)-ATPase KW - EC 3.6.1.- KW - Myosin Type II KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Animals KW - Fluorescence KW - Models, Molecular KW - Muscle, Skeletal -- physiology KW - Muscle, Skeletal -- chemistry KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Trinitrobenzenes -- chemistry KW - Kinetics KW - Protein Structure, Tertiary KW - Time Factors KW - Ca(2+) Mg(2+)-ATPase -- metabolism KW - Protein Conformation KW - Lysine -- chemistry KW - Myosin Type II -- physiology KW - Lysine -- physiology KW - Dictyostelium -- physiology KW - Myosin Type II -- genetics KW - Myosin Type II -- chemistry KW - Dictyostelium -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71966651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+muscle+research+and+cell+motility&rft.atitle=Engineering+lysine+reactivity+as+a+conformational+sensor+in+the+Dictyostelium+myosin+II+motor+domain.&rft.au=Kov%C3%A1cs%2C+Mih%C3%A1ly%3BT%C3%B3th%2C+Judit%3BM%C3%A1ln%C3%A1si-Csizmadia%2C+Andr%C3%A1s%3BBagshaw%2C+Clive+R%3BNyitray%2C+L%C3%A1szl%C3%B3&rft.aulast=Kov%C3%A1cs&rft.aufirst=Mih%C3%A1ly&rft.date=2004-01-01&rft.volume=25&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+muscle+research+and+cell+motility&rft.issn=01424319&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-22 N1 - Date created - 2004-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of transfection agents in forming complexes with ferumoxides, cell labeling efficiency, and cellular viability. AN - 71933875; 15142409 AB - By complexing ferumoxides or superparamagnetic iron oxide (SPIO) to transfection agents (TAs), it is possible to magnetically label mammalian cells. There has been no systematic study comparing TAs complexed to SPIO as far as cell labeling efficiency and viability. This study investigates the toxicity and labeling efficiency at various doses of FEs complexed to different TAs in mammalian cells. Different classes of TAs were used, such as polycationic amines, dendrimers, and lipid-based agents. Cellular toxicity was measured using doses of TAs from 1 to 50 microg/mL in incubation media. Iron incorporation efficiency was measured by combining various amounts of FEs and different doses of TAs. Lipofectamine2000 showed toxicity at lowest dose (1 microg/mL), whereas FuGENE6 and low molecular weight poly-L-lysine (PLL) showed the least toxicity. SPIO labeling efficiency was similar with high-molecular-weight PLL (388.1 kDa) and superfect, whereas FuGENE6 and low-molecular-weight PLL were inefficient in labeling cells. Concentrations of 25 to 50 microg/mL of FEs complexed to TAs in media resulted in sufficient endocytosis of the SPIO into endosomes to detect cells on cellular magnetic resonance imaging. JF - Molecular imaging AU - Arbab, Ali Syed AU - Yocum, Gene Thomus AU - Wilson, Lindsey Bashaw AU - Parwana, Ashari AU - Jordan, Elaine Kay AU - Kalish, Heather AU - Frank, Joseph Alan AD - Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, MD 20892, USA. saali@cc.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 24 EP - 32 VL - 3 IS - 1 SN - 1535-3508, 1535-3508 KW - Contrast Media KW - 0 KW - Dextrans KW - Indicators and Reagents KW - Lipids KW - Lipofectamine KW - Magnetite Nanoparticles KW - Oxides KW - Polyamines KW - polycations KW - Polylysine KW - 25104-18-1 KW - Iron KW - E1UOL152H7 KW - ferumoxides KW - G6N3J05W84 KW - Ferrosoferric Oxide KW - XM0M87F357 KW - Index Medicus KW - Contrast Media -- pharmacokinetics KW - Polylysine -- pharmacokinetics KW - HeLa Cells KW - Particle Size KW - Humans KW - Mesenchymal Stromal Cells -- metabolism KW - Cell Line, Tumor KW - Polyamines -- pharmacokinetics KW - Mesenchymal Stromal Cells -- drug effects KW - Endocytosis KW - Cell Line KW - Cell Division KW - Mesenchymal Stromal Cells -- cytology KW - Oxides -- metabolism KW - Magnetic Resonance Imaging KW - Transfection -- methods KW - Cell Survival -- drug effects KW - Indicators and Reagents -- pharmacokinetics KW - Iron -- pharmacokinetics KW - Oxides -- pharmacokinetics KW - Oxides -- toxicity KW - Iron -- toxicity KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71933875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+imaging&rft.atitle=Comparison+of+transfection+agents+in+forming+complexes+with+ferumoxides%2C+cell+labeling+efficiency%2C+and+cellular+viability.&rft.au=Arbab%2C+Ali+Syed%3BYocum%2C+Gene+Thomus%3BWilson%2C+Lindsey+Bashaw%3BParwana%2C+Ashari%3BJordan%2C+Elaine+Kay%3BKalish%2C+Heather%3BFrank%2C+Joseph+Alan&rft.aulast=Arbab&rft.aufirst=Ali&rft.date=2004-01-01&rft.volume=3&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Molecular+imaging&rft.issn=15353508&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-08 N1 - Date created - 2004-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regionally advanced nasopharyngeal carcinoma: long-term outcome after sequential chemotherapy and radiotherapy. AN - 71928101; 15143974 AB - To evaluate the long-term clinical outcome of 61 patients with regionally advanced nasopharyngeal carcinoma treated with sequential chemotherapy and radiotherapy within a phase II trial. The trial evaluated a combined modality regimen including 3 cycles of induction polychemotherapy (epirubicin 70 mg/m2 d1, and cisplatin 100 mg/m2 d1, both recycled every 3 weeks) followed by definitive radiotherapy to the primary site (64-70 Gy) and the neck (50-70 Gy). Patients included in the trial had pathologically confirmed nasopharyngeal carcinoma; stage (UICC 1987) T-any, N2-3, M0; ECOG performance status 0-1. Sixty-one patients were enrolled between 1990 and 1996; stage according to UICC 1997 was IIb in 8%, III in 36% and IV in 56% of the patients; histology was WHO type 1-2 in 11% and WHO type 3 in 89% of cases. Minimum follow-up of 33 surviving patients is 5.2 years. Clinical failure has been observed in 30 patients (49%): initial failure, observed within the third year of follow-up in all but one case, was local alone in 6 (20%), regional alone in 10 (33%), local and regional in 1 (3%), regional and distant in 1 (3%), and distant alone in 12 patients (40%). Seven patients received salvage surgery to the neck, 2 of them still disease-free at 10 and 11 years from salvage surgery; 4 patients with an isolated local relapse were re-irradiated, and one of them was alive and well at 6.5 years from salvage radiation. At 5-year local control, regional control and distant metastasis-free rates were 83%, 74% and 73%, respectively; overall and disease-free survival were 64% and 51%. Late effects of initial treatment, as evaluated in 30 patients surviving 5 years without relapse, were generally acceptable, but some degree of xerostomia, dental damage, trismus and hearing loss were reported by a significant proportion of patients (respectively 100%, 88%, 76% and 86%). In our experience, long-term clinical cure of regionally advanced nasopharyngeal carcinoma was obtained in 51% of cases treated with chemotherapy and radiotherapy. Salvage treatments (neck surgery, local re-irradiation) are worthy, as they increase the cure rate by approximately 10%, raising 5-year survival to over 60%. Late effects are significant, calling for refinements in radiation technique, better integration with chemotherapy to possibly decrease the need for higher radiation dose, and/or use of effective radioprotectants. JF - Tumori AU - Palazzi, Mauro AU - Guzzo, Marco AU - Bossi, Paolo AU - Tomatis, Stefano AU - Cerrotta, Annamaria AU - Cantú, Giulio AU - Locati, Laura D AU - Licitra, Lisa AD - Department of Radiotherapy, National Cancer Institute, Milan, Italy. mauro.palazzi@istitutotumori.mi.it PY - 2004 SP - 60 EP - 65 VL - 90 IS - 1 SN - 0300-8916, 0300-8916 KW - Index Medicus KW - Treatment Failure KW - Disease-Free Survival KW - Radiotherapy, Adjuvant KW - Radiotherapy Dosage KW - Humans KW - Treatment Outcome KW - Time Factors KW - Male KW - Female KW - Chemotherapy, Adjuvant KW - Survival Analysis KW - Remission Induction KW - Nasopharyngeal Neoplasms -- radiotherapy KW - Nasopharyngeal Neoplasms -- drug therapy KW - Carcinoma -- pathology KW - Carcinoma -- radiotherapy KW - Carcinoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Nasopharyngeal Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71928101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Regionally+advanced+nasopharyngeal+carcinoma%3A+long-term+outcome+after+sequential+chemotherapy+and+radiotherapy.&rft.au=Palazzi%2C+Mauro%3BGuzzo%2C+Marco%3BBossi%2C+Paolo%3BTomatis%2C+Stefano%3BCerrotta%2C+Annamaria%3BCant%C3%BA%2C+Giulio%3BLocati%2C+Laura+D%3BLicitra%2C+Lisa&rft.aulast=Palazzi&rft.aufirst=Mauro&rft.date=2004-01-01&rft.volume=90&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-04 N1 - Date created - 2004-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetic optimisation of treatment with oral etoposide. AN - 71916229; 15139794 AB - Etoposide is a derivative of podophyllotoxin widely used in the treatment of several neoplasms, including small cell lung cancer, germ cell tumours and non-Hodgkin's lymphomas. Prolonged administration of etoposide aims for continuous inhibition of topoisomerase II, the intracellular target of etoposide, thus preventing tumour cells from repairing DNA breaks. However, the clinical advantages of extended schedules as compared with conventional short-term infusions remain unclear. Oral administration of etoposide represents the most feasible and economic strategy to maintain effective concentrations of drug for extended times. Nevertheless, the efficacy of oral etoposide therapy is contingent on circumventing pharmacokinetic limitations, mainly low and variable bioavailability. Inhibition of small bowel and hepatic metabolism of etoposide with specific cytochrome P450 inhibitors or inhibition of the intestinal P-glycoprotein efflux pump have been attempted to increase the bioavailability of oral etoposide, but the best results were obtained with daily oral administration of low etoposide doses (50-100 mg/day for 14-21 days). Saturable absorption of etoposide was reported for doses greater than 200 mg/day, whereas lower doses were associated with increased bioavailability, although they were characterised by high inter- and intrapatient variability. Pharmacokinetic parameters such as plasma trough concentration between two oral administrations (C(24,trough)), drug exposure time above a threshold value and area under the plasma concentration-time curve have been correlated with the pharmacodynamic effect of oral etoposide. Pharmacokinetic-pharmacodynamic relationships indicate that severe toxicity is avoided when peak plasma concentrations do not exceed 3-5 mg/L and C(24,trough) is under the threshold limit of 0.3 mg/L. To maintain effective etoposide plasma concentrations during prolonged oral administration, pharmacokinetic variability must be monitored in each patient, taking account of factors from many pharmacokinetic studies of etoposide, including absorption, distribution, protein binding, metabolism and elimination. Dosage reduction is generally useful to avoid haematological toxicity in patients with renal dysfunction (creatinine clearance <50 mL/min). The need for dosage adjustment based on liver function in patients with liver dysfunction is not completely defined, but generally is not indicated in patients with minor liver dysfunction. Adaptive dosage adjustment based on individual pharmacokinetic parameters, estimated using limited sampling strategies and population pharmacokinetic models, is more appropriate. This approach has been used with success in different clinical trials to increase the etoposide dosage, without significantly increasing toxicity. Various pharmacodynamic models have been proposed to guide etoposide oral dosage. However, they lack precision and accuracy and need to be refined by considering other predictor variables in order to extend their application in current clinical practice. JF - Clinical pharmacokinetics AU - Toffoli, Giuseppe AU - Corona, Giuseppe AU - Basso, Barbara AU - Boiocchi, Mauro AD - Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. gtoffoli@cro.it Y1 - 2004 PY - 2004 DA - 2004 SP - 441 EP - 466 VL - 43 IS - 7 SN - 0312-5963, 0312-5963 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Etoposide KW - 6PLQ3CP4P3 KW - Index Medicus KW - Administration, Oral KW - Half-Life KW - Area Under Curve KW - Humans KW - Aged KW - Intestinal Absorption KW - Tissue Distribution KW - Structure-Activity Relationship KW - Biological Availability KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Neoplasms -- drug therapy KW - Etoposide -- pharmacokinetics KW - Etoposide -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Etoposide -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71916229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacokinetics&rft.atitle=Pharmacokinetic+optimisation+of+treatment+with+oral+etoposide.&rft.au=Toffoli%2C+Giuseppe%3BCorona%2C+Giuseppe%3BBasso%2C+Barbara%3BBoiocchi%2C+Mauro&rft.aulast=Toffoli&rft.aufirst=Giuseppe&rft.date=2004-01-01&rft.volume=43&rft.issue=7&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacokinetics&rft.issn=03125963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-31 N1 - Date created - 2004-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel family of P-loop NTPases with an unusual phyletic distribution and transmembrane segments inserted within the NTPase domain. AN - 71907569; 15128444 AB - Recent sequence-structure studies on P-loop-fold NTPases have substantially advanced the existing understanding of their evolution and functional diversity. These studies provide a framework for characterization of novel lineages within this fold and prediction of their functional properties. Using sequence profile searches and homology-based structure prediction, we have identified a previously uncharacterized family of P-loop NTPases, which includes the neuronal membrane protein and receptor tyrosine kinase substrate Kidins220/ARMS, which is conserved in animals, the F-plasmid PifA protein involved in phage T7 exclusion, and several uncharacterized bacterial proteins. We refer to these (predicted) NTPases as the KAP family, after Kidins220/ARMS and PifA. The KAP family NTPases are sporadically distributed across a wide phylogenetic range in bacteria but among the eukaryotes are represented only in animals. Many of the prokaryotic KAP NTPases are encoded in plasmids and tend to undergo disruption to form pseudogenes. A unique feature of all eukaryotic and certain bacterial KAP NTPases is the presence of two or four transmembrane helices inserted into the P-loop NTPase domain. These transmembrane helices anchor KAP NTPases in the membrane such that the P-loop domain is located on the intracellular side. We show that the KAP family belongs to the same major division of the P-loop NTPase fold with the AAA+, ABC, RecA-like, VirD4-like, PilT-like, and AP/NACHT-like NTPase classes. In addition to the KAP family, we identified another small family of predicted bacterial NTPases, with two transmembrane helices inserted into the P-loop domain. This family is not specifically related to the KAP NTPases, suggesting independent acquisition of the transmembrane helices. We predict that KAP family NTPases function principally in the NTP-dependent dynamics of protein complexes, especially those associated with the intracellular surface of cell membranes. Animal KAP NTPases, including Kidins220/ARMS, are likely to function as NTP-dependent regulators of the assembly of membrane-associated signaling complexes involved in neurite growth and development. One possible function of the prokaryotic KAP NTPases might be in the exclusion of selfish replicons, such as viruses, from the host cells. Phylogenetic analysis and phyletic patterns suggest that the common ancestor of the animals acquired a KAP NTPase via lateral transfer from bacteria. However, an earlier transfer into eukaryotes followed by multiple losses in several eukaryotic lineages cannot be ruled out. JF - Genome biology AU - Aravind, L AU - Iyer, Lakshminarayan M AU - Leipe, Detlef D AU - Koonin, Eugene V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. aravind@ncbi.nlm.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 1 VL - 5 IS - 5 KW - Bacterial Proteins KW - 0 KW - Caenorhabditis elegans Proteins KW - Drosophila Proteins KW - Insect Proteins KW - Membrane Proteins KW - Peptides KW - Zebrafish Proteins KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Nucleoside-Triphosphatase KW - EC 3.6.1.15 KW - Index Medicus KW - Animals KW - Drosophila Proteins -- chemistry KW - Bacterial Proteins -- genetics KW - Insect Proteins -- genetics KW - Caenorhabditis elegans Proteins -- genetics KW - Caenorhabditis elegans Proteins -- chemistry KW - Predictive Value of Tests KW - Evolution, Molecular KW - Adenosine Triphosphatases -- classification KW - Protein Structure, Tertiary -- genetics KW - Zebrafish Proteins -- chemistry KW - Insect Proteins -- chemistry KW - Bacterial Proteins -- chemistry KW - Adenosine Triphosphatases -- physiology KW - Databases, Protein KW - Drosophila Proteins -- genetics KW - Zebrafish Proteins -- genetics KW - Sequence Homology, Amino Acid KW - Adenosine Triphosphatases -- genetics KW - Mutagenesis, Insertional -- genetics KW - Phylogeny KW - Multigene Family -- genetics KW - Nucleoside-Triphosphatase -- genetics KW - Membrane Proteins -- chemistry KW - Nucleoside-Triphosphatase -- chemistry KW - Catalytic Domain -- genetics KW - Peptides -- genetics KW - Membrane Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71907569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+biology&rft.atitle=A+novel+family+of+P-loop+NTPases+with+an+unusual+phyletic+distribution+and+transmembrane+segments+inserted+within+the+NTPase+domain.&rft.au=Aravind%2C+L%3BIyer%2C+Lakshminarayan+M%3BLeipe%2C+Detlef+D%3BKoonin%2C+Eugene+V&rft.aulast=Aravind&rft.aufirst=L&rft.date=2004-01-01&rft.volume=5&rft.issue=5&rft.spage=R30&rft.isbn=&rft.btitle=&rft.title=Genome+biology&rft.issn=1474-760X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-07 N1 - Date created - 2004-05-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1999 Oct 22;293(2):381-99 [10529352] Genome Res. 2000 Jan;10(1):5-16 [10645945] Mol Biol Evol. 2000 Jan;17(1):189-97 [10666718] Trends Biochem Sci. 2000 May;25(5):223-4 [10782090] Q Rev Biophys. 1999 Feb;32(1):1-56 [10800520] J Biol Chem. 2000 Jun 2;275(22):16717-22 [10747959] Adv Protein Chem. 2000;54:245-75 [10829230] Genome Res. 2000 Aug;10(8):1204-10 [10958638] J Mol Biol. 2000 Sep 8;302(1):205-17 [10964570] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11319-24 [11016957] J Biol Chem. 2000 Dec 22;275(51):40048-56 [10998417] J Neurosci. 2001 Jan 1;21(1):176-85 [11150334] J Mol Biol. 2001 Jan 19;305(3):567-80 [11152613] Genome Res. 2001 Mar;11(3):356-72 [11230160] Nucleic Acids Res. 2001 Jul 15;29(14):2994-3005 [11452024] Genes Cells. 2001 Jul;6(7):575-97 [11473577] Genome Biol. 2002;3(2):REVIEWS3003 [11864377] J Mol Biol. 2002 Mar 15;317(1):41-72 [11916378] Nucleic Acids Res. 2002 Apr 1;30(7):1427-64 [11917006] Bioinformatics. 2002 Mar;18(3):502-4 [11934758] Proteins. 2002 Jul 1;48(1):1-14 [12012333] Curr Opin Struct Biol. 2002 Dec;12(6):746-53 [12504679] Bioinformatics. 2003 Feb 12;19(3):427-8 [12584134] Syst Biol. 2003 Oct;52(5):696-704 [14530136] J Mol Biol. 2003 Oct 31;333(4):781-815 [14568537] Science. 2003 Dec 5;302(5651):1727-36 [14605208] Curr Biol. 2003 Dec 16;13(24):2190-5 [14680636] J Struct Biol. 2004 Apr-May;146(1-2):11-31 [15037234] J Virol. 1975 Jan;17(1):94-105 [1107598] EMBO J. 1982;1(8):945-51 [6329717] Gene. 1984 Dec;32(1-2):251-4 [6099313] FEBS Lett. 1988 Aug 1;235(1-2):16-24 [2841153] Nucleic Acids Res. 1989 Jun 26;17(12):4713-30 [2546125] Cell. 1990 Jan 26;60(2):307-17 [2404612] Trends Biochem Sci. 1990 Nov;15(11):430-4 [2126155] J Bacteriol. 1991 Feb;173(4):1536-43 [1995595] J Bacteriol. 1991 Oct;173(20):6507-14 [1917875] J Mol Biol. 1991 Oct 5;221(3):751-4 [1942027] J Mol Biol. 1993 Jul 20;232(2):584-99 [8345525] Proteins. 1993 Dec;17(4):363-74 [8108379] Comput Appl Biosci. 1994 Dec;10(6):685-6 [7704669] Biochem Soc Trans. 1996 Feb;24(1):274-9 [8674685] Methods Enzymol. 1996;266:418-27 [8743697] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Proc Int Conf Intell Syst Mol Biol. 1997;5:333-9 [9322058] Protein Sci. 1998 Apr;7(4):1029-38 [9568909] Trends Biochem Sci. 1998 Sep;23(9):324-8 [9787636] Genome Res. 1999 Jan;9(1):27-43 [9927482] Nucleic Acids Res. 1999 Mar 1;27(5):1223-42 [9973609] Comput Chem. 1994 Sep;18(3):269-85 [7952898] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Convergences in course of illness and treatments of the epilepsies and recurrent affective disorders. AN - 71890526; 15112460 AB - The failure to achieve and maintain remission is a critical problem for a high percentage of patients with epilepsy and the primary affective disorders. Early illness onset and delayed initiation of treatment may contribute to primary treatment resistance or that associated with loss of efficacy (tolerance phenomenon). Neurobiological data and principles drawn from the amygdala kinding model of seizure progression are reviewed for their heuristic value in conceptualizing molecular mechanisms of illness progression and its prevention with pharmacological agents in the epilepsies and, indirectly, the recurrent affective disorders. Caveats in the use of this model and convergences and divergences in its predictive validity for seizures and affective disorders are noted. JF - Clinical EEG and neuroscience AU - Post, Robert M AU - Weiss, Susan R B AD - Biological Psychiatry Branch, NIMH, NIH, DHHS, Bethesda, MD, USA. Robert.Post@NIH.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 14 EP - 24 VL - 35 IS - 1 SN - 1550-0594, 1550-0594 KW - Anticonvulsants KW - 0 KW - Antidepressive Agents KW - Index Medicus KW - Animals KW - Bipolar Disorder -- physiopathology KW - Humans KW - Drug Resistance KW - Electroencephalography -- drug effects KW - Recurrence KW - Comorbidity KW - Rats KW - Drug Therapy, Combination KW - Amygdala -- physiopathology KW - Kindling, Neurologic -- drug effects KW - Bipolar Disorder -- epidemiology KW - Bipolar Disorder -- drug therapy KW - Treatment Outcome KW - Kindling, Neurologic -- physiology KW - Amygdala -- drug effects KW - Epilepsy, Complex Partial -- epidemiology KW - Anticonvulsants -- adverse effects KW - Mood Disorders -- physiopathology KW - Mood Disorders -- drug therapy KW - Antidepressive Agents -- therapeutic use KW - Epilepsy, Complex Partial -- drug therapy KW - Antidepressive Agents -- adverse effects KW - Mood Disorders -- epidemiology KW - Epilepsy, Complex Partial -- physiopathology KW - Anticonvulsants -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71890526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+EEG+and+neuroscience&rft.atitle=Convergences+in+course+of+illness+and+treatments+of+the+epilepsies+and+recurrent+affective+disorders.&rft.au=Post%2C+Robert+M%3BWeiss%2C+Susan+R+B&rft.aulast=Post&rft.aufirst=Robert&rft.date=2004-01-01&rft.volume=35&rft.issue=1&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=Clinical+EEG+and+neuroscience&rft.issn=15500594&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-26 N1 - Date created - 2004-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trimethyltin-induced neurogenesis in the murine hippocampus. AN - 71869251; 15111239 AB - Neurogenesis continues to occur in the mature rodent brain with one of the most prominent sources for new neurons being the subgranular layer (SGL) of the dentate gyrus (DG) in the hippocampus. A number of factors can stimulate this process including synaptic activity and injury. To determine if this process would occur upon a direct injury to the dentate region, we exposed young, 21 day old male CD-1 mice to the hippocampal toxicant, trimethyltin (TMT). An acute i.p. injection of TMT (2 mg/kg) produced extensive damage and loss of dentate granule neurons within 72 h. This active period of degeneration was accompanied by an increase in the generation of progenitor cells within the SGL as identified by BrdU uptake and Ki-67 immunostaining. As additional markers for neurogenesis, both nestin and doublecortin showed increased staining patterns within the blades of the dentate. In these young weanling mice, the level of proliferation was sufficient to significantly repopulate the dentate region by 4 weeks post-TMT, suggesting a high level of regenerative potential. Our data indicate a significant level of neurogenesis occurring during the active process of degeneration and in an environment of microglia activation. The TMT-induced injury offers a model system for further examination of the process of neurogenesis, neural adaptation, and the influence of inflammatory factors and glia interactions. JF - Neurotoxicity research AU - Harry, G Jean AU - McPherson, Christopher A AU - Wine, Robert N AU - Atkinson, Kelly AU - Lefebvre d'Hellencourt, Christian AD - Neurotoxicology Group, Laboratory of Molecular Toxicology, Department of Health and Human Services, National Institutes of Health, National Institute of Environmental Health Sciences, MD C1-04, Research Triangle Park, NC 27709, USA. harry@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 623 EP - 627 VL - 5 IS - 8 SN - 1029-8428, 1029-8428 KW - Trimethyltin Compounds KW - 0 KW - trimethyltin KW - 1631-73-8 KW - Index Medicus KW - Cell Death -- physiology KW - Animals KW - Cell Differentiation -- physiology KW - Mice KW - Cell Differentiation -- drug effects KW - Cell Death -- drug effects KW - Male KW - Trimethyltin Compounds -- pharmacology KW - Neurons -- drug effects KW - Neurons -- cytology KW - Hippocampus -- cytology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71869251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+research&rft.atitle=Trimethyltin-induced+neurogenesis+in+the+murine+hippocampus.&rft.au=Harry%2C+G+Jean%3BMcPherson%2C+Christopher+A%3BWine%2C+Robert+N%3BAtkinson%2C+Kelly%3BLefebvre+d%27Hellencourt%2C+Christian&rft.aulast=Harry&rft.aufirst=G&rft.date=2004-01-01&rft.volume=5&rft.issue=8&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+research&rft.issn=10298428&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-25 N1 - Date created - 2004-04-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurosci Res. 2000 Oct 1;62(1):146-55 [11002296] J Neurosci Res. 2000 Jul 1;61(1):10-20 [10861795] Hippocampus. 2000;10(2):169-80 [10791839] J Neurosci. 1999 Oct 15;19(20):8747-56 [10516294] Brain Res. 1999 Jun 12;831(1-2):283-7 [10412007] J Comp Neurol. 1999 Apr 19;406(4):449-60 [10205022] J Neurochem. 1998 Oct;71(4):1577-87 [9751191] Neuron. 1994 Feb;12(2):343-55 [8110463] Neurotoxicology. 1983 Spring;4(1):19-28 [6683824] Neurotox Res. 2003;5(5):339-54 [14715453] Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4710-5 [11296300] J Comp Neurol. 2001 Jul 9;435(4):406-17 [11406822] Brain Res. 2001 Sep 7;912(2):116-27 [11532427] J Neurosci. 2002 Feb 1;22(3):612-3 [11826087] Nature. 2002 Feb 28;415(6875):1030-4 [11875571] J Neurosci Methods. 2002 Mar 30;115(1):97-105 [11897369] Exp Neurol. 2002 May;175(1):152-60 [12009767] J Pathol. 2002 Jul;197(4):536-50 [12115869] Prog Brain Res. 2002;135:121-31 [12143334] Development. 2003 Jan;130(2):391-9 [12466205] J Neurosci Res. 2003 Feb 15;71(4):583-90 [12548715] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Saffron can prevent chemically induced skin carcinogenesis in Swiss albino mice. AN - 71819429; 15075009 AB - One of the most promising strategies for cancer prevention today is chemoprevention using readily available natural substances from vegetables, fruits, herbs and spices. Among the spices, saffron (Crocus sativus, L) a member of the large family Iridaceae, has drawn attention because apart from its use as a flavouring agent, pharmacological studies have demonstrated many health promoting properties including radical scavenging, anti- mutagenic and immuno-modulating effects. In the present study the effects of an aqueous infusion of saffron on two stage skin papillogenesis / carcinogenesis in mice initiated by 7-12 dimethyl benz[a] anthracin (DMBA) and promoted with croton oil were investigated. Significant reduction in papilloma formation was found with saffron application in the pre-initiation and post-initiation periods, and particular when the agent was given both pre- and post-initiation. The inhibition appeared to be at least partly due on modulatory effects of saffron on some phase II detoxifying enzymes like glutathione-S-transferase (GST) and glutahinoe peroxidase (GPx), as well as catalase (CAT) and superoxide dismutase (SOD). JF - Asian Pacific journal of cancer prevention : APJCP AU - Das, Ila AU - Chakrabarty, R N AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata-700026, India. PY - 2004 SP - 70 EP - 76 VL - 5 IS - 1 SN - 1513-7368, 1513-7368 KW - Carcinogens KW - 0 KW - Plant Preparations KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Animals KW - Carcinogens -- administration & dosage KW - 9,10-Dimethyl-1,2-benzanthracene -- administration & dosage KW - Mice KW - Female KW - Neoplasms, Experimental KW - Papilloma -- prevention & control KW - Crocus -- chemistry KW - Skin Neoplasms -- veterinary KW - Papilloma -- veterinary KW - Skin Neoplasms -- prevention & control KW - Plant Preparations -- pharmacology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71819429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Saffron+can+prevent+chemically+induced+skin+carcinogenesis+in+Swiss+albino+mice.&rft.au=Das%2C+Ila%3BChakrabarty%2C+R+N%3BDas%2C+Sukta&rft.aulast=Das&rft.aufirst=Ila&rft.date=2004-01-01&rft.volume=5&rft.issue=1&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-08 N1 - Date created - 2004-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The models for assessment of chemopreventive agents: single organ models. AN - 71818258; 15074999 AB - Research in cancer chemoprevention involves a number of activities, the first and foremost of which is acquisition of detailed knowledge concerning the process of carcinogenesis and identification of points of intervention whereby the process can be reversed or stalled. Parallel to this is the search for ideal chemopreventive agents--natural or synthetic--and screening for their activity and efficacy in vitro and in vivo. For ethical reasons it is not possible to test new agents on humans, so preclinical studies are dependent on results first being obtained with suitable animal models. Since it is not possible for a single model to reflect the diversity and heterogeneity of human cancers, it is necessary to have as many different models as possible, depending on the requirement of the studies on different aspects of cancer biology. Advances in research on carcinogenesis and chemoprevention therefore have to be accompanied by development of appropriate laboratory animal models using a variety of carcinogens that produce tumours at different sites. Animal models have contributed significantly to our understanding of carcinogenesis and ways to intervene in the underlying processes. Many animal carcinogenesis and tumour models have been found to mirror corresponding human cancers with respect to cell of origin, morphogenesis, phenotype markers and genetic alteration. In spite of the fact that interpolation of data from animal studies to humans is difficult for various reasons, animal models are widely used for assessment of new compounds with cancer chemopreventive potential and for preclinical trials. So despite the movements of animal rights activists, animal models will continue to be used for biomedical research for saving human lives. In doing so, care should be taken to treat and handle the animals with minimal discomfort to them and ensuring that alternatives are used whenever possible. JF - Asian Pacific journal of cancer prevention : APJCP AU - Das, Sukta AU - Banerjee, Sarmistha AU - Saha, Prosenjit AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India. suk_tadas@yahoo.com PY - 2004 SP - 15 EP - 23 VL - 5 IS - 1 SN - 1513-7368, 1513-7368 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Phenotype KW - Animals KW - Animal Testing Alternatives KW - Apoptosis KW - Reproducibility of Results KW - Humans KW - Animal Welfare KW - Cell Differentiation KW - Cell Transformation, Neoplastic KW - Anticarcinogenic Agents -- pharmacology KW - Disease Models, Animal KW - Chemoprevention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71818258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=The+models+for+assessment+of+chemopreventive+agents%3A+single+organ+models.&rft.au=Das%2C+Sukta%3BBanerjee%2C+Sarmistha%3BSaha%2C+Prosenjit&rft.aulast=Das&rft.aufirst=Sukta&rft.date=2004-01-01&rft.volume=5&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-08 N1 - Date created - 2004-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular recognition at purine and pyrimidine nucleotide (P2) receptors. AN - 71818112; 15078212 AB - In comparison to other classes of cell surface receptors, the medicinal chemistry at P2X (ligand-gated ion channels) and P2Y (G protein-coupled) nucleotide receptors has been relatively slow to develop. Recent effort to design selective agonists and antagonists based on a combination of library screening, empirical modification of known ligands, and rational design have led to the introduction of potent antagonists of the P2X(1) (derivatives of pyridoxal phosphates and suramin), P2X(3)(A-317491), P2X(7) (derivatives of the isoquinoline KN-62), P2Y(1)(nucleotide analogues MRS 2179 and MRS 2279), P2Y(2)(thiouracil derivatives such as AR-C126313), and P2Y(12)(nucleotide/nucleoside analogues AR-C69931X and AZD6140) receptors. A variety of native agonist ligands (ATP, ADP, UTP, UDP, and UDP-glucose) are currently the subject of structural modification efforts to improve selectivity. MRS2365 is a selective agonist for P2Y(1)receptors. The dinucleotide INS 37217 potently activates the P2Y(2)receptor. UTP-gamma-S and UDP-beta-S are selective agonists for P2Y(2)/P2Y(4)and P2Y(6)receptors, respectively. The current knowledge of the structures of P2X and P2Y receptors, is derived mainly from mutagenesis studies. Site-directed mutagenesis has shown that ligand recognition in the human P2Y(1)receptor involves individual residues of both the TMs (3, 5, 6, and 7), as well as EL 2 and 3. The binding of the negatively-charged phosphate moiety is dependent on positively charged lysine and arginine residues near the exofacial side of TMs 3 and 7. JF - Current topics in medicinal chemistry AU - Jacobson, Kenneth A AU - Costanzi, Stefano AU - Ohno, Michihiro AU - Joshi, Bhalchandra V AU - Besada, Pedro AU - Xu, Bin AU - Tchilibon, Susanna AD - Molecular Recognition Section, Laboratory of Biorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, MD 20892-0810, USA. E-mail: kajacobs@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 805 EP - 819 VL - 4 IS - 8 SN - 1568-0266, 1568-0266 KW - Adenine Nucleotides KW - 0 KW - Ligands KW - Purine Nucleotides KW - Purinergic P2 Receptor Agonists KW - Purinergic P2 Receptor Antagonists KW - Receptors, Purinergic P2 KW - Uracil Nucleotides KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Ion Channel Gating KW - Animals KW - Adenine Nucleotides -- pharmacology KW - Humans KW - Uracil Nucleotides -- pharmacology KW - Receptors, Purinergic P2 -- metabolism KW - Purine Nucleotides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71818112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicinal+chemistry&rft.atitle=Molecular+recognition+at+purine+and+pyrimidine+nucleotide+%28P2%29+receptors.&rft.au=Jacobson%2C+Kenneth+A%3BCostanzi%2C+Stefano%3BOhno%2C+Michihiro%3BJoshi%2C+Bhalchandra+V%3BBesada%2C+Pedro%3BXu%2C+Bin%3BTchilibon%2C+Susanna&rft.aulast=Jacobson&rft.aufirst=Kenneth&rft.date=2004-01-01&rft.volume=4&rft.issue=8&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+medicinal+chemistry&rft.issn=15680266&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-12 N1 - Date created - 2004-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation dosimetry estimates for the PET serotonin transporter probe 11C-DASB determined from whole-body imaging in non-human primates. AN - 71801168; 15061269 AB - The radiotracer 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile labelled in the N-methyl position (11C-DASB) is a selective radioligand for the in vivo quantification of serotonin transporters (SERTs) using positron emission tomography (PET). The current study quantified the distribution of activity in two rhesus monkeys after the injection of approximately 333 MBq (9 mCi) 11C-DASB. Whole-body images were acquired at 22 time points for a total of 120 min following injection of the radioligand. Source organs were identified at each time point from both tomographic images (using multiple regions of interest on each tomograph for each organ) and a single planar image (using a single region of interest for each organ). The peak activities in planar images in the five identified source organs (expressed as per cent injected dose (ID)) were lungs (24% ID at 1.5 min), kidneys (6.5% ID at 4 min), liver (8% ID at 3 min), brain (4% ID at 5 min) and spleen (0.42% ID at 3 min). Mono-exponential fitting of activity overlying the bladder suggested that approximately 14% of activity was excreted via the urine. The radiation burden to the body was calculated from residence times of these source organs and then scaled to corresponding human values. The calculated effective dose from tomographic and planar images was 6.0 and 6.4 microGy x MBq(-1) (22.3 and 23.7 mrad x mCi(-1)), respectively. The planar analysis was much easier to perform, and generally yielded slightly higher (i.e., more conservative) estimates of radiation burden than the tomographic analysis. The estimated radiation burden of 11C-DASB is relatively modest and would allow multiple scans per research subject per year. JF - Nuclear medicine communications AU - Tipre, D N AU - Lu, J Q AU - Fujita, M AU - Ichise, M AU - Vines, D AU - Innis, R B AD - Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland 20892-0135, USA. TipreD@intra.nimh.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 81 EP - 86 VL - 25 IS - 1 SN - 0143-3636, 0143-3636 KW - 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile KW - 0 KW - Aniline Compounds KW - Carbon Radioisotopes KW - Carrier Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Radiopharmaceuticals KW - Serotonin Plasma Membrane Transport Proteins KW - Sulfides KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Radiation Dosage KW - Radiopharmaceuticals -- pharmacokinetics KW - Reproducibility of Results KW - Body Burden KW - Metabolic Clearance Rate KW - Organ Specificity KW - Tissue Distribution KW - Radiopharmaceuticals -- urine KW - Carbon Radioisotopes -- pharmacokinetics KW - Carbon Radioisotopes -- urine KW - Macaca mulatta KW - Male KW - Tomography, Emission-Computed -- methods KW - Aniline Compounds -- urine KW - Carrier Proteins -- metabolism KW - Sulfides -- urine KW - Sulfides -- pharmacokinetics KW - Aniline Compounds -- pharmacokinetics KW - Nerve Tissue Proteins -- metabolism KW - Radiometry -- methods KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71801168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nuclear+medicine+communications&rft.atitle=Radiation+dosimetry+estimates+for+the+PET+serotonin+transporter+probe+11C-DASB+determined+from+whole-body+imaging+in+non-human+primates.&rft.au=Tipre%2C+D+N%3BLu%2C+J+Q%3BFujita%2C+M%3BIchise%2C+M%3BVines%2C+D%3BInnis%2C+R+B&rft.aulast=Tipre&rft.aufirst=D&rft.date=2004-01-01&rft.volume=25&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Nuclear+medicine+communications&rft.issn=01433636&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-14 N1 - Date created - 2004-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Workshop on Alcohol Use and Health Disparities 2002: a call to arms. AN - 71800508; 15066702 AB - The National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) sponsored a "Workshop on Alcohol Use and Health Disparities 2002: A Call to Arms," on December 5, 2002, in Bethesda, Maryland, USA. This workshop was part of the NIAAA/NIH comprehensive strategic plan to reduce, and ultimately eliminate, health disparities. Eleven topics were addressed: (1). biomedical risk factors that may contribute to disparities in the toxic effects of alcohol; (2). alcohol and gene-environment interactions that affect the health of diverse groups; (3). alcohol pharmacogenetics in Mexican-Americans; (4). determinants of risk for alcoholism in minority populations; (5). consideration of population groups in linkage-disequilibrium studies to identify genes associated with alcohol dependence; (6). interaction between alcohol dependence and African-American ethnicity in disordered sleep, nocturnal cytokines, and immunity; (7). disparities of brain functional reserve capacity affecting brain morbidity related to substance abuse; (8). alcohol and pregnancy disparities; (9). role of alcohol in cancer risk disparities; (10). ethnic diversity in alcoholic cardiomyopathy; and (11). postmenopausal health disparities. On the basis of these presentations, seven conclusions emerged: (1). Genetic variations in alcohol-metabolizing enzymes exist in various populations. (2). These enzymes play a role in the variation in health effect outcomes seen in different populations, owing to alcohol consumption. (3). Differences between and among population groups can be critically important for the design and interpretation of studies in genetics. These include differences in expression of phenotype, in locus heterogeneity, in risk alleles, and in population structure. (4). Incidence rates for fetal alcohol syndrome and fetal alcohol spectrum disorders are greater in African-Americans and Native-Americans than in Caucasians. Genetic polymorphisms, nutrition, and other factors may account for these differences. (5). The highest mortality rate for cirrhosis has been found in white Hispanic men. (6). Mexican-Americans have a low frequency of the protective alleles ADH1B(*)2 and ALDH2(*)2 and a relatively high frequency of CYP2E1 c2, which is associated with early onset alcoholism. (7). The incidence rate for cancer is greater for African-Americans than for Caucasians, and part of the higher risk may be attributed to heavier drinking. JF - Alcohol (Fayetteville, N.Y.) AU - Russo, Denise AU - Purohit, Vishnudutt AU - Foudin, Laurie AU - Salin, Marvin AD - Biomedical Research Branch/Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 6000 Executive Boulevard, Suite 402, Bethesda MD 20892-7003, USA. drusso@mail.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 37 EP - 43 VL - 32 IS - 1 SN - 0741-8329, 0741-8329 KW - Index Medicus KW - Polymorphism, Genetic -- genetics KW - Humans KW - Health Status Indicators KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- genetics KW - Alcoholism -- genetics KW - Alcohol Drinking -- epidemiology KW - Ethnic Groups -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71800508?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Workshop+on+Alcohol+Use+and+Health+Disparities+2002%3A+a+call+to+arms.&rft.au=Russo%2C+Denise%3BPurohit%2C+Vishnudutt%3BFoudin%2C+Laurie%3BSalin%2C+Marvin&rft.aulast=Russo&rft.aufirst=Denise&rft.date=2004-01-01&rft.volume=32&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-08 N1 - Date created - 2004-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Method for making selective lesions of the hippocampus in macaque monkeys using NMDA and a longitudinal surgical approach. AN - 71799246; 15058478 AB - We describe a method for making selective lesions of the hippocampus in macaque monkeys, using a magnetic resonance imaging (MRI)-guided stereotaxic approach in which the excitotoxin N-methyl-D-aspartic acid (NMDA) is injected at intervals along a single needle track that extends longitudinally through the rostrocaudal extent of the hippocampus. Procedures were conducted on six rhesus monkeys (Macaca mulatta) and were assessed with either in vivo MRI (n = 3) or postmortem microscopic examination of the tissue after standard histological processing of the brains (n = 3). Based on our extensive experience with the standard stereotaxic procedure in which ibotenic acid (IBO) is injected via the dorsal approach, we report that the new method provides a viable and potentially advantageous alternative to the standard procedure. First, the longitudinal approach combined with N-methyl-D-aspartic acid (NMDA) injections increases the reliability and efficacy of hippocampal excitotoxic lesions, probably by limiting the leakage of injectant into the ventricles. Second, the present procedure led to more rapid postoperative recovery compared with that after the standard procedure. Third, because the new method requires fewer needle penetrations than the standard method, it most likely reduces the chances of infarction in extrahippocampal tissue. Finally, the new surgical approach may provide a mechanism for infusing agents into the hippocampus from a single cannula. JF - Hippocampus AU - Hampton, Robert R AU - Buckmaster, Cindy A AU - Anuszkiewicz-Lundgren, Dawn AU - Murray, Elisabeth A AD - Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. robert@ln.nimh.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 9 EP - 18 VL - 14 IS - 1 SN - 1050-9631, 1050-9631 KW - Neurotoxins KW - 0 KW - N-Methylaspartate KW - 6384-92-5 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Microinjections -- methods KW - Animals KW - Reproducibility of Results KW - Microinjections -- instrumentation KW - Macaca mulatta KW - Male KW - Stereotaxic Techniques -- instrumentation KW - Denervation -- instrumentation KW - Hippocampus -- physiology KW - Neurosurgical Procedures -- instrumentation KW - Neurosurgical Procedures -- methods KW - Hippocampus -- surgery KW - Hippocampus -- anatomy & histology KW - Denervation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71799246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hippocampus&rft.atitle=Method+for+making+selective+lesions+of+the+hippocampus+in+macaque+monkeys+using+NMDA+and+a+longitudinal+surgical+approach.&rft.au=Hampton%2C+Robert+R%3BBuckmaster%2C+Cindy+A%3BAnuszkiewicz-Lundgren%2C+Dawn%3BMurray%2C+Elisabeth+A&rft.aulast=Hampton&rft.aufirst=Robert&rft.date=2004-01-01&rft.volume=14&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Hippocampus&rft.issn=10509631&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-07 N1 - Date created - 2004-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of potential human carcinogens using B6.129tm1Trp53 heterozygous null mice and loss of heterozygosity at the Trp53 locus. AN - 71797214; 15055301 AB - Rodent models are often used as surrogates for humans in toxicology and cancer research. Transgenic mice have been useful for studying gene function by loss of function or gain of function through mutation or overexpression. Thus, transgenic or genetically altered mouse models could play an important role in understanding environment-gene interactions. Wild-type Trp53 protein is critical for cell function and maintaining integrity of the genome, which suppresses cancer in humans and rodents. Mice heterozygous for a Trp53 null and a wild-type allele are p53 haplo-insufficient. This reduction in p53 protein results in deficiencies in cell cycle check-point control and induction of apoptosis. p53 Haplo-insufficient mice do not immediately develop neoplasia as a result of this signalling dysregulation. However, exposure to mutagenic carcinogens induces neoplasia during the period in which unexposed, co-isogenic haplo-insufficient and homozygous wild-type mice are free from neoplasia. These observations provide a basis for evaluation of p53 haplo-insufficient mice for mechanism-based identification of carcinogens. Maximum tolerated doses (MTD) determined and used for 2-year NCI/NTP cancer bioassays and/or by 28-day toxicokinetic studies to predict MTD for subchronic studies were, generally, effective in inducing neoplasia with reduced latency in 26-week exposure studies in p53 haplo-insufficient mice. The latency of tumour development may be shortened by requiring only an additional genetic alteration (or alterations) in p53 (mutation or loss of heterozygosity (LOH) involving the Trp53 locus) or in other tumour-suppressor genes by mutation or inactivation. LOH is a loss of genetic loci through chromosomal aberrations and reduction to homozygosity that often results in loss of tumour-suppressor genes. Interspecies extrapolation between rodents and humans is difficult owing to the possibility of species differences, but demonstration of an operational mechanism, such as mutation or loss of p53 function through LOH, may help in reducing uncertainty and, thus, lead to identification of carcinogens of presumed risk to humans. JF - IARC scientific publications AU - French, John E AD - Transgenic Carcinogenesis, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. french@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 271 EP - 287 IS - 157 SN - 0300-5038, 0300-5038 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Heterozygote KW - Mice KW - Chromosome Mapping KW - Loss of Heterozygosity KW - Genes, p53 KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71797214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+and+characterization+of+potential+human+carcinogens+using+B6.129tm1Trp53+heterozygous+null+mice+and+loss+of+heterozygosity+at+the+Trp53+locus.&rft.au=French%2C+John+E&rft.aulast=French&rft.aufirst=John&rft.date=2004-01-01&rft.volume=&rft.issue=157&rft.spage=271&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 - 2004-04-15 N1 - Date created - 2004-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The geographic distribution of radionuclide deposition across the continental US from atmospheric nuclear testing. AN - 71796926; 15063539 AB - For the first time, calculations for the more than 3000 counties of the US have been completed that estimate the average deposition density (Bq m(-2)) of more than 40 radionuclides in fallout from atmospheric nuclear weapons tests conducted in the US (1951-1962) and 19 radionuclides from tests conducted elsewhere in the world (1952-1963). The geographic pattern of deposition across the US, as well as the amount of fallout deposited, varied significantly depending on whether the tests were conducted within or outside of the US. Fallout deposited from the Nevada Test Site (NTS) varied geographically as a result of dispersion and dilution in the atmosphere, the wind patterns following each test, and the occurrence of localized rainfall events. In general, states immediately east of the NTS received the highest deposition from tests conducted there. In contrast, the variation in deposition across the country from global fallout was less than for NTS fallout primarily reflecting variations in annual precipitation across larger regions. Hence, in the eastern and mid-western US, where rainfall is above the national average, higher levels of global fallout were deposited than in the more arid southwestern states. This paper presents a summary of the methods used and findings of our studies on fallout from NTS and global fallout, with emphasis on two of the most important radionuclides, (131)I and (137)Cs. JF - Journal of environmental radioactivity AU - Simon, Steven L AU - Bouville, André AU - Beck, Harold L AD - Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Executive Plaza South, 6120 Executive Boulevard, Bethesda, MD 20892-7238, USA. ssimon@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 91 EP - 105 VL - 74 IS - 1-3 SN - 0265-931X, 0265-931X KW - Cesium Radioisotopes KW - 0 KW - Iodine Radioisotopes KW - Radioactive Fallout KW - Index Medicus KW - United States KW - Environmental Monitoring KW - Cesium Radioisotopes -- analysis KW - Iodine Radioisotopes -- analysis KW - Rain KW - Nuclear Warfare KW - Radioactive Fallout -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71796926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+environmental+radioactivity&rft.atitle=The+geographic+distribution+of+radionuclide+deposition+across+the+continental+US+from+atmospheric+nuclear+testing.&rft.au=Simon%2C+Steven+L%3BBouville%2C+Andr%C3%A9%3BBeck%2C+Harold+L&rft.aulast=Simon&rft.aufirst=Steven&rft.date=2004-01-01&rft.volume=74&rft.issue=1-3&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+radioactivity&rft.issn=0265931X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-14 N1 - Date created - 2004-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TP53 mutation spectra and load: a tool for generating hypotheses on the etiology of cancer. AN - 71793918; 15055300 AB - Among genetic alterations, the activation of proto-oncogenes and inactivation of tumour suppressor genes in affected cells are considered to be the core molecular events that provide a selective growth advantage and clonal expansion during the multistep process of carcinogenesis. The TP53 tumour suppressor gene is mutated in about half of all human cancer cases. The p53 protein modulates multiple cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence and apoptosis. Mutations in the TP53 gene can abrogate these functions, leading to genetic instability and progression to cancer. The molecular archaeology of the TP53 mutation spectrum generates hypotheses concerning the etiology and molecular pathogenesis of each type of cancer. The spectrum of somatic mutations in the TP53 gene, of which 75% are missense mutations, implicates environmental carcinogens and endogenous processes in the etiology of human cancer. The presence of a characteristic TP53 mutation can also manifest a molecular link between exposure to a particular carcinogen and a specific type of human cancer, e.g. exposure to aflatoxin B1 (AFB1) and codon 249 mutations in hepatocellular carcinoma; exposure to ultraviolet (UV) light and C:C-->T:T tandem mutations in skin cancer; and cigarette smoking and the prevalence of G-->T transversions in lung cancer. Although exogenous carcinogens have been shown to target p53 selectively, evidence supporting the endogenous insult of TP53 from oxyradicals and nitrogen-oxyradicals is also accumulating. TP53 mutations can be a biomarker of carcinogen effect. Determining the characteristic TP53 mutation load in non-tumorous tissue, using a highly sensitive mutation assay, can indicate exposure to a specific carcinogen and may also help in identifying individuals at an increased risk of cancer. JF - IARC scientific publications AU - Olivier, Magali AU - Hussain, S Perwez AU - Caron de Fromentel, Claude AU - Hainaut, Pierre AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 247 EP - 270 IS - 157 SN - 0300-5038, 0300-5038 KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Lung Neoplasms -- etiology KW - Hepatitis B -- complications KW - Humans KW - Smoking -- adverse effects KW - Nitric Oxide -- physiology KW - Liver Neoplasms -- etiology KW - Genes, p53 KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71793918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=TP53+mutation+spectra+and+load%3A+a+tool+for+generating+hypotheses+on+the+etiology+of+cancer.&rft.au=Olivier%2C+Magali%3BHussain%2C+S+Perwez%3BCaron+de+Fromentel%2C+Claude%3BHainaut%2C+Pierre%3BHarris%2C+Curtis+C&rft.aulast=Olivier&rft.aufirst=Magali&rft.date=2004-01-01&rft.volume=&rft.issue=157&rft.spage=247&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 - 2004-04-15 N1 - Date created - 2004-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allergen immunotherapy in historical perspective. AN - 71762005; 15042906 JF - Clinical allergy and immunology AU - Cohen, Sheldon G AU - Evans, Richard AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 1 EP - 36 VL - 18 SN - 1075-7910, 1075-7910 KW - Bacterial Vaccines KW - 0 KW - Index Medicus KW - Hypersensitivity -- immunology KW - Bacterial Vaccines -- history KW - Animals KW - Immunity -- immunology KW - Hypersensitivity -- therapy KW - Insect Bites and Stings -- immunology KW - Humans KW - Clinical Trials as Topic -- history KW - Hypersensitivity -- history KW - History, Ancient KW - Insect Bites and Stings -- therapy KW - Insect Bites and Stings -- history KW - History, Modern 1601- KW - Desensitization, Immunologic -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71762005?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+allergy+and+immunology&rft.atitle=Allergen+immunotherapy+in+historical+perspective.&rft.au=Cohen%2C+Sheldon+G%3BEvans%2C+Richard&rft.aulast=Cohen&rft.aufirst=Sheldon&rft.date=2004-01-01&rft.volume=18&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Clinical+allergy+and+immunology&rft.issn=10757910&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-23 N1 - Date created - 2004-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. AN - 71760960; 15032578 AB - Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or cathelicidins. The direct in vitro microbicidal activity of antimicrobial proteins has long been considered an important innate immune defense, although the in vivo relevance has only very recently been established for certain defensins and cathelicidins. Mammalian defensins and cathelicidins have also been shown to have multiple receptor-mediated effects on immune cells. Beta-defensins interact with CCR6; murine beta-defensin-2 in addition activates TLR4. Cathelicidins act on FPRL1-expressing cells. Furthermore, several defensins have considerable immunoenhancing activity. Thus, it appears that mammalian antimicrobial proteins contribute to both innate and adaptive antimicrobial immunity. JF - Annual review of immunology AU - Yang, De AU - Biragyn, Arya AU - Hoover, David M AU - Lubkowski, Jacek AU - Oppenheim, Joost J AD - Basic Research Program, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 181 EP - 215 VL - 22 SN - 0732-0582, 0732-0582 KW - Blood Proteins KW - 0 KW - Defensins KW - Protein Precursors KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Animals KW - Humans KW - Immunity, Innate -- physiology KW - Protein Precursors -- immunology KW - Signal Transduction -- immunology KW - Defensins -- immunology KW - Ribonucleases -- immunology KW - Blood Proteins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71760960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Multiple+roles+of+antimicrobial+defensins%2C+cathelicidins%2C+and+eosinophil-derived+neurotoxin+in+host+defense.&rft.au=Yang%2C+De%3BBiragyn%2C+Arya%3BHoover%2C+David+M%3BLubkowski%2C+Jacek%3BOppenheim%2C+Joost+J&rft.aulast=Yang&rft.aufirst=De&rft.date=2004-01-01&rft.volume=22&rft.issue=&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+immunology&rft.issn=07320582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-02 N1 - Date created - 2004-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial toxicity in fetal Erythrocebus patas monkeys exposed transplacentally to zidovudine plus lamivudine. AN - 71701760; 15000702 AB - This study was designed to investigate fetal mitochondrial toxicity in Erythrocebus patas monkeys exposed in utero to zidovudine (AZT) and lamivudine (3TC), and taken at term. Pregnant patas monkeys were given a daily dose of 40 mg AZT (86% of the human daily dose, based on body weight), for the last 10 weeks (50%) of gestation, and a daily dose of 24 mg 3TC (84% of the human daily dose, based on body weight) for the last 4 weeks of gestation. At term, AZT was found to be incorporated into fetal mitochondrial DNA from skeletal muscle, liver, kidney, and placenta. By transmission electron microscopy (EM) drug-exposed fetal cardiac and skeletal muscle cells showed mitochondrial membrane compromise, mitochondrial proliferation, and damaged sarcomeres, while mitochondria in brain cerebrum and cerebellum were morphologically normal. Substantial depletion of oxidative phosphorylation (OXPHOS) Complex I specific activities was observed in heart (87% reduction in mean, p = 0.02) and skeletal muscle (98% reduction in mean, p = 0.002) from drug-exposed fetuses, compared to unexposed fetuses. In addition Complex IV activity was highly depleted (85% reduction in mean, p = 0.004) in skeletal muscle from the drug-exposed fetuses (p = 0.004). Brain cerebrum and cerebellum showed no statistically significant OXPHOS changes with drug exposure. Mitochondrial DNA quantity was substantially depleted (>50%) in heart, skeletal muscle, cerebellum, and cerebrum from drug-exposed fetuses compared to unexposed controls. Overall, the data indicate that significant mitochondrial damage was observed at birth in monkey fetuses exposed in utero to AZT plus 3TC in a human-equivalent dosing protocol. JF - AIDS research and human retroviruses AU - Gerschenson, Mariana AU - Nguyen, Vi AU - Ewings, Ember L AU - Ceresa, Andrea AU - Shaw, Jaclyn A AU - St Claire, Marisa C AU - Nagashima, Kunio AU - Harbaugh, Steven W AU - Harbaugh, Jeffrey W AU - Olivero, Ofelia A AU - Divi, Rao L AU - Albert, Paul S AU - Poirier, Miriam C AD - Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, 6701 Rockledge Drive, Bethesda, MD 20892, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 91 EP - 100 VL - 20 IS - 1 SN - 0889-2229, 0889-2229 KW - Anti-HIV Agents KW - 0 KW - DNA, Mitochondrial KW - Reverse Transcriptase Inhibitors KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Maternal-Fetal Exchange KW - Animals KW - DNA, Mitochondrial -- drug effects KW - Brain -- drug effects KW - Placenta -- drug effects KW - Organ Specificity KW - Microscopy, Electron KW - Erythrocebus patas KW - Muscle, Skeletal -- drug effects KW - Female KW - Pregnancy KW - Myocardium KW - Anti-HIV Agents -- toxicity KW - Lamivudine -- toxicity KW - Zidovudine -- pharmacokinetics KW - Fetus -- drug effects KW - Zidovudine -- toxicity KW - Mitochondria -- drug effects KW - Lamivudine -- administration & dosage KW - Anti-HIV Agents -- administration & dosage KW - Mitochondria -- metabolism KW - Zidovudine -- administration & dosage KW - Reverse Transcriptase Inhibitors -- toxicity KW - Fetus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71701760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mitochondrial+toxicity+in+fetal+Erythrocebus+patas+monkeys+exposed+transplacentally+to+zidovudine+plus+lamivudine.&rft.au=Gerschenson%2C+Mariana%3BNguyen%2C+Vi%3BEwings%2C+Ember+L%3BCeresa%2C+Andrea%3BShaw%2C+Jaclyn+A%3BSt+Claire%2C+Marisa+C%3BNagashima%2C+Kunio%3BHarbaugh%2C+Steven+W%3BHarbaugh%2C+Jeffrey+W%3BOlivero%2C+Ofelia+A%3BDivi%2C+Rao+L%3BAlbert%2C+Paul+S%3BPoirier%2C+Miriam+C&rft.aulast=Gerschenson&rft.aufirst=Mariana&rft.date=2004-01-01&rft.volume=20&rft.issue=1&rft.spage=91&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 - 2004-05-06 N1 - Date created - 2004-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is male breast cancer similar or different than female breast cancer? AN - 71696257; 14997057 AB - To determine if male breast carcinogenesis was similar to its more common female counterpart, we compared incidence patterns among men and women with breast cancer. Breast cancer records were obtained from the SEER database. Women were stratified by age or = 50 years to simulate premenopausal and postmenopausal breast cancer. Age-adjusted incidence trends were stable among men but increased among women. Male to female breast cancer ratio was higher for blacks than for whites. Favorable prognostic factors reflective of tumor biology (nuclear grade and hormone receptor expression) were more common for men and postmenopausal women than for premenopausal women. For example, low nuclear grade, estrogen and progesterone receptor-positive expression were more common among men and postmenopausal women than among premenopausal women. The age-specific incidence rate curve for men increased steadily for all ages with a constant slope. On the other hand, age-specific rates for women increased rapidly until age 50 years then rose at a slower rate for postmenopausal women. Age-frequency distribution for male breast cancer was unimodal, with peak incidence at age 71 years. Age-frequency distribution for women was bimodal with early-onset and late-onset incidence at 52 and 71 years, respectively. Gender-specific incidence trends differed, most likely reflective of female-related changes in surveillance and/or reproductive risk factors. On the other hand, similar prognostic factor profiles reflective of tumor biology, age-specific incidence rate patterns, and age-frequency distributions suggested that male breast cancer was more like postmenopausal than premenopausal female breast cancer. JF - Breast cancer research and treatment AU - Anderson, William F AU - Althuis, Michelle D AU - Brinton, Louise A AU - Devesa, Susan S AD - NCI/Division of Cancer Prevention, Bethesda, MD 20892-7317, USA. wanderso@mail.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 77 EP - 86 VL - 83 IS - 1 SN - 0167-6806, 0167-6806 KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - SEER Program KW - Aged KW - Breast Neoplasms -- epidemiology KW - Neoplasms, Hormone-Dependent -- epidemiology KW - Aged, 80 and over KW - Risk Factors KW - Breast Neoplasms -- etiology KW - Incidence KW - Middle Aged KW - Neoplasms, Hormone-Dependent -- etiology KW - United States -- epidemiology KW - Female KW - Male KW - Breast Neoplasms, Male -- epidemiology KW - Breast Neoplasms, Male -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71696257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Is+male+breast+cancer+similar+or+different+than+female+breast+cancer%3F&rft.au=Anderson%2C+William+F%3BAlthuis%2C+Michelle+D%3BBrinton%2C+Louise+A%3BDevesa%2C+Susan+S&rft.aulast=Anderson&rft.aufirst=William&rft.date=2004-01-01&rft.volume=83&rft.issue=1&rft.spage=77&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 - 2004-05-13 N1 - Date created - 2004-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RTCGD: retroviral tagged cancer gene database. AN - 71601854; 14681473 AB - Retroviral insertional mutagenesis in mouse hematopoietic tumors provides a potent cancer gene discovery tool in the post-genome-sequence era. To manage multiple high-throughput insertional mutagenesis screening projects, we developed the Retroviral Tagged Cancer Gene Database (RTCGD; http://RTCGD.ncifcrf.gov). A sequence analysis pipeline determines the genomic position of each retroviral integration site cloned from a mouse tumor, the distance between it and the nearest candidate disease gene(s) and its orientation with respect to the candidate gene(s). The pipeline also identifies genomic regions that are targets of retroviral integration in more than one tumor (common integration sites, CISs) and are thus likely to encode a disease gene. Users can search the database using a specified gene symbol, chromosome number or tumor model to identify both CIS genes and unique viral integration sites or compare the integration sites cloned by different laboratories using different models. As a default setting, users first review the CIS Lists and then Clone Lists. CIS Lists describe CISs and their candidate disease genes along with links to other public databases and clone lists. Clone Lists describe the viral integration site clones along with the tumor model and tumor type from which they were cloned, candidate disease gene(s), genomic position and orientation of the integrated provirus with respect to the candidate gene(s). It also provides a pictorial view of the genomic location of each integration site relative to neighboring genes and markers. Researchers can identify integrations of interest and compare their results with those for multiple tumor models and tumor types using RTCGD. JF - Nucleic acids research AU - Akagi, Keiko AU - Suzuki, Takeshi AU - Stephens, Robert M AU - Jenkins, Nancy A AU - Copeland, Neal G AD - Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD 21701, USA. Y1 - 2004/01/01/ PY - 2004 DA - 2004 Jan 01 SP - D523 EP - D527 VL - 32 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Animals KW - Genetic Markers -- genetics KW - Physical Chromosome Mapping KW - Humans KW - Mice KW - Genetic Vectors -- genetics KW - Computational Biology KW - Information Storage and Retrieval KW - Genome KW - Internet KW - Genomics KW - Cloning, Molecular KW - Databases, Genetic KW - Retroviridae -- genetics KW - Neoplasms -- genetics KW - Mutagenesis, Insertional -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71601854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=RTCGD%3A+retroviral+tagged+cancer+gene+database.&rft.au=Akagi%2C+Keiko%3BSuzuki%2C+Takeshi%3BStephens%2C+Robert+M%3BJenkins%2C+Nancy+A%3BCopeland%2C+Neal+G&rft.aulast=Akagi&rft.aufirst=Keiko&rft.date=2004-01-01&rft.volume=32&rft.issue=&rft.spage=D523&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-20 N1 - Date created - 2003-12-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 2003 Jan 1;31(1):193-5 [12519980] EMBO J. 1998 Jul 1;17(13):3714-25 [9649441] Bioinformatics. 2003 Jan 22;19(2):241-8 [12538245] Nucleic Acids Res. 2003 Jan 1;31(1):34-7 [12519942] Nucleic Acids Res. 2003 Jan 1;31(1):38-42 [12519943] Nucleic Acids Res. 2003 Jan 1;31(1):51-4 [12519945] Nat Genet. 1999 Nov;23(3):348-53 [10610183] Nature. 2001 May 17;411(6835):349-54 [11357142] Nucleic Acids Res. 2002 Jan 1;30(1):42-6 [11752249] Genome Res. 2002 Apr;12(4):656-64 [11932250] Genome Res. 2002 Jun;12(6):996-1006 [12045153] Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11293-8 [12151601] Nat Genet. 2002 Sep;32(1):166-74 [12185365] Nat Genet. 2002 Sep;32(1):160-5 [12185367] Nature. 2002 Dec 5;420(6915):520-62 [12466850] Adv Cancer Res. 2003;88:53-99 [12665053] Genome Res. 2003 Jun;13(6B):1505-19 [12819150] J Virol. 1989 May;63(5):1924-8 [2704070] J Virol. 1993 Dec;67(12):7118-24 [8230434] Nucleic Acids Res. 1997 Nov 1;25(21):4419-21 [9336478] J Virol. 2003 Feb;77(3):2056-62 [12525640] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fibrovascular changes misdiagnosed as cytomegalovirus retinitis reactivation in a patient with immune recovery. AN - 71563338; 14679460 AB - A patient with human immunodeficiency virus infection and cytomegalovirus (CMV) retinitis developed immune recovery uveitis as a result of receipt of highly active antiretroviral therapy. Fibrovascular changes occurred in the CMV retinitis scar, were misdiagnosed as CMV retinitis reactivation, and were treated with anti-CMV medication. Fibrovascular membranes can be misdiagnosed as reactivated CMV retinitis, and a proper diagnosis is essential to avoid unnecessary therapy with potentially toxic antiviral medications. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Robinson, Michael R AU - Csaky, Karl G AU - Lee, Susan S AU - Masur, Henry AU - Polis, Michael A AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1863, USA. robinsonm@nei.nih.gov Y1 - 2004/01/01/ PY - 2004 DA - 2004 Jan 01 SP - 139 EP - 141 VL - 38 IS - 1 KW - Index Medicus KW - Humans KW - Adult KW - Male KW - Cytomegalovirus Retinitis -- etiology KW - HIV Infections -- complications KW - AIDS-Related Opportunistic Infections -- pathology KW - Cytomegalovirus Retinitis -- diagnosis KW - Diagnostic Errors KW - AIDS-Related Opportunistic Infections -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71563338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fibrovascular+changes+misdiagnosed+as+cytomegalovirus+retinitis+reactivation+in+a+patient+with+immune+recovery.&rft.au=Robinson%2C+Michael+R%3BCsaky%2C+Karl+G%3BLee%2C+Susan+S%3BMasur%2C+Henry%3BPolis%2C+Michael+A&rft.aulast=Robinson&rft.aufirst=Michael&rft.date=2004-01-01&rft.volume=38&rft.issue=1&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-23 N1 - Date created - 2003-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 15-Lipoxygenase-1 has anti-tumorigenic effects in colorectal cancer. AN - 71562553; 14643174 AB - The localization of 15-lipoxygenase-1 (15-LO-1) in human colorectal carcinoma and normal adjacent tissue was examined using immunohistochemistry. In normal tissues, 15-LO-1 was strongly localized in the mucosal epithelium. Conversely, in tumor tissues, staining for 15-LO-1 was dispersed throughout the tissue, weak in neoplastic epithelium, and strong in stromal inflammatory cells. The addition of 50 microM 13(S)-hydroxyeicosatetraenoic acid (HODE), resulted in decreased cell proliferation after 72 h, but lower concentrations (5 or 10 microM) had no effect compared to vehicle treated Caco-2 cells. In addition, 13(S)-HODE had no effect on apoptosis or differentiation of the Caco-2 cells. Microarray analyses of RNA from Caco-2 cells treated with 5 microM 13(S)-HODE revealed changes in 17 genes. HCT-116 colorectal cells were stably transfected with 15-LO-1. In athymic nude mice, transplantable tumors derived from 15-LO-1 HCT-116 cells were smaller than tumors derived from vector HCT-116 cells. These data demonstrate that 13(S)-HODE induces changes in gene expression and has anti-tumorigenic effects. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Nixon, Jennifer B AU - Kim, Kyung Su AU - Lamb, Patricia W AU - Bottone, Frank G AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 7 EP - 15 VL - 70 IS - 1 SN - 0952-3278, 0952-3278 KW - Antineoplastic Agents KW - 0 KW - Linoleic Acids KW - 13-hydroxy-9,11-octadecadienoic acid KW - 5204-88-6 KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Cell Division -- drug effects KW - Disease Progression KW - Mice KW - Caco-2 Cells KW - Cell Line, Tumor KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Inflammation -- enzymology KW - Neoplasm Transplantation KW - Linoleic Acids -- pharmacology KW - Apoptosis -- drug effects KW - Cell Differentiation -- drug effects KW - Immunohistochemistry KW - Male KW - Inflammation -- pathology KW - Arachidonate 15-Lipoxygenase -- metabolism KW - Colorectal Neoplasms -- pathology KW - Antineoplastic Agents -- metabolism KW - Colorectal Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71562553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=15-Lipoxygenase-1+has+anti-tumorigenic+effects+in+colorectal+cancer.&rft.au=Nixon%2C+Jennifer+B%3BKim%2C+Kyung+Su%3BLamb%2C+Patricia+W%3BBottone%2C+Frank+G%3BEling%2C+Thomas+E&rft.aulast=Nixon&rft.aufirst=Jennifer&rft.date=2004-01-01&rft.volume=70&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-12 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical diagnosis of pheochromocytoma. AN - 71559146; 14674306 JF - Frontiers of hormone research AU - Eisenhofer, Graeme AU - Lenders, Jacques W AU - Pacak, Karel AD - Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md., USA. ge@box-g.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 76 EP - 106 VL - 31 SN - 0301-3073, 0301-3073 KW - Index Medicus KW - Animals KW - Drug Interactions KW - Humans KW - Diet KW - Adrenal Gland Neoplasms -- metabolism KW - Pheochromocytoma -- diagnosis KW - Adrenal Gland Neoplasms -- diagnosis KW - Pheochromocytoma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71559146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Frontiers+of+hormone+research&rft.atitle=Biochemical+diagnosis+of+pheochromocytoma.&rft.au=Eisenhofer%2C+Graeme%3BLenders%2C+Jacques+W%3BPacak%2C+Karel&rft.aulast=Eisenhofer&rft.aufirst=Graeme&rft.date=2004-01-01&rft.volume=31&rft.issue=&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Frontiers+of+hormone+research&rft.issn=03013073&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-12 N1 - Date created - 2003-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA. AN - 71556346; 12974676 AB - The activities of PP1 (protein phosphatase 1), a principal cellular phosphatase that reverses serine/threonine protein phosphorylation, can be altered by inhibitors whose activities are themselves regulated by phosphorylation. We now describe a novel PKC (protein kinase C)-dependent PP1 inhibitor, namely GBPI (gut and brain phosphatase inhibitor). The shorter mRNA that encodes this protein, GBPI-1, is expressed in brain, stomach, small intestine, colon and kidney, whereas a longer GBPI-2 splice variant mRNA is found in testis. Human GBPI-1 mRNA encodes a 145-amino-acid, 16.5 kDa protein with pI 7.92. GBPI contains a consensus PP1-binding motif at residues 21-25 and consensus sites for phosphorylation by enzymes, including PKC, PKA (protein kinase A or cAMP-dependent protein kinase) and casein kinase II. Recombinant GBPI-1-fusion protein inhibits PP1 activity with IC50=3 nM after phosphorylation by PKC. Phospho-GBPI can even enhance PP2A activity by >50% at submicromolar concentrations. Non-phosphorylated GBPI-1 is inactive in both assays. Each of the mutations in amino acids located in potential PP1-binding sequences, K21E+K22E and W25A, decrease the ability of GBPI-1 to inhibit PP1. Mutations in the potential PKC phosphoacceptor site T58E also dramatically decrease the ability of GBPI-1 to inhibit PP1. Interestingly, when PKC-phosphorylated GBPI-1 is further phosphorylated by PKA, it no longer inhibits PP1. Thus, GBPI-1 is well positioned to integrate PKC and PKA modulation of PP1 to regulate differentially protein phosphorylation patterns in brain and gut. GBPI, its closest family member CPI (PKC-potentiated PP1 inhibitor) and two other family members, kinase-enhanced phosphatase inhibitor and phosphatase holoenzyme inhibitor, probably modulate integrated control of protein phosphorylation states in these and other tissues. JF - The Biochemical journal AU - Liu, Qing-Rong AU - Zhang, Ping-Wu AU - Lin, Zhicheng AU - Li, Qi-Fu AU - Woods, Amina S AU - Troncoso, Juan AU - Uhl, George R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program, NIH, Department of Health and Human Services, Box 5180, Baltimore, MD 21224, USA. Y1 - 2004/01/01/ PY - 2004 DA - 2004 Jan 01 SP - 171 EP - 181 VL - 377 KW - PPP1R14D protein, human KW - 0 KW - PPP1R14D protein, rat KW - Proteins KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 1 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Humans KW - Recombinant Fusion Proteins -- isolation & purification KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Tissue Distribution KW - Binding Sites KW - Protein Kinase C -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Brain -- enzymology KW - Proteins -- chemistry KW - Digestive System -- metabolism KW - Phosphoprotein Phosphatases -- metabolism KW - Brain -- metabolism KW - Digestive System -- enzymology KW - Proteins -- metabolism KW - Proteins -- genetics KW - Protein Phosphatase 1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71556346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=GBPI%2C+a+novel+gastrointestinal-+and+brain-specific+PP1-inhibitory+protein%2C+is+activated+by+PKC+and+inactivated+by+PKA.&rft.au=Liu%2C+Qing-Rong%3BZhang%2C+Ping-Wu%3BLin%2C+Zhicheng%3BLi%2C+Qi-Fu%3BWoods%2C+Amina+S%3BTroncoso%2C+Juan%3BUhl%2C+George+R&rft.aulast=Liu&rft.aufirst=Qing-Rong&rft.date=2004-01-01&rft.volume=377&rft.issue=&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=1470-8728&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-15 N1 - Date created - 2003-12-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY122323; GENBANK; AY050669; AY122322; AY122324; AY050673; AY050672; AY050671; AY050670; AF408400; AY179331 N1 - SuppNotes - Cited By: J Neurosci. 2003 Mar 1;23(5):1638-48 [12629168] J Biol Chem. 2003 May 23;278(21):18817-23 [12657641] Biochem Biophys Res Commun. 2003 Jun 27;306(2):382-7 [12804574] Annu Rev Biochem. 1989;58:453-508 [2549856] Biotechniques. 1990 Apr;8(4):404-7 [2340178] Biochem J. 1990 Sep 1;270(2):549-52 [2400401] J Biol Chem. 1990 Nov 25;265(33):20369-76 [2173704] Cell. 1991 Aug 23;66(4):807-15 [1715244] Eur J Biochem. 1991 Sep 15;200(3):715-21 [1915343] J Biol Chem. 1991 Dec 15;266(35):23796-801 [1660885] Crit Rev Biochem Mol Biol. 1992;27(3):227-81 [1350240] Eur J Biochem. 1992 Dec 15;210(3):1023-35 [1336455] J Biol Chem. 1993 Jan 25;268(3):2106-12 [8420981] J Biol Chem. 1993 Mar 25;268(9):6505-10 [8384214] J Biol Chem. 1993 Jun 25;268(18):13172-7 [8390458] J Biol Chem. 1994 Jan 14;269(2):944-54 [8288648] Nature. 1994 Jun 9;369(6480):486-8 [7515479] Mol Cell Biol. 1994 Oct;14(10):6789-96 [7935396] J Mol Biol. 1995 Dec 15;254(5):942-59 [7500362] J Biochem. 1995 Dec;118(6):1104-7 [8720121] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3536-41 [9108011] EMBO J. 1997 Apr 15;16(8):1876-87 [9155014] Bioorg Med Chem. 1997 Sep;5(9):1739-50 [9354230] J Physiol. 1998 May 1;508 ( Pt 3):871-81 [9518739] Science. 1998 Aug 7;281(5378):838-42 [9694658] J Biol Chem. 1999 Feb 5;274(6):3485-95 [9920894] J Biol Chem. 1999 Mar 19;274(12):7870-8 [10075680] J Neurochem. 1999 May;72(5):2015-21 [10217279] Neuron. 1999 Jul;23(3):435-47 [10433257] J Biol Chem. 2002 Apr 12;277(15):13312-20 [11812771] Biochem Biophys Res Commun. 2002 Oct 4;297(4):773-8 [12359219] Biochem J. 2002 Oct 15;367(Pt 2):517-24 [12144526] Biochem Biophys Res Commun. 2003 Mar 7;302(2):186-92 [12604330] Biochemistry. 1999 Dec 21;38(51):16952-7 [10606530] Chem Biol. 2000 Jan;7(1):R13-23 [10662690] Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1856-60 [10677546] FEBS Lett. 2000 Jun 23;475(3):197-200 [10869555] Biochem Biophys Res Commun. 2000 Aug 11;274(3):825-30 [10924361] Cell Signal. 2001 Jan;13(1):7-16 [11257442] J Biol Chem. 2001 Oct 26;276(43):39858-63 [11517233] J Biol Chem. 2001 Nov 23;276(47):44078-82 [11535607] J Cell Sci. 2002 Jan 15;115(Pt 2):241-56 [11839776] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 17Beta-estradiol confers a protective effect against transforming growth factor-beta2-induced cataracts in female but not male lenses. AN - 71554620; 14667828 AB - Transforming growth factor-beta2 (TGF-beta2) induces anterior subcapsular cataracts, with a marked increase in cytoskeletal and extracellular matrix proteins, such as alpha-smooth muscle actin (alphaSMA). It has been shown that 17beta-estradiol (E2) can prevent TGF-beta2-induced cataracts in lenses from ovariectomized female rats. The purpose of the current study was to extend this finding by testing whether E2 can prevent TGF-beta2-induced cataracts and inhibit the induction of alphaSMA gene expression in normal male and normal, non-ovariectomized female rats.Sex-specific differences were observed in 17-week-old rat lenses incubated in 0.15 ng ml(-1) TGF-beta2 and in 10(-8)M E2 plus TGF-beta2. TGF-beta2 induced approximately twice as many anterior subcapsular plaques and 1.5 times the level of alphaSMA transcripts in male lenses compared to female lenses. Notably, E2 inhibited plaque formation and the induction of alphaSMA transcripts in female rat lenses but not in male rat lenses. E2 also inhibited the induction of alphaSMA in TGF-beta2-incubated lenses from ovariectomized female rats.E2 prevented lens opacification and the induction of alphaSMA gene expression in female, but not male, lenses. This sex-specific difference may have implications for studies on the therapeutic use of estradiol for treatment of secondary cataract. JF - Experimental eye research AU - Chen, Zhengguang AU - John, Molykutty AU - Subramanian, Saradha AU - Chen, Hong AU - Carper, Deborah AD - Section on Molecular Therapeutics, Building 6, Room 232, National Eye Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 67 EP - 74 VL - 78 IS - 1 SN - 0014-4835, 0014-4835 KW - Actins KW - 0 KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta2 KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Rats KW - Animals KW - Actins -- genetics KW - Sex Factors KW - Ovariectomy KW - Gene Expression Regulation -- drug effects KW - Actins -- biosynthesis KW - Organ Culture Techniques KW - Male KW - Female KW - Cataract -- pathology KW - Lens, Crystalline -- pathology KW - Lens, Crystalline -- metabolism KW - Transforming Growth Factor beta -- toxicity KW - Lens, Crystalline -- drug effects KW - Estradiol -- pharmacology KW - Cataract -- prevention & control KW - Cataract -- chemically induced KW - Transforming Growth Factor beta -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71554620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+eye+research&rft.atitle=17Beta-estradiol+confers+a+protective+effect+against+transforming+growth+factor-beta2-induced+cataracts+in+female+but+not+male+lenses.&rft.au=Chen%2C+Zhengguang%3BJohn%2C+Molykutty%3BSubramanian%2C+Saradha%3BChen%2C+Hong%3BCarper%2C+Deborah&rft.aulast=Chen&rft.aufirst=Zhengguang&rft.date=2004-01-01&rft.volume=78&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Experimental+eye+research&rft.issn=00144835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-09 N1 - Date created - 2003-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert panel review. AN - 71550735; 14564513 AB - This article summarizes the views of an expert meeting of cardiologists and oncologists on the use of dexrazoxane in anthracycline-based chemotherapy. Anthracycline-induced cardiotoxicity remains a major concern and new trends in treatment (e.g., combination of an anthracycline with other agents) will ensure that it remains a problem. Dexrazoxane reduces this cardiotoxicity in adults and children with a range of tumor types. Further research may help to identify those patients who are at particular risk of cardiotoxicity and who would benefit the most from dexrazoxane. There are also numerous possibilities for dexrazoxane in other clinical situations, which must be addressed in future trials. JF - Journal of cancer research and clinical oncology AU - Swain, S M AU - Vici, P AD - National Institutes of Health, Department of Health and Human Services, 8901 Wisconsin Avenue, Building 8, Room 5101, Bethesda, MD 20889-5105, USA. swains@mail.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 1 EP - 7 VL - 130 IS - 1 SN - 0171-5216, 0171-5216 KW - Anthracyclines KW - 0 KW - Antibiotics, Antineoplastic KW - Cardiotonic Agents KW - Razoxane KW - 5AR83PR647 KW - Index Medicus KW - Humans KW - Razoxane -- therapeutic use KW - Antibiotics, Antineoplastic -- administration & dosage KW - Razoxane -- administration & dosage KW - Cardiotonic Agents -- administration & dosage KW - Heart -- drug effects KW - Cardiotonic Agents -- therapeutic use KW - Anthracyclines -- administration & dosage KW - Anthracyclines -- adverse effects KW - Antibiotics, Antineoplastic -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71550735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+current+and+future+role+of+dexrazoxane+as+a+cardioprotectant+in+anthracycline+treatment%3A+expert+panel+review.&rft.au=Swain%2C+S+M%3BVici%2C+P&rft.aulast=Swain&rft.aufirst=S&rft.date=2004-01-01&rft.volume=130&rft.issue=1&rft.spage=1&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 - 2004-04-15 N1 - Date created - 2003-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Legal barriers to alcohol screening in emergency departments and trauma centers. AN - 67309900; 19006994 JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Chezem, Linda AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. PY - 2004 SP - 73 EP - 79 VL - 28 IS - 2 SN - 1535-7414, 1535-7414 KW - Index Medicus KW - Insurance, Health -- statistics & numerical data KW - Humans KW - United States -- epidemiology KW - Alcoholism -- epidemiology KW - Trauma Centers -- statistics & numerical data KW - Mass Screening -- legislation & jurisprudence KW - Emergency Medical Services -- legislation & jurisprudence KW - Trauma Centers -- legislation & jurisprudence KW - Mass Screening -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67309900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Legal+barriers+to+alcohol+screening+in+emergency+departments+and+trauma+centers.&rft.au=Chezem%2C+Linda&rft.aulast=Chezem&rft.aufirst=Linda&rft.date=2004-01-01&rft.volume=28&rft.issue=2&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-12-11 N1 - Date created - 2008-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biomarkers for alcohol use and abuse--a summary. AN - 67307807; 19006989 AB - Clinicians can use several biochemical measurements to objectively assess patients' current or past alcohol use. However, none of these currently available biomarkers-including measures of various liver enzymes and blood volume--are ideal. Several more experimental markers hold promise for measuring acute alcohol consumption and relapse. These include certain alcohol byproducts, such as acetaldehyde, ethyl glucuronide (EtG), and fatty acid ethyl esters (FAEE), as well as two measures of sialic acid, a carbohydrate that appears to be altered in alcoholics. Some progress has been made in finding markers that predict people's genetic predisposition to alcoholism, such as genetic differences in several neurotransmitters, including beta-endorphin and gamma-aminobutryic acid (GABA). JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Peterson, Karen AD - Research Policy and Special Programs Branch, National Institute on Alcohol Abuse and Alcoholism's Office of Scientific Affairs, Bethesda, Maryland, USA. PY - 2004 SP - 30 EP - 37 VL - 28 IS - 1 SN - 1535-7414, 1535-7414 KW - Biomarkers KW - 0 KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - N-Acetylneuraminic Acid KW - GZP2782OP0 KW - Index Medicus KW - Aspartate Aminotransferases -- blood KW - Alanine Transaminase -- blood KW - Humans KW - gamma-Glutamyltransferase -- blood KW - N-Acetylneuraminic Acid -- blood KW - Alcoholism -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67307807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Biomarkers+for+alcohol+use+and+abuse--a+summary.&rft.au=Peterson%2C+Karen&rft.aulast=Peterson&rft.aufirst=Karen&rft.date=2004-01-01&rft.volume=28&rft.issue=1&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2008-12-11 N1 - Date created - 2008-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain hyperthermia during physiological and pathological conditions: causes, mechanisms, and functional implications. AN - 67297400; 16181068 AB - Although brain metabolism consumes high amounts of energy and is accompanied by intense heat production, brain temperature is usually considered a stable, tightly regulated homeostatic parameter. Current animal research, however, has shown that different forms of functional neural activation are accompanied by relatively large brain hyperthermia (2-3 degrees C), which has an intra-brain origin; cerebral circulation plays a crucial role in dissipating this potentially dangerous metabolic heat from brain tissue. Brain hyperthermia, therefore, reflects enhanced brain metabolism and is a normal physiological phenomenon that can be enhanced by interaction with common elements of an organism's environment. There are, however, instances when brain hyperthermia becomes pathological. Both exposure to extreme environmental heat and intense physical activity in a hot, humid environment restrict heat dissipation from the brain and may push brain temperatures to the limits of physiological functions, resulting in acute life-threatening complications and destructive effects on neural cells and functions of the brain as a whole. Brain hyperthermia may also result from metabolic activation induced by various addictive drugs, such as heroin, cocaine, and meth-amphetamine (METH). In contrast to heroin and cocaine, whose stimulatory effects on brain metabolism invert with increases in dose, METH increases brain metabolism dose-dependently and diminishes heat dissipation because of peripheral vasoconstriction. The thermogenic effects of this drug, moreover, are enhanced during physiological activation, resulting in pathological brain hyperthermia. Since brain hyperthermia exacerbates drug-induced toxicity and is destructive to neural cells, uncontrollable use of amphetamine-like drugs under conditions restricting heat dissipation from the brain may result both in acute life-threatening complications and clinically latent but dangerous morphological and functional brain destruction. JF - Current neurovascular research AU - Kiyatkin, Eugene A AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, DHHS, 5500 Nathan Shock, Baltimore, Maryland 21224, USA. ekiyatki@intra.nida.nih.gov Y1 - 2004/01// PY - 2004 DA - January 2004 SP - 77 EP - 90 VL - 1 IS - 1 SN - 1567-2026, 1567-2026 KW - Methamphetamine KW - 44RAL3456C KW - Heroin KW - 70D95007SX KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Heroin -- adverse effects KW - Methamphetamine -- adverse effects KW - Humans KW - Physical Exertion KW - Hot Temperature -- adverse effects KW - Brain -- metabolism KW - Cocaine -- adverse effects KW - Thermogenesis KW - Fever -- chemically induced KW - Fever -- etiology KW - Brain Diseases -- chemically induced KW - Fever -- physiopathology KW - Brain Diseases -- physiopathology KW - Brain Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67297400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurovascular+research&rft.atitle=Brain+hyperthermia+during+physiological+and+pathological+conditions%3A+causes%2C+mechanisms%2C+and+functional+implications.&rft.au=Kiyatkin%2C+Eugene+A&rft.aulast=Kiyatkin&rft.aufirst=Eugene&rft.date=2004-01-01&rft.volume=1&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Current+neurovascular+research&rft.issn=15672026&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-20 N1 - Date created - 2005-09-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Curr Neurovasc Res. 2004 Apr;1(2):191 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exploring tick saliva: from biochemistry to 'sialomes' and functional genomics. AN - 67288042; 15938506 AB - Tick saliva, a fluid once believed to be only relevant for lubrication of mouthparts and water balance, is now well known to be a cocktail of potent anti-haemostatic, anti-inflammatory and immunomodulatory molecules that helps these arthropods obtain a blood meal from their vertebrate hosts. The repertoire of pharmacologically active components in this cocktail is impressive as well as the number of targets they specifically affect. These salivary components change the physiology of the host at the bite site and, consequently, some pathogens transmitted by ticks take advantage of this change and become more infective. Tick salivary proteins have therefore become an attractive target to control tick-borne diseases. Recent advances in molecular biology, protein chemistry and computational biology are accelerating the isolation, sequencing and analysis of a large number of transcripts and proteins from the saliva of different ticks. Many of these newly isolated genes code for proteins with homologies to known proteins allowing identification or prediction of their function. However, most of these genes code for proteins with unknown functions therefore opening the road to functional genomic approaches to identify their biological activities and roles in blood feeding and hence, vaccine development to control tick-borne diseases. JF - Parasitology AU - Valenzuela, J G AD - Vector Molecular Biology Unit, Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, 4 Center Drive, 4/B2-35, Bethesda, MD 20892, USA. jvalenzuela@niaid.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - S83 EP - S94 VL - 129 Suppl SN - 0031-1820, 0031-1820 KW - Anti-Inflammatory Agents KW - 0 KW - Anticoagulants KW - Platelet Aggregation Inhibitors KW - Salivary Proteins and Peptides KW - Vaccines KW - Vasodilator Agents KW - Index Medicus KW - Saliva -- immunology KW - Anti-Inflammatory Agents -- metabolism KW - Animals KW - Saliva -- physiology KW - Vaccines -- classification KW - Vaccination -- methods KW - Saliva -- chemistry KW - Host-Parasite Interactions KW - Anticoagulants -- metabolism KW - Vasodilator Agents -- metabolism KW - Platelet Aggregation Inhibitors -- metabolism KW - Ticks -- physiology KW - Arachnid Vectors -- chemistry KW - Ticks -- chemistry KW - Bites and Stings -- immunology KW - Salivary Proteins and Peptides -- immunology KW - Arachnid Vectors -- physiology KW - Tick-Borne Diseases -- transmission KW - Tick-Borne Diseases -- prevention & control KW - Arachnid Vectors -- genetics KW - Salivary Proteins and Peptides -- genetics KW - Ticks -- genetics KW - Genomics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67288042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Parasitology&rft.atitle=Exploring+tick+saliva%3A+from+biochemistry+to+%27sialomes%27+and+functional+genomics.&rft.au=Valenzuela%2C+J+G&rft.aulast=Valenzuela&rft.aufirst=J&rft.date=2004-01-01&rft.volume=129+Suppl&rft.issue=&rft.spage=S83&rft.isbn=&rft.btitle=&rft.title=Parasitology&rft.issn=00311820&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-07-17 N1 - Date created - 2005-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selecting the best heart valve for your patient: mechanical or tissue. AN - 67273225; 15805765 AB - This review provides general guidance for heart valve selection. Mechanical heart valves exhibit excellent durability and hemodynamic performance but require anticoagulation to reduce thromboembolism, and therefore risk of anticoagulation-related hemorrhage is increased. Tissue valves were introduced to avoid anticoagulation, but in fact often do not, and lack durability. A literature review was performed to compare the complications of thromboembolism, anticoagulation-related hemorrhage, reoperation structural valve deterioration, and reoperative mortality associated with mechanical and tissue valves. The thromboembolism rates for mechanical and tissue valves are equivalent. During their lives, many recipients of tissue valves receive anticoagulation therapy due to comorbid conditions. The anticoagulation-related blood loss rates associated with mitral mechanical valves and mitral tissue valves are equivalent, whereas the blood loss rates associated with aortic tissue valves are less than those associated with aortic mechanical valves. JF - The American heart hospital journal AU - Phillips, Steven J AD - National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. sphillip@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 149 EP - 152 VL - 2 IS - 3 SN - 1541-9215, 1541-9215 KW - Anticoagulants KW - 0 KW - Index Medicus KW - Hemorrhage -- chemically induced KW - Risk Factors KW - Humans KW - Heart Valve Diseases -- surgery KW - Thromboembolism -- prevention & control KW - Prosthesis Design KW - Thromboembolism -- chemically induced KW - Decision Making KW - Risk Assessment KW - Anticoagulants -- therapeutic use KW - Anticoagulants -- adverse effects KW - Transplants -- utilization KW - Anticoagulants -- contraindications KW - Heart Valve Prosthesis -- adverse effects KW - Heart Valve Prosthesis -- utilization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67273225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+heart+hospital+journal&rft.atitle=Selecting+the+best+heart+valve+for+your+patient%3A+mechanical+or+tissue.&rft.au=Phillips%2C+Steven+J&rft.aulast=Phillips&rft.aufirst=Steven&rft.date=2004-01-01&rft.volume=2&rft.issue=3&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=The+American+heart+hospital+journal&rft.issn=15419215&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-06 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic, genomic, and bioinformatic tools for studying breast cancer progression. AN - 67237033; 15687700 AB - Cancer susceptibility is a complex interaction of an individual's genetic composition and environmental exposures. Huge strides have been made in understanding cancer over the past 100 years, from the recognition of cancer as a genetic disease, to the identification of specific carcinogens, isolation of oncogenes and the recognition of tumor suppressors. Analysis of high-risk familial cancers has led to the discovery of new tumor suppressor genes and important cancer pathways. These families however represent only a small fraction of cancer in the general population. Most cancer instead probably results of an intricate interaction of polymorphic susceptibility genes with the sea of environmental exposures that humans experience. Although the central cadre of cancer genes is known, little is understood about the peripheral genes that likely comprise the polymorphic susceptibility loci. The challenge for cancer genetics is therefore to move forward from the Mendelian genetics of the rare familial cancer syndromes into the field of quantitative trait loci, susceptibility factors, and modifier genes. By identifying the genes that modulate an individual's susceptibility to cancer after an environmental exposure, researchers will be able to gain important insights into human biology, cancer prevention and treatment. The most efficient strategies to identify and characterize modifier loci will likely be those that are transdisciplinary, encompassing a variety of different "-omic" technologies. The application of a "trans-omic" techniques in our laboratory to the study of breast cancer dissemination is presented here as an illustration of the strategy. JF - Breast disease AU - Hunter, Kent AD - Laboratory of Population Genetics, CCR/NCI/NIH, Bldg 41 Rm 702, 41 Library Drive, Bethesda, MD 20892, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 83 EP - 91 VL - 19 SN - 0888-6008, 0888-6008 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67237033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+disease&rft.atitle=Genetic%2C+genomic%2C+and+bioinformatic+tools+for+studying+breast+cancer+progression.&rft.au=Hunter%2C+Kent&rft.aulast=Hunter&rft.aufirst=Kent&rft.date=2004-01-01&rft.volume=19&rft.issue=&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Breast+disease&rft.issn=08886008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-21 N1 - Date created - 2005-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanisms of breast cancer progression: lessons from mouse mammary cancer models and gene expression profiling. AN - 67233477; 15687699 AB - The development of breast cancer is thought to occur through a multi-step process. The majority of breast cancers likely develop over extended periods of time arising from early, pre-invasive lesions such as atypical ductal hyperplasia (ADH) and carcinoma in situ (DCIS), progressing to invasive carcinoma and culminating in metastatic disease. However, the molecular mechanisms underlying this process are still poorly understood. The molecular analysis of this multi-step process in human patients is hampered by the difficulty in obtaining tissue samples at all tumor stages, especially from the same patient. In contrast, mouse models of mammary cancer progression are amenable to pathological, genetic and biochemical analyses at all tumor stages. Global gene expression profiling allows for simultaneous interrogation of the expression of thousands of genes and provides important opportunities to identify molecular signatures of tumor progression. This approach provides a means to define networks of cancer-related genes and their potential role in tumor progression. In this review, we discuss mouse models that have contributed substantially to understanding the molecular mechanisms of breast cancer progression and insights gained from gene expression profiling of mouse mammary cancer models and human breast cancer. JF - Breast disease AU - Ye, Yumei AU - Qiu, Ting Hu AU - Kavanaugh, Claudine AU - Green, Jeffrey E AD - Transgenic Oncogenesis Group, Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Building 41, Room C629, 41 Medlars Dr., Bethesda, MD 20892, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 69 EP - 82 VL - 19 SN - 0888-6008, 0888-6008 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67233477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+disease&rft.atitle=Molecular+mechanisms+of+breast+cancer+progression%3A+lessons+from+mouse+mammary+cancer+models+and+gene+expression+profiling.&rft.au=Ye%2C+Yumei%3BQiu%2C+Ting+Hu%3BKavanaugh%2C+Claudine%3BGreen%2C+Jeffrey+E&rft.aulast=Ye&rft.aufirst=Yumei&rft.date=2004-01-01&rft.volume=19&rft.issue=&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Breast+disease&rft.issn=08886008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-21 N1 - Date created - 2005-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identifying environmental contributions to autism: provocative clues and false leads. AN - 67225615; 15666339 AB - The potential role of environmental factors in autism spectrum disorders (ASD) is an area of emerging interest within the public and scientific communities. The high degree of heritability of ASD suggests that environmental influences are likely to operate through their interaction with genetic susceptibility during vulnerable periods of development. Evaluation of the plausibility of specific neurotoxicants as etiological agents in ASD should be guided by toxicological principles, including dose-effect dependency and pharmacokinetic parameters. Clinical and epidemiological investigations require the use of sufficiently powered study designs with appropriate control groups and unbiased case ascertainment and exposure assessment. Although much of the existing data that have been used to implicate environmental agents in ASD are limited by methodological shortcomings, a number of efforts are underway that will allow more rigorous evaluation of the role of environmental exposures in the etiology and/or phenotypic expression of the disorder. Surveillance systems are now in place that will provide reliable prevalence estimates going forward in time. Anticipated discoveries in genetics, brain pathology, and the molecular/cellular basis of functional impairment in ASD are likely to provide new opportunities to explore environmental aspects of this disorder. Copyright 2004 Wiley-Liss, Inc. JF - Mental retardation and developmental disabilities research reviews AU - Lawler, Cindy P AU - Croen, Lisa A AU - Grether, Judith K AU - Van de Water, Judy AD - Division of Extramural Research and Training, National Institute of Environmental Health Sciences, PO Box 1123, MD EC-23, Research Triangle Park, NC 27709, USA. lawler@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 292 EP - 302 VL - 10 IS - 4 SN - 1080-4013, 1080-4013 KW - Autoantibodies KW - 0 KW - Hazardous Substances KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Pregnancy Complications KW - Serotonin -- physiology KW - Hazardous Substances -- adverse effects KW - Humans KW - Brain -- drug effects KW - Brain -- embryology KW - Autoantibodies -- immunology KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - Autistic Disorder -- etiology KW - Environmental Exposure -- adverse effects KW - Autistic Disorder -- physiopathology KW - Autistic Disorder -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67225615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mental+retardation+and+developmental+disabilities+research+reviews&rft.atitle=Identifying+environmental+contributions+to+autism%3A+provocative+clues+and+false+leads.&rft.au=Lawler%2C+Cindy+P%3BCroen%2C+Lisa+A%3BGrether%2C+Judith+K%3BVan+de+Water%2C+Judy&rft.aulast=Lawler&rft.aufirst=Cindy&rft.date=2004-01-01&rft.volume=10&rft.issue=4&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=Mental+retardation+and+developmental+disabilities+research+reviews&rft.issn=10804013&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-07 N1 - Date created - 2005-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bone marrow transplantation reveals roles for brain macrophage/microglia TNF signaling and nitric oxide production in excitotoxic neuronal death. AN - 67224803; 15626822 AB - The signaling mechanisms by which brain macrophages and microglia (BMM) respond to injury and disease, and how their responses affect neurodegenerative processes are largely unknown. Here we show that bone marrow transplantation can be used to introduce genetically modified BMM into the adult mouse brain to reveal the functions of one or more BMM genes in neuronal injury responses. Mice in which endogenous BMM were replaced with cells from mice lacking p55 and p75 tumor necrosis factor (TNF) receptors exhibit increased vulnerability of hippocampal neurons to excitotoxic injury suggesting a role for TNF signaling in BMM in the excitotoxic injury response. Neurons in the brains of mice with BMM lacking nitric oxide synthase exhibit reduced protein nitration and are less vulnerable to excitotoxic damage, indicating a pivotal role for BMM nitric oxide production in excitotoxic neuronal damage. JF - Neuromolecular medicine AU - Guo, Zhihong AU - Iyun, Titilola AU - Fu, Weiming AU - Zhang, Peisu AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 219 EP - 234 VL - 5 IS - 3 SN - 1535-1084, 1535-1084 KW - Neurotoxins KW - 0 KW - Nitrates KW - Receptor, Nerve Growth Factor KW - Receptors, Nerve Growth Factor KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Animals KW - Cell Death -- physiology KW - Receptors, Nerve Growth Factor -- genetics KW - Hippocampus -- metabolism KW - Nitrates -- metabolism KW - Cell Differentiation -- genetics KW - Mice KW - Stem Cells -- physiology KW - Mice, Knockout KW - Genetic Predisposition to Disease -- genetics KW - Nitric Oxide Synthase -- genetics KW - Signal Transduction -- genetics KW - Mice, Inbred C57BL KW - Hippocampus -- physiopathology KW - Hippocampus -- pathology KW - Bone Marrow Transplantation KW - Macrophages -- cytology KW - Neurotoxins -- metabolism KW - Macrophages -- transplantation KW - Nerve Degeneration -- metabolism KW - Nitric Oxide -- genetics KW - Nerve Degeneration -- physiopathology KW - Microglia -- cytology KW - Nitric Oxide -- metabolism KW - Microglia -- transplantation KW - Tumor Necrosis Factor-alpha -- genetics KW - Microglia -- metabolism KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67224803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuromolecular+medicine&rft.atitle=Bone+marrow+transplantation+reveals+roles+for+brain+macrophage%2Fmicroglia+TNF+signaling+and+nitric+oxide+production+in+excitotoxic+neuronal+death.&rft.au=Guo%2C+Zhihong%3BIyun%2C+Titilola%3BFu%2C+Weiming%3BZhang%2C+Peisu%3BMattson%2C+Mark+P&rft.aulast=Guo&rft.aufirst=Zhihong&rft.date=2004-01-01&rft.volume=5&rft.issue=3&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Neuromolecular+medicine&rft.issn=15351084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-03 N1 - Date created - 2004-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Designing mouse behavioral tasks relevant to autistic-like behaviors. AN - 67215880; 15666335 AB - The importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e., similarity to the underlying causes of the disease; and (3) predictive validity, i.e., expected responses to treatments that are effective in the human disease. There is a growing need for mouse behavioral tasks with all three types of validity for modeling the symptoms of autism. We are in the process of designing a set of tasks with face validity for the defining features of autism: deficits in appropriate reciprocal social interactions, deficits in verbal social communication, and high levels of ritualistic repetitive behaviors. Social approach is tested in an automated three-chambered apparatus that offers the subject a choice between a familiar environment, a novel environment, and a novel environment containing a stranger mouse. Preference for social novelty is tested in the same apparatus, with a choice between the start chamber, the chamber containing a familiar mouse, and the chamber containing a stranger mouse. Social communication is evaluated by measuring the ultrasonic distress vocalizations emitted by infant mouse pups and the parental response of retrieving the pup to the nest. Resistance to change in ritualistic repetitive behaviors is modeled by forcing a change in habit, including reversal of the spatial location of a reinforcer in a T-maze task and in the Morris water maze. Mouse behavioral tasks that may model additional features of autism are discussed, including tasks relevant to anxiety, seizures, sleep disturbances, and sensory hypersensitivity. Applications of these tests include (1) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism, (2) characterization of mutant mice derived from random chemical mutagenesis, (3) DNA microarray analyses of genes in inbred strains of mice that differ in social interaction, social communication and resistance to change in habit, and (4) evaluation of proposed therapeutics for the treatment of autism. Copyright 2004 Wiley-Liss, Inc. JF - Mental retardation and developmental disabilities research reviews AU - Crawley, Jacqueline N AD - Mouse Behavioral Phenotyping Laboratory, Neurodevelopmental Disorders Research Center, University of North Carolina, Chapel Hill, North Carolina, USA. crawleyj@intra.nimh.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 248 EP - 258 VL - 10 IS - 4 SN - 1080-4013, 1080-4013 KW - Index Medicus KW - Maze Learning KW - Animals KW - Mice, Mutant Strains KW - Animal Communication KW - Social Behavior KW - Mice KW - Behavior, Animal KW - Autistic Disorder KW - Disease Models, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67215880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mental+retardation+and+developmental+disabilities+research+reviews&rft.atitle=Designing+mouse+behavioral+tasks+relevant+to+autistic-like+behaviors.&rft.au=Crawley%2C+Jacqueline+N&rft.aulast=Crawley&rft.aufirst=Jacqueline&rft.date=2004-01-01&rft.volume=10&rft.issue=4&rft.spage=248&rft.isbn=&rft.btitle=&rft.title=Mental+retardation+and+developmental+disabilities+research+reviews&rft.issn=10804013&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-07 N1 - Date created - 2005-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA polymerases eta and iota. AN - 67168897; 15588844 JF - Advances in protein chemistry AU - Vaisman, Alexandra AU - Lehmann, Alan R AU - Woodgate, Roger AD - Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 205 EP - 228 VL - 69 SN - 0065-3233, 0065-3233 KW - DNA polymerase iota KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Index Medicus KW - Animals KW - DNA Damage KW - Humans KW - Mutagenesis KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67168897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+protein+chemistry&rft.atitle=DNA+polymerases+eta+and+iota.&rft.au=Vaisman%2C+Alexandra%3BLehmann%2C+Alan+R%3BWoodgate%2C+Roger&rft.aulast=Vaisman&rft.aufirst=Alexandra&rft.date=2004-01-01&rft.volume=69&rft.issue=&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Advances+in+protein+chemistry&rft.issn=00653233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-16 N1 - Date created - 2004-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - History of the science of mutagenesis from a personal perspective. AN - 67167686; 15529325 AB - A career in the study of mutagenesis spanning 50 years is a gift few scientists have been bestowed. My tenure in the field started in 1953, the year the structure of DNA became known (Watson and Crick [1953]: Nature 171:737). Before that time, it was suspected that DNA was the genetic material based on the research of Oswald T. Avery (Avery et al. [1944]: J Exp Med 79:137), but many scientists still believed that proteins or polysaccharides could be the genetic material. The present article describes a lifetime of personal experience in the field of chemical mutagenesis. The methods used to treat viruses with chemical mutagens were well developed in the 1950s. Here I review the early use of nitrous acid and hydroxylamine as mutagens in eukaryotes, the development of methods for the metabolic activation of mutagens by microsomal preparations, and the selection of a mutant tester set for the qualitative characterization of the mutagenic activity of chemicals. These studies provided critical background information that was used by Bruce Ames in the development of his Salmonella/microsome assay, widely known as the Ames test (Ames et al. [1973]: Proc Nat Acad Sci USA 70:2281-2285). This article also describes how a set of diagnostic chemical mutagens was selected and used to identify the molecular nature of gene mutations. Today, DNA sequencing has replaced the use of diagnostic mutagens, but studies of this kind formed the foundation of modern mutation research. They also helped set the stage for the organization of the Environmental Mutagen Society and the Environmental Mutagen Information Center, which are described. The article ends with the development of mammalian single-cell mutation assays, the first system for studying in vivo mutagenesis using recoverable vectors in transgenic animals, other mutation assays in intact mammals, and my thoughts on the critically important area of germ cell mutagenesis. This narrative is not a complete autobiographical account, in that I have selected only those experiences that I feel are important for the history of the field and the edification of today's students. I hope I have shown that science not only is a valuable pursuit but can also be fun, stimulating, and satisfying. A good sense of humor and the knowledge that many discoveries come by serendipity are essential. JF - Environmental and molecular mutagenesis AU - Malling, Heinrich V AD - Laboratory of Toxicology, Environmental Toxicology Program, Department of Human Health Services, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. malling@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 372 EP - 386 VL - 44 IS - 5 SN - 0893-6692, 0893-6692 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Animals KW - History, 20th Century KW - Humans KW - Carcinogens, Environmental -- history KW - Mutagenicity Tests -- history KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67167686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=History+of+the+science+of+mutagenesis+from+a+personal+perspective.&rft.au=Malling%2C+Heinrich+V&rft.aulast=Malling&rft.aufirst=Heinrich&rft.date=2004-01-01&rft.volume=44&rft.issue=5&rft.spage=372&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 - 2005-03-08 N1 - Date created - 2004-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integrating phenotypic and expression profiles to map arsenic-response networks. AN - 67159728; 15575969 AB - Arsenic is a nonmutagenic carcinogen affecting millions of people. The cellular impact of this metalloid in Saccharomyces cerevisiae was determined by profiling global gene expression and sensitivity phenotypes. These data were then mapped to a metabolic network composed of all known biochemical reactions in yeast, as well as the yeast network of 20,985 protein-protein/protein-DNA interactions. While the expression data unveiled no significant nodes in the metabolic network, the regulatory network revealed several important nodes as centers of arsenic-induced activity. The highest-scoring proteins included Fhl1, Msn2, Msn4, Yap1, Cad1 (Yap2), Pre1, Hsf1 and Met31. Contrary to the gene-expression analyses, the phenotypic-profiling data mapped to the metabolic network. The two significant metabolic networks unveiled were shikimate, and serine, threonine and glutamate biosynthesis. We also carried out transcriptional profiling of specific deletion strains, confirming that the transcription factors Yap1, Arr1 (Yap8), and Rpn4 strongly mediate the cell's adaptation to arsenic-induced stress but that Cad1 has negligible impact. By integrating phenotypic and transcriptional profiling and mapping the data onto the metabolic and regulatory networks, we have shown that arsenic is likely to channel sulfur into glutathione for detoxification, leads to indirect oxidative stress by depleting glutathione pools, and alters protein turnover via arsenation of sulfhydryl groups on proteins. Furthermore, we show that phenotypically sensitive pathways are upstream of differentially expressed ones, indicating that transcriptional and phenotypic profiling implicate distinct, but related, pathways. JF - Genome biology AU - Haugen, Astrid C AU - Kelley, Ryan AU - Collins, Jennifer B AU - Tucker, Charles J AU - Deng, Changchun AU - Afshari, Cynthia A AU - Brown, J Martin AU - Ideker, Trey AU - Van Houten, Bennett AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. Haugen@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 1 VL - 5 IS - 12 KW - ARR1 protein, S cerevisiae KW - 0 KW - Basic-Leucine Zipper Transcription Factors KW - CAD1 protein, S cerevisiae KW - DNA-Binding Proteins KW - Environmental Pollutants KW - RPN4 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Transcription Factors KW - YAP1 protein, S cerevisiae KW - Sulfur KW - 70FD1KFU70 KW - Methionine KW - AE28F7PNPL KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Glutathione KW - GAN16C9B8O KW - Selenium KW - H6241UJ22B KW - Cysteine KW - K848JZ4886 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Saccharomyces cerevisiae Proteins -- physiology KW - Transcription Factors -- physiology KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Cysteine -- biosynthesis KW - Sulfur -- metabolism KW - Saccharomyces cerevisiae Proteins -- genetics KW - Glutathione -- metabolism KW - Methionine -- metabolism KW - Transcription, Genetic KW - Transcription Factors -- genetics KW - Glutathione -- biosynthesis KW - Phenotype KW - Selenium -- metabolism KW - Gene Expression Profiling KW - Proteasome Endopeptidase Complex -- metabolism KW - Oxidative Stress KW - Toxicity Tests -- methods KW - Biodegradation, Environmental KW - DNA-Binding Proteins -- physiology KW - Heat-Shock Response -- drug effects KW - Trans-Activators -- physiology KW - Gene Expression Regulation, Fungal -- drug effects KW - Saccharomyces cerevisiae -- genetics KW - Environmental Pollutants -- toxicity KW - Arsenic -- toxicity KW - Saccharomyces cerevisiae -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67159728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+biology&rft.atitle=Integrating+phenotypic+and+expression+profiles+to+map+arsenic-response+networks.&rft.au=Haugen%2C+Astrid+C%3BKelley%2C+Ryan%3BCollins%2C+Jennifer+B%3BTucker%2C+Charles+J%3BDeng%2C+Changchun%3BAfshari%2C+Cynthia+A%3BBrown%2C+J+Martin%3BIdeker%2C+Trey%3BVan+Houten%2C+Bennett&rft.aulast=Haugen&rft.aufirst=Astrid&rft.date=2004-01-01&rft.volume=5&rft.issue=12&rft.spage=R95&rft.isbn=&rft.btitle=&rft.title=Genome+biology&rft.issn=1474-760X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-19 N1 - Date created - 2004-12-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Microbiol. 1999 Jul;33(2):274-83 [10411744] Toxicol Appl Pharmacol. 2001 May 1;172(3):249-61 [11312654] Bioinformatics. 2001 Jun;17(6):564-5 [11395436] Mutat Res. 2001 Jul 1;478(1-2):159-68 [11406180] Biochem Cell Biol. 2001;79(4):441-8 [11527213] Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12608-13 [11606770] Cancer Res. 2004 Jun 1;64(11):3940-8 [15173006] Crit Rev Biochem Mol Biol. 1990;25(5):307-84 [2279393] Eur J Biochem. 1991 Sep 1;200(2):487-93 [1889413] Curr Genet. 1992 Apr;21(4-5):269-73 [1525853] Environ Health Perspect. 1992 Jul;97:259-67 [1396465] EMBO J. 1994 Feb 1;13(3):655-64 [8313910] Mol Cell Biol. 1994 May;14(5):2905-13 [8164651] Mol Cell Biol. 1994 Sep;14(9):5832-9 [7915005] Curr Genet. 1994 May;25(5):469-71 [8082194] Annu Rev Genomics Hum Genet. 2001;2:343-72 [11701654] Nucleic Acids Res. 2002 Jan 1;30(1):303-5 [11752321] J Infect Dis. 2002 Feb 15;185 Suppl 1:S25-36 [11865437] Mol Microbiol. 2002 Mar;43(5):1295-308 [11918814] Mol Cell. 2002 Apr;9(4):713-23 [11983164] Mol Biol Cell. 2002 May;13(5):1608-14 [12006656] Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8778-83 [12077312] Mol Microbiol. 2002 Jul;45(1):233-41 [12100562] Nature. 2002 Jul 25;418(6896):387-91 [12140549] Bioinformatics. 2002;18 Suppl 1:S233-40 [12169552] Toxicol Sci. 2002 Oct;69(2):306-16 [12377979] Science. 2002 Oct 25;298(5594):799-804 [12399584] Mol Cancer Res. 2002 Dec;1(2):103-12 [12496357] Genome Res. 2003 Feb;13(2):244-53 [12566402] Nature. 2003 May 15;423(6937):241-54 [12748633] Mol Endocrinol. 2003 Oct;17(10):2070-83 [12893882] Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11394-9 [14504397] Genome Res. 2003 Nov;13(11):2498-504 [14597658] Mol Cell Biochem. 2004 Jan;255(1-2):67-78 [14971647] Mol Biol Cell. 2004 May;15(5):2049-60 [14978214] FEBS Lett. 2004 May 21;566(1-3):141-6 [15147884] Cancer Lett. 1996 Jan 2;98(2):227-31 [8556713] J Cell Physiol. 1996 Nov;169(2):256-68 [8908193] Nat Genet. 1996 Dec;14(4):457-60 [8944026] J Cell Physiol. 2000 Jan;182(1):1-11 [10567911] Mol Cell Biol. 1999 Dec;19(12):8302-13 [10567555] Philos Trans R Soc Lond B Biol Sci. 1999 Sep 29;354(1389):1513-22 [10582237] J Biol Regul Homeost Agents. 1999 Oct-Dec;13(4):195-200 [10703942] Circ Res. 2000 Mar 17;86(5):514-9 [10720412] Mol Biol Cell. 2000 Jul;11(7):2335-47 [10888672] FEMS Microbiol Rev. 2000 Oct;24(4):469-86 [10978547] Mol Cell Biol. 2000 Nov;20(21):8157-67 [11027285] J Biol Chem. 2000 Oct 20;275(42):32611-6 [10921921] Mol Biol Cell. 2000 Dec;11(12):4241-57 [11102521] Mol Cell Biol. 2001 Feb;21(3):940-51 [11154280] Mol Biol Cell. 2001 Feb;12(2):323-37 [11179418] EMBO J. 1996 Nov 15;15(22):6269-79 [8947050] Mol Microbiol. 1996 Nov;22(4):739-46 [8951820] Blood. 1997 May 1;89(9):3354-60 [9129042] EMBO J. 1997 Apr 1;16(7):1710-20 [9130715] Yeast. 1997 Jul;13(9):819-28 [9234670] J Biol Chem. 1997 Aug 1;272(31):19304-13 [9235926] J Biol Chem. 1997 Sep 12;272(37):23224-30 [9287330] Mol Cell Biol. 1997 Dec;17(12):6982-93 [9372930] J Biol Chem. 1997 Nov 28;272(48):30061-6 [9374482] Cell. 1998 Feb 6;92(3):367-80 [9476896] Yeast. 1998 Sep 30;14(13):1209-21 [9791892] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1643-8 [11172004] Mol Microbiol. 2001 Mar;39(6):1523-32 [11260469] J Invest Dermatol. 1999 Jul;113(1):26-31 [10417614] Science. 1999 Aug 6;285(5429):901-6 [10436161] Ann Hematol. 1999 Jul;78(7):329-32 [10466445] J Biol Chem. 1999 Jul 30;274(31):21943-52 [10419517] Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5001-6 [10220408] FEBS Lett. 1999 Apr 30;450(1-2):27-34 [10350051] J Biol Chem. 1999 Jun 4;274(23):16040-6 [10347154] Trends Microbiol. 1999 May;7(5):207-12 [10354596] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cosmic radiation exposure and cancer risk among flight crew. AN - 67155545; 15581056 AB - Nearly 20 epidemiologic or related studies of cancer incidence and mortality have been published during or since 2000, with several reporting increased risks of female breast cancer among flight attendants and melanoma among both pilots and cabin crew. Occasionally, excesses of other cancers have been observed, but not consistently. Although the real causes of these excess cancer risks are not known, there is concern that they may be related to occupational exposures to ionizing radiation of cosmic origin. It is possible that confounding risk factors may partially or totally explain the observed relationships, but several investigations are beginning to address lack of past adjustment for reproductive factors and sun exposure with improved study designs. With progress in aviation technology, planes will fly longer and at higher altitudes, and presumably the number of flights and passengers will increase. To respond responsibly to the real and perceived risks associated with flying, more extensive data are needed, but special efforts should be considered to ensure new projects can genuinely add to our current knowledge. JF - Cancer investigation AU - Sigurdson, Alice J AU - Ron, Elaine AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-7238, USA. sigurdsa@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 743 EP - 761 VL - 22 IS - 5 SN - 0735-7907, 0735-7907 KW - Index Medicus KW - Risk Factors KW - Humans KW - Occupational Exposure -- adverse effects KW - Male KW - Female KW - Aviation KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Occupational Diseases -- etiology KW - Aerospace Medicine -- statistics & numerical data KW - Occupational Diseases -- epidemiology KW - Cosmic Radiation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67155545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cosmic+radiation+exposure+and+cancer+risk+among+flight+crew.&rft.au=Sigurdson%2C+Alice+J%3BRon%2C+Elaine&rft.aulast=Sigurdson&rft.aufirst=Alice&rft.date=2004-01-01&rft.volume=22&rft.issue=5&rft.spage=743&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 - 2004-12-29 N1 - Date created - 2004-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The past decade of experience with isolated hepatic perfusion. AN - 67108358; 15561809 AB - Metastatic or primary unresectable cancers confined to the liver are the sole or life-limiting component of disease for many patients with colorectal cancer, ocular melanoma, neuroendocrine tumors, or primary colangio- or hepatocellular carcinomas. Regional treatment strategies including infusional chemotherapy and local ablative therapy are under investigation, but have limitations with respect to the clinical conditions under which they can be employed. Isolated hepatic perfusion (IHP) was first clinically applied over 40 years ago, but because of its technical complexity, the attendant potential morbidity, and the lack of documented efficacy, it has not enjoyed consistent or widespread evaluation. In light of the antitumor activity with isolated limb perfusion with tumor necrosis factor (TNF) and melphalan in patients with unresectable extremity sarcoma or in transit melanoma, this regimen has been administered via IHP at several centers worldwide for patients with unresectable liver cancers. IHP with TNF and melphalan can result in significant regression of advanced refractory cancers from multiple histologies confined to the liver. Patient selection is important to ensure good results with minimal morbidity and mortality. Work to define the appropriate clinical groups is ongoing at many clinical centers. JF - The oncologist AU - Grover, Amelia AU - Alexander, H Richard AD - Surgical Metabolism Section, National Cancer Institute/NIH, 10 Center Drive, Building 10, Room 2B07, Bethesda, Maryland 20892-1502, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 653 EP - 664 VL - 9 IS - 6 SN - 1083-7159, 1083-7159 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Tumor Necrosis Factor-alpha KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Melanoma -- pathology KW - Colorectal Neoplasms -- pathology KW - Humans KW - Hyperthermia, Induced KW - Eye Neoplasms -- pathology KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Liver Neoplasms -- therapy KW - Liver Neoplasms -- mortality KW - Melphalan -- therapeutic use KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Liver Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67108358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+past+decade+of+experience+with+isolated+hepatic+perfusion.&rft.au=Grover%2C+Amelia%3BAlexander%2C+H+Richard&rft.aulast=Grover&rft.aufirst=Amelia&rft.date=2004-01-01&rft.volume=9&rft.issue=6&rft.spage=653&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=10837159&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-22 N1 - Date created - 2004-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospects for clinical introduction of nitroimidazole antibiotics for the treatment of tuberculosis. AN - 67072751; 15544513 AB - Nitroaromatic antibiotics have a long and controversial history in human and veterinary medicine. This controversy lies behind the presumption of many pharmaceutical companies that nitroaromatic compounds should be filtered from the list of drug-like compounds but stands at odds with the remarkably safe clinical record of use of such compounds. In this review, we will describe the whole-cell structure-activity relationships that have been reported for antimycobacterial nitroimidazoles as well as the available in vivo data supporting efficacy with a particular emphasis on nitroimidazo[2,1-b]oxazines such as PA-824. We will also explore the unique potential of such compounds to shorten the course of tuberculosis therapy by exerting a bactericidal effect on non-replicating bacilli. We will consider the mode of action of such compounds in sensitive organisms and discuss the mechanisms by which resistance may emerge. Finally, we will review the pharmacokinetics, toxicology and laboratory and animal studies linking nitroimidazoles with carcinogenicity and mutagenicity and assess the prospects for the clinical introduction of nitroimidazoles for the treatment of tuberculosis. JF - Current pharmaceutical design AU - Barry, Clifton E AU - Boshoff, Helena I M AU - Dowd, Cynthia S AD - Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. clifton_barry@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 3239 EP - 3262 VL - 10 IS - 26 SN - 1381-6128, 1381-6128 KW - Antibiotics, Antitubercular KW - 0 KW - Nitroimidazoles KW - Index Medicus KW - Animals KW - Randomized Controlled Trials as Topic KW - Single-Blind Method KW - Humans KW - Drug Evaluation, Preclinical -- methods KW - Antibiotics, Antitubercular -- chemistry KW - Antibiotics, Antitubercular -- adverse effects KW - Antibiotics, Antitubercular -- therapeutic use KW - Nitroimidazoles -- adverse effects KW - Nitroimidazoles -- chemistry KW - Tuberculosis, Pulmonary -- drug therapy KW - Nitroimidazoles -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67072751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmaceutical+design&rft.atitle=Prospects+for+clinical+introduction+of+nitroimidazole+antibiotics+for+the+treatment+of+tuberculosis.&rft.au=Barry%2C+Clifton+E%3BBoshoff%2C+Helena+I+M%3BDowd%2C+Cynthia+S&rft.aulast=Barry&rft.aufirst=Clifton&rft.date=2004-01-01&rft.volume=10&rft.issue=26&rft.spage=3239&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-16 N1 - Date created - 2004-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopaminergic differentiation of human embryonic stem cells. AN - 67066740; 15536184 AB - In this manuscript we report that human embryonic stem cells (hESCs) differentiated into dopaminergic neurons when cocultured with PA6 cells. After 3 weeks of differentiation, approximately 87% of hES colonies contained tyrosine hydroxylase (TH)-positive cells, and a high percentage of the cells in most of the colonies expressed TH. Differentiation was inhibited by exposure to BMP4 or serum. TH-positive cells derived from hESCs were postmitotic, as determined by bromodeoxyurindine colabeling. Differentiated cells expressed other markers of dopaminergic neurons, including the dopamine transporter, aromatic amino acid decarboxylase, and the transcription factors associated with neuronal and dopaminergic differentiation, Sox1, Nurr1, Ptx3, and Lmx1b. Neurons that had been differentiated on PA6 cells were negative for dopamine-beta-hydroxylase, a marker of noradrenergic neurons. PA6-induced neurons were able to release dopamine and 3,4-dihydroxphe-hylacetic acid (DOPAC) but not noradrenalin when depolarized by high K(+). When transplanted into 6-hydroxydopamine-treated animals, hES-derived dopaminergic cells integrated into the rat striatum. Five weeks after transplantation, surviving TH-positive cells were present but in very small numbers compared with the high frequency of TH-positive cells seen in PA6 coculture. Larger numbers of cells positive for smooth muscle actin, but no undifferentiated ES cells, were present after transplantation. Therefore, hESCs can be used to generate human dopaminergic cells that exhibit biochemical and functional properties consistent with the expected properties of mature dopaminergic neurons. JF - Stem cells (Dayton, Ohio) AU - Zeng, Xianmin AU - Cai, Jingli AU - Chen, Jia AU - Luo, Yongquan AU - You, Zhi-Bing AU - Fotter, Erin AU - Wang, Yun AU - Harvey, Brandon AU - Miura, Takumi AU - Backman, Cristina AU - Chen, Guann-Juh AU - Rao, Mahendra S AU - Freed, William J AD - Cellular Neurobiology Research Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. xzeng@intra.nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 925 EP - 940 VL - 22 IS - 6 SN - 1066-5099, 1066-5099 KW - Actins KW - 0 KW - Antimetabolites, Antineoplastic KW - BMP4 protein, human KW - Bmp4 protein, rat KW - Bone Morphogenetic Protein 4 KW - Bone Morphogenetic Proteins KW - Coloring Agents KW - DNA Primers KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Aromatic-L-Amino-Acid Decarboxylases KW - EC 4.1.1.28 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Potassium KW - RWP5GA015D KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Coculture Techniques KW - Animals KW - Coloring Agents -- pharmacology KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Actins -- metabolism KW - Brain -- metabolism KW - Antimetabolites, Antineoplastic -- pharmacology KW - Rats KW - Rats, Inbred F344 KW - Norepinephrine -- metabolism KW - Bone Morphogenetic Proteins -- physiology KW - Aromatic-L-Amino-Acid Decarboxylases -- metabolism KW - Time Factors KW - Tyrosine 3-Monooxygenase -- metabolism KW - Neurons -- metabolism KW - Cell Differentiation KW - Reverse Transcriptase Polymerase Chain Reaction KW - Potassium -- metabolism KW - Bromodeoxyuridine -- pharmacology KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Neurons -- cytology KW - Nerve Tissue Proteins -- metabolism KW - Immunohistochemistry KW - Membrane Transport Proteins -- metabolism KW - Cell Line KW - DNA Primers -- chemistry KW - Membrane Glycoproteins -- metabolism KW - Muscle, Smooth -- metabolism KW - Stem Cells -- cytology KW - Dopamine -- chemistry KW - Embryo, Mammalian -- cytology KW - Dopamine -- metabolism KW - Cell Culture Techniques -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67066740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopaminergic+differentiation+of+human+embryonic+stem+cells.&rft.au=Zeng%2C+Xianmin%3BCai%2C+Jingli%3BChen%2C+Jia%3BLuo%2C+Yongquan%3BYou%2C+Zhi-Bing%3BFotter%2C+Erin%3BWang%2C+Yun%3BHarvey%2C+Brandon%3BMiura%2C+Takumi%3BBackman%2C+Cristina%3BChen%2C+Guann-Juh%3BRao%2C+Mahendra+S%3BFreed%2C+William+J&rft.aulast=Zeng&rft.aufirst=Xianmin&rft.date=2004-01-01&rft.volume=22&rft.issue=6&rft.spage=925&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 - 2005-04-01 N1 - Date created - 2004-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic damage detected in CD-1 mouse pups exposed perinatally to 3'-azido-3'-deoxythymidine or dideoxyinosine via maternal dosing, nursing, and direct gavage: II. Effects of the individual agents compared to combination treatment. AN - 66978479; 15476197 AB - We previously reported extraordinary increases in micronucleated erythrocytes in CD-1 mouse pups exposed to 3'-azido-3'-deoxythymidine (AZT) and dideoxyinosine (ddI; 50/250, 75/375, 150/750 mg/kg/day AZT/ddI) by gavage throughout gestation and lactation, followed by direct pup dosing beginning postnatal day (PND) 4 (Bishop et al. [2004]: Environ Mol Mutagen 43: 3-9). That study was conducted to explore the potential for genetic damage in newborns exposed perinatally to antiretrovirals in order to reduce maternal-infant transmission of HIV-1. Because dramatic increases in frequencies of micronucleated erythrocytes were seen in exposed pups, additional studies were conducted to clarify the relative contribution of each drug to the observed damage. Pregnant CD-1 mice were administered AZT (50, 75, 150 mg/kg/day) or ddI (250, 375, 750 mg/kg/day) by gavage twice daily in equal fractions beginning prior to mating and continuing throughout gestation and lactation. Direct pup dosing (same regimens) began on PND 4. Peripheral blood erythrocytes of male pups were screened for micronuclei on PNDs 1, 4, 8, and 21. Significant increases in micronucleated erythrocytes were observed in pups and dams exposed to AZT at all doses and sampling times. The highest micronucleus levels were observed in pups on PND 8 after the initiation of direct dosing. In contrast, effects seen in pups and dams treated with ddI were minimal. These results demonstrate that AZT, a component of many anti-HIV combination therapies, induces chromosomal damage in perinatally exposed neonatal mice. Comparison of micronucleated cell frequencies induced by AZT alone or in combination with ddI suggests that ddI potentiates AZT-induced chromosomal damage following direct exposure. JF - Environmental and molecular mutagenesis AU - Witt, Kristine L AU - Tice, Raymond R AU - Wolfe, Gary W AU - Bishop, Jack B AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. witt@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 321 EP - 328 VL - 44 IS - 4 SN - 0893-6692, 0893-6692 KW - Anti-HIV Agents KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - Drug Therapy, Combination KW - Mice, Inbred Strains KW - Erythrocytes -- drug effects KW - Animals, Newborn KW - Animals KW - Analysis of Variance KW - Micronucleus Tests KW - Dose-Response Relationship, Drug KW - Mice KW - Male KW - Female KW - Pregnancy KW - Didanosine -- toxicity KW - Anti-HIV Agents -- toxicity KW - Micronuclei, Chromosome-Defective -- drug effects KW - Zidovudine -- toxicity KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66978479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+damage+detected+in+CD-1+mouse+pups+exposed+perinatally+to+3%27-azido-3%27-deoxythymidine+or+dideoxyinosine+via+maternal+dosing%2C+nursing%2C+and+direct+gavage%3A+II.+Effects+of+the+individual+agents+compared+to+combination+treatment.&rft.au=Witt%2C+Kristine+L%3BTice%2C+Raymond+R%3BWolfe%2C+Gary+W%3BBishop%2C+Jack+B&rft.aulast=Witt&rft.aufirst=Kristine&rft.date=2004-01-01&rft.volume=44&rft.issue=4&rft.spage=321&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 - 2004-12-27 N1 - Date created - 2004-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intramolecular quadruplex conformation of human telomeric DNA assessed with 125I-radioprobing. AN - 66954300; 15475390 AB - A repeated non-coding DNA sequence d(TTAGGG)n is present in the telomeric ends of all human chromosomes. These repeats can adopt multiple inter and intramolecular non-B-DNA conformations that may play an important role in biological processes. Two intramolecular structures of the telomeric oligonucleotide dAGGG(TTAGGG)3, antiparallel and parallel, have been solved by NMR and X-ray crystallography. In both structures, the telomeric sequence adopts an intramolecular quadruplex structure that is stabilized by G-4 quartets, but the ways in which the sequence folds into the quadruplex are different. The folds of the human telomeric DNA were described as an anti-parallel basket-type and a parallel propeller-type. We applied 125I-radioprobing to determine the conformation of the telomeric quadruplex in solution, in the presence of either Na+ or K+ ions. The probability of DNA breaks caused by decay of 125I is inversely related to the distance between the radionuclide and the sugar unit of the DNA backbone; hence, the conformation of the DNA backbone can be deduced from the distribution of breaks. The probability of breaks measured in the presence of Na+ and K+ were compared with the distances in basket-type and propeller-type quadruplexes obtained from the NMR and crystal structures. Our radioprobing data demonstrate that the antiparallel conformation was present in solution in the presence of both K+ and Na+. The preferable conformation in the Na+-containing solution was the basket-type antiparallel quadruplex whereas the presence of K+ favored the chair-type antiparallel quadruplex. Thus, we believe that the two antiparallel and the parallel conformations may coexist in solution, and that their relative proportion is determined by the type and concentration of ions. JF - Nucleic acids research AU - He, Yujian AU - Neumann, Ronald D AU - Panyutin, Igor G AD - Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, Building 10, Room 1C401, National Institutes of Health, Bethesda, MD 20892-1180, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 5359 EP - 5367 VL - 32 IS - 18 KW - Iodine Radioisotopes KW - 0 KW - Oligodeoxyribonucleotides KW - Sulfuric Acid Esters KW - DNA KW - 9007-49-2 KW - Sodium KW - 9NEZ333N27 KW - dimethyl sulfate KW - JW5CW40Z50 KW - Diethyl Pyrocarbonate KW - LMR3LZG146 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Base Sequence KW - G-Quadruplexes KW - Oligodeoxyribonucleotides -- chemistry KW - Humans KW - Sulfuric Acid Esters -- chemistry KW - Electrophoretic Mobility Shift Assay KW - Potassium -- pharmacology KW - Nucleic Acid Conformation KW - Sodium -- pharmacology KW - Diethyl Pyrocarbonate -- chemistry KW - Telomere -- chemistry KW - DNA -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66954300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intramolecular+quadruplex+conformation+of+human+telomeric+DNA+assessed+with+125I-radioprobing.&rft.au=He%2C+Yujian%3BNeumann%2C+Ronald+D%3BPanyutin%2C+Igor+G&rft.aulast=He&rft.aufirst=Yujian&rft.date=2004-01-01&rft.volume=32&rft.issue=18&rft.spage=5359&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-26 N1 - Date created - 2004-10-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Radiat Res. 2000 Mar;153(3):263-70 [10669547] Nature. 1992 Mar 12;356(6365):126-31 [1545863] J Mol Biol. 2000 Jun 9;299(3):629-40 [10835273] Biochemistry. 2000 Aug 8;39(31):9514-22 [10924148] Nucleic Acids Res. 2001 Mar 1;29(5):1087-96 [11222758] Radiat Res. 2001 Aug;156(2):158-66 [11448236] Nat Rev Cancer. 2002 Mar;2(3):188-200 [11990855] Nucleic Acids Res. 2002 Jun 1;30(11):2307-15 [12034817] Nature. 2002 Jun 20;417(6891):876-80 [12050675] Nature. 2002 Jun 20;417(6891):807-8 [12075337] Curr Opin Pharmacol. 2002 Aug;2(4):415-23 [12127874] Nucleic Acids Res. 2002 Nov 15;30(22):4960-5 [12434000] Nucleic Acids Res. 2003 Mar 15;31(6):1605-13 [12626701] J Biomol Struct Dyn. 2003 Apr;20(5):693-702 [12643772] Cancer Res. 2003 Jun 15;63(12):3247-56 [12810655] Curr Opin Struct Biol. 2003 Jun;13(3):275-83 [12831878] J Mol Biol. 2003 Nov 14;334(1):25-36 [14596797] Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14629-34 [14645716] Methods Enzymol. 2003;371:106-20 [14712694] Cell. 2004 Jan 23;116(2):273-9 [14744437] Biochemistry. 2004 Mar 9;43(9):2622-34 [14992600] Philos Trans R Soc Lond B Biol Sci. 2004 Jan 29;359(1441):109-21 [15065663] Nat Rev Mol Cell Biol. 2004 Apr;5(4):323-9 [15071557] Eur J Nucl Med Mol Imaging. 2004 Jun;31(6):837-45 [14762696] Nature. 1988 Jul 28;334(6180):364-6 [3393228] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6622-6 [3413114] Nucleic Acids Res. 1989 Oct 25;17(20):8257-71 [2554253] Cell. 1989 Dec 1;59(5):871-80 [2590943] Nature. 1989 Dec 14;342(6251):825-9 [2601741] Proc Natl Acad Sci U S A. 1990 Feb;87(3):867-70 [2300578] Nature. 1990 Mar 29;344(6265):410-4 [2320109] J Biomol Struct Dyn. 1991 Apr;8(5):967-75 [1878169] Nature. 1992 Mar 12;356(6365):164-8 [1545871] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10336-40 [1438219] Med Phys. 1992 Nov-Dec;19(6):1361-70 [1461198] Structure. 1993 Dec 15;1(4):263-82 [8081740] Annu Rev Biophys Biomol Struct. 1994;23:703-30 [7919797] Nucleic Acids Res. 1994 Nov 25;22(23):4979-82 [7800489] Nucleic Acids Res. 1997 Feb 15;25(4):883-7 [9016642] Int J Radiat Biol. 1998 Jan;73(1):45-51 [9464476] Nucleic Acids Res. 1998 Mar 1;26(5):1324-8 [9469844] Nat Struct Biol. 1999 Aug;6(8):747-50 [10426952] Radiat Res. 2000 Mar;153(3):271-8 [10669548] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polychlorinated biphenyls and breast cancer risk by combined estrogen and progesterone receptor status. AN - 66948161; 15469037 AB - Studies have suggested that breast cancer risk factor profiles may vary according to joint estrogen receptor (ER) and progesterone receptor (PR) tumor status. Most of the published literature to date which has investigated the association between exposure to organochlorine compounds and breast cancer has reported null or weak associations. If, indeed, the classification by hormonal receptor status identifies different forms of breast cancer, then assessing the risk of exposure to polychlorinated biphenyls (PCBs) on breast cancer as one disease or stratifying based on ER or PR status alone may obscure the association between PCBs and breast cancer. A hospital-based case-control study of 266 cases and 347 benign breast disease controls was conducted to examine the association of blood serum and adipose tissue concentrations of PCBs with breast cancer by joint ER/PR status. Total PCBs were measured in blood serum, and the following PCB congeners were measured in breast adipose tissue: 74, 118, 138, 153, 156, 170, 180, 183, 187. We did not detect any clear relationship or change in breast cancer risk based on joint ER/PR tumor status for body burden of PCBs, whether measured in blood serum or breast adipose tissue, by total PCBs or for specific congeners. These results confirm previous findings in the literature of no positive association between environmental exposure to PCBs and risk of breast cancer. JF - European journal of epidemiology AU - Rusiecki, Jennifer A AU - Holford, Theodore R AU - Zahm, Shelia H AU - Zheng, Tonzhang AD - Department of Epidemiology and Public Health, Yale University School of Medicine, USA. rusieckj@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 793 EP - 801 VL - 19 IS - 8 SN - 0393-2990, 0393-2990 KW - Biomarkers, Tumor KW - 0 KW - Receptors, Estrogen KW - Receptors, Progesterone KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Adipose Tissue -- metabolism KW - Risk Factors KW - Humans KW - Connecticut -- epidemiology KW - Case-Control Studies KW - Biomarkers, Tumor -- blood KW - Female KW - Receptors, Progesterone -- blood KW - Polychlorinated Biphenyls -- toxicity KW - Breast Neoplasms -- epidemiology KW - Breast Neoplasms -- chemically induced KW - Receptors, Estrogen -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66948161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Polychlorinated+biphenyls+and+breast+cancer+risk+by+combined+estrogen+and+progesterone+receptor+status.&rft.au=Rusiecki%2C+Jennifer+A%3BHolford%2C+Theodore+R%3BZahm%2C+Shelia+H%3BZheng%2C+Tonzhang&rft.aulast=Rusiecki&rft.aufirst=Jennifer&rft.date=2004-01-01&rft.volume=19&rft.issue=8&rft.spage=793&rft.isbn=&rft.btitle=&rft.title=European+journal+of+epidemiology&rft.issn=03932990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-29 N1 - Date created - 2004-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping of chemical trigger zones for reward. AN - 66946653; 15464137 AB - Addictive drugs are thought to activate brain circuitry that normally mediates more natural rewards such as food or water. Drugs activate this circuitry at synaptic junctions within the brain; identifying the junctions at which this occurs provides clues to the neurochemical and anatomical characteristics of the circuitry. One approach to identifying the junctions at which drugs interact with this circuitry is to determine if animals will lever-press for site-specific microinjections of addictive drugs. This approach has identified GABAergic, dopaminergic, glutamatergic, and cholinergic trigger zones within meso-corticolimbic circuitry important for natural reward function. JF - Neuropharmacology AU - Ikemoto, Satoshi AU - Wise, Roy A AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse (NIDA), National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. sikemoto@intra.nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 190 EP - 201 VL - 47 Suppl 1 SN - 0028-3908, 0028-3908 KW - Excitatory Amino Acids KW - 0 KW - Muscarinic Agonists KW - Neurotransmitter Agents KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Carbachol KW - 8Y164V895Y KW - Acetylcholine KW - N9YNS0M02X KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Drug Delivery Systems KW - Acetylcholine -- administration & dosage KW - Dopamine -- pharmacology KW - Excitatory Amino Acids -- administration & dosage KW - gamma-Aminobutyric Acid -- pharmacology KW - Acetylcholine -- pharmacology KW - gamma-Aminobutyric Acid -- administration & dosage KW - Dopamine -- administration & dosage KW - Rats KW - Behavior, Animal -- drug effects KW - Self Administration KW - Neurotransmitter Agents -- pharmacology KW - Muscarinic Agonists -- pharmacology KW - Excitatory Amino Acids -- pharmacology KW - Ventral Tegmental Area KW - Carbachol -- pharmacology KW - Brain Mapping -- methods KW - Reward KW - Substance-Related Disorders -- pathology KW - Brain -- anatomy & histology KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66946653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mapping+of+chemical+trigger+zones+for+reward.&rft.au=Ikemoto%2C+Satoshi%3BWise%2C+Roy+A&rft.aulast=Ikemoto&rft.aufirst=Satoshi&rft.date=2004-01-01&rft.volume=47+Suppl+1&rft.issue=&rft.spage=190&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-20 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process. AN - 66945551; 15464133 AB - Classical genetic studies document strong complex genetic contributions to abuse of multiple addictive substances. These genetic influences are more prominent in the later phases of individuals' progressions toward substance dependence. Individual differences in human addiction vulnerability could thus derive, in part, from individual differences in mnemonic systems. These variations could add to allelic variations that could produce effects on addiction vulnerability phenotypes by other routes that could include (1) differences in drug metabolism or biodistribution, (2) differences in drug's rewarding properties, (3) differences in traits manifest by the addict, including personality differences and (4) differences in the addict's psychiatric comorbidities. Data from linkage and association genome scans now identify chromosomal regions that are likely to contain allelic gene variants that contribute to human addiction vulnerability. Converging positive results are found in several different substance-abusing populations studied in several laboratories. This convergence supports the idea that common allelic variants contribute to individual differences in vulnerability to substance dependence. Genomic markers that identify allelic variants that reproducibly alter addiction vulnerability in several populations provide tools for research in addictions, tools to improve addiction treatments, tools to improve addiction prevention, clues to the genetic bases of individual differences in mnemonic processes and clues to the genetic bases of individual differences in the other traits and disorders that co-occur with substance dependencies. JF - Neuropharmacology AU - Uhl, George R AD - Molecular Neurobiology Branch, NIDA-IRP, NIH, Box 5180 Baltimore, MD 21224, USA. guhl@intra.nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 140 EP - 147 VL - 47 Suppl 1 SN - 0028-3908, 0028-3908 KW - Index Medicus KW - Environment KW - Animals KW - Alleles KW - Humans KW - Cloning, Molecular KW - Learning -- physiology KW - Memory -- physiology KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66945551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+genetic+underpinnings+of+human+substance+abuse+vulnerability%3A+likely+contributions+to+understanding+addiction+as+a+mnemonic+process.&rft.au=Uhl%2C+George+R&rft.aulast=Uhl&rft.aufirst=George&rft.date=2004-01-01&rft.volume=47+Suppl+1&rft.issue=&rft.spage=140&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-20 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selecting the appropriate rodent diet for endocrine disruptor research and testing studies. AN - 66924857; 15454679 AB - Selecting the optimum diet for endocrine disruptor (ED) research and testing studies in rodents is critical because the diet may determine the sensitivity to detect or properly evaluate an ED compound. Dietary estrogens can profoundly influence many molecular and cellular event actions on estrogen receptors and estrogen-sensitive genes. The source, concentration, relative potency, and significance of dietary estrogens in rodent diets are reviewed, including dietary factors that focus specifically on total metabolizable energy and phytoestrogen content, which potentially affect ED studies in rodents. Research efforts to determine dietary factors in commercially available rodent diets that affect uterotrophic assays and the time of vaginal opening in immature CD-1 mice are summarized. A checklist is provided of important factors to consider when selecting diets for ED research and testing studies in rodents. Specific metabolizable energy levels are recommended for particular bioassays. Discussions include the between-batch variation in content of the phytoestrogens daidzein and genistein, the effects of total metabolizable energy and phytoestrogens on the timing (i.e., acceleration) of vaginal opening, and increased uterine weight in immature CD-1 mice. It is concluded that rodent diets differ significantly in estrogenic activity primarily due to the large variations in phytoestrogen content; therefore animal diets used in all ED studies should ideally be free of endocrine-modulating compounds. JF - ILAR journal AU - Thigpen, Julius E AU - Setchell, Kenneth D R AU - Saunders, H E AU - Haseman, J K AU - Grant, M G AU - Forsythe, D B AD - Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 401 EP - 416 VL - 45 IS - 4 SN - 1084-2020, 1084-2020 KW - Hormone Antagonists KW - 0 KW - Index Medicus KW - Animals KW - Animal Husbandry KW - Mice KW - Environmental Exposure -- adverse effects KW - Female KW - Endocrine Glands -- physiopathology KW - Animal Feed KW - Endocrine Glands -- drug effects KW - Hormone Antagonists -- toxicity KW - Toxicity Tests -- methods KW - Endocrine Glands -- pathology KW - Diet KW - Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66924857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ILAR+journal&rft.atitle=Selecting+the+appropriate+rodent+diet+for+endocrine+disruptor+research+and+testing+studies.&rft.au=Thigpen%2C+Julius+E%3BSetchell%2C+Kenneth+D+R%3BSaunders%2C+H+E%3BHaseman%2C+J+K%3BGrant%2C+M+G%3BForsythe%2C+D+B&rft.aulast=Thigpen&rft.aufirst=Julius&rft.date=2004-01-01&rft.volume=45&rft.issue=4&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=ILAR+journal&rft.issn=10842020&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-05 N1 - Date created - 2004-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selecting appropriate animal models and experimental designs for endocrine disruptor research and testing studies. AN - 66924754; 15454677 AB - Evidence that chemicals in the environment may cause developmental and reproductive abnormalities in fish and wildlife by disrupting normal endocrine functions has increased concern about potential adverse human health effects from such chemicals. US laws have now been enacted that require the US Environmental Protection Agency (EPA) to develop and validate a screening program to identify chemicals in food and water with potential endocrine-disrupting activity. EPA subsequently proposed an Endocrine Disruptor Screening Program that uses in vitro and in vivo test systems to identify chemicals that may adversely affect humans and ecologically important animal species. However, the endocrine system can be readily modulated by many experimental factors, including diet and the genetic background of the selected animal strain or stock. It is therefore desirable to minimize or avoid factors that cause or contribute to experimental variation in endocrine disruptor research and testing studies. Standard laboratory animal diets contain high and variable levels of phytoestrogens, which can modulate physiologic and behavioral responses similar to both endogenous estrogen as well as exogenous estrogenic chemicals. Other studies have determined that some commonly used outbred mice and rats are less responsive to estrogenic substances than certain inbred mouse and rat strains for various estrogen-sensitive endpoints. It is therefore critical to select appropriate biological models and diets for endocrine disruptor studies that provide optimal sensitivity and specificity to accomplish the research or testing objectives. An introduction is provided to 11 other papers in this issue that review these and other important laboratory animal experimental design considerations in greater detail, and that review laboratory animal and in vitro models currently being used or evaluated for endocrine disruptor research and testing. Selection of appropriate animal models and experimental design parameters for endocrine disruptor research and testing will minimize confounding experimental variables, increase the likelihood of replicable experimental results, and contribute to more reliable and relevant test systems. JF - ILAR journal AU - Stokes, William S AD - US Public Health Service, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 387 EP - 393 VL - 45 IS - 4 SN - 1084-2020, 1084-2020 KW - Hormone Antagonists KW - 0 KW - Index Medicus KW - United States KW - Animals KW - United States Environmental Protection Agency KW - Environmental Exposure -- adverse effects KW - Endocrine Glands -- physiopathology KW - Endocrine Glands -- drug effects KW - Hormone Antagonists -- toxicity KW - Toxicity Tests -- methods KW - Endocrine Glands -- pathology KW - Disease Models, Animal KW - Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66924754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ILAR+journal&rft.atitle=Selecting+appropriate+animal+models+and+experimental+designs+for+endocrine+disruptor+research+and+testing+studies.&rft.au=Stokes%2C+William+S&rft.aulast=Stokes&rft.aufirst=William&rft.date=2004-01-01&rft.volume=45&rft.issue=4&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=ILAR+journal&rft.issn=10842020&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-05 N1 - Date created - 2004-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen receptor knockout mice as a model for endocrine research. AN - 66924740; 15454684 AB - The biological effects of estrogen in mammalian target tissues are important for multiple organ systems including the male and female reproductive tract and the neuroendocrine, skeletal, and cardiovascular systems. Numerous physiological effects of estradiol are modulated by the estrogen receptor (ER), a Class I member of the nuclear receptor superfamily. However, more recent studies have also implicated nongenomic effects of estrogen, which may involve a membrane-binding site. The two forms of the ER are the classical estrogen receptor-alpha (ERalpha) and the more recently discovered estrogen receptor-beta (ERbeta). Gene-targeting techniques were used to generate mice lacking either functional ERalpha (alphaERKO), ERbeta (betaERKO), or both ERs (alphabetaERKO) to provide a model for evaluating estrogen receptor action. These knockout models provide a unique tool to study the effects of estrogen in the context of the whole animal and to discern the role of each ER in various tissues. The reproductive phenotypes as well as some of the nonreproductive phenotypes of the different ERKO models are summarized. JF - ILAR journal AU - Walker, Vickie R AU - Korach, Kenneth S AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 455 EP - 461 VL - 45 IS - 4 SN - 1084-2020, 1084-2020 KW - Hormone Antagonists KW - 0 KW - Receptors, Estrogen KW - Index Medicus KW - Animals KW - Mice KW - Male KW - Female KW - Models, Animal KW - Endocrine Glands -- physiopathology KW - Receptors, Estrogen -- genetics KW - Endocrine Glands -- drug effects KW - Hormone Antagonists -- toxicity KW - Receptors, Estrogen -- deficiency KW - Endocrine Glands -- pathology KW - Mice, Knockout UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66924740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ILAR+journal&rft.atitle=Estrogen+receptor+knockout+mice+as+a+model+for+endocrine+research.&rft.au=Walker%2C+Vickie+R%3BKorach%2C+Kenneth+S&rft.aulast=Walker&rft.aufirst=Vickie&rft.date=2004-01-01&rft.volume=45&rft.issue=4&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=ILAR+journal&rft.issn=10842020&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-05 N1 - Date created - 2004-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons. AN - 66892862; 15289798 AB - Valproic acid (VPA), used to treat bipolar mood disorder and seizures, also inhibits histone deacetylase (HDAC). Here, we found that VPA and other HDAC inhibitors, butyrate and trichostatin A, robustly protected mature cerebellar granule cell cultures from excitotoxicity induced by SYM 2081 ((2S, 4R)-4-methylglutamate), an inhibitor of excitatory amino-acid transporters and an agonist of low-affinity kainate receptors. These neuroprotective effects required protracted treatment and were correlated with enhanced acetylated histone levels, indicating HDAC inhibition. SYM-induced excitotoxicity was blocked by MK-801 ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate), supporting that the toxicity was largely N-methyl-D-aspartate receptor dependent. SYM excitotoxicity had apoptotic characteristics and was prevented by a caspase inhibitor. SYM-induced apoptosis was associated with a rapid and robust nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a housekeeping gene previously shown to be proapoptotic. VPA pretreatment suppressed SYM 2081-induced GAPDH nuclear accumulation, concurrent with its neuroprotective effects. Chromatin immunoprecipitation (ChIP) revealed that GAPDH is copresent with acetylated histone H3, including Lys9-acetylated histone, and that VPA treatment caused a time-dependent decrease in the levels of nuclear GAPDH with a concomitant increase in acetylated histones in the ChIP complex. Our results strongly suggest that VPA protects neurons from excitotoxicity through inhibition of HDAC activity and that this protective effect may involve suppression of excitotoxicity-induced accumulation of GAPDH protein in the nucleus. JF - The pharmacogenomics journal AU - Kanai, H AU - Sawa, A AU - Chen, R-W AU - Leeds, P AU - Chuang, D-M AD - Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 336 EP - 344 VL - 4 IS - 5 SN - 1470-269X, 1470-269X KW - Enzyme Inhibitors KW - 0 KW - Excitatory Amino Acid Antagonists KW - Glutamates KW - Histone Deacetylase Inhibitors KW - 4-methylglutamic acid KW - 14561-55-8 KW - Valproic Acid KW - 614OI1Z5WI KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Index Medicus KW - Rats KW - Cell Death -- physiology KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Neurons -- drug effects KW - Histone Deacetylases -- metabolism KW - Neurons -- enzymology KW - Enzyme Inhibitors -- pharmacology KW - Glutamates -- toxicity KW - Cell Death -- drug effects KW - Valproic Acid -- pharmacology KW - Cell Nucleus -- enzymology KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- metabolism KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Cell Nucleus -- drug effects KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66892862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacogenomics+journal&rft.atitle=Valproic+acid+inhibits+histone+deacetylase+activity+and+suppresses+excitotoxicity-induced+GAPDH+nuclear+accumulation+and+apoptotic+death+in+neurons.&rft.au=Kanai%2C+H%3BSawa%2C+A%3BChen%2C+R-W%3BLeeds%2C+P%3BChuang%2C+D-M&rft.aulast=Kanai&rft.aufirst=H&rft.date=2004-01-01&rft.volume=4&rft.issue=5&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=The+pharmacogenomics+journal&rft.issn=1470269X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-11 N1 - Date created - 2004-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzymatic switching for efficient and accurate translesion DNA replication. AN - 66824084; 15333698 AB - When cyclobutane pyrimidine dimers stall DNA replication by DNA polymerase (Pol) delta or epsilon, a switch occurs to allow translesion synthesis by DNA polymerase eta, followed by another switch that allows normal replication to resume. In the present study, we investigate these switches using Saccharomyces cerevisiae Pol delta, Pol epsilon and Pol eta and a series of matched and mismatched primer templates that mimic each incorporation needed to completely bypass a cis-syn thymine-thymine (TT) dimer. We report a complementary pattern of substrate use indicating that enzymatic switching involving localized translesion synthesis by Pol eta and mismatch excision and polymerization by a major replicative polymerase can account for the efficient and accurate dimer bypass known to suppress sunlight-induced mutagenesis and skin cancer. JF - Nucleic acids research AU - McCulloch, Scott D AU - Kokoska, Robert J AU - Chilkova, Olga AU - Welch, Carrie M AU - Johansson, Erik AU - Burgers, Peter M J AU - Kunkel, Thomas A AD - Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 4665 EP - 4675 VL - 32 IS - 15 KW - Pyrimidine Dimers KW - 0 KW - DNA Polymerase II KW - EC 2.7.7.- KW - DNA Polymerase III KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Index Medicus KW - Pyrimidine Dimers -- metabolism KW - Models, Genetic KW - DNA Polymerase II -- metabolism KW - Base Pair Mismatch KW - Saccharomyces cerevisiae -- enzymology KW - DNA Polymerase III -- metabolism KW - Exodeoxyribonucleases -- metabolism KW - DNA Damage KW - DNA Replication KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66824084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enzymatic+switching+for+efficient+and+accurate+translesion+DNA+replication.&rft.au=McCulloch%2C+Scott+D%3BKokoska%2C+Robert+J%3BChilkova%2C+Olga%3BWelch%2C+Carrie+M%3BJohansson%2C+Erik%3BBurgers%2C+Peter+M+J%3BKunkel%2C+Thomas+A&rft.aulast=McCulloch&rft.aufirst=Scott&rft.date=2004-01-01&rft.volume=32&rft.issue=15&rft.spage=4665&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-08-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Jun 4;274(23):15975-7 [10347143] Science. 1999 Feb 12;283(5404):1001-4 [9974380] Science. 1999 Jul 9;285(5425):263-5 [10398605] Sci Aging Knowledge Environ. 2003 Feb 26;2003(8):RE3 [12844548] Nature. 2003 Aug 28;424(6952):1083-7 [12904819] Nature. 2003 Sep 11;425(6954):188-91 [12968183] Mol Cell Biol. 2003 Nov;23(22):8316-22 [14585988] EMBO J. 2003 Dec 15;22(24):6621-30 [14657033] J Biol Chem. 2003 Dec 12;278(50):50537-45 [14523013] J Biol Chem. 2004 Jan 16;279(3):1907-15 [14594808] J Biol Chem. 2000 Mar 17;275(11):7447-50 [10713043] J Biol Chem. 2000 Mar 17;275(11):8233-9 [10713149] Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3094-9 [10725365] Nature. 2000 Apr 27;404(6781):1011-3 [10801132] EMBO J. 2000 Jun 15;19(12):3100-9 [10856253] Nat Genet. 2000 Aug;25(4):458-61 [10932195] Nucleic Acids Res. 2000 Dec 1;28(23):4717-24 [11095682] J Biol Chem. 2001 Jan 19;276(3):2263-6 [11054429] J Biol Chem. 2001 Jan 26;276(4):2317-20 [11113111] Mol Cell. 2001 Aug;8(2):407-15 [11545742] Mol Cell Biol. 2001 Nov;21(21):7199-206 [11585903] Cell. 2001 Oct 5;107(1):9-12 [11595180] Cell. 2001 Oct 5;107(1):91-102 [11595188] Biochemistry. 2002 May 14;41(19):6090-9 [11994004] Genes Dev. 2002 Aug 1;16(15):1872-83 [12154119] Nature. 2002 Sep 12;419(6903):135-41 [12226657] Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15560-5 [12429860] Mutat Res. 2002 Dec 29;510(1-2):23-35 [12459440] Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15965-70 [12456887] DNA Repair (Amst). 2002 Jun 21;1(6):425-35 [12509231] EMBO J. 2003 Mar 3;22(5):1223-33 [12606586] J Biol Chem. 2003 Apr 18;278(16):14082-6 [12571237] Nature. 2004 Mar 4;428(6978):97-100 [14999287] J Mol Biol. 2004 Mar 5;336(5):1023-34 [15037066] J Biol Chem. 2004 Apr 23;279(17):16895-8 [14988392] Mol Cell. 2004 May 21;14(4):491-500 [15149598] Biochemistry. 1990 Jun 5;29(22):5226-31 [2166556] Nucleic Acids Res. 1990 Dec 25;18(24):7279-86 [2259623] Nucleic Acids Res. 1992 Oct 25;20(20):5403-6 [1359505] J Bacteriol. 1993 May;175(9):2607-12 [8478326] Hum Mol Genet. 1995 Sep;4(9):1685-7 [8541864] Methods Enzymol. 1995;262:217-32 [8594349] J Biol Chem. 1998 Jul 31;273(31):19756-62 [9677406] Nature. 1999 Jun 17;399(6737):700-4 [10385124] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair. AN - 66818069; 15327889 AB - Keratinocyte growth factor (KGF) is a paracrine-acting, epithelial mitogen produced by cells of mesenchymal origin. It is a member of the fibroblast growth factor (FGF) family, and acts exclusively through a subset of FGF receptor isoforms (FGFR2b) expressed predominantly by epithelial cells. The upregulation of KGF after epithelial injury suggested it had an important role in tissue repair. This hypothesis was reinforced by evidence that intestinal damage was worse and healing impaired in KGF null mice. Preclinical data from several animal models demonstrated that recombinant human KGF could enhance the regenerative capacity of epithelial tissues and protect them from a variety of toxic exposures. These beneficial effects are attributed to multiple mechanisms that collectively act to strengthen the integrity of the epithelial barrier, and include the stimulation of cell proliferation, migration, differentiation, survival, DNA repair, and induction of enzymes involved in the detoxification of reactive oxygen species. KGF is currently being evaluated in clinical trials to test its ability to ameliorate severe oral mucositis (OM) that results from cancer chemoradiotherapy. In a phase 3 trial involving patients who were treated with myeloablative chemoradiotherapy before autologous peripheral blood progenitor cell transplantation for hematologic malignancies, KGF significantly reduced both the incidence and duration of severe OM. Similar investigations are underway in patients being treated for solid tumors. On the basis of its success in ameliorating chemoradiotherapy-induced OM in humans and tissue damage in a variety of animal models, additional clinical applications of KGF are worthy of investigation. JF - Advances in cancer research AU - Finch, Paul W AU - Rubin, Jeffrey S AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 69 EP - 136 VL - 91 SN - 0065-230X, 0065-230X KW - Antineoplastic Agents KW - 0 KW - FGF7 protein, human KW - Fgf7 protein, mouse KW - Proteoglycans KW - Receptors, Fibroblast Growth Factor KW - heparin proteoglycan KW - Fibroblast Growth Factor 7 KW - 126469-10-1 KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Heparin KW - 9005-49-6 KW - Receptor, Fibroblast Growth Factor, Type 2 KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Models, Molecular KW - Humans KW - Clinical Trials as Topic KW - Graft vs Host Disease -- drug therapy KW - Organ Specificity KW - Mice KW - Amino Acid Sequence KW - Stomatitis -- drug therapy KW - Mice, Transgenic KW - Mice, Knockout KW - Antineoplastic Agents -- adverse effects KW - Stomatitis -- chemically induced KW - Transplantation Conditioning -- adverse effects KW - Proteoglycans -- metabolism KW - Carcinoma -- pathology KW - Molecular Sequence Data KW - Cell Physiological Phenomena -- drug effects KW - Gene Expression Regulation KW - Receptors, Fibroblast Growth Factor -- metabolism KW - Mesoderm -- metabolism KW - Drug Evaluation, Preclinical KW - Protein Conformation KW - Epithelial Cells -- cytology KW - Epithelial Cells -- drug effects KW - Wound Healing -- drug effects KW - Heparin -- analogs & derivatives KW - Fibroblast Growth Factors -- physiology KW - Heparin -- metabolism KW - Fibroblast Growth Factors -- chemistry KW - Wound Healing -- physiology KW - Fibroblast Growth Factors -- genetics KW - Fibroblast Growth Factors -- adverse effects KW - Fibroblast Growth Factors -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66818069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+research&rft.atitle=Keratinocyte+growth+factor%2Ffibroblast+growth+factor+7%2C+a+homeostatic+factor+with+therapeutic+potential+for+epithelial+protection+and+repair.&rft.au=Finch%2C+Paul+W%3BRubin%2C+Jeffrey+S&rft.aulast=Finch&rft.aufirst=Paul&rft.date=2004-01-01&rft.volume=91&rft.issue=&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Advances+in+cancer+research&rft.issn=0065230X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-04 N1 - Date created - 2004-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of markers for the detection and treatment of lung cancer. AN - 66802562; 15322315 AB - The unacceptably high morbidity and mortality associated with the diagnosis of lung cancer mandates new approaches toward the early detection and treatment of this disease. Enhanced understanding of the molecular biology of the carcinogenic process is identifying many potential markers of risk of lung cancer occurrence as well as of poor prognosis. Identification of high risk populations who are at greatest risk of being diagnosed with and dying from lung cancer would allow delivery of more intensive screening and interventions to the individuals who are most likely to benefit from such strategies. This review examines the current status of markers of lung cancer risk, early detection, and prognosis, and their applicability to current standards of clinical care. JF - Disease markers AU - Vourlekis, Jason S AU - Szabo, Eva AD - Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6130 Executive Blvd., Rm 2132, Bethesda, MD 20892, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 71 EP - 85 VL - 20 IS - 2 SN - 0278-0240, 0278-0240 KW - Biomarkers, Tumor KW - 0 KW - Index Medicus KW - Risk Factors KW - Humans KW - Prognosis KW - Lung Neoplasms -- diagnosis KW - Biomarkers, Tumor -- analysis KW - Lung Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66802562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Disease+markers&rft.atitle=Use+of+markers+for+the+detection+and+treatment+of+lung+cancer.&rft.au=Vourlekis%2C+Jason+S%3BSzabo%2C+Eva&rft.aulast=Vourlekis&rft.aufirst=Jason&rft.date=2004-01-01&rft.volume=20&rft.issue=2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Disease+markers&rft.issn=02780240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-09 N1 - Date created - 2004-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns? AN - 66801580; 15320756 AB - The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na(+), Ca(2+) and K(+) channels often leading to life-threatening arrhythmia. To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors. Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na(+), Ca(2+) and K(+) channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with cardiovascular disorders. The primary goal of this review is to shed light on the recently observed clinically important cardiovascular effects of new antidepressants and antipsychotics and discuss the mechanism beyond this phenomenon. JF - Current pharmaceutical design AU - Pacher, Pal AU - Kecskemeti, Valeria AD - National Institutes of Health, National Institute on Alcohol Abuse & Alcoholism, Laboratory Physiologic Studies, Bethesda, MD 20892-8115, USA. ppacher@lycos.com Y1 - 2004 PY - 2004 DA - 2004 SP - 2463 EP - 2475 VL - 10 IS - 20 SN - 1381-6128, 1381-6128 KW - Antidepressive Agents, Tricyclic KW - 0 KW - Antipsychotic Agents KW - Serotonin Uptake Inhibitors KW - Index Medicus KW - Animals KW - Attitude to Health KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Humans KW - Serotonin Uptake Inhibitors -- classification KW - Serotonin Uptake Inhibitors -- adverse effects KW - Antipsychotic Agents -- therapeutic use KW - Antidepressive Agents, Tricyclic -- classification KW - Antidepressive Agents, Tricyclic -- therapeutic use KW - Cardiovascular Diseases -- chemically induced KW - Antidepressive Agents, Tricyclic -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Cardiovascular Diseases -- physiopathology KW - Cardiovascular Diseases -- prevention & control KW - Antipsychotic Agents -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66801580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmaceutical+design&rft.atitle=Cardiovascular+side+effects+of+new+antidepressants+and+antipsychotics%3A+new+drugs%2C+old+concerns%3F&rft.au=Pacher%2C+Pal%3BKecskemeti%2C+Valeria&rft.aulast=Pacher&rft.aufirst=Pal&rft.date=2004-01-01&rft.volume=10&rft.issue=20&rft.spage=2463&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-07 N1 - Date created - 2004-08-23 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Biochem 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Mar;288(3):1261-8 [10027867] Crit Care Med. 1999 Feb;27(2):332-9 [10075058] Eur J Pharmacol. 1999 Feb 12;367(1):113-8 [10082273] Curr Med Chem. 1999 Jun;6(6):469-80 [10213794] Cell. 1999 Apr 16;97(2):175-87 [10219239] N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Prevention and repair of DNA damage by selected phytochemicals as measured by single cell gel electrophoresis. AN - 66788044; 15312044 AB - We assessed the ability of some natural products--namely, curcumin, resveratrol, indole-3-carbinol, and ellagic acid--to modify the DNA damaging ability of the alkylating carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in cultured Chinese hamster lung fibroblast cells (CH V-79). MNNG produced DNA single strand breaks in a dose- and time-dependent manner, as observed by increase in the tail moments of the comet, when the cells were subjected to alkaline single cell gel electrophoresis. When the cells were treated in the presence of each of the natural compounds, the DNA damage caused by MNNG was considerably reduced. This effect was found to be dose related. Preincubation of cells with each of these compounds individually afforded significant protection to DNA against damage caused by subsequent treatment with MNNG, indicating a true chemopreventive role of these substances. The most remarkable aspect of the present study was that all four compounds helped in the recovery of DNA damage by accelerating DNA repair efficiency in the damaged cells. This was further substantiated by the observation on unscheduled DNA synthesis. Our results suggest that these agents are chemopreventive by virtue of their ability to protect DNA as well as to induce DNA repair. JF - Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer AU - Chakraborty, Sutapa AU - Roy, Madhumita AU - Bhattacharya, Rathin K AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata, India. Y1 - 2004 PY - 2004 DA - 2004 SP - 215 EP - 226 VL - 23 IS - 3 SN - 0731-8898, 0731-8898 KW - Anticarcinogenic Agents KW - 0 KW - Antineoplastic Agents KW - Antineoplastic Agents, Phytogenic KW - Carcinogens KW - Indoles KW - Stilbenes KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Ellagic Acid KW - 19YRN3ZS9P KW - indole-3-carbinol KW - C11E72455F KW - Curcumin KW - IT942ZTH98 KW - resveratrol KW - Q369O8926L KW - Index Medicus KW - Comet Assay KW - Animals KW - Methylnitronitrosoguanidine -- toxicity KW - Cricetulus KW - Dose-Response Relationship, Drug KW - Cell Culture Techniques KW - Carcinogens -- toxicity KW - Fibroblasts KW - Cricetinae KW - Ellagic Acid -- pharmacology KW - DNA Repair KW - Stilbenes -- pharmacology KW - DNA Damage KW - Anticarcinogenic Agents -- pharmacology KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Indoles -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Curcumin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66788044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+environmental+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.atitle=Prevention+and+repair+of+DNA+damage+by+selected+phytochemicals+as+measured+by+single+cell+gel+electrophoresis.&rft.au=Chakraborty%2C+Sutapa%3BRoy%2C+Madhumita%3BBhattacharya%2C+Rathin+K&rft.aulast=Chakraborty&rft.aufirst=Sutapa&rft.date=2004-01-01&rft.volume=23&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.issn=07318898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-31 N1 - Date created - 2004-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A review of depsipeptide and other histone deacetylase inhibitors in clinical trials. AN - 66760543; 15279609 AB - The histone deacetylase inhibitors (HDIs) are a new class of antineoplastic agents currently being evaluated in clinical trials. While these agents have been studied extensively in the laboratory, only recently has their mechanism of action begun to be elucidated. Several structural classes of compounds have been shown to exert histone deacetylase inhibition, including sodium n-butyrate, suberoylanilide hydroxamic acid, LAQ824, CI-994, MS-275, and depsipeptide. The HDIs have been shown to induce differentiation, to decrease cell proliferation, and to induce cell death. HDIs are thought to exert their anti-neoplastic effects by altering the expression of genes that play a role in the control of cell growth, and transformation. The HDIs have specific and well-defined effects on cancer cells. Preliminary results from clinical trials suggest that these agents are very promising. While there were sporadic case reports of activity using the early generation HDIs, dramatic responses have recently been observed in patients with T-cell lymphomas treated with depsipeptide, one of the newer agents. With the well-defined molecular effects on cancer cells, surrogate markers can be analyzed for evidence of activity and efficacy using either tumor samples or normal tissue. Presented in this review are details from clinical trials with both earlier and newer generations of HDIs. Toxicities specific to this class of agents are outlined and possibilities for rational combination therapies are discussed. JF - Current pharmaceutical design AU - Piekarz, Richard AU - Bates, Susan AD - Cancer Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 2289 EP - 2298 VL - 10 IS - 19 SN - 1381-6128, 1381-6128 KW - Antineoplastic Agents KW - 0 KW - Depsipeptides KW - Histone Deacetylase Inhibitors KW - Peptides, Cyclic KW - romidepsin KW - CX3T89XQBK KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Peptides, Cyclic -- administration & dosage KW - Peptides, Cyclic -- therapeutic use KW - Antineoplastic Agents -- administration & dosage KW - Peptides, Cyclic -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66760543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmaceutical+design&rft.atitle=A+review+of+depsipeptide+and+other+histone+deacetylase+inhibitors+in+clinical+trials.&rft.au=Piekarz%2C+Richard%3BBates%2C+Susan&rft.aulast=Piekarz&rft.aufirst=Richard&rft.date=2004-01-01&rft.volume=10&rft.issue=19&rft.spage=2289&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-31 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Small molecule toxins targeting tumor receptors. AN - 66760234; 15279611 AB - Targeting toxic therapeutics to tumors through receptors over expressed on the surface of cancer cells can reduce systemic toxicity and increase the effectiveness of the targeted compounds. Small molecule targeted therapeutics have a number of advantages over toxic immunoconjugates including better tumor penetration, lack of neutralizing host immune response and superior flexibility in selection of drug components with optimal specificity, potency and stability in circulation. Three major components of the targeted drug, the toxic warhead, tumor-specific ligand and the linker can influence the properties of each other and thus have to be optimized for each system. All receptor-targeted drugs are delivered inside the cells through endocytosis and undergo processing liberating the toxins in endosomes and lysosomes. Common delivery route defines a number of general requirements for each drug component. The review addresses currently known possible receptor targets and their ligands along with toxins that have been used and that have a potential to be successfully applied in tumor targeting. Linkers that are stable in circulation, but efficiently cleaved in lysosomes constitute an essential component of receptor-targeted drugs and are evaluated in greater detail. JF - Current pharmaceutical design AU - Dyba, Marcin AU - Tarasova, Nadya I AU - Michejda, Christopher J AD - NCI-Frederick, P. O. Box B, Frederick, MD 21702, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 2311 EP - 2334 VL - 10 IS - 19 SN - 1381-6128, 1381-6128 KW - Antineoplastic Agents KW - 0 KW - Immunotoxins KW - Ligands KW - Receptors, Cell Surface KW - Toxins, Biological KW - Index Medicus KW - Immunotoxins -- chemistry KW - Animals KW - Humans KW - Immunotoxins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Structure-Activity Relationship KW - Neoplasms -- drug therapy KW - Drug Delivery Systems KW - Toxins, Biological -- chemistry KW - Toxins, Biological -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- chemistry KW - Receptors, Cell Surface -- physiology KW - Toxins, Biological -- therapeutic use KW - Receptors, Cell Surface -- drug effects KW - Neoplasms -- metabolism KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66760234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmaceutical+design&rft.atitle=Small+molecule+toxins+targeting+tumor+receptors.&rft.au=Dyba%2C+Marcin%3BTarasova%2C+Nadya+I%3BMichejda%2C+Christopher+J&rft.aulast=Dyba&rft.aufirst=Marcin&rft.date=2004-01-01&rft.volume=10&rft.issue=19&rft.spage=2311&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-31 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer-specific ligands identified from screening of peptide-display libraries. AN - 66759317; 15279612 AB - Although monoclonal antibodies have demonstrated clinical potentials as tumor targeting agents, poor tumor penetration of the antibodies due to the size of molecules and liver/bone marrow toxicity by non-specific uptake of the antibodies are the two major limitations of antibody therapy. Peptidic targeting agents may ease the problems associated with antibody cancer therapy. Combinatorial libraries displayed on microorganisms have successfully been utilized to discover cell surface-binding peptides, which can be tumor-targeting agents. Among many molecular display techniques, phage display has been the most popular approach. Peptides can be used as targeting molecules of receptor-targeted toxins and gene therapy, imaging and/or therapeutic agents, and nano-medical technologies. Recent results from preclinical studies with various peptides support their targeting potential and suggest that the role of peptides as targeting molecules in drug development should be further exploited. JF - Current pharmaceutical design AU - Mori, T AD - Molecular Targets Development Program, Center for Cancer Research, National Cancer Institute, NCI-Frederick, Frederick, MD 21702-1201, USA. mori@ncifcrf.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 2335 EP - 2343 VL - 10 IS - 19 SN - 1381-6128, 1381-6128 KW - Antineoplastic Agents KW - 0 KW - Ligands KW - Peptide Library KW - Peptides KW - Receptors, Cell Surface KW - Index Medicus KW - Receptors, Cell Surface -- metabolism KW - Animals KW - Humans KW - Combinatorial Chemistry Techniques KW - Receptors, Cell Surface -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- diagnosis KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- chemistry KW - Peptides -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66759317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmaceutical+design&rft.atitle=Cancer-specific+ligands+identified+from+screening+of+peptide-display+libraries.&rft.au=Mori%2C+T&rft.aulast=Mori&rft.aufirst=T&rft.date=2004-01-01&rft.volume=10&rft.issue=19&rft.spage=2335&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-31 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DMB (DNMT-magnetic beads) assay: measuring DNA methyltransferase activity in vitro. AN - 66749387; 15273420 AB - DNA methylation is an epigenetic modification of DNA that leads to heritable alterations in transcriptional regulation and conformational changes in chromatin structure of higher eukaryotes. Mammalian DNA methyltransferases, which are the enzymes responsible for DNA methylation, have attracted the attention of both basic and clinical researchers because they appear to participate in embryogenesis and carcinogenesis via chromatin modification. DNA methyltransferase catalyzes the transfer of a methyl group into DNA strands. Since traditional assays for DNA methyltransferase activity in vitro have insufficient reproducibility, there is a need in the art for more sensitive and quantitative methods for measuring enzymatic activity. We report a novel assay system, in which the activity of a DNA methyltransferase is measured as the incorporation of tritium into biotinylated DNA oligonucleotides. The DNA is immobilized onto magnetic beads with streptavidin covalently attached to the bead surface. The radioactive DNA can easily be separated from the unreacted radioactive substrate using a magnet. The radioactivity is counted by the liquid scintillation system. This DMB assay is simple and easy, has very low background, and, most importantly, is highly reproducible for the precise enzymatic analysis of any DNA methyltransferase in vitro. JF - Methods in molecular biology (Clifton, N.J.) AU - Yokochi, Tomoki AU - Robertson, Keith D AD - Epigenetic Gene Regulation and Cancer Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 285 EP - 296 VL - 287 SN - 1064-3745, 1064-3745 KW - Recombinant Proteins KW - 0 KW - Tritium KW - 10028-17-8 KW - S-Adenosylmethionine KW - 7LP2MPO46S KW - DNA (Cytosine-5-)-Methyltransferase KW - EC 2.1.1.37 KW - DNA (cytosine-5-)-methyltransferase 1 KW - Index Medicus KW - Animals KW - Mammals KW - Substrate Specificity KW - Recombinant Proteins -- genetics KW - S-Adenosylmethionine -- chemistry KW - Tritium -- chemistry KW - DNA (Cytosine-5-)-Methyltransferase -- genetics KW - Magnetics KW - Molecular Biology -- methods KW - DNA (Cytosine-5-)-Methyltransferase -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66749387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DMB+%28DNMT-magnetic+beads%29+assay%3A+measuring+DNA+methyltransferase+activity+in+vitro.&rft.au=Yokochi%2C+Tomoki%3BRobertson%2C+Keith+D&rft.aulast=Yokochi&rft.aufirst=Tomoki&rft.date=2004-01-01&rft.volume=287&rft.issue=&rft.spage=285&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 - 2004-10-21 N1 - Date created - 2004-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Challenges in implementing evidence-based treatment practices for co-occurring disorders in the criminal justice system. AN - 66748548; 15282833 AB - The presence of adults with mental health and substance abuse disorders within the criminal justice system has become increasingly evident over the past decade. Interventions and treatment services have been designed and research conducted in an effort to establish evidence-based practices that effectively address the complex needs of this population. However, adopting and implementing these evidence-based interventions and practices within the real-world setting of criminal justice environments is challenging. This article reviews the research literature related to evidence-based treatment practices for offenders with co-occurring mental health and substance abuse disorders and explores the inherent challenges of fitting these interventions and services within criminal justice settings. Copyright 2004 John Wiley & Sons, Ltd. JF - Behavioral sciences & the law AU - Chandler, Redonna K AU - Peters, Roger H AU - Field, Gary AU - Juliano-Bult, Denise AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. rchandle@nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 431 EP - 448 VL - 22 IS - 4 SN - 0735-3936, 0735-3936 KW - Index Medicus KW - Humans KW - Comorbidity KW - Substance-Related Disorders -- therapy KW - Criminal Law -- statistics & numerical data KW - Evidence-Based Medicine KW - Mental Disorders -- therapy KW - Mental Disorders -- epidemiology KW - Mental Health Services -- organization & administration KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66748548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioral+sciences+%26+the+law&rft.atitle=Challenges+in+implementing+evidence-based+treatment+practices+for+co-occurring+disorders+in+the+criminal+justice+system.&rft.au=Chandler%2C+Redonna+K%3BPeters%2C+Roger+H%3BField%2C+Gary%3BJuliano-Bult%2C+Denise&rft.aulast=Chandler&rft.aufirst=Redonna&rft.date=2004-01-01&rft.volume=22&rft.issue=4&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Behavioral+sciences+%26+the+law&rft.issn=07353936&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-14 N1 - Date created - 2004-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contrasting effects of mu opioid receptor and delta opioid receptor deletion upon the behavioral and neurochemical effects of cocaine. AN - 66722319; 15262338 AB - Conventional brain microdialysis was used to assess basal and cocaine-induced dopamine (DA) levels in the nucleus accumbens of wildtype (WT) C57BL/6J mice and mice with constitutive deletion of ether mu- or delta-opioid receptors (MOR or DOR knockout [KO], respectively). Locomotor activity was assessed in these same animals. Basal locomotor activity of DOR KO was elevated relative to MOR KO, but did not differ from that of WT mice. DOR mice, but not WT or MOR KO, exhibited a significant increase in activity in response to an injection of saline. The acute administration of cocaine produced a dose-related increase in locomotor activity in the three genotypes. The locomotor activating effects of a low dose (10 mg/kg) of cocaine were enhanced in DOR KO mice whereas the locomotor activating effects of both a low and higher (20 mg/kg) dose of cocaine were reduced in MOR KO animals. Microdialysis studies revealed no difference between genotypes in basal DA levels. Acute administration of cocaine, but not saline, increased DA levels in WT and KO animals. Paradoxically, however, the magnitude of this effect was smaller in DOR KO as compared with that in either WT or MOR KO. These data indicate that constitutive deletion of either MOR or DOR results in contrasting effects upon responsiveness to cocaine, which is consistent with the distinct phenotypes previously described for these mutants. JF - Neuroscience AU - Chefer, V I AU - Kieffer, B L AU - Shippenberg, T S AD - Integrative Neuroscience Section, Behavioral Neuroscience Branch, DHHS/NIH/National Institute on Drug Abuse/IRP/BNRB/INS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. vchefer@intra.nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 497 EP - 503 VL - 127 IS - 2 SN - 0306-4522, 0306-4522 KW - Opioid Peptides KW - 0 KW - Receptors, Opioid, delta KW - Receptors, Opioid, mu KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Nucleus Accumbens -- drug effects KW - Extracellular Fluid -- drug effects KW - Dopamine -- metabolism KW - Mice KW - Motor Activity -- physiology KW - Mice, Knockout KW - Genotype KW - Microdialysis KW - Extracellular Fluid -- metabolism KW - Nucleus Accumbens -- metabolism KW - Motor Activity -- drug effects KW - Opioid Peptides -- metabolism KW - Brain -- drug effects KW - Brain Chemistry -- drug effects KW - Brain -- metabolism KW - Receptors, Opioid, mu -- deficiency KW - Receptors, Opioid, mu -- genetics KW - Brain -- physiopathology KW - Receptors, Opioid, mu -- physiology KW - Cocaine-Related Disorders -- genetics KW - Receptors, Opioid, delta -- deficiency KW - Cocaine-Related Disorders -- physiopathology KW - Receptors, Opioid, delta -- physiology KW - Receptors, Opioid, delta -- genetics KW - Cocaine -- pharmacology KW - Cocaine-Related Disorders -- metabolism KW - Brain Chemistry -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66722319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Contrasting+effects+of+mu+opioid+receptor+and+delta+opioid+receptor+deletion+upon+the+behavioral+and+neurochemical+effects+of+cocaine.&rft.au=Chefer%2C+V+I%3BKieffer%2C+B+L%3BShippenberg%2C+T+S&rft.aulast=Chefer&rft.aufirst=V&rft.date=2004-01-01&rft.volume=127&rft.issue=2&rft.spage=497&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-09 N1 - Date created - 2004-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of intron gain over intron loss in the evolution of paralogous gene families. AN - 66708224; 15254274 AB - The mechanisms and evolutionary dynamics of intron insertion and loss in eukaryotic genes remain poorly understood. Reconstruction of parsimonious scenarios of gene structure evolution in paralogous gene families in animals and plants revealed numerous gains and losses of introns. In all analyzed lineages, the number of acquired new introns was substantially greater than the number of lost ancestral introns. This trend held even for lineages in which vertical evolution of genes involved more intron losses than gains, suggesting that gene duplication boosts intron insertion. However, dating gene duplications and the associated intron gains and losses based on the molecular clock assumption showed that very few, if any, introns were gained during the last approximately 100 million years of animal and plant evolution, in agreement with previous conclusions reached through analysis of orthologous gene sets. These results are generally compatible with the emerging notion of intensive insertion and loss of introns during transitional epochs in contrast to the relative quiet of the intervening evolutionary spans. JF - Nucleic acids research AU - Babenko, Vladimir N AU - Rogozin, Igor B AU - Mekhedov, Sergei L AU - Koonin, Eugene V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bldg 38A, Bethesda, MD 20894, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 3724 EP - 3733 VL - 32 IS - 12 KW - Index Medicus KW - Animals KW - Multigene Family KW - Molecular Sequence Data KW - Plants -- genetics KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Mutagenesis, Insertional KW - Sequence Deletion KW - Introns KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66708224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prevalence+of+intron+gain+over+intron+loss+in+the+evolution+of+paralogous+gene+families.&rft.au=Babenko%2C+Vladimir+N%3BRogozin%2C+Igor+B%3BMekhedov%2C+Sergei+L%3BKoonin%2C+Eugene+V&rft.aulast=Babenko&rft.aufirst=Vladimir&rft.date=2004-01-01&rft.volume=32&rft.issue=12&rft.spage=3724&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-26 N1 - Date created - 2004-07-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 2000 Jan;154(1):459-73 [10629003] Mol Biol Evol. 2003 Dec;20(12):1947-54 [12949122] Trends Genet. 2000 May;16(5):227-31 [10782117] Science. 2000 Nov 10;290(5494):1151-5 [11073452] Genome Res. 2001 Apr;11(4):555-65 [11282971] Cell. 2001 Nov 16;107(4):419-25 [11719183] Genome Res. 2001 Dec;11(12):2101-14 [11731501] J Mol Biol. 2001 Dec 14;314(5):1041-52 [11743721] Genome Biol. 2002;3(2):RESEARCH0008 [11864370] Genome Res. 2002 Jul;12(7):1048-59 [12097341] Curr Opin Genet Dev. 2002 Dec;12(6):701-10 [12433585] Trends Genet. 2002 Dec;18(12):619-20 [12446146] Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16128-33 [12444254] Nat Rev Genet. 2003 Mar;4(3):216-24 [12610526] Trends Genet. 2003 Apr;19(4):200-6 [12683973] Proc Natl Acad Sci U S A. 2003 May 27;100(11):6580-3 [12750476] Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7158-62 [12777620] J Struct Funct Genomics. 2003;3(1-4):111-6 [12836690] Curr Biol. 2003 Sep 2;13(17):1512-7 [12956953] Genome Biol. 2004;5(2):R7 [14759257] Curr Biol. 2004 Mar 23;14(6):505-9 [15043816] Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6536-41 [15084738] Cell Cycle. 2004 Mar;3(3):280-5 [14726650] J Theor Biol. 1965 Mar;8(2):357-66 [5876245] Syst Zool. 1970 Jun;19(2):99-113 [5449325] Trends Genet. 1989 Jul;5(7):213-6 [2551082] EMBO J. 1989 Jul;8(7):2015-21 [2792080] J Theor Biol. 1991 Aug 7;151(3):405-16 [1943150] J Mol Biol. 1992 Dec 20;228(4):1124-36 [1474582] Proc Biol Sci. 1994 May 23;256(1346):119-24 [8029240] Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 [7984417] Methods Enzymol. 1996;266:418-27 [8743697] J Mol Evol. 1997 Jun;44(6):573-84 [9169549] Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6820-5 [9192649] Science. 1997 Oct 24;278(5338):631-7 [9381173] Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):606-11 [9435239] Gene. 1997 Dec 31;205(1-2):151-60 [9461389] Science. 1998 Dec 11;282(5396):2022-8 [9851918] Curr Opin Genet Dev. 1998 Dec;8(6):637-48 [9914210] Nature. 1999 Feb 25;397(6721):655-6 [10067889] Proc Biol Sci. 1999 Jan 22;266(1415):163-71 [10097391] Genome Res. 2003 Oct;13(10):2236-41 [12975308] BMC Bioinformatics. 2003 Sep 11;4:41 [12969510] BMC Evol Biol. 2001;1:4 [11580860] Science. 2003 Nov 21;302(5649):1401-4 [14631042] Curr Biol. 2003 Dec 16;13(24):2170-4 [14680632] Genomics. 2000 Jan 15;63(2):227-45 [10673334] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agents in development for the management of cocaine abuse. AN - 66678246; 15233592 AB - Cocaine abuse is a serious health problem in many areas of the world, yet there are no proven effective medications for the treatment of cocaine dependence. Preclinical studies suggest that the reinforcing effect of cocaine that promotes its abuse is mediated by blockade of the presynaptic dopamine transporter. This results in increased dopamine activity in the mesolimbic or meso-accumbens dopamine reward system of brain. Development of new medications to treat cocaine dependence has focused on manipulation of this dopamine system, either by direct action on dopamine binding sites (transporter or receptors) or indirectly by affecting other neurotransmitter systems that modulate the dopamine system. In principle, a medication could act via one of three mechanisms: (i) as a substitute for cocaine by producing similar dopamine effects; (ii) as a cocaine antagonist by blocking the binding of cocaine to the dopamine transporter; or (iii) as a modulator of cocaine effects by acting at other than the cocaine binding site. The US National Institute on Drug Abuse has a Clinical Research Efficacy Screening Trial (CREST) programme to rapidly screen existing medications. CREST identified four medications warranting phase II controlled clinical trials: cabergoline, reserpine, sertraline and tiagabine. In addition, disulfiram and selegiline (deprenyl) have been effective and well tolerated in phase II trials. However, selegiline was found ineffective in a recent phase III trial. Promising existing medications probably act via the first or third aforementioned mechanisms. Sustained-release formulations of stimulants such as methylphenidate and amfetamine (amphetamine) have shown promise in a stimulant substitution approach. Disulfiram and selegiline increase brain dopamine concentrations by inhibition of dopamine-catabolising enzymes (dopamine-beta-hydroxylase and monoamine oxidase B, respectively). Cabergoline is a direct dopamine receptor agonist, while reserpine depletes presynaptic stores of dopamine (as well as norepinephrine and serotonin). Sertraline, baclofen and vigabatrin indirectly reduce dopamine activity by increasing activity of neurotransmitters (serotonin and GABA) that inhibit dopamine activity. Promising new medications act via the second or third aforementioned mechanisms. Vanoxerine is a long-acting inhibitor of the dopamine transporter which blocks cocaine binding and reduces cocaine self-administration in animals. Two dopamine receptor ligands that reduce cocaine self-administration in animals are also undergoing phase I human safety trials. Adrogolide is a selective dopamine D(1) receptor agonist; BP 897 is a D(3) receptor partial agonist.A pharmacokinetic approach to treatment would block the entry of cocaine into the brain or enhance its catabolism so that less cocaine reached its site of action. This is being explored in animals using the natural cocaine-metabolising enzyme butyrylcholinesterase (or recombinant versions with enhanced capabilities), catalytic antibodies, and passive or active immunisation to produce anti-cocaine binding antibodies. A recent phase I trial of a "cocaine vaccine" found it to be well tolerated and producing detectable levels of anti-cocaine antibodies for up to 9 months after immunisation. JF - Drugs AU - Gorelick, David A AU - Gardner, Eliot L AU - Xi, Zheng-Xiong AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. dgorelick@intra.nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 1547 EP - 1573 VL - 64 IS - 14 SN - 0012-6667, 0012-6667 KW - Index Medicus KW - Animals KW - Technology, Pharmaceutical -- methods KW - Humans KW - Disease Management KW - Clinical Trials as Topic -- statistics & numerical data KW - Cocaine-Related Disorders -- psychology KW - Cocaine-Related Disorders -- drug therapy KW - Drug Delivery Systems -- methods KW - Cocaine-Related Disorders -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66678246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drugs&rft.atitle=Agents+in+development+for+the+management+of+cocaine+abuse.&rft.au=Gorelick%2C+David+A%3BGardner%2C+Eliot+L%3BXi%2C+Zheng-Xiong&rft.aulast=Gorelick&rft.aufirst=David&rft.date=2004-01-01&rft.volume=64&rft.issue=14&rft.spage=1547&rft.isbn=&rft.btitle=&rft.title=Drugs&rft.issn=00126667&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-25 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine-induced Fos expression in rat striatum is blocked by chloral hydrate or urethane. AN - 66664225; 15219685 AB - Anesthetics used in electrophysiological studies alter the effects of cocaine and amphetamine on neural activity in the striatum. However, the mechanism underlying this alteration has not been established. In the present study, we examined the effects of anesthetics on cocaine-induced neural activity in the striatum. We first assayed the ability of 20 mg/kg cocaine to induce Fos expression in the striatum following pretreatment with 400 mg/kg chloral hydrate or 1.3 g/kg urethane, two of the most commonly used anesthetics for in vivo electrophysiology. Chloral hydrate blocked, while urethane strongly attenuated cocaine-induced Fos expression without affecting basal levels of expression. We then examined dopaminergic and glutamatergic mechanisms for anesthetic effects on cocaine-induced Fos expression. Chloral hydrate and urethane did not attenuate basal or cocaine-induced increases of dopamine levels as assessed by microdialysis in dorsal striatum. In contrast, chloral hydrate attenuated glutamatergic neurotransmission as assessed by microdialysis in the presence of the glutamate transport blocker L-trans-pyrrolidone-2,4-dicarboxylic acid. Chloral hydrate attenuated basal levels of glutamate by 70%, while cocaine had no effect on glutamate levels. Since glutamate levels were tetrodotoxin-sensitive, the majority of glutamate measured in our assay was by synaptic release. To assess a causal role for a reduction of glutamatergic neurotransmission in anesthetic effects on cocaine-induced Fos expression, we injected the glutamate receptor agonists AMPA and NMDA into the dorsal striatum of chloral hydrate-anesthetized rats. The glutamate receptor agonists partially reinstated cocaine-induced Fos expression in anesthetized rats. We conclude anesthetics attenuate cocaine-induced neuronal activity by reducing glutamatergic neurotransmission. JF - Neuroscience AU - Kreuter, J D AU - Mattson, B J AU - Wang, B AU - You, Z-B AU - Hope, B T AD - Behavioral Neuroscience Branch, Intramural Research Program, The National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 233 EP - 242 VL - 127 IS - 1 SN - 0306-4522, 0306-4522 KW - Amino Acid Transport System X-AG KW - 0 KW - Dicarboxylic Acids KW - Excitatory Amino Acid Agonists KW - Neurotransmitter Uptake Inhibitors KW - Proto-Oncogene Proteins c-fos KW - Pyrrolidines KW - Urethane KW - 3IN71E75Z5 KW - Glutamic Acid KW - 3KX376GY7L KW - Chloral Hydrate KW - 418M5916WG KW - pyrrolidine-2,4-dicarboxylic acid KW - 99319-03-6 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Neurons -- metabolism KW - Glutamic Acid -- metabolism KW - Synaptic Transmission -- drug effects KW - Neurons -- drug effects KW - Extracellular Fluid -- drug effects KW - Amino Acid Transport System X-AG -- metabolism KW - Dopamine -- metabolism KW - Dicarboxylic Acids -- pharmacology KW - Synaptic Transmission -- physiology KW - Drug Interactions -- physiology KW - Rats KW - Microdialysis KW - Rats, Sprague-Dawley KW - Extracellular Fluid -- metabolism KW - Neurotransmitter Uptake Inhibitors -- pharmacology KW - Pyrrolidines -- pharmacology KW - Excitatory Amino Acid Agonists -- pharmacology KW - Amino Acid Transport System X-AG -- antagonists & inhibitors KW - Male KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Corpus Striatum -- metabolism KW - Corpus Striatum -- drug effects KW - Urethane -- pharmacology KW - Cocaine -- pharmacology KW - Cocaine -- antagonists & inhibitors KW - Chloral Hydrate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66664225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cocaine-induced+Fos+expression+in+rat+striatum+is+blocked+by+chloral+hydrate+or+urethane.&rft.au=Kreuter%2C+J+D%3BMattson%2C+B+J%3BWang%2C+B%3BYou%2C+Z-B%3BHope%2C+B+T&rft.aulast=Kreuter&rft.aufirst=J&rft.date=2004-01-01&rft.volume=127&rft.issue=1&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-14 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic polymorphisms, smoking, and oral cancer in Puerto Rico. AN - 66653675; 15206494 AB - Genetic polymorphisms resulting in variation in metabolism of tobacco carcinogens may influence oral cancer risk. In a population-based case-control study in Puerto Rico, genotypes of CYP1A1, GSTM1, and GSTT1 were determined by a PCR-based method for 132 oral cancer patients and 143 control subjects. Genotype-associated risks were estimated by logistic regression. The null variant of GSTM1 was associated with a marginally significant decrease in oral cancer risk [odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.3-1.0, and P for trend = 0.09]. Risks increased with increasing cigarette use among subjects with the GSTM1-present genotype (P for trend <0.0001), rising to OR = 9.5, 95% CI = 3.0-30, among the heaviest cigarette users. In contrast, among subjects with the GSTM1-null genotype, risks did not clearly increase with increasing cigarette use (P for trend <0.61; OR = 1.8, 95% CI = 0.6-5.2 among the heaviest tobacco users). The GSTT1-null variant (OR = 1.0, 95% CI = 0.5-1.9) and CYP1A1(462Val) variant (OR = 0.9, 95% CI = 0.5-1.7) were not associated with the risk. Risks rose with increasing cigarette use in a similar manner for subjects with or without the CYP1A1(462Val) variant (P for interaction = 0.3) and for subjects with or without the GSTT1-null genotype (P for interaction = 0.4). In conclusion, cigarette use significantly increased the risk of oral cancer in this population. The GSTM1-present genotype was associated with higher tobacco-associated risk for oral cancer among heavy smokers than the null genotype. JF - Oncology research AU - Xie, Heng AU - Hou, Lifang AU - Shields, Peter G AU - Winn, Deborah M AU - Gridley, Gloria AU - Bravo-Otero, Eleuterio AU - Diehl, Scott R AU - Bowman, Elise D AU - Brown, Linda M AU - Hayes, Richard B AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004 PY - 2004 DA - 2004 SP - 315 EP - 320 VL - 14 IS - 6 SN - 0965-0407, 0965-0407 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - glutathione S-transferase T1 KW - EC 2.5.1.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase M1 KW - Index Medicus KW - Vegetables KW - Cytochrome P-450 CYP1A1 -- genetics KW - Humans KW - Aged KW - Glutathione Transferase -- genetics KW - Alcohol Drinking KW - Genotype KW - Risk Factors KW - Diet KW - Fruit KW - Puerto Rico -- epidemiology KW - Female KW - Male KW - Polymorphism, Genetic -- genetics KW - Smoking -- genetics KW - Mouth Neoplasms -- genetics KW - Mouth Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66653675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+research&rft.atitle=Metabolic+polymorphisms%2C+smoking%2C+and+oral+cancer+in+Puerto+Rico.&rft.au=Xie%2C+Heng%3BHou%2C+Lifang%3BShields%2C+Peter+G%3BWinn%2C+Deborah+M%3BGridley%2C+Gloria%3BBravo-Otero%2C+Eleuterio%3BDiehl%2C+Scott+R%3BBowman%2C+Elise+D%3BBrown%2C+Linda+M%3BHayes%2C+Richard+B&rft.aulast=Xie&rft.aufirst=Heng&rft.date=2004-01-01&rft.volume=14&rft.issue=6&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Oncology+research&rft.issn=09650407&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-01 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methodologic implications of the Precautionary Principle: causal criteria. AN - 66644075; 15212209 AB - Applying the Precautionary Principle to public health requires a re-evaluation of the methods of inference currently used to make claims about disease causation from epidemiologic and other forms of scientific evidence. In current thinking, a well-established, near-certain causal relationship implies highly consistent statistically significant results across many different studies, large relative risk estimates, extensive understanding of biological mechanisms and dose-response relationships, positive prevention trial results, a clear temporal relationship between cause and effect, and other conditions spelled out in terms of the widely-used causal criteria. The Precautionary Principle, however, states that preventive measures are to be taken when cause and effect relationships are not fully established scientifically. What evidentiary conditions, as reflected in the causal criteria, will be certain enough to warrant precautionary preventive action? This paper argues that minimum evidentiary requirements for causation need to be articulated if the Precautionary Principle is to be successfully incorporated into public health practice. Two precautionary changes to criteria-based methods of causal inference are examined: reducing the number of criteria and weakening the rules of inference accompanying the criteria. Such changes point in the direction of identifying minimum evidentiary conditions, but would be premature without better understanding how well current methods of causal inference work. JF - International journal of occupational medicine and environmental health AU - Weed, Douglas L AD - Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20852, USA. dw102i@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 77 EP - 81 VL - 17 IS - 1 SN - 1232-1087, 1232-1087 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - United States KW - Public Health KW - Humans KW - Health Policy KW - Environmental Pollutants -- adverse effects KW - Primary Prevention -- organization & administration KW - Public Health Practice KW - Epidemiologic Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66644075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+occupational+medicine+and+environmental+health&rft.atitle=Methodologic+implications+of+the+Precautionary+Principle%3A+causal+criteria.&rft.au=Weed%2C+Douglas+L&rft.aulast=Weed&rft.aufirst=Douglas&rft.date=2004-01-01&rft.volume=17&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=International+journal+of+occupational+medicine+and+environmental+health&rft.issn=12321087&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-22 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Students' of Color and European American Students' Stigma-Relevant Perceptions of University Instructors AN - 60476549; 200412957 AB - In classrooms, students of color may experience stigma (ie, concern about being stereotyped) because negative stereotypes of their intellect are salient. Two studies included African American, European American, & Latina/Latino female & male undergraduates. Study 1 (n = 86) demonstrated while students of color generally had positive expectations of teachers, their expectations declined when imagining class with a European American instructor who would repeatedly vs never evaluate their work or an ethnically matched instructor across conditions. Study 2 (n = 136) revealed all students had more positive expectations of culturally tolerant vs culturally intolerant instructors. Students of color more than European American students perceived that intolerant instructors could grade them unfairly. We discuss implications for ethnically diverse classrooms. 2 Figures, 53 References. Adapted from the source document. JF - Journal of Social Issues AU - Brown, Lisa M AU - Dobbins, Heather AD - NIMH Center Study Emotion & Attention, U Florida, Gainesville Y1 - 2004///0, PY - 2004 DA - 0, 2004 SP - 157 EP - 174 VL - 60 IS - 1 SN - 0022-4537, 0022-4537 KW - Whites KW - Student Teacher Relationship KW - Black Americans KW - Tolerance KW - Hispanic Americans KW - Student Attitudes KW - College Students KW - Stigma KW - College Faculty KW - article KW - 1432: sociology of education; sociology of education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60476549?accountid=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+Social+Issues&rft.atitle=Students%27+of+Color+and+European+American+Students%27+Stigma-Relevant+Perceptions+of+University+Instructors&rft.au=Brown%2C+Lisa+M%3BDobbins%2C+Heather&rft.aulast=Brown&rft.aufirst=Lisa&rft.date=2004-01-01&rft.volume=60&rft.issue=1&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Journal+of+Social+Issues&rft.issn=00224537&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Number of references - 53 N1 - Last updated - 2016-09-28 N1 - CODEN - JSISAF N1 - SubjectsTermNotLitGenreText - Student Teacher Relationship; College Students; College Faculty; Stigma; Student Attitudes; Tolerance; Black Americans; Hispanic Americans; Whites ER - TY - JOUR T1 - Are child developmental outcomes related to before- and after-school care arrangements? Results from the NICHD study of early child care AN - 37892284; 2794842 AB - Data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care, a prospective, longitudinal study involving 933 children, were used to examine relations between cumulative participation in 5 types of out-of-school care (before- and after-school programs, extracurricular activities, sitters, fathers, and nonadult care) and child developmental outcomes in the latter part of first grade (approximately age 7 years). Children who consistently participated in extracurricular activities during kindergarten and first grade obtained higher standardized test scores than children who did not consistently participate in these activities, controlling for child and family factors and children's prior functioning. Participation in other types of out-of-school care was not associated with child functioning in first grade when background factors were controlled. Reprinted by permission of the University of Chicago Press. © All rights reserved JF - Child development Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 280 EP - 295 VL - 75 IS - 1 SN - 0009-3920, 0009-3920 KW - Sociology KW - Child protection KW - Children KW - Child care KW - Developmental psychology KW - Child development KW - Family studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37892284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+development&rft.atitle=Are+child+developmental+outcomes+related+to+before-+and+after-school+care+arrangements%3F+Results+from+the+NICHD+study+of+early+child+care&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2004-01-01&rft.volume=75&rft.issue=1&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Child+development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 4783; 2197 2212 6075 3483; 2212; 2204 2208 2212; 3518 10404; 2192 ER - TY - JOUR T1 - Prevention or Delay of Type 2 Diabetes AN - 223051989; 14693925 AB - Diabetes is one of the most costly and burdensome chronic diseases and is a condition that is increasing in epidemic proportions in the US and throughout the world. The complications resulting from the disease are a significant cause of morbidity and mortality and are associated with the damage or failure of various organs such as eyes, kidneys, and nerves. A position statement on the prevention or delay of type 2 diabetes is presented. JF - Diabetes Care AU - Sherwin, Robert S AU - Anderson, Robert M AU - Buse, John B AU - Chin, Marshall H AU - et al Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - S47 EP - 54 CY - Alexandria PB - American Diabetes Association VL - 27 SN - 01495992 KW - Medical Sciences--Endocrinology KW - Diabetes KW - Preventive medicine KW - Chronic illnesses KW - Cardiovascular disease KW - Medical screening KW - Anatomy & physiology KW - Risk Factors KW - Humans KW - Diabetes Mellitus, Type 2 -- epidemiology KW - Glucose Tolerance Test -- standards KW - Quality Assurance, Health Care KW - Diabetes Mellitus, Type 2 -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/223051989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Diabetes+Care&rft.atitle=Prevention+or+Delay+of+Type+2+Diabetes&rft.au=Sherwin%2C+Robert+S%3BAnderson%2C+Robert+M%3BBuse%2C+John+B%3BChin%2C+Marshall+H%3Bet+al&rft.aulast=Sherwin&rft.aufirst=Robert&rft.date=2004-01-01&rft.volume=27&rft.issue=&rft.spage=S47&rft.isbn=&rft.btitle=&rft.title=Diabetes+Care&rft.issn=01495992&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Diabetes Association Jan 2004 N1 - Last updated - 2013-02-06 N1 - CODEN - DICAD2 ER - TY - JOUR T1 - VIRULENCE FACTORS OF THE COAGULASE-NEGATIVE STAPHYLOCOCCI AN - 21186581; 11273219 AB - Coagulase-negative staphylococci (CNS) have gained substantial interest as pathogens involved in nosocomial, particularly catheter-related infections. The pathogenic potential of CNS is mainly due to their capacity to form biofilms on indwelling medical devices. In a biofilm, the bacteria are protected against antibiotics and from attacks by the immune system. The factors contributing to biofilm formation are among the best-studied virulence factors of CNS and comprise factors involved in the adhesion to a catheter surface and in cell accumulation. CNS usually persist in the host in relative silence, but may cause sepsis, for which the recently found inflammatory peptides called phenol-soluble modulins are prime candidates. Many CNS also produce several lipases, proteases, and other exoenzymes, which possibly contribute to the persistence of CNS in the host and may degrade host tissue. We are also beginning to understand how regulators of virulence trigger the expression of virulence factors in CNS. A better conception of the mechanisms underlying the pathogenicity and the frequently encountered antibiotic resistance of CNS may help to develop novel, efficient anti-staphylococcal therapeutics. JF - Frontiers in Bioscience AU - Otto, M AD - Rocky Mountain Laboratories, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, 903 S 4th Street, Hamilton, MT 59840, USA Y1 - 2004 PY - 2004 DA - 2004 SP - 841 EP - 863 VL - 9 SN - 1093-9946, 1093-9946 KW - Microbiology Abstracts B: Bacteriology KW - Cell surface KW - Central nervous system KW - virulence factors KW - Immune system KW - Antibiotics KW - Pathogens KW - Infection KW - Inflammation KW - Triacylglycerol lipase KW - Sepsis KW - Pathogenicity KW - Catheters KW - Proteinase KW - Biofilms KW - Antibiotic resistance KW - Hospitals KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21186581?accountid=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=Frontiers+in+Bioscience&rft.atitle=VIRULENCE+FACTORS+OF+THE+COAGULASE-NEGATIVE+STAPHYLOCOCCI&rft.au=Otto%2C+M&rft.aulast=Otto&rft.aufirst=M&rft.date=2004-01-01&rft.volume=9&rft.issue=&rft.spage=841&rft.isbn=&rft.btitle=&rft.title=Frontiers+in+Bioscience&rft.issn=10939946&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-12-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Central nervous system; Cell surface; virulence factors; Immune system; Antibiotics; Pathogens; Infection; Inflammation; Triacylglycerol lipase; Sepsis; Pathogenicity; Catheters; Proteinase; Biofilms; Antibiotic resistance; Hospitals ER - TY - JOUR T1 - Familial immunodeficiency with cutaneous vasculitis, myoclonus, and cognitive impairment AN - 20673842; 5846623 AB - We report a family with five of six siblings (including identical male twins) with a novel constellation of immunologic and neurologic impairments. Affected subjects experienced severe dermatitis starting around 9 months of age, Stevens-Johnson syndrome in early childhood, and extreme elevations of IgE (9,400-43,000 IU/ml). The oldest sibling died at age 27 of respiratory failure following recurrent, severe pneumonias. All four surviving affected siblings have had chronic sinusitis or otitis, cutaneous vasculitis, and recurrent bacterial pneumonias leading to bronchiectasis. Neurologic features in all five siblings included oral motor deficits, dysarthria, low average IQ (70-80), and essential myoclonus. Four had documented ataxia and/or mild sensory loss with increased patellar but diminished ankle reflexes. The nonconsanguineous parents and one sibling had none of the above findings, consistent with autosomal recessive inheritance. This primary immunodeficiency with distinctive neurological impairments represents a new syndrome. Published 2003 Wiley-Liss, Inc. JF - American Journal of Medical Genetics Part A AU - Hay, B N AU - Martin, JE AU - Karp, B AU - Davis, J AU - Darnell, D AU - Solomon, B AU - Turner, M AU - Holland, S M AU - Puck, J M AD - National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, jpuck@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 145 EP - 151 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 125A IS - 2 SN - 0148-7299, 0148-7299 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - immunodeficiency KW - myoclonus KW - vasculitis KW - Myoclonus KW - Age KW - Vasculitis KW - Heredity KW - Bronchiectasis KW - Immunodeficiency KW - Stevens-Johnson syndrome KW - Sinusitis KW - Children KW - Intelligence KW - Twins KW - Reflexes KW - Cognitive ability KW - Otitis KW - Immunoglobulin E KW - Ataxia KW - Ankle KW - Siblings KW - Pneumonia KW - Dermatitis KW - G 07720:Immunogenetics KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20673842?accountid=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=American+Journal+of+Medical+Genetics+Part+A&rft.atitle=Familial+immunodeficiency+with+cutaneous+vasculitis%2C+myoclonus%2C+and+cognitive+impairment&rft.au=Hay%2C+B+N%3BMartin%2C+JE%3BKarp%2C+B%3BDavis%2C+J%3BDarnell%2C+D%3BSolomon%2C+B%3BTurner%2C+M%3BHolland%2C+S+M%3BPuck%2C+J+M&rft.aulast=Hay&rft.aufirst=B&rft.date=2004-01-01&rft.volume=125A&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics+Part+A&rft.issn=01487299&rft_id=info:doi/10.1002%2Fajmg.a.20595 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-06-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Myoclonus; Age; Vasculitis; Heredity; Bronchiectasis; Immunodeficiency; Stevens-Johnson syndrome; Sinusitis; Children; Intelligence; Reflexes; Twins; Cognitive ability; Immunoglobulin E; Otitis; Ataxia; Siblings; Ankle; Pneumonia; Dermatitis DO - http://dx.doi.org/10.1002/ajmg.a.20595 ER - TY - JOUR T1 - Direct ampholyte-free liquid-phase isoelectric peptide focusing: Application to the human serum proteome AN - 20396402; 7761858 AB - In this study, we utilized a multidimensional peptide separation strategy combined with tandem mass spectrometry (MS/MS) for the identification of proteins in human serum. After enzymatically digesting serum with trypsin, the peptides were fractionated using liquid-phase isoelectric focusing (IEF) in a novel ampholyte-free format. Twenty IEF fractions were collected and analyzed by reversed-phase microcapillary liquid chromatography (LC)-MS/MS. Bioinformatic analysis of the raw MS/MS spectra resulted in the identification of 844 unique peptides, corresponding to 437 proteins. This study demonstrates the efficacy of ampholyte-free peptide autofocusing, which alleviates peptide losses in ampholyte removal strategies. The results show that the separation strategy is effective for high-throughput characterization of proteins from complex proteomic mixtures. JF - Electrophoresis AU - Xiao, Zhen AU - Conrads, Thomas P AU - Lucas, David A AU - Janini, George M AU - Schaefer, Carl F AU - Buetow, Kenneth H AU - Issaq, Haleem J AU - Veenstra, Timothy D AD - Laboratory of Proteomics and Analytical Technologies, National Cancer Institute at Frederick, SAIC-Frederick, Frederick, MD, USA, veenstra@ncifcrf.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 128 EP - 133 PB - Wiley-VCH, Postfach 101161 Weinheim 69451 Germany, [mailto:info@wiley-vch.de], [URL:http://www.wiley-vch.de/publish/en/] VL - 25 IS - 1 SN - 0173-0835, 0173-0835 KW - Biotechnology and Bioengineering Abstracts KW - Trypsin KW - Liquid chromatography KW - Bioinformatics KW - proteomics KW - Isoelectric focusing KW - Mass spectroscopy KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20396402?accountid=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=Electrophoresis&rft.atitle=Direct+ampholyte-free+liquid-phase+isoelectric+peptide+focusing%3A+Application+to+the+human+serum+proteome&rft.au=Xiao%2C+Zhen%3BConrads%2C+Thomas+P%3BLucas%2C+David+A%3BJanini%2C+George+M%3BSchaefer%2C+Carl+F%3BBuetow%2C+Kenneth+H%3BIssaq%2C+Haleem+J%3BVeenstra%2C+Timothy+D&rft.aulast=Xiao&rft.aufirst=Zhen&rft.date=2004-01-01&rft.volume=25&rft.issue=1&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/10.1002%2Felps.200305700 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Isoelectric focusing; Trypsin; Mass spectroscopy; proteomics; Bioinformatics; Liquid chromatography DO - http://dx.doi.org/10.1002/elps.200305700 ER - TY - JOUR T1 - Albumin enhanced morphometric image analysis in CLL AN - 20379693; 7760239 AB - BACKGROUND The heterogeneity of lymphocytes from patients with chronic lymphocytic leukemia (CLL) and blood film artifacts make morphologic subclassification of this disease difficult. METHODS We reviewed paired blood films prepared from ethylene-diamine-tetraacetic acid (ETDA) samples with and without bovine serum albumin (BSA) from 82 CLL patients. Group 1 adhered to NCCLS specifications for the preparations of EDTA blood films. Group 2 consisted of blood films containing EDTA and a 1:12 dilution of 22% BSA. Eight patients were selected for digital photomicroscopy and statistical analysis. Approximately 100 lymphocytes from each slide were digitally captured. RESULTS The mean cell area - standard error was 127.8 m2 - 1.42 for (n = 793) for group 1 versus 100.7 m2 - 1.39 (n = 831) for group 2. The nuclear area was 88.9 m2 - 0.85 for group 1 versus 76.4 m2 - 0.83 for group 2. For the nuclear transmittance, the values were 97.6 - 0.85 for group 1 and 104.1 - 0.83 for group 2. The nuclear:cytoplasmic ratios were 0.71 - 0.003 for group 1 and 0.78 - 0.003 for group 2. All differences were statistically significant (P < 0.001). CONCLUSIONS BSA addition results in the reduction of atypical lymphocytes and a decrease in smudge cells. BSA also decreases the lymphocyte area and nuclear area, whereas nuclear transmittance and nuclear:cytoplasmic ratio are increased. A standardized method of slide preparation would allow accurate interlaboratory comparison. The use of BSA may permit better implementation of the blood film-based subclassification of CLL and lead to a better correlation of morphology with cytogenetics and immunophenotyping. JF - Cytometry Part B AU - Lunning, Matthew A AU - Zenger, Vincent E AU - Dreyfuss, Ricardo AU - Stetler-Stevenson, Maryalice AU - Rick, Margaret E AU - White, Therese A AU - Wilson, Wyndham H AU - Marti, Gerald E AD - Flow and Image Cytometry Section, Laboratory Stem Cell Biology, Division of Cell and Gene Therapies, Center for Biologics Research and Evaluation, Food and Drug Administration, Bethesda, Maryland, gemarti@helix.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 7 EP - 14 PB - John Wiley & Sons, Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 57B IS - 1 SN - 1552-4949, 1552-4949 KW - Biotechnology and Bioengineering Abstracts KW - Blood KW - Bovine serum albumin KW - Statistical analysis KW - Image processing KW - Slide preparation KW - Lymphocytes KW - Chronic lymphatic leukemia KW - Cytometry KW - Edetic acid KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20379693?accountid=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=Cytometry+Part+B&rft.atitle=Albumin+enhanced+morphometric+image+analysis+in+CLL&rft.au=Lunning%2C+Matthew+A%3BZenger%2C+Vincent+E%3BDreyfuss%2C+Ricardo%3BStetler-Stevenson%2C+Maryalice%3BRick%2C+Margaret+E%3BWhite%2C+Therese+A%3BWilson%2C+Wyndham+H%3BMarti%2C+Gerald+E&rft.aulast=Lunning&rft.aufirst=Matthew&rft.date=2004-01-01&rft.volume=57B&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+B&rft.issn=15524949&rft_id=info:doi/10.1002%2Fcyto.b.10059 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Blood; Chronic lymphatic leukemia; Lymphocytes; Statistical analysis; Edetic acid; Slide preparation; Image processing; Cytometry; Bovine serum albumin DO - http://dx.doi.org/10.1002/cyto.b.10059 ER - TY - JOUR T1 - Multipathogen oligonucleotide microarray for environmental and biodefense applications AN - 20194613; 6964765 AB - Food-borne pathogens are a major health problem. The large and diverse number of microbial pathogens and their virulence factors has fueled interest in technologies capable of detecting multiple pathogens and multiple virulence factors simultaneously. Some of these pathogens and their toxins have potential use as bioweapons. DNA microarray technology allows the simultaneous analysis of thousands of sequences of DNA in a relatively short time, making it appropriate for biodefense and for public health uses. This paper describes methods for using DNA microarrays to detect and analyze microbial pathogens. The FDA-1 microarray was developed for the simultaneous detection of several food-borne pathogens and their virulence factors including Listeria spp., Campylobacter spp., Staphylococcus aureus enterotoxin genes and Clostridium perfringens toxin genes. Three elements were incorporated to increase confidence in the microarray detection system: redundancy of genes, redundancy of oligonucleotide probes (oligoprobes) for a specific gene, and quality control oligoprobes to monitor array spotting and target DNA hybridization. These elements enhance the reliability of detection and reduce the chance of erroneous results due to the genetic variability of microbes or technical problems with the microarray. The results presented demonstrate the potential of oligonucleotide microarrays for detection of environmental and biodefense relevant microbial pathogens. JF - Biosensors and Bioelectronics AU - Sergeev, Nikolay AU - Distler, Margaret AU - Courtney, Shannon AU - Al-Khaldi, Sufian F AU - Volokhov, Dmitriy AU - Chizhikov, Vladimir AU - Rasooly, Avraham AD - FDA Center for Food Safety and Applied Nutrition, College Park, MD, USA, rasoslya@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 684 EP - 698 PB - Elsevier Advanced Technology, 660 White Plains Rd. Tarrytown NY 10591-5153 USA VL - 20 IS - 4 SN - 0956-5663, 0956-5663 KW - Microbiology Abstracts B: Bacteriology; Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Oligonucleotide microarray KW - Microbial pathogens KW - virulence factors KW - DNA probes KW - Nucleotide sequence KW - Food KW - Clostridium perfringens KW - Probes KW - Campylobacter KW - Pathogens KW - DNA microarrays KW - Oligonucleotides KW - Listeria KW - Toxins KW - Public health KW - Biosensors KW - Quality control KW - Enterotoxins KW - Staphylococcus aureus KW - W4 230:Biosensors, Bioelectronics & Bioindicators KW - J 02400:Human Diseases KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20194613?accountid=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=Biosensors+and+Bioelectronics&rft.atitle=Multipathogen+oligonucleotide+microarray+for+environmental+and+biodefense+applications&rft.au=Sergeev%2C+Nikolay%3BDistler%2C+Margaret%3BCourtney%2C+Shannon%3BAl-Khaldi%2C+Sufian+F%3BVolokhov%2C+Dmitriy%3BChizhikov%2C+Vladimir%3BRasooly%2C+Avraham&rft.aulast=Sergeev&rft.aufirst=Nikolay&rft.date=2004-01-01&rft.volume=20&rft.issue=4&rft.spage=684&rft.isbn=&rft.btitle=&rft.title=Biosensors+and+Bioelectronics&rft.issn=09565663&rft_id=info:doi/10.1016%2Fj.bios.2004.04.030 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - virulence factors; Food; Nucleotide sequence; DNA probes; Probes; Pathogens; Oligonucleotides; DNA microarrays; Toxins; Public health; Biosensors; Quality control; Enterotoxins; Clostridium perfringens; Campylobacter; Staphylococcus aureus; Listeria DO - http://dx.doi.org/10.1016/j.bios.2004.04.030 ER - TY - JOUR T1 - Flotillin-1 in the substantia Nigra of the Parkinson brain and a predominant localization in catecholaminergic nerves in the rat brain AN - 20136040; 10263094 AB - The substantia nigra cells of a normal and Parkinson's disease human brain were obtained by the micropunch procedure and total RNA was isolated. Differential display RT-PCR of the total RNA revealed differentially expressed cDNAs that were identified by sequencing. This resulted in the identification of a panel of known and unknown differentially expressed genes. Complex I (NADH ubiquinone oxidoreductase) and Complex IV (cytochrome oxidase) whose expressions are decreased in Parkinson's disease were reduced in the Parkinson brain. Of the various differentially expressed genes, flotillin-1, also known as reggie-2, was of great interest to us. It is a relatively new protein which is an integral membrane component of lipid rafts and has been implicated in signal transduction pathway events. In situ hybridization histochemical studies with human and rat brain sections revealed the presence of this mRNA in discrete neuronal (and possibly glial) cells of the substantia nigra, locus coeruleus, cortex, hippocampus, hypothalamus, thalamus, motor nuclei, nucleus basalis, raphe nucleus, and other brain regions. Immunohistochemical studies revealed that flotillin-1 is not present in all the regions where the message was found. In the rat brain, the most prominent observation was the revelation of all cate-cholamine cells (dopamine, norepinephrine, epinephrine) by the flotillin-1 antibody (1:100 dilution). At a more concentrated dilution (1:10) other neuronal cells (e.g., cortex, thalamus, hindbrain) were observed. At both dilutions dense dopaminergic fibers were observed in the rat caudate-putamen, nigrostriatal tract, and substantia nigra. It is significant that there is an increased gene expression of flotillin-1 in the Parkinson substantia nigra/ventral tegmental area. The role of flotillin in these cells is unclear although it is interesting that the reggie-2/flotillin-1 gene was upregulated during retinal axon regeneration in the goldfish visual pathway (Schulteet al., Development 124:577--87, 1997) which suggests that flotillin-1/reggie-2 might play a role in axonal growth from the remaining substantia nigra cells of the Parkinson brain. JF - Neurotoxicity Research AU - Jacobowitz, D M AU - Kallarakal, A T AD - Laboratory of Clinical Science, NIMH, NIH, 20892 Bethesda, MD, USA, dwj@helix.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 245 EP - 257 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 6 IS - 4 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Retina KW - Parkinson's disease KW - Ventral tegmentum KW - Cytochrome-c oxidase KW - Hindbrain KW - Carassius auratus KW - Thalamus KW - Lipid rafts KW - Nerves KW - Visual pathways KW - nucleus basalis KW - Cortex KW - Dopamine KW - Polymerase chain reaction KW - Epinephrine KW - Differential display KW - ubiquinone oxidoreductase KW - Substantia nigra KW - Cortex (motor) KW - Caudate-putamen KW - NADH KW - Brain KW - Fibers KW - Neurodegenerative diseases KW - Antibodies KW - Movement disorders KW - Motor nuclei KW - Neurotoxicity KW - Norepinephrine KW - Axons KW - Signal transduction KW - X 24310:Pharmaceuticals KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20136040?accountid=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=Neurotoxicity+Research&rft.atitle=Flotillin-1+in+the+substantia+Nigra+of+the+Parkinson+brain+and+a+predominant+localization+in+catecholaminergic+nerves+in+the+rat+brain&rft.au=Jacobowitz%2C+D+M%3BKallarakal%2C+A+T&rft.aulast=Jacobowitz&rft.aufirst=D&rft.date=2004-01-01&rft.volume=6&rft.issue=4&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033435 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Retina; Parkinson's disease; Ventral tegmentum; Hindbrain; Cytochrome-c oxidase; Thalamus; Lipid rafts; Nerves; Visual pathways; nucleus basalis; Dopamine; Cortex; Polymerase chain reaction; Epinephrine; Differential display; ubiquinone oxidoreductase; Substantia nigra; Cortex (motor); Caudate-putamen; NADH; Brain; Neurodegenerative diseases; Fibers; Antibodies; Movement disorders; Norepinephrine; Neurotoxicity; Motor nuclei; Axons; Signal transduction; Carassius auratus DO - http://dx.doi.org/10.1007/BF03033435 ER - TY - JOUR T1 - The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis AN - 20055641; 8719889 AB - The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC). The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance ( arrow right H-NMR) spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC). We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping) as a fitness test for a supervised system (a genetic algorithm). With this approach, a training set comprised of mass spectra and arrow right H-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in $n$-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%. JF - Disease Markers AU - Van, Que N AU - Klose, John R AU - Lucas, David A AU - Prieto, DaRue A AU - Luke, Brian AU - Collins, Jack AU - Burt, Stanley K AU - Chmurny, Gwendolyn N AU - Issaq, Haleem J AU - Conrads, Thomas P AU - Veenstra, Timothy D AD - Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD, USA Y1 - 2004 PY - 2004 DA - 2004 SP - 169 EP - 183 PB - IOS Press, Nieuwe Hemweg 6B VL - 19 IS - 4-5 SN - 0278-0240, 0278-0240 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Fitness KW - Genomes KW - Bacteria KW - Algorithms KW - Cystitis KW - biomarkers KW - Mass spectroscopy KW - Pattern recognition KW - Urine KW - N.M.R. KW - proteomics KW - Bioinformatics KW - Gene mapping KW - A 01300:Methods KW - J 02300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20055641?accountid=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=conference&rft.jtitle=Disease+Markers&rft.atitle=The+use+of+urine+proteomic+and+metabonomic+patterns+for+the+diagnosis+of+interstitial+cystitis+and+bacterial+cystitis&rft.au=Van%2C+Que+N%3BKlose%2C+John+R%3BLucas%2C+David+A%3BPrieto%2C+DaRue+A%3BLuke%2C+Brian%3BCollins%2C+Jack%3BBurt%2C+Stanley+K%3BChmurny%2C+Gwendolyn+N%3BIssaq%2C+Haleem+J%3BConrads%2C+Thomas+P%3BVeenstra%2C+Timothy+D&rft.aulast=Van&rft.aufirst=Que&rft.date=2004-01-01&rft.volume=19&rft.issue=4-5&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Disease+Markers&rft.issn=02780240&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; Fitness; Pattern recognition; Urine; Algorithms; Cystitis; N.M.R.; Bioinformatics; proteomics; biomarkers; Mass spectroscopy; Gene mapping; Bacteria ER - TY - JOUR T1 - Non-Hodgkin's lymphoma among asthmatics exposed to pesticides AN - 19969169; 6930487 AB - We conducted a pooled analysis of population-based case-control studies in Iowa, Minnesota and Nebraska to investigate whether asthma modifies risk of non- Hodgkin's lymphoma (NHL) associated with pesticide exposures. Cases (n = 872) diagnosed with NHL from 1980 to 1986 and frequency-matched controls (n = 2,381) randomly selected from the same geographic areas as the cases were included. Information on use of pesticides and history of asthma was based on interviews. Unconditional logistic regression was used to calculate ORs, adjusted for age, state and vital status. Of all subjects, 177 (45 cases, 132 controls) reported having been told by their doctor that they had asthma. Subjects with an asthma history had a nonsignificantly lower risk of NHL than nonasthmatics (OR = 0.6, 95% CI 0.3-1.4), and there was no main effect of pesticide exposure (OR = 1.0, 95% CI 0.8-1.2). However, asthmatics tended to have larger ORs associated with exposure to pesticides than nonasthmatics. The OR among asthmatics was 1.8 (95% CI 1.1-3.2) for ever-use of crop insecticides, 2.7 (95% CI 1.0-7.2) for chlordane, 2.4 (95% CI 1.0-5.7) for lindane and 3.7 (95% CI 1.3-10.9) for fonofos. Among nonasthmatics, ORs were 1.1 (0.9-1.3), 1.5 (1.1-2.2), 1.3 (0.97-1.8) and 1.6 (1.0-2.4), respectively. Although there is limited power for assessing interaction, our results suggest that the risk of NHL among asthmatics with pesticide exposure may be higher than among nonasthmatics with pesticide exposure. JF - International Journal of Cancer AU - Lee, Won Jin AU - Cantor, Kenneth P AU - Berzofsky, Jay A AU - Zahm, Shelia H AU - Blair, Aaron AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health, Rockville, MD, USA, Leewj@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 298 EP - 302 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 111 IS - 2 SN - 0020-7136, 0020-7136 KW - Immunology Abstracts; Risk Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - asthma KW - insecticide KW - farmer KW - non-Hodgkin's lymphoma KW - pesticide exposure KW - Historical account KW - Hodgkin's disease KW - Chlordane KW - Asthma KW - Lindane KW - Respiratory diseases KW - Agrochemicals KW - USA, Minnesota KW - Non-Hodgkin's lymphoma KW - Insecticides KW - USA, Iowa KW - Risk factors KW - Pesticides KW - USA, Nebraska KW - lymphoma KW - H 5000:Pesticides KW - F 06915:Cancer Immunology KW - R2 23060:Medical and environmental health KW - X 24136:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19969169?accountid=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=International+Journal+of+Cancer&rft.atitle=Non-Hodgkin%27s+lymphoma+among+asthmatics+exposed+to+pesticides&rft.au=Lee%2C+Won+Jin%3BCantor%2C+Kenneth+P%3BBerzofsky%2C+Jay+A%3BZahm%2C+Shelia+H%3BBlair%2C+Aaron&rft.aulast=Lee&rft.aufirst=Won&rft.date=2004-01-01&rft.volume=111&rft.issue=2&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20273 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Non-Hodgkin's lymphoma; Insecticides; Hodgkin's disease; Chlordane; Risk factors; Pesticides; Asthma; Lindane; Historical account; Respiratory diseases; Agrochemicals; lymphoma; USA, Iowa; USA, Nebraska; USA, Minnesota DO - http://dx.doi.org/10.1002/ijc.20273 ER - TY - JOUR T1 - Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells AN - 19939330; 6084718 AB - Multipotential adult mesenchymal stem cells (MSCs) are able to differentiate along several known lineages, and lineage commitment is tightly regulated through specific cellular mediators and interactions. Recent observations of a low/high bone-mass phenotype in patients expressing a loss-/gain-of-function mutation in LRP5, a coreceptor of the Wnt family of signaling molecules, suggest the importance of Wnt signaling in bone formation, possibly involving MSCs. To analyze the role of Wnt signaling in mesenchymal osteogenesis, we have profiled the expression of WNTs and their receptors, FRIZZLEDs (FZDs), and several secreted Wnt inhibitors, such as SFRPs, and examined the effect of Wnt 3a, as a representative canonical Wnt member, during MSC osteogenesis in vitro. WNT11, FZD6, SFRP2, and SFRP3 are upregulated during MSC osteogenesis, while WNT9A and FZD7 are downregulated. MSCs also respond to exogenous Wnt 3a, based on increased [beta]-catenin nuclearization and activation of a Wnt-responsive promoter, and the magnitude of this response depends on the MSC differentiation state. Wnt 3a exposure inhibits MSC osteogenic differentiation, with decreased matrix mineralization and reduced alkaline phosphatase mRNA and activity. Wnt 3a treatment of fully osteogenically differentiated MSCs also suppresses osteoblastic marker gene expression. The Wnt 3a effect is accompanied by increased cell number, resulting from both increased proliferation and decreased apoptosis, particularly during expansion of undifferentiated MSCs. The osteo- suppressive effects of Wnt 3a are fully reversible, i.e. treatment prior to osteogenic induction does not compromise subsequent MSC osteogenesis. The results also showed that sFRP3 treatment attenuates some of the observed Wnt 3a effects on MSCs, and that inhibition of canonical Wnt signaling using a dominant negative TCF1 enhances MSC osteogenesis. Interestingly, expression of Wnt 5a, a non-canonical Wnt member, appeared to promote osteogenesis. Taken together, these findings suggest that canonical Wnt signaling functions in maintaining an undifferentiated, proliferating progenitor MSC population, whereas non-canonical Wnts facilitate osteogenic differentiation. Release from canonical Wnt regulation is a prerequisite for MSC differentiation. Thus, loss-/gain-of- function mutations of LRP5 would perturb Wnt signaling and depress/promote bone formation by affecting the progenitor cell pool. Elucidating Wnt regulation of MSC differentiation is important for their potential application in tissue regeneration. Published 2004 Wiley-Liss, Inc. JF - Journal of Cellular Biochemistry AU - Boland, Genevieve M AU - Perkins, Geraldine AU - Hall, David J AU - Tuan, Rocky S AD - Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, tuanr@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 1210 EP - 1230 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 93 IS - 6 SN - 0730-2312, 0730-2312 KW - Biotechnology and Bioengineering Abstracts; Calcium & Calcified Tissue Abstracts KW - Wnt KW - mesenchymal stem cell KW - osteogenesis KW - LRP5 KW - frizzled KW - signaling KW - Hepatocyte nuclear factor 1 KW - Apoptosis KW - Wnt protein KW - Cell number KW - Frizzled protein KW - Mineralization KW - LRP5 protein KW - Gene expression KW - Promoters KW - Differentiation KW - Osteoblasts KW - Stem cells KW - Alkaline phosphatase KW - Regeneration KW - Cell proliferation KW - Mesenchyme KW - Mutation KW - Signal transduction KW - Osteogenesis KW - W 30965:Miscellaneous, Reviews KW - T 2025:Bone and Bone Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19939330?accountid=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+Cellular+Biochemistry&rft.atitle=Wnt+3a+promotes+proliferation+and+suppresses+osteogenic+differentiation+of+adult+human+mesenchymal+stem+cells&rft.au=Boland%2C+Genevieve+M%3BPerkins%2C+Geraldine%3BHall%2C+David+J%3BTuan%2C+Rocky+S&rft.aulast=Boland&rft.aufirst=Genevieve&rft.date=2004-01-01&rft.volume=93&rft.issue=6&rft.spage=1210&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cellular+Biochemistry&rft.issn=07302312&rft_id=info:doi/10.1002%2Fjcb.20284 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-04-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Hepatocyte nuclear factor 1; Wnt protein; Apoptosis; Cell number; Frizzled protein; Mineralization; LRP5 protein; Gene expression; Osteoblasts; Differentiation; Promoters; Stem cells; Alkaline phosphatase; Regeneration; Mesenchyme; Cell proliferation; Mutation; Osteogenesis; Signal transduction DO - http://dx.doi.org/10.1002/jcb.20284 ER - TY - JOUR T1 - BG01V: A variant human embryonic stem cell line which exhibits rapid growth after passaging and reliable dopaminergic differentiation AN - 19880415; 8724007 AB - Purpose: To explore a karyotypically abnormal variant human embryonic stem cell (hESC) line, BG01V, as a potential model for studies of dopaminergic neuronal differentiation.Methods: The properties of BG01V cells were compared to those of normal BG01 cells using immunocytochemistry, RT-PCR, focused microarrays and in vitro differentiation, including dopaminergic differentiation, by culturing with the stromal cell line PA6.Results: Despite the karyotypic abnormality (49, +12, +17 and XXY), undifferentiated BG01V cells expressed pluripotent ESC markers similar to BG01 cells, and retained the ability to differentiate into cell types characteristic of all three germ layers. When co-cultured with the stromal cell line PA6, BG01V cells differentiated into dopaminergic cells which exhibited properties similar to those of mature dopaminergic neurons.Conclusions: BG01V cells were easier to maintain in culture than karyotypically normal BG01 cells and can be used as an alternative pluripotent hESC type for in vitro developmental studies. JF - Restorative Neurology and Neuroscience AU - Zeng, Xianmin AU - Chen, Jia AU - Liu, Ying AU - Luo, Yongquan AU - Schulz, Thomas C AU - Robins, Allan J AU - Rao, Mahendra S AU - Freed, William J AD - Cellular Neurobiology Branch, National Institute on Drug Abuse and NIH, DHHS, Baltimore, MD 212, USA Y1 - 2004 PY - 2004 DA - 2004 SP - 421 EP - 428 PB - IOS Press, Nieuwe Hemweg 6B VL - 22 IS - 6 SN - 0922-6028, 0922-6028 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - hESCs KW - karyotype KW - dopaminergic differentiation KW - PA6 stromal cells KW - Differentiation KW - Immunocytochemistry KW - Stem cells KW - Nervous system KW - Dopamine KW - stromal cells KW - Embryo cells KW - Polymerase chain reaction KW - Cell culture KW - G 07730:Development & Cell Cycle KW - N3 11027:Neurology & neuropathology KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19880415?accountid=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=Restorative+Neurology+and+Neuroscience&rft.atitle=BG01V%3A+A+variant+human+embryonic+stem+cell+line+which+exhibits+rapid+growth+after+passaging+and+reliable+dopaminergic+differentiation&rft.au=Zeng%2C+Xianmin%3BChen%2C+Jia%3BLiu%2C+Ying%3BLuo%2C+Yongquan%3BSchulz%2C+Thomas+C%3BRobins%2C+Allan+J%3BRao%2C+Mahendra+S%3BFreed%2C+William+J&rft.aulast=Zeng&rft.aufirst=Xianmin&rft.date=2004-01-01&rft.volume=22&rft.issue=6&rft.spage=421&rft.isbn=&rft.btitle=&rft.title=Restorative+Neurology+and+Neuroscience&rft.issn=09226028&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 - Immunocytochemistry; Differentiation; Nervous system; Stem cells; Dopamine; Embryo cells; stromal cells; Polymerase chain reaction; Cell culture ER - TY - JOUR T1 - Effects of antimicrobial agents on oral biofilms in a saliva-conditioned flowcell AN - 19847218; 6972029 AB - Oral bacteria form mixed-species biofilms known as dental plaque. Growth of these complex microbial communities is often controlled with the use of antimicrobial mouthrinses. Novel laboratory methods for testing the efficacy of antimicrobials in situ are necessary to complement current clinical testing protocols. In this study, we examined the effects of antimicrobial agents on a streptococcal biofilm grown in a saliva-conditioned flowcell. The flowcell coupled with confocal laser scanning microscopy enabled examination of growing oral biofilms in situ without disruption of the microbial community. Biofilms composed of Streptococcus gordonii DL1 were grown in an in vitro flowcell and treated with several commercially available antimicrobial mouthrinses containing essential oils, triclosan, cetylpyridinium chloride/domiphen or chlorhexidine. The results of this study revealed varying abilities of the antimicrobial agents to cause cellular damage on the growing biofilm in situ. This study therefore demonstrated the usefulness of the flowcell in the rapid assessment of antimicrobial efficacy. JF - Biofilms AU - Foster, J S AU - Pan, P C AU - Kolenbrander, P E AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4350, USA, pkolenbrander@dir.nidcr.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 5 EP - 12 PB - Cambridge University Press, UK, The Edinburgh Building, Shaftesbury Road Cambridge CB2 2RU UK, [mailto:journals@cambridge.org], [URL:http://journals.cambridge.org] VL - 1 IS - 1 SN - 1479-0505, 1479-0505 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Chlorhexidine KW - Streptococcus gordonii KW - Mouthwashes KW - Complement KW - Confocal microscopy KW - Essential oils KW - Biofilms KW - Dental plaque KW - Triclosan KW - Antimicrobial agents KW - Cetylpyridinium chloride KW - J 02320:Cell Biology KW - A 01066:Antibacterial & bactericidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19847218?accountid=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=Biofilms&rft.atitle=Effects+of+antimicrobial+agents+on+oral+biofilms+in+a+saliva-conditioned+flowcell&rft.au=Foster%2C+J+S%3BPan%2C+P+C%3BKolenbrander%2C+P+E&rft.aulast=Foster&rft.aufirst=J&rft.date=2004-01-01&rft.volume=1&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Biofilms&rft.issn=14790505&rft_id=info:doi/10.1017%2FS1479050503001017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-09-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Chlorhexidine; Mouthwashes; Confocal microscopy; Complement; Essential oils; Biofilms; Dental plaque; Triclosan; Cetylpyridinium chloride; Antimicrobial agents; Streptococcus gordonii DO - http://dx.doi.org/10.1017/S1479050503001017 ER - TY - JOUR T1 - Improved generation of C57BL/6J mouse embryonic stem cells in a defined serum-free media AN - 19844185; 6931372 AB - Summary: C57BL/6 is a well-characterized mouse strain that is used extensively for immunological and neurological research. The establishment of C57BL/6 ES cell lines has facilitated the study of gene-altered mice in a pure genetic background - however, relatively few such lines exist. Using a defined media supplement, knockout serum replacement (KSR) with knockout DMEM (KSR- KDMEM), we find that we can readily establish ES cell lines from blastocysts of C57BL/6J mice. Six lines were established, all of which were karyotypically normal and could be maintained in the undifferentiated state on mouse embryonic fibroblast (MEF) feeders. One line was further tested and found to be karyotypically stable and germline competent, both prior to manipulation and after gene targeting. For this cell line, efficiencies of cell cloning and chimera generation were greater when maintained in KSR-KDMEM. Our work suggests that the use of defined serum-free media may facilitate the generation of ES cells from inbred mouse strains. genesis 39:100-104, 2004. JF - Genesis AU - Cheng, Jun AU - Dutra, Amalia AU - Takesono, Aya AU - Garrett-Beal, Lisa AU - Schwartzberg, Pamela L AD - Genetic Diseases Research Branch, National Human Genome Research Institute, Bethesda, Maryland, lgarrett@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 100 EP - 104 Published 2004 Wiley-Liss, Inc. Technology Report PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 39 IS - 2 SN - 1526-954X, 1526-954X KW - mice KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts KW - embryonic stem cells KW - gene targeting KW - defined media KW - KSR-KDMEM KW - C57BL/6J KW - Chimeras KW - Gene targeting KW - blastocysts KW - Stem cells KW - Embryo cells KW - Serum KW - Embryo fibroblasts KW - Cloning KW - Inbreeding KW - Fibroblasts KW - W 30905:Medical Applications KW - G 07250:Developmental genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19844185?accountid=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=Genesis&rft.atitle=Improved+generation+of+C57BL%2F6J+mouse+embryonic+stem+cells+in+a+defined+serum-free+media&rft.au=Cheng%2C+Jun%3BDutra%2C+Amalia%3BTakesono%2C+Aya%3BGarrett-Beal%2C+Lisa%3BSchwartzberg%2C+Pamela+L&rft.aulast=Cheng&rft.aufirst=Jun&rft.date=2004-01-01&rft.volume=39&rft.issue=2&rft.spage=100&rft.isbn=&rft.btitle=&rft.title=Genesis&rft.issn=1526954X&rft_id=info:doi/10.1002%2Fgene.20031 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Chimeras; Stem cells; blastocysts; Gene targeting; Embryo cells; Serum; Embryo fibroblasts; Cloning; Inbreeding; Fibroblasts DO - http://dx.doi.org/10.1002/gene.20031 ER - TY - JOUR T1 - Caffeine suppresses metastasis in a transgenic mouse model: a prototype molecule for prophylaxis of metastasis AN - 19837308; 6650516 AB - A significant fraction of cancer patients have occult disseminated tumors at the time of primary diagnosis, which usually progress to become clinically relevant lesions. Since the majority of cancer mortality is associated with metastatic disease, the ability to inhibit the growth of the secondary tumors would significantly reduce cancer-related morbidity and mortality. We have investigated whether caffeine, which has been shown to suppress tumor cell invasiveness and experimental metastasis, can suppress metastasis in a spontaneous transgene-induced mammary tumor model. Chronic exposure to caffeine prior to the appearance of palpable mammary tumors significantly reduced both tumor burden and metastatic colonization. However, when caffeine exposure began after the appearance of frank tumors, caffeine suppressed metastasis without changing primary tumor burden. The means by which caffeine suppressed metastatic activity may be associated with inhibition of malignant transformation of mammary epithelial cells, inhibition of conversion of dormant tumor cells to micrometastases, micrometastases to macrometastases, or inhibition of tumor cell adhesion and motility. Gene and protein expression patterns resulting from caffeine treatment showed that metastasis suppression may be associated with up-regulation the mRNA expression of multiple extracellular matrix genes, including Fbln1, Bgn, Sparc, Fbn1, Loxl1, Col1a1, Col3a1, Col5a1, Col5a2, Col5a3, Col6a1, Col6a2, and Col6a3. These data suggested that caffeine or other methyl xanthine derivatives may improve the clinical outcome in patients prior to and following the diagnosis of metastatic disease, and could potentially reduce the morbidity and mortality associated with disseminated tumors. JF - Clinical & Experimental Metastasis AU - Yang, Haiyan AU - Rouse, Jessica AU - Lukes, Luanne AU - Lancaster, Mindy AU - Veenstra, Timothy AU - Zhou, Ming AU - Shi, Ying AU - Park, Yeong-Gwan AU - Hunter, Kent AD - National Cancer Institute, 41 Library Drive, Bethesda, MD, 20892, USA, hunterk@mail.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 719 EP - 735 PB - Kluwer Academic Publishers, Postbus 17 Dordrecht 3300 AA Netherlands, [mailto:services@wkap.nl] VL - 21 IS - 8 SN - 0262-0898, 0262-0898 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Transformation KW - Molecular modelling KW - Epithelial cells KW - Invasiveness KW - Animal models KW - Tumor cells KW - Morbidity KW - Metastases KW - Gene expression KW - Colonization KW - Chronic exposure KW - Caffeine KW - Cell migration KW - Collagen (type I) KW - Mortality KW - Data processing KW - Mammary gland KW - Xanthine KW - Tumors KW - Transgenic mice KW - Cancer KW - Motility KW - Extracellular matrix KW - Prophylaxis KW - Osteonectin KW - W 30925:Genetic Engineering KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19837308?accountid=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+%26+Experimental+Metastasis&rft.atitle=Caffeine+suppresses+metastasis+in+a+transgenic+mouse+model%3A+a+prototype+molecule+for+prophylaxis+of+metastasis&rft.au=Yang%2C+Haiyan%3BRouse%2C+Jessica%3BLukes%2C+Luanne%3BLancaster%2C+Mindy%3BVeenstra%2C+Timothy%3BZhou%2C+Ming%3BShi%2C+Ying%3BPark%2C+Yeong-Gwan%3BHunter%2C+Kent&rft.aulast=Yang&rft.aufirst=Haiyan&rft.date=2004-01-01&rft.volume=21&rft.issue=8&rft.spage=719&rft.isbn=&rft.btitle=&rft.title=Clinical+%26+Experimental+Metastasis&rft.issn=02620898&rft_id=info:doi/10.1007%2Fs10585-004-8251-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Transformation; Epithelial cells; Molecular modelling; Invasiveness; Animal models; Tumor cells; Morbidity; Gene expression; Metastases; Colonization; Chronic exposure; Caffeine; Cell migration; Collagen (type I); Mortality; Data processing; Mammary gland; Xanthine; Tumors; Transgenic mice; Cancer; Motility; Extracellular matrix; Prophylaxis; Osteonectin DO - http://dx.doi.org/10.1007/s10585-004-8251-4 ER - TY - JOUR T1 - Cryopreservation of Xenopus Transgenic Lines AN - 19826709; 5870259 AB - Xenopus laevis has been widely used for molecular, cellular, and developmental studies. With the development of the sperm-mediated transgenic method, it is now possible to study gene function during vertebrate development by using this popular model. On the other hand, like other animal species, it is labor intensive, and the maintenance of transgenic lines is expensive. In this article, we investigated the possibility of using sperm-cryopreservation as a means to preserve transgenic frog lines. We demonstrated that cryopreserved sperms are viable but not fertile under our in vitro fertilization (IVF) conditions. However, by microinjecting cryopreserved sperm nuclei, we successfully regenerated a transgenic line carrying a double promoter transgene construct, where the marker gene encoding the green fluorescent protein (GFP) is driven by the gamma -crystallin gene promoter and a gene of interest, encoding a fusion protein of GFP with the matrix metalloproteinase stromelysin-3 (ST3-GFP), is driven by a heat shock-inducible promoter. We demonstrated the functional transmission of the ST3-GFP transgene by analyzing the phenotype of the F1 animals after heat-shock to induce its expression. Our method thus provides an inexpensive means to preserve transgenic frog lines and a convenient way for distribution of transgenic lines. Furthermore, the ease with which to microinject nuclei compared to the technically demanding transgenesis procedure with variable outcome should facilitate more laboratories to use transgenic Xenopus laevis for functional studies in vivo. JF - Molecular Reproduction and Development AU - Buchholz AU - Fu, Liezhen AU - Shi, Yun-Bo AD - Building 18 T, Rm 106, LGRD, NICHD, NIH, Bethesda, MD 20892, USA, shi@helix.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 65 EP - 69 VL - 67 IS - 1 SN - 1040-452X, 1040-452X KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts; ASFA Aquaculture Abstracts; ASFA 1: Biological Sciences & Living Resources KW - Biological development KW - Amphibiotic species KW - Transgenes KW - Anura KW - Green fluorescent protein KW - Matrix metalloproteinase KW - Sperm KW - Spawning KW - Cryopreservation KW - Phenotypes KW - Freezing storage KW - Xenopus laevis KW - Promoters KW - Labour KW - Fertilization KW - Heat KW - Fusion protein KW - Nuclei KW - Aquaculture techniques KW - Q3 08584:Culture of other aquatic animals KW - Q1 08584:Culture of other aquatic animals KW - G 07730:Development & Cell Cycle KW - W 30945:Fermentation & Cell Culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19826709?accountid=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=Molecular+Reproduction+and+Development&rft.atitle=Cryopreservation+of+Xenopus+Transgenic+Lines&rft.au=Buchholz%3BFu%2C+Liezhen%3BShi%2C+Yun-Bo&rft.aulast=Buchholz&rft.aufirst=&rft.date=2004-01-01&rft.volume=67&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Molecular+Reproduction+and+Development&rft.issn=1040452X&rft_id=info:doi/10.1002%2Fmrd.20005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Labour; Promoters; Biological development; Amphibiotic species; Spawning; Phenotypes; Freezing storage; Aquaculture techniques; Fertilization; Heat; Transgenes; Green fluorescent protein; Matrix metalloproteinase; Fusion protein; Sperm; Nuclei; Cryopreservation; Xenopus laevis; Anura DO - http://dx.doi.org/10.1002/mrd.20005 ER - TY - JOUR T1 - VIP receptor antagonists inhibit mammary carcinogenesis in C3(1)SV40T antigen mice AN - 19817081; 5803654 AB - The effects of a vasoactive intestinal peptide (VIP) receptor antagonist on mammary carcinogenesis were investigated using the C3(1)SV40T antigen (ag) mice. ten mu g/day VIPhybrid (VIPhyb) administered daily subcutaneously increased significantly the survival of C3(1)SV40Tag mice. At 5.2 months, VIPhyb significantly reduced the mammary tumor burden in C3(1)SV40Tag mice relative to control animals. super(125)I-VIP bound with high affinity to mouse mammary tumor homogenate. Because (Lys, Arg, Leu super(27))VIP super(1-7)GRF super(8-27) (VPAC sub(1) selective) but not Ro25-1553 (VPAC sub(2) selective) inhibited specific super(125)I- VIP binding to mammary tumor membranes with high affinity, VPAC sub(1) receptors predominate. By RT-PCR, VPAC sub(1) receptor mRNA was detected in mammary tumors. By Western blot, a major 60 Kdalton band was detected in mammary tumor extracts using VPAC sub(1) receptor antisera. By immunocytochemistry, VPAC sub(1)-R immunostaining was detected in the cytosol and plasma membrane but not the nucleus of fixed mammary tumor tissue. Using laser capture microdissected tumor cells and surface enhanced laser desorption/ionization (SELDI) techniques on mammary tumor cells, the proteomic profile was altered in mice treated with VIPhyb. Because VPAC sub(1) receptor antagonists increase the survival and reduce the tumor burden in C3(1)SV40Tag mice, they may function as chemopreventive agents in mammary cancer. JF - Life Sciences AU - Moody, T W AU - Dudek, J AU - Zakowicz, H AU - Walters, J AU - Jensen, R T AU - Petricoin, E AU - Couldrey, C AU - Green, JE AD - Department of Health and Human Services, National Institutes of Health, NCI Office of the Director, Center for Cancer Research, NCI, Bldg. 31, Rm. 3A34, 31 Center Drive, Bethesda, MD 20892, USA, moodyt@mail.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 1345 EP - 1357 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 74 IS - 11 SN - 0024-3205, 0024-3205 KW - Toxicology Abstracts KW - VIP receptor antagonist KW - Mammary carcinogenesis KW - Transgenic mice KW - Chemoprevention KW - Proteomics KW - Immunocytochemistry KW - Western blotting KW - Desorption KW - Receptor mechanisms KW - Mammary gland KW - Survival KW - Tumors KW - Tumor cells KW - Antagonists KW - Cancer KW - mRNA KW - Antisera KW - Plasma membranes KW - Carcinogenesis KW - Cytosol KW - chemopreventive agents KW - Polymerase chain reaction KW - Lasers KW - proteomics KW - Nuclei KW - Ionization KW - Vasoactive intestinal peptide KW - X 24390:Radioactive Materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19817081?accountid=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=Life+Sciences&rft.atitle=VIP+receptor+antagonists+inhibit+mammary+carcinogenesis+in+C3%281%29SV40T+antigen+mice&rft.au=Moody%2C+T+W%3BDudek%2C+J%3BZakowicz%2C+H%3BWalters%2C+J%3BJensen%2C+R+T%3BPetricoin%2C+E%3BCouldrey%2C+C%3BGreen%2C+JE&rft.aulast=Moody&rft.aufirst=T&rft.date=2004-01-01&rft.volume=74&rft.issue=11&rft.spage=1345&rft.isbn=&rft.btitle=&rft.title=Life+Sciences&rft.issn=00243205&rft_id=info:doi/10.1016%2Fj.lfs.2003.07.043 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Western blotting; Immunocytochemistry; Desorption; Receptor mechanisms; Mammary gland; Survival; Tumors; Tumor cells; Cancer; Antagonists; mRNA; Antisera; Plasma membranes; Carcinogenesis; Cytosol; Polymerase chain reaction; chemopreventive agents; Lasers; proteomics; Nuclei; Vasoactive intestinal peptide; Ionization DO - http://dx.doi.org/10.1016/j.lfs.2003.07.043 ER - TY - JOUR T1 - Respiratory symptoms in relation to residential coal burning and environmental tobacco smoke among early adolescents in Wuhan, China: a cross- sectional study AN - 19789785; 7249840 AB - Cigarette smoking and coal burning are the primary sources of indoor air pollution in Chinese households. However, effects of these exposures on Chinese children's respiratory health are not well characterized. Methods Seventh grade students (N = 5051) from 22 randomly selected schools in the greater metropolitan area of Wuhan, China, completed an in-class self-administered questionnaire on their respiratory health and home environment. Results Coal burning for cooking and/or heating increased odds of wheezing with colds [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.07-2.29] and without colds (OR = 1.44, 95% CI: 1.05-1.97). For smoking in the home, the strongest associations were seen for cough (OR = 1.74, 95% CI: 1.17-2.60) and phlegm production (OR = 2.25, 95% CI: 1.36-3.72) without colds among children who lived with two or more smokers. Conclusions Chinese children living with smokers or in coal-burning homes are at increased risk for respiratory impairment. While economic development in China may decrease coal burning by providing cleaner fuels for household energy use, the increasing prevalence of cigarette smoking is a growing public health concern due to its effects on children. Adverse effects of tobacco smoke exposure were seen despite the low rates of maternal smoking (3.6%) in this population. JF - Environmental Health AU - Salo, Paeivi M AU - Xia, Jiang AU - Johnson, C Anderson AU - Li, Yan AU - Kissling, Grace E AU - Avol, Edward L AU - Liu, Chunhong AU - London, Stephanie J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, MD A3-05, PO Box 12233, Research Triangle Park, NC 27709, USA, salo1@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 3 SN - 1476-069X, 1476-069X KW - Pollution Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Article No. 14 KW - economic development KW - Fuels KW - Indoor air pollution KW - Economic development KW - Coal KW - Public health KW - households KW - schools KW - Cigarette smoking KW - Cooking KW - Tobacco KW - cooking KW - metropolitan areas KW - Adolescents KW - Energy consumption KW - burning KW - Children KW - China, People's Rep., Hubei Prov., Wuhan KW - Smoke KW - Passive smoking KW - Schools KW - Households KW - Burning KW - Side effects KW - Metropolitan areas KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19789785?accountid=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&rft.atitle=Respiratory+symptoms+in+relation+to+residential+coal+burning+and+environmental+tobacco+smoke+among+early+adolescents+in+Wuhan%2C+China%3A+a+cross-+sectional+study&rft.au=Salo%2C+Paeivi+M%3BXia%2C+Jiang%3BJohnson%2C+C+Anderson%3BLi%2C+Yan%3BKissling%2C+Grace+E%3BAvol%2C+Edward+L%3BLiu%2C+Chunhong%3BLondon%2C+Stephanie+J&rft.aulast=Salo&rft.aufirst=Paeivi&rft.date=2004-01-01&rft.volume=3&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+Health&rft.issn=1476069X&rft_id=info:doi/10.1186%2F1476-069X-3-14 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-03-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - economic development; Indoor air pollution; Fuels; Economic development; Coal; Energy consumption; Children; burning; Public health; Smoke; households; Schools; Passive smoking; schools; Households; Cooking; Cigarette smoking; Tobacco; cooking; Burning; metropolitan areas; Metropolitan areas; Side effects; Adolescents; China, People's Rep., Hubei Prov., Wuhan DO - http://dx.doi.org/10.1186/1476-069X-3-14 ER - TY - JOUR T1 - A new member of the bacterial ribonuclease inhibitor family from Saccharopolyspora erythraea AN - 19770998; 6683562 AB - We have identified Sti, the gene of a ribonuclease inhibitor from Saccharopolyspora erythraea, by using a T7 phage display system. A specific phage has been isolated from a genome library by a biopanning procedure, using RNase Sa3, a ribonuclease from Streptomyces aureofaciens, as bait. Sti, a protein of 121 amino acid residues, with molecular mass 13059 Da, is a homolog of barstar and other microbial ribonuclease inhibitors. To overexpress its gene in Escherichia coli, we optimized the secondary structure of its mRNA by introducing a series of silent mutations. Soluble protein was isolated and purified to homogeneity. Inhibition constants of complex of Sti and RNase Sa3 or barnase were determined at pH 7 as 5x10 super(-12) or 7x10 super(-7), respectively. JF - FEBS Letters AU - Cesareni, Gianni 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 - 2004/01// PY - 2004 DA - Jan 2004 SP - 164 EP - 168 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 557 IS - 1-3 SN - 0014-5793, 0014-5793 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Barstar KW - Barnase KW - Ribonuclease KW - Ribonuclease inhibitor KW - Phage display KW - mRNA secondary structure KW - Genomes KW - Amino acids KW - Secondary structure KW - Streptomyces aureofaciens KW - mRNA KW - Saccharopolyspora erythraea KW - Protein structure KW - ribonuclease A KW - Escherichia coli KW - pH effects KW - Mutation KW - N 14065:Pre-mRNA and mRNA, editing, transcription KW - A 01310:Products of Microorganisms KW - J 02430:Symbiosis, Antibiosis & Phages UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19770998?accountid=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+new+member+of+the+bacterial+ribonuclease+inhibitor+family+from+Saccharopolyspora+erythraea&rft.au=Cesareni%2C+Gianni&rft.aulast=Cesareni&rft.aufirst=Gianni&rft.date=2004-01-01&rft.volume=557&rft.issue=1-3&rft.spage=164&rft.isbn=&rft.btitle=&rft.title=FEBS+Letters&rft.issn=00145793&rft_id=info:doi/10.1016%2FS0014-5793%2803%2901468-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Protein structure; Genomes; Barstar; ribonuclease A; Amino acids; Secondary structure; Phage display; Ribonuclease; Mutation; pH effects; Barnase; mRNA; Saccharopolyspora erythraea; Escherichia coli; Streptomyces aureofaciens DO - http://dx.doi.org/10.1016/S0014-5793(03)01468-6 ER - TY - JOUR T1 - MPSS profiling of human embryonic stem cells AN - 19762657; 6214926 AB - Background: Pooled human embryonic stem cells (hESC) cell lines were profiled to obtain a comprehensive list of genes common to undifferentiated human embryonic stem cells. Results: Pooled hESC lines were profiled to obtain a comprehensive list of genes common to human ES cells. Massively parallel signature sequencing (MPSS) of approximately three million signature tags (signatures) identified close to eleven thousand unique transcripts, of which approximately 25% were uncharacterised or novel genes. Expression of previously identified ES cell markers was confirmed and multiple genes not known to be expressed by ES cells were identified by comparing with public SAGE databases, EST libraries and parallel analysis by microarray and RT-PCR. Chromosomal mapping of expressed genes failed to identify major hotspots and confirmed expression of genes that map to the X and Y chromosome. Comparison with published data sets confirmed the validity of the analysis and the depth and power of MPSS. Conclusions: Overall, our analysis provides a molecular signature of genes expressed by undifferentiated ES cells that can be used to monitor the state of ES cells isolated by different laboratories using independent methods and maintained under differing culture conditions JF - BMC Developmental Biology AU - Brandenberger, Ralph AU - Khrebtukova, Irina AU - Thies, R Scott AU - Miura, Takumi AU - Jingli, Cai AU - Puri, Raj AU - Vasicek, Tom AU - Lebkowski, Jane AU - Rao, Mahendra AD - National Institute on Aging; GRC; Laboratory of Neuroscience, 5600 Nathan Shock Drive; Room 4E02; Baltimore, MD 21224, USA, RBrandenberger@Geron.com Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Data processing KW - Hot spots KW - Cell culture KW - DNA microarrays KW - expressed sequence tags KW - Y chromosome KW - Databases KW - Stem cells KW - Depth perception KW - Embryo cells KW - Polymerase chain reaction KW - Gene mapping KW - G 07730:Development & Cell Cycle KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19762657?accountid=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=BMC+Developmental+Biology&rft.atitle=MPSS+profiling+of+human+embryonic+stem+cells&rft.au=Brandenberger%2C+Ralph%3BKhrebtukova%2C+Irina%3BThies%2C+R+Scott%3BMiura%2C+Takumi%3BJingli%2C+Cai%3BPuri%2C+Raj%3BVasicek%2C+Tom%3BLebkowski%2C+Jane%3BRao%2C+Mahendra&rft.aulast=Brandenberger&rft.aufirst=Ralph&rft.date=2004-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Developmental+Biology&rft.issn=1471-213X&rft_id=info:doi/10.1186%2F1471-213X-4-10 L2 - http://www.biomedcentral.com/1471213/4/10 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Y chromosome; Databases; Stem cells; Depth perception; Data processing; Embryo cells; Hot spots; Polymerase chain reaction; Cell culture; expressed sequence tags; DNA microarrays; Gene mapping DO - http://dx.doi.org/10.1186/1471-213X-4-10 ER - TY - JOUR T1 - Endangered species AN - 19699622; 6025510 AB - No abstract JF - American Journal of Medical Genetics Part A AU - Biesecker, Leslie AD - National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, leslieb@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 429 EP - 430 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 128A IS - 4 SN - 0148-7299, 0148-7299 KW - Genetics Abstracts; Sustainability Science Abstracts KW - Genetics KW - Endangered species KW - M3 1010:Issues in Sustainable Development KW - G 07700:Molecular Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19699622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Assamodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics+Part+A&rft.atitle=Endangered+species&rft.au=Biesecker%2C+Leslie&rft.aulast=Biesecker&rft.aufirst=Leslie&rft.date=2004-01-01&rft.volume=128A&rft.issue=4&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics+Part+A&rft.issn=01487299&rft_id=info:doi/10.1002%2Fajmg.a.30202 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-09-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Endangered species; Genetics DO - http://dx.doi.org/10.1002/ajmg.a.30202 ER - TY - JOUR T1 - Different Roles of Electrostatics in Heat and in Cold: Adaptation by Citrate Synthase AN - 19271482; 5846713 AB - Electrostatics plays a major role in heat adaptation by thermophilic proteins. Here we ask whether electrostatics similarly contributes to cold adaptation in psychrophilic proteins. We compare the sequences and structures of citrate synthases from the psychrophile Arthobacter Ds2-3R, from chicken, and from the hyperthermophile Pyrococcus furiosus. The three enzymes share similar packing, burial of nonpolar surface area, and main-chain hydrogen bonding. However, both psychrophilic and hyperthermophilic citrate synthases contain more charged residues, salt bridges, and salt-bridge networks than the mesophile. The electrostatic free-energy contributions toward protein stability by individual charged residues show greater variabilities in the psychrophilic citrate synthase than in the hyperthermophilic enzyme. The charged residues in the active-site regions of the psychrophile are more destabilizing than those in the active-site regions of the hyperthermophile. In the hyperthermophilic enzyme, salt bridges and their networks largely cluster in the active-site regions and at the dimer interface. In contrast, in the psychrophile, they are more dispersed throughout the structure. On average, salt bridges and their networks provide greater electrostatic stabilization to the thermophilic citrate synthase at 100 degree C than to the psychrophilic enzyme at 0 degree C. Electrostatics appears to play an important role in both heat and cold adaptation of citrate synthase. However, remarkably, the role may be different in the two types of enzyme: In the hyperthermophile, it may contribute to the integrity of both the protein dimer and the active site by possibly countering conformational disorder at high temperatures. On the other hand, in the psychrophile at low temperatures, electrostatics may contribute to enhance protein solvation and to ensure active-site flexibility. JF - ChemBioChem AU - Kumar, S AU - Nussinov, R AD - Basic Research Program, SAIC-Frederick, Inc. Laboratory of Experimental and Computational Biology, NCI-Frederick, Building 469, Room 151, Frederick, MD 21702, USA,, ruthn@ncifcrf.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 280 EP - 290 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 5 IS - 3 SN - 1439-4227, 1439-4227 KW - chickens KW - psychrophilic proteins KW - salt bridges KW - thermophilic proteins KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - citrate synthases KW - electrostatic interactions KW - protein structures KW - psychrophiles KW - thermophiles KW - Residues KW - Clusters KW - Interfaces KW - Stabilization KW - Flexibility KW - Heat tolerance KW - Enzymes KW - Electrostatic properties KW - Hydrogen KW - Stability KW - Pyrococcus furiosus KW - Dimers KW - Structure KW - Proteins KW - Citrate (si)-synthase KW - Active sites KW - Arthrobacter KW - Citric acid KW - Conformational analysis KW - A 01006:Enzymes & cofactors KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19271482?accountid=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=ChemBioChem&rft.atitle=Different+Roles+of+Electrostatics+in+Heat+and+in+Cold%3A+Adaptation+by+Citrate+Synthase&rft.au=Kumar%2C+S%3BNussinov%2C+R&rft.aulast=Kumar&rft.aufirst=S&rft.date=2004-01-01&rft.volume=5&rft.issue=3&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=ChemBioChem&rft.issn=14394227&rft_id=info:doi/10.1002%2Fcbic.200300627 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Residues; Clusters; Flexibility; Stabilization; Interfaces; Heat tolerance; Enzymes; Electrostatic properties; Hydrogen; Stability; Dimers; Structure; Proteins; Citrate (si)-synthase; Active sites; Conformational analysis; Citric acid; Arthrobacter; Pyrococcus furiosus DO - http://dx.doi.org/10.1002/cbic.200300627 ER - TY - JOUR T1 - A detergent- and cyanogen bromide-free method for integral membrane proteomics: Application to Halobacterium purple membranes and the human epidermal membrane proteome AN - 19268925; 5847273 AB - A simple and rapid method for characterizing hydrophobic integral membrane proteins and its utility for membrane proteomics using microcapillary liquid chromatography coupled on-line with tandem mass spectrometry ( mu LC-MS/MS) is described. The present technique does not rely on the use of detergents, strong organic acids or cyanogen bromide-mediated proteolysis. A buffered solution of 60% methanol was used to extract, solubilize, and tryptically digest proteins within a preparation of Halobacterium (H.) halobium purple membranes. Analysis of the digested purple membrane proteins by mu LC-MS/MS resulted in the identification of all the predicted tryptic peptides of bacteriorhodopsin, including those that are known to be post-translationally modified. In addition, 40 proteins from the purple membrane preparation were also identified, of which 80% are predicted to contain between 1 and 16 transmembrane domains. To evaluate the general applicability of the method, the same extraction, solubilization, and digestion conditions were applied to a plasma membrane fraction prepared from human epidermal sheets. A total of 117 proteins was identified in a single mu LC-MS/MS analysis, of which 55% are known to be integral or associated with the plasma membrane. Due to its simplicity, efficiency, and absence of MS interfering compounds, this technique can be used for the characterization of other integral membrane proteins and may be concomitantly applied for the analysis of membrane protein complexes or large-scale proteomic studies of different membrane samples. JF - Proteomics AU - Blonder, J AU - Conrads, T P AU - Yu, Li-Rong AU - Terunuma, Atsushi AU - Janini, G M AU - Issaq, HJ AU - Vogel, J C AU - Veenstra, T D AD - Biomedical Proteomics Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA, veenstra@ncifcrf.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 31 EP - 45 VL - 4 IS - 1 SN - 1615-9853, 1615-9853 KW - bacteriorhodopsin KW - cyanogen bromide KW - man KW - proteomics KW - Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology KW - Proteolysis KW - Epidermis KW - Bacteriorhodopsin KW - Membrane proteins KW - Purple membranes KW - Mass spectroscopy KW - Halobacterium halobium KW - W3 33340:Other proteins, peptides, amino acids KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19268925?accountid=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=Proteomics&rft.atitle=A+detergent-+and+cyanogen+bromide-free+method+for+integral+membrane+proteomics%3A+Application+to+Halobacterium+purple+membranes+and+the+human+epidermal+membrane+proteome&rft.au=Blonder%2C+J%3BConrads%2C+T+P%3BYu%2C+Li-Rong%3BTerunuma%2C+Atsushi%3BJanini%2C+G+M%3BIssaq%2C+HJ%3BVogel%2C+J+C%3BVeenstra%2C+T+D&rft.aulast=Blonder&rft.aufirst=J&rft.date=2004-01-01&rft.volume=4&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/10.1002%2Fpmic.200300543 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Proteolysis; Epidermis; Bacteriorhodopsin; Membrane proteins; Purple membranes; Mass spectroscopy; Halobacterium halobium DO - http://dx.doi.org/10.1002/pmic.200300543 ER - TY - JOUR T1 - Toxicogenomic Analysis of Aberrant Gene Expression in Liver Tumors and Nontumorous Livers of Adult Mice Exposed in utero to Inorganic Arsenic AN - 19248126; 5830873 AB - Arsenic is a known human carcinogen. We have reported that brief exposure of pregnant C3H mice to arsenite in their drinking water during gestation induced hepatocellular carcinoma (HCC) in male offspring after they became adults. Tumor formation is typically associated with multiple gene expression changes, and this study examined aberrant gene expression associated with transplacental arsenic hepatocarcinogenesis. Liver tumors and nontumorous liver samples were taken at necropsy from adult male mice exposed in utero to either 42.5 or 85 ppm arsenic as sodium arsenite or unaltered water from day 8 to 18 of gestation. Total RNA was extracted and subjected to microarray analysis. Among 600 genes, arsenic-induced HCC showed a higher rate of aberrant gene expression (>2-fold and p < 0.05, 14%) than spontaneous tumors (7.8%). Overexpression of alpha - fetoprotein, c-myc, cyclin D1, proliferation-associated protein PAG, and cytokeratin-18 were more dramatic in arsenic-induced HCC than spontaneous tumors. In nontumorous liver samples of arsenic-exposed animals, 60 genes (10%) were differentially expressed, including the increased expression of alpha - fetoprotein, c-myc, insulin-like growth factor binding protein-1, superoxide dismutase, glutathione S-transferases, and CYP2A4, and the depressed expression of CYP7B1. Real-time RT-PCR analysis largely confirmed these findings. This toxicogenomic analysis revealed several aberrant gene expression changes associated with transplacental arsenic carcinogenesis. It is indeed remarkable that expression changes occurred in adulthood even though arsenic exposure ended during gestation. Some of these aberrantly expressed genes could play a role in the development of arsenic-induced tumors, at least in the liver. JF - Toxicological Sciences AU - Liu, J AU - Xie, Y AU - Ward, J M AU - Diwan, BA AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, NCI at NIEHS, Research Triangle Park, NC 27709 Y1 - 2004 PY - 2004 DA - 2004 SP - 249 EP - 257 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 77 IS - 2 SN - 1096-6080, 1096-6080 KW - mice KW - DNA microarrays KW - Toxicology Abstracts KW - Gene expression KW - Arsenic KW - Prenatal experience KW - Liver KW - Tumors KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19248126?accountid=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=Toxicological+Sciences&rft.atitle=Toxicogenomic+Analysis+of+Aberrant+Gene+Expression+in+Liver+Tumors+and+Nontumorous+Livers+of+Adult+Mice+Exposed+in+utero+to+Inorganic+Arsenic&rft.au=Liu%2C+J%3BXie%2C+Y%3BWard%2C+J+M%3BDiwan%2C+BA%3BWaalkes%2C+M+P&rft.aulast=Liu&rft.aufirst=J&rft.date=2004-01-01&rft.volume=77&rft.issue=2&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&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 - Arsenic; Gene expression; Liver; Tumors; Prenatal experience ER - TY - JOUR T1 - Influence of body temperature on the BOLD effect in murine SCC tumors AN - 19247871; 5815671 AB - Changes in the blood oxygen level dependent (BOLD) enhancements in tumors (squamous cell carcinoma, (SCCVII)) implanted in mice maintained at core temperatures of 30 degree C or 37 degree C were measured using MRI and compared to tumor oxygen levels obtained using an oxygen-sensitive Eppendorf electrode. Tumors were implanted in a hindleg of the mice intramuscularly. Tumor-bearing mice were imaged by BOLD MRI, while first breathing air and then carbogen (95% O sub(2), 5% CO sub(2)) for 15-min intervals at a core temperature of 30 degree C. After an equilibration period, the identical regimen was conducted with the same animal maintained at 37 degree C. This procedure was repeated with additional mice starting at 37 degree C followed by imaging at 30 degree C. Likewise, oxygen electrode measurements of the tumor were determined at core temperatures of 30 degree C and 37 degree C. The Eppendorf measurements showed that tumors in animals maintained at 30 degree C were significantly more hypoxic than at 37 degree C. MRI studies demonstrated stronger BOLD enhancement at 30 degree C than at 37 degree C, suggesting significant changes in hypoxia and/or blood flow in tumors at these temperatures. The findings of the study stress the importance of maintaining normal core temperature when assessing tumor oxygen status using functional imaging modalities or oxygen-sensitive electrodes. JF - Magnetic Resonance in Medicine AU - Reijnders, K AU - English, S J AU - Krishna, M C AU - Cook, JA AU - Sowers, AL AU - Mitchell, J B AU - Zhang, Y AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, murali@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 389 EP - 393 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 2 SN - 0740-3194, 0740-3194 KW - mice KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Oxygen KW - Body temperature KW - Hypoxia KW - Magnetic resonance imaging KW - Squamous cells KW - Electrodes KW - Carcinoma KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19247871?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Influence+of+body+temperature+on+the+BOLD+effect+in+murine+SCC+tumors&rft.au=Reijnders%2C+K%3BEnglish%2C+S+J%3BKrishna%2C+M+C%3BCook%2C+JA%3BSowers%2C+AL%3BMitchell%2C+J+B%3BZhang%2C+Y&rft.aulast=Reijnders&rft.aufirst=K&rft.date=2004-01-01&rft.volume=51&rft.issue=2&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10695 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Body temperature; Electrodes; Squamous cells; Carcinoma; Hypoxia; Oxygen; Magnetic resonance imaging DO - http://dx.doi.org/10.1002/mrm.10695 ER - TY - JOUR T1 - Mice Deficient in LRG-47 Display Increased Susceptibility to Mycobacterial Infection Associated with the Induction of Lymphopenia AN - 19243740; 5805837 AB - Although IFN- gamma is essential for host control of mycobacterial infection, the mechanisms by which the cytokine restricts pathogen growth are only partially understood. LRG-47 is an IFN-inducible GTP-binding protein previously shown to be required for IFN- gamma -dependent host resistance to acute Listeria monocytogenes and Toxoplasma gondii infections. To examine the role of LRG-47 in control of mycobacterial infection, LRG-47 super(-/-) and wild-type mice were infected with Mycobacterium avium, and host responses were analyzed. LRG-47 protein was strongly induced in livers of infected wild-type animals in an IFN- gamma -dependent manner. LRG-47 super(-/-) mice were unable to control bacterial replication, but survived the acute phase, succumbing 11-16 wk postinfection. IFN- gamma -primed, bone marrow-derived macrophages from LRG-47 super(-/-) and wild-type animals produced equivalent levels of TNF and NO upon M. avium infection in vitro and developed similar intracellular bacterial loads. In addition, priming for IFN- gamma production was observed in T cells isolated from infected LRG-47 super(-/-) mice. Importantly, however, mycobacterial granulomas in LRG-47 super(-/-) mice showed a marked lymphocyte deficiency. Further examination of these animals revealed a profound systemic lymphopenia and anemia triggered by infection. As LRG47 super(-/-) T lymphocytes were found to both survive and confer resistance to M. avium in recipient recombinase-activating gene-2 super(-/-) mice, the defect in cellular response and bacterial control in LRG-47 super(-/-) mice may also depend on a factor(s) expressed in a nonlymphocyte compartment. These findings establish a role for LRG-47 in host control of mycobacteria and demonstrate that in the context of the IFN- gamma response to persistent infection, LRG-47 can have downstream regulatory effects on lymphocyte survival. JF - Journal of Immunology AU - Feng, C G AU - Collazo-Custodio, C M AU - Eckhaus, M AU - Hieny, S AU - Belkaid, Y AU - Elkins, K AU - Jankovic, D AU - Taylor, G A AU - Sher, A AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and Veterinary Resources Program, Office of Research Services, National Institutes of Health, Bethesda, MD 20892 Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 1163 EP - 1168 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 172 IS - 2 SN - 0022-1767, 0022-1767 KW - mice KW - GTP-binding proteins KW - LRG-47 protein KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts KW - Cell survival KW - Listeria monocytogenes KW - g-Interferon KW - Mycobacterium avium KW - Lymphopenia KW - Lymphocytes KW - ^g-Interferon KW - Toxoplasma gondii KW - K 03086:Immunology & vaccination KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19243740?accountid=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+Immunology&rft.atitle=Mice+Deficient+in+LRG-47+Display+Increased+Susceptibility+to+Mycobacterial+Infection+Associated+with+the+Induction+of+Lymphopenia&rft.au=Feng%2C+C+G%3BCollazo-Custodio%2C+C+M%3BEckhaus%2C+M%3BHieny%2C+S%3BBelkaid%2C+Y%3BElkins%2C+K%3BJankovic%2C+D%3BTaylor%2C+G+A%3BSher%2C+A&rft.aulast=Feng&rft.aufirst=C&rft.date=2004-01-01&rft.volume=172&rft.issue=2&rft.spage=1163&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Toxoplasma gondii; Listeria monocytogenes; Mycobacterium avium; g-Interferon; Lymphopenia; Cell survival; Lymphocytes; ^g-Interferon ER - TY - JOUR T1 - Artifact suppression in imaging of myocardial infarction using B sub(1)- weighted phased-array combined phase-sensitive inversion recovery AN - 19241718; 5815675 AB - Regions of the body with long T sub(1), such as cerebrospinal fluid (CSF), may create ghost artifacts on gadolinium-hyperenhanced images of myocardial infarction when inversion recovery (IR) sequences are used with a segmented acquisition. Oscillations in the transient approach to steady state for regions with long T sub(1) may cause ghosts, with the number of ghosts being equal to the number of segments. B sub(1)-weighted phased-array combining provides an inherent degree of ghost artifact suppression because the ghost artifact is weighted less than the desired signal intensity by the coil sensitivity profiles. Example images are shown that illustrate the suppression of CSF ghost artifacts by the use of B sub(1)-weighted phased-array combining of multiple receiver coils. JF - Magnetic Resonance in Medicine AU - Kellman, P AU - Dyke, C K AU - Aletras, AH AU - McVeigh, E R AU - Arai, A E AD - Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, DHHS, Bethesda, Maryland, kellman@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 408 EP - 412 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 2 SN - 0740-3194, 0740-3194 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Cerebrospinal fluid KW - Ghosts KW - Gadolinium KW - Magnetic resonance imaging KW - Image processing KW - Myocardial infarction KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19241718?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Artifact+suppression+in+imaging+of+myocardial+infarction+using+B+sub%281%29-+weighted+phased-array+combined+phase-sensitive+inversion+recovery&rft.au=Kellman%2C+P%3BDyke%2C+C+K%3BAletras%2C+AH%3BMcVeigh%2C+E+R%3BArai%2C+A+E&rft.aulast=Kellman&rft.aufirst=P&rft.date=2004-01-01&rft.volume=51&rft.issue=2&rft.spage=408&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10689 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Myocardial infarction; Cerebrospinal fluid; Image processing; Gadolinium; Ghosts DO - http://dx.doi.org/10.1002/mrm.10689 ER - TY - JOUR T1 - Developing a convenient large animal model for gene transfer to salivary glands in vivo AN - 19237326; 5805612 AB - Localized gene transfer to salivary glands has great potential for the treatment of salivary gland, systemic, and oral diseases. The minipig parotid gland, given its volume and morphological similarities to the human parotid gland, may be useful as a large animal model for pre-clinical gene transfer experiments. The purpose of this study was to perform an initial assessment of the efficacy and safety of adenoviral-vector-mediated gene transfer to parotid glands of miniature pigs. AdCMVluc, a recombinant type 5 adenoviral (rAd5) vector containing a luciferase reporter gene, was administered to miniature pig parotid glands by intraductal cannulation. Five regions of gland tissue were obtained to measure the distribution of luciferase activity. The effects of time, viral dose, infusate buffer volume, and gland anatomical region on transgene expression were determined. Detailed serum chemistry and hematological analyses were performed. In addition, AdCMVlacZ, a similar rAd5 vector encoding beta -galactosidase, was also delivered to determine the parotid gland cell types transduced. Luciferase assays indicated that gene transfer to miniature pig salivary glands could be readily accomplished using rAd5 vectors. Highest transgene expression was found in the center of glands, which was > posterior > inferior > anterior > superior tissue regions. Expression was maximal on day 2 and declined to background by day 14, and observed in both acinar and ductal cells. Several serum chemistry and hematology parameters were transiently changed following rAd5 administration. Transgene expression by, and inflammatory response to, rAd5 vectors in minipig parotid glands are similar to results seen earlier in rodent studies. This suggests that results of salivary gland gene transfer from rodent studies can be extended to a larger animal model, and supports the value of using minipigs for pre-clinical applications of gene transfer to these tissues. JF - Journal of Gene Medicine AU - Li, J AU - Zheng, C AU - Zhang, X AU - Liu, X AU - Zhang, C AU - Goldsmith, C M AU - Baum, B J AU - Wang, S AD - Salivary Gland Disease Center and the Molecular Laboratory for Gene Therapy, Faculty of Stomatology, Capital University of Medical Sciences, Beijing, P. R. China, bbaum@dir.nidcr.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 55 EP - 63 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 6 IS - 1 SN - 1099-498X, 1099-498X KW - pigs KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Animal models KW - Salivary gland KW - Inflammation KW - Expression vectors KW - Gene expression KW - b-Galactosidase KW - Reporter gene KW - Gene transfer KW - ^b-Galactosidase KW - W3 33056:Animal models of human disease KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19237326?accountid=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+Gene+Medicine&rft.atitle=Developing+a+convenient+large+animal+model+for+gene+transfer+to+salivary+glands+in+vivo&rft.au=Li%2C+J%3BZheng%2C+C%3BZhang%2C+X%3BLiu%2C+X%3BZhang%2C+C%3BGoldsmith%2C+C+M%3BBaum%2C+B+J%3BWang%2C+S&rft.aulast=Li&rft.aufirst=J&rft.date=2004-01-01&rft.volume=6&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Journal+of+Gene+Medicine&rft.issn=1099498X&rft_id=info:doi/10.1002%2Fjgm.476 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene transfer; Inflammation; Gene expression; Expression vectors; b-Galactosidase; Reporter gene; Salivary gland; Animal models; ^b-Galactosidase DO - http://dx.doi.org/10.1002/jgm.476 ER - TY - JOUR T1 - Lung Deposition and Clearance of Inhaled Vanadium Pentoxide in Chronically Exposed F344 Rats and B6C3F1 Mice AN - 19227222; 5811446 AB - Female F344 rats and B6C3F1 mice were exposed to vanadium pentoxide (V sub(2)O sub(5)) at concentrations of 0, 0.5, 1, or 2 mg/m super(3) (rats) and 0, 1, 2, or 4 mg/m super(3) (mice) for 6 h/day, 5 days/week (for up to 18 months), by whole-body inhalation. Lung weights and lung burdens of vanadium were determined for exposed animals after 1, 5, and 12 days and after 1, 2, 6, 12, and 18 months of V sub(2)O sub(5) exposure. Blood vanadium concentrations were determined at 1, 2, 6, 12, and 18 months for all animals including controls. A model that assumed a first-order deposition rate and a first-order elimination rate for vanadium was employed to fit the lung burden data. Comparisons between exposed groups indicated a progressive increase in lung weight with exposure concentration and time on exposure for both species. The vanadium lung burdens appeared to reach steady state in the lowest exposure groups (0.5 and 1 mg/m super(3) for rats and mice, respectively) but showed a decline in the higher exposure groups. This deposition pattern was similar between rats and mice but the maximum lung burdens were observed at different times (1 or 2 months in mice vs. 6 months in rats). The vanadium deposition rate decreased faster in mice, while the elimination half-lives of vanadium lung burdens were about six- to nine-fold shorter in mice than in rats at 1 and 2 mg/m super(3). Thus, the retention of vanadium in the lungs at 18 months was lower in mice (~2% retained) compared with rats (13-15% retained) at the common exposure concentrations of 1 and 2 mg/m super(3). The lung burden data were approximately proportional to the exposure concentration in both species, likely due to concomitant decreases in deposition and elimination to a similar extent with increasing exposure. The area under the lung burden versus time curves and the area under the blood concentration (control-normalized) versus time curves were also proportional to exposure concentration. The progression of pathological changes in the lung with exposure and time is thought to affect the pattern and/or extent of vanadium deposition in the lungs following repeated exposures to V sub(2)O sub(5). JF - Toxicological Sciences AU - Dill, JA AU - Lee, K M AU - Mellinger, KH AU - Bates, D J AU - Burka, L T AU - Roycroft, J H AD - Battelle, Toxicology Northwest, Richland, Washington 99352, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 6 EP - 18 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 77 IS - 1 SN - 1096-6080, 1096-6080 KW - rats KW - mice KW - clearance KW - deposition KW - vanadium pentoxide KW - Toxicology Abstracts KW - Inhalation KW - Heavy metals KW - Lung KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19227222?accountid=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=Toxicological+Sciences&rft.atitle=Lung+Deposition+and+Clearance+of+Inhaled+Vanadium+Pentoxide+in+Chronically+Exposed+F344+Rats+and+B6C3F1+Mice&rft.au=Dill%2C+JA%3BLee%2C+K+M%3BMellinger%2C+KH%3BBates%2C+D+J%3BBurka%2C+L+T%3BRoycroft%2C+J+H&rft.aulast=Dill&rft.aufirst=JA&rft.date=2004-01-01&rft.volume=77&rft.issue=1&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&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 - Inhalation; Lung; Heavy metals ER - TY - JOUR T1 - Efficient Intracellular Assembly of Papillomaviral Vectors AN - 19225333; 5794192 AB - Although the papillomavirus structural proteins, L1 and L2, can spontaneously coassemble to form virus-like particles, currently available methods for production of L1/L2 particles capable of transducing reporter plasmids into mammalian cells are technically demanding and relatively low-yield. In this report, we describe a simple 293 cell transfection method for efficient intracellular production of papillomaviral-based gene transfer vectors carrying reporter plasmids. Using bovine papillomavirus type 1 (BPV1) and human papillomavirus type 16 as model papillomaviruses, we have developed a system for producing papillomaviral vector stocks with titers of several billion transducing units per milliliter. Production of these vectors requires both L1 and L2, and transduction can be prevented by papillomavirus-neutralizing antibodies. The stocks can be purified by an iodixanol (OptiPrep) gradient centrifugation procedure that is substantially more effective than standard cesium chloride gradient purification. Although earlier data had suggested a potential role for the viral early protein E2, we found that E2 protein expression did not enhance the intracellular production of BPV1 vectors. It was also possible to encapsidate reporter plasmids devoid of BPV1 DNA sequences. BPV1 vector production efficiency was significantly influenced by the size of the target plasmid being packaged. Use of 6-kb target plasmids resulted in BPV1 vector yields that were higher than those with target plasmids closer to the native 7.9-kb size of papillomavirus genomes. The results suggest that the intracellular assembly of papillomavirus structural proteins around heterologous reporter plasmids is surprisingly promiscuous and may be driven primarily by a size discrimination mechanism. JF - Journal of Virology AU - Buck, C B AU - Pastrana, D V AU - Lowy AU - Schiller, J T AD - Laboratory of Cellular Oncology, National Cancer Institute, Building 37, Room 4106, Bethesda, MD 20892-4263, schillej@dc37a.nci.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 751 EP - 757 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 78 IS - 2 SN - 0022-538X, 0022-538X KW - double prime E2 protein KW - double prime L1 protein KW - double prime L2 protein KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - L1 protein KW - L2 protein KW - E2 protein KW - ^AL1 protein KW - ^AL2 protein KW - ^AE2 protein KW - Bovine papillomavirus 1 KW - Encapsidation KW - Structural proteins KW - Expression vectors KW - Human papillomavirus 16 KW - Cloning vectors KW - Assembly KW - Reporter gene KW - Transfection KW - Transduction KW - N 14682:Cloning vectors KW - W3 33181:Gene therapy vectors KW - V 22050:Viral genetics including virus reactivation KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19225333?accountid=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=Efficient+Intracellular+Assembly+of+Papillomaviral+Vectors&rft.au=Buck%2C+C+B%3BPastrana%2C+D+V%3BLowy%3BSchiller%2C+J+T&rft.aulast=Buck&rft.aufirst=C&rft.date=2004-01-01&rft.volume=78&rft.issue=2&rft.spage=751&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.78.2.751-757.2004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human papillomavirus 16; Bovine papillomavirus 1; Encapsidation; Transfection; Expression vectors; Transduction; Reporter gene; Structural proteins; Assembly; Cloning vectors DO - http://dx.doi.org/10.1128/JVI.78.2.751-757.2004 ER - TY - JOUR T1 - Risk of lung cancer and residential radon in China: Pooled results of two studies AN - 19224069; 5811529 AB - Studies of radon-exposed underground miners predict that residential radon is the second leading cause of lung cancer mortality; however, case-control studies of residential radon have not provided unambiguous evidence of an association. Owing to small expected risks from residential radon and uncertainties in dosimetry, large studies or pooling of multiple studies are needed to fully evaluate effects. We pooled data from 2 case-control studies of residential radon representing 2 large radon studies conducted in China. The studies included 1,050 lung cancer cases and 1,996 controls. In the pooled data, odds ratios (OR) increased significantly with greater radon concentration. Based on a linear model, the OR with 95% confidence intervals (CI) at 100 Becquerel/cubic-meter (Bq/m super(3)) was 1.33 (1.01,1.36). For subjects resident in the current home for 30 years or more, the OR at 100 Bq/m super(3) was 1.32 (1.07,1.91). Results across studies were consistent with homogeneity. Estimates of ORs were similar to extrapolations from miner data and consistent with published residential radon studies in North American and Europe, suggesting long-term radon exposure at concentrations found in many homes increases lung cancer risk. JF - International Journal of Cancer AU - Lubin, J H AU - Wang, Z Y AU - Boice, JD Jr AU - Xu, Z Y AU - Blot, W J AU - De Wang, L AU - Kleinerman, R A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA, lubinj@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 132 EP - 137 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 109 IS - 1 SN - 0020-7136, 0020-7136 KW - man KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - Risk assessment KW - Radiation KW - Lung cancer KW - Mortality KW - Cancer KW - Radon KW - Lung KW - Radioisotopes KW - Residential areas KW - China, People's Rep. KW - R2 23030:Natural hazards KW - H 8000:Radiation Safety/Electrical Safety KW - X 24210:Radiation & radioactive materials KW - P 8000:RADIATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19224069?accountid=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=International+Journal+of+Cancer&rft.atitle=Risk+of+lung+cancer+and+residential+radon+in+China%3A+Pooled+results+of+two+studies&rft.au=Lubin%2C+J+H%3BWang%2C+Z+Y%3BBoice%2C+JD+Jr%3BXu%2C+Z+Y%3BBlot%2C+W+J%3BDe+Wang%2C+L%3BKleinerman%2C+R+A&rft.aulast=Lubin&rft.aufirst=J&rft.date=2004-01-01&rft.volume=109&rft.issue=1&rft.spage=132&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.11683 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.; Radon; Lung cancer; Residential areas; Mortality; Radiation; Radioisotopes; Lung; Cancer; Risk assessment DO - http://dx.doi.org/10.1002/ijc.11683 ER - TY - JOUR T1 - Childhood leukemia and road traffic: A population-based case-control study AN - 19221929; 5795126 AB - To assess the effect of road traffic exhaust on the risk of childhood leukemia, we carried out a population-based case-control study in the Province of Varese, northern Italy, covered by a population-based cancer registry. All 120 incident cases from 1978-97 were included in the study. Four controls per case, matched by age and gender, were sampled from population files. As index of exposure to traffic exhaust we estimated the annual mean concentration of benzene outside the home using a Gaussian diffusion model. This model uses traffic density (vehicles/day) on nearby main roads, distance between roads and residence, and information on vehicle emissions and weather conditions to estimate benzene concentration. Compared to children whose homes was not exposed to road traffic emissions (<0.1 mu g/m super(3) of benzene as estimated by the model), the risk of childhood leukemia was significantly higher (relative risk [RR] = 3.91; 95% confidence interval [CI] = 1.36-11.27) for heavily exposed children (over 10 mu g/m super(3) estimated annual average). For the intermediate exposure group (0.1-10 mu g/m super(3)) the relative risk was 1.51 (95% CI = 0.91- 2.51). These data, considered with other available evidence, suggest that motor traffic emissions can be involved in the etiology of childhood leukemia. JF - International Journal of Cancer AU - Crosignani, P AU - Tittarelli, A AU - Borgini, A AU - Codazzi, T AU - Rovelli, A AU - Porro, E AU - Contiero, P AU - Bianchi, N AU - Tagliabue, G AU - Fissi, R AU - Rossitto, F AU - Berrino, F AD - Lombardy Cancer Registry, National Cancer Institute, Milano, Italy, occam@istitutotumori.mi.it Y1 - 2004 PY - 2004 DA - 2004 SP - 596 EP - 599 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 108 IS - 4 SN - 0020-7136, 0020-7136 KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Environmental health KW - Pollution effects KW - Italy KW - Leukemia KW - Children KW - benzene KW - Air pollution KW - Automotive exhaust emissions KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19221929?accountid=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=International+Journal+of+Cancer&rft.atitle=Childhood+leukemia+and+road+traffic%3A+A+population-based+case-control+study&rft.au=Crosignani%2C+P%3BTittarelli%2C+A%3BBorgini%2C+A%3BCodazzi%2C+T%3BRovelli%2C+A%3BPorro%2C+E%3BContiero%2C+P%3BBianchi%2C+N%3BTagliabue%2C+G%3BFissi%2C+R%3BRossitto%2C+F%3BBerrino%2C+F&rft.aulast=Crosignani&rft.aufirst=P&rft.date=2004-01-01&rft.volume=108&rft.issue=4&rft.spage=596&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.11597 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Italy; Leukemia; Children; Automotive exhaust emissions; benzene; Air pollution; Pollution effects; Environmental health DO - http://dx.doi.org/10.1002/ijc.11597 ER - TY - JOUR T1 - Comprehensive approach for correction of motion and distortion in diffusion- weighted MRI AN - 19221490; 5795499 AB - Patient motion and image distortion induced by eddy currents cause artifacts in maps of diffusion parameters computed from diffusion-weighted (DW) images. A novel and comprehensive approach to correct for spatial misalignment of DW imaging (DWI) volumes acquired with different strengths and orientations of the diffusion sensitizing gradients is presented. This approach uses a mutual information-based registration technique and a spatial transformation model containing parameters that correct for eddy current-induced image distortion and rigid body motion in three dimensions. All parameters are optimized simultaneously for an accurate and fast solution to the registration problem. The images can also be registered to a normalized template with a single interpolation step without additional computational cost. Following registration, the signal amplitude of each DWI volume is corrected to account for size variations of the object produced by the distortion correction, and the b-matrices are properly recalculated to account for any rotation applied during registration. Both qualitative and quantitative results show that this approach produces a significant improvement of diffusion tensor imaging (DTI) data acquired in the human brain. JF - Magnetic Resonance in Medicine AU - Rohde, G K AU - Barnett, A S AU - Basser, P J AU - Marenco, S AU - Pierpaoli, C AD - NICHD, National Institutes of Health, Bethesda, Maryland, rohdeg@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 103 EP - 114 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 1 SN - 0740-3194, 0740-3194 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Magnetic resonance imaging KW - Brain KW - Image processing KW - Diffusion KW - Data acquisition KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19221490?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Comprehensive+approach+for+correction+of+motion+and+distortion+in+diffusion-+weighted+MRI&rft.au=Rohde%2C+G+K%3BBarnett%2C+A+S%3BBasser%2C+P+J%3BMarenco%2C+S%3BPierpaoli%2C+C&rft.aulast=Rohde&rft.aufirst=G&rft.date=2004-01-01&rft.volume=51&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10677 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Brain; Magnetic resonance imaging; Image processing; Diffusion; Data acquisition DO - http://dx.doi.org/10.1002/mrm.10677 ER - TY - JOUR T1 - Physical activity and renal cell cancer risk in a cohort of male smokers AN - 19221414; 5795127 AB - Few studies have examined exercise in relation to risk of renal cell cancer. We examined the association between leisure-time and occupational physical activity and renal cell cancer in a cohort of 29,133 male smokers 50-69 years of age in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study. Physical activity was assessed at baseline using a self-administered questionnaire that inquired about usual level of physical activity during leisure-time and at work during the past year. Cox proportional hazards modeling was used to adjust simultaneously for known or suspected risk factors for renal cell cancer. During 12 years (354,407 person-years) of follow-up, 210 incident cases of renal cell cancer were identified. In age-adjusted analysis, the RRs of renal cell cancer in increasing categories of leisure-time physical activity (light, moderate and heavy) were 1.0, 0.89 (95% CI = 0.67-1.17) and 0.38 (95% CI = 0.15-0.94), respectively (p-value for trend = 0.06). After adjustment for body mass index, energy intake, smoking, hypertension, education and fruit and vegetable intake, the multivariate RRs of renal cell cancer in increasing categories of leisure-time physical activity (light, moderate and heavy), were 1.0, 0.89 (95% CI = 0.66-1.19), and 0.46 (95% CI = 0.18-1.13) (p-value for trend = 0.12). Occupational physical activity was unrelated to renal cell cancer risk. These data suggest that recreational physical activity may play a role in the prevention of renal cell cancer in men. JF - International Journal of Cancer AU - Mahabir, S AU - Leitzmann, M F AU - Pietinen, P AU - Albanes, D AU - Virtamo, J AU - Taylor, PR AD - Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA, mahabirs@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 600 EP - 605 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 108 IS - 4 SN - 0020-7136, 0020-7136 KW - man KW - Physical Education Index; Toxicology Abstracts; Risk Abstracts KW - Boys KW - Physical activity KW - Evaluation KW - Smoking KW - Risk factors KW - Cigarette smoking KW - Tobacco KW - physical activity KW - Preventive health KW - Surveys KW - Exercise KW - Cancer KW - Leisure KW - Analysis KW - Kidney KW - PE 090:Sports Medicine & Exercise Sport Science KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19221414?accountid=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=International+Journal+of+Cancer&rft.atitle=Physical+activity+and+renal+cell+cancer+risk+in+a+cohort+of+male+smokers&rft.au=Mahabir%2C+S%3BLeitzmann%2C+M+F%3BPietinen%2C+P%3BAlbanes%2C+D%3BVirtamo%2C+J%3BTaylor%2C+PR&rft.aulast=Mahabir&rft.aufirst=S&rft.date=2004-01-01&rft.volume=108&rft.issue=4&rft.spage=600&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.11580 LA - English DB - Physical Education Index; ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Exercise; Cancer; Risk factors; Boys; Smoking; Leisure; Preventive health; Evaluation; Surveys; Analysis; Tobacco; Kidney; Cigarette smoking; physical activity; Physical activity DO - http://dx.doi.org/10.1002/ijc.11580 ER - TY - JOUR T1 - Extended coverage first-pass perfusion imaging using slice-interleaved TSENSE AN - 19221052; 5795511 AB - Parallel imaging applied to first-pass, contrast-enhanced cardiac MR can yield greater spatial coverage for a fixed temporal resolution. The method combines rate R = 2 acceleration using TSENSE with shot-to-shot interleaving of two slices. The [radic]R SNR loss is largely compensated for by a longer effective repetition time (TR) and increased flip angle associated with slice interleaving. In this manner, increased spatial coverage is achieved while comparable or better image quality is maintained. Single-heartbeat temporal resolution was accomplished with spatial coverage of eight slices at heart rates up to 71 bpm, six slices up to 95 bpm, and four slices up to 143 bpm. Experiments in normal subjects (N = 6) were performed to assess signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values. JF - Magnetic Resonance in Medicine AU - Kellman, P AU - Derbyshire, JA AU - Agyeman, KO AU - McVeigh, E R AU - Arai, A E AD - Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, DHHS, Bethesda, Maryland, kellman@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 200 EP - 204 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Heart KW - Perfusion KW - Magnetic resonance imaging KW - Noise KW - Image processing KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19221052?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Extended+coverage+first-pass+perfusion+imaging+using+slice-interleaved+TSENSE&rft.au=Kellman%2C+P%3BDerbyshire%2C+JA%3BAgyeman%2C+KO%3BMcVeigh%2C+E+R%3BArai%2C+A+E&rft.aulast=Kellman&rft.aufirst=P&rft.date=2004-01-01&rft.volume=51&rft.issue=1&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10663 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Image processing; Perfusion; Heart; Noise DO - http://dx.doi.org/10.1002/mrm.10663 ER - TY - JOUR T1 - Signal-to-noise ratio and parallel imaging performance of a 16-channel receive-only brain coil array at 3.0 Tesla AN - 19220963; 5795490 AB - The performance of a 16-channel receive-only RF coil for brain imaging at 3.0 Tesla was investigated using a custom-built 16-channel receiver. Both the image signal-to-noise ratio (SNR) and the noise amplification (g-factor) in sensitivity-encoding (SENSE) parallel imaging applications were quantitatively evaluated. Furthermore, the performance was compared with that of hypothetical coils with one, two, four, and eight elements (n) by combining channels in software during image reconstruction. As expected, both the g-factor and SNR improved substantially with n. Compared to an equivalent (simulated) single- element coil, the 16-channel coil showed a 1.87-fold average increase in brain SNR. This was mainly due to an increase in SNR in the peripheral brain (an up to threefold SNR increase), whereas the SNR increase in the center of the brain was 4%. The incremental SNR gains became relatively small at large n, with a 9% gain observed when n was increased from 8 to 16. Compared to the (larger) product birdcage head coil, SNR increased by close to a factor of 2 in the center, and by up to a factor of 6 in the periphery of the brain. For low SENSE acceleration (rate-2), g-factors leveled off for n > 4, and improved only slightly (1.4% averaged over brain) going from n = 8 to n = 16. Improvements in g for n > 8 were larger for higher acceleration rates, with the improvement for rate-3 averaging 12.0%. JF - Magnetic Resonance in Medicine AU - De Zwart, JA AU - Ledden, P J AU - Van Gelderen, P AU - Bodurka, J AU - Chu, R AU - Duyn, J H AD - Advanced MRI Section, Laboratory of Functional and Molecular Imaging, NINDS, National Institutes of Health, Bethesda, Maryland, Jacco.deZwart@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 22 EP - 26 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Magnetic resonance imaging KW - Noise KW - Brain KW - Image processing KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19220963?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Signal-to-noise+ratio+and+parallel+imaging+performance+of+a+16-channel+receive-only+brain+coil+array+at+3.0+Tesla&rft.au=De+Zwart%2C+JA%3BLedden%2C+P+J%3BVan+Gelderen%2C+P%3BBodurka%2C+J%3BChu%2C+R%3BDuyn%2C+J+H&rft.aulast=De+Zwart&rft.aufirst=JA&rft.date=2004-01-01&rft.volume=51&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10678 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Brain; Noise; Image processing DO - http://dx.doi.org/10.1002/mrm.10678 ER - TY - JOUR T1 - Urinary mutagenesis and fried red meat intake: Influence of cooking temperature, phenotype, and genotype of metabolizing enzymes in a controlled feeding study AN - 19220613; 5811555 AB - Meat cooked at high temperatures contains potential carcinogenic compounds, such as heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Samples from a 2-week controlled feeding study were used to examine the relationship between the intake of mutagenicity from meat fried at different temperatures and the levels of mutagenicity subsequently detected in urine, as well as the influence of the genotype of drug metabolizing enzymes on urinary mutagenicity. Sixty subjects consumed ground beef patties fried at low temperature (100 degree C) for 1 week, followed by ground beef patties fried at high temperature (250 degree C) the second week. Mutagenicity in the meat was assayed in Salmonella typhimurium TA98 (+S9), and urinary mutagenicity was determined using Salmonella YG1024 (+S9). Genotypes for NAT1, NAT2, GSTM1, and UGT1A1 were analyzed using blood samples from the subjects. Meat fried at 100 degree C was not mutagenic, whereas meat fried at 250 degree C was mutagenic (1023 rev/g). Unhydrolyzed and hydrolyzed urine samples were 22X and 131X more mutagenic, respectively, when subjects consumed red meat fried at 250 degree C compared with red meat fried at 100 degree C. We found that hydrolyzed urine was ~8X more mutagenic than unhydrolyzed urine, likely due to the deconjugation of mutagens from glucuronide. The intake of meat cooked at high temperature correlated with the mutagenicity of unhydrolyzed urine (r = 0.32, P = 0.01) and hydrolyzed urine (r = 0.34, P = 0.008). Mutagenicity in unhydrolyzed urine was not influenced by NAT1, NAT2, or GSTM1 genotypes. However, a UGT1A1*28 polymorphism that reduced UGT1A1 expression and conjugation modified the effect of intake of meat cooked at high temperature on mutagenicity of unhydrolyzed urine (P for interaction = 0.04). These mutagenicity data were also compared with previously determined levels of HCAs (measured as MeIQx, DiMeIQx, and PhIP) and polycyclic aromatic hydrocarbons (PAHs) in the meat, levels of HCAs in the urine, and CYP1A2 and NAT2 phenotypes. The levels of mutagenicity in the meat fried at low and high temperatures correlated with levels of HCAs, but not levels of PAHs, in the meat. Also, levels of mutagenicity in unhydrolyzed urine correlated with levels of MeIQx in unhydrolyzed urine (r = 0.36; P = 0.01), and the levels of mutagenicity of hydrolyzed urine correlated with levels of MeIQx (r = 0.34; P = 0.01) and PhIP (r = 0.43; P = 0.001) of hydrolyzed urine. Mutagenicity in unhydrolyzed urine was not influenced by either the CYP1A2 or NAT2 phenotype. The data from this study indicate that urinary mutagenicity correlates with mutagenic exposure from cooked meat and can potentially be used as a marker in etiological studies on cancer. JF - Environmental and Molecular Mutagenesis AU - Peters, U AU - Sinha, R AU - Bell, DA AU - Rothman, N AU - Grant, D J AU - Watson, MA AU - Kulldorff, M AU - Brooks, L R AU - Warren, SH AU - DeMarini, D M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, petersu@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 53 EP - 74 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 43 IS - 1 SN - 0893-6692, 0893-6692 KW - man KW - Genetics Abstracts; Toxicology Abstracts KW - Temperature effects KW - Mutagens KW - Mutagenicity KW - Food KW - Ames test KW - Meat KW - Urine KW - Cooking KW - Heat treatments KW - X 24120:Food, additives & contaminants KW - G 07220:General theory/testing systems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19220613?accountid=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+and+Molecular+Mutagenesis&rft.atitle=Urinary+mutagenesis+and+fried+red+meat+intake%3A+Influence+of+cooking+temperature%2C+phenotype%2C+and+genotype+of+metabolizing+enzymes+in+a+controlled+feeding+study&rft.au=Peters%2C+U%3BSinha%2C+R%3BBell%2C+DA%3BRothman%2C+N%3BGrant%2C+D+J%3BWatson%2C+MA%3BKulldorff%2C+M%3BBrooks%2C+L+R%3BWarren%2C+SH%3BDeMarini%2C+D+M&rft.aulast=Peters&rft.aufirst=U&rft.date=2004-01-01&rft.volume=43&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/10.1002%2Fem.10205 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Food; Mutagens; Heat treatments; Cooking; Temperature effects; Mutagenicity; Urine; Meat; Ames test DO - http://dx.doi.org/10.1002/em.10205 ER - TY - JOUR T1 - Self-gated cardiac cine MRI AN - 19204249; 5795498 AB - The need for ECG gating presents many difficulties in cardiac magnetic resonance imaging (CMRI). Real-time imaging techniques eliminate the need for ECG gating in cine CMRI, but they cannot offer the spatial and temporal resolution provided by segmented acquisition techniques. Previous MR signal- based techniques have demonstrated an ability to provide cardiac gating information; however, these techniques result in decreased imaging efficiency. The purpose of this work was to develop a new "self-gated" (SG) acquisition technique that eliminates these efficiency deficits by extracting the motion synchronization signal directly from the same MR signals used for image reconstruction. Three separate strategies are proposed for deriving the SG signal from data acquired using radial k-space sampling: echo peak magnitude, kymogram, and 2D correlation. The SG techniques were performed on seven normal volunteers. A comparison of the results showed that they provided cine image series with no significant differences in image quality compared to that obtained with conventional ECG gating techniques. SG techniques represent an important practical advance in clinical MRI because they enable the acquisition of high temporal and spatial resolution cardiac cine images without the need for ECG gating and with no loss in imaging efficiency. JF - Magnetic Resonance in Medicine AU - Larson, A C AU - White, R D AU - Laub, G AU - McVeigh, E R AU - Li, D AU - Simonetti, O P AD - Laboratory of Cardiac Energetics, NHLBI, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, larsona@nhlbi.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 93 EP - 102 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 1 SN - 0740-3194, 0740-3194 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Heart KW - Magnetic resonance imaging KW - Image processing KW - Signals KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19204249?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Self-gated+cardiac+cine+MRI&rft.au=Larson%2C+A+C%3BWhite%2C+R+D%3BLaub%2C+G%3BMcVeigh%2C+E+R%3BLi%2C+D%3BSimonetti%2C+O+P&rft.aulast=Larson&rft.aufirst=A&rft.date=2004-01-01&rft.volume=51&rft.issue=1&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10664 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Heart; Signals; Image processing DO - http://dx.doi.org/10.1002/mrm.10664 ER - TY - JOUR T1 - EPI-BOLD fMRI of human motor cortex at 1.5 T and 3.0 T: Sensitivity dependence on echo time and acquisition bandwidth AN - 19200640; 5795132 AB - To investigate the sensitivity dependence of BOLD functional imaging on MRI acquisition parameters in motor stimulation experiments using a finger tapping paradigm. Gradient-echo echo-planar fMRI experiments were performed at 1.5 T and 3.0 T with varying acquisition echo time and bandwidth, and with a 4 mm isotropic voxel size. To analyze the BOLD sensitivity, the relative contributions of BOLD signal amplitude and thermal and physiologic noise sources were evaluated, and statistical t-scores were compared in the motor area. At 1.5 T, the number of activated pixels and the average t-score showed a relatively broad optimum over a te range of 60-160 msec. At 3.0 T, an optimum range was observed between TEs of 30-130 msec. Averaged over nine subjects, maxima in the number of pixels and t-score values were 59% and 18% higher at 3.0 T than at 1.5 T, respectively, an improvement that was lower than the observed 100% to 110% increase in signal-to-noise ratio at 3.0 T. The somewhat disappointing increase in t-scores at 3.0 T was attributed to the increased contribution of physiologic noise at the higher field strength under the given experimental conditions. At both field strengths, reducing the effective image acquisition bandwidth from 35 to 17 Hz per pixel did not affect or only marginally affect the BOLD sensitivity. JF - Journal of Magnetic Resonance Imaging AU - Fera, F AU - Yongbi, M N AU - Van Gelderen, P AU - Frank, JA AU - Mattay, V S AU - Duyn, J H AD - Clinical Brain Disorder Branch, National Institutes of Mental Health, NIH, Bethesda, Maryland, jhd@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 19 EP - 26 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 19 IS - 1 SN - 1053-1807, 1053-1807 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Cortex (motor) KW - Magnetic resonance imaging KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19200640?accountid=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+Magnetic+Resonance+Imaging&rft.atitle=EPI-BOLD+fMRI+of+human+motor+cortex+at+1.5+T+and+3.0+T%3A+Sensitivity+dependence+on+echo+time+and+acquisition+bandwidth&rft.au=Fera%2C+F%3BYongbi%2C+M+N%3BVan+Gelderen%2C+P%3BFrank%2C+JA%3BMattay%2C+V+S%3BDuyn%2C+J+H&rft.aulast=Fera&rft.aufirst=F&rft.date=2004-01-01&rft.volume=19&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.10440 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Cortex (motor) DO - http://dx.doi.org/10.1002/jmri.10440 ER - TY - JOUR T1 - Scalable multichannel MRI data acquisition system AN - 19200245; 5795506 AB - A scalable multichannel digital MRI receiver system was designed to achieve high bandwidth echo-planar imaging (EPI) acquisitions for applications such as BOLD-fMRI. The modular system design allows for easy extension to an arbitrary number of channels. A 16-channel receiver was developed and integrated with a General Electric (GE) Signa 3T VH/3 clinical scanner. Receiver performance was evaluated on phantoms and human volunteers using a custom-built 16-element receive-only brain surface coil array. At an output bandwidth of 1 MHz, a 100% acquisition duty cycle was achieved. Overall system noise figure and dynamic range were better than 0.85 dB and 84 dB, respectively. During repetitive EPI scanning on phantoms, the relative temporal standard deviation of the image intensity time-course was below 0.2%. As compared to the product birdcage head coil, 16-channel reception with the custom array yielded a nearly 6-fold SNR gain in the cerebral cortex and a 1.8-fold SNR gain in the center of the brain. The excellent system stability combined with the increased sensitivity and SENSE capabilities of 16-channel coils are expected to significantly benefit and enhance fMRI applications. JF - Magnetic Resonance in Medicine AU - Bodurka, J AU - Ledden, P J AU - Van Gelderen, P AU - Chu, R AU - De Zwart, JA AU - Morris, D AU - Duyn, J H AD - Functional MRI Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, jhd@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 165 EP - 171 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 1 SN - 0740-3194, 0740-3194 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Standard deviation KW - Magnetic resonance imaging KW - Statistical analysis KW - Brain KW - Image processing KW - Data acquisition KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19200245?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Scalable+multichannel+MRI+data+acquisition+system&rft.au=Bodurka%2C+J%3BLedden%2C+P+J%3BVan+Gelderen%2C+P%3BChu%2C+R%3BDe+Zwart%2C+JA%3BMorris%2C+D%3BDuyn%2C+J+H&rft.aulast=Bodurka&rft.aufirst=J&rft.date=2004-01-01&rft.volume=51&rft.issue=1&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10693 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Data acquisition; Brain; Image processing; Standard deviation; Statistical analysis DO - http://dx.doi.org/10.1002/mrm.10693 ER - TY - JOUR T1 - The use of degraded and shade cocoa forests by Endangered golden-headed lion tamarins Leontopithecus chrysomelas AN - 18046607; 5997262 AB - Determining habitat requirements for threatened primates is critical to implementing conservation strategies, and plans incorporating metapopulation structure require understanding the potential of available habitats to serve as corridors. We examined how three groups of golden-headed lion tamarins Leontopithecus chrysomelas in Southern Bahia, Brazil, used mature, swamp, secondary and shade cocoa (cabruca) forests. Unlike callitrichids that show affinities for degraded forest, Leontopithecus species are presumed to depend on primary or mature forests for sleeping sites in tree holes and epiphytic bromeliads for animal prey. In this study we quantified resource availability within each habitat, compared the proportion of time spent in each habitat to that based on availability, investigated preferences for sleeping site selection, and determined how golden-headed lion tamarins allocated time to foraging behaviour in different habitats. Each group preferred to range in certain habitats during the day, yet patterns were not consistent across groups. In contrast, all groups preferred to sleep in mature or cabruca forest. Golden-headed lion tamarins spent a greater proportion of time foraging and eating fruits, flowers and nectar in cabruca than in mature or secondary forests. Although the extent to which secondary and cabruca forests can completely sustain breeding groups is unresolved, we conclude that both habitats would make suitable corridors for the movement of tamarins between forest fragments, and that the large trees remaining in cabruca are important sources of food and sleeping sites. We suggest that management plans for golden-headed lion tamarins should focus on protecting areas that include access to tall forest, either as mature or cabruca, for the long-term conservation of the species. JF - Oryx AU - Raboy, B E AU - Christman, M C AU - Dietz, J M AD - Department of Conservation Biology, Conservation and Research Center, National Zoological Park, Smithsonian Institution, Washington, DC 20008, USA, raboyb@mail.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 75 EP - 83 VL - 38 IS - 1 SN - 0030-6053, 0030-6053 KW - Sustainability Science Abstracts; Ecology Abstracts KW - Cocoa KW - Leontopithecus chrysomelas KW - Resource availability KW - Wildlife conservation KW - Habitat changes KW - Management plans KW - Habitat preferences KW - Forests KW - Primates KW - Habitat fragmentation KW - Site selection KW - Brazil KW - Endangered species KW - Conservation KW - Metapopulations KW - M3 1140:Biodiversity KW - D 04705:Conservation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18046607?accountid=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=Oryx&rft.atitle=The+use+of+degraded+and+shade+cocoa+forests+by+Endangered+golden-headed+lion+tamarins+Leontopithecus+chrysomelas&rft.au=Raboy%2C+B+E%3BChristman%2C+M+C%3BDietz%2C+J+M&rft.aulast=Raboy&rft.aufirst=B&rft.date=2004-01-01&rft.volume=38&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Oryx&rft.issn=00306053&rft_id=info:doi/10.1017%2FS0030605304000122 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Leontopithecus chrysomelas; Brazil; Forests; Habitat fragmentation; Wildlife conservation; Cocoa; Habitat preferences; Primates; Management plans; Site selection; Resource availability; Metapopulations; Conservation; Endangered species; Habitat changes DO - http://dx.doi.org/10.1017/S0030605304000122 ER - TY - JOUR T1 - Occupation, pesticide exposure and risk of multiple myeloma AN - 18020491; 5980365 AB - This population-based case-control study examined the relationship between occupation, living or working on a farm, pesticide exposure, and the risk of multiple myeloma. The study included 573 persons newly diagnosed with myeloma and 2131 controls. Information was obtained on sociodemographic factors, occupational history, and history of living and working on a farm. Occupational and industrial titles were coded by standardized classification systems. A job-exposure matrix was developed for occupational pesticide exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. Farmers and farm workers had odds ratios of 1.9 (95% CI 0.8-4.6) and 1.4 (95% CI 0.8-2.3), respectively. An odds ratio of 1.7 (95% CI 1.0-2.7) was observed for sheep farm residents or workers, whereas no increased risks were found for cattle, beef, pig, or chicken farm residents or workers. A modestly increased risk was observed for pesticides (OR 1.3, 95% CI 0.9-1.8). Significantly increased risks were found for pharmacists, dieticians and therapists (OR 6.1, 95% CI 1.7-22.5), service occupations (OR 1.3, 95% CI 1.02-1.7), roofers (OR 3.3, 95% CI 1.1-9.8), precision printing occupations (OR 10.1, 95% CI 1.03-99.8), heating equipment operators (OR 4.7, 95% CI 1.4-15.8), and hand molders and casters (OR 3.0, 95% CI 1.0-8.4). A modest increased risk of multiple myeloma is suggested for occupational pesticide exposure. The increased risk for sheep farm residents or workers indicates that certain animal viruses may be involved in myeloma risk. JF - Scandinavian Journal of Work, Environment & Health AU - Baris, D AU - Silverman, D T AU - Brown, L M AU - Swanson, G M AU - Hayes, R B AU - Schwartz, A G AU - Liff, J M AU - Schoenberg, J B AU - Pottern, L M AU - Greenberg, R S AU - Stewart, P A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Department of Health and Human Services, Executive Plaza South, Room 8122, Bethesda, MD 20892, USA, barisd@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 215 EP - 222 VL - 30 IS - 3 SN - 0355-3140, 0355-3140 KW - man KW - multiple myeloma KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Farms KW - Multiple myeloma KW - Epidemiology KW - Risk factors KW - Pesticides KW - Agrochemicals KW - Occupational exposure KW - R2 23080:Industrial and labor KW - H 5000:Pesticides KW - X 24132:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18020491?accountid=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=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Occupation%2C+pesticide+exposure+and+risk+of+multiple+myeloma&rft.au=Baris%2C+D%3BSilverman%2C+D+T%3BBrown%2C+L+M%3BSwanson%2C+G+M%3BHayes%2C+R+B%3BSchwartz%2C+A+G%3BLiff%2C+J+M%3BSchoenberg%2C+J+B%3BPottern%2C+L+M%3BGreenberg%2C+R+S%3BStewart%2C+P+A&rft.aulast=Baris&rft.aufirst=D&rft.date=2004-01-01&rft.volume=30&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Farms; Epidemiology; Multiple myeloma; Risk factors; Pesticides; Occupational exposure; Agrochemicals ER - TY - JOUR T1 - Radioimmunotherapy of Human Colon Carcinoma Xenografts Using a super(213)Bi-Labeled Domain-Deleted Humanized Monoclonal Antibody AN - 18017058; 5986936 AB - The data presented within this paper is the first report of a humanized domain-deleted monoclonal antibody (HuCC49 Delta CH2) to be utilized in a radioimmunotherapeutic (RIT) application with super(213)Bi. An initial study indicated that super(111)In-HuCC49 Delta CH2 targets the subcutaneously implanted human colon carcinoma xenograft, LS-174T, when injected via a peritoneal route. The HuCC49 Delta CH2 was then radiolabeled with super(213)Bi, an alpha -emitting radionuclide with a half-life of 45.6 minutes, and evaluated for therapeutic efficacy. Dose titration studies indicated that a single dose of 500-1000 mu Ci, when injected by an intraperitoneal route, resulted in the growth inhibition or regression of the tumor xenograft. The radioimmunotherapeutic effect was found to be dose-dependent. Specificity of the therapeutic efficacy was confirmed in a subsequent experiment with athymic mice bearing TAG-72 negative MIP (human colorectal) xenografts. A preliminary study was also performed to assess a multiple-dose administration of super(213)Bi-HuCC49 Delta CH2. Doses (500 mu Ci) were administered at 14-day intervals after tumor implantation. A reduction in volume and/or delay in tumor growth was evident following the second and third injections of super(213)Bi-HuCC49 Delta CH2. As further validation of the use of super(213)Bi-HuCC49 Delta CH2 for RIT, a study using super(131)I was conducted. The overall survival of mice receiving super(213)Bi-HuCC49 Delta CH2 was greater than those that received super(131)I-HuCC49 Delta CH2. JF - Cancer Biotherapy and Radiopharmaceuticals AU - Milenic, D AU - Garmestani, K AU - Dadachova, E AU - Chappell, L AU - Albert, P AU - Hill, D AU - Schlom, J AU - Brechbiel, M AD - National Institutes of Health; 10 Center Drive, MSC-1002, Room B3B69, Bethesda, MD 20892, USA, Martinwb@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 135 EP - 148 VL - 19 IS - 2 SN - 1084-9785, 1084-9785 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Monoclonal antibodies KW - Immunotherapy KW - Radiotherapy KW - Colorectal carcinoma KW - Xenografts KW - Carcinoma KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18017058?accountid=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+Biotherapy+and+Radiopharmaceuticals&rft.atitle=Radioimmunotherapy+of+Human+Colon+Carcinoma+Xenografts+Using+a+super%28213%29Bi-Labeled+Domain-Deleted+Humanized+Monoclonal+Antibody&rft.au=Milenic%2C+D%3BGarmestani%2C+K%3BDadachova%2C+E%3BChappell%2C+L%3BAlbert%2C+P%3BHill%2C+D%3BSchlom%2C+J%3BBrechbiel%2C+M&rft.aulast=Milenic&rft.aufirst=D&rft.date=2004-01-01&rft.volume=19&rft.issue=2&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Cancer+Biotherapy+and+Radiopharmaceuticals&rft.issn=10849785&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 - Xenografts; Carcinoma; Colorectal carcinoma; Monoclonal antibodies; Immunotherapy; Radiotherapy ER - TY - JOUR T1 - Parental lead exposure and total anomalous pulmonary venous return AN - 17987048; 5907934 AB - Investigators from the Baltimore-Washington Infant Study (BWIS) reported an association between self-reported maternal lead exposure and total anomalous pulmonary venous return (TAPVR) in their offspring. This association was further evaluated in the BWIS population using a more sensitive exposure estimate. Cases included 54 live-born infants with TAPVR; controls were a stratified random sample of 522 live-born infants from the BWIS control group. Parental lead exposure was based on three assessment methods, including: an industrial hygiene assessment, an a priori job exposure matrix, and self-reported exposures. A parent was classified as exposed to lead if he/she was classified as exposed by any one of the assessment methods. Approximately 17% of case mothers and 11% of control mothers were classified as exposed to lead during the three months prior to conception through the first trimester (odds ratio [OR], 1.57; 95% confidence interval [CI], 0.64-3.47). Among fathers, 61% of case fathers and 46% of control fathers were classified as exposed to lead during the six months prior to conception (paternal critical period) (OR, 1.83; 95% CI, 1.00-3.42). During the paternal critical period, when only the father was exposed compared to neither parent exposed, the OR for any lead exposure and TAPVR was 1.65 (95% CI, 0.84- 3.25). This study supports a possible association between paternal lead exposure and TAPVR. Further studies are warranted using validated assessment methods for occupational and nonoccupational lead exposures to corroborate this association and to elucidate the possible biological mechanism. JF - Birth Defects Research Part A: Clinical and Molecular Teratology AU - Jackson, Leila W AU - Correa-Villasenor, Adolfo AU - Lees, Peter SJ AU - Dominici, Francesca AU - Stewart, Patricia A AU - Breysse, Patrick N AU - Matanoski, Genevieve AD - Epidemiology Branch, Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, Rockville, Maryland, jacksole@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 185 EP - 193 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 70 IS - 4 SN - 1542-0752, 1542-0752 KW - man KW - Toxicology Abstracts KW - Prenatal experience KW - Heavy metals KW - Lead KW - Pregnancy KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17987048?accountid=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=Birth+Defects+Research+Part+A%3A+Clinical+and+Molecular+Teratology&rft.atitle=Parental+lead+exposure+and+total+anomalous+pulmonary+venous+return&rft.au=Jackson%2C+Leila+W%3BCorrea-Villasenor%2C+Adolfo%3BLees%2C+Peter+SJ%3BDominici%2C+Francesca%3BStewart%2C+Patricia+A%3BBreysse%2C+Patrick+N%3BMatanoski%2C+Genevieve&rft.aulast=Jackson&rft.aufirst=Leila&rft.date=2004-01-01&rft.volume=70&rft.issue=4&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Birth+Defects+Research+Part+A%3A+Clinical+and+Molecular+Teratology&rft.issn=15420752&rft_id=info:doi/10.1002%2Fbdra.20014 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lead; Heavy metals; Prenatal experience; Pregnancy DO - http://dx.doi.org/10.1002/bdra.20014 ER - TY - JOUR T1 - Multidisciplinary research: Strategies for assessing chemical mixtures to reduce risk of exposure and disease AN - 17984882; 5941344 AB - The Precautionary Principle is founded on the use of comprehensive, coordinated research to protect human health in the face of uncertain risks. Research directed at key data gaps may significantly reduce the uncertainty underlying the complexities of assessing risk to mixtures. The National Institute of Environmental Health Sciences (NIEHS) has taken a leadership role in building the scientific infrastructure to address these uncertainties. The challenge is to incorporate the objectives as defined by the Precautionary Principle with the knowledge gained in understanding the multifactorial nature of gene-environment interactions. Through efforts such as the National Center for Toxicogenomics, the National Toxicology Program, and the Superfund Basic Research Program, NIEHS is translating research findings into public health prevention strategies using a 3-pronged approach: 1) identify/evaluate key deviations from additivity for mixtures; 2) develop/apply/link advanced technologies and bioinformatics to quantitative tools for an integrated science-based approach to chemical mixtures; 3) translate/disseminate these technologies into useable, practical means to reduce exposure and the risk of disease. Preventing adverse health effects from environmental exposures requires translation of research findings to affected communities and must include a high level of public involvement. Integrating these approaches are necessary to advance understanding of the health relevance of exposure to mixtures. JF - International Journal of Occupational Medicine and Environmental Health AU - Suk, WA AU - Olden, K AD - Center for Risk and Integrated Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, suk@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 103 EP - 110 VL - 17 IS - 1 SN - 1232-1087, 1232-1087 KW - Risk Abstracts KW - Chemicals KW - Public health KW - risk reduction KW - Hazardous materials KW - precautionary principle KW - uncertainty KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17984882?accountid=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=International+Journal+of+Occupational+Medicine+and+Environmental+Health&rft.atitle=Multidisciplinary+research%3A+Strategies+for+assessing+chemical+mixtures+to+reduce+risk+of+exposure+and+disease&rft.au=Suk%2C+WA%3BOlden%2C+K&rft.aulast=Suk&rft.aufirst=WA&rft.date=2004-01-01&rft.volume=17&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Occupational+Medicine+and+Environmental+Health&rft.issn=12321087&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 - precautionary principle; risk reduction; Hazardous materials; Chemicals; uncertainty; Public health ER - TY - JOUR T1 - NvAssign: protein NMR spectral assignment with NMRView AN - 17982906; 5915575 AB - Nuclear magnetic resonance (NMR) protein studies rely on the accurate assignment of resonances. The general procedure is to (1) pick peaks, (2) cluster data from various experiments or spectra, (3) assign peaks to the sequence and (4) verify the assignments with the spectra. Many algorithms already exist for automating the assignment process (step 3). What is lacking is a flexible interface to help a spectroscopist easily move from clustering (step 2) to assignment algorithms (step 3) and back to verification of the algorithm output with spectral analysis (step 4). Results: A software module, NvAssign, was written for use with NMRView. It is a significant extension of the previous CBCA module. The module provides a flexible interface to cluster data and interact with the existing assignment algorithms. Further, the software module is able to read the results of other algorithms so that the data can be easily verified by spectral analysis. The generalized interface is demonstrated by connecting the clustered data with the assignment algorithms PACES and MONTE using previously assigned data for the lyase domain of DNA polymerase lambda . The spectral analysis program NMRView is now able to read the output of these programs for simplified analysis and verification. JF - Bioinformatics AU - Kirby, Nigel I AU - DeRose, Eugene F AU - London, Robert E AU - Mueller, Geoffrey A AD - Laboratory of Structural Biology, MR-01, National Institute of Environmental Health Sciences, National Institutes of Health, Box 12233, Research Triangle Park, NC 27709, USA, mueller3@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 1201 EP - 1203 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 20 IS - 7 SN - 1367-4803, 1367-4803 KW - NMRView KW - NvAssign KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Algorithms KW - Proteins KW - N.M.R. KW - Bioinformatics KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17982906?accountid=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=Bioinformatics&rft.atitle=NvAssign%3A+protein+NMR+spectral+assignment+with+NMRView&rft.au=Kirby%2C+Nigel+I%3BDeRose%2C+Eugene+F%3BLondon%2C+Robert+E%3BMueller%2C+Geoffrey+A&rft.aulast=Kirby&rft.aufirst=Nigel&rft.date=2004-01-01&rft.volume=20&rft.issue=7&rft.spage=1201&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/10.1093%2Fbioinformatics%2Fbth064 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - NvAssign is available from http://dir.niehs.nih.gov/dirnmr/nvassign Supplementary information: Extensive manual pages with installation instructions, procedures and screen shots can also found at http://dir.niehs.nih.gov/dirnmr/nvassign N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; N.M.R.; Proteins; Algorithms DO - http://dx.doi.org/10.1093/bioinformatics/bth064 ER - TY - JOUR T1 - Large-scale analysis of non-synonymous coding region single nucleotide polymorphisms AN - 17980670; 5915546 AB - Single nucleotide polymorphisms (SNPs) are the most common form of genetic variant in humans. SNPs causing amino acid substitutions are of particular interest as candidates for loci affecting susceptibility to complex diseases, such as diabetes and hypertension. To efficiently screen SNPs for disease association, it is important to distinguish neutral variants from deleterious ones. Results: We describe the use of Pfam protein motif models and the HMMER program to predict whether amino acid changes in conserved domains are likely to affect protein function. We find that the magnitude of the change in the HMMER E- value caused by an amino acid substitution is a good predictor of whether it is deleterious. We provide internet-accessible display tools for a genomewide collection of SNPs, including 7391 distinct non-synonymous coding region SNPs in 2683 genes. JF - Bioinformatics AU - Clifford, Robert J AU - Edmonson, Michael N AU - Nguyen, Cu AU - Buetow, Kenneth H AD - Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, buetowk@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 1006 EP - 1014 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 20 IS - 7 SN - 1367-4803, 1367-4803 KW - Pfam protein motif KW - HMMER program KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Bioengineering Abstracts KW - Single-nucleotide polymorphism KW - N 14510:Occurrence, isolation & assay KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17980670?accountid=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=Bioinformatics&rft.atitle=Large-scale+analysis+of+non-synonymous+coding+region+single+nucleotide+polymorphisms&rft.au=Clifford%2C+Robert+J%3BEdmonson%2C+Michael+N%3BNguyen%2C+Cu%3BBuetow%2C+Kenneth+H&rft.aulast=Clifford&rft.aufirst=Robert&rft.date=2004-01-01&rft.volume=20&rft.issue=7&rft.spage=1006&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/10.1093%2Fbioinformatics%2Fbth029 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - http://lpgws.nci.nih.gov/cgi-bin/GeneViewer.cgi N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Single-nucleotide polymorphism DO - http://dx.doi.org/10.1093/bioinformatics/bth029 ER - TY - JOUR T1 - Occupation and risk of meningioma and acoustic neuroma in the United States AN - 17974136; 5911287 AB - Workplace exposures may be related to the development of brain tumors. In this case-control study, we examine occupation as a risk factor for meningioma and acoustic neuroma. A lifetime work history was obtained for 197 incident cases of meningioma, 96 cases of acoustic neuroma and 799 controls with non- malignant diseases enrolled from three hospitals in the United States between 1994 and 1998. Jobs considered to have similar tasks and chemical exposures were assigned to an occupational group. Logistic regression was used to estimate odds ratios (OR) adjusted for study matching factors (hospital, age, sex, race/ethnicity, and proximity of residence to the hospital) and education. Elevated risk of meningioma was observed for individuals who had ever worked in the following occupational groups: auto body painters, designers and decorators, military occupations, industrial production supervisors, teachers, and managers. For acoustic neuroma, increased risk was noted for having worked as an athlete, gas station attendant, purchasing agent, sales representative, or teacher. Although limited by multiple comparisons and the relatively small number of cases and controls in many occupational groups, these results nevertheless provide clues that deserve additional study in future epidemiologic studies. JF - American Journal of Industrial Medicine AU - Rajaraman, Preetha AU - De Roos, Anneclaire J AU - Stewart, Patricia A AU - Linet, Martha S AU - Fine, Howard A AU - Shapiro, William R AU - Selker, Robert G AU - Black, Peter M AU - Inskip, Peter D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, rajarama@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 395 EP - 407 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 45 IS - 5 SN - 0271-3586, 0271-3586 KW - meningioma KW - Health & Safety Science Abstracts; Risk Abstracts KW - Risk assessment KW - Chemicals KW - Brain KW - USA KW - Occupational exposure 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/17974136?accountid=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+Industrial+Medicine&rft.atitle=Occupation+and+risk+of+meningioma+and+acoustic+neuroma+in+the+United+States&rft.au=Rajaraman%2C+Preetha%3BDe+Roos%2C+Anneclaire+J%3BStewart%2C+Patricia+A%3BLinet%2C+Martha+S%3BFine%2C+Howard+A%3BShapiro%2C+William+R%3BSelker%2C+Robert+G%3BBlack%2C+Peter+M%3BInskip%2C+Peter+D&rft.aulast=Rajaraman&rft.aufirst=Preetha&rft.date=2004-01-01&rft.volume=45&rft.issue=5&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2Fajim.10363 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; Occupational exposure; Brain; Chemicals; Risk assessment DO - http://dx.doi.org/10.1002/ajim.10363 ER - TY - JOUR T1 - High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma- - Incidence, treatment, and outcome AN - 17973446; 5911382 AB - High-dose methotrexate (HDMTX)-induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX-induced nephrotoxicity has been managed with high-dose leucovorin, dialysis-based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase-G sub(2) (CPDG sub(2)), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX-induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis-based methods of MTX removal with treatment using CPDG sub(2). The literature was reviewed for osteosarcoma trials, use of dialysis- based methods for MTX removal, and reports of MTX-induced nephrotoxicity, including information regarding recovery of renal function. Clinical trial databases of select osteosarcoma studies were reviewed. The efficacy of CPDG sub(2) and renal recovery after CPDG sub(2) rescue was obtained from the database of a compassionate-release trial. Approximately 1.8% of patients with osteosarcoma (68 of 3887 patients) who received HDMTX developed nephrotoxicity Grade => 2. The mortality rate among those patients was 4.4% (3 of 68 patients). Dialysis-based methods of MTX removal were used frequently but had limited effectiveness in removing MTX compared with the rapid reductions > 98% in plasma MTX concentrations achieved with CPDG sub(2). CPDG sub(2) did not appear to increase the time to recovery of renal function compared with supportive treatment that included dialysis-based methods. HDMTX-induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma who are treated on clinical protocols with optimal supportive care. For patients with delayed MTX excretion and high plasma MTX concentrations, CPDG sub(2) should be considered over hemodialysis to lower plasma MTX concentrations rapidly and efficiently. JF - Cancer AU - Widemann, Brigitte C AU - Balis, Frank M AU - Kempf-Bielack, Beate AU - Bielack, Stefan AU - Pratt, Charles B AU - Ferrari, Stefano AU - Bacci, Gaetano AU - Craft, Alan W AU - Adamson, Peter C AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, bw42y@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 2222 EP - 2232 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 100 IS - 10 SN - 0008-543X, 0008-543X KW - man KW - Toxicology Abstracts KW - Chemotherapy KW - Kidney KW - Methotrexate KW - Antineoplastic drugs KW - Side effects KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17973446?accountid=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&rft.atitle=High-dose+methotrexate-induced+nephrotoxicity+in+patients+with+osteosarcoma-+-+Incidence%2C+treatment%2C+and+outcome&rft.au=Widemann%2C+Brigitte+C%3BBalis%2C+Frank+M%3BKempf-Bielack%2C+Beate%3BBielack%2C+Stefan%3BPratt%2C+Charles+B%3BFerrari%2C+Stefano%3BBacci%2C+Gaetano%3BCraft%2C+Alan+W%3BAdamson%2C+Peter+C&rft.aulast=Widemann&rft.aufirst=Brigitte&rft.date=2004-01-01&rft.volume=100&rft.issue=10&rft.spage=2222&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/10.1002%2Fcncr.20255 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chemotherapy; Side effects; Antineoplastic drugs; Kidney; Methotrexate DO - http://dx.doi.org/10.1002/cncr.20255 ER - TY - JOUR T1 - Extended Histopathology in Immunotoxicity Testing: Interlaboratory Validation Studies AN - 17966154; 5915509 AB - There has been considerable interest in the use of expanded histopathology as a primary screen for immunotoxicity assessment. To determine the utility of a semiquantitative histopathology approach for examining specific structural and architectural changes in lymphoid tissues, a validation effort was initiated. This study addresses the interlaboratory reproducibility of extended histopathology, using tissues from studies of ten test chemicals and both negative and positive controls from the National Toxicology Program's immunotoxicology testing program. We examined the consistency between experienced toxicologic pathologists, who had varied expertise in immunohistopathology in identifying lesions in immune tissues, and in the sensitivity of the individual and combined histopathological endpoints to detect chemical effects and dose response. Factor analysis was used to estimate the association of each pathologist with a so-called "common factor" and analysis- of-variance methods were used to evaluate biases. Agreement between pathologists was highest in the thymus, in particular, when evaluating cortical cellularity of the thymus; good in spleen follicular cellularity and in spleen and lymph node-germinal center development; and poorest in spleen red-pulp changes. In addition, the ability to identify histopathological change in lymphoid tissues was dependent upon the experience/training that the individual pathologist possessed in examining lymphoid tissue and the apparent severity of the specific lesion. JF - Toxicological Sciences AU - Germolec AU - Nyska, A AU - Kashon, M AU - Kuper, C F AU - Portier, C AU - Kommineni, C AU - Johnson, KA AU - Luster, MI AD - Laboratory of Molecular Toxicology/National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Biostatistics Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia, germolec@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 107 EP - 115 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 78 IS - 1 SN - 1096-6080, 1096-6080 KW - Toxicology Abstracts KW - Immunotoxicity KW - Histopathology KW - Lesions KW - Toxicity testing KW - Lymphoid tissue KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17966154?accountid=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=Toxicological+Sciences&rft.atitle=Extended+Histopathology+in+Immunotoxicity+Testing%3A+Interlaboratory+Validation+Studies&rft.au=Germolec%3BNyska%2C+A%3BKashon%2C+M%3BKuper%2C+C+F%3BPortier%2C+C%3BKommineni%2C+C%3BJohnson%2C+KA%3BLuster%2C+MI&rft.aulast=Germolec&rft.aufirst=&rft.date=2004-01-01&rft.volume=78&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&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 - Lesions; Lymphoid tissue; Toxicity testing; Histopathology; Immunotoxicity ER - TY - JOUR T1 - Efficient gene transfer into the human natural killer cell line, NKL, using the Amaxa nucleofection system registered AN - 17946562; 5877635 AB - Natural killer (NK) cell lines are useful for studying facets of NK cell biology. Such cell lines are notoriously difficult to transfect by traditional methods, a fact that has hampered NK cell biology studies for a long time. To overcome this, we investigated the use of the Amaxa nucleofection system registered that directly transfers DNA into the nucleus of the cell. This technology has revolutionized transfection studies with heretofore relatively transfection resistant cell types such as T cells, B cells and dendritic cells. Despite these advances, NK cells and NK cell lines have remained relatively resistant to transfection, including nucleofection. In this study we employed cDNA for SHP1 and various Rab proteins cloned in enhanced green/yellow fluorescent protein (EGFP/EYFP) expression plasmids for transient transfections into NKL cells. The expression of EGFP/EYFP fusion proteins was analyzed by flow cytometry, immunoblot and confocal microscopic analyses. We achieved 40-70% transfection efficiency with high levels of expression in this cell line with 85-90% viability. The method used in this report proves to be far superior to existing methods for delivering DNA into this well studied NK cell line and, consequently, provides new experimental opportunities. JF - Journal of Immunological Methods AU - Maasho, K AU - Marusina, A AU - Reynolds, N M AU - Coligan, JE AU - Borrego, F AD - Receptor Cell Biology Section, Laboratory of Allergic Diseases, NIAID, NIH, 12441 Parklawn Drive, Room 205, Rockville, MD 20852, USA, jcoligan@niaid.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 133 EP - 140 VL - 284 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Green fluorescent protein KW - Natural killer cells KW - Plasmids KW - Flow cytometry KW - Transfection KW - yellow fluorescent protein KW - Gene transfer KW - Confocal microscopy KW - Fusion protein KW - F 06780:Genetics KW - F 06713:Physicochemical methods KW - W 30965:Miscellaneous, Reviews KW - F 06757:NK cells KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17946562?accountid=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=Efficient+gene+transfer+into+the+human+natural+killer+cell+line%2C+NKL%2C+using+the+Amaxa+nucleofection+system+registered&rft.au=Maasho%2C+K%3BMarusina%2C+A%3BReynolds%2C+N+M%3BColigan%2C+JE%3BBorrego%2C+F&rft.aulast=Maasho&rft.aufirst=K&rft.date=2004-01-01&rft.volume=284&rft.issue=1-2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2Fj.jim.2003.10.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Natural killer cells; Gene transfer; yellow fluorescent protein; Green fluorescent protein; Transfection; Flow cytometry; Confocal microscopy; Fusion protein; Plasmids DO - http://dx.doi.org/10.1016/j.jim.2003.10.010 ER - TY - JOUR T1 - Genomewide conserved epitope profiles of HIV-1 predicted by biophysical properties of MHC binding peptides AN - 17943186; 5901948 AB - We propose a new method for predicting MHC binding of peptides using biophysical parameters of the constituent amino acids. Unlike conventional matrix-based methods, our method does not assume independent binding of the individual side chains and uses a model that simultaneously represents all the residues. The model discovers the quantified 9-mer 'property model' within the longer peptides that are most common among binders. Prediction for a new peptide is based on its statistical 'distance' from the extracted peptide property model. MHC-specific peptide property models were constructed from compiled binder/nonbinder data using this method. We report the results of cross-validation of the prediction method and comparison with other methods. The comparison suggests that our method performs substantially better for some MHC class II molecules and equally well for other MHC types. To demonstrate large-scale utility, 30 HIV-1 reference genomes covering diverse subtypes were analyzed. Regions that are likely to bind MHC (A2, DR1, or DR4) and that are conserved across the HIV-1 subtypes were identified. These 'epitope profiles' of the diverse HIV-1 strains can also be visually presented to facilitate discovery of conserved patterns naturally occurring in the viral genomes. As an essential step in designing vaccines, the revealed patterns may provide valuable information in identifying the immunologically important regions. JF - Journal of Computational Biology AU - Sung, M-H AU - Simon, R AD - Biometric Research Branch, National Cancer Institute, National Institutes of Health, 6130 Executive Blvd., EPN 8146, MSC 7434, Bethesda, MD 20892, USA, sungm@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 125 EP - 145 VL - 11 IS - 1 SN - 1066-5277, 1066-5277 KW - HIV-1 KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Bioengineering Abstracts KW - Genomes KW - Human immunodeficiency virus 1 KW - Major histocompatibility complex KW - Vaccines KW - Computer applications KW - Epitopes KW - Models KW - V 22002:AIDS: Molecular and in vitro aspects KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17943186?accountid=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+Computational+Biology&rft.atitle=Genomewide+conserved+epitope+profiles+of+HIV-1+predicted+by+biophysical+properties+of+MHC+binding+peptides&rft.au=Sung%2C+M-H%3BSimon%2C+R&rft.aulast=Sung&rft.aufirst=M-H&rft.date=2004-01-01&rft.volume=11&rft.issue=1&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Journal+of+Computational+Biology&rft.issn=10665277&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; Major histocompatibility complex; Models; Computer applications; Epitopes; Genomes; Vaccines ER - TY - JOUR T1 - Developmental toxicity evaluation of emodin in rats and mice AN - 17933058; 5878330 AB - Emodin, a widely available herbal remedy, was evaluated for potential effects on pregnancy outcome. Emodin was administered in feed to timed-mated Sprague-Dawley (CD) rats (0, 425, 850, and 1700 ppm; gestational day [GD] 6-20), and Swiss Albino (CD-1) mice (0, 600, 2500 or 6000 ppm; GD 6-17). Ingested dose was 0, 31, 57, and ~80-144 mg emodin/kg/day (rats) and 0, 94, 391, and 1005 mg emodin/kg/day (mice). Timed-mated animals (23-25/group) were monitored for body weight, feed/water consumption, and clinical signs. At termination (rats: GD 20; mice: GD 17), confirmed pregnant dams (21-25/group) were evaluated for clinical signs: body, liver, kidney, and gravid uterine weights, uterine contents, and number of corpora lutea. Fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations/variations. There were no maternal deaths. In rats, maternal body weight, weight gain during treatment, and corrected weight gain exhibited a decreasing trend. Maternal body weight gain during treatment was significantly reduced at the high dose. In mice, maternal body weight and weight gain was decreased at the high dose. Prenatal mortality, live litter size, fetal sex ratio, and morphological development were unaffected in both rats and mice. At the high dose, rat average fetal body weight per litter was unaffected, but was significantly reduced in mice. The rat maternal lowest observed adverse effect level (LOAEL) was 1700 ppm; the no observed adverse effect level (NOAEL) was 850 ppm. The rat developmental toxicity NOAEL was =>1700 ppm. A LOAEL was not established. In mice, the maternal toxicity LOAEL was 6000 ppm and the NOAEL was 2500 ppm. The developmental toxicity LOAEL was 6000 ppm (reduced fetal body weight) and the NOAEL was 2500 ppm. JF - Birth Defects Research Part B: Developmental and Reproductive Toxicology AU - Jahnke, G D AU - Price, C J AU - Marr, M C AU - Myers, C B AU - George, J D AD - Sciences International Inc. Alexandria, Virginia, jahnke@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 89 EP - 101 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 71 IS - 2 SN - 1542-9733, 1542-9733 KW - LOAEL KW - consumption KW - corpora lutea KW - emodin KW - mice KW - rats KW - Toxicology Abstracts KW - development KW - birth defects KW - pregnancy KW - herbal remedy KW - Malformations KW - Sex ratio KW - Weight KW - Liver KW - Kidney KW - Toxicity KW - Development KW - Fetuses KW - X 24172:Plants KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17933058?accountid=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=Birth+Defects+Research+Part+B%3A+Developmental+and+Reproductive+Toxicology&rft.atitle=Developmental+toxicity+evaluation+of+emodin+in+rats+and+mice&rft.au=Jahnke%2C+G+D%3BPrice%2C+C+J%3BMarr%2C+M+C%3BMyers%2C+C+B%3BGeorge%2C+J+D&rft.aulast=Jahnke&rft.aufirst=G&rft.date=2004-01-01&rft.volume=71&rft.issue=2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Birth+Defects+Research+Part+B%3A+Developmental+and+Reproductive+Toxicology&rft.issn=15429733&rft_id=info:doi/10.1002%2Fbdrb.20002 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Malformations; Weight; Sex ratio; Kidney; Liver; Development; Toxicity; Fetuses DO - http://dx.doi.org/10.1002/bdrb.20002 ER - TY - JOUR T1 - In vivo gene marking of rhesus macaque long-term repopulating hematopoietic cells using a VSV-G pseudotyped versus amphotropic oncoretroviral vector AN - 17931422; 5878942 AB - Gene transfer efficiency into primitive hematopoietic cells may be limited by their expression of surface receptors allowing vector entry. Vectors pseudotyped with the vesicular stomatitis virus (VSV-G) envelope do not need receptors to enter cells, and therefore may provide superior transduction efficiency. Using a competitive repopulation model in the rhesus macaque, we examined in vivo gene marking levels of blood cells transduced with two vectors: (i) a VSV-G pseudotyped retrovirus and (ii) a conventional amphotropic retrovirus. The VSV-G vector, containing the human glucose-6-phosphate dehydrogenase (G6PD) gene, was constructed for treatment of severe hemolytic anemia caused by G6PD deficiency. Three myeloablated animals were transplanted with peripheral blood CD34+ cells, half of which were transduced with the VSV-G vector and the other half with the amphotropic vector. In all animals post- transplantation, levels of in vivo marking in circulating granulocytes and mononuclear cells were similar: 1% or less with both vectors. In one animal, the human G6PD enzyme transferred by the VSV-G vector was expressed in erythrocytes, early after transplantation, at a level of 45% of the endogenous rhesus G6PD protein. In a clinically relevant animal model, we found similar in vivo marking with a VSV-G pseudotyped and a standard amphotropic oncoretroviral vector. Amphotropic receptor expression may not be a limiting factor in transduction efficiency, but VSV-G pseudotypes possess other practical advantages that may make them advantageous for clinical use. JF - Journal of Gene Medicine AU - Shi, P A AU - De Angioletti, M AU - Donahue, R E AU - Notaro, R AU - Luzzatto, L AU - Dunbar, CE AD - Hematology Branch, NHLBI, NIH, Bethesda, MD 20892, USA, dunbarc@nhlbi.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 367 EP - 373 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 6 IS - 4 SN - 1099-498X, 1099-498X KW - Rhesus monkey KW - Rhesus macaque KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Hemolytic anemia KW - Animal models KW - Typing KW - Gene transfer KW - Glucose-6-phosphate 1-dehydrogenase KW - Hemopoiesis KW - Macaca mulatta KW - Transduction KW - Vesicular stomatitis virus KW - N 14682:Cloning vectors KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17931422?accountid=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+Gene+Medicine&rft.atitle=In+vivo+gene+marking+of+rhesus+macaque+long-term+repopulating+hematopoietic+cells+using+a+VSV-G+pseudotyped+versus+amphotropic+oncoretroviral+vector&rft.au=Shi%2C+P+A%3BDe+Angioletti%2C+M%3BDonahue%2C+R+E%3BNotaro%2C+R%3BLuzzatto%2C+L%3BDunbar%2C+CE&rft.aulast=Shi&rft.aufirst=P&rft.date=2004-01-01&rft.volume=6&rft.issue=4&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Journal+of+Gene+Medicine&rft.issn=1099498X&rft_id=info:doi/10.1002%2Fjgm.514 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Macaca mulatta; Vesicular stomatitis virus; Hemopoiesis; Typing; Hemolytic anemia; Glucose-6-phosphate 1-dehydrogenase; Animal models; Transduction; Gene transfer DO - http://dx.doi.org/10.1002/jgm.514 ER - TY - JOUR T1 - Evidence-Based Rating of Upper-Extremity Motor Function Tests Used for People Following a Stroke AN - 17893459; 5858398 AB - Tests of upper-extremity motor function used for people following a stroke have been described, but reliability and validity (psychometric properties) of measurements obtained with these tests have not been consistently established. This investigation was performed: (1) to review literature relative to upper-extremity motor function testing during rehabilitation following a stroke, (2) to develop selection criteria for identifying these tests in the literature, and (3) to rate the tests relative to their psychometric properties. Literature searches were done using 2 databases. Reports of 4 psychometric properties were sought: interrater reliability, test-retest reliability, convergent validity or concurrent validity, and predictive validity. Nine tests met the inclusion criteria of having psychometric properties reported in the literature. No test had evidence for all 4 psychometric properties. Only the Nine-Hole Peg Test was supported by 3 out of 4 properties. Most tests had 2 properties supported. Concurrent validity or convergent validity was most frequently described; test-retest reliability was least frequently described. More complete psychometric support is needed for upper-extremity motor function tests applied following a stroke. The absence of psychometric support, however, does not mean that a test has no value. Clinicians are cautioned not to generalize psychometric evidence. JF - Physical Therapy AU - Croarkin, E AU - Danoff, J AU - Barnes, C AD - Physical Therapy Section, National Institutes of Health, Bldg 10, Room 6S-235, 9000 Rockville Pike, Bethesda, MD 20892-1604, USA, ecroarkin@cc.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 62 EP - 74 VL - 84 IS - 1 SN - 0031-9023, 0031-9023 KW - Physical Education Index KW - Physical therapy KW - Stroke KW - Motor performance tests KW - Motor ability KW - Arms KW - PE 110:Physical Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17893459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Physical+Therapy&rft.atitle=Evidence-Based+Rating+of+Upper-Extremity+Motor+Function+Tests+Used+for+People+Following+a+Stroke&rft.au=Croarkin%2C+E%3BDanoff%2C+J%3BBarnes%2C+C&rft.aulast=Croarkin&rft.aufirst=E&rft.date=2004-01-01&rft.volume=84&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Physical+Therapy&rft.issn=00319023&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Physical therapy; Motor ability; Motor performance tests; Arms; Stroke ER - TY - JOUR T1 - Reduced field of view and undersampled PR combined for interventional imaging of a fully dynamic field of view AN - 17827731; 5878793 AB - Active catheter imaging was investigated using real-time undersampled projection reconstruction (PR) combined with the temporal filtering technique of reduced field of view (rFOV). Real-time rFOV processing was interactively enabled during highly undersampled catheter imaging, resulting in improved artifact suppression with better temporal resolution than that obtained by view- sharing. Imaging with 64 to 32 projections provided a resolution of 2 X 2 X 8 mm, and four to eight true frames per second. Image artifacts were reduced when rFOV processing was applied to the undersampled images. A comparison with Cartesian rFOV showed that PR image quality is less susceptible to aliasing that results from rFOV imaging with a wholly dynamic outer FOV. Simulations and MRI experiments demonstrated that PR rFOV provides significant artifact suppression, even for a fully dynamic FOV. The near doubling of temporal resolution that is possible with PR rFOV permits accurate monitoring of highly dynamic events, such as catheter movements, and arrhythmias, such as ventricular ectopy. JF - Magnetic Resonance in Medicine AU - Peters, D C AU - Guttman, MA AU - Dick, A J AU - Raman, V K AU - Lederman, R J AU - McVeigh, E R AD - Laboratory of Cardiac Energetics, NHLBI, National Institutes of Health, DHHS, Bethesda, Maryland, dcpeters@bidmc.harvard.edu Y1 - 2004 PY - 2004 DA - 2004 SP - 761 EP - 767 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 4 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Arrhythmia KW - Magnetic resonance imaging KW - Catheters KW - N.M.R. KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17827731?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Reduced+field+of+view+and+undersampled+PR+combined+for+interventional+imaging+of+a+fully+dynamic+field+of+view&rft.au=Peters%2C+D+C%3BGuttman%2C+MA%3BDick%2C+A+J%3BRaman%2C+V+K%3BLederman%2C+R+J%3BMcVeigh%2C+E+R&rft.aulast=Peters&rft.aufirst=D&rft.date=2004-01-01&rft.volume=51&rft.issue=4&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20037 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Catheters; Magnetic resonance imaging; N.M.R.; Arrhythmia DO - http://dx.doi.org/10.1002/mrm.20037 ER - TY - JOUR T1 - Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestational exposure to statins AN - 17826907; 6097546 AB - The cholesterol-lowering "statin" drugs are contraindicated in pregnancy, but few data exist on their safety in human gestation. We reviewed case reports for patterns suggesting drug-related effects on prenatal development and considered a variety of mechanisms by which such effects, if confirmed, might occur. This uncontrolled case series included all FDA reports of statin exposures during gestation, as well as others from the literature and from manufacturers. Exposures and outcomes were reviewed and were tabulated by individual drug. Age-specific rates of exposure to each drug among women of child-bearing age were estimated. Of 214 ascertained pregnancy exposures, 70 evaluable reports remained after excluding uninformative cases. Among 31 adverse outcomes were 22 cases with structural defects, 4 cases of intrauterine growth restriction, and 5 cases of fetal demise. There were two principal categories of recurrent structural defects: cerivastatin and lovastatin were associated with four reports of severe midline CNS defects; simvastatin, lovastatin, and atorvastatin were all associated with reports of limb deficiencies, including two similar complex lower limb defects reported following simvastatin exposure. There were also two cases of VACTERL association among the limb deficiency cases. All adverse outcomes were reported following exposure to cerivastatin, simvastatin, lovastatin, or atorvastatin, which are lipophilic and equilibrate between maternal and embryonic compartments. None were reported following exposure to pravastatin, which is minimally present in the embryo. Statins reaching the embryo may down-regulate biosynthesis of cholesterol as well as many important metabolic intermediates, and may have secondary effects on sterol-dependent morphogens such as Sonic Hedgehog. The reported cases display patterns consistent with dysfunction of cholesterol biosynthesis and Sonic Hedgehog activity. Controlled studies are needed to investigate the teratogenicity of individual drugs in this class. JF - American Journal of Medical Genetics Part A AU - Edison, Robin J AU - Muenke, Maximilian AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, mmuenke@nhgri.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 287 EP - 298 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 131A IS - 3 SN - 0148-7299, 0148-7299 KW - Toxicology Abstracts KW - Central nervous system KW - statins KW - Fetuses KW - Pregnancy KW - Birth KW - Limbs KW - Case reports KW - Reviews KW - Gestation KW - Teratogenicity KW - Embryos KW - Drugs KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17826907?accountid=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+Medical+Genetics+Part+A&rft.atitle=Mechanistic+and+epidemiologic+considerations+in+the+evaluation+of+adverse+birth+outcomes+following+gestational+exposure+to+statins&rft.au=Edison%2C+Robin+J%3BMuenke%2C+Maximilian&rft.aulast=Edison&rft.aufirst=Robin&rft.date=2004-01-01&rft.volume=131A&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics+Part+A&rft.issn=01487299&rft_id=info:doi/10.1002%2Fajmg.a.30386 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - statins; Drugs; Embryos; Limbs; Gestation; Pregnancy; Reviews; Central nervous system; Case reports; Teratogenicity; Birth; Fetuses DO - http://dx.doi.org/10.1002/ajmg.a.30386 ER - TY - JOUR T1 - Cytotoxicant-induced trophoblast dysfunction and abnormal pregnancy outcomes: Role of zinc and metallothionein AN - 17825121; 6129073 AB - Normal trophoblast function, including implantation, hormone production, and formation of the selectively permeable maternofetal barrier, is essential for the establishment and maintenance of the fetoplacental unit and proper fetal development. Maternal cytotoxicant exposure causes the destruction of these cells, especially the terminally differentiated syncytiotrophoblasts, and results in a myriad of poor pregnancy outcomes. These outcomes range from intrauterine growth retardation and malformation to spontaneous abortion or stillbirth. There is recent evidence that the metal-binding protein, metallothionein, is involved in the protection of human trophoblastic cells from heavy metal-induced and severe oxidative stress-induced apoptosis. Metallothionein, with its unique biochemical structure, can both bind essential metal ions, such as the transcription modulator zinc, and yet allow their ready displacement by toxic nonessential metal ions or damaging free radicals. These properties suggest that metallothionein may be responsible not only for sequestering the cytotoxic agents, but also for altering signal transduction in the affected cells. Here, we review several identified causes of adverse pregnancy outcomes (specifically, prenatal exposure to cigarette smoke and alcohol, gestational infection, and exposure to environmental contaminants), discuss the role of zinc in modulating the cellular response to these toxic insults, and then propose how metallothionein may function to mediate this protective response. Birth Defects Research (Part C) 72:361-370, 2005. Published 2005 Wiley-Liss, Inc. JF - Birth Defects Research Part C: Embryo Today: Reviews AU - McAleer, Mary Frances AU - Tuan, Rocky S AD - Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, tuanr@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 361 EP - 370 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 72 IS - 4 SN - 1542-975X, 1542-975X KW - Toxicology Abstracts KW - Metals KW - Ions KW - Metallothionein KW - Free radicals KW - Trophoblasts KW - Cytotoxic agents KW - Pregnancy KW - Reviews KW - Zinc KW - Congenital defects KW - Embryos KW - Contaminants KW - X 24164:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17825121?accountid=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=Birth+Defects+Research+Part+C%3A+Embryo+Today%3A+Reviews&rft.atitle=Cytotoxicant-induced+trophoblast+dysfunction+and+abnormal+pregnancy+outcomes%3A+Role+of+zinc+and+metallothionein&rft.au=McAleer%2C+Mary+Frances%3BTuan%2C+Rocky+S&rft.aulast=McAleer&rft.aufirst=Mary&rft.date=2004-01-01&rft.volume=72&rft.issue=4&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Birth+Defects+Research+Part+C%3A+Embryo+Today%3A+Reviews&rft.issn=1542975X&rft_id=info:doi/10.1002%2Fbdrc.20024 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Metallothionein; Pregnancy; Zinc; Trophoblasts; Congenital defects; Ions; Reviews; Metals; Free radicals; Embryos; Cytotoxic agents; Contaminants DO - http://dx.doi.org/10.1002/bdrc.20024 ER - TY - JOUR T1 - Generation of a large gene/protein lexicon by morphological pattern analysis AN - 17820362; 5890314 AB - The identification of gene/protein names in natural language text is an important problem in named entity recognition. In previous work we have processed MEDLINE registered documents to obtain a collection of over two million names of which we estimate that perhaps two thirds are valid gene/protein names. Our problem has been how to purify this set to obtain a high quality subset of gene/protein names. Here we describe an approach which is based on the generation of certain classes of names that are characterized by common morphological features. Within each class inductive logic programming (ILP) is applied to learn the characteristics of those names that are gene/protein names. The criteria learned in this manner are then applied to our large set of names. We generated 193 classes of names and ILP led to criteria defining a select subset of 1,240,462 names. A simple false positive filter was applied to remove 8% of this set leaving 1,145,913 names. Examination of a random sample from this gene/protein name lexicon suggests it is composed of 82% ( plus or minus 3%) complete and accurate gene/protein names, 12% names related to genes/proteins (too generic, a valid name plus additional text, part of a valid name, etc.), and 6% names unrelated to genes/proteins. The lexicon is freely available at ftp.ncbi.nlm.nih.gov/pub/tanabe/Gene.Lexicon. JF - Journal of Bioinformatics and Computational Biology AU - Tanabe, L AU - Wilbur, W J AD - National Center for Biotechnology Information, 8600 Rockville Pike, Bethesda, MD 20894, USA, tanabe@ncbi.nlm.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 611 EP - 626 PB - World Scientific Publishing Co. Pte. Ltd., 1060 Main Street Suite 202 River Edge NJ 07661 USA, [mailto:wspc@wspc.com], [URL:http://www.wspc.com] VL - 1 IS - 4 SN - 0219-7200, 0219-7200 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Filters KW - Genes KW - Proteins KW - Language KW - Bioinformatics KW - Computer applications KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17820362?accountid=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+Bioinformatics+and+Computational+Biology&rft.atitle=Generation+of+a+large+gene%2Fprotein+lexicon+by+morphological+pattern+analysis&rft.au=Tanabe%2C+L%3BWilbur%2C+W+J&rft.aulast=Tanabe&rft.aufirst=L&rft.date=2004-01-01&rft.volume=1&rft.issue=4&rft.spage=611&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bioinformatics+and+Computational+Biology&rft.issn=02197200&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 - Proteins; Genes; Language; Filters; Bioinformatics; Computer applications ER - TY - JOUR T1 - Chemical and physical characteristics of cellulose insulation particulates, and evaluation of potential acute pulmonary toxicity AN - 17792121; 6084689 AB - During installation of cellulose insulation (CI) in new and older houses, significant quantities of airborne material are generated. This study characterized the chemical and physical properties, and potential acute pulmonary toxicity of CI. CI from four manufacturers was analyzed for inorganic additives and trace element impurities. Aerosols were generated and size fractionated. The number and size of fibrous and nonfibrous particles in the respirable fractions were determined. Respirable CI particulates were intratracheally instilled in rats (5 mg/kg) to evaluate potential pulmonary toxicity. CI samples were similar in composition with small differences due primarily to fire retardants. Less than 0.1% of CI was respirable and contained few fibers. Acute exposure to CI caused transient inflammation in the lungs and increased 4-hydroxyproline. Microscopic evaluation revealed a minimal to mild, non-progressing granulomatous pneumonitis. Low concentrations of respirable particles were found in CI aerosols. Particles consisted primarily of fire retardants with few fibers, and caused mild pulmonary toxicity in rats. JF - American Journal of Industrial Medicine AU - Morgan, Daniel L AU - Su, Yin-Fong AU - Dill, Jeffrey A AU - Turnier, John C AU - Westerberg, RBruce AU - Smith, Cynthia S AD - National Institute of Environmental Health Sciences and the National Toxicology Program, Research Triangle Park, North Carolina, morgand@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 554 EP - 569 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 46 IS - 6 SN - 0271-3586, 0271-3586 KW - Toxicology Abstracts KW - cellulose insulation KW - chemical composition KW - particulates KW - fibers KW - instillation KW - rats KW - respiratory toxicity KW - Fires KW - Houses KW - Physical characteristics KW - Aerosols KW - Impurities KW - Cellulose KW - Airborne KW - Trace elements KW - Inflammation KW - Acute effects KW - Fibers KW - Lung KW - Pneumonitis KW - X 24151:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17792121?accountid=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=Chemical+and+physical+characteristics+of+cellulose+insulation+particulates%2C+and+evaluation+of+potential+acute+pulmonary+toxicity&rft.au=Morgan%2C+Daniel+L%3BSu%2C+Yin-Fong%3BDill%2C+Jeffrey+A%3BTurnier%2C+John+C%3BWesterberg%2C+RBruce%3BSmith%2C+Cynthia+S&rft.aulast=Morgan&rft.aufirst=Daniel&rft.date=2004-01-01&rft.volume=46&rft.issue=6&rft.spage=554&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2Fajim.20101 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Fires; Aerosols; Physical characteristics; Houses; Cellulose; Impurities; Airborne; Inflammation; Trace elements; Acute effects; Fibers; Lung; Pneumonitis DO - http://dx.doi.org/10.1002/ajim.20101 ER - TY - JOUR T1 - The Small RNA Regulators of Escherichia coli: Roles and Mechanisms AN - 17775115; 6109277 AB - Small noncoding RNAs have been found in all organisms, primarily as regulators of translation and message stability. The most exhaustive searches have taken place in E. coli, resulting in identification of more than 50 small RNAs, or 1%-2% of the number of protein-coding genes. One large class of these small RNAs uses the RNA chaperone Hfq; members of this class act by pairing to target messenger RNAs. Among the members of this class are DsrA and RprA, which positively regulate rpoS translation, OxyS, which negatively regulates rpoS translation and fhlA translation, RyhB, which reapportions iron use in the cell by downregulating translation of many genes that encode Fe-containing proteins, and Spot 42, which changes the polarity of translation in the gal operon. The promoters of these small RNAs are tightly regulated, frequently as part of well-understood regulons. Lessons learned from the study of small RNAs in E. coli can be applied to finding these important regulators in other organisms. JF - Annual Review of Microbiology AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA, susang@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 303 EP - 328 VL - 58 SN - 0066-4227, 0066-4227 KW - Hfq protein KW - Microbiology Abstracts B: Bacteriology KW - Promoters KW - Translation KW - Reviews KW - Escherichia coli KW - Polarity KW - Chaperones KW - Iron KW - Galactose operon KW - mRNA KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17775115?accountid=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=The+Small+RNA+Regulators+of+Escherichia+coli%3A+Roles+and+Mechanisms&rft.au=Gottesman%2C+S&rft.aulast=Gottesman&rft.aufirst=S&rft.date=2004-01-01&rft.volume=58&rft.issue=&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Microbiology&rft.issn=00664227&rft_id=info:doi/10.1146%2Fannurev.micro.58.030603.123841 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; mRNA; Translation; Reviews; Promoters; Chaperones; Iron; Galactose operon; Polarity DO - http://dx.doi.org/10.1146/annurev.micro.58.030603.123841 ER - TY - JOUR T1 - Nonmyeloablative allogeneic immunotherapy for solid tumors AN - 17773021; 6144982 AB - Over the past decade, considerable advances have been made in the field of allogeneic hematopoietic stem cell transplantation. Recognition that transplanted donor immune cells can cure patients with leukemia has led to the development of nonmyeloablative or "low-intensity" conditioning regimens, which have expanded the application of allogeneic transplantation to a growing number of hematological malignancies. The improved safety and preliminary success of this transplant approach have justified applying allogeneic immunotherapy to patients with treatment-refractory solid tumors. JF - Annual Review of Medicine AU - Childs, R W AU - Barrett, J AD - Allogeneic Hematopoietic Cell Transplant Unit, Hematology Branch, National Heart, Lung, and Blood Institutes, National Institutes of Health, Bethesda, MD 20892, USA, childsr@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 459 EP - 475 VL - 55 SN - 0066-4219, 0066-4219 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Leukemia KW - Donors KW - Malignancy KW - Solid tumors KW - stem cell transplantation KW - Immunotherapy KW - Hemopoiesis KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17773021?accountid=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=Annual+Review+of+Medicine&rft.atitle=Nonmyeloablative+allogeneic+immunotherapy+for+solid+tumors&rft.au=Childs%2C+R+W%3BBarrett%2C+J&rft.aulast=Childs&rft.aufirst=R&rft.date=2004-01-01&rft.volume=55&rft.issue=&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Medicine&rft.issn=00664219&rft_id=info:doi/10.1146%2Fannurev.med.55.091902.104511 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Immunotherapy; Solid tumors; Hemopoiesis; Malignancy; Donors; stem cell transplantation; Leukemia DO - http://dx.doi.org/10.1146/annurev.med.55.091902.104511 ER - TY - JOUR T1 - Contribution of Magnetic Resonance Microscopy in the 12-Week Neurotoxicity Evaluation of Carbonyl Sulfide in Fischer 344 Rats AN - 17760026; 6036321 AB - In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200-600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure. JF - Toxicologic Pathology AU - Sills, R C AU - Morgan, D L AU - Herr, D W AU - Little, P B AU - George, N M AU - Ton, T V AU - Love, N E AU - Maronpot, R R AU - Johnson, G A AD - Laboratory of Experimental Pathology, NIEHS, Research Triangle Park, North Carolina, USA Y1 - 2004 PY - 2004 DA - 2004 SP - 501 EP - 510 VL - 32 IS - 5 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Heart KW - Data processing KW - Gadolinium KW - Brain KW - Electrophysiology KW - imaging KW - Sulfide KW - Fixatives KW - Neurotoxicity KW - Microscopy KW - N.M.R. KW - cytochrome oxidase KW - carbonyls KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17760026?accountid=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=Contribution+of+Magnetic+Resonance+Microscopy+in+the+12-Week+Neurotoxicity+Evaluation+of+Carbonyl+Sulfide+in+Fischer+344+Rats&rft.au=Sills%2C+R+C%3BMorgan%2C+D+L%3BHerr%2C+D+W%3BLittle%2C+P+B%3BGeorge%2C+N+M%3BTon%2C+T+V%3BLove%2C+N+E%3BMaronpot%2C+R+R%3BJohnson%2C+G+A&rft.aulast=Sills&rft.aufirst=R&rft.date=2004-01-01&rft.volume=32&rft.issue=5&rft.spage=501&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1080%2F01926230490493918 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Heart; Data processing; Gadolinium; Brain; Electrophysiology; imaging; Sulfide; Fixatives; Microscopy; Neurotoxicity; N.M.R.; cytochrome oxidase; carbonyls DO - http://dx.doi.org/10.1080/01926230490493918 ER - TY - JOUR T1 - Risk Factors to Musculoskeletal Disorders and Anthropometric Measurements of Filipino Manufacturing Workers AN - 17719232; 6134400 AB - This study looked into the risk factors to musculoskeletal disorders and established anthropometric measurements of Filipino workers in 29 manufacturing industries. Anthropometric measurements of 1,805 workers were taken, and 495 workers were surveyed. Limitation of motion was found in 0.8% of the respondents, affectation in activities of daily living was seen in 1.6% and 3.2% felt discomfort in the head and neck. Upper trunk and low back pain was experienced by 23.8%. Odds ratio results (p = .05) showed that it is 29 times likely for workers to develop low back pain when they stand for 2-8 hrs a day than when they sit all the time. Anthropometry can be used for the design of workstations and work furniture. JF - International Journal of Occupational Safety and Ergonomics AU - Del Prado-Lu, JL AD - National Institutes of Health, University of the Philippines, Manila, Philippines, jinky_lu@yahoo.com Y1 - 2004 PY - 2004 DA - 2004 SP - 349 EP - 359 VL - 10 IS - 4 SN - 1080-3548, 1080-3548 KW - Health & Safety Science Abstracts KW - Manufacturing industry KW - Philippines KW - Materials handling KW - low back pain KW - Working conditions KW - musculoskeletal system KW - Ergonomics KW - Occupational health KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17719232?accountid=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=International+Journal+of+Occupational+Safety+and+Ergonomics&rft.atitle=Risk+Factors+to+Musculoskeletal+Disorders+and+Anthropometric+Measurements+of+Filipino+Manufacturing+Workers&rft.au=Del+Prado-Lu%2C+JL&rft.aulast=Del+Prado-Lu&rft.aufirst=JL&rft.date=2004-01-01&rft.volume=10&rft.issue=4&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Occupational+Safety+and+Ergonomics&rft.issn=10803548&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 - Philippines; low back pain; musculoskeletal system; Occupational health; Working conditions; Materials handling; Manufacturing industry; Ergonomics ER - TY - JOUR T1 - Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil AN - 17700909; 6026635 AB - A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI techniques have been demonstrated in recent years. One of the reasons these methods are still not routinely used is the limited extent of the imaging region. Of the ASL methods proposed to date, continuous ASL (CASL) with a separate labeling coil is particularly attractive for whole-brain studies at high fields. This approach can provide an increased signal-to-noise ratio (SNR) in perfusion images because there are no magnetization transfer (MT) effects, and lessen concerns regarding RF power deposition at high field because it uses a local labeling coil. In this work, we demonstrate CASL whole-brain quantitative perfusion imaging at 3.0 T using a combination of strategies: 3D volume acquisition, background tissue signal suppression, and a separate labeling coil. The results show that this approach can be used to acquire perfusion images in all brain regions with good sensitivity. Further, it is shown that the method can be performed safely on humans without exceeding the current RF power deposition limits. The current method can be extended to higher fields, and further improved by the use of multiple receiver coils and parallel imaging techniques to reduce scan time or provide increased resolution. Magn Reson Med 52:131-140, 2004. Published 2004 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - Talagala, SLalith AU - Ye, Frank Q AU - Ledden, Patrick J AU - Chesnick, Scott AD - NINDS, National Institutes of Health, Bethesda, Maryland, talagala@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 131 EP - 140 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 52 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17700909?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Whole-brain+3D+perfusion+MRI+at+3.0+T+using+CASL+with+a+separate+labeling+coil&rft.au=Talagala%2C+SLalith%3BYe%2C+Frank+Q%3BLedden%2C+Patrick+J%3BChesnick%2C+Scott&rft.aulast=Talagala&rft.aufirst=SLalith&rft.date=2004-01-01&rft.volume=52&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20124 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/mrm.20124 ER - TY - JOUR T1 - Opiate tolerance by heroin self-administration: An fMRI study in rat AN - 17700548; 6026632 AB - Functional MRI (fMRI) was employed to determine whether repeated heroin self-administration (SA) produces tolerance or sensitization in the brain of heroin-SA rats. Twelve rats were evenly divided into saline and heroin (0.06 mg/kg, 4 hr/day) SA groups. There was a progressive increase in drug-SA behavior and daily heroin intake during the 8-9 days of heroin-SA training. Within 24 hr after the last session of daily SA, acute heroin (0.1 mg/kg) administration induced regional blood oxygen level-dependent (BOLD) signals in both groups of rats. The positive BOLD signals appeared mainly in the cortical regions, including the prefrontal cortex, cingulate, and olfactory cortex, while the negative BOLD signals were predominantly located in subcortical regions such as caudate and putamen, nucleus accumbens, thalamus, and hypothalamus. However, the number of activated voxels or BOLD-signal intensity was significantly less in heroin-SA rat in regions of prefrontal cortex, nucleus accumbens, and thalamus, etc. compared to the changes in the saline control rats. Application of gamma - vinyl GABA (100 mg/kg), an irreversible GABA-transaminase inhibitor, failed to block opiate actions in the heroin-SA rats. Together, these data suggest that repeated heroin-SA produces tolerance or desensitization of opiate actions in the rat brain, which may in turn potentiate drug SA behavior and drug intake. Magn Reson Med 52:108-114, 2004. JF - Magnetic Resonance in Medicine AU - Xi, Zheng-Xiong AU - Wu, Gaohong AU - Stein, Elliot A AU - Li, Shi-Jiang AD - Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, Maryland, sjli@mcw.edu Y1 - 2004 PY - 2004 DA - 2004 SP - 108 EP - 114 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 52 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17700548?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Opiate+tolerance+by+heroin+self-administration%3A+An+fMRI+study+in+rat&rft.au=Xi%2C+Zheng-Xiong%3BWu%2C+Gaohong%3BStein%2C+Elliot+A%3BLi%2C+Shi-Jiang&rft.aulast=Xi&rft.aufirst=Zheng-Xiong&rft.date=2004-01-01&rft.volume=52&rft.issue=1&rft.spage=108&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20119 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/mrm.20119 ER - TY - JOUR T1 - System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner AN - 17700500; 6026615 AB - A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14-15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle- placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized. Magn Reson Med 52:683-687, 2004. Published 2004 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - Susil, Robert C AU - Camphausen, Kevin AU - Choyke, Peter AU - McVeigh, Elliot R AU - Gustafson, Gary S AU - Ning, Holly AU - Miller, Robert W AU - Atalar, Ergin AU - Coleman, CNorman AU - Menard, Cynthia AD - Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, menardc@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 683 EP - 687 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 52 IS - 3 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17700500?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=System+for+prostate+brachytherapy+and+biopsy+in+a+standard+1.5+T+MRI+scanner&rft.au=Susil%2C+Robert+C%3BCamphausen%2C+Kevin%3BChoyke%2C+Peter%3BMcVeigh%2C+Elliot+R%3BGustafson%2C+Gary+S%3BNing%2C+Holly%3BMiller%2C+Robert+W%3BAtalar%2C+Ergin%3BColeman%2C+CNorman%3BMenard%2C+Cynthia&rft.aulast=Susil&rft.aufirst=Robert&rft.date=2004-01-01&rft.volume=52&rft.issue=3&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20138 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/mrm.20138 ER - TY - JOUR T1 - Flow-gated phase-contrast MRI using radial acquisitions AN - 17698284; 6026467 AB - Phase-contrast (PC) MRI is a noninvasive method for imaging blood and tissue velocity. PC experiments are typically segmented into many cardiac cycles in order to obtain sufficient spatial and temporal resolution, and thus require a gating signal to properly combine the data from multiple cardiac cycles. Although the surface electrode ECG is the gating waveform of choice for cardiovascular MRI, alternative gating methods are required for fetal cardiac imaging (due to the unavailability of fetal ECG signals) and for cases of ECG contamination via the strong magnetic fields within the MR scanner. This study demonstrates the feasibility of using imaging data from flow-encoded MRI experiments to derive times for cardiac gating. An undersampled radial k-space acquisition method is used to measure an image-derived flow-gating waveform in real-time, from which the gating times are derived. These gating times are used to reconstruct a conventional gated-segmented image series by combining the real-time data from multiple heartbeats. Flow-gated PC experiments were performed on five normal volunteers with slice prescriptions in four anatomic regions. The standard deviation (SD) of the difference between the flow-gating and ECG gating times ranged from 5 ms to 12 ms. Magn Reson Med 52:598-604, 2004. Published 2004 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - Thompson, Richard B AU - McVeigh, Elliot R AD - Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, Maryland, thompsor@nhlbi.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 598 EP - 604 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 52 IS - 3 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17698284?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Flow-gated+phase-contrast+MRI+using+radial+acquisitions&rft.au=Thompson%2C+Richard+B%3BMcVeigh%2C+Elliot+R&rft.aulast=Thompson&rft.aufirst=Richard&rft.date=2004-01-01&rft.volume=52&rft.issue=3&rft.spage=598&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20187 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/mrm.20187 ER - TY - JOUR T1 - CD studies on films of amyloid proteins and polypeptides: Quantitative g- factor analysis indicates a common folding motif AN - 17693123; 6026533 AB - Irrespective of the constituent protein, all amyloid fibrils show similar morphology in the electron microscope and x-ray diffraction patterns characteristic of a "cross- beta " structure, with extended beta -strands perpendicular to the fibril's long axis. Little is known about the amount or type of this structure. I have measured CD spectra of films formed from a number of amyloid proteins and polypeptides, and estimated their contents of extended secondary structure, by analysis of their g-factor spectra, the ratio of the CD and absorbance signals (P. McPhie, Analytical Biochemistry, 2001, Vol. 293, pp. 109-119). Amyloid films of A beta -(1-40) peptide, beta -2-microglobulin, insulin, and three homopolypeptides show very intense CD spectra, compatible with the presence of a beta -helix-like structure, arranged in a common framework in the fibrils. The extent of this structure was estimated as 45-80% in the protein fibrils and 30-80% in the polypeptide fibrils. JF - Biopolymers AU - McPhie, Peter AD - Laboratory of Biochemistry and Genetics, Building 8, Room 215, NIDDK, NIH, Bethesda, MD 20892-0830, pmcphie@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 140 EP - 147 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 75 IS - 2 SN - 0006-3525, 0006-3525 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 330:Biopolymers & Food Biotechnology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17693123?accountid=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=Biopolymers&rft.atitle=CD+studies+on+films+of+amyloid+proteins+and+polypeptides%3A+Quantitative+g-+factor+analysis+indicates+a+common+folding+motif&rft.au=McPhie%2C+Peter&rft.aulast=McPhie&rft.aufirst=Peter&rft.date=2004-01-01&rft.volume=75&rft.issue=2&rft.spage=140&rft.isbn=&rft.btitle=&rft.title=Biopolymers&rft.issn=00063525&rft_id=info:doi/10.1002%2Fbip.20095 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/bip.20095 ER - TY - JOUR T1 - Polyamine dendrimer-based MRI contrast agents for functional kidney imaging to diagnose acute renal failure AN - 17685092; 6026668 AB - To choose an efficacious renal functional MRI contrast agent to image early renal tubular damage. We synthesized and compared smaller polyamine dendrimer- based MRI contrast agents (<60 kD) that, unlike Gd-[DTPA], transiently accumulate in renal tubules and can be used to visualize renal structural and functional damage. Six dendrimer-based MRI contrast agents smaller than 60 kD were studied by high resolution dynamic micro-MRI and compared to Gd-[DTPA]- dimeglumine and Gadomer-17. The best agent, DAB-G2, was further tested in a mouse ischemia/reperfusion model to validate its efficacy. Despite unequal renal clearance rates, all polyamine dendrimer agents visualized the renal functional anatomy of the mice better than Gd-[DTPA]-dimeglumine and Gadomer-17. DAB-G2 was excreted most rapidly, yet was able to visualize mild renal tubular injury very early after injury. DAB-G2 was found to be the best candidate for functional kidney imaging and enabled early diagnosis of acute renal injury. JF - Journal of Magnetic Resonance Imaging AU - Kobayashi, Hisataka AU - Jo, Sang-Kyung AU - Kawamoto, Satomi AU - Yasuda, Hideo AU - Hu, Xuzhen AU - Knopp, Michael V AU - Brechbiel, Martin W AU - Choyke, Peter L AU - Star, Robert A AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, Kobayash@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 512 EP - 518 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 20 IS - 1 SN - 1053-1807, 1053-1807 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17685092?accountid=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+Magnetic+Resonance+Imaging&rft.atitle=Polyamine+dendrimer-based+MRI+contrast+agents+for+functional+kidney+imaging+to+diagnose+acute+renal+failure&rft.au=Kobayashi%2C+Hisataka%3BJo%2C+Sang-Kyung%3BKawamoto%2C+Satomi%3BYasuda%2C+Hideo%3BHu%2C+Xuzhen%3BKnopp%2C+Michael+V%3BBrechbiel%2C+Martin+W%3BChoyke%2C+Peter+L%3BStar%2C+Robert+A&rft.aulast=Kobayashi&rft.aufirst=Hisataka&rft.date=2004-01-01&rft.volume=20&rft.issue=1&rft.spage=512&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.20147 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/jmri.20147 ER - TY - JOUR T1 - Functional MRI of the rodent somatosensory pathway using multislice echo planar imaging AN - 17684693; 6026630 AB - A multislice EPI sequence was used to obtain functional MR images of the entire rat brain with BOLD contrast at 11.7 T. ten to 11 slices covering the rat brain, with an in-plane resolution of 300 mu m, provided enough sensitivity to detect activation in brain regions known to be involved in the somatosensory pathway during stimulation of the forelimbs. These regions were identified by warping a digitized rat brain atlas to each set of images. Data analysis was constrained to four major areas of the somatosensory pathway: primary and secondary somatosensory cortices, thalamus, and cerebellum. Incidence maps were generated. Electrical stimulation at 3 Hz led to significant activation in the primary sensory cortex in all rats. Activation in the secondary sensory cortex and cerebellum was observed in 70% of the studies, while thalamic activation was observed in 40%. The amplitude of activation was measured for each area, and average response time courses were calculated. Finally, the frequency dependence of the response to forepaw stimulation was measured in each of the activated areas. Optimal activation occurred in all areas at 3 Hz. These results demonstrate that whole-brain fMRI can be performed on rodents at 11.7 T to probe a well-defined neural network. Magn Reson Med 52:89-99, 2004. Published 2004 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - Keilholz, Shella D AU - Silva, Afonso C AU - Raman, Mira AU - Merkle, Hellmut AU - Koretsky, Alan P AD - Laboratory of Functional and Molecular Imaging, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, KoretskyA@ninds.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 89 EP - 99 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 52 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17684693?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Functional+MRI+of+the+rodent+somatosensory+pathway+using+multislice+echo+planar+imaging&rft.au=Keilholz%2C+Shella+D%3BSilva%2C+Afonso+C%3BRaman%2C+Mira%3BMerkle%2C+Hellmut%3BKoretsky%2C+Alan+P&rft.aulast=Keilholz&rft.aufirst=Shella&rft.date=2004-01-01&rft.volume=52&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20114 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/mrm.20114 ER - TY - JOUR T1 - Ovarian cancer risk and use of phenolphthalein-containing laxatives AN - 17667589; 6500160 AB - Purpose Experimental studies in rodents demonstrated the carcinogenic potential of phenolphthalein, the active ingredient in some laxatives, administered at doses similar to the dose that could be used by humans. Ovarian cancer was one of the cancers observed in these studies. We examined the association between epithelial ovarian cancer and use of phenolphthalein-containing laxatives in a population-based case-control study. Methods The study includes 356 epithelial ovarian cancer cases (256 invasive, 100 borderline) and 424 controls. Cases were identified through a population-based registry in Los Angeles County in 1992-1998, and controls were matched to cases by age, race/ethnicity and neighborhood. Data on laxative use (specific brands, frequency of use, usual dose) were obtained by structured in-person interview. Results Compared to women who never used a laxative, ever use of a phenolphthalein-containing laxative was not associated with an increased risk of invasive ovarian cancer (odds ratio (OR) 1.1, 95% confidence interval (CI) 0.75, 1.5) or of borderline ovarian cancer (OR 0.75, 95%CI 0.37, 1.5). Total days used, mean number of pills per day and cumulative dose were also unrelated to risk. Conclusions This study provides some assurance that phenolphthalein-containing laxatives do not increase the risk of ovarian cancer in humans. These findings are of particular importance to those countries in which phenolphthalein is still used in over-the-counter medications. JF - Pharmacoepidemiology and Drug Safety AU - Cooper, G S AU - Longnecker, M P AU - Peters, R K AD - Epidemiology Branch A3-05, NIEHS, Durham, NC 27709, USA, cooper1@niehs.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 35 EP - 39 VL - 13 IS - 1 SN - 1053-8569, 1053-8569 KW - laxatives KW - ovarian carcinoma KW - phenolphthalein KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - R2 23060:Medical and environmental health KW - H 4000:Food and Drugs KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17667589?accountid=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=Pharmacoepidemiology+and+Drug+Safety&rft.atitle=Ovarian+cancer+risk+and+use+of+phenolphthalein-containing+laxatives&rft.au=Cooper%2C+G+S%3BLongnecker%2C+M+P%3BPeters%2C+R+K&rft.aulast=Cooper&rft.aufirst=G&rft.date=2004-01-01&rft.volume=13&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Pharmacoepidemiology+and+Drug+Safety&rft.issn=10538569&rft_id=info:doi/10.1002%2Fpds.824 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-12-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/pds.824 ER - TY - JOUR T1 - Meat-related mutagens/carcinogens in the etiology of colorectal cancer AN - 17655301; 6538279 AB - Diets containing substantial amounts of red or preserved meats may increase the risk of various cancers, including colorectal cancer. This association may be due to a combination of factors such as the content of fat, protein, iron, and/or meat preparation (e.g., cooking or preserving methods). Red meat may be associated with colorectal cancer by contributing to N-nitroso compound (NOC) exposure. Humans can be exposed to NOCs by exogenous routes (from processed meats in particular) and by endogenous routes. Endogenous exposure to NOCs is dose-dependently related to the amount of red meat in the diet. Laboratory results have shown that meats cooked at high temperatures contain other potential mutagens in the form of heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). To investigate the role of these compounds, we have created separate databases for HCAs and PAHs, which we have used in conjunction with a validated meat-cooking food frequency questionnaire. The role of meat type, cooking methods, doneness levels, and meat-cooking mutagens has been examined in both case-control studies and prospective cohort studies, with mixed results. Here, we review the current epidemiologic knowledge of meat-related mutagens, and evaluate the types of studies that may be required in the future to clarify the association between meat consumption and colorectal cancer. JF - Environmental and Molecular Mutagenesis AU - Cross, A J AU - Sinha, R AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, 6120 Executive Plaza, Rockville, MD 20852, USA, crossa@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 44 EP - 55 VL - 44 IS - 1 SN - 0893-6692, 0893-6692 KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants KW - X 24200:Nitrosamines & related compounds UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17655301?accountid=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+and+Molecular+Mutagenesis&rft.atitle=Meat-related+mutagens%2Fcarcinogens+in+the+etiology+of+colorectal+cancer&rft.au=Cross%2C+A+J%3BSinha%2C+R&rft.aulast=Cross&rft.aufirst=A&rft.date=2004-01-01&rft.volume=44&rft.issue=1&rft.spage=44&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 revised - 2005-12-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Protective Effect of Diphenylmethyl Selenocyanate Against Carbon Tetrachloride-Induced Hepatotoxicity In Vivo AN - 17652057; 6492728 AB - Carbon tetrachloride (CCl sub(4)) is a known hepatotoxic compound working through the generation of reactive free radicals. Selenium (Se) is an essential trace element required by animals and humans for protection against xenobiotic compounds. In this study, Se, as diphenylmethyl selenocyanate, has been evaluated for its protective action against CCl sub(4)-induced hepatotoxicity in Swiss albino mice. Treatment with Se compound was found to upregulate different phase II detoxifying enzymes (catalase, superoxide dismutases, reduced glutathione, and glutathione transferase) in liver of mice challenged with different doses of CCl sub(4) as compared to the CCl4 control, when measured after 24 hours of CCl sub(4) treatment (p < 0.01). The Se compound also significantly (p < 0.01) inhibited the level of membrane lipid peroxidation and serum transferase activity (ALT and AST) in the treated group as compared to the control group. JF - Journal of Environmental Pathology, Toxicology and Oncology AU - Das, R K AU - Das, S AU - Bhattacharya, S AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India Y1 - 2004 PY - 2004 DA - 2004 SP - 10 VL - 23 IS - 4 SN - 0731-8898, 0731-8898 KW - Toxicology Abstracts KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17652057?accountid=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+Environmental+Pathology%2C+Toxicology+and+Oncology&rft.atitle=Protective+Effect+of+Diphenylmethyl+Selenocyanate+Against+Carbon+Tetrachloride-Induced+Hepatotoxicity+In+Vivo&rft.au=Das%2C+R+K%3BDas%2C+S%3BBhattacharya%2C+S&rft.aulast=Das&rft.aufirst=R&rft.date=2004-01-01&rft.volume=23&rft.issue=4&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Pathology%2C+Toxicology+and+Oncology&rft.issn=07318898&rft_id=info:doi/10.1615%2FJEnvPathToxOncol.v23.i4.50 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1615/JEnvPathToxOncol.v23.i4.50 ER - TY - JOUR T1 - The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies AN - 17605902; 6034463 AB - Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the findings from imaging studies to propose a model of drug addiction. The process of addiction is initiated in part by the fast and high increases in da induced by drugs of abuse. We hypothesize that this supraphysiological effect of drugs trigger a series of adaptations in neuronal circuits involved in saliency/reward, motivation/drive, memory/conditioning, and control/disinhibition, resulting in an enhanced (and long lasting) saliency value for the drug and its associated cues at the expense of decreased sensitivity for salient events of everyday life (including natural reinforcers). Although acute drug intake increases da neurotransmission, chronic drug consumption results in a marked decrease in da activity, associated with, among others, dysregulation of the orbitofrontal cortex (region involved with salience attribution) and cingulate gyrus (region involved with inhibitory control). The ensuing increase in motivational drive for the drug, strengthened by conditioned responses and the decrease in inhibitory control favors emergence of compulsive drug taking. This view of how drugs of abuse affect the brain suggests strategies for intervention, which might include: (a) those that will decrease the reward value of the drug of choice; (b) interventions to increase the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned drug behaviors; and (d) methods to strengthen frontal inhibitory and executive control. Though this model focuses mostly on findings from PET studies of the brain da system it is evident that other neurotransmitters are involved and that a better understanding of their roles in addiction would expand the options for therapeutic targets. JF - Neuropharmacology AU - Volkow, N D AU - Fowler, J S AU - Wang, G-J AD - Office of the Director, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5274, MSC 9581, Bethesda, MD 20892, USA, nvolkow@nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 3 EP - 13 PB - Elsevier Science Ltd., Pergamon, P.O. Box 800 Kidlington Oxford OX5 1DX UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 47 SN - 0028-3908, 0028-3908 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17605902?accountid=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=Neuropharmacology&rft.atitle=The+addicted+human+brain+viewed+in+the+light+of+imaging+studies%3A+brain+circuits+and+treatment+strategies&rft.au=Volkow%2C+N+D%3BFowler%2C+J+S%3BWang%2C+G-J&rft.aulast=Volkow&rft.aufirst=N&rft.date=2004-01-01&rft.volume=47&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/10.1016%2Fj.neuropharm.2004.07.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.neuropharm.2004.07.019 ER - TY - JOUR T1 - Incubation of cocaine craving after withdrawal: a review of preclinical data AN - 17605225; 6034449 AB - Using a rat model of drug craving and relapse, we recently found that cocaine seeking induced by re-exposure to drug-associated cues progressively increases over the first 2 months after withdrawal from cocaine self-administration, suggesting that drug craving incubates over time [Nature 412 (2001) 141]. Here, we summarize data from studies that further characterized this incubation phenomenon and briefly discuss its implications for drug addiction. The main findings of our ongoing research are: 1. Incubation of cocaine craving is long-lasting, but not permanent: cocaine seeking induced by exposure to cocaine cues remains elevated for up to 3 months of withdrawal, but decreases after 6 months. 2. Incubation of reward craving is not drug specific: sucrose seeking induced by re-exposure to the reward cues also increases after withdrawal, but for a time period that is shorter than that of cocaine. 3. Incubation of cocaine craving is not evident after acute re-exposure to cocaine itself: cocaine seeking induced by cocaine priming injections remains essentially unchanged over the first 6 months of withdrawal. 4. Incubation of cocaine craving after withdrawal is associated with increases in the levels of brain-derived neurotrophic factor (BDNF) in mesolimbic dopamine areas. JF - Neuropharmacology AU - Lu, L AU - Grimm, J W AU - Hope, B T AU - Shaham, Y AD - Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, yshaham@intra.nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 214 EP - 226 PB - Elsevier Science Ltd., Pergamon, P.O. Box 800 Kidlington Oxford OX5 1DX UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 47 SN - 0028-3908, 0028-3908 KW - CSA Neurosciences Abstracts; Toxicology Abstracts 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/17605225?accountid=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=Neuropharmacology&rft.atitle=Incubation+of+cocaine+craving+after+withdrawal%3A+a+review+of+preclinical+data&rft.au=Lu%2C+L%3BGrimm%2C+J+W%3BHope%2C+B+T%3BShaham%2C+Y&rft.aulast=Lu&rft.aufirst=L&rft.date=2004-01-01&rft.volume=47&rft.issue=&rft.spage=214&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/10.1016%2Fj.neuropharm.2004.06.027 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.neuropharm.2004.06.027 ER - TY - JOUR T1 - Evidence for alterations in alpha 2-adrenergic receptor sensitivity in rats exposed to repeated cocaine administration AN - 17601005; 5887379 AB - It is well established that cocaine stimulates monoamine transmission by blocking reuptake of norepinephrine (NE), dopamine and serotonin into nerve cells, yet few investigations have addressed the effects of chronic cocaine on NE function. In the present study, we examined the effects of repeated cocaine injections on neuroendocrine responses evoked by the alpha 2-adrenergic receptor agonist, clonidine. Previous findings show that clonidine increases pituitary growth hormone (GH) secretion by a central mechanism involving postsynaptic alpha 2-adrenergic receptors. Male rats previously fitted with indwelling jugular catheters received two daily injections of cocaine (15 mg/kg, i.p.) or saline for 7 days. At 42 h and 8 days after treatment, rats were challenged with clonidine (25 mu g/kg, i.v.) or saline, and serial blood samples were withdrawn. Plasma GH and corticosterone levels were measured by radioimmunoassay. Prior cocaine exposure did not affect basal levels of either hormone. However, cocaine-pretreated rats displayed a significant reduction in clonidine-evoked GH secretion at 42 h, and this blunted response was still apparent 8 days later. Corticosterone responses produced by clonidine were similar regardless of pretreatment. The present data suggest that withdrawal from repeated cocaine injections may be accompanied by desensitization of postsynaptic alpha 2-adrenoreceptors coupled to GH secretion. Since human patients with depression often exhibit blunted GH responses to clonidine, our findings provide evidence that cocaine withdrawal might produce depressive-like symptoms via dysregulation of NE mechanisms. JF - Neuroscience AU - Baumann, M H AU - Milchanowski, AB AU - Rothman, R B AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, P.O. Box 5180, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, mbaumann@irp.nida.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 683 EP - 690 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 125 IS - 3 SN - 0306-4522, 0306-4522 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17601005?accountid=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=Evidence+for+alterations+in+alpha+2-adrenergic+receptor+sensitivity+in+rats+exposed+to+repeated+cocaine+administration&rft.au=Baumann%2C+M+H%3BMilchanowski%2C+AB%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=2004-01-01&rft.volume=125&rft.issue=3&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/10.1016%2Fj.neuroscience.2004.02.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.neuroscience.2004.02.013 ER - TY - JOUR T1 - Health effects of chronic pesticide exposure: Cancer and Neurotoxicity AN - 17599637; 6499645 AB - Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers. JF - Annual Review of Public Health AU - Alavanja, MCR AU - Hoppin, JA AU - Kamel, F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Rockville, Maryland 20892, USA, alavanjm@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 155 EP - 197 VL - 25 SN - 0163-7525, 0163-7525 KW - Health & Safety Science Abstracts KW - Agrochemicals KW - Cancer KW - Public health KW - Carcinogenicity KW - Reviews KW - Neurotoxicity KW - Pesticides KW - H 5000:Pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17599637?accountid=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=Annual+Review+of+Public+Health&rft.atitle=Health+effects+of+chronic+pesticide+exposure%3A+Cancer+and+Neurotoxicity&rft.au=Alavanja%2C+MCR%3BHoppin%2C+JA%3BKamel%2C+F&rft.aulast=Alavanja&rft.aufirst=MCR&rft.date=2004-01-01&rft.volume=25&rft.issue=&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Public+Health&rft.issn=01637525&rft_id=info:doi/10.1146%2Fannurev.publhealth.25.101802.123020 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pesticides; Reviews; Public health; Neurotoxicity; Carcinogenicity; Agrochemicals; Cancer DO - http://dx.doi.org/10.1146/annurev.publhealth.25.101802.123020 ER - TY - JOUR T1 - Newer imaging modalities in the prenatal diagnosis of skeletal dysplasias AN - 17585733; 6026223 AB - No Abstract. JF - Ultrasound in Obstetrics and Gynecology AU - Goncalves, L F AU - Espinoza, J AU - Mazor, M AU - Romero, R AD - Department of Obstetrics Gynecology, Wayne State University, NIH/DHHS, Detroit, MI, USA, warfiela@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 115 EP - 120 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 24 IS - 2 SN - 0960-7692, 0960-7692 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Gynecology KW - Dysplasia KW - Prenatal diagnosis KW - Ultrasound KW - imaging KW - Obstetrics KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17585733?accountid=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=Ultrasound+in+Obstetrics+and+Gynecology&rft.atitle=Newer+imaging+modalities+in+the+prenatal+diagnosis+of+skeletal+dysplasias&rft.au=Goncalves%2C+L+F%3BEspinoza%2C+J%3BMazor%2C+M%3BRomero%2C+R&rft.aulast=Goncalves&rft.aufirst=L&rft.date=2004-01-01&rft.volume=24&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Ultrasound+in+Obstetrics+and+Gynecology&rft.issn=09607692&rft_id=info:doi/10.1002%2Fuog.1712 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Obstetrics; Dysplasia; imaging; Gynecology; Prenatal diagnosis; Ultrasound DO - http://dx.doi.org/10.1002/uog.1712 ER - TY - JOUR T1 - In vitro release of vascular endothelial growth factor from gadolinium-doped biodegradable microspheres AN - 17513431; 5912139 AB - A drug delivery vehicle was constructed that could be visualized noninvasively with MRI. The biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) was used to fabricate microspheres containing vascular endothelial growth factor (VEGF) and the MRI contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The microspheres were characterized in terms of size, drug and contrast agent encapsulation, and degradation rate. The PLGA microspheres had a mean diameter of 48 +/- 18 mu m. The gadolinium loading was 17 +/- 3 mu g/mg polymer and the VEGF loading was 163 +/- 22 ng/mg polymer. Electron microscopy revealed that the Gd was dispersed throughout the microspheres and it was confirmed that the Gd loading was sufficient to visualize the microspheres under MRI. VEGF and Gd-DTPA were released from the microspheres in vitro over a period of ~6 weeks in three phases: a burst, followed by a slow steady-state, then a rapid steady-state. Biodegradable Gd-doped microspheres can be effectively used to deliver drugs in a sustained manner, while being monitored noninvasively with MRI. JF - Magnetic Resonance in Medicine AU - Faranesh, Anthony Z AU - Nastley, Monet T AU - De la Cruz, Cristina Perez AU - Haller, Michael F AU - Laquerriere, Patrice AU - Leong, Kam W AU - McVeigh, Elliot R AD - Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, faranesh@nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 1265 EP - 1271 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 51 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Vascular endothelial growth factor KW - Drug delivery KW - Gadolinium KW - Magnetic resonance imaging KW - Contrast media KW - microspheres KW - N.M.R. KW - Electron microscopy KW - Encapsulation KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17513431?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=In+vitro+release+of+vascular+endothelial+growth+factor+from+gadolinium-doped+biodegradable+microspheres&rft.au=Faranesh%2C+Anthony+Z%3BNastley%2C+Monet+T%3BDe+la+Cruz%2C+Cristina+Perez%3BHaller%2C+Michael+F%3BLaquerriere%2C+Patrice%3BLeong%2C+Kam+W%3BMcVeigh%2C+Elliot+R&rft.aulast=Faranesh&rft.aufirst=Anthony&rft.date=2004-01-01&rft.volume=51&rft.issue=6&rft.spage=1265&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20092 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - microspheres; Vascular endothelial growth factor; Magnetic resonance imaging; Gadolinium; Contrast media; Encapsulation; N.M.R.; Drug delivery; Electron microscopy DO - http://dx.doi.org/10.1002/mrm.20092 ER - TY - JOUR T1 - Iterative class discovery and feature selection using Minimal Spanning Trees AN - 17344369; 6234133 AB - Background: Clustering is one of the most commonly used methods for discovering hidden structure in microarray gene expression data. Most current methods for clustering samples are based on distance metrics utilizing all genes. This has the effect of obscuring clustering in samples that may be evident only when looking at a subset of genes, because noise from irrelevant genes dominates the signal from the relevant genes in the distance calculation. Results: We describe an algorithm for automatically detecting clusters of samples that are discernable only in a subset of genes. We use iteration between Minimal Spanning Tree based clustering and feature selection to remove noise genes in a step-wise manner while simultaneously sharpening the clustering. Evaluation of this algorithm on synthetic data shows that it resolves planted clusters with high accuracy in spite of noise and the presence of other clusters. It also shows a low probability of detecting spurious clusters. Testing the algorithm on some well known micro-array data-sets reveals known biological classes as well as novel clusters. Conclusions: The iterative clustering method offers considerable improvement over clustering in all genes. This method can be used to discover partitions and their biological significance can be determined by comparing with clinical correlates and gene annotations. The MATLAB super([copyright] )programs for the iterative clustering algorithm are available from http://linus.nci.nih.gov/supplement.html JF - BMC Bioinformatics AU - Varma, Sudhir AU - Simon, Richard AD - Biometric Research Branch, National Cancer Institute, Rockville, USA, varmas@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17344369?accountid=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=BMC+Bioinformatics&rft.atitle=Iterative+class+discovery+and+feature+selection+using+Minimal+Spanning+Trees&rft.au=Varma%2C+Sudhir%3BSimon%2C+Richard&rft.aulast=Varma&rft.aufirst=Sudhir&rft.date=2004-01-01&rft.volume=5&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-5-126 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-02-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1471-2105-5-126 ER - TY - JOUR T1 - Mistaken Identifiers: Gene name errors can be introduced inadvertently when using Excel in bioinformatics AN - 17331050; 6234291 AB - Background: When processing microarray data sets, we recently noticed that some gene names were being changed inadvertently to non-gene names. Results: A little detective work traced the problem to default date format conversions and floating-point format conversions in the very useful Excel program package. The date conversions affect at least 30 gene names; the floating-point conversions affect at least 2,000 if Riken identifiers are included. These conversions are irreversible; the original gene names cannot be recovered. Conclusions: Users of Excel for analyses involving gene names should be aware of this problem, which can cause genes, including medically important ones, to be lost from view and which has contaminated even carefully curated public databases. We provide work- arounds and scripts for circumventing the problem. JF - BMC Bioinformatics AU - Zeeberg, Barry R AU - Riss, Joseph AU - Kane, David W AU - Bussey, Kimberly J AU - Uchio, Edward AU - Linehan, W Marston AU - Barrett, J Carl AU - Weinstein, John N AD - Genomics & Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bldg 37 Rm 5041, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, barry@discover.nci.nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17331050?accountid=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=BMC+Bioinformatics&rft.atitle=Mistaken+Identifiers%3A+Gene+name+errors+can+be+introduced+inadvertently+when+using+Excel+in+bioinformatics&rft.au=Zeeberg%2C+Barry+R%3BRiss%2C+Joseph%3BKane%2C+David+W%3BBussey%2C+Kimberly+J%3BUchio%2C+Edward%3BLinehan%2C+W+Marston%3BBarrett%2C+J+Carl%3BWeinstein%2C+John+N&rft.aulast=Zeeberg&rft.aufirst=Barry&rft.date=2004-01-01&rft.volume=5&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-5-80 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1471-2105-5-80 ER - TY - JOUR T1 - A double classification tree search algorithm for index SNP selection AN - 17328762; 6234300 AB - Background: In population-based studies, it is generally recognized that single nucleotide polymorphism (SNP) markers are not independent. Rather, they are carried by haplotypes, groups of SNPs that tend to be coinherited. It is thus possible to choose a much smaller number of SNPs to use as indices for identifying haplotypes or haplotype blocks in genetic association studies. We refer to these characteristic SNPs as index SNPs. In order to reduce costs and work, a minimum number of index SNPs that can distinguish all SNP and haplotype patterns should be chosen. Unfortunately, this is an NP-complete problem, requiring brute force algorithms that are not feasible for large data sets. Results: We have developed a double classification tree search algorithm to generate index SNPs that can distinguish all SNP and haplotype patterns. This algorithm runs very rapidly and generates very good, though not necessarily minimum, sets of index SNPs, as is to be expected for such NP-complete problems. Conclusions: A new algorithm for index SNP selection has been developed. A webserver for index SNP selection is available at http://cognia.cu-genome.org/cgi-bin/genome/snpIndex.cgi/ JF - BMC Bioinformatics AU - Zhang, Peisen AU - Sheng, Huitao AU - Uehara, Ryuhei AD - Laboratory of Population Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA, zhangpeis@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17328762?accountid=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=BMC+Bioinformatics&rft.atitle=A+double+classification+tree+search+algorithm+for+index+SNP+selection&rft.au=Zhang%2C+Peisen%3BSheng%2C+Huitao%3BUehara%2C+Ryuhei&rft.aulast=Zhang&rft.aufirst=Peisen&rft.date=2004-01-01&rft.volume=5&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-5-89 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1471-2105-5-89 ER - TY - JOUR T1 - The tissue microarray data exchange specification: implementation by the Cooperative Prostate Cancer Tissue Resource AN - 17327975; 6234203 AB - Background: Tissue Microarrays (TMAs) have emerged as a powerful tool for examining the distribution of marker molecules in hundreds of different tissues displayed on a single slide. TMAs have been used successfully to validate candidate molecules discovered in gene array experiments. Like gene expression studies, TMA experiments are data intensive, requiring substantial information to interpret, replicate or validate. Recently, an open access Tissue Microarray Data Exchange Specification has been released that allows TMA data to be organized in a self-describing XML document annotated with well-defined common data elements. While this specification provides sufficient information for the reproduction of the experiment by outside research groups, its initial description did not contain instructions or examples of actual implementations, and no implementation studies have been published. The purpose of this paper is to demonstrate how the TMA Data Exchange Specification is implemented in a prostate cancer TMA. Results: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is funded by the National Cancer Institute to provide researchers with samples of prostate cancer annotated with demographic and clinical data. The CPCTR now offers prostate cancer TMAs and has implemented a TMA database conforming to the new open access Tissue Microarray Data Exchange Specification. The bulk of the TMA database consists of clinical and demographic data elements for 299 patient samples. These data elements were extracted from an Excel database using a transformative Perl script. The Perl script and the TMA database are open access documents distributed with this manuscript. Conclusions: TMA databases conforming to the Tissue Microarray Data Exchange Specification can be merged with other TMA files, expanded through the addition of data elements, or linked to data contained in external biological databases. This article describes an open access implementation of the TMA Data Exchange Specification and provides detailed guidance to researchers who wish to use the Specification. JF - BMC Bioinformatics AU - Berman, Jules J AU - Datta, Milton AU - Kajdacsy-Balla, Andre AU - Melamed, Jonathan AU - Orenstein, Jan AU - Dobbin, Kevin AU - Patel, Ashok AU - Dhir, Rajiv AU - Becich, Michael J AD - Cancer Diagnosis Program, National Cancer Institute, National Institutes of Health, Bethesda, USA, bermanj@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17327975?accountid=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=BMC+Bioinformatics&rft.atitle=The+tissue+microarray+data+exchange+specification%3A+implementation+by+the+Cooperative+Prostate+Cancer+Tissue+Resource&rft.au=Berman%2C+Jules+J%3BDatta%2C+Milton%3BKajdacsy-Balla%2C+Andre%3BMelamed%2C+Jonathan%3BOrenstein%2C+Jan%3BDobbin%2C+Kevin%3BPatel%2C+Ashok%3BDhir%2C+Rajiv%3BBecich%2C+Michael+J&rft.aulast=Berman&rft.aufirst=Jules&rft.date=2004-01-01&rft.volume=5&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-5-19 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-02-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1471-2105-5-19 ER - TY - JOUR T1 - Performance of a genetic algorithm for mass spectrometry proteomics AN - 17327617; 6234193 AB - Background: Recently, mass spectrometry data have been mined using a genetic algorithm to produce discriminatory models that distinguish healthy individuals from those with cancer. This algorithm is the basis for claims of 100% sensitivity and specificity in two related publicly available datasets. To date, no detailed attempts have been made to explore the properties of this genetic algorithm within proteomic applications. Here the algorithm's performance on these datasets is evaluated relative to other methods. Results: In reproducing the method, some modifications of the algorithm as it is described are necessary to get good performance. After modification, a cross-validation approach to model selection is used. The overall classification accuracy is comparable though not superior to other approaches considered. Also, some aspects of the process rely upon random sampling and thus for a fixed dataset the algorithm can produce many different models. This raises questions about how to choose among competing models. How this choice is made is important for interpreting sensitivity and specificity results as merely choosing the model with lowest test set error rate leads to overestimates of model performance. Conclusions: The algorithm needs to be modified to reduce variability and care must be taken in how to choose among competing models. Results derived from this algorithm must be accompanied by a full description of model selection procedures to give confidence that the reported accuracy is not overstated. JF - BMC Bioinformatics AU - Jeffries, Neal O AD - Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, Bethesda MD, USA, neal.jeffries@nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17327617?accountid=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=BMC+Bioinformatics&rft.atitle=Performance+of+a+genetic+algorithm+for+mass+spectrometry+proteomics&rft.au=Jeffries%2C+Neal+O&rft.aulast=Jeffries&rft.aufirst=Neal&rft.date=2004-01-01&rft.volume=5&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-5-180 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-02-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1471-2105-5-180 ER - TY - JOUR T1 - Bioterrorism and the Responsible Conduct of Biomedical Research AN - 17325921; 6191944 AB - This article discusses the ethical responsibilities of biomedical researchers to prevent bioterrorism, including duties related to research, publication, editorial review, public education, expert opinion, advocacy, and reporting suspicious activity. Since actions taken to avert bioterrorism may also undermine important scientific norms, such as openness, freedom, and collegiality, and individual rights, such as privacy, biomedical scientists may encounter ethical dilemmas and problems when they consider taking steps against terrorism. This article proposes some policies and recommendations that attempt to strike a fair and reasonable balance between protecting scientific norms and individual rights and promoting national and international security. This article articulates policies and recommendations that will help ensure that the norms that govern biomedical research and individual rights are not casualties in the struggle against terrorism. Drug Dev Res 63:121-133, 2004. JF - Drug Development Research AU - Resnik, David B AU - Shamoo, Adil E AD - National Institutes of Environmental Health, National Institutes of Health, Research Triangle Park, North Carolina, resnikd@mail.niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 121 EP - 133 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 63 IS - 3 SN - 0272-4391, 0272-4391 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 240:Bioterrorism & Biological Warfare KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17325921?accountid=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=Drug+Development+Research&rft.atitle=Bioterrorism+and+the+Responsible+Conduct+of+Biomedical+Research&rft.au=Resnik%2C+David+B%3BShamoo%2C+Adil+E&rft.aulast=Resnik&rft.aufirst=David&rft.date=2004-01-01&rft.volume=63&rft.issue=3&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Drug+Development+Research&rft.issn=02724391&rft_id=info:doi/10.1002%2Fddr.10406 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/ddr.10406 ER - TY - JOUR T1 - Recent advances in pharmacogenetic approaches to anticancer drug development AN - 17301848; 6097706 AB - A great deal of effort has been spent in defining the pharmacokinetics and pharmacodynamics of investigational and registered anticancer agents. There is often a marked variability in drug handling between individual patients, which contributes to variability in the pharmacodynamic effects of a given dose of a drug. A combination of physiological variables, genetic characteristics (pharmacogenetics), and environmental factors are known to alter the relationship between the absolute dose and the concentration-time profile in plasma. A variety of strategies is now being evaluated in patients with cancer to improve the therapeutic index of anticancer drugs, by implementation of pharmacogenetic imprinting through genotyping or phenotyping individual patients. The efforts have mainly focused on variants in genes encoding the drug-metabolizing enzymes thiopurine S-methyltransferase, dihydropyrimidine dehydrogenase, members of the cytochrome P450 family, including the CYP2B, 2C, 2D, and 3A subfamilies, members of the UGT family, as well as the ATP-binding cassette transporters ABCB1 (P-glycoprotein) and ABCG2 (breast-cancer resistance protein). Several of these genotyping strategies have been shown to have substantial impact on therapeutic outcome and should eventually lead to improved anticancer chemotherapy. JF - Drug Development Research AU - Smith, Nicola F AU - Figg, William D AU - Sparreboom, Alex AD - Molecular Pharmacology Section, Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, wdfigg@helix.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 233 EP - 253 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 62 IS - 3 SN - 0272-4391, 0272-4391 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17301848?accountid=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=Drug+Development+Research&rft.atitle=Recent+advances+in+pharmacogenetic+approaches+to+anticancer+drug+development&rft.au=Smith%2C+Nicola+F%3BFigg%2C+William+D%3BSparreboom%2C+Alex&rft.aulast=Smith&rft.aufirst=Nicola&rft.date=2004-01-01&rft.volume=62&rft.issue=3&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Drug+Development+Research&rft.issn=02724391&rft_id=info:doi/10.1002%2Fddr.10361 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/ddr.10361 ER - TY - JOUR T1 - Resources for comparing the speed and performance of medical autocoders AN - 17292806; 6060660 AB - Concept indexing is a popular method for characterizing medical text, and is one of the most important early steps in many data mining efforts. Concept indexing differs from simple word or phrase indexing because concepts are typically represented by a nomenclature code that binds a medical concept to all equivalent representations. A concept search on the term renal cell carcinoma would be expected to find occurrences of hypernephroma, and renal carcinoma (concept equivalents). The purpose of this study is to provide freely available resources to compare speed and performance among different autocoders. These tools consist of: 1) a public domain autocoder written in Perl (a free and open source programming language that installs on any operating system); 2) a nomenclature database derived from the unencumbered subset of the publicly available Unified Medical Language System; 3) a large corpus of autocoded output derived from a publicly available medical text. A simple lexical autocoder was written that parses plain-text into a listing of all 1,2,3, and 4-word strings contained in text, assigning a nomenclature code for text strings that match terms in the nomenclature. The nomenclature used is the unencumbered subset of the 2003 Unified Medical Language System (UMLS). The unencumbered subset of UMLS was reduced to exclude homonymous one-word terms and proper names, resulting in a term/code data dictionary containing about a half million medical terms. The Online Mendelian Inheritance in Man (OMIM), a 92+ Megabyte publicly available medical opus, was used as sample medical text for the autocoder. The autocoding Perl script is remarkably short, consisting of just 38 command lines. The 92+ Megabyte OMIM file was completely autocoded in 869 seconds on a 2.4 GHz processor (less than 10 seconds per Megabyte of text). The autocoded output file (9,540,442 bytes) contains 367,963 coded terms from OMIM and is distributed with this manuscript. A public domain Perl script is provided that can parse through plain-text files of any length, matching concepts against an external nomenclature. The script and associated files can be used freely to compare the speed and performance of autocoding software. JF - BMC Medical Informatics and Decision Making AU - Berman, Jules J AD - Cancer Diagnosis Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, bermanj@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17292806?accountid=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=BMC+Medical+Informatics+and+Decision+Making&rft.atitle=Resources+for+comparing+the+speed+and+performance+of+medical+autocoders&rft.au=Berman%2C+Jules+J&rft.aulast=Berman&rft.aufirst=Jules&rft.date=2004-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Medical+Informatics+and+Decision+Making&rft.issn=1472-6947&rft_id=info:doi/10.1186%2F1472-6947-4-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1472-6947-4-8 ER - TY - JOUR T1 - Doublet method for very fast autocoding AN - 17285512; 6060646 AB - Autocoding (or automatic concept indexing) occurs when a software program extracts terms contained within text and maps them to a standard list of concepts contained in a nomenclature. The purpose of autocoding is to provide a way of organizing large documents by the concepts represented in the text. Because textual data accumulates rapidly in biomedical institutions, the computational methods used to autocode text must be very fast. The purpose of this paper is to describe the doublet method, a new algorithm for very fast autocoding. An autocoder was written that transforms plain-text into intercalated word doublets (e.g. "The ciliary body produces aqueous humor" becomes "The ciliary, ciliary body, body produces, produces aqueous, aqueous humor"). Each doublet is checked against an index of doublets extracted from a standard nomenclature. Matching doublets are assigned a numeric code specific for each doublet found in the nomenclature. Text doublets that do not match the index of doublets extracted from the nomenclature are not part of valid nomenclature terms. Runs of matching doublets from text are concatenated and matched against nomenclature terms (also represented as runs of doublets). The doublet autocoder was compared for speed and performance against a previously published phrase autocoder. Both autocoders are Perl scripts, and both autocoders used an identical text (a 170+ Megabyte collection of abstracts collected through a PubMed search) and the same nomenclature (neocl.xml, containing over 102,271 unique names of neoplasms). In side-by-side comparison on the same computer, the doublet method autocoder was 8.4 times faster than the phrase autocoder (211 seconds versus 1,776 seconds). The doublet method codes 0.8 Megabytes of text per second on a desktop computer with a 1.6 GHz processor. In addition, the doublet autocoder successfully matched terms that were missed by the phrase autocoder, while the phrase autocoder found no terms that were missed by the doublet autocoder. The doublet method of autocoding is a novel algorithm for rapid text autocoding. The method will work with any nomenclature and will parse any ascii plain-text. An implementation of the algorithm in Perl is provided with this article. The algorithm, the Perl implementation, the neoplasm nomenclature, and Perl itself, are all open source materials. JF - BMC Medical Informatics and Decision Making AU - Berman, Jules J AD - Cancer Diagnosis Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, bermanj@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17285512?accountid=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=BMC+Medical+Informatics+and+Decision+Making&rft.atitle=Doublet+method+for+very+fast+autocoding&rft.au=Berman%2C+Jules+J&rft.aulast=Berman&rft.aufirst=Jules&rft.date=2004-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Medical+Informatics+and+Decision+Making&rft.issn=1472-6947&rft_id=info:doi/10.1186%2F1472-6947-4-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1472-6947-4-16 ER - TY - JOUR T1 - Coronary age as a risk factor in the modified Framingham risk score AN - 17283688; 6060619 AB - Clinical guidelines emphasize risk assessment as vital to patient selection for medical primary intervention. However, risk assessment methods are restricted in their ability to predict further coronary events. The most widely accepted tool in the United States is the Framingham risk score. In these equations age is a powerful risk factor. Although the extent of coronary atherosclerosis increases with age, there is large inter-individual variability in the rate of development and progression of this disease. This fact limits the utility of Framingham scoring when applied to individuals. Electron beam tomography (EBT), which measures coronary calcium, provides a non-invasive method for assessing coronary plaque burden, thus offering the possibility of providing a more accurate estimate of an individual's "arterial age" than from chronological age alone. In this paper we discuss a new and simple method for incorporating the coronary calcium score (CCS) to modify the Framingham Risk Assessment (FRA). Using this method, a coronary artery calcium (CAC) age equivalent is generated that replaces chronological age in Framingham scoring. Using a percentile table of CCS scores by age group and sex, individuals are matched to the age group whose calcium score most closely approximates their own individual score. The original 10-year absolute risk score of a 65-year old man with a CCS of 6 based on chronological age is 10%, whereas the modified absolute risk score based on CAC age equivalents is 2%. Our approach of replacing chronological age with CAC age equivalents in the Framingham equations possesses simplicity of application combined with precision. Physicians can easily derive adjusted Framingham risk scores and prescribe intervention methods based on patients' ten-year risks. The adjusted ten-year risks are likely to be more accurate than unadjusted risks since they are based on coronary calcium score information. The modified FRA approach not only may increase the predicted risk for some patients, but also may decrease the predicted risk for others, making it a more precise adjustment than other methods. JF - BMC Medical Imaging AU - Schisterman, Enrique F AU - Whitcomb, Brian W AD - Division of Epidemiology, Statistics and Prevention, National Institute of Child Health and Human Development, National Institute of Health, Department of Human Health Services, Bethesda, Maryland, USA, Schistee@mail.nih.gov Y1 - 2004 PY - 2004 DA - 2004 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17283688?accountid=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=BMC+Medical+Imaging&rft.atitle=Coronary+age+as+a+risk+factor+in+the+modified+Framingham+risk+score&rft.au=Schisterman%2C+Enrique+F%3BWhitcomb%2C+Brian+W&rft.aulast=Schisterman&rft.aufirst=Enrique&rft.date=2004-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Medical+Imaging&rft.issn=1471-2342&rft_id=info:doi/10.1186%2F1471-2342-4-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1186/1471-2342-4-1 ER - TY - JOUR T1 - Methodologic and Statistical Approaches to Studying Human Fertility and Environmental Exposure AN - 17269653; 5854895 AB - Although there has been growing concern about the effects of environmental exposures on human fertility, standard epidemiologic study designs may not collect sufficient data to identify subtle effects while properly adjusting for confounding. In particular, results from conventional time to pregnancy studies can be driven by the many sources of bias inherent in these studies. By prospectively collecting detailed records of menstrual bleeding, occurrences of intercourse, and a marker of ovulation day in each menstrual cycle, precise information on exposure effects can be obtained, adjusting for many of the primary sources of bias. This article provides an overview of the different types of study designs, focusing on the data required, the practical advantages and disadvantages of each design, and the statistical methods required to take full advantage of the available data. We conclude that detailed prospective studies allowing inferences on day-specific probabilities of conception should be considered as the gold standard for studying the effects of environmental exposures on fertility. JF - Environmental Health Perspectives AU - Tingen, C AU - Stanford, J B AU - Dunson, D B AD - Biostatistics Branch, NIEHS, MD A3-03, NIH, DHHS, PO Box 12233, Research Triangle Park, NC 27709 USA, dunson1@niehs.nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 87 EP - 93 VL - 112 IS - 1 SN - 0091-6765, 0091-6765 KW - environmental exposure KW - man KW - methodology KW - statistics KW - Toxicology Abstracts KW - Fertility KW - Toxicity testing KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17269653?accountid=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=Methodologic+and+Statistical+Approaches+to+Studying+Human+Fertility+and+Environmental+Exposure&rft.au=Tingen%2C+C%3BStanford%2C+J+B%3BDunson%2C+D+B&rft.aulast=Tingen&rft.aufirst=C&rft.date=2004-01-01&rft.volume=112&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.6263 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Fertility; Toxicity testing DO - http://dx.doi.org/10.1289/ehp.6263 ER - TY - JOUR T1 - Mean Total Arsenic Concentrations in Chicken 1989-2000 and Estimated Exposures for Consumers of Chicken AN - 17266066; 5854885 AB - The purpose of this study was to estimate mean concentrations of total arsenic in chicken liver tissue and then estimate total and inorganic arsenic ingested by humans through chicken consumption. We used national monitoring data from the Food Safety and Inspection Service National Residue Program to estimate mean arsenic concentrations for 1994-2000. Incorporating assumptions about the concentrations of arsenic in liver and muscle tissues as well as the proportions of inorganic and organic arsenic, we then applied the estimates to national chicken consumption data to calculate inorganic, organic, and total arsenic ingested by eating chicken. The mean concentration of total arsenic in young chickens was 0.39 ppm, 3- to 4-fold higher than in other poultry and meat. At mean levels of chicken consumption (60 g/person/day), people may ingest 1.38-5.24 mu g/day of inorganic arsenic from chicken alone. At the 99th percentile of chicken consumption (350 g chicken/day), people may ingest 21.13-30.59 mu g inorganic arsenic/day and 32.50-47.07 mu g total arsenic/day from chicken. These concentrations are higher than previously recognized in chicken, which may necessitate adjustments to estimates of arsenic ingested through diet and may need to be considered when estimating overall exposure to arsenic. JF - Environmental Health Perspectives AU - Lasky, T AU - Sun, W AU - Kadry, A AU - Hoffman, M K AD - National Institute of Child Health and Development, MSC 7510, 6100 Executive Boulevard, Bethesda, MD 20892 USA, TL177G@nih.gov Y1 - 2004/01// PY - 2004 DA - Jan 2004 SP - 18 EP - 21 VL - 112 IS - 1 SN - 0091-6765, 0091-6765 KW - chickens KW - exposure KW - man KW - poultry KW - Health & Safety Science Abstracts; Toxicology Abstracts KW - Diets KW - Arsenic KW - Poultry KW - Food KW - Food contamination KW - Ingestion KW - USA KW - Liver KW - X 24120:Food, additives & contaminants KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17266066?accountid=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=Mean+Total+Arsenic+Concentrations+in+Chicken+1989-2000+and+Estimated+Exposures+for+Consumers+of+Chicken&rft.au=Lasky%2C+T%3BSun%2C+W%3BKadry%2C+A%3BHoffman%2C+M+K&rft.aulast=Lasky&rft.aufirst=T&rft.date=2004-01-01&rft.volume=112&rft.issue=1&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.6407 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Poultry; Arsenic; Food; Liver; Diets; Ingestion; Food contamination; USA DO - http://dx.doi.org/10.1289/ehp.6407 ER - TY - JOUR T1 - Biocomplexity in the oral cavity - the basics of structure in supragingival bacterial communities AN - 17255426; 6972056 AB - The human oral microbial ecosystem is one of the best characterized and highly complex bacterial communities known. It is estimated that about 600 bacterial species exist in the mouth and that 85% of those are currently known at the molecular (16 S rRNA) level. The major bacterial physiologies occurring in the oral cavity have been known for many years, and knowledge exists of the distribution of organisms in time (as plaque accumulates) and in space (different environments within the mouth). However, only rudimentary data are available on interactions between the bacterial species. It is precisely these interactions that, along with the interactions of the developing community with its human host, must drive the succession of genera that is observed to occur. In the reductionist scientific approach to studying such interactions, disrupted plaque is used to isolate single organisms, and interactions between these organisms are examined by recombining the organisms ex situ. Lessons learned from these in vitro studies can be applied to understand empirical observations made in vivo. However, this approach begins with the primary assumption that the chosen interaction does in fact occur in vivo. The accessibility and the well-characterized nature of the oral ecosystem presents an opportunity for approaching the problem from the opposite direction; one can capture a community very early in development in vivo, then apply in vitro methods to sort out the interactions within that community. This latter approach begins with a set of organisms known to interact in vivo. A combination of both approaches should yield robust microbiological data suitable for in silico modeling and analyses. JF - Biofilms AU - Palmer Jr, RJ AU - Diaz, P I AU - Kolenbrander, P E AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 310, Bethesda, MD 20892, USA, rjpalmer@dir.nidcr.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 329 EP - 335 PB - Cambridge University Press, UK, The Edinburgh Building, Shaftesbury Road Cambridge CB2 2RU UK, [mailto:journals@cambridge.org], [URL:http://journals.cambridge.org] VL - 1 IS - 4 SN - 1479-0505, 1479-0505 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - Biocomplexity KW - Bacteria KW - rRNA KW - Data processing KW - Plaques KW - Biofilms KW - Mouth KW - Succession KW - Oral cavity KW - A 01450:Environmental Pollution & Waste Treatment KW - J 02844:Dental and oral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17255426?accountid=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=Biofilms&rft.atitle=Biocomplexity+in+the+oral+cavity+-+the+basics+of+structure+in+supragingival+bacterial+communities&rft.au=Palmer+Jr%2C+RJ%3BDiaz%2C+P+I%3BKolenbrander%2C+P+E&rft.aulast=Palmer+Jr&rft.aufirst=RJ&rft.date=2004-01-01&rft.volume=1&rft.issue=4&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Biofilms&rft.issn=14790505&rft_id=info:doi/10.1017%2FS1479050504001498 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-09-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Biocomplexity; rRNA; Data processing; Plaques; Biofilms; Succession; Mouth; Oral cavity; Bacteria DO - http://dx.doi.org/10.1017/S1479050504001498 ER - TY - JOUR T1 - Developmental exposure to diethylstilbestrol (DES) alters uterine response to estrogens in prepubescent mice: low versus high dose effects AN - 17240407; 6976167 AB - Outbred CD-1 mice received subcutaneous injections on neonatal days 1-5 with DES (0.0001-1000 mu g/kg per day), a model xenoestrogen. At 17 days of age, uterine wet weight increase in response to estrogen was altered in neonatally DES-treated mice compared to controls. The response varied depending on the neonatal DES dose; a low dose (0.01 mu g/kg) caused an enhanced uterine response but higher neonatal doses dampened the response. Western blots and immunolocalization of estrogen receptor alpha (ER alpha ) showed high ER levels at DES 0.01 mu g/kg, but decreased levels at higher doses compared to controls. Genes responding through ER-mediated pathways (c-fos, proliferating cell nuclear antigen (PCNA), and lactoferrin (LF)) mirrored altered wet weight responses, i.e., enhancement at low doses and dampening at higher doses. A similar dose- response curve was seen in 4 months old ovariectomized DES-treated mice suggesting the altered response was long-term. These data suggest xenoestrogen exposure during critical developmental windows alters hormone programming so that the uterus responds abnormally to estrogen later in life, and that the response differs following high versus low doses of neonatal exposure. JF - Reproductive Toxicology AU - Newbold, Retha R AU - Jefferson, Wendy N AU - Padilla-Banks, Elizabeth AU - Haseman, Joseph AD - Developmental Endocrinology Section, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, newbold1@niehs.nih.gov Y1 - 2004 PY - 2004 DA - 2004 SP - 399 EP - 406 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 18 IS - 3 SN - 0890-6238, 0890-6238 KW - Toxicology Abstracts KW - Author Keywords: Environmental estrogens KW - Endocrine disruptors KW - Developmental programming KW - Estrogen receptor alpha KW - ER alpha KW - Uterine lactoferrin KW - Dose-response KW - Low dose effects KW - Western blotting KW - Uterus KW - lactoferrin KW - Ovariectomy KW - Neonates KW - c-Fos protein KW - Proliferating cell nuclear antigen KW - Diethylstilbestrol KW - Estrogen receptors KW - Hormones KW - Xenoestrogens KW - X 24114:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17240407?accountid=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=Developmental+exposure+to+diethylstilbestrol+%28DES%29+alters+uterine+response+to+estrogens+in+prepubescent+mice%3A+low+versus+high+dose+effects&rft.au=Newbold%2C+Retha+R%3BJefferson%2C+Wendy+N%3BPadilla-Banks%2C+Elizabeth%3BHaseman%2C+Joseph&rft.aulast=Newbold&rft.aufirst=Retha&rft.date=2004-01-01&rft.volume=18&rft.issue=3&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2Fj.reprotox.2004.01.007 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Western blotting; Uterus; lactoferrin; Ovariectomy; c-Fos protein; Neonates; Diethylstilbestrol; Proliferating cell nuclear antigen; Hormones; Estrogen receptors; Xenoestrogens DO - http://dx.doi.org/10.1016/j.reprotox.2004.01.007 ER -